Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

[Objective] To explore the relationship between neutrophil activation under cardiopulmonary bypass (CPB) and the incidence of cardiac surgery-associated acute kidney injury (CS-AKI). [Methods] This prospective cohort study enrolled adult patients who scheduled for cardiac surgery under CPB at West China Hospital between May 1, 2022 and March 31, 2023. The primary outcome was acute kidney injury (AKI). Blood samples (5 mL) were obtained from the central vein before surgery, at rewarming, at the end of CPB, and 24 hours after surgery. Neutrophils were labeled with CD11b, CD54 and other markers. To assess the effect of neutrophils activation on AKI, propensity score matching (PSM) was employed to equilibrate covariates between the groups. [Results] A total of 120 patients included into the study, and 17 (14.2%) developed AKI. Both CD11b⁺ and CD54⁺ neutrophils significantly increased during the rewarming phase and the increases were kept until 24 hours after surgery. During rewarming, the numbers of CD11b⁺ neutrophils were significantly higher in AKI compared to non-AKI (4.71×10⁹/L vs 3.31×10⁹/L, Z=-2.14, P<0.05). Similarly, the CD54⁺ neutrophils counts were also significantly higher in AKI than in non-AKI before surgery (2.75×10⁹/L vs 1.79×10⁹/L, Z=-2.99, P<0.05), during rewarming (3.12×10⁹/L vs 1.62×10⁹/L, Z=-4.34, P<0.05), and at the end of CPB (4.28×10⁹/L vs 2.14×10⁹/L, Z=-3.91, P<0.05). An analysis of 32 matched patients (16 in each group) revealed that CD11b⁺ and CD54⁺ neutrophil levels of AKI were 1.74 folds (4.83×10⁹/L vs 2.77×10⁹/L, Z=-2.72, P<0.05) and 2.34 folds (3.32×10⁹/L vs 1.42×10⁹/L, Z=-4.12, P<0.05), respectively, of non-AKI at rewarming phase. [Conclusion] Neutrophils are activated during CPB, and they can be identified by CD11b/CD54 markers. The activated neutrophils of AKI patients are approximately 2 folds of non-AKI during the rewarming phase, with disparity reached peak between groups during rewarming. These findings suggest the removal of 50% of activated neutrophils during the rewarming phase may be effective to reduce the risk of AKI.

Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×10⁹/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

Objective:To evaluate the efficacy of cerebral-placental-uterine ratio(CPUR)in predicting late-on-set fetal growth restriction(FGR).Methods:From May 2020 to May 2021,1255 women with singleton pregnancy who underwent prenatal examinations at the University of Hong Kong Shenzhen Hospital were selected for fetal growth and Doppler measurements at 35-37 +6 weeks of gestation.Pregnant women with birth weight of newbo-rns＜the 10th percentile were the FGR group.The pulsatility index(PI)of uterine artery(UtA),umbilical artery(UA)and fetal middle cerebral artery(MCA)were analyzed separately and in combination.ROC curve was used to analyze the cerebral-placental-uterine ratio(CPUR),cerebral-placental ratio(CPR),cerebral-uterine ratio(C-UtA)for predicting late-onset FGR;and to evaluate the sensitivity,positive and negative predictive value and of CPUR in the prediction of late-onset FGR.Results:The area under the curve(AUC)of CPUR,CPR,C-UtA and mean UtA-PI for FGR grope were 0.88,0.86,0.84 and 0.72.Under certain cut-off values and 87% specificity,the specificity of CPUR,CPR,C-UtA and mean UtA-Pifor predicting FGR group was 43.2%,46.6%,39.8% and 23.9%,respectively.The positive predictive values of CPUR,CPR,C-UtA and mean UtA-PI,UA-PI for predicting FGR group were 90.5%,71.9%,83.3%,63.6%and 5.2%,respectively.Conclusions:CPUR is more effective in predicting late onset FGR than CPR,C-UtA and mean UtA-PI.It can effectively increase the detection rate of fetal growth restrictionand reduce the FGR risk.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective To enhance CT radiation dose management in radiology department via applying Six Sigma management method.Methods The radiation quality control processes in the radiology department were optimized according to the Six Sigma quality management DMAIC pattern.The volume CT dose index(CTDIvol),dose length product(DLP),radiation quality control problems of adult and pediatric CT scans from January 2022 to February 2022 were collected as baseline data,and data collected from August 2022 to September 2022 were taken as the control group for analysis via Six Sigma management method.All data of the dose values and problem rates were compared and analyzed between before and after Six Sigma management methods.Results The DLP in the adult group was decreased by 65.5％in computed tomography urography(CTU),decreased by 25.5％in neck enhancement,decreased by 9.8％in head,decreased by 24％in facial cranial,and decreased by 27.7％in chest enhancement,with a statistical difference(P＜0.05).While DLP in the adult group was decreased by 9.7％in abdominal enhancement,with no significant difference(P＞0.05).The DLP in the pediatric(＜1 year)group was increased by 35％in head scans,with no significant difference(P＞0.05).While the DLP was decreased by 30.2％in 1 to 5 years group,decreased by 21.8％in 6 to 10 years group,decreased by 27.6％in 11 to 15 years group,with statistical difference(P＜0.05).The DLP of facial cranial was decreased by 43.3％in 6 to 10 years group,decreased by 29.1％in 11 to 15 years group,with statistical difference(P＜0.05).The DLP of chest was decreased by 13％in＜1 year group(P＞0.05),increased by 2.2％in 1 to 5 years group(P＞0.05),decreased by 42.6％in 6 to 10 years group,decreased by 54.2％in 11 to 15 years group(P＜0.05).The incidence of radiological quality control problems of after Six Sigma management was significantly lower than that of before Six Sigma management(P＜0.05).Conclusion Six Sigma management method can identify problems in the clinical practice and enhance the ability of radiation quality control through optimization.

Objective To analyze the radiation dose in low-dose chest CT examination of pediatric patients with mycoplasma pneumoniae pneumonia(MPP)by using size-specific dose estimation(SSDE).Methods A total of 95 patients who were scanned with low-dose chest CT were prospectively selected,65 patients with weight ≤50 kg,using 80 kV and DoseRight Z-DOM(30-50 mAs);30 patients with weight＞50 kg,using 100 kV and DoseRight Z-DOM(50-100 mAs).A total of 65 patients who were scanned with conventional chest CT were retrospectively collected,40 patients with weight ≤50 kg,25 patients with weight＞50 kg,using 120 kV,DoseRight Z-DOM(50-100 mAs)and fixed mAs.Image noise,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were used to objectively evaluate image quality.The subjective evaluation of image quality was performed by two radiologists using a 5-score system and a double-blind method.The volume CT dose index(CTDIvol)and dose length product(DLP)were collected,the SSDE and effective dose(ED)were measured,respectively.Results Compared with conventional scan,CTDIvol,DLP,SSDE,and ED values of 80 kV scan was decreased by 81.3％,80.3％,81.5％,and 82.4％,respectively,with a statistical difference(Z=-8.433,-8.137,-8.146,-8.142,P＜0.05).There were statistically significant differences in image noise,SNR,and CNR between 80 kV scan and conventional scan in patients with weight ≤50 kg(Z=-6.762,-5.075,-3.430,P＜0.05).In 100 kV scan,CTDIvol,DLP,SSDE,and ED values was decreased by 75.7％,76.3％,75.3％,and 75.3％,respectively,with a statistical difference(Z=-6.301,-6.173,-6.347,-6.308,P＜0.05).There were statistically significant differences in image noise and SNR between 100 kV scan and conventional scan in patients with weight＞50 kg(Z=-5.367,-4.650,P＜0.05).The subjective evaluation scores of the two groups images were all greater than 3 points,all images could be used for clinical diagnosis.SSDE was 45.3％and 29.9％higher than CTDIvol for 80 kV and 100 kV scans,respectively,SSDE was 45.7％and 28.8％higher than CTDIvol for conventional scans with weight ≤50 kg and weight＞50 kg,respectively.Conclusion Low kV combined with DoseRight Z-DOM effectively reduces radiation dose to pediatric patients with MPP;SSDE more accurately assesses radiation dose than CTDIvol in children.

Objective:To explore the definition and connotation of the thriving in the elderly, so as to provide reference for clinical practice.Methods:This study systematically searched databases such as China National Knowledge Infrastructure, WanFangdata, CINAHL, PsycINFO, PubMed, and Web of Science using keywords such as "aged" and "thriving". The search period was from database establishment to June 10, 2023. Walker's eight-step analysis method was used to conduct concept analysis on the thriving in the elderly.Results:A total of 14 articles were included. The defining attributes of the thriving in the elderly included good self-perception, utilizing existing resources to adjust self-expectation, and achieving self-growth and development. The antecedents were a positive attitude, high-quality caregivers and care services, a good physical and humanistic environment. The consequence was that elderly people had great adaptability, subjective experience, and health level.Conclusions:The thriving in the elderly is a subjective well-being achieved by the interaction among an individual, the humanistic and physical environment, which is affected by various factors such as individuals and environment. It is a new concept that has emerged in the international field of geriatric nursing in recent years, focusing on the positive aspects of aging and providing new directions for research in geriatric nursing.

Objective: To analyze the trend of the burden of leukemia among people under 35 years in China from 1990 to 2019. Methods: Incidence, mortality and disability-adjusted life years (DALY) of leukemia among people under 35 years in China from 1990 to 2019 were collected by using the Global Burden of Disease (GBD) Study Database 2019. The trends in leukemia incidence, mortality and DALY rates were analyzed using the average annual percent change (AAPC) and age-period-cohort model. Results: From 1990 to 2019, the incidence, mortality and DALY rates of leukemia among people under 35 years in China showed a downward trend (AAPC=-2.336%, -3.604% and -3.589%, all P<0.05), with more pronounced downward trends in females (AAPC=-3.209%, -3.787% and -3.818%, all P<0.05) than in males (AAPC=-2.521%, -3.292% and -3.306%, all P<0.05). According to the age-period-cohort model, the risks of leukemia incidence, mortality and DALY rates decreased with increasing age. Among them, the children under 5 years had the highest risks of leukemia incidence, mortality and DALY rates (RR=4.697, 2.718 and 3.059). Over time, the risks of leukemia incidence, mortality and DALY rates also decreased from 1990-1994 (RR=1.217, 1.264 and 1.296) to 2015-2019 (RR=0.901, 0.696 and 0.691). With regard to birth cohorts, the risks of leukemia incidence, mortality and DALY rates first increased and then decreased, peaking in the 1986-1990 birth cohort (RR=1.335, 1.192 and 1.231). Conclusions The incidence, mortality and DALY rates of leukemia among people under 35 years in China from 1990 to 2019 showed a downward trend. Males and children under 5 years were the key populations for leukemia prevention and control.