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.

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 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 correlation between blood glucose variability index(GLUCV)and postoperative delirium(POD)in elderly patients undergoing knee arthroplasty.Methods A total of 112 elderly patients undergoing elective knee arthroplasty were analyzed retrospectively,16 males and 96 females,aged 65-80 years,BMI 22.0-28.0 kg/m2,ASA physical status Ⅰ or Ⅱ.They were di-vided into two groups according to whether they had POD within 5 days after operation:POD group and non-POD group.The score of the last preoperative mini-mental state examination(MMSE),operation time,the duration of the intraoperative regional cerebral oxygen saturation(rScO2)value decreased by more than 13％of the rScO2 basic value(△rScO2＞13％),the preoperative hemoglobin(Hb)and C-reactive protein(CRP)concentration,the fingertip blood glucose concentration before entry,before anesthesia induction,5 minutes after anesthesia induction,1 minute after skin incision,and before leaving the chamber were col-lected,and the GLUCV was calculated.The risk factors of POD in elderly patients undergoing knee arthro-plasty were analyzed by univariate and multivariate logistic regression,and the odds ratio(OR)and 95％confidence interval(CI)were calculated.The receiver operating characteristic(ROC)curve was drawn to calculate the area under the curve(AUC)and analyze the predictive value of GLUCV.Results Thirty patients(26.8％)showed POD symptoms within 5 days after surgery.Compared with the non-POD group,the operation time and duration of intraoperative △rScO2＞13％in the POD group were significantly prolonged(P＜0.05),the CRP concentration and GLUCV were significantly increased(P＜0.05).Multi-variate logistic regression analysis showed that prolonged time of △rScO2＞13％(OR=3.542,95％CI 1.380-9.093,P=0.011),elevated CRP concentration(OR=1.984,95％CI 1.078-3.650.P=0.015),and elevated GLUCV(OR=5.257,95％CI 1.690-16.353,P=0.008)were risk factors of POD in elderly patients undergoing knee arthroplasty.ROC curve analysis showed that the area under the AUC of GLUCV in predicting POD in elderly patients undergoing knee arthroplasty was 0.747(95％CI 0.650-0.844,P＜0.001),while the optimal cutoff value was 23.4％,the sensitivity was 71.4％,and the specificity was 63.3％.Conclusion GLUCV is closely related to POD,and GLUCV level has a good pre-dictive effect on POD in elderly patients undergoing knee arthroplasty.

Objective:To investigate the impacts of periodontal-orthodontic treatment on periodontal indicators,bone metabolism and serum levels of soluble intercellular adhesion molecule-1(sICAM-1)and monocyte chemotactic protein-1(MCP-1)in patients with an-terior tooth displacement(ATD)caused by periodontitis.Methods:60 patients with ATD caused by periodontitis were included and randomly divided into a reference group(n=30,periodontal basic treatment+periodontal splint treatment)and a study group(n=30,combination of orthodontic treatment with the reference treatment).31 ATD patients who only received periodontal basic treatment were included into the blank control group.The probing depth(PD),plaque index(PLI)and gingival index(GI),tooth looseness,bone me-tabolism indicators osteocalcin(OCN)and osteoprotegerin(OPG),and serum inflammatory indicators(sICAM-1 and MCP-1)were compared among the 3 groups before and after treatment.Results:After 6 months of treatment,the levels of PD,PLI,GI,and serum sICAM-1 and MCP-1 in the 3 groups were lower than those before treatment(P＜0.05),and lower in the study group than in the refer-ence group and blank control group(P＜0.05);the looseness of the affected teeth in the 3 groups was decreased(P＜0.05),and in the study group was less than in the reference group and blank control group(P＜0.05);the levels of OCN and OPG in the 3 groups were higher(P＜0.05)than those before treatment,and in the study group were higher than in the reference group and blank control group(P＜0.05).Conclusion:Periodontal-orthodontic treatment can obviously reduce the levels of inflammatory factors in serum,effectively regulate bone metabolism and improve periodontal health in patients with ATD caused by periodontitis.

Breast cancer (BC) is the most prevalent malignancy worldwide, and a continued upward trend has been predicted in the coming decades. Screening in selected targeted populations, which is effective in reducing cancer-related mortality, has been widely implemented in many countries. This review summarizes the advances in BC screening techniques, organized or opportunistic BC screening programs across different countries, and screening modalities recommended by different academic authorities. Mammography is the most widely used and effective technique for BC screening. Other complementary techniques include ultrasound, clinical breast examination, and magnetic resonance imaging. Novel screening tests, including digital breast tomosynthesis and liquid biopsies, are still under development. Globally, the implementation status of BC screening programs is uneven, which is reflected by differences in screening modes, techniques, and population coverage. The recommended optimal screening strategies varied according to the authoritative guidelines. The effectiveness of current screening programs is influenced by several factors, including low detection rate, high false-positive rate, and unsatisfactory coverage and uptake rates. Exploration of accurate BC risk prediction models and the development of risk-stratified screening strategies are highly warranted in future research.

Breast cancer (BC) is the most prevalent malignancy worldwide, and a continued upward trend has been predicted in the coming decades. Screening in selected targeted populations, which is effective in reducing cancer-related mortality, has been widely implemented in many countries. This review summarizes the advances in BC screening techniques, organized or opportunistic BC screening programs across different countries, and screening modalities recommended by different academic authorities. Mammography is the most widely used and effective technique for BC screening. Other complementary techniques include ultrasound, clinical breast examination, and magnetic resonance imaging. Novel screening tests, including digital breast tomosynthesis and liquid biopsies, are still under development. Globally, the implementation status of BC screening programs is uneven, which is reflected by differences in screening modes, techniques, and population coverage. The recommended optimal screening strategies varied according to the authoritative guidelines. The effectiveness of current screening programs is influenced by several factors, including low detection rate, high false-positive rate, and unsatisfactory coverage and uptake rates. Exploration of accurate BC risk prediction models and the development of risk-stratified screening strategies are highly warranted in future research.

BACKGROUND: Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC. METHODS: FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression. RESULTS: FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality. CONCLUSIONS Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, disease burden became even severer in developing countries, especially for the population aged ≥40 years. Effective targeted preventive programs are strongly encouraged to reduce the FBC disease burden worldwide.
Breast Neoplasms/epidemiology* ; Female ; Global Health ; Humans ; Incidence ; Registries ; Risk Factors

Objective:To investigate the treatment, safety and prognosis of advanced non-small cell lung cancer patients with leptomeningeal metastasis and performance status score more than 3.Methods:The clinical data of 6 NSCLC patients with leptomeningeal metastasis admitted to the People's Hospital of Wuhan University from November 2016 to September 2018 were analyzed retrospectively. The curative effect and adverse reactions were observed, and the prognosis was analyzed.Results:There were 5 females and 1 male among 6 patients. The median age was 57 years old (46-74 years old). All 6 patients were diagnosed as stage Ⅳ lung adenocarcinoma. There were 3 patients with epidermal growth factor receptor (EGFR) exon 21 mutation, 2 patients with exon 19 mutation and one with anaplastic lymphoma kinase (ALK) fusion mutation. The time window of leptomeningeal metastasis occurred after the progression of adenocarcinoma of lung: 3 cases was more than 12 months, the other 3 cases was less than 12 months, and the average was 20.3 month. Performance status score was more than 3 when leptomeningeal metastasis occurred. The brain magnetic resonance imaging of 6 patients showed linear enhancement of leptomeningeal, cancer cells were found in cerebrospinal fluid in one case, 4 cases were treated with a combination of bevacizumab and EGFR-tyrosine kinase inhibitor (EGFR-TKI), 1 case was treated with oral administration of EGFR-TKI, 1 case was treated with oral administration of EGFR-TKI combined with temozolomide. The median overall survival (mOS) was 9 months (2-13 months), and the median progression free survival was 6 months (2-11 months).Conclusion:Lung adenocarcinoma may be prone to leptomeningeal metastasis; for NSCLC patients with leptomeningeal metastasis and performance status score more than 3, a combination of EGFR-TKI and bevacizumab has good tolerance, high safety and considerable curative effect.