Epidemiological investigation and ß-lactam antibiotic resistance of Riemerella anatipestifer isolates with waterfowl origination in Anhui Province, China.

Riemerella anatipestifer (R. anatipestifer) is a highly pathogenic and complex serotypes waterfowl pathogen with inherent resistance to multiple antibiotics. This study was aimed to investigate the antibiotic resistance characteristics and genomic features of R. anatipestifer isolates in Anhui Province, China in 2023. A total of 287 cases were analysed from duck farms and goose farms, and the R. anatipestifer isolates were subjected to drug resistance tests for 30 antimicrobials. Whole genome sequencing (WGS) and bioinformatics analysis were performed on the bacterial genomes, targeting the ß-lactam resistance genes. The results showed that a total of 74 isolates of R. anatipestifer were isolated from 287 cases, with a prevalence of 25.8%. The antimicrobial susceptibility testing (AST) revealed that all the 74 isolates were resistant to multiple drugs, ranging from 13 to 26 kinds of drugs. Notably, these isolates showed significant resistance to aminoglycosides and macrolides, which are also commonly used in clinical practices. Data revealed the presence of several ß-lactamase-related genes among the isolates, including a novel blaRASA-1 variant (16.2%), the class A extended-spectrum ß-lactamase blaRAA-1 (12.2%), and a blaOXA-209 variant (98.6%). Functional analysis of the variants blaRASA-1 and blaOXA-209 showed that the blaRASA-1 variant exhibited activity against various ß-lactam antibiotics while their occurrence in R. anatipestifer were not common. The blaOXA-209 variant, on the other hand, did not perform any ß-lactam antibiotic resistance. Furthermore, we observed that blaRAA-1 could undergo horizontal transmission among different bacteria via the insertion sequence IS982. In conclusion, this study delves into the high prevalence of R. anatipestifer infection in waterfowl in Anhui, China. The isolated strains exhibit severe drug resistance issues, closely associated with the prevalence of antibiotic resistance genes (ARG). Additionally, our research investigates the ß-lactam antibiotic resistance mechanism in R. anatipestifer.

Excellent ultraviolet-blocking properties of chiral nematic liquid crystals.

We report the evaluation of chiral nematic liquid crystal (CNLC) in blocking ultraviolet (UV). The CNLC was coated on a calcium fluoride substrate to measure the spectral transmittance, which was measured to detect the UV-blocking effect of CNLC. The results show that CNLC could reduce UVB (290-320 nm) by 99.9% and UVA (320-400 nm) by 95.6%. The barrier effect of cake-shaped semi-solidified CNLC microspheres was further investigated, and it was found that cake-shaped semi-solidified CNLC microspheres could reduce UVB by 58.2% and UVA by 34.1%. This is due to the chemical absorption property of CNLC, which has UV-absorbing functional groups such as the benzene rings. And the physical reflection properties of CNLC could periodically reflect a certain wavelength of light. Liquid crystal (LC) is a rich set of soft materials with rod-like structures widely existing in nature, which is harmless to the human body and environment. Therefore, using CNLC's function of blocking UV, a new sunscreen can be developed.

Esketamine accelerates emergence from isoflurane general anaesthesia by activating the paraventricular thalamus glutamatergic neurones in mice.

BACKGROUND: Delayed emergence from general anaesthesia poses a significant perioperative safety hazard. Subanaesthetic doses of ketamine not only deepen anaesthesia but also accelerate recovery from isoflurane anaesthesia; however, the mechanisms underlying this phenomenon remain elusive. Esketamine exhibits a more potent receptor affinity and fewer adverse effects than ketamine and exhibits shorter recovery times after brief periods of anaesthesia. As the paraventricular thalamus (PVT) plays a pivotal role in regulating wakefulness, we studied its role in the emergence process during combined esketamine and isoflurane anaesthesia. METHODS: The righting reflex and cortical electroencephalography were used as measures of consciousness in mice during isoflurane anaesthesia with coadministration of esketamine. The expression of c-Fos was used to determine neuronal activity changes in PVT neurones after esketamine administration. The effect of esketamine combined with isoflurane anaesthesia on PVT glutamatergic (PVTGlu) neuronal activity was monitored by fibre photometry, and chemogenetic technology was used to manipulate PVTGlu neuronal activity. RESULTS: A low dose of esketamine (5 mg kg-1) accelerated emergence from isoflurane general anaesthesia (474 [30] s vs 544 [39] s, P=0.001). Esketamine (5 mg kg-1) increased PVT c-Fos expression (508 [198] vs 258 [87], P=0.009) and enhanced the population activity of PVTGlu neurones (0.03 [1.7]% vs 6.9 [3.4]%, P=0.002) during isoflurane anaesthesia (1.9 [5.7]% vs -5.1 [5.3]%, P=0.016) and emergence (6.1 [6.2]% vs -1.1 [5.0]%, P=0.022). Chemogenetic suppression of PVTGlu neurones abolished the arousal-promoting effects of esketamine (459 [33] s vs 596 [33] s, P<0.001). CONCLUSIONS: Our results suggest that esketamine promotes recovery from isoflurane anaesthesia by activating PVTGlu neurones. This mechanism could explain the rapid arousability exhibited upon treatment with a low dose of esketamine.

Association and prediction of subjective sleep quality and postoperative delirium during major non-cardiac surgery: a prospective observational study.

BACKGROUND: Postoperative delirium (POD) is an acute form of brain dysfunction that can result in serious adverse consequences. There has been a link between cognitive dysfunction and poor sleep. The present study aimed to determine the association and prediction of subjective sleep quality and postoperative delirium during major non-cardiac surgery. METHODS: One hundred and thirty-four patients, aged 60 years or older, were scheduled for elective laparotomy or orthopaedic procedures. The Pittsburgh Sleep Quality Index (PSQI) and sleep log were used to assess perioperative subjective sleep quality in participants. Nursing Delirium Screening Checklist (NU-DESC) was used for screening, and the Confusion Assessment Method (CAM) was used to diagnose POD during the first seven days following surgery. The association between subjective sleep quality and POD was assessed using a multivariate logistic regression model. Thereafter, the prediction performance of subjective sleep quality was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: All assessments were completed on 119 patients who had an average PSQI score of 7.0 ± 2.4 before surgery. 23 patients (19.3%) suffered from POD. The multivariate logistic regression analysis showed that the occurrence of POD was closely related to age, BMI, PSQI and operation time. After adjusting for related factors, there was a statistically significant association between PSQI and POD occurrence (OR = 1.422, 95%CI 1.079-1.873, per 1-point increase in PSQI). The ROC curve analysis showed that the optimal PSQI cutoff value was 8.0 for predicting POD, and the area under the ROC (AUROC) value of PSQI was 0.741 (95%CI 0.635 to 0.817). The AUROC of the model developed by the multivariate logistic regression analysis was 0.870 (95%CI 0.797 to 0.925). CONCLUSIONS: The study found that preoperative subjective sleep quality was strongly associated with POD during major non-cardiac surgery. Additionally, PSQI combined with age, BMI, and operation time improved POD prediction.

Liquid-crystal-based fiber laser sensor for non-invasive gas detection.

This Letter reports a new optical fiber gas sensor for measuring breath acetone. The sensor is based on photonic bandgap (PBG) mode laser emission sensing technology using liquid crystal (LC), which is combined with silica fiber and chiral nematic liquid crystal (CNLC), thus providing an ultra-compact, fast-response and simple-to-produce sensing system with a fast response that can accurately and quantitatively determine the concentration of respiratory acetone within the normal oral temperature range (35-38°C). Since LCs are affected by temperature, we propose a method that eliminates the influence of the temperature to solve the problem of the temperature influence when measuring gas. The detection of acetone leads to splitting of the dual laser peaks, with a linear correlation of 0.99. The sensor has a limit of detection of 65 ppm for acetone vapor and thus is suitable for breath acetone detection in diabetic patients.

Dorsal BNST DRD2+ neurons mediate sex-specific anxiety-like behavior induced by chronic social isolation.

The dorsal bed nucleus of stria terminalis (dBNST) is a pivotal hub for stress response modulation. Dysfunction of dopamine (DA) network is associated with chronic stress, but the roles of DA network of dBNST in chronic stress-induced emotional disorders remain unclear. We examine the role of dBNST Drd1+ and Drd2+ neurons in post-weaning social isolation (PWSI)-induced behavior deficits. We find that male, but not female, PWSI rats exhibit negative emotional phenotypes and the increase of excitability and E-I balance of dBNST Drd2+ neurons. More importantly, hypofunction of dBNST Drd2 receptor underlies PWSI-stress-induced male-specific neuronal plasticity change of dBNST Drd2+ neurons. Furthermore, chemogenetic activation of dBNST Drd2+ neurons is sufficient to induce anxiogenic effects, while Kir4.1-mediated chronic inhibition of dBNST Drd2+ neurons ameliorate PWSI-induced anxiety-like behaviors. Our findings reveal an important neural mechanism underlying PWSI-induced sex-specific behavioral abnormalities and potentially provide a target for the treatment of social stress-related emotional disorder.

Silencing circPalm2 inhibits sepsis-induced acute lung injury by sponging miR-376b-3p and targeting MAP3K1.

The apoptosis and inflammation of pulmonary epithelial cells are important pathogenic factors of sepsis-induced acute lung injury (ALI). Upregulation of circPalm2 (circ_0001212) expression levels has been previously detected in the lung tissue of ALI rats. Herein, the biological significance and detailed mechanism of circPalm2 in ALI pathogenesis were investigated. In vivo models of sepsis-induced ALI were established by treating C57BL/6 mice with cecal ligation and puncture (CLP) surgery. Murine pulmonary epithelial cells (MLE-12 cells) were stimulated with lipopolysaccharide (LPS) to establish in vitro septic ALI models. MLE-12 cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometry analysis, respectively. The pathological alterations of the lung tissue were analysed based on hematoxylin-eosin (H&E) staining. Cell apoptosis in the lung tissue samples was examined by TUNEL staining assay. LPS administration suppressed the viability and accelerated the inflammation and apoptotic behaviours of MLE-12 cells. CircPalm2 displayed high expression in LPS-stimulated MLE-12 cells and possessed circular characteristics. The silencing of circPalm2 impeded apoptosis and inflammation in LPS-stimulated MLE-12 cells. Mechanistically, circPalm2 bound with miR-376b-3p, which targeted MAP3K1. In rescue assays, MAP3K1 enhancement reversed the repressive effects of circPalm2 depletion on LPS-triggered inflammatory injury and MLE-12 cell apoptosis. Furthermore, the lung tissue collected from CLP model mice displayed low miR-376b-3p expression and high levels of circPalm2 and MAP3K1. CircPalm2 positively regulated MAP3K1 expression by downregulating miR-376b-3p in murine lung tissues. Importantly, circPalm2 knockdown attenuated CLP-induced inflammation, apoptosis, and pathological alterations in lung tissues collected from mice. Silenced circPalm2 inhibits LPS-induced pulmonary epithelial cell dysfunction and mitigates abnormalities in lung tissues collected from CLP-stimulated mice via the miR-376b-3p/MAP3K1 axis in septic ALI. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00169-7.

Knocking down Trim47 ameliorated sevoflurane-induced neuronal cell injury and cognitive impairment in rats.

Sevoflurane (SEV), usually causing neuronal damage and cognitive dysfunction, is one of the most commonly used anesthetics in clinical practice. However, the function of Trim47 in SEV-induced neuronal impairment remains elusive. The aim of this study was to study the effect of knocking down Trim47 on the nerve injury induced by SEV. Nerve injury was induced in rats by 3% SEV, and H19-7 was used to establish a pathological model, and sh-Trim47 was transfected into H19-7 to study the function of Trim47. The effects of SEV on the expression of Trim47 in the hippocampus and cognitive function of rats were studied by neurological function score and Moris water maze (MWM). The mRNA and protein expression of TNF-α, IL-1ß and IL-6 in the cells, along with the neuronal apoptosis in the hippocampus of rats in each group were studied by TUNEL or WB. Flow cytometry was used to study the effect of knockdown of Trim47 on cell apoptosis. CCK-8 was used to detect cell viability of H19-7 cells. Finally, the potential signaling pathway affected by knockdown of Trim47 after abrogation of SEV induction was investigated by WB. The results showed that, knockdown of Trim47 ameliorated SEV-induced neurological damage and cognitive deficits, inflammation and neuronal cell apoptosis in rats, and promoted hippocampal neuronal activity. Knockdown of Trim47 can inhibit the NF-κB signaling pathway and improve neuronal cell damage and cognitive impairment induced by SEV in neonatal rats by regulating NF-κB signaling pathway, alleviating inflammatory response, and inhibiting neuronal apoptosis.

Lin28A Reduced Sevoflurane-Induced Nerve Injury and Cognitive Dysfunction by Inhibiting Tau Acetylation and Phosphorylation via Activating SIRT1 in Elderly Rats.

Sevoflurane (Sev) might cause neurotoxicity in elderly rats. However, the role of Lin28A in Sev-induced neurotoxicity remains unclear in elderly rats. In this study, elderly rats were used to construct an Sev-induced nerve injury model. Learning and memory abilities were assessed by Morris water maze (MWM) trainings; pathological alterations in hippocampal region were assessed by HE staining; neuronal apoptosis was assessed by TUNEL; related protein expression was analyzed by immunofluorescence, immunohistochemistry, and Western blotting. Results of this study showed that Sev treatment caused nerve injury and cognitive dysfunction in elderly rats, with increased neuronal apoptosis and decreased Lin28A levels. Pathological impairment and learning and memory abilities of elderly rats were significantly improved after forced overexpression of Lin28A using AAV, accompanied by decreased expression of CD68, Iba-1, and GFAP. TUNEL analysis showed that Lin28A overexpression significantly reversed Sev-induced neuronal apoptosis. Further mechanistic analysis showed that Lin28A significantly promoted SIRT1 expression, which further reversed Sev-induced Tau acetylation at lysine 280 and 686 and Tau hyperphosphorylation, thereby alleviating nerve injury and cognitive dysfunction in elderly rats. The introduction of SIRT1 inhibitor EX527 further confirmed the involvement of SIRT1 in the regulation of Lin28A in elderly rats. In conclusion, our findings demonstrated that Lin28A reduced sevoflurane-induced nerve injury and cognitive dysfunction by inhibiting Tau acetylation and phosphorylation via activating SIRT1 in elderly rats.

Knockdown of UAF1 alleviates sevoflurane-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress.

Evidence has shown that suppression of the activation of NLRP3 inflammasome could ameliorate surgery/sevoflurane (SEV)-induced post-operative cognitive dysfunction (POCD). However, the underlying mechanisms remain unclear. UAF1 acts as a binding partner of USP1, which inhibits the ubiquitination-mediated degradation of NLRP3, indicating that UAF1 may be implicated in POCD through regulating the NLRP3 inflammasome. Here, we studied the role of UAF1/NLRP3 in SEV-induced cognitive impairment and neurotoxicity in rats. Neonatal rats were randomly divided into control, SEV, SEV+AAV-shNC and SEV+AAV-shUAF1 (UAF1-downregulated) groups. Morris water maze (MWM) test was applied to assess cognitive impairment. TUNEL staining, qRT-PCR and ELISA were used to assess the apoptosis and inflammation markers, respectively. The levels of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were quantified to determine oxidative stress. The results showed that SEV treatment led to significant cognitive impairment, increased apoptosis in hippocampal tissues, upregulation of MDA and inflammatory factors (TNF-α, IL-1ß, IL-18), as well as a decrease in SOD and CAT levels. All of the above observations were reversed by UAF1 downregulation. Furthermore, depletion of UAF1 neutralized SEV-mediated increase in p-NLRP3, p-IκBα and p-p65 levels. Altogether, the current study demonstrated that knockdown of UAF1 could alleviate SEV-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress.

Probiotic Saccharomyces boulardii attenuates cardiopulmonary bypass-induced acute lung injury by inhibiting ferroptosis.

OBJECTIVE: Acute lung injury (ALI) is one of the most common and fatal complications of cardiopulmonary bypass (CPB). Probiotics treatment has been shown to reduce lung injury in different experimental models. However, the effect of probiotics on CPB-induced ALI is still poorly understood. This study aimed to investigate whether probiotic Saccharomyces boulardii CNCM I-745 treatment protects against lung injury in a rat model of CPB. METHODS: Rats were orally gavaged with Saccharomyces boulardii CNCM I-745 once a day for 5 days before being subjected to CPB. Rats were euthanized post-CPB, and samples of lung tissue were processed for later investigation. The levels of inflammatory cytokines were measured by ELISA. The expression levels of ferroptosis markers in lungs were assessed by western blot. The microbes in feces and proximal colon of rats were analyzed by using 16S rDNA amplicon sequencing method. The ratio and maturity of conventional dendritic cells (cDCs) were determined by flow-cytometry. RESULTS: Saccharomyces boulardii CNCM I-745 treatment improved lung function, attenuated pathologic lung changes and decelerated the exacerbation of inflammatory cytokine level after experimental CPB. Saccharomyces boulardii CNCM I-745 treatment also inhibited CPB-induced ferroptosis, as evidenced by the changes of main markers of ferroptosis, namely, the increase of Glutathione peroxidase 4 (GPX4) and the decrease of Acyl-CoA synthetase long chain family member 4 (ACSL4). In addition, after Saccharomyces boulardii CNCM I-745 treatment, the ratio and maturity of conventional dendritic cells (cDCs) in the guts of rats with CPB were significantly up-regulated. CONCLUSION: Our findings suggest that probiotic Saccharomyces boulardii CNCM I-745 reduces CPB-induced lung injury through suppression of the ferroptosis in lung and up-regulation of the ratio and maturity of cDCs in gut.

The role of PTEN in primary sensory neurons in processing itch and thermal information in mice.

PTEN is known as a tumor suppressor and plays essential roles in brain development. Here, we report that PTEN in primary sensory neurons is involved in processing itch and thermal information in adult mice. Deletion of PTEN in the dorsal root ganglia (DRG) is achieved in adult Drg11-CreER: PTENflox/flox (PTEN CKO) mice with oral administration of tamoxifen, and CKO mice develop pathological itch and elevated itch responses on exposure to various pruritogens. PTEN deletion leads to ectopic expression of TRPV1 and MrgprA3 in IB4+ non-peptidergic DRG neurons, and the TRPV1 is responsive to capsaicin. Importantly, the elevated itch responses are no longer present in Drg11-CreER: PTENflox/flox: TRPV1flox/flox (PTEN: TRPV1 dCKO) mice. In addition, thermal stimulation is enhanced in PTEN CKO mice but blunted in dCKO mice. PTEN-involved regulation of itch-related gene expression in DRG neurons provides insights for understanding molecular mechanism of itch and thermal sensation at the spinal level.

Efficacy of small-dose ganciclovir on cytomegalovirus infections in children and its effects on liver function and miR-UL112-3p expression.

The aim of the study was to explore the efficacy of small-dose ganciclovir on cytomegalovirus infections as well as its effects on the liver function and miR-UL112-3p of children. A total of 141 children infected with cytomegalovirus admitted to the Affiliated Hospital of Weifang Medical University from May 2015 to August 2017 were enrolled, of which 74 children were treated with small-dose ganciclovir as an observation group (Obs group), and the rest were treated with conventional-dose ganciclovir as a control group (Con group). The two groups were compared in efficacy after treatment, changes of liver function indexes [total bilirubin (TB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] and miR-UL112-3p before and after treatment, and adverse reactions after treatment. A receiver operating characteristic (ROC) curve was drawn to analyze the value of miR-UL112-3p in predicating efficacy on cytomegalovirus infections in children, and Pearson's correlation analysis was carried out to analyze the correlation between miR-UL112-3p expression and TB, ALT and AST. The MV-DNA level between the two groups after treatment was compared. The two groups showed no significant difference in efficacy and adverse reactions (both P>0.05), and before treatment, there was also no significant difference between the two groups in miR-UL112-3p, TB, ALT, and AST, while after treatment, both groups showed lower levels of miR-UL112-3p, TB, ALT, and AST, and the Obs group showed significantly lower levels thereof than the Con group (all P<0.05). In addition, the area under the curve (AUC), specificity, and sensitivity of miR-UL112-3p in the ROC curve of the Obs group were 0.866, 73.77 and 84.62%, respectively, while the AUC, specificity, and sensitivity of the ROC of the Con group were 0.837, 75.44, and 90.00%, respectively. Furthermore, miR-UL112-3p was positively correlated with TB, ALT, and AST, respectively. The CMV-DNA level in the Obs group was lower than that in the Con group, but the difference was not significant, and the level of CMV-DNA was positively correlated with that of miR-UL112-3p. In conclusion, small-dose ganciclovir can better improve the liver function of the children, and downregulate miR-UL112-3p in them. The AUC, specificity, and sensitivity of miR-UL112-3p for predicting the efficacy of small-dose ganciclovir were 0.866, 73.77 and 84.62%, respectively, and the AUC, specificity, and sensitivityfor predicting the efficacy of conventional-dose ganciclovir were 0.837, 75.44 and 90.00%, respectively.

The Long-Term Presence of SARS-CoV-2 on Cold-Chain Food Packaging Surfaces Indicates a New COVID-19 Winter Outbreak: A Mini Review.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a highly infectious virus that is transmitted primarily through droplets or by coming in close contact with an infected person. In 2020, there was a global outbreak of COVID-19, resulting in an unprecedented global burden of disease, health care costs, and had a significant economic impact. Recently, SARS-CoV-2 was detected on the outer packaging of imported cold chain items in China and has led to virus transmission events, causing great concern. This paper analyses the factors of SARS-CoV-2 survival and transmission in different places and environments, especially the characteristics of low temperatures and object surfaces. It was found that SARS-CoV-2 could survive on surfaces of cold and moist objects in the cold chain for more than 3 weeks, potentially causing COVID-19 transmission. We believe that the low-temperature environment in winter may accelerate the spread of the outbreak and new outbreaks may occur. Overall, SARS-CoV-2 transmission that is susceptible to low winter temperatures is critical for predicting winter pandemics, allowing for the appropriate action to be taken in advance.

Restoring VTA DA neurons excitability accelerates emergence from sevoflurane general anesthesia of anxiety state.

Preoperative anxiety is common and often comes with a higher probability of worse recovery. However, the neurological mechanism of the effect of preoperative anxiety on general anesthesia and subsequent awakening remains unknown. In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.

Transcriptome-Wide Gene Expression in a Murine Model of Ventilator-Induced Lung Injury.

BACKGROUND: Mechanical ventilation could lead to ventilator-induced lung injury (VILI), but its underlying pathogenesis remains largely unknown. In this study, we aimed to determine the genes which were highly correlated with VILI as well as their expressions and interactions by analyzing the differentially expressed genes (DEGs) between the VILI samples and controls. METHODS: GSE11434 was downloaded from the gene expression omnibus (GEO) database, and DEGs were identified with GEO2R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using DAVID. Next, we used the STRING tool to construct protein-protein interaction (PPI) network of the DEGs. Then, the hub genes and related modules were identified with the Cytoscape plugins: cytoHubba and MCODE. qRT-PCR was further used to validate the results in the GSE11434 dataset. We also applied gene set enrichment analysis (GSEA) to discern the gene sets that had a significant difference between the VILI group and the control. Hub genes were also subjected to analyses by CyTargetLinker and NetworkAnalyst to predict associated miRNAs and transcription factors (TFs). Besides, we used CIBERSORT to detect the contributions of different types of immune cells in lung tissues of mice in the VILI group. By using DrugBank, small molecular compounds that could potentially interact with hub genes were identified. RESULTS: A total of 141 DEGs between the VILI group and the control were identified in GSE11434. Then, seven hub genes were identified and were validated by using qRT-PCR. Those seven hub genes were largely enriched in TLR and JAK-STAT signaling pathways. GSEA showed that VILI-associated genes were also enriched in NOD, antigen presentation, and chemokine pathways. We predicted the miRNAs and TFs associated with hub genes and constructed miRNA-TF-gene regulatory network. An analysis with CIBERSORT showed that the proportion of M0 macrophages and activated mast cells was higher in the VILI group than in the control. Small molecules, like nadroparin and siltuximab, could act as potential drugs for VILI. CONCLUSION: In sum, a number of hub genes associated with VILI were identified and could provide novel insights into the pathogenesis of VILI and potential targets for its treatment.

Mining the key genes for ventilator-induced lung injury using co-expression network analysis.

Mechanical ventilation is extensively adopted in general anesthesia and respiratory failure management, but it can also induce ventilator-induced lung injury (VILI). Therefore, it is of great urgency to explore the mechanisms involved in the VILI pathogenesis, which might contribute to its future prevention and treatment. Four microarray datasets from the GEO database were selected in our investigation, and were subjected to the Weighted Gene Co-Expression Network Analysis (WGCNA) to identify the VILI-correlated gene modules. The limma package in R software was used to identify the differentially expressed genes (DEGs) between the VILI and control groups. WGCNA was constructed by merging the GSE9314, GSE9368, GSE11434 and GSE11662 datasets. A total of 49 co-expression network modules were determined as associated with VILI. The intersected genes between hub genes screened from DEGs for VILI and those identified using WGCNA were as follows: Tlr2, Hmox1, Serpine1, Mmp9, Il6, Il1b, Ptgs2, Fos and Atf3, which were determined to be key genes for VILI. Those key genes were validated by GSE86229 and quantitative PCR (qPCR) experiment to have significantly statistical difference in their expression between the VILI and control groups. In a nutshell, nine key genes with expression differences in VILI were screened by WGCNA by integrating multiple datasets.

Risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population: a systematic review and meta-analysis.

Patients with rheumatic diseases are often more susceptible to different bacteria and viruses because of immune impairment, but it is not clear whether there is a higher risk of infection and a more serious course of disease for novel coronavirus (SARS-CoV-2). We performed this systematic review and meta analysis to assess the risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population. We searched PubMed, EMBASE, Scopus and Web of Science databases from January 1, 2020 to October 20, 2020 to determine epidemiological information related to patients with rheumatic diseases and COVID-19, including clear risk estimate or data that could be converted and extracted. We included 26 observational studies, totaling about 2000 patients with rheumatic diseases of whom were infected with COVID-19. Meta-analysis showed that the risk of COVID-19 infection in rheumatic patients was significantly higher than that in the general population (OR = 1.53, 95% CI 1.24-1.88, P = 0.000). In terms of hospitalization and severe clinical outcomes associated with COVID-19, we found that rheumatic patients showed similar results to the reference population (hospitalization OR = 1.36, 95% CI 0.81-2.29, P = 0.247; admitted to ICU OR = 1.94, 95% CI 0.88-4.27, P = 0.098; death OR = 1.29, 95% CI 0.84-1.97, P = 0.248). The presence of comorbidities, hypertension, lung diseases were significantly associated with the increased risk of COVID-19-related hospitalization in rheumatic patients and anti-TNF drugs were associated with lower hospitalization risk. Older age was related to severe COVID-19. Our meta-analysis indicated that rheumatic patients were at a higher risk of COVID-19 infection but might not lead to a more serious disease process.

Ketamine inhibits neuronal differentiation by regulating brain-derived neurotrophic factor (BDNF) signaling.

Ketamine is widely used in pediatric anesthesia, perioperative sedation, and analgesia. Knowledge of anesthesia neurotoxicity in humans is currently limited by the difficulty of obtaining neurons and performing developmental toxicity studies in fetal and pediatric populations. However, mouse embryonic stem cells (mESCs) derived from embryos at the preimplantation stage demonstrate an unlimited ability to self-renew and generate different cell types and are a valuable tool for clinical research. Thus, in this study, a model was employed to investigate the mechanism by which ketamine (200 nM) influences the neuronal differentiation of mESCs. Mouse ESCs were treated with an anesthetic dose of ketamine, and neuronal differentiation was significantly inhibited on day 5. Downregulation of brain-derived neurotrophic factor (BDNF) by shRNA was found to have the same inhibitory effect. Furthermore, a rescue experiment indicated that BDNF overexpression markedly restored the neuronal differentiation inhibited by ketamine in the ketamine/BDNF group on day 5. Taken together, these data suggested that ketamine inhibited the neuronal differentiation of mESCs, possibly by interfering with BDNF. The results of the current study may provide novel ideas for preventing ketamine toxicity in the developing fetus.