Characteristics and risk factors for renal recovery after acute kidney injury in critically ill patients in cohorts of elderly and non-elderly: a multicenter retrospective cohort study.

BACKGROUND: The purpose of this study was to explore the risk factors for renal nonrecovery among elderly and nonelderly patients with acute kidney injury (AKI) in critically ill patients. METHODS: A multicenter retrospective cohort of 583 critically ill patients with AKI was examined. We found the best cutoff value for predicting renal recovery by age was 63 years old through logistic regression. All patients were divided into two cohorts, age <63 and age ≥63-years old; on the basis of renal recovery at 30 days after AKI, the two patient cohorts were further divided into a renal recovery group and a renal nonrecovery group. Multivariate logistic regression was used to analyze the risk factors affecting renal recovery in the two cohorts. RESULTS: The 30-day renal recovery rate of patients aged <63 years was 70.0% (198/283), multivariate analysis showed that the independent risk factors affecting renal nonrecovery in age <63 years old included AKI stage, blood lactate level and hemoglobin level. The 30-day renal recovery rate of patients aged ≥63 years was 28.7% (86/300), multivariate analysis showed that the independent risk factors for renal nonrecovery in age ≥63-years old included diabetes mellitus, surgery with general anesthesia, AKI stage, APACHE II score, eGFR, and hemoglobin level. CONCLUSIONS: The renal nonrecovery after AKI in critically ill patients in patients aged ≥63 years was more strongly affected by multiple risk factors, such as diabetes mellitus, surgery with general anesthesia, eGFR, and APACHE II score, in addition to hemoglobin and AKI stage.

Transcriptome Analysis Reveals Brassinolide Signaling Pathway Control of Foxtail Millet Seedling Starch and Sucrose Metabolism under Freezing Stress, with Implications for Growth and Development.

Low-temperature stress limits the growth and development of foxtail millet. Freezing stress caused by sudden temperature drops, such as late-spring coldness, often occurs in the seedling stage of foxtail millet. However, the ability and coping strategies of foxtail millet to cope with such stress are not clear. In the present study, we analyzed the self-regulatory mechanisms of freezing stress in foxtail millet. We conducted a physiological study on foxtail millet leaves at -4 °C for seven different durations (0, 2, 4, 6, 8, 10, and 12 h). Longer freezing time increased cell-membrane damage, relative conductance, and malondialdehyde content. This led to osmotic stress in the leaves, which triggered an increase in free proline, soluble sugar, and soluble protein contents. The increases in these substances helped to reduce the damage caused by stress. The activities of superoxide dismutase, peroxidase, and catalase increased reactive oxygen species (ROS) content. The optimal time point for the response to freezing stress was 8 h after exposure. The transcriptome analysis of samples held for 8 h at -4 °C revealed 6862 differentially expressed genes (DEGs), among which the majority are implicated in various pathways, including the starch and sucrose metabolic pathways, antioxidant enzyme pathways, brassinolide (BR) signaling pathway, and transcription factors, according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. We investigated possible crosstalk between BR signals and other pathways and found that BR signaling molecules were induced in response to freezing stress. The beta-amylase (BAM) starch hydrolase signal was enhanced by the BR signal, resulting in the accelerated degradation of starch and the formation of sugars, which served as emerging ROS scavengers and osmoregulators to resist freezing stress. In conclusion, crosstalk between BR signal transduction, and both starch and sucrose metabolism under freezing stress provides a new perspective for improving freezing resistance in foxtail millet.

Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis.

Peritonitis caused by LPS is a severe clinical challenge, which causes organ damage and death. However, the mechanism of LPS-induced peritonitis has not been fully revealed yet. Here, we investigated the transcriptome profile of the peritoneal tissue of LPS-induced peritonitis in mice. A model of LPS-induced peritonitis in mice was established (LPS 10 mg/kg, i.p.), and the influence of TAK 242 (TLR4 inhibitor) on the level of inflammatory cytokines in mouse peritoneal lavage fluid was investigated by using an ELISA test. Next, the peritoneal tissues of the three groups of mice (Control, LPS, and LPS+TAK 242) (n = 6) were isolated and subjected to RNA-seq, followed by a series of bioinformatics analyses, including differentially expressed genes (DEGs), enrichment pathway, protein-protein interaction, and transcription factor pathway. Then, qPCR verified-hub genes that may interact with TAK 242 were obtained. Subsequently, the three-dimensional structure of hub proteins was obtained by using homology modeling and molecular dynamics optimization (300 ns). Finally, the virtual docking between TAK 242 and hub proteins was analyzed. Our results showed that TAK 242 significantly inhibited the production of inflammatory cytokines in the peritoneal lavage fluid of mice with peritonitis, including IL-6, IFN-γ, IL-1ß, NO, and TNF-α. Compared with the Control group, LPS treatment induced 4201 DEGs (2442 down-regulated DEGs and 1759 up-regulated DEGs). Compared with the LPS group, 30 DEGs were affected by TAK 242 (8 down-regulated DEGs and 22 up-regulated DEGs). A total of 10 TAK 242-triggered hub genes were obtained, and the possible docking modes between TAK 242 and hub proteins were acquired. Overall, our data demonstrated that a large number of DEGs were affected in LPS-triggered peritonitis mice. Moreover, the TLR4 inhibitor TAK 242 is capable of suppressing the inflammatory response of LPS-induced peritonitis. Our work provides clues for understanding the pathogenesis of LPS-induced peritonitis in mice.

miR-365 regulates liver cancer stem cells via RAC1 pathway.

Liver cancer stem cells (CSCs) were involved in tumorigenesis, progression, recurrence, and drug resistance of hepatocellular carcinoma (HCC). miR-365 was downregulated in hepatocellular carcinoma and inhibited HCC cell proliferation and invasion. However, the role of miR-365 in liver cancer stem cells was unknown. Herein, we observed a remarkable decrease of miR-365 expression in CD133 or EpCAM-positive liver CSCs as well as in CSC-enriched hepatoma spheres. Up-regulated miR-365 suppressed liver CSC expansion by inhibiting the dedifferentiation of hepatoma cells and decreasing the self-renewal ability of liver CSCs. Mechanistically, bioinformatic and luciferase reporter analysis identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as a direct target of miR-365. Overexpression of miR-365 in hepatoma cells downregulated the RAC1 mRNA and protein expression. RAC1 also could promote the expansion of liver CSCs. The special RAC1 inhibitor EHop-106 or RAC1 overexpression abolished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-365 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-365-suppressed liver CSCs expansion. miR-365 was downregulated in liver CSCs and could inhibit HCC cells dedifferentiation and liver CSCs expansion by targeting RAC1 signaling.

Four differentially methylated gene pairs to predict the prognosis for early stage hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) was the second most common malignant tumor with a poor prognostic condition. We aimed to identify novel methylation signatures to predict HCC patients at their early stages. Differentially expressed methylated genes between HCC patients and normal liver tissues retrieved from TCGA were screened out by SAM. Genes highly related to patients' survival were figured out by COX. The signatures that could identify relapse HCC patients were identified by the forwarding search algorithm. Besides, functional enrichment analysis was performed on the methylation genes in the signature. A total of 5,392 CPG sites that differentially methylated expressed were found out and 4,294 differentially expressed genes were obtained. A total of 197 genes among were associated with RFS of HCC patients at both stage I and stage II. Signature composed of 21 pairs was obtained to predict the prognostic situation by C-index forward search method. The function of these genes was figured out by functional enrichment analysis. To summary, the signature composed of 21 gene pairs that can predict the prognostic situation of HCC patients at both stage I and stage II, provided a reference standard for the adjuvant therapy of HCC patients after surgery.

miR-365 inhibits the progression of gallbladder carcinoma and predicts the prognosis of Gallbladder carcinoma patients.

Gallbladder carcinoma (GBC) is one of the most common fatal biliary tract tumors in the world. Its 3-year survival rate is 30% and the recurrence rate remains very high. miR-365 was downregulated in numerous tumors and worked as tumor suppressor gene. However, the role of miR-365 in GBC was unclear. In this study, our results found that the expression of miR-365 in GBC tissues was reduced rather than that in non-cancerous tissues. miR-365 overexpression inhibited the proliferation, metastasis and expansion of GBC CSCs. Mechanically, bioinformatic and luciferase reporter analysis identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as a direct target of miR-365. Overexpression of miR-365 in GBC cells reduced the RAC1 mRNA and protein expression. The special RAC1 inhibitor EHop-106 abolished the discrepancy of growth, metastasis and self-renewal ability between miR-365-overexpression GBC cells and their control cells, which further demonstrated that RAC1 was involved in miR-365-disrupted GBC cells growth, metastasis and self-renewal. More importantly, reduced expression of miR-365 was a predictor of poor prognosis of GBC patients. In conclusion, miR-365 inhibited GBC cell growth, metastasis and self-renewal capacity by directly targeting RAC1, and may therefore prove to be a novel prognosis biomarker for GBC patients.

Circular RNA circ_0001105 protects the intestinal barrier of septic rats by inhibiting inflammation and oxidative damage and YAP1 expression.

The integrity of the intestinal barrier is critical for protecting the host against the intestinal lumen and pathogens. The roles of circRNAs in the intestinal barrier dysfunction in sepsis remained unclear. The present study aims to investigate the role of circ_0001105 in the intestinal mucosal permeability, oxidative damage and morphological changes during sepsis. We found that upregulation of circ_0001105 decreased the levels of serum D-lactic acid, diamine oxidase and fluorescence isothiocyanate dextran in septic rats. Upregulation of circ_0001105 also decreased the malondialdehyde content but enhanced superoxide dismutase activity in the intestinal tissues. Upregulation of circ_0001105 reduced the production of tumor necrosis factor α, interleukin (IL)-6, and IL-1ß and the expression of YAP1. Furthermore, upregulation of circ_0001105 improved the survival of rats with sepsis. In summary, our findings showed that circ_0001105 protects the intestinal barrier function of septic rats by inhibiting intestinal inflammation, oxidative damage and YAP1 expression. Our results provide a novel insight for developing sepsis treatment.

Fourier transform near-infrared spectroscopy used for purity determination of rhein-L-arginine cocrystal (argirein).

A method is described using rapid and sensitive Fourier transform near-infrared spectroscopy (FT-NIRS) for the determination of rhein-L-arginine cocrystal (argirein). By mixing different values of argirein into different proportions with rhein and arginine, we obtained 41 batches of samples to deatermine. Partial least squares (PLS) regression was selected as the analysis type and standard normal variate (SNV) and original spectra were adopted for the spectral pretreatment. The correlation coefficient (R) of the calibration model was above 0.99 and the root mean square error of predictions (RMSEP) was under 0.012. The developed model was applied to 10 batches of known samples with satisfactory results. The established method is validated and can be applied to the intrinsic quality control of synthetic products and other cocrystals.

Laparoscopic versus open surgery for colon cancer: a meta-analysis of 5-year follow-up outcomes.

BACKGROUND: Colon cancer is one of the most common malignant tumors of digestive tract with a rather high incidence rate. Currently, surgery is the only radical therapy for colon cancer, while Laparoscopic colectomy (LAC) has become another focus since studies reported LAC could improve the short-time outcomes and quick recovery of patients compared with open colectomy (OC). However, it's still unclear whether LAC can better improve patients' long-time survival than OC. OBJECTIVE: We aimed to perform a meta-analysis to answer whether the 5-year recurrence and survival rate after LAC are comparable to those reported after OC in patient with colon cancer. METHODS: We searched Cochrane Library, PubMed, Embase, CBM, VIP, and CNKI for relevant studies. The time searched was from the establishment time of the databases to September 15, 2011. At the same time, we searched Google, Medical Martix and Baidu for more studies as well as a hand-search. We limited the language to English and Chinese. Two reviewers independently screened articles to identify randomized controlled trials (RCTs) according to the inclusion and exclusion criteria and assessed the methodological quality of included trials, and then extracted data. Meta-analysis was performed using RevMan5.0. RESULTS: Five RCTs involving 2695 patients reported long-term outcomes based on 5-year data and were included in the analysis. No significant differences between LAC and OC were found in the overall mortality (RR = 0.94; 95% CI (0.82, 1.09); P = 0.23, I(2) = 21%), total recurrence rate (RR = 0.94; 95% CI (0.81, 1.10); P = 0.24, I(2) = 27%), 5-year tumor free survival rate (RR = 1.00, 95% CI (0.94, 1.06); P = 0.96, I(2) = 0%). and overall 5-year survival (RR = 1.02; 95% CI (0.97, 1.07); P = 0.55, I(2) = 0%). CONCLUSIONS: This meta-analysis suggests that LAC was as effective and safe as OC for colon cancer.