Dragon's blood attenuates LPS-induced intestinal epithelial barrier dysfunction via upregulation of FAK-DOCK180-Rac1-WAVE2-Arp3 and downregulation of TLR4/NF-κB signaling pathways.

Inflammation-induced intestinal epithelial barrier (IEB) dysfunction is one of the important reasons for the occurrence and development of intestinal inflammatory-related diseases, including ulcerative colitis (UC), Crohn's disease and necrotizing enterocolitis (NEC). Dragon's blood (DB) is a traditional Chinese medicine and has been clinically used to treat UC. However, the protective mechanism of DB on intestinal inflammatory-related diseases has still not been elucidated. The present study aimed to explore the protection mechanism of DB on IEB dysfunction in rat ileum and human colorectal adenocarcinoma cells (Caco-2)/human umbilical vein endothelial cells (HUVECs) coculture system induced by lipopolysaccharide (LPS). DB could ameliorate rat ileum mucosa morphological injury, reduce the accumulation of lipid-peroxidation products and increase the expression of junction proteins. DB also alleviated LPS-induced Caco-2 cells barrier integrity destruction in Caco-2/ HUVECs coculture system, leading to increased trans-endothelial electrical resistance (TEER), reduced cell permeability, and upregulation of expressions of F-actin and junction proteins. DB contributed to the assembly of actin cytoskeleton by upregulating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway and contributed to the formation of intercellular junctions by downregulating TLR4-MyD88-NF-κB pathway, thus reversing LPS-induced IEB dysfunction. These novel findings illustrated the potential protective mechanism of DB on intestinal inflammatory-related diseases and might be useful for further clinical application of DB.

Hypoxia-inducible factor-2α promotes fibrosis in non-alcoholic fatty liver disease by enhancing glutamine catabolism and inhibiting yes-associated protein phosphorylation in hepatic stellate cells.

Non-alcoholic fatty liver disease (NAFLD) has a high global prevalence and affects approximately one-third of adults, owing to high-fat dietary habits and a sedentary lifestyle. The role of hypoxia-inducible factor 2α (HIF-2α) in NAFLD progression remains unknown. This study aimed to investigate the effects of chronic hypoxia on NAFLD progression by examining the role of hypoxia-inducible factor 2α (HIF-2α) activation and that of hepatic stellate cell (HSC)-derived myofibroblasts through glutaminolysis. We hypothesised that hypoxia exacerbates NAFLD by promoting HIF-2α upregulation and inhibiting phosphorylated yes-associated protein (YAP), and that increasing YAP expression enhances HSC-derived myofibroblasts. We studied patients with NAFLD living at high altitudes, as well as animal models and cultured cells. The results revealed significant increases in HSC-derived myofibroblasts and collagen accumulation caused by HIF-2α and YAP upregulation, both in patients and in a mouse model for hypoxia and NAFLD. HIF-2α and HIF-2α-dependent YAP downregulation reduced HSC activation and myofibroblast levels in persistent chronic hypoxia. Furthermore, hypoxia-induced HIF-2α upregulation promoted YAP and inhibited YAP phosphorylation, leading to glutaminase 1 (GLS1), SLC38A1, α-SMA, and Collagen-1 overexpression. Additionally, hypoxia restored mitochondrial adenosine triphosphate production and reactive oxygen species (ROS) overproduction. Thus, chronic hypoxia-induced HIF-2α activation enhances fibrosis and NAFLD progression by restoring mitochondrial ROS production and glutaminase-1-induced glutaminolysis, which is mediated through the inhibition of YAP phosphorylation and increased YAP nuclear translocation. In summary, HIF-2α plays a pivotal role in NAFLD progression during chronic hypoxia.

Metabolomic profiling of early inactive hepatic alveolar and cystic echinococcosis.

Hepatic alveolar echinococcosis (AE) and cystic echinococcosis (CE) are severe helminthic zoonoses and leading causes of parasitic liver damage. They pose a high mortality risk due to invisible clinical signs, especially at the early inactive stage. However, the specific metabolic profiles induced by inactive AE and CE lesions remain largely unclear. Therefore, we used gas chromatography-mass spectrometry-based metabolomic profiling to identify the global metabolic variations in AE and CE patient sera to differentiate between the two diseases and reveal the mechanisms underlying their pathogenesis. In addition, specific serum biomarkers of inactive hepatic AE and CE were screened using receiver operating curves, which can contribute to the clinical diagnosis of both diseases, especially in the earlier phase. These differential metabolites are involved in glycine, serine, tyrosine, and phenylalanine metabolism. Further analysis of key metabolic pathways showed that inactive AE lesions strongly alter amino acid metabolism in the host. CE lesions have an altered metabolism of oxidative stress response. These changes suggest these metabolite-associated pathways can serve as biomarkers to distinguish individuals with inactive AE and CE from healthy populations. This study also investigated the differences in serum metabolic profiles in patients with CE and AE. The biomarkers identified belonged to different metabolic pathways, including lipid, carnitine, androgen, and bile acid metabolism. Taken together, by investigating the different phenotypes of CE and AE with metabolomic profiling, serum biomarkers facilitating early diagnosis were identified.

Propensity score matching comparing short-term nerve electrical stimulation to pulsed radiofrequency for herpes zoster-associated pain: A retrospective study.

Background: Zoster-associated pain (ZAP) is notoriously difficult to treat. Pulsed radiofrequency (PRF) and short-term nerve electrical stimulation (st-NES) have been proven effective treatments for ZAP. However, it is still unclear which technique provides improved analgesia in ZAP. This study is based on a large-scale, long-term follow-up to evaluate the efficacy and safety between st-NES and PRF. Materials and methods: All eligible ZAP patients treated with st-NES or PRF in our department were enrolled. Cohorts were divided into the st-NES group and the PRF group. A 1:1 ratio propensity score matching (PSM) was used to balance the baseline characteristics. The PS-matched cohort was adopted to investigate the efficacy and safety of the two treatments. The ordinal regression analysis was performed to determine the variables affecting the treatment effect of ZAP. Results: A total of 226 patients were included after PSM. The numerical rating scale (NRS) scores in st-NES and PRF groups considerably reduced compared to baseline levels after treatment. The NRS scores in the st-NES group were obviously lower than those in the PRF group at discharge, 1, 3, 6, 12, and 24 months. During the follow-up period, the NRS reduction rate remained higher in the st-NES group than in the PRF group (P < 0.01). The dosage of medication, Pittsburgh Sleep Quality Index (PSQI) score, and the number of patients with aggravated pain after discharge in the st-NES group were significantly less than in the PRF group after treatment. Conclusion: Short-term nerve electrical stimulation has been shown to be more advantageous than PRF for pain relief and quality of life improvement for ZAP patients.

Spatial-topographic nestedness of interoceptive regions within the networks of decision making and emotion regulation: Combining ALE meta-analysis and MACM analysis.

Prominent theories propose that interoception modulates our behavioral and emotional responses involving decision-making and emotion regulation. Are the regions implicated in interoception also spatially related to and possibly nested within the networks of decision making and emotion regulation? Addressing this question, we performed three meta-analyses of functional magnetic resonance imaging studies to identify the regions that are commonly activated by the three domains using activation likelihood estimation (ALE). Additionally, we assessed the coactivation pattern of identified common regions using meta-analytic connectivity modeling (MACM). The results showed major overlaps of interoception with both decision making and emotion regulation in specifically the right dorsal anterior insula. The pairwise contrast analyses confirmed this finding and revealed conjunction-based activities in decision making and emotion regulation in the dorsal anterior cingulate cortex (dACC). MACM based on the identified insula revealed a widespread convergent coactivation pattern with the left anterior insula, dACC, and bilateral thalamus which, together, constitute the salience network. Among these co-activated regions, bilateral insula and the dACC were shared among all three domains. These results suggest that the regions mediating interoception including intero-exteroceptive integration and salience attribution are contained and thus spatially nested within the more extensive networks recruited during decision making and emotion regulation.

Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy.

The blood-brain barrier (BBB) is critical to maintaining central nervous system (CNS) homeostasis. However, the effects of microgravity (MG) on the BBB remain unclear. This study aimed to investigate the influence of simulated MG (SMG) on the BBB and explore its potential mechanism using a proteomic approach. Rats were tail-suspended to simulate MG for 21 days. SMG could disrupt the BBB, including increased oxidative stress levels, proinflammatory cytokine levels, and permeability, damaged BBB ultrastructure, and downregulated tight junctions (TJs) and adherens junctions (AJs) protein expression in the rat brain. A total of 554 differentially expressed proteins (DEPs) induced by SMG were determined based on the label-free quantitative proteomic strategy. The bioinformatics analysis suggested that DEPs were mainly enriched in regulating the cell-cell junction and cell-extracellular matrix biological pathways. The inhibited Ras-related C3 botulinum toxin substrate 1 (Rac1)/Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 (Wave2)/actin-related protein 3 (Arp3) pathway and the decreased ratio of filamentous actin (F-actin) to globular actin contributed to BBB dysfunction induced by SMG. In the human brain microvascular endothelial cell (HBMECs), SMG increased the oxidative stress levels and proinflammatory cytokine levels, promoted apoptosis, and arrested the cell cycle phase. Expression of TJs and AJs proteins were downregulated and the distribution of F-actin was altered in SMG-treated HBMECs. The key role of the Rac1/Wave2/Arp3 pathway in BBB dysfunction was confirmed in HBMECs with a specific Rac1 agonist. This study demonstrated that SMG induced BBB dysfunction and revealed that Rac1/Wave2/Arp3 could be a potential signaling pathway responsible for BBB disruption under SMG. These results might shed a novel light on maintaining astronaut CNS homeostasis during space travel.

[Research progress on risk predictors of refeeding syndrome in intensive care unit patients].

Refeeding syndrome (RFS) is a potentially fatal complication of clinical nutritional therapy. Patients in intensive care unit (ICU) consuming nutrients under high stress and high metabolism are more likely to develop RFS, which is closely related to the poor prognosis and higher mortality. However, due to the lack of characteristic clinical manifestations of RFS and the incomplete evaluation of risk factors, there are few reports on the related research of RFS risk prediction model, and it is easily ignored by clinicians. The key to prevention and treatment is to clarify the risk factors of RFS in ICU patients, early identify high-risk patients and initiate intervention. In this paper, the diagnostic criteria, current domestic and abroad situation, risk prediction indexes and preventive therapy of RFS are reviewed. It provides a reference for constructing an RFS risk prediction model that is in line with our national conditions, in order to improve the ability of medical staff to early identify RFS and improve the survival rate of ICU patients.

Adipose-derived exosomal miR-210/92a cluster inhibits adipose browning via the FGFR-1 signaling pathway in high-altitude hypoxia.

Cold and hypoxia are critical drivers of adaptation to high altitudes. Organisms at high altitudes have adapted to maximize the efficiency of oxygen utilization and are less prone to obesity and diabetes than those at low altitudes. Brown adipose tissue (BAT) dissipates energy in the form of heat in both humans and rodents; it also serves to regulate metabolism to curb obesity. However, the role of BAT in high-altitude populations is poorly understood. Serum exosomes can be easily obtained, enabling the study of BAT functions and identification of biomarkers in serum exosomes, both of which contribute to understanding the role of BAT in high-altitude populations. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography integrated with computed tomography (PET/CT) is the gold standard for studying BAT in human adults. Here, we studied BAT in healthy high-altitude populations via PET/CT and serum exosomal microRNAs (miRNAs). The observations were validated in mouse tissues and demonstrated that high-altitude hypoxia activated BAT through attenuated white adipose tissue (WAT) secreted exosomal miR-210/92a, which enhanced the FGFR-1 expression in BAT.

[Application of early exercise safety management in patients undergoing mechanical ventilation in intensive care unit].

OBJECTIVE: To evaluate the effectiveness and safety of early exercise safety management in patients undergoing mechanical ventilation in intensive care unit (ICU). METHODS: A prospective historical control observation was conducted. Forty-five patients with severe respiratory failure undergoing mechanical ventilation admitted to the ICU of Affiliated Hospital of Jining Medical University from April to June in 2019 were enrolled in the observation group and implemented early exercise safety management, including establishing multidisciplinary safety management team with ICU doctors, ICU nurses, respiratory therapists, rehabilitation therapists, dietitians and psychological consultants to jointly develop early exercise plan; equipping with sports and safety protection equipment; assessing the early exercise risks, formulating early exercise prescriptions; formulating the nutritional and psychological prescriptions; carrying out the propaganda and education in the early exercise process of patients and communicating with patients timely; strengthening team training. Other 45 patients with severe respiratory failure admitted for mechanical ventilation from January to March in 2019 were enrolled in the control group, whose gender, age and artificial airway conditions were matched with those in the observation group. Routine mechanical ventilation nursing was performed, including condition monitoring, medication nursing, environmental management and routine examination assistance. The improvement of depression, anxiety, comfort, lung function, and quality of life before and after nursing intervention were observed, and the occurrence of complications was recorded. RESULTS: There was no significant difference in gender, age or artificial airway conditions between the two groups. Before nursing intervention, there was no significant difference in depression, anxiety, comfort, lung function and quality of life between the two groups. After the intervention of different nursing programs, the above conditions of the two groups were significantly improved, and the improvement was more significant in the observation group, which showed that the hospital anxiety and depression scale (HAD) score and forced vital capacity (FVC) of the observation group were significantly lower than those of the control group [HAD score: 10.80±2.54 vs. 17.51±3.66, FVC (L): 1.81±0.42 vs. 2.23±0.39, both P < 0.01], while the general comfort questionnaire (GCQ) score, forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, FEV1 percentage of predicted (FEV1%) and each dimension score of 36-item short form health survey (SF-36) scale were significantly higher than those of the control group [GCQ score: 110.87±5.33 vs. 96.93±3.02, FEV1 (L): 1.99±0.37 vs. 1.71±0.15, FEV1/FVC ratio: 0.88±0.04 vs. 0.84±0.03, FEV1%: (88.98±8.57)% vs. (80.41±4.45)%, mental function score: 49.74±9.88 vs. 40.17±8.95, physical function score: 27.65±9.46 vs. 20.32±9.53, social relationship score: 62.14±6.33 vs. 50.28±8.76, general health score: 38.61±8.48 vs. 30.63±8.93, all P < 0.01]. The overall incidence of complications in the observation group was significantly lower than that in the control group (24.44% vs. 57.78%, P < 0.01). CONCLUSIONS: Early exercise safety management scheme for patients undergoing mechanical ventilation in ICU can improve clinical efficacy and reduce complications. At the same time, it can further standardize the behaviors of medical staff and ensure the early exercise.

Primary glioblastoma transcriptome data analysis for screening survival-related genes.

PURPOSE: The aim of this study was to screen survival-related genes for glioblastoma (GBM). METHODS: GSE53733 was downloaded from Gene Expression Omnibus (GEO) database, including 16 short-term (ST), 31 intermediate (IM), and 23 long-term (LT) survivors. Analysis of variance was used to analyze the expression in three groups. The genes with P < .01 were screened as differentially expressed genes (DEGs). Soft clustering was performed using Mfuzz to mine the expression patterns of differential genes in three groups of overall survival (OS) classification. The cytoscape plugin clueGO was used for functional enrichment analysis. The protein interaction between differential genes was extracted from the STRING V10 database, and the protein-protein interaction (PPI) network was constructed and displayed with cytoscape. The hub genes were verified by quantitative reverse-transcription polymerase chain reaction. RESULTS: Total 662 DEGs were obtained among three groups and enriched in 12 clusters. The overlap analysis between clusters could classify these 12 clusters Cluster A and B. Total 264 OS.DEGs were contained in Cluter A and Cluster B, and enriched in 28 Gene Ontology terms, such as trophoblast giant cell differentiation (P value = 6.18E-04), muscle fiber development (P value = 9.09E-04), and negative regulation of stem cell differentiation (P value = 1.76E-03). The top five nodes with highest degree in OS.PPI were HDAC1, DECR1, RASL11A, PDIA3, and POLR2F. The expression of DECR1 and POLR2F was significantly lower, while the levels of HDAC1 and PDIA3 were highly expressed in GBM tissues. CONCLUSION: DECR1, POLR2F, HDAC1, and PDIA3 might be potential key genes affected the overall survival time of patients with GBM.

LncRNA DLX6-AS1 promotes the proliferation, invasion, and migration of non-small cell lung cancer cells by targeting the miR-27b-3p/GSPT1 axis.

Background: Non-small cell lung cancer (NSCLC) has a significant impact on human health. The aim of this study was to explore the role of long non-coding RNA DLX6-AS1 in the proliferation, migration, and invasion of NSCLC cells. Methods: The expression of DLX6-AS1 in NSCLC tumor tissues and cell lines was examined by qRT-PCR. The effects of DLX6-AS1 knockdown on cell proliferation, migration, and invasion were assessed by Cell Counting Kit-8, wound healing, and transwell assays, respectively. Bioinformatics analyses, luciferase reporter assays, and RNA pull-down assays were employed to examine the mechanism by which DLX6-AS1 exerted its oncogenesis effects in NSCLC. The anti-tumor effect of silencing DLX6-AS1 in vivo was also evaluated. Results: DLX6-AS1 was over-expressed in NSCLC tumor tissues and cell lines and its level of expression was found to be associated with tumor size and advanced clinical stage in patients with NSCLC. Downregulation of DLX6-AS1 inhibited cell proliferation, cell clone formation, migration, and invasion of NSCLC cells. DLX6-AS1 was found to interact with miR-27b-3p/GSPT1. DLX6-AS1 expression was negatively correlated with miR-27b-3p expression, but positively correlated with GSPT1 expression in NSCLC samples. DLX6-AS1 knockdown also effectively suppressed tumor growth in an in vivo xenograft model. Conclusion: DLX6-AS1 regulated NSCLC progression by targeting the miR-27b-3p/GSPT1 axis, which may provide novel insights for NSCLC prognosis and therapy.

[Qualitative research on the family management and family needs of children with asthma].

OBJECTIVE: A qualitative research was conducted to investigate the problems on the family management of asthmatic children and the needs for family health services in order to provide basis for family-centered care. METHODS: Fifteen caregivers of children with asthma were interviewed with open-ended questions. The collected data were studied using Colaizzi's seven-step method of phenomenological analysis. RESULTS: The problems of family management and the needs for family health services were shown as follows: insufficient knowledge to prevention and treatment of asthma, poor compliance, ignoring psychological effects of asthma on children, a family's failure to cope with the distress and financial burden. CONCLUSIONS: It is important to provide asthma education and prevention program for caregivers and encourage them to participate in the design of medical program for asthmatic children. Individual asthma education and guides are also necessary for caregivers.