Effect of Remimazolam on Induction and Maintenance of General Anesthesia in Kidney Transplant Patients.

Purpose: This study aims to evaluate the effect of remimazolam on induction and maintenance of general anesthesia in kidney transplant patients. Methods: 120 patients undergoing kidney transplant were divided into two groups: Propofol group (Group P) and Remimazolam group (Group R). Anesthesia induction: remimazolam had injected IV at a dose of 0.15-0.35 mg/kg in Group R, while propofol had injected IV at a dose of 2.0-2.5 mg/kg in Group P. Anesthesia maintenance: remimazolam was injected IV at a dose of 0.3-1.0 mg·kg-1·h-1 and propofol was injected IV at a dose of 1-12 mg·kg-1·h-1 in Group R, propofol was injected IV at a dose of 3-12 mg·kg-1·h-1 in Group P. All patients have the same remaining anesthesia durgs. Results: Compared with Group P, in Group R the time of disappearance of the eyelash reflex and the time to drop to 60 in BIS was longer (P < 0.05), the time of awakening was shorted (P < 0.05), the MAP of T6 was fluctuated less (P < 0.05), the incidence of hypotension and injection pain during induction was reduced (P < 0.001), the incidence of intraoperative bradycardia during operation was reduced (P < 0.05), the dosages of sedatives drug during maintenance was reduced (P < 0.05). There was no statistically significant difference in postoperative renal function between the two groups of patients (P > 0.05). Conclusion: Remimazolam can be safely and effectively used for the induction and maintenance of general anesthesia in kidney transplant patients.

Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) without symptomatic pulmonary involvement has been thought to be non-transmissible, but EPTB with asymptomatic pulmonary tuberculosis (PTB) could transmit tuberculosis (TB). Genomic investigation of Mycobacterium tuberculosis (Mtb) isolates from EPTB may provide insight into its epidemiological role in TB transmission. METHODS: Between January 2017 and May 2020, 107 Mtb isolates were obtained from surgical drainage of bone TB patients at the Beijing Chest Hospital, and 218 Mtb strains were isolated from PTB cases. These 325 Mtb isolates were whole-genome sequenced to reconstruct a phylogenetic tree, identify transmission clusters, and infer transmission links using a Bayesian approach. Possible subclinical PTB in the bone TB patients was investigated with chest imaging by two independent experts. RESULTS: Among 107 bone TB patients, 10 were in genomic clusters (≤12 SNPs). Phylogenetic analysis suggested that three bone TB patients transmitted the infection to secondary cases, supported by epidemiological investigations. Pulmonary imaging of 44 bone TB patients revealed that 79.5 % (35/44) had radiological abnormalities suggestive of subclinical PTB. CONCLUSIONS: This study provides genomic evidence that bone TB patients without clinically diagnosed PTB can be sources of TB transmission, underscoring the importance of screening for subclinical, transmissible PTB among EPTB cases.

B-lymphocyte-induced maturation protein-1 inhibits inflammation and pyroptosis to alleviate sepsis injury.

Liver and lung tissue damage caused by sepsis is still one of the causes of death. B-lymphocyte-induced maturation protein-1 (Blimp-1) has a protective role in inflammation-related disease. However, whether Blimp-1 can regulate cell pyroptosis and affect disease progression in sepsis is still unclear. Animal and cell models were established by the cecal ligation and puncture method and lipopolysaccharides (LPS)-induced RAW 264.7 cells, respectively, and the role of Blimp-1 in regulation inflammatory response and pyroptosis was verified. The changes of inflammation and pyroptosis in liver and lung tissues of septic mice were determined by the addition of TAK-242 (TLR4 inhibitor). Cell pyroptosis and the level of inflammation was detected after Blimp-1 knockdown and TAK-242 treatment in the cell model. The expression of Blimp-1 was continuously increased in a septic mice model. After treatment with TAK-242, the expression of Blimp-1, pyroptosis and inflammatory levels were reduced in mice. In the LPS-induced cell model, cell injury by knockout Blimp-1 was increased, and cell activity was restored after TAK-242 intervention. Overexpression of Blimp-1 relieved LPS-induced cellular inflammatory damage and pyroptosis. Our study had shown that Blimp-1 could improve septic damage by regulating the level of cellular inflammation and pyroptosis in sepsis.

A Pure Electric Driverless Crawler Construction Machinery Walking Method Based on the Fusion SLAM and Improved Pure Pursuit Algorithms.

Driverless technology refers to the technology that vehicles use to drive independently with the help of driverless system under the condition of unmanned intervention. The working environment of construction machinery is bad, and the working conditions are complex. The use of driverless technology can greatly reduce the risk of driver operation, reduce labor costs and improve economic benefits.Aiming at the problem of the GPS positioning signal in the working environment of construction machinery being weak and not able to achieve accurate positioning, this paper uses the fusion SLAM algorithm based on improved NDT to realize the real-time positioning of the whole vehicle through reconstruction of the scene. Considering that the motion characteristics of crawler construction machinery are different from those of ordinary passenger cars, this paper improves the existing pure pursuit algorithm. Simulations and real vehicle tests show that the algorithm combined with the fusion SLAM algorithm can realize the motion control of driverless crawler construction machinery well, complete the tracking of the set trajectory perfectly and have high robustness. Considering that there is no mature walking method of driverless crawler construction machinery for reference, the research of this paper will lay a foundation for the development of driverless crawler construction machinery.

Integrated bioinformatic analyses investigate macrophage-M1-related biomarkers and tuberculosis therapeutic drugs.

Tuberculosis (TB) is a common infectious disease linked to host genetics and the innate immune response. It is vital to investigate new molecular mechanisms and efficient biomarkers for Tuberculosis because the pathophysiology of the disease is still unclear, and there aren't any precise diagnostic tools. This study downloaded three blood datasets from the GEO database, two of which (GSE19435 and 83456) were used to build a weighted gene co-expression network for searching hub genes associated with macrophage M1 by the CIBERSORT and WGCNA algorithms. Furthermore, 994 differentially expressed genes (DEGs) were extracted from healthy and TB samples, four of which were associated with macrophage M1, naming RTP4, CXCL10, CD38, and IFI44. They were confirmed as upregulation in TB samples by external dataset validation (GSE34608) and quantitative real-time PCR analysis (qRT-PCR). CMap was used to predict potential therapeutic compounds for tuberculosis using 300 differentially expressed genes (150 downregulated and 150 upregulated genes), and six small molecules (RWJ-21757, phenamil, benzanthrone, TG-101348, metyrapone, and WT-161) with a higher confidence value were extracted. We used in-depth bioinformatics analysis to investigate significant macrophage M1-related genes and promising anti-Tuberculosis therapeutic compounds. However, more clinical trials were necessary to determine their effect on Tuberculosis.

m6A Modification Involves in Enriched Environment-Induced Neurogenesis and Cognition Enhancement.

Although previous studies have shown that an enriched environment (EE) promotes neurogenesis and alters DNA and histone modifications, it remains largely unknown whether an EE affects epitranscriptome in the context of neuronal development. Here, we showed that EE exposure enhanced the pool of adult neural stem/progenitor cells (aNSPCs) and promoted neuronal differentiation of aNSPCs. EE exposure also improved cognitive capabilities and altered the expression of genes relating to neuronal development, neurogenesis, and memory. N 6-Methyladenosine (m6A) immunoprecipitation combined with deep sequencing (MeRIP-seq) data analysis revealed that EE exposure increased the global level of m6A and led to differential m6A mRNA modification. Differential m6A modification-associated genes are involved in neuronal development, neurogenesis, and so on. Notably, EE exposure decreased the protein level of m6A eraser Fto, but did not affect the protein level of m6A writers METTL3 and METTL14. Taken together, our results suggest that enriched environment exposure induces differential m6A mRNA modification and adds a novel layer to the interaction between the environment and epigenetics in the context of postnatal neuronal development.

Selecting Hub Genes and Predicting Target Genes of microRNAs in Tuberculosis via the Bioinformatics Analysis.

Tuberculosis (TB) is the world's most prevalently infectious disease. Molecular mechanisms behind tuberculosis remain unknown. microRNA (miRNA) is involved in a wide variety of diseases. To validate the significant genes and miRNAs in the current sample, two messenger RNA (mRNA) expression profile datasets and three miRNA expression profile datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed (DE) genes (DEGs) and miRNAs (DE miRNAs) between healthy and TB patients were filtered out. Enrichment analysis was executed, and a protein-protein interaction (PPI) network was developed to understand the enrich pathways and hub genes of TB. Additionally, the target genes of miRNA were predicted and overlapping target genes were identified. We studied a total of 181 DEGs (135 downregulated and 46 upregulated genes) and two DE miRNAs (2 downregulated miRNAs) from two gene profile datasets and three miRNA profile datasets, respectively. 10 hub genes were defined based on high degree of connectivity. A PPI network's top module was constructed. The 23 DEGs identified have a significant relationship with miRNAs. 25 critically significant Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were discovered. The detailed study revealed that, in tuberculosis, the DE miRNA and DEGs form an interaction network. The identification of novel target genes and main pathways would aid with our understanding of miRNA's function in tuberculosis progression.

Screening of potential biomarkers for distinguishing between latent and active tuberculosis in children using bioinformatics analysis.

ABSTRACT: Tuberculosis (TB) is one of the leading causes of childhood morbidity and death globally. Lack of rapid, effective non-sputum diagnosis and prediction methods for TB in children are some of the challenges currently faced. In recent years, blood transcriptional profiling has provided a fresh perspective on the diagnosis and predicting the progression of tuberculosis. Meanwhile, combined with bioinformatics analysis can help to identify the differentially expressed genes (DEGs) and functional pathways involved in the different clinical stages of TB. Therefore, this study investigated potential diagnostic markers for use in distinguishing between latent tuberculosis infection (LTBI) and active TB using children's blood transcriptome data.From the Gene Expression Omnibus database, we downloaded two gene expression profile datasets (GSE39939 and GSE39940) of whole blood-derived RNA sequencing samples, reflecting transcriptional signatures between latent and active tuberculosis in children. GEO2R tool was used to screen for DEGs in LTBI and active TB in children. Database for Annotation, Visualization and Integrated Discovery tools were used to perform Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis. STRING and Cytoscape analyzed the protein-protein interaction network and the top 15 hub genes respectively. Receiver operating characteristics curve was used to estimate the diagnostic value of the hub genes.A total of 265 DEGs were identified, including 79 upregulated and 186 downregulated DEGs. Further, 15 core genes were picked and enrichment analysis revealed that they were highly correlated with neutrophil activation and degranulation, neutrophil-mediated immunity and in defense response. Among them TLR2, FPR2, MMP9, MPO, CEACAM8, ELANE, FCGR1A, SELP, ARG1, GNG10, HP, LCN2, LTF, ADCY3 had significant discriminatory power between LTBI and active TB, with area under the curves of 0.84, 0.84, 0.84, 0.80, 0.87, 0.78, 0.88, 0.84, 0.86, 0.82, 0.85, 0.85, 0.79, and 0.88 respectively.Our research provided several genes with high potential to be candidate gene markers for developing non-sputum diagnostic tools for childhood Tuberculosis.

Prediction and identification of CD4+ T cell epitope for the protective antigens of Mycobacterium tuberculosis.

ABSTRACT: CD4+T cell epitopes plays a key role in anti-tuberculosis (TB) immunity, CD4+T cell epitopes suitable for the domestic population are lacking. Therefore, we predicted and identified novel CD4+T cell epitopes.The bioinformatics software, namely, DNAStar (DNASTAR of the United States), SYFPEITHI (INTERFACTORS INSTITUT Für ZELL Biologie of Germany), RANKPEP, and NetMHC IIpan (National Cancer Institute, United States of America), were used to comprehensively predict the CD4+T cell immune epitope of Mycobacterium TB, and the predicted epitope polypeptide was synthesized by the standard Fmoc scheme. The proliferation of PBMC and CD4+T cells stimulated by peptides was preliminarily detected by the CCK8 method. Then, the candidate polypeptides screened out by the CCK8 method were verified again by the BrdU assay, and flow cytometry was performed to analyze further the extent of their stimulation on the proliferation of CD4+T cells. The changes in the secreted cytokines IFN-γ, TNF-α, IL-2, and IL-10 before and after the candidate polypeptide stimulation of CD4+T lymphocytes were detected by ELISA. The preliminary humoral immunity test was conducted by indirect ELISA to evaluate the serological diagnostic value of the CD4+T cell epitope polypeptide.In this study, 5 novel candidate CD4+T cell epitope polypeptides with the amino acid sequences of LQGQWRGAAGTAAQA, PVTLAETGSTLLYPL, AAAWGGSGSEAYQGV, QFVYAGAMSGLLDPS, and KAALTRTASNMNAAA and others that have not been reported in the research were predicted. For convenience, the 5 candidates were successively named as P39, P50, P40, P185, and P62. P39, P62, and the mixed peptide P39+P62 could effectively induce the proliferation of CD4+T cells and increase the secretion of IFN-γ, TNF-α, and IL-2 from the CD4+T cells, while reducing the content of IL-10. The serological test showed that the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of P39 were 75%, 67.71%, and 0.844, respectively. The sensitivity, specificity, and AUC of P62 were 91.66%, 46.87%, and 0.649, respectively. The sensitivity of the mixed peptide P39+P62 was 95.83%, the specificity was 97.91%, and the AUC was 0.793.The P39 and P62 polypeptides were predicted and identified as potential CD4+T cell immune epitope polypeptides of M. TB. The polypeptide had better diagnosis effect, which provided potential candidate epitope polypeptides for the development of TB-specific diagnosis reagents and novel TB epitope vaccines.

Expression and Clinical Significance of POLR1D in Colorectal Cancer.

PURPOSE: RNA polymerase I subunit D (POLR1D) is involved in the synthesis of ribosomal RNA precursors and small RNAs, but its mechanism in the development and progression of colorectal cancer (CRC) remains ambiguous. Thus, this research aimed to investigate POLR1D's expression and significance in human CRC patients and evaluate its association with clinicopathological characteristics. METHODS: Matched fresh-frozen cancerous and non-cancerous tissues were collected from 100 patients diagnosed with CRC. Immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction analyses were adopted to validate the correlation between POLR1D expression and clinicopathological parameters in CRC tissues and adjacent normal tissues (ANTs). RESULTS: POLR1D expression in CRC tissues was significantly higher than in the ANTs. χ2 test and Spearman's correlative analysis showed that a high POLR1D expression is significantly associated with clinical stage, Dukes stage, tumor differentiation, depth of invasion, and metastasis (p < 0.05). It is not correlated with gender, age, and tumor location and size (p > 0.05). Kaplan-Meier survival curves show that the overall survival (OS) time for the low expression group is remarkably longer than for the high expression group (p < 0.0015). Univariate and multivariate analyses indicate that a high POLR1D expression is an independent prognostic factor for poor OS (p = 0.000). CONCLUSION: The findings of this study strongly indicate that POLR1D plays a pivotal role in the occurrence and progression of CRC. It might be an independent adverse prognostic factor for CRC patients and could serve as a potential therapeutic target for clinical diagnosis in CRC and anticancer drug development.

Association of human leukocyte antigens-DQB2/DPA1/DPB1 polymorphism and pulmonary tuberculosis in the Chinese Uygur population.

BACKGROUND: Tuberculosis (TB) is the second-leading cause of death globally. Genetic polymorphisms in human leukocyte antigens (HLA)-DQB2, HLA-DPA1, and HLA-DPB1 may partly explain individual differences in TB susceptibility. METHODS: We performed a hospital-based case-control study to assess the genetic influence of single-nucleotide polymorphisms (SNPs) in the HLA (HLA-DPA, HLA-DPB, and HLA-DQB) on the development of TB. There were 248 TB-infected cases and 340 healthy controls in this study. RESULTS: The HLA-DQB2 rs7453920 genotype GG was applied as the reference group, the GA genotype was related to a considerably magnified risk of TB (GA vs. GG: adjusted OR = 1.547, 95% CI = 1.039-2.304, p = 0.032). Nevertheless, the other two SNPs were not associated with TB risk. Stratified analyses suggested that tobacco was associated with an increased risk of TB in HLA-DQB2 rs7453920 G>A. CONCLUSION: These results suggested that the functional HLA-DQB2 rs7453920 G>A polymorphism may contribute to the genetic susceptibility to TB. Nevertheless, the results were based on a limited sample size, and larger well-designed studies are expected to confirm these preliminary findings.

MBL2 rs7095891 G > A polymorphism was associated with an increased risk of tuberculosis in the Chinese Uygur population.

INTRODUCTION: Tuberculosis (TB) is a foremost infectious disease in most parts of the world. Globally, tuberculosis is the second-leading cause of infectious diseases. This has become a significant world-wide social and public health issue, and one of the major diseases in China. In addition to environmental risk factors, genetic factors may play an important role in the development of tuberculosis. METHODS: We conducted a case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): MBL2 rs1800450 C > T, MBL2 rs7095891 G > A and MBL2 rs7096206 C > G, and their influences on the development of tuberculosis. A total of 231 tuberculosis cases and 240 controls were included in this study. Genotypes were determined using a custom-designed 48-Plex SNPscanTM kit. RESULTS: The MBL2 rs7095891 G > A polymorphism was associated with an increased risk of TB. However, there were no significant links with the other two SNPs. In any subgroup, there was no relvant risk of TB associated with MBL2 rs7095891 G > A polymorphism. CONCLUSION: These findings suggest that functional polymorphism MBL2 rs7095891 G > A may be positively correlated with susceptibility to tuberculosis. These findings may be somewhat limited by sample size. A further study with more focus on different regions, ethnic groups and larger sample sizes is therefore suggested.

Effects of imipenem combined with low-dose cyclophosphamide on the intestinal barrier in septic rats.

Anti-infection therapy combined with immunotherapy is one of the important research approaches for treating sepsis. However, the combination of anti-infection and immunotherapy therapeutic agents may have an adverse effect on intestinal barrier function. In the present study, it was hypothesized that imipenem combined with low-dose cyclophosphamide (CTX) could improve the sepsis survival rate compared with imipenem treatment alone. In addition, the alterations in the intestinal barrier were investigated and the possible mechanisms of altering intestinal barrier function in septic rats treated with imipenem combined with low-dose CTX or imipenem alone were explored. To investigate the effect of imipenem combined with low-dose CTX on the intestinal barrier, the markers of histopathology, intestinal permeability, intestinal epithelial apoptosis, cytokines interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α, and tight junction proteins zonula occludens (ZO)-1, occludin and claudin-2, were quantitatively and qualitatively evaluated. The results indicated that imipenem combined with low-dose CTX significantly improved the survival rate of rats compared with imipenem alone (P<0.05). However, no significantly difference between the treatment with imipenem combined with low-dose CTX and imipenem treatment alone was indicated with regard to histopathology, intestinal permeability, intestinal epithelial apoptosis and the expression of claudin-2, ZO-1 and TNF-α. However, imipenem combined with low-dose CTX significantly reduced IL-6 and IL-10 expression and significantly increased occludin expression compared with imipenem alone (P<0.05). It was concluded that imipenem combined with low-dose CTX could improve the survival rate of rats with sepsis compared with rats treated with imipenem alone. The present findings suggest that imipenem combined with low-dose CTX may cause damage to the intestinal barrier function and the mechanism may be associated with a reduction in IL-10 expression.

Effect of early fluid resuscitation combined with low dose cyclophosphamide on intestinal barrier function in severe sepsis rats.

To investigate the effect of early fluid resuscitation on intestinal microecology in rats with severe sepsis. The severe sepsis model used was mainly cecal ligation perforation (CLP) model. Male SD rats were randomly divided into five groups: sham, CLP, CLP + normal saline (NS), CLP + cyclophosphamide (CTX), and CLP + NS + CTX. (1) The levels of IL-6, IL-10, and TNF-α in peripheral blood were measured by ELISA. (2) The expression of occludin/ß-action in colonic tissue of mice was examined by Western Blot. (3) The intestinal permeability was measured by FD70 detection. (4) The length of the chorionic membrane was measured by colon histopathological staining. (5) The intestinal epithelial cell apoptosis was measured with the apoptosis index. (1) The rat model of severe sepsis was successfully replicated, and the 7-day survival rate of sepsis mice in each group was analyzed. (2) The expression level of splenic junction protein and the pathological damage in colonic tissue of the severe sepsis mice was significantly different between sham, CLP, CTX, NS, and NS + CTX (P < 0.05). The expression of tight junction protein in the NS + CTX mice was the highest, and the pathological damage was the smallest. (3) The colonic tissue apoptosis and intestinal permeability in the severe sepsis mice were compared with those of the colon tissues (P < 0.05). (4) The expression levels of IL-6, IL-10, and TNF-α in peripheral blood were significantly increased after severe sepsis (P < 0.01). The expression of IL-6 and TNF-alpha in each treatment group decreased (P < 0.05), while the expression of IL-10 in NS + CTX group increased significantly (P < 0.01). (1) We successfully replicated the rat model of severe sepsis. (2) Early fluid intervention and cyclophosphamide treatment can significantly improve the 7-day survival rate of the sepsis mice. (3) The fluid resuscitation and cyclophosphamide can delay intestinal damage to the intestinal tract barrier function and play a protective role.

Identification of key genes and pathways using bioinformatics analysis in septic shock children.

BACKGROUND AND HYPOTHESIS: Sepsis is still one of the reasons for serious infectious diseases in pediatric intensive care unit patients despite the use of anti-infective therapy and organ support therapy. As it is well-known, the effect of single gene or pathway does not play a role in sepsis. We want to explore the interaction of two more genes or pathways in sepsis patients for future works. We hypothesize that the discovery from the available gene expression data of pediatric sepsis patients could know the process or improve the situation. METHODS AND RESULTS: The gene expression profile dataset GSE26440 of 98 septic shock samples and 32 normal samples using whole blood-derived RNA samples were generated. A total of 1,108 upregulated and 142 downregulated differentially expressed genes (DEGs) were identified in septic shock children using R software packages. The Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed using DAVID software; Gene Set Enrichment Analysis method was also used for enrichment analysis of the DEGs. The protein-protein interaction (PPI) network and the top 10 hub genes construction of the DEGs were constructed via plug-in Molecular Complex Detection and cytoHubba of Cytoscape software. From the PPI network, the top 10 hub genes, which are all upregulated DEGs in the septic shock children, were identified as GAPDH, TNF, EGF, MAPK3, IL-10, TLR4, MAPK14, IL-1ß, PIK3CB, and TLR2. Some of them were involved in one or more significant inflammatory pathways, such as the enrichment of tumor necrosis factor (TNF) pathway in the activation of mitogen-activated protein kinase activity, toll-like receptor signaling pathway, nuclear factor-κB signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway. These findings support future studies on pediatric septic shock.

Imipenem and normal saline with cyclophosphamide have positive effects on the intestinal barrier in rats with sepsis.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused the dysregulation of host inflammatory response and immunosuppression to infection Early recognition and intervention are hence of paramount importance. In this respect the "sepsis bundle" was proposed in 2004 to be instituted in cases of suspected sepsis. OBJECTIVE AND HYPOTHESIS: We hypothesised that a combination treatment of the sepsis bundle with cyclophosphamide would improve the function of the intestinal mucosa and enhance survival in rats with induced sepsis. METHODS AND RESULTS: Sprague-Dawley rats were divided into 5 different groups: sham, cecal ligation and puncture (CLP), cyclophosphamide (CTX), imipenem+normal saline (NS) and imipenem+NS+CTX. Cecal ligation and puncture were used for inducing the polymicrobial sepsis. Western-blot was used to measure the occludin protein, and ELISA for examining the plasma level of cytokines IL-6, IL-10 and TNF-α. TUNEL assay for testing the intestinal mucosal apoptosis, and hematoxylin-eosin staining for observing the intestinal mucosal changes. The permeability of intestinal mucosa was determined by the plasma level of FD-70. The results showed that the combination treatment of the sepsis bundle with cyclophosphamide attenuated cytokine levels, inhibited epithelial cell apoptosis and improved the function of the intestinal barrier. The survival rate of the group treated with the combined therapy was significantly higher than that of the other groups. CONCLUSION: The combination treatment of sepsis bundle with cyclophosphamide improves the function of the intestinal barrier and enhances survival in septic rats.

Expression Profiles of Six Atherosclerosis-Associated microRNAs That Cluster in Patients with Hyperhomocysteinemia: A Clinical Study.

The aim of this study is to discuss the hypothesis that expression of plasma atherosclerosis-associated microRNAs (miRNAs) in hyperhomocysteinemia (Hhcy) patients could predict the presence of atherosclerosis from different channels. Six plasma miRNAs (miR-145, miR-155, miR-222, miR-133, miR-217, and miR-30) selected for our study have been confirmed as critical gene regulators involved in atherosclerosis and can be steadily determined in plasma. Expression of the above six plasma circulating miRNAs revealed significant upregulation of two miRNAs (miR-133 and miR-217) and downregulation of three miRNAs (miR-145, miR-155, and miR-222). Six candidate miRNAs showed a significant correlation with homocysteine (Hcy) or lipid parameters. The results of this study indicated that miR-217 was further significantly upregulated in Hhcy + ATH groups than in normal control, Hhcy-, and atherosclerosis-alone (ATH) groups and it showed a significant negative correlation with Hcy and triglycerides. More specifically, miR-217 showed the most specific expression patterns in all patients with atherosclerosis (ATH and Hhcy + ATH groups), which may have been a diagnostic value for Hhcy complicated with atherosclerosis, and predicted the progress of atherosclerosis in Hhcy patients effectively.

Heat transfer analysis of cylindrical anaerobic reactors with different sizes: a heat transfer model.

The temperature is the essential factor that influences the efficiency of anaerobic reactors. During the operation of the anaerobic reactor, the fluctuations of ambient temperature can cause a change in the internal temperature of the reactor. Therefore, insulation and heating measures are often used to maintain anaerobic reactor's internal temperature. In this paper, a simplified heat transfer model was developed to study heat transfer between cylindrical anaerobic reactors and their surroundings. Three cylindrical reactors of different sizes were studied, and the internal relations between ambient temperature, thickness of insulation, and temperature fluctuations of the reactors were obtained at different reactor sizes. The model was calibrated by a sensitivity analysis, and the calibrated model was well able to predict reactor temperature. The Nash-Sutcliffe model efficiency coefficient was used to assess the predictive power of heat transfer models. The Nash coefficients of the three reactors were 0.76, 0.60, and 0.45, respectively. The model can provide reference for the thermal insulation design of cylindrical anaerobic reactors.

Effects of peritoneal macrophage autophagy on the immune function of sepsis mice.

OBJECTIVE: To investigate the effect of peritoneal macrophage autophagy on immune function in sepsis mice. METHODS: Seventy-two male BALB/C mice were intraperitoneally injected with LPS to induce sepsis. The mice were randomly divided into six groups: LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h. LPS with a dose of 10 mg/kg was intraperitoneally injected into the abdominal cavity of the sepsis mice, and the control group was injected with the same dose of saline. ELISA was used to detect the concentrations of inflammatory factors IL-2, IL-10 and TNF-α in the peripheral blood, and the CD4+T/CD8+T ratio in the peripheral blood was detected by flow cytometry. The expression levels of LC3II and Beclin-1/beta-action in the mouse macrophages were measured using Western blot to determine the level of autophagy. RESULTS: The expression levels of LC3II and Beclin-1 were significantly higher in the peritoneal macrophages of the mice from the LPS+2 h group than in those of the mice from the normal group (P<0.05). Meanwhile, these levels continuously declined in the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups (P<0.05). The peripheral blood CD4+T/CD8+T cell ratio was significantly higher in the LPS+2 h and LPS+6 h groups than in the normal group (P<0.05). The ratio peaked at 6 h and then continuously declined (P<0.05). Furthermore, the concentrations of IL-2 and Tnf-α were significantly higher in the peripheral blood serum of the LPS+2 h, LPS+6 h and LPS+12 h groups than in those of the normal group (P<0.05). The peak was observed at 12 h followed by a continuous decline in the LPS+24 h and 3 LPS+6 h groups (P<0.05). The peripheral serum IL-10 concentration was significantly higher in the LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups than in the normal group (P<0.05). In the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups, the peritoneal macrophages LC3II, Beclin-1 and peripheral serum CD+4T/CD+8T ratio correlation index R2=0.716 (P=0.043), R2=0.954 (P=0.023). CONCLUSION: Autophagy in peritoneal macrophages plays an important role in the immune function of sepsis mice. In addition, the autophagy of peritoneal macrophages and the immune function of sepsis mice are strongly correlated. Furthermore, macrophage autophagy plays an important role in the immune function changes in sepsis mice, and the underlying mechanism may be involved in inflammation and macrophage antigen presentation by regulating the secretion of inflammatory cytokines and lymphocyte apoptosis antagonism.

Expression levels of atherosclerosis-associated miR-143 and miR-145 in the plasma of patients with hyperhomocysteinaemia.

BACKGROUND: An elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients. METHODS: A total of 100 participants were enrolled and included normal control subjects (NC = 20), hyperhomocysteinaemia alone subjects (Hhcy = 25), hyperhomocysteinaemia and carotid artery atherosclerosis combined subjects (Hhcy + ATH = 30) and patients with standalone carotid artery atherosclerosis (ATH = 25). Plasma Hcy, supplementary biochemical parameters and carotid artery ultrasonography (USG) were measured in all participants. MicroRNA expression levels in the peripheral blood were calculated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The correlations of miR-143 and miR-145 with Hcy, blood lipid parameters and carotid artery atherosclerotic plaques were evaluated using Pearson's correlation coefficients. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the capacities of miR-143 and miR-145 for the detection of Hhcy and atherosclerosis patients. RESULTS: MiR-143 and miR-145 exhibited trends towards significance with stepwise decreases from the NC to Hhcy groups and then to the Hhcy + ATH and ATH groups. Similar results were observed in the carotid artery plaque group (Hhcy + ATH and ATH grups) compared with the no-plaque group (NC and Hhcy groups). The miR-143 expression level exhibited significant negative correlations with Hcy, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). The miR-145 expression level exhibited significant negative correlations with Hcy, TC, triglyceride (TG) and LDL-c. MiR-143 and miR-145 exhibited the greatest area under the curves (AUCs) (0.775 and 0.681, respectively) for the detection of every Hhcy patient, including those in the Hhcy and Hhcy + ATH groups, from among all subjects. CONCLUSION: The results indicated that the levels of atherosclerosis-associated circulating miR-143 and miR-145 are linked to Hhcy. MiR-143 may be used as a potential non-invasive biomarkers of Hhcy and thus may be helpful in predicting the progress of atherosclerosis in Hhcy patients.