Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

Objective To construct an XGBoost predictive model using clinical characteristic data from patients with chronic obstructive pulmonary disease(COPD)and evaluate the efficacy of the predictive model in early risk prediction of lung cancer occurrence in COPD patients.Methods In this retrospective cross-sectional study,cluster sampling was used.We selected clinically diagnosed COPD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University from January 1,2018,to December 31,2022.A total of 4 008 patients with complete data were included.First,the baseline of each characteristic was analyzed,and then XGBoost was used to construct the lung cancer risk prediction model for COPD patients,and SHAP(SHapley Additive exPlanation)value was used to quantify and attribute the importance of each characteristic.DC A curve was used to evaluate the clinical application value.Results After constructing a lung cancer risk model for COPD patients using 28 variables,eight variables were selected according to the importance of the variables and clinical experience,and the prediction model was reconstructed.The model efficacy in the training set and the test set was 0.948(0.938,0.958)and 0.797(0.738,0.856),respectively.SHAP diagram showed that elevated CEA,CA125,FIB,eosinophils,PLT and D-dimer and reduced TT all contributed to an increased risk of lung cancer in COPD patients.DCA curve showed that the prediction model had clinical application value,which could help doctors make more accurate prognosis prediction and treatment decisions.Conclusion The successful establishment of an XGBoost predictive model,utilizing a subset of features,enables early prediction of lung cancer occurrence in COPD patients.

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 evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Objective:To investigate the influence of four preoperative CT image characteristics on the outcome of thoracoscopic surgery for chronic tuberculous empyema.Methods:This is a retrospective cohort study. Two hundred and eleven patients of tuberculous empyema who underwent video-assisted thoracic surgery(VATS) decortication at the First Department of Surgery , Wuhan Pulmonary Hospital from June 2020 to June 2023 were retrospectively analyzed. There were 162 male cases and 49 female cases, with an age ( M (IQR)) of 33 (27) years (range: 8 to 76 years). Patients were divided into two groups according to whether low-density lines, mass-patchy density, pleural fusion were observed, and the lesion size. Compare the clinical indicators of two groups of cases. Using the rapeutic efficacy as the dependent variable and four CT features as covariates, cases with cure or improve were included in Logistic regression analysis to calculate OR (95% CI) values. Results:Preoperative chest CT images showed that 127 cases (60.2%) had low-density lines, 102 cases (48.3%) had mass-patchy density, and 88 cases (47.7%) had pleural fusion. The lesions spanned 2 to 11 intercostal spaces, with a median of 7 intercostal spaces. The lesion size was divided into two groups according to <7 intercostal spaces and ≥7 intercostal spaces, with 101 cases (47.9%) and 110 cases (52.1%), respectively. In the intra-group comparison, there were no difference in age, lesion location and pulmonary tuberculosis. In the comparison of gender, except that the proportion of female patients in the group with lesion size <7 intercostal spaces ( χ2=6.064, P=0.010) was higher than ≥7 intercostal spaces, there were no significant difference between other groups. In low-density lines group, there was no difference in the incidence of anemia and hypoproteinemia between the two groups. Compared with the non low-density line group, patients with low-density line group exhibited fewer cases of abnormal elevation in ESR and CRP was lower(all P<0.01), the period of preoperative treatment ( U=7 281.00, P<0.01) was longer than the non low-density line group, while the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration, and therapeutic efficacy were all better than the non low-density line group(all P<0.05). In the comparison between the mass-patchy density group, there were fewer cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP in the without mass-patchy density group(all P<0.05), and the period of preoperative treatmentwas shorter ( U=4 581.50, P=0.026), and the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration and therapeutic effect were better too(all P<0.05). In the grouping comparison of pleural fusion, there were no difference in cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP, and the period of preoperative treatment between the two groups; the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration, and therapeutic efficacy of the group without pleural fusion were better than the group with pleural fusion(all P<0.05). The group with <7 intercostal spaces had fewer cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP (all P<0.05), the period of preoperative treatment was longer ( U=4 295.00, P=0.004), the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours,postoperative drainage duration, lung re-expansion duration and complications were less (all P<0.05), the therapeutic efficacy was better than the group with ≥7 intercostal spaces ( χ2=27.912, P<0.01). The Logistic regression analysis of cured and improved cases showed that mass-patchy density and lesion size were independent risk factors affecting the therapeutic efficacy (all P<0.05). Conclusions:For patients with CT images showing mass-patchy density, pleural fusion, and a large lesion size, the difficulty and risk of surgery may be relatively high.The preoperative CT images can provide objective reference for clinical preoperative evaluation.

Objective To construct an XGBoost predictive model using clinical characteristic data from patients with chronic obstructive pulmonary disease(COPD)and evaluate the efficacy of the predictive model in early risk prediction of lung cancer occurrence in COPD patients.Methods In this retrospective cross-sectional study,cluster sampling was used.We selected clinically diagnosed COPD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University from January 1,2018,to December 31,2022.A total of 4 008 patients with complete data were included.First,the baseline of each characteristic was analyzed,and then XGBoost was used to construct the lung cancer risk prediction model for COPD patients,and SHAP(SHapley Additive exPlanation)value was used to quantify and attribute the importance of each characteristic.DC A curve was used to evaluate the clinical application value.Results After constructing a lung cancer risk model for COPD patients using 28 variables,eight variables were selected according to the importance of the variables and clinical experience,and the prediction model was reconstructed.The model efficacy in the training set and the test set was 0.948(0.938,0.958)and 0.797(0.738,0.856),respectively.SHAP diagram showed that elevated CEA,CA125,FIB,eosinophils,PLT and D-dimer and reduced TT all contributed to an increased risk of lung cancer in COPD patients.DCA curve showed that the prediction model had clinical application value,which could help doctors make more accurate prognosis prediction and treatment decisions.Conclusion The successful establishment of an XGBoost predictive model,utilizing a subset of features,enables early prediction of lung cancer occurrence in COPD patients.

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 evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Objective:To investigate the influence of four preoperative CT image characteristics on the outcome of thoracoscopic surgery for chronic tuberculous empyema.Methods:This is a retrospective cohort study. Two hundred and eleven patients of tuberculous empyema who underwent video-assisted thoracic surgery(VATS) decortication at the First Department of Surgery , Wuhan Pulmonary Hospital from June 2020 to June 2023 were retrospectively analyzed. There were 162 male cases and 49 female cases, with an age ( M (IQR)) of 33 (27) years (range: 8 to 76 years). Patients were divided into two groups according to whether low-density lines, mass-patchy density, pleural fusion were observed, and the lesion size. Compare the clinical indicators of two groups of cases. Using the rapeutic efficacy as the dependent variable and four CT features as covariates, cases with cure or improve were included in Logistic regression analysis to calculate OR (95% CI) values. Results:Preoperative chest CT images showed that 127 cases (60.2%) had low-density lines, 102 cases (48.3%) had mass-patchy density, and 88 cases (47.7%) had pleural fusion. The lesions spanned 2 to 11 intercostal spaces, with a median of 7 intercostal spaces. The lesion size was divided into two groups according to <7 intercostal spaces and ≥7 intercostal spaces, with 101 cases (47.9%) and 110 cases (52.1%), respectively. In the intra-group comparison, there were no difference in age, lesion location and pulmonary tuberculosis. In the comparison of gender, except that the proportion of female patients in the group with lesion size <7 intercostal spaces ( χ2=6.064, P=0.010) was higher than ≥7 intercostal spaces, there were no significant difference between other groups. In low-density lines group, there was no difference in the incidence of anemia and hypoproteinemia between the two groups. Compared with the non low-density line group, patients with low-density line group exhibited fewer cases of abnormal elevation in ESR and CRP was lower(all P<0.01), the period of preoperative treatment ( U=7 281.00, P<0.01) was longer than the non low-density line group, while the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration, and therapeutic efficacy were all better than the non low-density line group(all P<0.05). In the comparison between the mass-patchy density group, there were fewer cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP in the without mass-patchy density group(all P<0.05), and the period of preoperative treatmentwas shorter ( U=4 581.50, P=0.026), and the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration and therapeutic effect were better too(all P<0.05). In the grouping comparison of pleural fusion, there were no difference in cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP, and the period of preoperative treatment between the two groups; the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration, and therapeutic efficacy of the group without pleural fusion were better than the group with pleural fusion(all P<0.05). The group with <7 intercostal spaces had fewer cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP (all P<0.05), the period of preoperative treatment was longer ( U=4 295.00, P=0.004), the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours,postoperative drainage duration, lung re-expansion duration and complications were less (all P<0.05), the therapeutic efficacy was better than the group with ≥7 intercostal spaces ( χ2=27.912, P<0.01). The Logistic regression analysis of cured and improved cases showed that mass-patchy density and lesion size were independent risk factors affecting the therapeutic efficacy (all P<0.05). Conclusions:For patients with CT images showing mass-patchy density, pleural fusion, and a large lesion size, the difficulty and risk of surgery may be relatively high.The preoperative CT images can provide objective reference for clinical preoperative evaluation.