Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial.

BACKGROUND: A history of SARS-CoV-2 infection has been reported to be associated with an increased risk of postoperative pulmonary complications (PPCs). Even mild PPCs can elevate the rates of early postoperative mortality, intensive care unit (ICU) admission and prolong the length of ICU and/or hospital stays. Consequently, it is crucial to develop perioperative management strategies that can mitigate these increased risks in surgical patients who have recently been infected with SARS-CoV-2. Accumulating evidence suggests that nitric oxide (NO) inhalation might be effective in treating COVID-19. NO functions in COVID-19 by promoting vasodilation, anticoagulation, anti-inflammatory and antiviral effects. Therefore, our study hypothesises that the perioperative use of NO can effectively reduce PPCs in patients with recent SARS-CoV-2 infection. METHOD AND ANALYSIS: A prospective, double-blind, single-centre, randomised controlled trial is proposed. The trial aims to include participants who are planning to undergo surgery with general anaesthesia and have been recently infected with SARS-CoV-2 (within 7 weeks). Stratified allocation of eligible patients will be performed at a 1:1 ratio based on the predicted risk of PPCs using the Assess Respiratory Risk in Surgical Patients in Catalonia risk index and the time interval between infection and surgery.The primary outcome of the study will be the presence of PPCs within the first 7 days following surgery, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm and aspiration pneumonitis. The primary outcome will be reported as counts (percentage) and will be compared using a two-proportion χ2 test. The common effect across all primary components will be estimated using a multiple generalised linear model. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Review Board of Xijing Hospital (KY20232058-F1). The findings, including positive, negative and inconclusive results, will be published in scientific journals with peer-review processes. TRIAL REGISTRATION NUMBER: NCT05721144.

Inhaled nitric oxide and postoperative outcomes in cardiac surgery with cardiopulmonary bypass: A systematic review and meta-analysis.

Cardiac surgeries under cardiopulmonary bypass (CPB) are complex procedures with high incidence of complications, morbidity and mortality. The inhaled nitric oxide (iNO) has been frequently used as an important composite of perioperative management during cardiac surgery under CPB. We conducted a meta-analysis of published randomized clinical trials (RCTs) to assess the effects of iNO on reducing postoperative complications, including the duration of postoperative mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, mortality, hemodynamic improvement (the composite right ventricular failure, low cardiac output syndrome, pulmonary arterial pressure, and vasoactive inotropic score) and myocardial injury biomarker (postoperative troponin I levels). Subgroup analyses were performed to assess the effect of modification and interaction. These included iNO dosage, the timing and duration of iNO therapy, different populations (children and adults), and comparators (other vasodilators and placebo or standard care). A comprehensive search for iNO and cardiac surgery was performed on online databases. Twenty-seven studies were included after removing the duplicates and irrelevant articles. The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality. This may be attributed to the small sample size of the most included studies and heterogeneity in timing, dosage and duration of iNO administration. Well-designed, large-scale, multicenter clinical trials are needed to further explore the effect of iNO in improving postoperative prognosis in cardiovascular surgical patients.

Extraction Of LiCl From Low-Purity Chlorides Through Solid Electrolyte Towards High-Purity Li2 CO3 Production.

Lithium carbonate (Li2 CO3 ) plays a crucial role in advancing state-of-the-art lithium-ion batteries (LIBs) for efficient energy storage. The primary source of lithium is lithium-rich brines, which have complex compositions. Conventional extraction processes from brines involve cumbersome methods that often lead to emissions and/or large volumes of wastewater. To address these environmental challenges, a novel and eco-friendly lithium extraction process under ambient pressure is necessary. In this project, we developed an electrolytic process utilizing a NASICON-type solid-state electrolyte (LATP) to extract lithium chloride from low-purity sources at a temperature of 380 °C. To reduce the melting points of the lithium sources, ZnCl2 was introduced as a fluxing agent. The electrolytic process effectively separated Li+ from other coexisting ions, but resulted in their mixture with Zn2+ . Subsequently, purification and carbonation processes were employed to produce high-purity Li2 CO3 (98.9 %). We also obtained high-purity Zn(OH)2 (>99.9 %) as a value by-product. Despite the formation of color centers that caused the LATP disk to change from white to black during the electrolytic process, it exhibited sufficient ionic conductivity for successful lithium extraction. Our environmentally friendly approach offers a promising pathway for efficient and sustainable lithium extraction, contributing to the advancement of LIB technology for energy storage applications.

Association between postoperative nadir platelet count and postoperative cardiovascular complications following septal myectomy in patients with hypertrophic cardiomyopathy: a retrospective cohort study.

BACKGROUND: Platelet count is associated with cardiovascular risk and mortality in several cardiovascular diseases, but the association of the nadir platelet counts post-septal myectomy with the cardiovascular complication risk in hypertrophic obstructive cardiomyopathy patients remains unclear. METHODS: This retrospective cohort study reviewed all adult patients who underwent septal myectomy at a single tertiary referral center over a 5-year period. Postoperative nadir platelet count was defined as the lowest platelet count in the first 4 postoperative days or until hospital discharge. The composite outcome included cardiovascular death, myocardial infarction, heart failure, malignant arrhythmia, cardiac tamponade, and major bleeding events within 30 days postoperatively. Univariable and multivariable logistic regression and restricted cubic spline models were used to assess the association between postoperative nadir platelet count and the 30-day postoperative cardiovascular complication risk. RESULTS: Among the 113 enrolled patients, 23 (20.4%) developed cardiovascular events within 30 days postoperatively. The incidence of postoperative cardiovascular complications was significantly higher in patients with a nadir platelet count ≤ 99 × 109/L than in those with a nadir platelet count > 99 × 109/L (33.3% vs. 7.1%, crude risk ratio: 4.67, 95% confidence interval: 1.69-12.85, P < 0.001). Multivariable logistic regression revealed that postoperative nadir platelet count was negatively associated with 30-day postoperative cardiovascular complications (adjusted odds ratio: 0.97; 95% confidence interval: 0.95-0.99; P = 0.005) and the association was linear (Pnonlinearity = 0.058) after full adjustment. The association between nadir platelet count and cardiovascular complications within 30 days post-surgery was consistent in all predefined subgroups (Pinteraction > 0.05). CONCLUSION: The postoperative nadir platelet count was significantly associated with the 30-day post-myectomy risk of cardiovascular complications in hypertrophic obstructive cardiomyopathy patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04275544).

Comparison of magnetoimpedance behaviors in meander CoFeNiSiB amorphous ribbon for deformation sensing applications.

In this work, micro-ribbon strips and meanders based on CoFeNiSiB amorphous ribbons were fabricated by using the lithography technique and chemical etching. Flat and curved holders with different radius of curvature were obtained via 3D printing techniques for GMI testing. Longitudinal and transverse GMI (LGMI and TGMI) behaviors of micro-ribbon sensors in different bending directions and degrees were systematically investigated. The results show the LGMI and TGMI effects of micro-ribbon meanders with one turn is most sensitive to bending. It can be used in the development of deformation sensors. In addition, there is a linear range of field in the LGMI and TGMI curves of micro ribbons under different bending conditions, and the sensitivity of micro-ribbon sensors shows no significant change in the range. In particular, the micro-ribbon meanders with three turns are the least sensitive to bending deformation and can be used to develop stable and flexible GMI sensors for wearable electronics devices.

Association Between Loop Diuretics and Mortality in Patients With Cardiac Surgery-Associated Acute Kidney Injury: A Retrospective Propensity Score-Weighted Analysis.

BACKGROUND: Although loop diuretics (LDs) have been widely used in clinical practice, their effect on mortality when administered to patients experiencing cardiac surgery-associated acute kidney injury (CS-AKI) remains unknown. The study aimed to investigate the effectiveness of LD use in patients with CS-AKI. METHODS: Patients who underwent cardiac surgery with AKI were identified from the Medical Information Mart for Intensive Care III. Postoperative LD use in intensive care units (ICUs) was exposure. There were 2 primary outcome measures, the in-hospital mortality and ICU mortality; both were treated as time-to-event data and were analyzed via multivariable Cox proportional hazard models. Inverse probability weighting (IPW) was used to minimize bias. RESULTS: The study enrolled a total of 5478 patients, with a median age of 67 years, among which 2205 (40.3%) were women. The crude in-hospital and ICU mortality rates were significantly lower in the LD use group (525 of 4150 [12.7%] vs 434 of 1328 [32.7%], P < .001; 402 of 4150 [9.69%] vs 333 of 1328 [25.1%], P < .001). Adjusted hazard ratios suggested significant reductions in both in-hospital (hazard ratio [HR], 0.428; 95% confidence interval [CI], 0.374-0.489) and ICU mortality (HR, 0.278; 95% CI, 0.238-0.327). The IPW data showed a similar reduction, in-hospital mortality (HR, 0.434; 95% CI, 0.376-0.502) and ICU mortality (HR, 0.296; 95% CI, 0.251-0.349). Such association may act differently for patients with different fluid balance (P value for interaction < .001). CONCLUSIONS: LD use is associated with lower hospital and ICU mortality in CS-AKI patients in general. Patients under different conditions showed diverse responses toward such treatment indicating that personalized management is needed.

Association of intraoperative cerebral and somatic tissue oxygen saturation with postoperative acute kidney injury in adult patients undergoing multiple valve surgery.

BACKGROUND: The association between tissue oxygenation with postoperative acute kidney injury (AKI) in adult patients undergoing multiple valve surgery has not been specifically studied. METHODS: In this prospective exploratory cohort study, 99 patients were enrolled. The left forehead, the left forearm, the left upper thigh, and the left renal region tissue oxygen saturation using near-infrared spectroscopy were monitored. The association between each threshold and AKI was assessed. The relative and absolute thresholds were < 70%, < 75%, < 80%, < 85%, < 90%, < 95%, and < 100% baseline, and baseline-standard deviation (SD), -1.5 SD, -2 SD, -2.5 SD, and -3 SD. Multivariate logistic regression analysis was adopted to explore the association. RESULTS: AKI occurred in 53 (54%) patients. The absolute value-based SrrO2 thresholds associated with AKI were baseline-3 SD (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.238-17.314; P = 0.023) and baseline-2.5 SD (OR, 2.842; 95% CI, 1.025-7.881; P = 0.045) after adjusting for the potential confounders, those are renal region tissue oxygen saturation of 55% and 60%, but not statistically significant after correcting for multiple testing (corrected P = 0.114 and 0.179, respectively). CONCLUSION: The SrrO2 desaturation, defined as < baseline - 2.5 SD or < baseline - 3 SD, may be associated with AKI. The thresholds need to be verified in future large-scale studies. TRIAL REGISTRATIONS: The study was registered at ClinicalTrials.gov, first trial registration: 26/10/2017, identifier: NCT03323203.

Impact of SARS-CoV-2 infection on postoperative complications of patients undergoing surgery after general outbreak in China: a protocol for multicentre prospective cohort study.

INTRODUCTION: There is currently limited evidence addressing perioperative prognosis of surgical patients during COVID-19 pandemic; especially targeting on the Chinese population since the wave in 2022. Considering a distinct feature from the rest of the world demonstrated and the fast mutation and spread of the virus, evidence most relevant to China is urgently in need. The objective of this study is to seek for supporting evidence via evidence-based risk evaluations for postoperative complications to accumulate experience for coming infection waves. METHODS AND ANALYSIS: This protocol proposes a multicentral, prospective, observational cohort study aiming to explore the link between SARS-CoV-2 infection and postoperative complications among surgical patients under general or regional anaesthesia between 16 January 2023 and 31 December 2023. A retrospective cohort covering the same period in 2019 is extracted for historic reference. Data are extracted from the health information system and anaesthesia information management system. The COVID-19 information is collected via an online survey. Missing values in weight or height will be imputed by each other with age and gender via multiple imputation. Other missing values will not be handled specially. Standard descriptive statistics will be reported followed by statistical modelling. Binomial regression with logit link is used for binary outcome. The time-to-event outcome is analysed using Cox regression with discharge from hospital further treated as a competing state. Hierarchical models will be assessed to account for temporal or central random effects. Temporal trends will be displayed with future expectations. ETHICS AND DISSEMINATION: Ethical approval is obtained from the ethical committee in Xijing Hospital (No. KY20232002-C-1); approvals are expected for each participating institute. Verbal consent will be informed and obtained prior to online survey collection. Personal information remains confidential, and publications will be deidentified. TRIAL REGISTRATION NUMBER: NCT05677815.

Association between marital status and all-cause mortality of patients with metastatic breast cancer: a population-based study.

This study aimed to investigate the association between marital status and the prognosis of patients with metastatic breast cancer (MBC). Data of patients with MBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified into married and unmarried groups. Kaplan-Meier analysis with the log-rank test was conducted to compare breast cancer-specific survival (BCSS) and overall survival (OS) between the groups. Univariable and multivariable Cox proportional models were used to determine whether marital status was independently associated with OS, and the Fine-Gray subdistribution hazard method was performed to determine whether marital status was independently associated with BCSS. In total, 16,513 patients with MBC were identified, including 8949 married (54.19%) and 7564 unmarried (45.81%) patients. The married patients were significantly younger [median age (interquartile range), 59.0 (50.0-68.0) vs. 63.0 (53.0-75.0); p < 0.001] and received more aggressive treatments, such as chemotherapy (p < 0.001) and surgery (p < 0.001), than the unmarried patients. Moreover, married patients had higher 5-year BCSS (42.64% vs. 33.17%, p < 0.0001) and OS (32.22% vs. 21.44%, p < 0.0001) rates. Multivariable analysis revealed that marital status was an independent prognostic factor, and married status was associated with a significant reduction in the risk of breast cancer-specific (sub-hazard ratio, 0.845; 95% confidence interval, 0.804-0.888; p < 0.001) and all-cause (hazard ratio, 0.810; 95% confidence interval, 0.777-0.844; p < 0.001) mortality. Unmarried patients had a 15.5% increased risk of breast cancer-specific mortality and a 19.0% increased risk of overall mortality compared with married patients with MBC. BCSS and OS were superior in married populations compared with unmarried populations in most subgroups. Marital status was an independent prognostic indicator for survival in patients with MBC and was associated with significant survival benefits.

Conditional Cancer-Specific Survival for Inflammatory Breast Cancer: Analysis of SEER, 2010 to 2016.

BACKGROUND: Conditional survival takes into account the time that has elapsed since diagnosis and may have additional informative value. Compared with the static traditional survival evaluation method, conditional survival predictions can be adapted to incorporate the dynamic changes during the disease and provide a more suitable way of identifying time-evolved prognoses. METHODS: Of 3333 patients diagnosed with inflammatory breast cancer between 2010 and 2016 were extracted from the Surveillance, Epidemiology, and End Results database. The trend of the hazard rate over time was represented by the kernel density smoothing curve. The traditional cancer-specific survival (CSS) rate was estimated by the Kaplan-Meier method. Conditional CSS assessment was defined as the probability that a patient will survive y years given the x years who already survived after diagnosis, and the formula is as follows: CS(y)=CSS(x + y)/CSS(x). 3-year cancer-specific survival (CSS3) and 3-year conditional cancer-specific survival (CS3) were estimated. The Fine-Gray proportional subdistribution hazard model was constructed to screen for time-dependent risk factors associated with cancer-specific death. Subsequently, a nomogram was applied to predict a 5-year survival rate based on the number of years already survived. RESULTS: Of 3333 patients, the cancer-specific survival (CSS) rate decreased from 57% in the 4th year to 49% in the 6th year, while the comparable 3-year CS (CS3) rate improved from 65% in the first year to 76% in the third year. Overall, the CS3 rate was superior to actuarial cancer-specific survival, which was also found in subgroup analysis, especially in patients with high-risk characteristics. The Fine-Gray's model indicated that remote organ metastasis (M stage), lymph node metastasis (N stage), and surgery all significantly impacted the prognosis for cancer-specific survival. The Fine-Gray's model-based nomogram was constructed to predict 5-year cancer-specific survival immediately after diagnosis and given survival for 1, 2, 3, and 4 years after diagnosis. CONCLUSION: High-risk patients had a significantly improved cancer-specific survival prognosis after surviving for 1 or more years after diagnosis with inflammatory breast cancer. The probability of reaching 5-year cancer-specific survival following diagnosis improves with each additional year survived. More effective follow-up is required for patients diagnosed at an advanced N stage, remote organ metastasis, or not received surgery. Additionally, a nomogram and web-based calculator may be helpful for patients with inflammatory breast cancer during follow-up counseling (https://ibccondsurv.shinyapps.io/dynnomapp/).

Changes in early postoperative outcomes and complications observed in a single center during the 2022 COVID-19 pandemic wave in China: A single-center ambispective cohort study.

BACKGROUND: Currently, the effect of the 2022 nationwide coronavirus disease 2019 (COVID-19) wave on the perioperative prognosis of surgical patients in China is unclear. Thus, we aimed to explore its influence on postoperative morbidity and mortality in surgical patients. METHODS: An ambispective cohort study was conducted at Xijing Hospital, China. We collected 10-day time-series data from December 29 until January 7 for the 2018-2022 period. The primary outcome was major postoperative complications (Clavien-Dindo class III-V). The association between COVID-19 exposure and postoperative prognosis was explored by comparing consecutive 5-year data at the population level and by comparing patients with and without COVID-19 exposure at the patient level. RESULTS: The entire cohort consisted of 3350 patients (age: 48.5 ± 19.2 years), including 1759 females (52.5%). Overall, 961 (28.7%) underwent emergency surgery, and 553 (16.5%) had COVID-19 exposure (from the 2022 cohort). At the population level, major postoperative complications occurred in 5.9% (42/707), 5.7% (53/935), 5.1% (46/901), 9.4% (11/117), and 22.0% (152/690) patients in the 2018-2022 cohorts, respectively. After adjusting for potential confounding factors, the 2022 cohort (80% patients with COVID-19 history) had a significantly higher postoperative major complication risk than did the 2018 cohort (adjusted risk difference [aRD], 14.9% (95% confidence interval [CI], 11.5-18.4%); adjusted odds ratio [aOR], 8.19 (95% CI, 5.24-12.81)). At the patient level, the incidence of major postoperative complications was significantly greater in patients with (24.6%, 136/553) than that in patients without COVID-19 history (6.0% [168/2797]; aRD, 17.8% [95% CI, 13.6-22.1%]; aOR, 7.89 [95% CI, 5.76-10.83]). Secondary outcomes of postoperative pulmonary complications were consistent with primary findings. These findings were verified through sensitivity analyses using time-series data projections and propensity score matching. CONCLUSION: Based on a single-center observation, patients with recent COVID-19 exposure were likely to have a high incidence of major postoperative complications. REGISTRATION: NCT05677815 at https://clinicaltrials.gov/ .

Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is a main subtype of kidney cancers. Cuproptosis and ferroptosis are correlated with immune infiltration and prognosis in tumors. However, the role of Cuproptosis-related Ferroptosis genes (CRFGs) in KIRC has rarely been fully understood. Therefore, we constructed a prognostic signature based on different expression of CRFGs in KIRC. All raw data of this study were extracted from public TCGA datasets. Cuproptosis and Ferroptosis genes were collected from the previous research. Finally, a total of 36 significantly different CRFGs were identified from TCGA-KIRC cohort. Six-gene signature (TRIB3, SLC2A3, PML, CD44, CDKN2A and MIOX) was identified by LASSO Cox regression based on the significantly different CRFGs. The CRFGs signature was correlated with worse overall survival and the AUC was 0.750. Functional enrichment indicated that CRFGs were mainly enriched in metabolism, drug resistance, tumor immunity pathways. Besides, the IC50 and immune checkpoint differentially expressed between different groups. The proposed 6-CRFGs signature is a promising biomarker to predict clinical outcomes and therapeutic responses for KIRC patient.

Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

OBJECTIVE: The combination of stereotactic body radiation therapy (SBRT) and immune checkpoint inhibitors (ICIs) is actively being explored in advanced non-small-cell lung cancer (NSCLC) patients. However, little is known about the optimal fractionation and radiotherapy target lesions in this scenario. This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs. METHODS: The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec. 2015 to Sep. 2021. Patients were grouped according to radiation sites. Progression-free survival (PFS) and overall survival (OS) were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank (Mantel-Cox) test. RESULTS: A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study. Radiation sites included lung lesions (lung group, n=43), bone metastases (bone group, n=24), and brain metastases (brain group, n=57). Compared with the brain group, the mean PFS (mPFS) in the lung group was significantly prolonged by 13.3 months (8.5 months vs. 21.8 months, HR=0.51, 95%CI: 0.28-0.92, P=0.0195), and that in the bone group prolonged by 9.5 months with a 43% reduction in the risk of disease progression (8.5 months vs. 18.0 months, HR=0.57, 95%CI: 0.29-1.13, P=0.1095). The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group. The mean OS (mOS) in the lung and bone groups was longer than that of the brain group, and the risk of death decreased by up to 60% in the lung and bone groups as compared with that of the brain group. When SBRT was concurrently given with ICIs, the mPFS in the lung and brain groups were significantly longer than that of the bone group (29.6 months vs. 16.5 months vs. 12.1 months). When SBRT with 8-12 Gy per fraction was combined with ICIs, the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups (25.4 months vs. 15.2 months vs. 12.0 months). Among patients receiving SBRT on lung lesions and brain metastases, the mPFS in the concurrent group was longer than that of the SBRT→ICIs group (29.6 months vs. 11.4 months, P=0.0003 and 12.1 months vs. 8.9 months, P=0.2559). Among patients receiving SBRT with <8 Gy and 8-12 Gy per fraction, the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group (20.1 months vs. 5.3 months, P=0.0033 and 24.0 months vs. 13.4 months, P=0.1311). The disease control rates of the lung, bone, and brain groups were 90.7%, 83.3%, and 70.1%, respectively. CONCLUSION: The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients. This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens. Dose fractionation regimens of 8-12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Perioperative parameters-based prediction model for acute kidney injury in Chinese population following valvular surgery.

Background: Acute kidney injury (AKI) is a relevant complication after cardiac surgery and is associated with significant morbidity and mortality. Existing risk prediction tools have certain limitations and perform poorly in the Chinese population. We aimed to develop prediction models for AKI after valvular cardiac surgery in the Chinese population. Methods: Models were developed from a retrospective cohort of patients undergoing valve surgery from December 2013 to November 2018. Three models were developed to predict all-stage, or moderate to severe AKI, as diagnosed according to Kidney Disease: Improving Global Outcomes (KDIGO) based on patient characteristics and perioperative variables. Models were developed based on lasso logistics regression (LLR), random forest (RF), and extreme gradient boosting (XGboost). The accuracy was compared among three models and against the previously published reference AKICS score. Results: A total of 3,392 patients (mean [SD] age, 50.1 [11.3] years; 1787 [52.7%] male) were identified during the study period. The development of AKI was recorded in 50.5% of patients undergoing valve surgery. In the internal validation testing set, the LLR model marginally improved discrimination (C statistic, 0.7; 95% CI, 0.66-0.73) compared with two machine learning models, RF (C statistic, 0.69; 95% CI, 0.65-0.72) and XGBoost (C statistic, 0.66; 95% CI, 0.63-0.70). A better calibration was also found in the LLR, with a greater net benefit, especially for the higher probabilities as indicated in the decision curve analysis. All three newly developed models outperformed the reference AKICS score. Conclusion: Among the Chinese population undergoing CPB-assisted valvular cardiac surgery, prediction models based on perioperative variables were developed. The LLR model demonstrated the best predictive performance was selected for predicting all-stage AKI after surgery. Clinical trial registration: Trial registration: Clinicaltrials.gov, NCT04237636.

BMMSC-derived Exosomes Attenuate Cardiopulmonary Bypass-related Acute Lung Injury by Reducing Inflammatory Response and Oxidative Stress.

BACKGROUND: Acute lung injury (ALI), which is characterized by inflammation and oxidative stress, is a common complication after cardiopulmonary bypass (CPB). Exosomes from bone marrow mesenchymal stem cells (BMMSC-Exo) have recently been identified as promising treatments for ALI. However, the effects of BMMSC-Exo on inflammation and oxidative stress in CPB-related ALI remain unclear. OBJECTIVE: We aim to evaluate the effects of BMMSC-Exo on post-CPB ALI and explore their potential mechanisms. METHODS: We randomly divided rats into three groups: sham, ALI, and ALI+BMMSC-Exo groups. Histological changes were evaluated by lung histo-pathology and bronchoalveolar lavage fluid (BALF). ELISA assay was used to determine inflammatory cytokine levels and oxidative stress. RESULTS AND DISCUSSION: BMMSC-Exo attenuated histological changes (including the invasion of inflammatory cells), reduced the wet/dry (W/D) weight ratio, and downregulated inflammatory cytokine levels, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1ß. BMMSC-Exo also alleviated oxidative stress. In vitro, we further administered lipopolysaccharide (LPS) to alveolar macrophages (AMs) to mimic the pathological changes of ALI and found that BMMSC-Exo suppressed reactive oxygen species (ROS) production and downregulated the levels of inflammatory cytokines. Mechanistically, BMMSC-Exo inhibited the phosphorylation of nuclear factor-κB (NF-κB), the nuclear translocation of p65, also facilitated the phosphorylation of Akt and the nuclear translocation of Nrf2, while upregulating the expression of HO-1. CONCLUSION: In summary, we indicate that BMMSC-Exo reduces CPB-related ALI by alleviating inflammation and oxidative stress. The underlying mechanism may involve the NF-κB p65 and Akt/Nrf2/HO-1 signaling pathways.

Exosome from BMMSC Attenuates Cardiopulmonary Bypass-Induced Acute Lung Injury Via YAP/ß-Catenin Pathway: Downregulation of Pyroptosis.

Acute lung injury (ALI) accompanied with systemic inflammatory response is an important complication after cardiopulmonary bypass (CPB). Pyroptosis, which is induced by the secretion of inflammatory factors, has been implicated in ALI. However, recent studies have suggested that bone marrow mesenchymal stem cell-derived exosomes (BMMSC-Exo) can ameliorate ALI, but the mechanism is poorly understood. Therefore, we aim to examine the effects of BMMSC-Exo in CPB-induced ALI, and its underlying mechanism. CPB rat models (male Sprague-Dawley rats) were administered BMMSC-Exo intravenously before induction of ALI. Lung tissue, bronchoalveolar lavage fluid (BALF), and alveolar macrophage (AM) were collected after the treatments for further analysis, and rat AM NR8383 cells were used for in vitro study. HE staining was performed to detect macrophage infiltration. Western blot was used to detect related proteins expression. And ELISA assay was performed to investigate secretion of inflammatory factors. These results showed that BMMSC-Exo treatment ameliorated macrophage infiltration and oxidative stress, and downregulated expression of pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and GSDMD-N, in the lung tissue and AM, as well as decreased the secretion of IL-18 and IL-1ß in BALF. Moreover, BMMSC-Exo activated YAP/ß-catenin signaling pathway. Overall, these findings of this study indicated that BMMSC-Exo suppressed CPB-induced pyroptosis in ALI by activating YAP/ß-catenin axis, which could be a novel strategy for lung protection during CPB.

Neuroprotective effect of remote ischemic preconditioning in patients undergoing cardiac surgery: A randomized controlled trial.

Background: The neuroprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing elective cardiopulmonary bypass (CPB)-assisted coronary artery bypass graft (CABG) or valvular cardiac surgery remains unclear. Methods: A randomized, double-blind, placebo-controlled superior clinical trial was conducted in patients undergoing elective on-pump coronary artery bypass surgery or valve surgery. Before anesthesia induction, patients were randomly assigned to RIPC (three 5-min cycles of inflation and deflation of blood pressure cuff on the upper limb) or the control group. The primary endpoint was the changes in S-100 calcium-binding protein ß (S100-ß) levels at 6 h postoperatively. Secondary endpoints included changes in Neuron-specific enolase (NSE), Mini-mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) levels. Results: A total of 120 patients [mean age, 48.7 years; 36 women (34.3%)] were randomized at three cardiac surgery centers in China. One hundred and five patients were included in the modified intent-to-treat analysis (52 in the RIPC group and 53 in the control group). The primary result demonstrated that at 6 h after surgery, S100-ß levels were lower in the RIPC group than in the control group (50.75; 95% confidence interval, 67.08 to 64.40 pg/ml vs. 70.48; 95% CI, 56.84 to 84.10 pg/ml, P = 0.036). Compared to the control group, the concentrations of S100-ß at 24 h and 72 h and the concentration of NSE at 6 h, 24 h, and 72 h postoperatively were significantly lower in the RIPC group. However, neither the MMSE nor the MoCA revealed significant between-group differences in postoperative cognitive performance at 7 days, 3 months, and 6 months after surgery. Conclusion: In patients undergoing CPB-assisted cardiac surgery, RIPC attenuated brain damage as indicated with the decreased release of brain damage biomarker S100-ß and NSE. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT01231789].

Dysregulated glucuronic acid metabolism exacerbates hepatocellular carcinoma progression and metastasis through the TGFß signalling pathway.

BACKGROUND: Glucuronic acid metabolism participates in cellular detoxification, extracellular matrix remodeling and cell adhesion and migration. Here, we aimed to explore the crosstalk between dysregulated glucuronic acid metabolism and crucial metastatic signalling in glutathione S-transferase zeta 1 (GSTZ1)-deficient hepatocellular carcinoma (HCC). METHODS: Transwell, HCC xenograft and Gstz1-/- mouse models were used to examine the role of GSTZ1 in HCC metastasis. Non-targeted and targeted metabolomics and global transcriptomic analyses were performed to screen significantly altered metabolic and signalling pathways in GSTZ1 overexpressing hepatoma cells. Further, RNA-binding protein immunoprecipitation, Biotin-RNA pull-down, mRNA decay assays and luciferase reporter assays were used to explore the interaction between RNA and RNA-binding proteins. RESULTS: GSTZ1 was universally silenced in both human and murine HCC cells, and its deficiency contributed to HCC metastasis in vitro and in vivo. UDP-glucose 6-dehydrogenase (UGDH)-mediated UDP-glucuronic acid (UDP-GlcUA) accumulation promoted hepatoma cell migration upon GSTZ1 loss. UDP-GlcUA stabilized TGFßR1 mRNA by enhancing its binding to polypyrimidine tract binding protein 3, contributing to the activation of TGFß/Smad signalling. UGDH or TGFßR1 blockade impaired HCC metastasis. In addition, UGDH up-regulation and UDP-GlcUA accumulation correlated with increased metastatic potential and decreased patient survival in GSTZ1-deficient HCC. CONCLUSIONS: GSTZ1 deficiency and subsequent up-regulation of the glucuronic acid metabolic pathway promotes HCC metastasis by increasing the stability of TGFßR1 mRNA and activating TGFß/Smad signalling. UGDH and a key metabolite, UDP-GlcUA, may serve as prognostic markers. Targeting UGDH might be a promising strategy for HCC therapy.