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.

Objective:To construct a diagnostic prediction nomogram for antibody-mediated rejection (AMR) after kidney transplantation (KT) based upon peripheral blood gene expression profiling and preliminarily screening potential drugs for AMR.Methods:Seven large kidney transplant cohort datasets related to AMR were retrieved from the database of GEO. Differential expression analysis was utilized for identifying differentially expressed genes between AMR and normal recipients. Multiple machine learning algorithms of random forest (RF), extreme gradient boosting (XGB), support vector machine (SVM) and generalized linear model (GLM) were employed for constructing diagnostic models for AMR after kidney transplantation. Receiver operating characteristic (ROC) curve was plotted for comparing the accuracy of each model. The key genes of optimal model were integrated for creating a diagnostic prediction nomogram for AMR. Calibration curve and decision curve analyses were employed for evaluating the accuracy of nomogram. The differentially expressed genes from biopsy tissues of AMR recipients were uploaded to the database of CMap for identifying potential therapeutic drugs through screening Top 5 compounds with opposite expression patterns to AMR.Results:Seven genes of CXCL10, FCGR1B, GBP5, CD69, LY96, BCL2A1 and EVI2A were over-expressed in both peripheral blood and biopsy tissues of AMR recipients. There were statistically significant differences with recipients without AMR (FDR<0.05). The AMR diagnostic model based upon RF algorithm demonstrated the highest AUC value (0.904) among various machine learning algorithms. Its AUC values were 0.876 and 0.824 in external datasets of GSE50084 and GSE175718. As for the diagnostic prediction nomogram constructed through integrating five key genes of BCL2A1, CXCL10, FCGR1BP, CD69 & EVI2A from RF model, calibration curve indicated that the predicted outcomes of nomogram approximated actual outcomes. Decision curve indicated that net benefit rate of nomogram was higher than that of extreme curves over a wide range of horizontal axis. The predicted results of CMap suggested that Top 5 compounds were raltegravir, rilmenidine, hydrastine, metyrapone and valproic acid.Conclusions:The nomogram constructed based upon peripheral blood gene expression profiling demonstrates high accuracy and generalizability in the diagnosis of AMR. As predicted by CMap, raltegravir, rilmenidine, hydrastine, metyrapone and valproic acid may be potential therapeutic drugs for AMR.

Fibrosis, which is a manifestation of the physiological response to injury characterized by excessive accumulation of extracellular matrix components, is a ubiquitous outcome of the repair process. However, in cases of repetitive or severe injury, fibrosis may become dysregulated, leading to a pathological state and organ failure. In recent years, a novel form of regulated cell death, referred to as ferroptosis, has been identified as a possible contributor to fibrosis; it is characterized by iron-mediated lipid peroxidation. It has garnered attention due to the growing body of evidence linking ferroptosis and fibrogenesis, which is believed to be driven by underlying inflammation and immune responses. Despite the increasing interest in the relationship between ferroptosis and fibrosis, a comprehensive understanding of the precise role that ferroptosis plays in the formation of fibrotic tissue remains limited. This review seeks to synthesize previous research related to the topic. We categorized the different direct and indirect mechanisms by which ferroptosis may contribute to fibrosis into three categories: (1) iron overload toxicity; (2) ferroptosis-evoked necroinflammation, with a focus on ferroptosis and macrophage interplay; and (3) ferroptosis-associated pro-fibrotic factors and pathways. Furthermore, the review considers the potential implications of these findings and highlights the utilization of ferroptosis-targeted therapies as a promising strategy for mitigating the progression of fibrosis. In conclusion, novel anti-fibrotic treatments targeting ferroptosis could be an effective treatment for fibrosis.

Objective     To explore the clinical effect of hemoperfusion (HP) in cardiopulmonary bypass (CPB) on postoperative inflammation in patients with acute type A aortic dissection (AAD). Methods    Adult patients with AAD who planned to undergo total aortic arch replacement from July 2020 to November 2021 were continuously enrolled in our heart center. Patients were randomly divided into a HP group and a control (C) group. The HP group was treated with disposable HP device (Model: HA380, Zhuhai Jafron Biomedical, China) in CPB during the operation. Results    Finally,  70 patients were included with 59 males and 11 females at an age range of 21-67 years. There were 35 patients in both groups. In this study, 3 patients died within 3 days after surgery, 2 in the HP group and 1 in the C group, and the remaining 67 patients survived to the follow-up end point (30 days after surgery). There was no statistical difference in preoperative baseline data, operative method, CPB time, block time, or other intraoperative data between the two groups. Blood product dosage, intubation time, hospital stays, and hospitalization expenses were similar between the two groups. Intraoperative hemoglobin (82.70±2.31 g/L vs. 82.50±1.75 g/L, P=0.954] and platelet concentration [(77.87±7.99)×109/L vs.(89.17±9.99)×109/L, P=0.384] were not statistically different between the HP group and C group. In the HP group, postoperative (ICU-12 h) interleukin-6 (IL-6) [338.14 (128.00, 450.70) pg/mL vs. 435.75 (180.50, 537.00) pg/mL, P=0.373], IL-8 [35.04 (18.02, 40.35) pg/mL vs. 43.50 (17.70, 59.95) pg/mL, P=0.383], and IL-10 [21.19 (6.46, 23.50) pg/mL vs. 43.41 (6.34, 50.80) pg/mL, P=0.537] were slightly lower than those in the C group, and the difference was not statistically different. The incidences of pulmonary infection (0.00% vs. 11.76%, P=0.042) and liver injury (2.94% vs. 20.58%, P=0.027) in the HP group were significantly lower than those in the C group, and the incidence of other postoperative complications, such as arrhythmia, nervous system complications and urinary system complications, showed no statistical difference between the two groups. Conclusion     HP therapy in CPB is safe, but its effect on reducing postoperative inflammatory factors, postoperative inflammatory reactions and postoperative complications in the patients with AAD is limited, and it may be of application value to some high-risk patients with lung and liver injury.

With the rapid aging of the global population posing a serious problem, frailty, a non-specific state that reflects physiological senescence rather than aging in time, has become more widely addressed by researchers in various medical fields. A high prevalence of frailty is found among kidney transplant (KT) candidates and recipients. Therefore, their frailty has become a research hotspot in the field of transplantation. However, current studies mainly focus on the cross-sectional survey of the incidence of frailty among KT candidates and recipients and the relationship between frailty and transplantation. Research on the pathogenesis and intervention is scattered, and relevant review literature is scarce. Exploring the pathogenesis of frailty in KT candidates and recipients and determining effective intervention measures may reduce waiting list mortality and improve the long-term quality of life of KT recipients. Therefore, this review explains the pathogenesis and intervention measures for frailty in KT candidates and recipients to provide a reference for the formulation of effective intervention strategies.
Humans ; Frailty/epidemiology* ; Risk Factors ; Quality of Life ; Kidney Failure, Chronic ; Kidney Transplantation/adverse effects* ; Cross-Sectional Studies ; Transplant Recipients

Objective To review the experience and early clinical results of eversion carotid endartotectomy (eCEA) in treatment of patients with symptomatic carotid stenosis. Methods eCEA were performed on 32 patients who suffered from the extracranial carotid stonosis. The treatment results were retrospectively reviewed. Results Thirty-two patients were successfully treated with eCEA. The symptom in 17 patients with transient ischemia attach (TIA) admitted to hospital did not recurrence, the other original symptoms of the patients had different degrees of improvement or disappeared. Two patients had TIA during 72 h after surgery, but 24 h repeatedly CTA examination without infarcts oecurring, and recovered after the treatment of small doses of urokinase. Two cases of severe swelling appeared tracheal shift incision, and went smoothly through edema by treatment of tracheal intubatian. In 4 patients headache reliefed in 2-3 d after medical treatment of the dehydration. Seven patients appeared different degree of hoarseness, and got recovery through neurotrophic medication for 1 month. No other serious complication occurred. Follow-up by 6 months, no CTA carotid artery stenosis appeared again. Conclusion eCEA is an effective method to treat symptomatic carotid stenosis.