Disulfidptosis: A new type of cell death.

Disulfidptosis is a novel form of cell death that is distinguishable from established programmed cell death pathways such as apoptosis, pyroptosis, autophagy, ferroptosis, and oxeiptosis. This process is characterized by the rapid depletion of nicotinamide adenine dinucleotide phosphate (NADPH) in cells and high expression of solute carrier family 7 member 11 (SLC7A11) during glucose starvation, resulting in abnormal cystine accumulation, which subsequently induces andabnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. This review aimed to summarize the underlying mechanisms, influencing factors, comparisons with traditional cell death pathways, associations with related diseases, application prospects, and future research directions related to disulfidptosis.

Monocytes to lymphocytes multiplying platelets ratio as an early indicator of acute kidney injury in cardiac surgery with cardiopulmonary bypass: a retrospective analysis.

OBJECTIVE: The monocyte-to-lymphocyte multiplying platelets ratio (MLPR) is a novel systemic inflammatory marker, deriving from the monocyte-to-lymphocyte ratio (MLR). However, the link between MLPR and acute kidney injury following cardiac surgery (CSA-AKI) with cardiopulmonary bypass (CPB) has not been investigated yet. We comprehensively explored the potential linear and nonlinear relationship between MLPR or MLR and CSA-AKI. METHODS: Data of patients who underwent cardiac surgery with CPB between December 2018 and April 2021 were retrospectively collected at Fuwai Hospital, Beijing, China. MLPR was defined as monocyte count (×109/L) × 1000/(lymphocyte count (×109/L) × platelets (×109/L)). MLR was defined as monocyte count (×109/L)/lymphocyte count (×109/L). Logistic regression and restricted cubic spline (RCS) were used for linear and nonlinear analysis. The primary outcome was postoperative AKI within 48 h of after cardiac surgery. RESULTS: Of the 2420 patients screened, 2387 eligible patients were enrolled in the final analysis; the mean age was 54.7 years, and 1501 [62.9%] were men. The incidence of AKI was 25.8%. Logistic regression showed that MLPR (odds ratio [OR] = 1.31, 95% confidence interval [CI]: 1.16-1.48, p < .001) and MLR (OR = 3.06, 95% CI: 1.29-7.29, p = .012) were independent risk factors for AKI. Moreover, in the RCS model with adjustment for age (median: 56), female sex, and history of diabetes, a significant statistical difference was detected between preoperative MLPR, MLR, and AKI (p for non-linearity <.001). The subgroup analyses revealed similar results. CONCLUSIONS: The study revealed a nonlinear relationship between MLPR and MLR with AKI. MLPR exhibited a J-shaped curve, and MLR showed a favorable S-shaped curve in relation to AKI. Particularly, MLPR emerges as a promising clinical composite index for early CSA-AKI prediction. These findings emphasize the significance of MLPR as a valuable tool in clinical practice for timely identification and management of CSA-AKI.

Hybrid feature selection in a machine learning predictive model for perioperative myocardial injury in noncoronary cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Perioperative myocardial injury (PMI) is associated with increased mobility and mortality after noncoronary cardiac surgery. However, limited studies have developed a predictive model for PMI. Therefore, we used hybrid feature selection (FS) methods to establish a predictive model for PMI in noncoronary cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This was a single-center retrospective study conducted at the Fuwai Hospital in China. Patients aged 18-70 years who underwent elective noncoronary surgery with CPB at our institution from December 2018 to April 2021 were enrolled. The primary outcome was PMI, defined as the postoperative cardiac troponin I (cTnI) levels exceeding 220 times of upper reference limit (URL). Statistical analyses were conducted by Python (Python Software Foundation, version 3.9.7 and integrated development environment Jupyter Notebook 1.1.0) and SPSS software version 26.0 (IBM Corp., Armonk, New York, USA). RESULTS: A total of 1130 patients were eventually eligible for this study. The incidence of PMI was 20.3% (229/1130) in the overall patients, 20.6% (163/791) in the training dataset, and 19.5% (66/339) in the testing dataset. The logistic regression model performed the best AUC of 0.6893 (95 CI%: 0.6371-0.7382) by the traditional selection method, and the random forest model performed the best AUC of 0.6937 (95 CI%: 0.6416-0.7423) by the union of Wrapper and Embedded method, and the CatBoost model performed the best AUC of 0.6828 (95 CI%: 0.6304-0.7320) by the union of Embedded and forward logistic regression technique, and the Naïve Bayes model achieved the best AUC with 0.7254 (95 CI%: 0.6746-0.7723) by forwarding logistic regression method. Moreover, the decision tree, KNeighborsClassifier, and support vector machine models performed the worse AUC in all selection forms. Furthermore, the SHapley Additive exPlanations plot showed that prolonged CPB, aortic clamp time, and preoperative low platelets count were strongly related to the PMI risk. CONCLUSIONS: In total, four category feature selection methods were utilized, comprising five individual selection techniques and 15 combined methods. Notably, the combination of logistic regression and embedded methods demonstrated outstanding performance in predicting PMI risk. We also concluded that the machine learning model, including random forest, catboost, and Naive Bayes, were suitable candidates for establishing PMI predictive model. Nevertheless, additional investigation and validation are imperative for substantiating these finding.

The effects of chemotherapy, primary tumor location and histological subtype on the survival of stage III colon cancer patients.

OBJECTIVE: Colon cancer (CC) is one of the most common cancers worldwide and has a poor prognosis. Surgery followed by adjuvant chemotherapy is the standard treatment strategy for stage III CC patients. Primary tumor location (PTL) is an important factor for the long-term survival of CC. However, the difference in the prognosis between the histological subtypes of mucinous adenocarcinoma (MAC) and nonspecific adenocarcinoma (AC) in stage III CC patients is unclear. The correlation of chemotherapy, PTL and histological subtype with the overall survival (OS) of stage III CC patients has not yet been explored. METHODS: Patients diagnosed with stage III CC from 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The clinicopathological features and OS were analyzed according to the chemotherapy, PTL and histological subtype. RESULTS: A total of 28,765 eligible stage III CC patients were enrolled in this study. The results showed that chemotherapy, left-sided CC (LCC) and AC were favorable prognostic factors for OS. Right-sided CC (RCC) had worse OS than LCC regardless of chemotherapy. MAC had worse OS than AC in the patients with chemotherapy, but the survival benefits disappeared in the patients without chemotherapy. Additionally, in LCC, MAC had worse OS than AC regardless of chemotherapy. However, in RCC, MAC had worse OS than AC in patients with chemotherapy but had similar OS to AC in patients without chemotherapy. In the AC group, RCC had worse OS than LCC regardless of chemotherapy. In the MAC group, RCC had comparable OS to LCC regardless of chemotherapy. Four subgroups, i.e., RCC/MAC, RCC/AC, LCC/MAC and LCC/AC, all showed benefits from chemotherapy. Among them, LCC/AC had the best OS, and RCC/MAC had the worst OS compared with the other three subgroups. CONCLUSION: The prognosis of MAC is worse than that of AC in stage III CC. LCC/AC has the best OS, while RCC/MAC has the worst OS but still benefits from chemotherapy. The impact of chemotherapy on survival is greater than that of histological subtype, but the impact of histological subtype on survival is similar to that of PTL.

Dietary cholesterol consumption and incidence of type 2 diabetes mellitus: A dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND AIM: The purpose of this meta-analysis was to evaluate the dose-response relationship between dietary cholesterol (DC) consumption and the incidence of type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Prospective studies with the endpoint of T2DM were included. The Random-effect model weighted by inverse variance was used. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics. Restricted cubic splines regression models were used to estimate the dose-response relationship. 11 prospective studies comprising of 355 230 subjects were included. Compared to lowest DC consumption, highest DC consumption was associated with an increased risk of T2DM (RR 1.15, 95% CI 1.03 to 1.28, P = 0.012; chi-squared = 31.41, I-squared 58.6%, P heterogeneity = 0.003). Subgroup analyses have shown that this positive association was more evident in western countries than in eastern countries (RR 1.19, 95% CI 1.06 to 1.36 VS 1.34, 95% CI 0.84 to 1.29; P subgroup difference = 0.02). For 100 mg/d increment in DC intake, the pooled RR was 1.05, (95% CI 1.04 to 1.07, Plinearity = 0.000, Pnonlinearity = 0.02), 1.06 (95% CI 1.04 to 1.07, Plinearity=0.000), and 1.01 (95% CI 0.98 to 1.05, Plinearity = 0.525) for the incidence of T2DM, in western and eastern countries, respectively. CONCLUSIONS: Our study suggests that there is a positive dose-response association between DC consumption and the incidence of T2DM, especially in western countries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020216318.

Hypertensive status is associated with renoprotection by remote ischemic conditioning for acute myocardial infarction-a meta-regression and trial sequential analysis of randomized clinical trials.

The potential modifiable factors for remote ischemic conditioning (RIC) in reducing contrast-associated acute kidney injury (CA-AKI) in patients with acute myocardial infarction (AMI) have not been investigated. The aim of this meta-regression was to address these issues.We searched Pubmed, Embase and the Cochrane Library database for published randomized controlled trials (RCTs) with registration number CRD42020155532. Nine RCTs comprising of 1540 subjects were included in our meta-analysis. Compared with control group, RIC was associated with reduced incidence of CA-AKI [(9 studies, 1540 subjects, relative risk (RR) 0.51, 95% confidence intervals (CI) 0.35 to 0.76, p = 0.000, I2 = 52%, p for heterogeneity 0.04)] and major adverse cardiovascular events (MACE) (5 studies, 1078 subjects, RR 0.52, 95% CI 0.38 to 0.73, p = 0.000, I2 = 9%, p for heterogeneity 0.36) for AMI. In addition, both meta-regression and subgroup analyses have shown that RIC was more effective in the hypertensive patients in reducing CA-AKI for AMI (regression coefficient = -0.05, p = 0.021; for subgroup with more hypertensive patients: RR 0.36, 95% CI 0.25 to 0.52 vs the one with less hypertensive patients: RR 0.72, 95% CI (0.40 to 1.30, p for subgroup difference 0.008). Subsequent trial sequential analysis confirmed the effect of RIC in both CA-AKI and MACE. RIC is an effective strategy in reducing CA-AKI and MACE in patients with AMI, especially for patients with hypertension.

Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery: The OPTIMAL Randomized Clinical Trial.

Importance: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery. Objective: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to April 21, 2021; final follow-up was on May 21, 2021. Interventions: Participants received either a high-dose tranexamic acid regimen comprising a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime (n = 1525) or a low-dose regimen comprising a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime (n = 1506). Main Outcomes and Measures: The primary efficacy end point was the rate of allogeneic red blood cell transfusion after start of operation (superiority hypothesis), and the primary safety end point was a composite of the 30-day postoperative rate of mortality, seizure, kidney dysfunction (stage 2 or 3 Kidney Disease: Improving Global Outcomes [KDIGO] criteria), and thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism) (noninferiority hypothesis with a margin of 5%). There were 15 secondary end points, including the individual components of the primary safety end point. Results: Among 3079 patients who were randomized to treatment groups (mean age, 52.8 years; 38.1% women), 3031 (98.4%) completed the trial. Allogeneic red blood cell transfusion occurred in 333 of 1525 patients (21.8%) in the high-dose group and 391 of 1506 patients (26.0%) in the low-dose group (risk difference [RD], -4.1% [1-sided 97.55% CI, -∞ to -1.1%]; relative risk, 0.84 [1-sided 97.55% CI, -∞ to 0.96; P = .004]). The composite of postoperative seizure, thrombotic events, kidney dysfunction, and death occurred in 265 patients in the high-dose group (17.6%) and 249 patients in the low-dose group (16.8%) (RD, 0.8%; 1-sided 97.55% CI, -∞ to 3.9%; P = .003 for noninferiority). Fourteen of the 15 prespecified secondary end points were not significantly different between groups, including seizure, which occurred in 15 patients (1.0%) in the high-dose group and 6 patients (0.4%) in the low-dose group (RD, 0.6%; 95% CI, -0.0% to 1.2%; P = .05). Conclusions and Relevance: Among patients who underwent cardiac surgery with cardiopulmonary bypass, high-dose compared with low-dose tranexamic acid infusion resulted in a modest statistically significant reduction in the proportion of patients who received allogeneic red blood cell transfusion and met criteria for noninferiority with respect to a composite primary safety end point consisting of 30-day mortality, seizure, kidney dysfunction, and thrombotic events. Trial Registration: ClinicalTrials.gov Identifier: NCT03782350.

The effect of marital and insurance status on the survival of elderly patients with stage M1b colon cancer: a SEER-based study.

BACKGROUND: Colon cancer is largely implicated in elderly patients (age ≥ 60 years). The prognosis of patients diagnosed with the M1b stage is vastly poor. Marital and insurance status has been considered important prognostic factors in various cancer types. However, how these factors influence elderly patients with stage M1b colon cancer remains to be explored. This study aims to uncover the role of marital and insurance status in the survival of elderly patients with stage M1b colon cancer. METHODS: We retrieved data for patients diagnosed with stage M1b colon cancer between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis of the clinicopathological features, overall survival (OS), and cancer-specific survival (CSS) was based on the marital and insurance status, respectively. RESULTS: In sum, 5709 stage M1b colon cancer patients with complete information from SEER were enrolled for analysis. The OS and CSS of the Non-married group were poorer compared to that of the Married group. The OS and CSS of the Uninsured group were poorer than both of the Insured group and Medicaid group. However, OS was comparable between Uninsured group and Medicaid groups. The findings allude that marital and insurance status potentially impact the long-term survival of elderly patients with M1b colon cancer. The subgroup survival analyses revealed the lowest risk for death among the Insured Married group based on the comparison of the OS and CSS across all other groups. Moreover, Univariate and multivariate analyses revealed race, marital status, surgery, and chemotherapy as independent predictors for OS, whereas insurance status, surgery,and chemotherapy were independent predictors for CSS in elderly patients with M1b colon cancer. CONCLUSION: The marital and insurance status greatly impact the survival of elderly patients with M1b colon cancer. Therefore, it is imperative to provide more support to this vulnerable patient group who are lonely and uninsured, particularly in the psychological and health insurance aspect.

Incidence and Risk Factors for Silent Brain Infarction After On-Pump Cardiac Surgery: A Meta-analysis and Meta-regression of 29 Prospective Cohort Studies.

BACKGROUND: Silent brain infarction (SBI) happens at a considerable rate after on-pump cardiac surgery. Though termed silent, SBI is related to unfavorable clinical outcomes including higher incidence of future stroke and neurocognitive impairment in the general population. The risk factors of SBI have not been fully identified in both individual studies and several meta-analyses addressing the topic. In this meta-analysis, we aimed to conduct meta-regression analysis for the first time to explore risk factors for SBI after on-pump cardiac surgery. METHODS: This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Medline, Embase, Central, Web of Science, and Wiley databases were searched for relevant studies. Preoperative patient baseline characteristics and intraoperative surgical parameters were extracted from included studies. For meta-regression, a P value of less than 0.1 was considered statistically significant in both univariable and multivariable analyses. RESULTS: Twenty-nine studies with 1478 patients were included in this meta-analysis. The summarized SBI rate after on-pump cardiac surgery was 37% (95% CI 0.27-0.47, P < 0.0001). Heterogeneity between studies was significant (I2 = 94.9%, P < 0.0001). In multivariable meta-regression, we found that age (coefficient 0.014, 95% CI 0.001-0.029, P = 0.043), diabetes (coefficient 0.006, 95% CI - 0.001 to 0.013, P = 0.075), and proportion of CABG (coefficient - 0.001, 95% CI - 0.003 to 0.0003, P = 0.096) were significantly associated with SBI incidence. CONCLUSION: From the meta-regression, we concluded that advanced age and diabetes were related to increased SBI incidence after on-pump cardiac surgery, while CABG procedure alone was associated with less SBI onset. Studies with more accurate diagnoses of SBI are required to add more conclusive evidence to the field.

Outcome impact of different tranexamic acid regimens in cardiac surgery with cardiopulmonary bypass (OPTIMAL): Rationale, design, and study protocol of a multicenter randomized controlled trial.

Tranexamic acid (TxA) reduces perioperative blood transfusion in cardiac surgery; however, the optimal dose of TxA remains unknown. METHODS AND RESULTS: This large-scale, double-blind, randomized controlled trial with a 1-year follow-up enrolls patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients are randomly assigned 1:1 into either the high-dose TxA group (intravenous bolus [30 mg/kg] after anesthesia followed by intravenous maintenance [16 mg/kg/h] throughout the operation, and a pump prime dose of 2 mg/kg) or the low-dose TxA group (intravenous bolus and maintenance are 10 mg/kg and 2 mg/kg/h, respectively, and a pump prime dose of 1 mg/kg). The primary efficacy end point is the rate of perioperative allogeneic red blood cell (RBC) transfusion defined as the number (%) of patients who will receive at least 1 RBC unit from operation day to discharge. The primary safety end point is the 30-day rate of the composite of perioperative seizures, renal dysfunction, myocardial infarction, ischemic stroke, deep vein thrombosis, pulmonary embolism, and all-cause mortality. The secondary end points are perioperative allogeneic RBC transfusion volume, the non-RBC blood transfusion rate, postoperative bleeding, reoperation rate, mechanical ventilation duration, intensive care unit stay, hospital length of stay, total hospitalization cost, each component of composite primary safety end point, and the 6-month/1-year follow-up mortality and morbidity. We estimated a sample size of 3,008 participants. CONCLUSIONS: The study is designed to identify a TxA dose with maximal efficacy and minimal complications. We hypothesize that the high dose has superior efficacy and noninferior safety to the low dose.

Pre-procedural elevated cardiac troponin predict risk of long-term all-cause mortality after transcatheter aortic valve replacement: a meta-analysis of prospective studies.

Background: The purpose of this meta-analysis was to evaluate the relationship between elevated cardiac troponin pre-transcatheter aortic valve replacement (TAVR) and long-term all-cause mortality.Methods: Prospective studies with the endpoint of all-cause mortality were included. We primarily used the fixed-effect model weighted by inverse variance. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics.Results: Seven prospective studies comprising of 3049 subjects were included in our meta-analysis. Pre-procedural elevated cardiac troponin was associated with increased risk of long-term mortality post TAVR [hazard ratio (HR) 2.25, 95% CI 1.83-2.78, p = 0.000, I2 = 30.3%, p for heterogeneity 0.197]. In addition, subgroup analyses have shown that the group with an younger age (<82 y) seemed to have a higher risk of all-cause mortality than the group with older age (≥82 y) [HR 4.08 (2.41 to 6.89) VS 2.01 (1.60 to 2.53), p = 0.016 for subgroup difference].Conclusions: Pre-procedural elevated cardiac troponin was associated with increased long-term all-cause mortality in patients undergoing TAVR.

Mir-455-3p-1 represses FGF7 expression to inhibit pulmonary arterial hypertension through inhibiting the RAS/ERK signaling pathway.

OBJECTIVE: To analyze the effects of miR-455-3p-1 and its possible mechanisms in pulmonary arterial hypertension (PAH). METHODS: A microarray assay was used to examine the expressed genes between normal and PAH. The expressed genes in PAH was assessed by qRT-PCR. The targeted interaction between miRNAs and FGF7 was confirmed using a dual luciferase reporter assay. A CCK-8 assay and cell count were used to analyze the pulmonary artery smooth muscle cells (PASMCs) activity and proliferation level, respectively. Apoptotic PASMCs were detected by flow cytometry. In addition, the mRNA and protein expression levels of RAS/ERK signaling pathway were determined by qRT-PCR and a Western blot assay, respectively. A PAH rat model was used to identify the effects of miR-455-3p-1 in vivo. RESULTS: FGF7 was upregulated in PAH. MiR-455-3p-1 was downregulated in PAH. MiR-455-3p-1 targeted FGF7. MiR-455-3p-1 decreased the expression of FGF7. Moreover, the effect of FGF7 on PASMCs was suppressed by miR-455-3p-1. MiR-455-3p-1 upregulation was associated with reduced mRNA and protein levels of core RAS/ERK signal genes, suggesting the inhibition of the RAS/ERK pathway. Furthermore, miR-455-3p-1 upregulation improved the RVSP, mPAP, ratio of RV/LV + S, CO and RV function of PAH rat model in vivo. CONCLUSION: Our findings illustrate a role for miR-455-3p-1 in modulating FGF7-RAS/ERK signaling and suggest that an agomir of miR-455-3p-1 could inhibit the proliferation of PASMCs and mitigate PAH in vivo.

Cardiac troponins predict adverse clinical outcomes in stable coronary artery disease: a dose-response meta-analysis of prospective studies.

Background: Predictive value of cardiac tropnins (cTns) in stable coronary artery disease (SCAD) has not been fully investigated. Methods: We performed a meta-analysis to evaluate the dose-response relationship between serum detectable/rising cTns and adverse clinical outcomes, including all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), heart failure (HF) or major adverse cardiovascular events (MACEs) in SCAD. Results: Sixteen studies involved 34,854 subjects were included. Compared with patients with negative/undetectable cTns, those with rising/detectable cTns were associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs [the hazard ratio (HR) was 1.83 (95% confidence interval (CI) 1.61-2.08), 2.11 (1.80-2.48), 1.43 (1.26-1.62), 2.36 (1.97-2.83) and 1.99 (1.57-2.53), respectively]. Dose-response analysis have revealed that per 1-SD increment of cTnT was associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs [the HR was 1.78 (1.20-2.63), 1.62 (1.41-1.85), 1.26 (1.12-1.42), 1.78 (1.17-2.69) and 1.26 (1.00-1.59), respectively]. Conclusion: Rising/detectable cTns was associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs in SCAD in a dose-response manner.

[Expression of ZNF207 in hepatocellular carcinoma and its significance].

OBJECTIVE: To investigate the expression of zinc finger protein 207 (ZNF207) in hepatocellular carcinoma (HCC) tissues, and analyze the correlation of ZNF207 with clinicopathological factors and HCC patients' survival.
 Methods: Real-time PCR was used to detect ZNF207 mRNA expression in 10 paired fresh HCC and adjacent non-tumor liver tissue samples. Immunohistochemical (IHC) analysis was used to detect ZNF207 protein expression in 135 cases of randomly selected paraffin-embedded HCC tissues. The correlation of ZNF207 expression with clinicopathological factors and survival of HCC was analyzed.
 Results: The ZNF207 mRNA expression level in HCC was significantly higher than that in the adjacent non-tumor liver tissue (P<0.01). IHC results showed that ZNF207 protein level was elevated in HCC tissues and ZNF207 expression was correlated with cirrhosis, nodule number, tumor capsule, vascular invasion, and TNM stage (P<0.05). Survival analysis showed that patients with high ZNF207 expression had poorer overall survival (OS) and disease-free survival (DFS) than those with the low ZNF207 expression (P<0.01), and ZNF207 was an independent risk factor for OS and DFS of HCC (P<0.05).
 Conclusion: ZNF207 expression is elevated in HCC and associated with adverse clinicopathological factors, indicating poor prognosis for HCC.

Cytokines increase engraftment of human acute myeloid leukemia cells in immunocompromised mice but not engraftment of human myelodysplastic syndrome cells.

Patient-derived xenotransplantation models of human myeloid diseases including acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms are essential for studying the biology of the diseases in pre-clinical studies. However, few studies have used these models for comparative purposes. Previous work has shown that acute myeloid leukemia blasts respond to human hematopoietic cytokines whereas myelodysplastic syndrome cells do not. We compared the engraftment of acute myeloid leukemia cells and myelodysplastic syndrome cells in NSG mice to that in NSG-S mice, which have transgene expression of human cytokines. We observed that only 50% of all primary acute myeloid leukemia samples (n=77) transplanted in NSG mice provided useful levels of engraftment (>0.5% human blasts in bone marrow). In contrast, 82% of primary acute myeloid leukemia samples engrafted in NSG-S mice with higher leukemic burden and shortened survival. Additionally, all of 5 injected samples from patients with myelodysplastic syndrome showed persistent engraftment on week 6; however, engraftment was mostly low (<2%), did not increase over time, and was only transiently affected by the use of NSG-S mice. Co-injection of mesenchymal stem cells did not enhance human myelodysplastic syndrome cell engraftment. Overall, we conclude that engraftment of acute myeloid leukemia samples is more robust compared to that of myelodysplastic syndrome samples and unlike those, acute myeloid leukemia cells respond positively to human cytokines, whereas myelodysplastic syndrome cells demonstrate a general unresponsiveness to them.

Levosimendan for Prevention of Acute Kidney Injury After Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Levosimendan has been shown to confer direct renoprotection in renal endotoxemic and ischemia-reperfusion injury and could increase renal blood flow in patients with low-cardiac-output heart failure. Results from clinical trials of levosimendan on acute kidney injury (AKI) following cardiac surgery are controversial. STUDY DESIGN: A random-effect meta-analysis was conducted based on evidence from PubMed, EMBASE, and Cochrane Library. SETTINGS & POPULATION: Adult patients undergoing cardiac surgery. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing the renal effect of levosimendan versus placebo or other inotropic drugs during cardiac surgery. INTERVENTION: Perioperative levosimendan continuous infusion at a rate of 0.1 to 0.2µg/kg/min following a loading dose (6-24µg/kg) for 24 hours or only 1 loading dose (24µg/kg) within 1 hour. OUTCOMES: AKI, need for renal replacement therapy, mechanical ventilation duration, intensive care unit stay during hospitalization, and postoperative mortality (in-hospital or within 30 days). RESULTS: 13 trials with a total of 1,345 study patients were selected. Compared with controls, levosimendan reduced the incidence of postoperative AKI (40/460 vs 78/499; OR, 0.51; 95% CI, 0.34-0.76; P=0.001; I(2)=0.0%), renal replacement therapy (22/492 vs 49/491; OR, 0.43; 95% CI, 0.25-0.76; P=0.002; I(2)=0.0%), postoperative mortality (35/658 vs 94/657; OR, 0.41; 95% CI, 0.27-0.62; P<0.001; I(2)=0.0%), mechanical ventilation duration (in days; n=235; weighted mean difference, -0.34; 95% CI, -0.58 to -0.09; P=0.007], and intensive care unit stay (in days; n=500; weighted mean difference, -2.2; 95% CI, -4.21 to -0.13; P=0.04). LIMITATIONS: Different definitions for AKI among studies. Small sample size for some trials. CONCLUSIONS: Perioperative administration of levosimendan in patients undergoing cardiac surgery may reduce complications. Future trials are needed to determine the dose effect of levosimendan in improving outcomes, especially in patients with decreased baseline kidney function.

Delayed remote preconditioning induces cardioprotection: role of heme oxygenase-1.

BACKGROUND: The role of heme oxygenase-1 (HO-1) in the cardioprotection induced by delayed remote ischemic preconditioning (DRIPC) has not been investigated. Therefore, this study was designed to investigate whether HO-1 is involved in DRIPC-mediated cardioprotection in an isolated perfused rat heart model. MATERIALS AND METHODS: Isolated rat hearts were subjected to 30 min ischemia followed by 60 min reperfusion. DRIPC (four cycles 5-min occlusion and 5-min reflow at the unilateral hind limb once per day for 1, 2, or 3 d before heart isolation, abbreviated as D1RIPC, D2RIPC, or D3RIPC respectively). Infarct size, myocardial troponin levels, and heart function were measured. The protein and messenger RNA levels of HO-1 were determined. RESULTS: DRIPC facilitated postischemic cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect of DRIPC was more pronounced in the D3RIPC group (10.22 ± 2.57%) than the D1RIPC group (22.34 ± 4.02%, P < 0.001) or the D2RIPC group (14.60 ± 3.13%, P = 0.034). These effects in the D1RIPC group could be blocked by Zinc Protoporphyrin IX (ZnPP) (an HO-1 specific inhibitor). DRIPC-mediated cardioprotection was associated with enhanced HO-1 protein expression (D1RIPC, 0.11 ± 0.03; versus 0.15 ± 0.06 in the D2RIPC group, P = 0.06; versus 0.20 ± 0.04 in the D3RIPC group, P = 0.04) and messenger RNA levels of HO-1 expression. CONCLUSIONS: Our findings suggest that HO-1 is involved in the cardioprotection induced by DRIPC, and that increase in the number of preconditioning stimuli may enhance cardioprotective effects accompanied with increased HO-1 level.

Restoration of autophagic flux in myocardial tissues is required for cardioprotection of sevoflurane postconditioning in rats.

AIM: Sevoflurane postconditioning (SpostC) has been shown to protect the heart from ischemia-reperfusion (I/R) injury. In this study, we examined whether SpostC affected autophagic flux in myocardial tissues that contributed to its cardioprotective effects in rats following acute I/R injury. METHODS: SD rats underwent 30 min of left anterior descending coronary artery ligation followed by 120 min of reperfusion. The rats were subjected to inhalation of 2.4% (v/v) sevoflurane during the first 5 min of reperfusion, and chloroquine (10 mg/kg, ip) was injected 1 h before I/R. Myocardial infarct size was estimated using TTC staining. Autophagosomes in myocardial tissues were detected under TEM. Expression of LC3B-II, beclin-1, p62/SQSTM1, cathepsin B, caspase-3 and cleaved PARP was assessed using Western blot analysis. Plasma cardiac troponin I was measured using ELISA. Cardiomyocyte apoptosis was evaluated with TUNEL staining. RESULTS: I/R procedure produced severe myocardium infarct and apoptosis accompanied by markedly increased number of autophagosomes, as well as increased levels of LC3B-II, beclin-1 and p62 in myocardial tissues. SpostC significantly reduced infarct size, attenuated myocardial apoptosis, restored intact autophagic flux and improved the lysosomal function in myocardial tissues. Administration of chloroquine that blocked autophagic flux abrogated the cardioprotective effects of SpostC. CONCLUSION: SpostC exerts its cardioprotective effects in rats following I/R injury via restoring autophagic flux in myocardial tissues.