Search

Performing cardiopulmonary bypass (CPB) to reduce ischemic injury during surgery is a common approach to cardiac surgery. However, this procedure can lead to systemic inflammation and multiorgan dysfunction. Therefore, elucidating the molecular mechanisms of CPB-induced inflammatory cytokine release is essential as a critical first step in identifying new targets for therapeutic intervention. The GSE143780 dataset which is mRNA sequencing from total circulating leukocytes of the neonatorum was downloaded from the Gene Expression Omnibus (GEO) database. A total of 21 key module genes were obtained by analyzing the intersection of differentially expressed gene (DEG) and gene coexpression network analysis (WGCNA), and then, 4 genes (TRAF3IP2-AS1, PPARGC1B, CD4, and PDLIM5) were further confirmed after the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) screening and were used as hub genes for CPB-induced inflammatory cytokine release in patients with congenital heart defects. The enrichment analysis revealed 21 key module genes mainly related to the functions of developmental cell growth, regulation of monocyte differentiation, regulation of myeloid leukocyte differentiation, ERK1 and ERK2 cascade, volume-sensitive anion channel activity, and estrogen receptor binding. The result of gene set enrichment analysis (GSEA) showed that the hub genes were related to different physiological functions of cells. The ceRNA network established for hub genes includes 3 hub genes (PPARGC1B, CD4, and PDLIM5), 55 lncRNAs, and 34 miRNAs. In addition, 4 hub genes have 215 potential therapeutic agents. Finally, expression validation of the four hub genes revealed that they were all significantly low expressed in the surgical samples than before.

Brain injury is a major complication resulted from cardiopulmonary bypass (CPB). Dexmedetomidine (DEX) has potential brain-protective effects; however, the mechanism is unclear. The aim of this study is to investigate the effect of DEX on brain injury in CPB rats and its mechanism. The levels of interleukin-6 (IL-6), interleukin-10 (IL-10), S100β, and neuron-specific enolase (NSE) were measured by enzyme-linked immunosorbent assay. The hippocampus CA1 region in rats was observed by hematoxylin-eosin staining. Western blot and quantitative real-time polymerase chain reaction were performed to detect related proteins and mRNA expressions in the hippocampus tissues. We found that after CPB, the neuron cells in hippocampus CA1 region of rats were randomly arranged, and that the levels of IL-6, IL-10, S100β, NSE, Cleaved Caspase-3, and Bax were upregulated, while Bal-2 level was downregulated. However, after DEX treatment, the neuron cells arranged in an orderly manner, and the levels of IL-6, IL-10, S100β, NSE, Cleaved Caspase-3, and Bax were downregulated, but Bal-2 level was upregulated. DEX suppressed Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathway activated by CPB, ameliorated CPB-induced brain injury in rats by reducing inflammatory response, and inhibited neuronal apoptosis. The brain-protective effect of DEX may be related to the inhibition of the activation of JAK2/STAT3 pathway.

Background: Metabolic reprogramming has emerged as an important feature of cancer, and the metabolism-related indexes are closely related to prognosis. Therefore, we develop and verify a large sample clinical prediction model to predict the prognosis in patients with solid tumors.Methods: This retrospective analysis was conducted on a primary cohort of 5006 patients with solid tumor from INSCOC database. A total of 1720 cancer patients treated at the Fujian Cancer Hospital was used to form the validation cohort. A multivariate Cox regression analysis was performed to test the independent significance of different factors and then establish the model. The prediction model was simplified into a nomogram to predict the 1-, 3-and 5-year OS rates. To determine the discriminatory and predictive accuracy capacity of the model, the C-index and calibration curve were evaluated.Results: Multivariate analysis indicated that age, smoking history, tumor stage, tumor metastasis, PGSGA score, FBG, NLR, ALB, TG, and HDL-C were independent factors. Moreover, the nomogram combining the score and clinical parameters can predict patient survival accurately.Conclusions: Clinical indicators based on metabolism reprogramming coould well fit and predict the prognosis of cancer patients, and could provide assistance for the individual treatment of tumor patients in the clinic.

The aim of this study was to evaluate the association of differential body water composition with survival in patients with lung cancer.This retrospective cohort study included 1314 patients diagnosed with lung cancer in 80 Chinese institutions from May 2013 to August 2020. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with extracellular water (ECW) and intracellular water (ICW). Cox proportional risk regression models were adjusted for sociodemographic characteristics, tumor characteristics, treatment, body mass index (BMI), and body composition measures. We also evaluated cross-classification of the dichotomy of ECW and ICW with outcomes. The association among ECW, ICW, and survival was evaluated via Cox regression and the restricted cubic-spline model using a two-sided P value.The study included 819 (62%) men and 495 (28%) women. The HR of lung cancer mortality significantly decreased as ECW increased (HR, 0.96; 95% confidence interval [CI], 0.93-1.00) and ICW (HR, 0.97; 95% CI, 0.95-1.00) with cutoff values of 10.5 and 16.3 L, respectively. When patients were cross-classified into categories of sex, age, BMI, visceral fat index, pathology, tumor stage, tumor burden, total bilirubin, and neutrophil count, ICW and ECW were protective factors. Only sex interacted significantly with ICW or ECW. High ICW and ECW had significant protective effects, and women had a greater risk for death than men in the case of either poor ICW or poor ECW. Sensitivity analysis showed the protective effect of the higher dichotomy of ICW (HR, 0.52; 95% CI, 0.35-0.78) and ECW (HR, 0.45; 95% CI, 0.31-0.66) on female lung cancer patients by removing patients who died within 12 mo of diagnosis.Greater ICW and ECW, especially ICW, were independent predictors for better survival in patients with lung cancer. Female patients were more vulnerable to dehydration than male patients.

BackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and MethodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan–Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.ResultsForty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33–2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.

Background Aberrant DNA methylation is a crucial epigenetic regulator that is closely related to the occurrence and development of various cancers, including breast cancer (BC). The present study aimed to identify a novel methylation-based prognosis biomarker panel by integrally analyzing gene expression and methylation patterns in BC patients. Methods DNA methylation and gene expression data of breast cancer (BRCA) were downloaded from The Cancer Genome Atlas (TCGA). R packages, including ChAMP, SVA, and MethylMix, were applied to identify the unique methylation-driven genes. Subsequently, these genes were subjected to Metascape for GO analysis. Univariant Cox regression was used to identify survival-related genes among the methylation-driven genes. Robust likelihood-based survival modeling was applied to define the prognosis markers. An independent data set (GSE72308) was used for further validation of our risk score system. Results A total of 879 DNA methylation-driven genes were identified from 765 BC patients. In the discovery cohort, we identified 50 survival-related methylation-driven genes. Finally, we built an eight-methylation-driven gene panel that serves as prognostic predictors. Conclusions Our analysis of transcriptome and methylome variations associated with the survival status of BC patients provides a further understanding of basic biological processes and a basis for the genetic etiology in BC.

Shaohua Guo,1,2 Jiajin Zhang,2 Baishi Wang,2 Bingdong Zhang,1 Xuning Wang,1 Liang Huang,1 Hongyi Liu,2 Baoqing Jia1,2 1Chinese PLA Medical School, Beijing, China; 2General Surgery Department II, Chinese PLA General Hospital, Beijing, China Objective: The study aimed to screen microRNAs (miRNAs) that can be used for the early detection of colorectal cancer (CRC) based on differential expression of miRNA in serum.Materials and methods: A three-stage study was designed with a total of 217 CRCs, 168 colorectal adenomas (CRAs), and 190 healthy controls (HCs). A quantitative reverse transcription polymerase chain reaction was performed in three stages. We screened 528 miRNA expression profiles in the sera of 40 patients (CRC n=20, CRA n=10, and HC n=10) for candidate miRNAs, then 210 serum samples (CRC n=90, CRA n=60, and HC n=60) were used for screening of candidate miRNAs. Three hundred and twenty-five independent individual samples (CRC n=107, CRA n=98, and HC n=120) were used to validate the most differentially-expressed miRNAs in the screening stage, and binary logistic regression was used in the validation stage. A receiver operating characteristic curve was drawn to evaluate the diagnostic accuracy.Results: A 5-serum miRNA panel (miRNA-1246, miRNA-202-3p, miRNA-21-3p, miRNA-1229-3p, and miRNA-532-3p) effectively distinguished CRCs from HCs with 91.6% sensitivity and 91.7% specificity. The area under the curve (AUC) was 0.960 (95% confidence interval [CI]: 0.937–0.983). In addition, the panel also accurately distinguished CRCs from CRAs with 94.4% sensitivity and 84.7% specificity. The AUC was 0.951 (95% CI: 0.922–0.980).Conclusion: Our 5-serum miRNA panel accurately distinguished CRCs from CRAs and HCs with high sensitivity and specificity. The 5-serum miRNA panel may be a promising prospect for application as a nonintrusive and inexpensive method for the early detection of CRC. Keywords: colorectal cancer, colorectal adenoma, miRNA&nbsp

Biochar is the solid product of biomass pyrolysis that can be used for carbon sequestration, soil amendment, and pollution remediation. The use of biochar as an adsorbent for the removal of water contaminants has elicited increasing interest due to the multifunctional properties of this material. The application of biochar in the adsorption of inorganic nutrients from eutrophic water has not been reviewed. This review focuses on recent research on the use of biochar for the adsorption of inorganic nitrogen (ammonium and nitrate) and phosphorus (phosphate) from water, especially for the main influence factors and mechanisms for nitrogen and phosphorus adsorption on biochar.

Yanhua Chen,1,* Xu Zhang,2,* Bingdong Zhang,1 Guodong He,2 Lifang Zhou,2 Yubo Xie2 1Department of Anesthesiology, Cardiovascular Institute, 2Department of Anesthesiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China *These authors contributed equally to this work Abstract: Cardiopulmonary bypass (CPB) constitutes one of the primary methodologies pertaining to cardiac surgery. However, this form of surgery can cause damage to the body. Many studies have reported that dexmedetomidine confers cerebral protection. In this study, we aimed to investigate the effect and mechanism of dexmedetomidine on neuronal apoptosis caused by CPB. Here, rats were treated with different doses of dexmedetomidine by intravenous infusion 2 hours after CPB. We observed that dexmedetomidine treatment to rats reduces the S100ß, NSE levels in plasma, and neuronal apoptosis following CPB in a dose-dependent manner. Furthermore, we observed that the beneficial effect of dexmedetomidine treatment following CPB was associated with a reduction in IL6, an inflammatory cytokine in plasma and cortex. Our results suggest that dexmedetomidine provides neuroprotective effects by inhibiting inflammation and reducing neuronal apoptosis. There was a correlation between the protective effect on the brain and the dose of dexmedetomidine. In addition, dexmedetomidine administration inhibits phosphorylation of JAK2 and STAT3 proteins in the hippocampus of rats 2 hours after CPB. Therefore, we speculate that the JAK2–STAT3 pathway plays an important role in the neuroprotective effects of dexmedetomidine following brain injury induced by CPB. Keywords: apoptosis, cardiopulmonary bypass, dexmedetomidine, neuroprotective effect, JAK2, STAT3

Non-esterified fatty acids (NEFAs) promote de novo lipogenesis, which caused abnormal hepatic lipid accumulation, by the NFκB–Orai1 pathway. Oxidative stress and endoplasmic reticulum (ER) stress have been recognized as key mechanisms in non-alcoholic fatty liver disease (NAFLD) pathogenesis. Whether Orai1 facilitates ER stress by oxidative stress remains unknown. The rat model of NAFLD was constructed by feeding high-fat diet (HFD). BRL-3A cells were treated with NEFAs, Orai1inhibtor BTP2, NFκB inhibitor wogonin, or small interfering Orai (siOrai) 1, respectively. The content of intracellular reduced glutathione (GSH) and malondialdehyde (MDA), indicating oxidative stress, was measured by a spectrophotometer. ER stress major proteins PERK, IRE1, ATF6, CHOP, and GRP78 were quantified using Western blot and qRT-PCR analyses. For the intracellular location of reactive oxygen species (ROS) and Orai1 were measured by Western blot and immunofluorescence, and cytosolic Ca2+ was measured by flow cytometry. As we expected, the liver of rats with NAFLD showed lipid droplets in HE and Oil Red O. The decreased GSH and increased MDA were found in rats fed with HFD. ER stress major proteins PERK, IRE1, ATF6, GRP78, and CHOP were significantly increased in the HFD group. In BRL-3A cells, GSH content dramatically decreased from 1 h, MDA content dramatically increased from 3 h, and expression levels of ER stress significantly increased from 3 h by NEFA treatment. Furthermore, cytosolic Ca2+ increased from 0.5 h by NEFAs treated in BRL-3A cells. It indicated that NEFAs increased cytosolic Ca2+ to induce oxidative stress, thus ER stress. The content of oxidative stress and ER stress proteins showed the same trends by NEFAs treated in BRL-3A cells. These effects were reversed by the Orai1 inhibitor BTP2 and the NFκB inhibitor wogonin. Moreover, siOrai1 abrogated NEFAs’ influence in BRL-3A cells. Last, ROS was found by NEFAs treated in BRL-3A cells, and NEFA treatment enhanced the nuclear localization of NF-κB p65 and ORAI1. It was considered that high NEFAs increased cytosolic Ca2+ and enhanced NFκB-dependent SOCE and its moiety protein Orai1 to decrease GSH and thus induced oxidative stress at earlier stages and furthermore tempted ER stress in the pathologic progress of NAFLD.

The adsorption of $$ \mathrm{N}{\mathrm{H}}_4^{+} $$ and $$ {\mathrm{PO}}_4^{3-} $$ by sesame straw biochars (C-300, C-500, and C-700) prepared under different temperatures (300, 500, and 700 °C) was investigated in this study. The physicochemical properties of the biochars were characterized using Brunauer–Emmett–Teller method, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectrometry. In batch experiments, C-300 showed the best $$ \mathrm{N}{\mathrm{H}}_4^{+} $$ adsorption capacity of 3.45 mg/g because of its abundant surface functional groups at low pyrolysis temperature. C-700 achieved the optimal $$ {\mathrm{PO}}_4^{3-} $$ adsorption capacity of 34.17 mg/g because of its high Ca, Mg, and Al contents and high surface area at high pyrolysis temperature. The isothermal study showed that the Langmuir–Freundlich model could sufficiently describe the $$ \mathrm{N}{\mathrm{H}}_4^{+} $$ and $$ {\mathrm{PO}}_4^{3-} $$ adsorption values, indicating the multiple adsorption processes of nutrients on biochars. The maximum $$ \mathrm{N}{\mathrm{H}}_4^{+} $$ adsorption capacity was 93.61 mg/g on C-300, whereas the maximum $$ {\mathrm{PO}}_4^{3-} $$ adsorption capacity was as high as 116.58 mg/g on C-700. Kinetic study showed that $$ \mathrm{N}{\mathrm{H}}_4^{+} $$ adsorption on C-300 was mainly controlled by intraparticle diffusion, and the pseudo-second-order model could well describe $$ {\mathrm{PO}}_4^{3-} $$ adsorption on C-700.

Objective The purpose of this article was to systematically review randomized controlled trials in which cold blood cardioplegia was compared with cold crystalloid cardioplegia for cardiac surgery. Design Correlation studies were searched independently in the EMBASE, MEDLINE and Cochrane library databases. The primary endpoints of interest were spontaneous sinus rhythm (SSR) after declamping, perioperative myocardial infarction (MI) and mortality (within 30 days). Setting A hospital. Participants Randomized controlled trials. Intervention A meta-analysis of 12 studies. Measurements and Main Results The 12 included trials recruited a total of 2866 participants; 1357 patients received cold crystalloid cardioplegia, and 1509 patients received cold blood cardioplegia. The pooled analysis showed no significant difference favoring either cold crystalloid cardioplegia or cold blood cardioplegia in terms of spontaneous sinus rhythm (SSR) after declamping (789/1028 [76.75%] v 773/1025 [75.41%], relative risk (RR) = 0.92 [0.76, 1.13], p = 0.43 with 6 studies included), mortality (within 30 days) (20/1335 [1.50%] v 24/1469 [1.63%], relative risk (RR) = 1.09 [0.62, 1.91], p = 0.77 with 11 studies included), atrial fibrillation (AF) (329/1043 [31.54%] v 365/1040 [35.10%], RR =0.90 [0.80, 1.01], p = 0.08 with 6 studies included) or stroke (45/1114 [4.04%] v 20/1240 [1.61%], RR = 2.18 [0.69, 6.93], p = 0.19 with 4 studies included). The aggregate data showed that the incidence of perioperative myocardial infarction was lower in patients who received cold blood cardioplegia (CB) (32/1310 [2.44%] v 17/1434 [1.19%], RR = 2.30 [1.33, 3.98], p = 0.003 with 11 studies included). Conclusions Cold blood cardioplegia reduced perioperative myocardial infarction when compared with cold crystalloid cardioplegia. No differences in the overall incidence rates of spontaneous sinus rhythm, mortality (within 30 days), atrial fibrillation or stroke were observed.

This paper proposes a new method for equal quality distribution of gas–liquid two-phase flow by partial separate-phase distribution with a dual-header distributor. The upper and liquid (lower) headers are interconnected with five vertical downward arms. A gas–liquid two-phase mixture enters the distributor from the upper header where most of the liquid of the mixture is removed through the downward arms into the liquid header. Hence, firstly, the remaining gas-rich fluid can be uniformly distributed into the outlet branches, and then secondly, the liquid collected in the liquid header can be uniformly re-distributed into the individual outlet branches. Because both distribution processes are conducted in the condition of single or near single-phase flow, mal-distribution of the two-phase flow is essentially eliminated, and a satisfactory equal quality distribution of gas–liquid two-phase flow is reached. Experiments were conducted in an air–water two-phase flow test loop. The inner diameter of the inlet pipe was 60 mm, the superficial velocity ranges of gas and liquid were 3–32 m/s and 0.02–0.17 m/s respectively, and the quality ranged from 0.02 to 0.44. The flow pattern in the inlet pipe included stratified flow, wavy stratified, slug flow, and annular flow. The experimental results showed that this new method could significantly improve the distribution performance of the two-phase flow. The maximum quality deviation between each outlet branch and the inlet pipe is less than ±1% under the conditions of stratified, wavy stratified and slug flows in the upper header, and less than ±5% in annular flow.

Introduction Apolipoprotein A1 (apoA1) is the major apoprotein constituent of high density lipoprotein (HDL) which exerts innate protective effects in systemic inflammation. However, its role in the acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) has not been well studied. The objective of this study was to investigate the potential association between APOA1 -75 G/A polymorphism and the development of ALI after cardiopulmonary bypass (CPB) surgery. Materials and methods A hospital-based case–control study was conducted in patients with ALI (n = 300), patients without ALI (n = 300) and healthy controls (n = 300). Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the APOA1 -75 G/A genotypes. Results Patients with ALI had a significantly higher frequency of APOA1 -75 AA genotype [odds ratio (OR) =1.75, 95% confidence interval (CI) = 1.04, 2.92; P = 0.03] than patients without ALI. APOA1 -75 AA genotype (OR =3.47, 95% CI = 1.60, 7.52; P = 0.002) and A allele (OR =1.92, 95% CI = 1.24, 2.96; P = 0.003) were the significant independent prognostic factors for the 30-day survival rate of patients with ALI after CPB surgery. Conclusion Our study suggested that APOA1 -75 AA genotype was associated with a higher ALI risk after CPB surgery. Patients with the APOA1 -75 AA genotype and A allele had higher 30-day mortality of ALI after CPB surgery. Additional studies are needed to confirm this finding.