Effectiveness of concentrated growth factor and laser therapy on wound healing, inferior alveolar nerve injury and periodontal bone defects post-mandibular impacted wisdom tooth extraction: A randomized clinical trial.

The extraction of wisdom teeth with mandibular impact frequently results in complications including damage to the inferior alveolar nerve (IAN) and malformations of the bone. The objective of this research endeavour was to assess the efficacy of low-level laser therapy and concentrated growth factor (CGF) in facilitating nerve recovery and wound healing in such instances. A total of thirty-one patients (mean age 27.52 ± 5.79 years) who presented with IAN injury after extraction were randomly assigned to one of three groups: control group (which received oral mecobalamin), CGF group (which received CGF gel applied to the extraction sockets) and laser group (which received low-level lasers (808 nm, 30 mW, 10 J/cm2 )) at the extraction site. Patients' recovery from IAN paresthesia was evaluated seven times over the course of 14 days utilizing visual analogue scale (VAS) and the pinprick test (PP). At multiple intervals following surgery, periodontal probing and bone level measurements were utilized to assess the recovery of both soft and hard tissues. The findings revealed that, compared with the control group, both the CGF and laser treatment groups exhibited a markedly greater improvement in VAS scores and wound healing of soft tissues, as well as in PP results (p < 0.001), indicating enhanced wound healing processes. Despite these improvements, there was no significant difference in wound healing outcomes between the CGF and laser groups. Notably, the CGF group showed a statistically significant improvement in healing bone defects at 30 and 90 days post-treatment compared with the control group (p = 0.003 and p = 0.004, respectively), underscoring its effectiveness in bone healing as a critical aspect of the overall wound healing process. However, in terms of other wound healing comparisons, no significant differences were observed. CGF and laser therapy significantly enhanced the healing of wounds, including soft tissue and bone recovery, in addition to accelerating the recovery of IAN injuries following mandibular wisdom tooth extraction. Although both treatments were equally effective in nerve recovery, CGF notably excelled in promoting bone healing, suggesting its pivotal role in comprehensive wound healing. This highlights that both CGF and laser therapy are viable options for not only nerve recovery but also for overall wound healing in such dental procedures.

Integrative analysis of genome and transcriptome reveal the genetic basis of high temperature tolerance in pleurotus giganteus (Berk. Karun & Hyde).

BACKGROUND: Pleurotus giganteus is a commonly cultivated mushroom with notable high temperature resistance, making it significant for the growth of the edible fungi industry in the tropics. Despite its practical importance,, the genetic mechanisms underlying its ability to withstand high temperature tolerance remain elusive. RESULTS: In this study, we performed high-quality genome sequencing of a monokaryon isolated from a thermotolerant strain of P. giganteus. The genome size was found to be 40.11 Mb, comprising 17 contigs and 13,054 protein-coding genes. Notably, some genes related to abiotic stress were identified in genome, such as genes regulating heat shock protein, protein kinase activity and signal transduction. These findings provide valuable insights into the genetic basis of P. giganteus' high temperature resistance. Furthermore, the phylogenetic tree showed that P. giganteus was more closely related to P. citrinopileatus than other Pleurotus species. The divergence time between Pleurotus and Lentinus was estimated as 153.9 Mya, and they have a divergence time with Panus at 168.3 Mya, which proved the taxonomic status of P. giganteus at the genome level. Additionally, a comparative transcriptome analysis was conducted between mycelia treated with 40 °C heat shock for 18 h (HS) and an untreated control group (CK). Among the 2,614 differentially expressed genes (DEGs), 1,303 genes were up-regulated and 1,311 were down-regulated in the HS group. The enrichment analysis showed that several genes related to abiotic stress, including heat shock protein, DnaJ protein homologue, ubiquitin protease, transcription factors, DNA mismatch repair proteins, and zinc finger proteins, were significantly up-regulated in the HS group. These genes may play important roles in the high temperature adaptation of P. giganteus. Six DEGs were selected according to fourfold expression changes and were validated by qRT-PCR, laying a good foundation for further gene function analysis. CONCLUSION: Our study successfully reported a high-quality genome of P. giganteus and identified genes associated with high-temperature tolerance through an integrative analysis of the genome and transcriptome. This study lays a crucial foundation for understanding the high-temperature tolerance mechanism of P. giganteus, providing valuable insights for genetic modification of P. giganteus strains and the development of high-temperature strains for the edible fungus industry, particularly in tropical regions.

Dietary supplementation with probiotics increases growth performance, improves the intestinal mucosal barrier and activates the Wnt/ß-catenin pathway activity in chicks.

BACKGROUND: Probiotics comprise effective feed additives that can replace antibiotics in animal livestock production. However, mono-strain probiotics appear less effective because of their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics (CPP) on growth performance, diarrhea rate and intestinal mucosal barrier, as well as the possible molecular mechanism, in chicks. In total, 360 1-day-old chicks of the Hy-Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg kg-1 CTC) and compound probiotics group (1000 mg kg-1 CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium and yeast). The experiment period was 56 days. RESULTS: The results showed that, in comparison with the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduced diarrhea (P < 0.05). The probiotic group exhibited increased immune organ (i.e. spleen and thymus) mass and increased levels of serum immunoglobulin (Ig)A, IgM and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin-1, and diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of proliferating cell nuclear antigen-labeled mitotic cells and villin-labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/ß-catenin signaling pathway, including ß-catenin, TCF4, c-Myc, cyclin D1 and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05). CONCLUSION: The present study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/ß-catenin signaling and enhanced immune function in chicks. © 2023 Society of Chemical Industry.

Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort.

BACKGROUND: The immune system plays a vital role in the pathophysiology of acute myocardial infarction (AMI). However, the exact immune related mechanism is still unclear. This research study aimed to identify key immune-related genes involved in AMI. METHODS: CIBERSORT, a deconvolution algorithm, was used to determine the proportions of 22 subsets of immune cells in blood samples. The weighted gene co-expression network analysis (WGCNA) was used to identify key modules that are significantly associated with AMI. Then, CIBERSORT combined with WGCNA were used to identify key immune-modules. The protein-protein interaction (PPI) network was constructed and Molecular Complex Detection (MCODE) combined with cytoHubba plugins were used to identify key immune-related genes that may play an important role in the occurrence and progression of AMI. RESULTS: The CIBERSORT results suggested that there was a decrease in the infiltration of CD8 + T cells, gamma delta (γδ) T cells, and resting mast cells, along with an increase in the infiltration of neutrophils and M0 macrophages in AMI patients. Then, two modules (midnightblue and lightyellow) that were significantly correlated with AMI were identified, and the salmon module was found to be significantly associated with memory B cells. Gene enrichment analysis indicated that the 1,171 genes included in the salmon module are mainly involved in immune-related biological processes. MCODE analysis was used to identify four different MCODE complexes in the salmon module, while four hub genes (EEF1B2, RAC2, SPI1, and ITGAM) were found to be significantly correlated with AMI. The correlation analysis between the key genes and infiltrating immune cells showed that SPI1 and ITGAM were positively associated with neutrophils and M0 macrophages, while they were negatively associated with CD8 + T cells, γδ T cells, regulatory T cells (Tregs), and resting mast cells. The RT-qPCR validation results found that the expression of the ITGAM and SPI1 genes were significantly elevated in the AMI samples compared with the samples from healthy individuals, and the ROC curve analysis showed that ITGAM and SPI1 had a high diagnostic efficiency for the recognition of AMI. CONCLUSIONS: Immune cell infiltration plays a crucial role in the occurrence and development of AMI. ITGAM and SPI1 are key immune-related genes that are potential novel targets for the prevention and treatment of AMI.

Identification of immune-related key genes in the peripheral blood of ischaemic stroke patients using a weighted gene coexpression network analysis and machine learning.

BACKGROUND: The immune system plays a vital role in the pathological process of ischaemic stroke. However, the exact immune-related mechanism remains unclear. The current research aimed to identify immune-related key genes associated with ischaemic stroke. METHODS: CIBERSORT was utilized to reveal the immune cell infiltration pattern in ischaemic stroke patients. Meanwhile, a weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules significantly correlated with ischaemic stroke. The characteristic genes correlated with ischaemic stroke were identified by the following two machine learning methods: the support vector machine-recursive feature elimination (SVM-RFE) algorithm and least absolute shrinkage and selection operator (LASSO) logistic regression. RESULTS: The CIBERSORT results suggested that there was a decreased infiltration of naive CD4 T cells, CD8 T cells, resting mast cells and eosinophils and an increased infiltration of neutrophils, M0 macrophages and activated memory CD4 T cells in ischaemic stroke patients. Then, three significant modules (pink, brown and cyan) were identified to be significantly associated with ischaemic stroke. The gene enrichment analysis indicated that 519 genes in the above three modules were mainly involved in several inflammatory or immune-related signalling pathways and biological processes. Eight hub genes (ADM, ANXA3, CARD6, CPQ, SLC22A4, UBE2S, VIM and ZFP36) were revealed to be significantly correlated with ischaemic stroke by the LASSO logistic regression and SVM-RFE algorithm. The external validation combined with a RT‒qPCR analysis revealed that the expression levels of ADM, ANXA3, SLC22A4 and VIM were significantly increased in ischaemic stroke patients and that these key genes were positively associated with neutrophils and M0 macrophages and negatively correlated with CD8 T cells. The mean AUC value of ADM, ANXA3, SLC22A4 and VIM was 0.80, 0.87, 0.91 and 0.88 in the training set, 0.85, 0.77, 0.86 and 0.72 in the testing set and 0.87, 0.83, 0.88 and 0.91 in the validation samples, respectively. CONCLUSIONS: These results suggest that the ADM, ANXA3, SLC22A4 and VIM genes are reliable serum markers for the diagnosis of ischaemic stroke and that immune cell infiltration plays a crucial role in the occurrence and development of ischaemic stroke.

A Series of Functionalized Zirconium Metal-Organic Cages for Efficient CO2/N2 Separation.

Global warming associated with CO2 emission has led to frequent extreme weather events in recent years. Carbon capture using porous solid adsorbents is promising for addressing the greenhouse effect. Herein, we report a series of robust metal-organic cages (MOCs) featuring various functional groups, such as methyl and amine groups, for CO2/N2 separation. Significantly, the amine-group-functionalized MOC-QW-3-NH2 displays the best selective CO2 adsorption performance, as confirmed by single-component adsorption and transient breakthrough experiments. The distinct CO2 adsorption mechanism has been well studied via theoretical calculations, confirming that the amine groups play a vital role for efficiently selective CO2 adsorption resulting from hierarchical adsorbate-framework interaction.

Genes associated with inflammation may serve as biomarkers for the diagnosis of coronary artery disease and ischaemic stroke.

BACKGROUND: The current research aimed to expound the genes and pathways that are involved in coronary artery disease (CAD) and ischaemic stroke (IS) and the related mechanisms. METHODS: Two array CAD datasets of (GSE66360 and GSE97320) and an array IS dataset (GSE22255) were downloaded. Differentially expressed genes (DEGs) were identified using the limma package. The online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) (version 6.8; david.abcc.ncifcrf.gov) was used to annotate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses of the DEGs. A protein-protein interaction (PPI) network was constructed by Cytoscape software, and then Molecular Complex Detection (MCODE) analysis was used to screen for hub genes. The hub genes were also confirmed by RT-qPCR and unconditional logistic regression analysis in our CAD and IS patients. RESULTS: A total of 20 common DEGs (all upregulated) were identified between the CAD/IS and control groups. Eleven molecular functions, 3 cellular components, and 49 biological processes were confirmed by GO enrichment analysis, and the 20 common upregulated DEGs were enriched in 21 KEGG pathways. A PPI network including 24 nodes and 68 edges was constructed with the STRING online tool. After MCODE analysis, the top 5 high degree genes, including Jun proto-oncogene (JUN, degree = 9), C-X-C motif chemokine ligand 8 (CXCL8, degree = 9), tumour necrosis factor (TNF, degree = 9), suppressor of cytokine signalling 3 (SOCS3, degree = 8) and TNF alpha induced protein 3 (TNFAIP3, degree = 8) were noted. RT-qPCR results demonstrated that the expression levels of CXCL8 were increased in IS patients than in normal participants and the expression levels of SOCS3, TNF and TNFAIP were higher in CAD/IS patients than in normal participants. Meanwhile, unconditional logistic regression analysis revealed that the incidence of CAD or IS was positively correlated with the CXCL8, SOCS3, TNF and TNFAIP3. CONCLUSIONS: The CXCL8, TNF, SOCS3 and TNFAIP3 associated with inflammation may serve as biomarkers for the diagnosis of CAD or IS. The possible mechanisms may involve the Toll-like receptor, TNF, NF-kappa B, cytokine-cytokine receptor interactions and the NOD-like receptor signalling pathways.

A novel and validated prognostic nomogram based on liver fibrosis and tumor burden for patients with hepatocellular carcinoma after curative resection.

BACKGROUND AND OBJECTIVES: Most conventional staging systems were formulated concerning the tumor burden rather than the severity of liver fibrosis, which plays a central role in tumor promotion. The aim of this study was to formulate a prognostic nomogram comprehensively considering these two aspects for HCC after hepatectomy. METHODS: The prognostic significances of the four indicators namely laminin, hyaluronic acid, human procollagen type-III, and collagen type-IV that reflect liver fibrosis were explored in two independent cohorts. A nomogram was established based on the results of multivariate analysis. The predictive accuracy of the nomogram was measured by concordance index (C-index) and calibration. The decision curve analysis (DCA) was used to evaluate the clinical benefit of the nomogram. RESULTS: Preoperative serum laminin level is an independent prognostic factor for overall survival in HCC patients after resection. The C-indices of the nomogram in the training and validation cohorts were 0.779 and 0.719, respectively. The calibration showed optimal agreement between the prediction by nomogram and actual observation. Moreover, the C-indices and DCA revealed that the nomogram provided better clinical benefit compared with the BCLC stage, CLIP score, and AJCC 7th edition. CONCLUSIONS: The prognostic nomogram constructed on laminin represents a superior predictive model.

[Application of extracorporeal membrane oxygenation in children with acute respiratory distress syndrome].

The children with acute respiratory distress syndrome (ARDS) usually require ventilatory support treatment. At present, lung protective ventilation strategy is recommended for the treatment of ARDS. Extracorporeal membrane oxygenation (ECMO) can improve oxygenation and remove carbon dioxide by extracorporeal circuit, and can partially or completely take over cardiopulmonary function. ECMO support showed many advantages in treating severe ARDS, such as reducing ventilator-induced lung injury and correcting hypoxemia. Over the past few years, there has been an increase in the use of ECMO for ARDS in children. This paper reviews the applications of ECMO for the treatment of ARDS in children.

Prognostic Nomograms Stratify Survival of Patients with Hepatocellular Carcinoma Without Portal Vein Tumor Thrombosis After Curative Resection.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) without portal vein tumor thrombosis (PVTT) after curative resection is at variance. We identified the risk factors of poor postoperative prognosis and consequently developed prognostic nomograms generating individual risk of death and recurrence for this subgroup of patients with HCC. METHODS: The risk factors were identified and nomograms were developed based on a retrospective study of 734 patients in the primary cohort who underwent curative resection for HCC from 2010 to 2012. The predictive accuracy and discriminative ability of the nomograms were determined by concordance index (C-index) and calibration curve and compared with traditional staging systems of HCC. The results were validated in an independent cohort of 349 patients operated at the same institution in 2007. RESULTS: All of the independent factors for survival in multivariate analysis in the primary cohort were selected into the nomograms. The calibration curve for probability of survival showed good agreement between prediction by nomograms and actual observation. The C-indices of the nomograms for predicting overall survival and recurrence-free survival were 0.755 (95% confidence interval [CI], 0.752-0.758) and 0.665 (95% CI, 0.662-0.668), respectively, which were statistically higher than the C-indices of other HCC prognostic models. The results were further confirmed in the validation cohort. CONCLUSION: The proposed nomograms resulted in more accurate prognostic prediction for patients with HCC without PVTT after curative resection. The Oncologist 2017;22:561-569 IMPLICATIONS FOR PRACTICE: Hepatocellular carcinoma (HCC) poses a great therapeutic challenge due to the poor prognosis in patients underwent surgical resection. The portal vein tumor thrombosis (PVTT) as a robust risk factor for survival has been routinely integrated to staging systems. Nonetheless, the prognosis stratification for patients without PVTT was neglected to some extent. Herein, independent risk factors of OS and RFS in HCC patients without PVTT were reconfirmed. A predictive nomogram was constructed on these risk factors and was demonstrated to be a more accurate predictive model in HCC patients without PVTT, compared with the traditional staging systems.

Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.

BACKGROUND: Aberrant expression of interleukin-35 (IL-35) has been implicated in dampening antitumour immunity. The aim of this study was to explore the prognostic significance of IL-35 expression in patients with hepatocellular carcinoma (HCC) following curative resection. Furthermore, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy. METHODS: Immunohistochemistry was applied to explore IL-35 expression as well as CD39(+)Foxp3(+) and Foxp3(+) regulatory T cell (Treg) infiltration in tissue microarrays in primary cohort comprising 210 randomly selected HCC patients who underwent curative resection. The results were further verified in an independent validation cohort of 138 HCC patients. RESULTS: Patients with higher expression of IL-35 are more likely to suffer postoperative recurrence. Interleukin-35 was also identified as an independent prognostic factor for recurrence free survival in multivariate analysis. No correlation was detected between IL-35 expression and Foxp3(+) Treg infiltration, whereas significant positive correlation was found between IL-35 expression and CD39(+)Foxp3(+) Treg infiltration. In addition, CD39(+)Foxp3(+) Treg infiltration was also an independent predictor for postoperative recurrence. The nomogram comprising tumour size, tumour vascular invasion, IL-35 and CD39(+)Foxp3(+) Tregs had better predictive accuracy when compared with BCLC stage for RFS. These results were further validated in the validation cohort. CONCLUSIONS: Our data suggest for the first time that IL-35 expression correlates with HCC aggressiveness and emerged as a novel independent prognostic factor for recurrence, thus conferring the rationale to develop a novel therapy of targeting IL-35. Furthermore, IL-35 should be incorporated into nomogram to generate a more accurate predictive model.

Metformin ameliorates obesity-associated hypertriglyceridemia in mice partly through the apolipoprotein A5 pathway.

INTRODUCTION: Apolipoprotein A5 (apoA5) is a key regulator of triglyceride (TG) metabolism. This study is to investigate the role of apoA5 in obesity-associated hypertriglyceridemia and metformin-related hypotriglyceridemic actions. METHODS: Two obese mouse models, including high-fat diet-induced obese mice and ob/ob obese mice, were adopted. The effects of low- and high-dose metformin were determined on plasma and hepatic TG and apoA5 of these obese mice. Besides, the effects of metformin on TG and apoA5 were also detected in mouse and human hepatocytes in vitro. RESULTS: (1) Plasma apoA5 levels in the obese mice were markedly elevated and positively correlated with TG. Hepatic TG contents and apoA5 expressions were also remarkably increased in the obese mice. (2) Metformin dose-dependently decreased hepatic and plasma TG and apoA5 in the obese mice. Similarly, metformin dose-dependently reduced cellular TG contents and apoA5 expressions in hepatocytes in vitro. Compared to APOA5 knock-down (KD), metformin plus APOA5 KD resulted in more TG reduction of hepatocytes. CONCLUSION: Increased hepatic and plasma apoA5 could be a result of obesity-associated hypertriglyceridemia, and metformin displays hypotriglyceridemic effects on obese mice partly via the apoA5 pathway.

Anionic Ni-Based Metal-Organic Framework with Li(I) Cations in the Pores for Efficient C2H2/CO2 Separation.

Acetylene (C2H2) is widely used as a raw material for producing various downstream commodities in the petrochemical and electronic industry. Therefore, the acquisition of high-purity C2H2 from a C2H2/CO2 mixture produced by partial methane combustion or thermal hydrocarbon cracking is of great significance yet highly challenging due to their similar physical and chemical properties. Herein, we report an anionic metal-organic framework (MOF) named LIFM-210, which has Li+ cations in the pores and shows a higher adsorption affinity for C2H2 than CO2. LIFM-210 is constructed by a unique tetranuclear Ni(II) cluster acting as a 10-connected node and an organic ligand acting as a 5-connected node. Single-component adsorption and transient breakthrough experiments demonstrate the good C2H2 selective separation performance of LIFM-210. Theoretical calculations revealed that Li+ ions strongly prefer C2H2 to CO2 and are primary adsorption sites, playing vital roles in the selective separation of C2H2/CO2.

l-Malic Acid Facilitates Stem Cell-Driven Intestinal Epithelial Renewal through the Amplification of ß-Catenin Signaling by Targeting Frizzled7 in Chicks.

l-Malic acid (l-MA) contributes to energy metabolism and nutrient digestion, which is an alternative to antibiotics for livestock; however, it is not clear whether l-MA can replace antibiotics to promote intestinal development in chicks. To investigate the effects of l-MA on intestinal stem cells (ISCs) driving epithelial renewal, we employed in vivo chick feeding experiments, chick intestinal organoid (IO) models, and in vitro chick intestinal epithelial cell models. The results showed that the feed conversion rate and diarrhea scores were decreased with improved jejunal morphology and barrier function in the 0.5% l-MA group. l-MA promoted the proliferation and differentiation of ISCs, inhibited the cell apoptosis, increased the IO formation efficiency, surface area, budding efficiency, and number of buds, suggesting that l-MA promoted the expansion of ISCs. Furthermore, l-MA treatment dramatically upregulated the Wnt/ß-catenin signaling pathway in the jejunum. Importantly, Wnt transmembrane receptor Frizzled7 (FZD7) mRNA abundance was increased in response to dietary 0.5% l-MA. In addition, molecular docking analysis using Autodock software and isothermal titration calorimetry revealed that l-MA binds to Lys91 of FZD7 with high affinity, indicating a spontaneous interaction. The chick intestinal epithelial cells treated with 10 µM l-MA significantly increased cell viability, and the Wnt/ß-catenin signaling pathway was activated, but l-MA failed to upregulate the Wnt/ß-catenin signaling when treated with the FZD7-specific inhibitor Fz7-21 in chick intestinal epithelial cells, indicating that FZD7 is indispensable for l-MA activation of the Wnt/ß-catenin signaling. Collectively, l-MA stimulated ß-catenin signaling by targeting transmembrane receptor FZD7, which promoted ISC expansion and inhibited cell apoptosis to accelerate intestinal epithelial renewal in chicks.

m6A regulator-mediated RNA methylation modification patterns are involved in the regulation of the immune microenvironment in ischaemic cardiomyopathy.

The role of RNA N6-methyladenosine (m6A) modification in the regulation of the immune microenvironment in ischaemic cardiomyopathy (ICM) remains largely unclear. This study first identified differential m6A regulators between ICM and healthy samples, and then systematically evaluated the effects of m6A modification on the characteristics of the immune microenvironment in ICM, including the infiltration of immune cells, the human leukocyte antigen (HLA) gene, and HALLMARKS pathways. A total of seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15 and YTHDF3, were identified using a random forest classifier. A diagnostic nomogram based on these seven key m6A regulators could effectively distinguish patients with ICM from healthy subjects. We further identified two distinct m6A modification patterns (m6A cluster-A and m6A cluster-B) that are mediated by these seven regulators. Meanwhile, we also noted that one m6A regulator, WTAP, was gradually upregulated, while the others were gradually downregulated in the m6A cluster-A vs. m6A cluster-B vs. healthy subjects. In addition, we observed that the degree of infiltration of the activated dendritic cells, macrophages, natural killer (NK) T cells, and type-17 T helper (Th17) cells gradually increased in m6A cluster-A vs. m6A cluster-B vs. healthy subjects. Furthermore, m6A regulators, including FTO, YTHDC1, YTHDF3, FMR1, ZC3H13, and RBM15 were significantly negatively correlated with the above-mentioned immune cells. Additionally, several differential HLA genes and HALLMARKS signalling pathways between the m6A cluster-A and m6A cluster-B groups were also identified. These results suggest that m6A modification plays a key role in the complexity and diversity of the immune microenvironment in ICM, and seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15, and YTHDF3, may be novel biomarkers for the accurate diagnosis of ICM. Immunotyping of patients with ICM will help to develop immunotherapy strategies with a higher level of accuracy for patients with a significant immune response.

Effect of continuous blood purification on concentrations of plasma vasoactive substances and cardiac function in endotoxic shock.

OBJECTIVE: To evaluate the effect of continuous blood purification on cardiac function and plasma vasoactive substances in endotoxic shock in piglets. DESIGN: This was a randomized controlled trial in an animal laboratory in a tertiary care pediatric center. MATERIALS AND METHODS: Twenty-three healthy Shanghai white piglets weighing 8-14 kg were randomly assigned to one of the four groups: control group (n = 5), continuous blood purification without lipopolysaccharide infusion group (continuous blood purification, n = 6), lipopolysaccharide-induced endotoxin shock without continuous blood purification group (lipopolysaccharide, n = 6), and lipopolysaccharide-induced endotoxin shock with continuous blood purification group (continuous blood purification/lipopolysaccharide, n = 6). INTERVENTIONS: The lipopolysaccharide and continuous blood purification/lipopolysaccharide groups were injected intravenously with Escherichia coli endotoxin to induce septic shock. The continuous blood purification and continuous blood purification/lipopolysaccharide groups received continuous venovenous hemodiafiltration right after model establishment. At baseline state (T0), following the injection of lipopolysaccharide (T), 1 hr later (T1), 3 hrs later (T3), and 5 hrs later (T5) after model establishment, clinical systemic inflammatory response syndrome parameters, hemodynamic indexes, and plasma concentration of vasoactive substances were obtained. Plasma concentration of dopamine was measured by enzyme-linked immunosorbent assay (DSL Company) and endothelin-1 by enzyme-linked immunosorbent assay (R&D Company). Nitric oxide synthase activity was measured by chromatometry (Nanjing Jiancheng Bioengineering Institute, China). MEASUREMENTS AND MAIN RESULTS: In continuous blood purification/lipopolysaccharide group, after treatment with CPB, heart rate decreased significantly (p < .05) and pulse contour cardiac index, systematic vascular resistance index, and stroke volume index increased significantly (p < .05) when compared with lipopolysaccharide and continuous blood purification groups. After treatment with continuous blood purification, dopamine and endothelin-1 level increased and nitric oxide synthase activities decreased in continuous blood purification/lipopolysaccharide group when compared with the lipopolysaccharide group. In the continuous blood purification/lipopolysaccharide group, improvement in hemodynamic indexes was strongly correlated with increases in plasma dopamine and endothelin-1 level and decreases in nitric oxide synthase activity (r > .9, p < .05). CONCLUSIONS: The adverse cardiovascular effects of lipopolysaccharide-induced endotoxin shock can be improved by continuous blood purification. Improvement is correlated with increases in the concentration of plasma vasoactive substances (endothelin and dopamine) and decreases in nitric oxide synthase activity.

[Recruitment maneuver in the treatment of young piglets with acute lung injury].

OBJECTIVE: To study the feasibility, efficiency and any benefits of recruitment maneuver (RM) in the facilitation of lung repair during recovery from ALI in acute lung injury (ALI) model of young piglets. METHODS: The piglet model of ALI was established by an intravenous injection of lipopolysaccharide (LPS). Twelve ALI piglets were randomly divided into two groups: conventional ventilation (CON) and RM with low tidal volume. Arterial blood gas, dynamic lung compliance (Cdyn) and systematic hemodynamics were monitored during the treatment. TGF-ß1 levels in bronchoalveolar lavage fluid (BALF) and plasma were measured. The mRNA expression of TGF-ß1 in the lungs was assessed by real time PCR. Lung tissue was examined for morphological changes. RESULTS: No significant difference was observed in cardiac output and peripheral vascular resistance (PVR) between the two groups. The extravascular lung water index (ELWI) from 6 hrs after ALI inducement and the pulmonary vascular permeability index (PVPI) 8 hrs after ALI inducement in the RM group decreased significantly compared with the CON group. Cdyn in the RM group increased quickly 1 hr after ALI inducement, and there was a significant difference between the two groups (P<0.05). P/F (ratio of PaO2 to FiO2) in the RM group was significantly higher than in the CON group from 2 hrs after ALI inducement (P<0.05). Alveolar-to-arterial oxygen difference in the RM group was obviously lower compared with the CON group from 2 hrs after ALI inducement (P<0.05). The levels of TGF-ß1 in plasma and BALF and the mRNA expression of TGF-ß1 in the lung tissue were lower than in the CON group. Volume density of alveolar aeration in the RM group was significantly higher than in the CON group, and the injury score in the RM group was lower (P<0.05). CONCLUSIONS: RM can improve gas exchange and Cdyn in the treatment of piglets with ALI. RM is a safe and effective approach to alveolar recruitment and can alleviate ventilation induced lung injury.

A novel lncRNA-miRNA-mRNA triple network identifies lncRNA XIST as a biomarker for acute myocardial infarction.

Despite the well-established role of long non-coding RNAs (lncRNAs) across various biological processes, their mechanisms in acute myocardial infarction (AMI) are not fully elucidated. The GSE34198 dataset from the Gene Expression Omnibus (GEO) database, which comprised 49 specimens from individuals with AMI and 47 specimens from controls, was extracted and analysed using the weighted gene co-expression network analysis (WGCNA) package. Twenty-seven key genes were identified through a combination of the degree and gene significance (GS) values, and the CDC42 (degree = 64), JAK2 (degree = 41), and CHUK (degree = 30) genes were identified as having the top three-degree values among the 27 genes. Potential interactions between lncRNA, miRNAs and mRNAs were predicted using the starBase V3.0 database, and a lncRNA-miRNA-mRNA triple network containing the lncRNA XIST, twenty-one miRNAs and three hub genes (CDC42, JAK2 and CHUK) was identified. RT-qPCR validation showed that the expression of the JAK2 and CDC42 genes and the lncRNA XIST was noticeably increased in samples from patients with AMI compared to normal samples. Pearson's correlation analysis also proved that JAK2 and CDC42 expression levels correlated positively with lncRNA XIST expression levels. The area under ROC curve (AUC) of lncRNA XIST was 0.886, and the diagnostic efficacy of the lncRNA XIST was significantly better than that of JAK2 and CDC42. The results suggested that the lncRNA XIST appears to be a risk factor for AMI likely through its ability to regulate JAK2 and CDC42 gene expressions, and it is expected to be a novel and reliable biomarker for the diagnosis of AMI.

Effects of USF1 SNPs and SNP-Environment Interactions on Serum Lipid Profiles and the Risk of Early-Onset Coronary Artery Disease in the Chinese Population.

Background: Upstream transcription factor 1 (USF1) single-nucleotide polymorphisms (SNPs) are significantly associated with serum lipid levels in several different ethnic groups or populations, but their association with lipid levels and the risk of early-onset coronary artery disease (EOCAD) has not been reported in Han populations of southern China. Methods: Six USF1 SNPs (rs3737787, rs2774276, rs2516839, rs2516838, rs1556259, and rs2516837) were genotyped by next-generation sequencing (NGS) techniques in 686 control subjects and 728 patients with EOCAD. Results: The genotypic and allelic frequencies of the USF1 rs3737787 SNP were significantly different between the control and EOCAD groups. The subgroup analysis identified that the rs3737787T allele was related to a decreased risk of EOCAD, whereas the rs3737787C-rs2774276G-rs2516839A and rs3737787C-rs2774276G-rs2516839G haplotypes were related to an increased risk of EOCAD in men, and the rs3737787C-rs2774276G-rs2516839A and rs3737787T-rs2774276C-rs2516839A haplotypes were correlated with an increased risk of EOCAD in women (p < 0.05-0.01). Male rs3737787T allele carriers had lower low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations than the rs3737787T allele non-carriers (p < 0.01). The interactions of rs3737787 with alcohol consumption and rs2516839 with smoking affected serum TC and LDL-C levels in men, whereas the interaction of rs3737787 with alcohol consumption affected serum high-density lipoprotein cholesterol (HDL-C) levels and the rs2516839-smoking interaction affected serum TC levels in women (p I < 0.001). The expression levels of the USF1 mRNA, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were significantly lower in controls than in patients with EOCAD, and rs3737787T allele carriers displayed lower IL-1ß, TNF-α, IL-6, and USF1 mRNA expression levels than the rs3737787T allele non-carriers. In addition, IL-1ß, TNF-α, and IL-6 expression levels were significantly positively correlated with USF1 mRNA levels (p < 0.01). Conclusion: Sex-specific correlations were identified between the USF1 rs3737787T allele with blood lipid levels and the risk of EOCAD. The USF1 rs3737787T allele affects the risk of EOCAD by modulating serum lipid levels and the expression of inflammatory factors, including IL-1ß, TNF-α, and IL-6.

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning.

Background: The immune system significantly participates in the pathologic process of atrial fibrillation (AF). However, the molecular mechanisms underlying this participation are not completely explained. The current research aimed to identify critical genes and immune cells that participate in the pathologic process of AF. Methods: CIBERSORT was utilized to reveal the immune cell infiltration pattern in AF patients. Meanwhile, weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules that were significantly correlated with AF. The characteristic genes correlated with AF were identified by the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithm. Results: In comparison to sinus rhythm (SR) individuals, we observed that fewer activated mast cells and regulatory T cells (Tregs), as well as more gamma delta T cells, resting mast cells, and M2 macrophages, were infiltrated in AF patients. Three significant modules (pink, red, and magenta) were identified to be significantly associated with AF. Gene enrichment analysis showed that all 717 genes were associated with immunity- or inflammation-related pathways and biological processes. Four hub genes (GALNT16, HTR2B, BEX2, and RAB8A) were revealed to be significantly correlated with AF by the SVM-RFE algorithm and LASSO logistic regression. qRT-PCR results suggested that compared to the SR subjects, AF patients exhibited significantly reduced BEX2 and GALNT16 expression, as well as dramatically elevated HTR2B expression. The AUC measurement showed that the diagnostic efficiency of BEX2, HTR2B, and GALNT16 in the training set was 0.836, 0.883, and 0.893, respectively, and 0.858, 0.861, and 0.915, respectively, in the validation set. Conclusions: Three novel genes, BEX2, HTR2B, and GALNT16, were identified by WGCNA combined with machine learning, which provides potential new therapeutic targets for the early diagnosis and prevention of AF.