MERITS: a web-based integrated Mycobacterial PE/PPE protein database.

Motivation: PE/PPE proteins, highly abundant in the Mycobacterium genome, play a vital role in virulence and immune modulation. Understanding their functions is key to comprehending the internal mechanisms of Mycobacterium. However, a lack of dedicated resources has limited research into PE/PPE proteins. Results: Addressing this gap, we introduce MycobactERIal PE/PPE proTeinS (MERITS), a comprehensive 3D structure database specifically designed for PE/PPE proteins. MERITS hosts 22 353 non-redundant PE/PPE proteins, encompassing details like physicochemical properties, subcellular localization, post-translational modification sites, protein functions, and measures of antigenicity, toxicity, and allergenicity. MERITS also includes data on their secondary and tertiary structure, along with other relevant biological information. MERITS is designed to be user-friendly, offering interactive search and data browsing features to aid researchers in exploring the potential functions of PE/PPE proteins. MERITS is expected to become a crucial resource in the field, aiding in developing new diagnostics and vaccines by elucidating the sequence-structure-functional relationships of PE/PPE proteins. Availability and implementation: MERITS is freely accessible at http://merits.unimelb-biotools.cloud.edu.au/.

Association Between Atherogenic Index of Plasma and Risk of Incident Major Adverse Cardiovascular Events.

It is unclear whether the atherogenic index of plasma (AIP) is associated with major adverse cardiovascular events (MACEs) in the general population. A total of 361,644 participants (aged 56.19 ± 8.09 years; 44.79% male) free of a history of MACEs at baseline from the UK Biobank data were included in the analysis. The AIP was calculated using log (triglyceride/high-density lipoprotein-cholesterol). Over a mean follow-up of 12.19 ± 1.60 years, 16,683 participants developed MACEs. After adjustment for traditional risk factors, each 1 unit increase in AIP was associated with a 45.3% higher risk of incident MACEs (hazard ratio (HR), 1.453 [95% confidence interval (CI) 1.371-1.540], P < 0.001). Results were similar when individuals were categorized by the AIP quartiles (HR, 1.283 [95% CI 1.217-1.351]; comparing extreme quartiles). The subgroup analyses showed that the association between AIP and risk of incident MACEs was more obvious in female participants who are < 60 years old and free of hypertension or diabetes. Sensitivity analysis included participants without any lipid-lowering medication or excluded incident MACEs in the first 2 years of follow-up confirming the robustness of the findings. Elevated AIP is a risk factor of incident MACEs in the general population, independent of traditional risk factors.Dynamic monitoring of the AIP may help select the population at high risk of cardiovascular events and guide primary prevention.

PLANNER: a multi-scale deep language model for the origins of replication site prediction.

Origins of replication sites (ORIs) are crucial genomic regions where DNA replication initiation takes place, playing pivotal roles in fundamental biological processes like cell division, gene expression regulation, and DNA integrity. Accurate identification of ORIs is essential for comprehending cell replication, gene expression, and mutation-related diseases. However, experimental approaches for ORI identification are often expensive and time-consuming, leading to the growing popularity of computational methods. In this study, we present PLANNER (DeeP LeArNiNg prEdictor for ORI), a novel approach for species-specific and cell-specific prediction of eukaryotic ORIs. PLANNER uses the multi-scale ktuple sequences as input and employs the DNABERT pre-training model with transfer learning and ensemble learning strategies to train accurate predictive models. Extensive empirical test results demonstrate that PLANNER achieved superior predictive performance compared to state-of-the-art approaches, including iOri-Euk, Stack-ORI, and ORI-Deep, within specific cell types and across different cell types. Furthermore, by incorporating an interpretable analysis mechanism, we provide insights into the learned patterns, facilitating the mapping from discovering important sequential determinants to comprehensively analysing their biological functions. To facilitate the widespread utilisation of PLANNER, we developed an online webserver and local stand-alone software, available at http://planner.unimelb-biotools.cloud.edu.au/ and https://github.com/CongWang3/PLANNER, respectively.

A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins. METHODS: The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms. RESULTS: PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription. CONCLUSIONS: Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer.

Diagnostic and prognostic value of autophagy-related key genes in sepsis and potential correlation with immune cell signatures.

Background: Autophagy is involved in the pathophysiological process of sepsis. This study was designed to identify autophagy-related key genes in sepsis, analyze their correlation with immune cell signatures, and search for new diagnostic and prognostic biomarkers. Methods: Whole blood RNA datasets GSE65682, GSE134347, and GSE134358 were downloaded and processed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify autophagy-related key genes in sepsis. Then, key genes were analyzed by functional enrichment, protein-protein interaction (PPI), transcription factor (TF)-gene and competing endogenous RNA (ceRNA) network analysis. Subsequently, key genes with diagnostic efficiency and prognostic value were identified by receiver operating characteristic (ROC) curves and survival analysis respectively. The signatures of immune cells were estimated using CIBERSORT algorithm. The correlation between significantly different immune cell signatures and key genes was assessed by correlation analysis. Finally, key genes with both diagnostic and prognostic value were verified by RT-qPCR. Results: 14 autophagy-related key genes were identified and their TF-gene and ceRNA regulatory networks were constructed. Among the key genes, 11 genes (ATIC, BCL2, EEF2, EIF2AK3, HSPA8, IKBKB, NLRC4, PARP1, PRKCQ, SH3GLB1, and WIPI1) had diagnostic efficiency (AUC > 0.90) and 5 genes (CAPN2, IKBKB, PRKCQ, SH3GLB1 and WIPI1) were associated with survival prognosis (p-value < 0.05). IKBKB, PRKCQ, SH3GLB1 and WIPI1 had both diagnostic and prognostic value, and their expression were verified by RT-qPCR. Analysis of immune cell signatures showed that the abundance of neutrophil, monocyte, M0 macrophage, gamma delta T cell, activated mast cell and M1 macrophage subtypes increased in the sepsis group, while the abundance of resting NK cell, resting memory CD4+ T cell, CD8+ T cell, naive B cell and resting dendritic cell subtypes decreased. Most of the key genes correlated with the predicted frequencies of CD8+ T cells, resting memory CD4+ T cells, M1 macrophages and naive B cells. Conclusion: We identified autophagy-related key genes with diagnostic and prognostic value in sepsis and discovered associations between key genes and immune cell signatures. This work may provide new directions for the discovery of promising biomarkers for sepsis.

An advanced remote sensing retrieval method for urban non-optically active water quality parameters: An example from Shanghai.

The optical insensitivity of non-optically active water quality parameters (NAWQPs) presents a significant challenge for remote sensing-based quantitative monitoring, which is an important tool for water quality assessment and management. Based on the analysis of the samples from Shanghai, China, it was found that the spectral morphological characteristics of the water body were obviously different under the combined effect of multiple NAWQPs. In view of this, in this paper, a machine learning method was proposed for the retrieval of urban NAWQPs by using multi-spectral scale morphological combined feature (MSMCF). The proposed method integrates both local and global spectral morphological features, and employs a multi-scale approach to enhance its applicability and stability, providing a more accurate and robust solution. To explore the applicability of the MSMCF method in retrieving urban NAWQPs, different methods were tested in terms of the retrieval accuracy and stability on the measured data and three different hyperspectral data. As can be seen from the results, the proposed method has good retrieval performance, which can be applied to hyperspectral data with different spectral resolutions with certain ability to suppress noise. Further analysis indicates that the sensitivity of each NAWQP to spectral morphological features varies. The research methods and findings in this paper can promote the development of hyperspectral and remote sensing technology in the prevention and treatment of urban water quality deterioration, and provide reference for related research.

Optimized Cingulate Island Sign in Discriminating Dementia With Lewy Bodies From Alzheimer Disease.

PURPOSE: This study aimed to optimize the analysis of cingulate island sign (CIS) to improve its diagnostic accuracy in discriminating dementia with Lewy bodies (DLB) from Alzheimer disease (AD). PATIENTS AND METHODS: Patients with DLB (n = 80), AD (n = 75), and normal controls (n = 22) with 18 F-FDG PET imaging were enrolled in this study. Sixty-two DLB patients also underwent dopaminergic PET scans. The optimized/conventional CIS ratios and metabolism in associated brain regions were evaluated by diagnostic accuracy among groups and correlation with cognitive/dopaminergic dysfunction. RESULTS: In discriminating DLB from AD, the optimized CIS ratio calculated by dorsal posterior cingulate cortex (PCC)/lateral occipital lobe metabolism achieved the highest specificity, sensitivity, and accuracy at 0.907, 0.750, and 0.825, respectively. The metabolism of dorsal-PCC positively correlated with cognitive impairment in DLB patients cross-sectionally and longitudinally ( P < 0.001, r = 0.601; P = 0.044, r = 0.645), and also correlated with dopaminergic impairment in the caudate ( P = 0.048, r = 0.315). CONCLUSIONS: Optimized CIS ratios of incorporated metabolic activity of dorsal-PCC and occipital subregions are clinically useful for differentiating DLB from AD, in which dorsal-PCC metabolism may provide an objective biomarker to reflect the severity of cognitive impairment in DLB.

The effects of external diaphragmatic pacing on diaphragm function and weaning outcomes of critically ill patients with mechanical ventilation: a prospective randomized study.

Background: Diaphragmatic pacing can improve diaphragm function, which is beneficial for the prognosis of patients treated with prolonged mechanical ventilation (MV). While most previous studies have focused on the role of implanted diaphragm pacing (IDP), our study is the first to examine the effects of external diaphragmatic pacing (EDP) in mechanically ventilated patients. Specifically, the effect of EDP on diaphragm function, the success rate of weaning, the duration of MV (DMV), and the intensive care unit (ICU) length of stay (ILOS) were assessed. Methods: From September 2019 to December 2020, a total of 51 mechanically ventilated patients in the ICU of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University were enrolled and randomly divided into an EDP group of 27 patients and a control group of 24 patients. The control group received routine treatment, and the EDP group received EDP treatment in addition to routine treatment. The diaphragm excursion (DE), diaphragm thickening fraction (DTF), DMV, ILOS, and average survival time were recorded to evaluate efficacy. Results: Patients treated with EDP had increased DE [exp(B) =1.86, 95% CI: 1.39 to 2.50, P<0.001] and DTF [exp(B) =1.35, 95% CI: 1.05 to 1.76, P=0.022], shortened weaning time (P=0.026) and prolonged average survival time (P<0.001) compared to patients who did not receive EDP therapy. Especially in cases with difficult weaning, the improvement of DE and DTF in the EDP treatment group was more obvious than that in the control group (P=0.013 and P=0.032). Moreover, the DTF upon attempted spontaneous breathing trial (SBT) was negatively correlated with the fraction of inspired oxygen (FiO2) [r=-0.54; 95% confidence interval (CI): -0.77 to -0.19; P=0.004], the arterial partial pressure of oxygen (PaO2) (r=-0.58; 95% CI: -0.79 to -0.25; P=0.001), the PaO2/FiO2 ratio (r=-0.52; 95% CI: -0.75 to -0.16; P=0.006), and the serum lactate concentration (Lac) (r=-0.39; 95% CI: -0.68 to 0.003; P=0.046). Conclusions: EDP treatment can effectively reduce the DMV and prolong the average survival time of mechanically ventilated patients. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900024096.

Brain Metabolic Connectivity Patterns in Patients with Prolonged Disorder of Consciousness after Hypoxic-Ischemic Injury: A Preliminary Study.

Understanding the patterns of brain glucose metabolism and connectivity in hypoxic-ischemic encephalopathy (HIE) patients with prolonged disorders of consciousness (DOC) may be of positive significance to the accurate assessment of consciousness and the optimization of neuromodulation strategy. We retrospectively analyzed the brain glucose metabolism pattern and its correlation with clinical Coma Recovery Scale-Revised (CRS-R) score in six HIE patients with prolonged DOC who had undergone 18F-deoxyglucose brain positron emission tomography scanning (FDG-PET). We also compared the differences in global metabolic connectivity patterns and the characteristics of several brain networks between HIE patients and healthy controls (HC). The metabolism of multiple brain regions decreased significantly in HIE patients, and the degree of local metabolic preservation was correlated with CRS-R score. The internal metabolic connectivity of occipital lobe and limbic system in HIE patients decreased, and their metabolic connectivity with frontal lobe, parietal lobe and temporal lobe also decreased. The metabolic connectivity patterns of default mode network, dorsal attention network, salience network, executive control network and subcortex network of HIE also changed compared with HC. The present study suggested that pattern of cerebral glucose metabolism and network connectivity of HIE patients with prolonged DOC were significantly different from those of healthy people.

Identification of differentially expressed genes, transcription factors, microRNAs and pathways in neutrophils of sepsis patients through bioinformatics analysis.

Sepsis has been recognized to be a life-threatening organ dysfunction caused by the dysregulation of the host response to infections. Our work aims to screen key biomarkers related to neutrophils in sepsis using bioinformatics analysis. For this purpose, the microarray datasets related to neutrophils in sepsis patients were downloaded from the Gene Expression Omnibus (GEO) database. According to the Bayesian test, the Limma package in R was used to screen differentially expressed genes (DEGs). Then, DEGs were uploaded to the DAVID online diagnostic tool for subsequent Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment on the selected DEGs. Next, protein-protein interaction (PPI) network was established based on the selected DEGs using the STRING website and the Cytoscape software. Furthermore, according to the function of the iRegulon plug-in in Cytoscape, our study further predicts and established regulatory networks related to transcription factors and regulatory genes. In addition, the miRWalk2.0 database was used to search for miRNA-DEG pairs, associated with the conduction of intersections of miRNAs predicted by TargetScan, Miranda, miRDB and RNA22 databases. Then, these miRNA-DEG pairs were also displayed in the form of a regulatory network through Cytoscape. Finally, two datasets were selected to verify the screened genes, regulatory factors, and miRNAs, to plot receiver operating characteristics (ROC) curves and compute the area under the curve (AUC) values. The results showed that AKT1, MMP9, ARG1, ETS1 targeting AKT1, and has-miR-124-3p targeting RPS6KA5 may have diagnostic value for patients with sepsis and septic shock. While further experimental studies are required to confirm their role in septic neutrophils.

The validity, reliability and feasibility of four instruments for assessing the consciousness of stroke patients in a neurological intensive care unit compared.

BACKGROUND: Early rehabilitation is the foundation for recovery for those admitted to an intensive care unit. Appropriate assessment of consciousness is needed before any rehabilitative intervention begins. METHODS: This prospective study compared the validity, reliability and applicability of the sedation-agitation scale, the Richmond Agitation-Sedation Scale, the motor activity assessment scale and the Glasgow Coma Scale in a working neurological intensive care unit. Eighty-three stroke patients were assessed with the four scales by the same 3 raters acting independently: a senior physician, a senior therapist and a trainee. That generated 996 assessment records for comparison. RESULTS: Good agreement (r=0.98-0.99) was found among the sedation-agitation scale, the Richmond Agitation-Sedation Scale, the motor activity assessment scale scores, but the Glasgow Coma Scale ratings correlated less well (r=0.72-0.76) with the others. Consistent results were also found among the three raters. After stratification of the ratings by age, gender, level of consciousness and Acute Physiology and Chronic Health Evaluation score, the scales reported significant differences among the levels of consciousness and among those with different Acute Physiology and Chronic Health Evaluation results, but not with different age or gender strata. CONCLUSIONS: The four instruments tested are all reliable enough and feasible for use as a tool for consciousness screening in a neurological intensive care unit.

Identification of Immune-Related Key Genes as Potential Diagnostic Biomarkers of Sepsis in Children.

Objective: The pathogenesis of sepsis is still unclear due to its complexity, especially in children. This study aimed to analyse the immune microenvironment and regulatory networks related to sepsis in children at the molecular level and to identify key immune-related genes to provide a new basis for the early diagnosis of sepsis. Methods: The GSE145227 and GSE26440 datasets were downloaded from the Gene Expression Omnibus. The analyses included differentially expressed genes (DEGs), functional enrichment, immune cell infiltration, the competing endogenous RNA (ceRNA) interaction network, weighted gene coexpression network analysis (WGCNA), protein-protein interaction (PPI) network, key gene screening, correlation of sepsis molecular subtypes/immune infiltration with key gene expression, the diagnostic capabilities of key genes, and networks describing the interaction of key genes with transcription factors and small-molecule compounds. Finally, real-time quantitative PCR (RT-qPCR) was performed to verify the expression of key genes. Results: A total of 236 immune-related DEGs, most of which were enriched in immune-related biological functions, were found. Further analysis of immune cell infiltration showed that M0 macrophages and neutrophils infiltrated more in the sepsis group, while fewer activated memory CD4+ T cells, resting memory CD4+ T cells, and CD8+ T cells did. The interaction network of ceRNA was successfully constructed. Six key genes (FYN, FBL, ATM, WDR75, FOXO1 and ITK) were identified by WGCNA and PPI analysis. We found strong associations between key genes and constructed septic molecular subtypes or immune cell infiltration. Receiver operating characteristic analysis showed that the area under the curve values of the key genes for diagnosis were all greater than 0.84. Subsequently, we successfully constructed an interaction network of key genes and transcription factors/small-molecule compounds. Finally, the key genes in the samples were verified by RT-qPCR. Conclusion: Our results offer new insights into the pathogenesis of sepsis in children and provide new potential diagnostic biomarkers for the disease.

Protection of toll-like receptor 9 against lipopolysaccharide-induced inflammation and oxidative stress of pulmonary epithelial cells via MyD88-mediated pathways.

Acute lung injury (ALI) caused by lipopolysaccharide (LPS) is a common, severe clinical syndrome. Injury caused by inflammation and oxidative stress in vascular endothelial and alveolar epithelial cells is a vital process in the pathogenesis of ALI. Toll-like receptor 9 (TLR9) is highly expressed in LPS-induced ALI rats. In this study, Beas-2B human pulmonary epithelial cells and A549 alveolar epithelial cells were stimulated by LPS, resulting in the upregulation of TLR9 in a concentrationdependent manner. Furthermore, TLR9 overexpression and interference vectors were transfected before LPS administration to explore the role of TLR9 in LPS-induced ALI in vitro. The findings revealed that inhibition of TLR9 reduced inflammation and oxidative stress while suppressing apoptosis of LPS-induced Beas-2B and A549 cells, whereas TLR9 overexpression aggravated these conditions. Moreover, TLR9 inhibition resulted in downregulated protein expression of myeloid differentiation protein 88 (MyD88) and activator activator protein 1 (AP-1), as well as phosphorylation of nuclear factor-?B (NF-kappaB), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). The phosphorylation of extracellular-regulated protein kinases 1/2 was upregulated compared to that of cells subjected to only LPS administration, and this was reversed by TLR9 overexpression. These results indicate that inhibition of TLR9 plays a protective role against LPS-induced inflammation and oxidative stress in Beas-2B and A549 cells, possibly via the MyD88/NF-kappaB and MyD88/MAPKs/AP-1 pathways.

Relation Between Sensorimotor Rhythm During Motor Attempt/Imagery and Upper-Limb Motor Impairment in Stroke.

Motor attempt (MA)/motor imagery (MI)-based brain-computer interface (BCI) is a newly developing rehabilitation technology for motor impairment. This study aims to explore the relationship between electroencephalography sensorimotor rhythm and motor impairment to provide reference for a BCI design. Twenty-eight stroke survivors with varying levels of motor dysfunction and spasticity status in the subacute or chronic stage were enrolled in the study to perform MA and MI tasks. Event-related desynchronization (ERD)/event-related synchronization (ERS) during and immediately after motor tasks were calculated. The Fugl-Meyer assessment scale (FMA) and the modified Ashworth scale (MAS) were applied to characterize upper-limb motor dysfunction and spasticity. There was a positive correlation between FMA total scores and ERS in the contralesional hemisphere in the MI task (P < .05) and negative correlations between FMA total scores and ERD in both hemispheres in the MA task (P < .05). Negative correlations were found between MAS scores of wrist flexors and ERD in the ipsilesional hemisphere (P < .05) in the MA task. It suggests that motor dysfunction may be more correlated to ERS in the MI task and to ERD in the MA task while spasticity may be more correlated to ERD in the MA task.

Exercise-induced neuroprotection against cerebral ischemia/reperfusion injury is mediated via alleviating inflammasome-induced pyroptosis.

As a primary nonpharmacological tool, exercise training is neuroprotective after experimental ischemic stroke by relieving neuroinflammation. However, the specific mechanism of which and anti-inflammatory effect of exercise at different intensities require in-depth investigations. To explore the issue, middle cerebral artery occlusion-reperfusion (MCAO-r) in mice were utilized, with subsequent exercise training at different intensities (high-intensity interval training versus moderate-intensity continuous training, i.e. HIIT vs. MICT) during an early phase post-modeling. The neurobehavioral assessment showed that MICT improved the performance of neurological deficit scores and rotarod test earlier, while HIIT appeared to be more efficacious to meliorate locomotor impairments and aerobic fitness at the end of intervention. Both exercise regimens inhibited the expressions of NLRP3 inflammasome components (NLRP3, ASC, and Cl.caspase-1) and pyroptosis-associated proteins (GSDMD, Cl.IL-1ß, and Cl.IL-18) as indicated by western blot and immunofluorescence co-staining. Multiplex assay panel revealed that both exercise regimens reduced the levels of pro-inflammatory cytokines and upregulated anti-inflammatory cytokine. Furthermore, an increased proportion of M2-like microglia and a diminished proportion of M1-like microglia in the peri-infarct zone were observed by colocalization analysis, which was jointly validated by western blot. Here, for the first time, our study demonstrated that HIIT elicited better improvements at functional and cardiovascular levels than MICT after ischemic stroke, and anti-inflammatory effect of exercise might result from suppression in inflammasome-mediated pyroptosis by shifting microglial polarization toward neuroprotective M2 phenotype.

Application of Immersive Virtual-Reality-Based Puzzle Games in Elderly Patients with Post-Stroke Cognitive Impairment: A Pilot Study.

Background: The society is aging in China, and the cognitive level of elderly post-stroke patients gradually declines. Face-to-face cognitive functional training is no longer sufficient. Immersive virtual reality (IVR) is a promising rehabilitation training device. In this study, we developed an IVR-based puzzle game to explore its effectiveness, feasibility, and safety in elderly stroke patients with cognitive dysfunction. Methods: A total of 30 patients with mild post-stroke cognitive impairment after stroke were randomly assigned to a control or IVR group. Patients in both groups received routine rehabilitation therapy. Patients in the control group received traditional cognitive training, and those in the IVR group received IVR-based puzzle game therapy. Before and after treatment, Montreal cognitive assessment (MOCA), trail-making test-A (TMT-A), digit symbol substitution test (DSST), digital span test (DST), verbal fluency test (VFT), and modified Barthel index (MBI) were evaluated in both groups. In addition, the IVR group was administered a self-report questionnaire to obtain feedback on user experience. Results: There was no significant difference in the baseline data between the two groups. After six weeks of treatment, the cognitive assessment scores were improved in both groups. Moreover, the IVR group showed more improvements than the control group in the DSST (Z = 2.203, p = 0.028 < 0.05, η2 = 0.16); MOCA (T = 1.186, p = 0.246 > 0.05, d = 0.44), TMT-A (T = 1.791, p = 0.084 > 0.05, d = 0.65), MBI (T = 0.783, p = 0.44 > 0.05, d = 0.28), FDST (Z = 0.78, p = 0.435 > 0.05, η2 = 0.02), BDST (Z = 0.347, p = 0.728 > 0.05, η2 = 0.004), and VFT(Z = 1.087, p = 0.277 > 0.05, η2 = 0.039) did not significantly improve. The significant difference in DSST represents an improvement in executive function and visual−spatial cognitive characteristics. The other assessment scores did not show such features. Therefore, we did not observe significant differences through this measure. According to the results of the self-report questionnaire, most of the patients were satisfied with the equipment stability and training content. Several individuals reported mild adverse reactions. Conclusions: This pilot study suggests that IVR-based puzzle games are a promising approach to improve post-stroke cognitive function, especially executive cognitive function, and visual−spatial attention in older adults.

The Effect of Applying Robot-Assisted Task-Oriented Training Using Human-Robot Collaborative Interaction Force Control Technology on Upper Limb Function in Stroke Patients: Preliminary Findings.

Stroke is one of the leading causes of death and the primary cause of acquired disability worldwide. Many stroke survivors have difficulty using their upper limbs, which have important functional roles in the performance of daily life activities. Consequently, the independence and quality of life of most stroke patients are reduced. Robot-assisted therapy is an effective intervention for improving the upper limb function of individuals with stroke. Human-robot collaborative interaction force control technology is critical for improving the flexibility and followability of the robot's motion, thereby improving rehabilitation training outcomes. However, there are few reports on the effect of robot-assisted rehabilitative training on upper limb function. We applied this technology using a robot to assist patients with task-oriented training. Posttreatment changes in Fugl-Meyer and modified Barthel index (MBI) scores were assessed to determine whether this technology could improve the upper limb function of stroke patients. One healthy adult and five stroke patients, respectively, participated in functional and clinical experiments. The MBI and Fugl-Meyer scores of the five patients in the clinical experiments showed significant improvements after the intervention. The experimental results indicate that human-robot collaborative interaction force control technology is valuable for improving robots' properties and patients' recovery. This trial was registered in the Chinese clinical trial registry (ChiCTR2000038676).

Silencing of LncRNA-PVT1 ameliorates lipopolysaccharide-induced inflammation in THP-1-derived macrophages via inhibition of the p38 MAPK signaling pathway.

BACKGROUND: Sepsis is common in intensive care units and has a high mortality rate; yet, its pathogenesis and treatment remain unclear. Recent studies have shown that long non-coding RNA plasmacytoma variant translocation 1 (lncRNA-PVT1) plays a pro-inflammatory role in immune-related inflammatory diseases. Therefore, we investigated whether lncRNA-PVT1 plays an important pro-inflammatory effect in the inflammatory response of sepsis. METHODS: Quantitative real-time PCR (RT-qPCR) was employed for the detection of lncRNA-PVT1, interleukin 1ß (IL-1ß), and tumor necrosis factor α (TNF-α) mRNA, and the correlations between their expressions were analyzed. After lncRNA-PVT1 knockdown by lncRNA Smart Silencer, abnormal expressions of lncRNA-PVT1, and IL-1ß and TNF-α mRNA were detected. The expressions of total and phosphorylated protein of p38 were detected by western blotting. The effect of silencing lncRNA-PVT1 on p38 mitogen-activated protein kinase (MAPK) signaling pathway during lipopolysaccharide (LPS)-induced inflammation was subsequently analyzed. The MAPK selective inhibitor, SB202190, was used to block this signaling pathway, and the expressions of lncRNA-PVT1 and TNF-α were detected by RT-qPCR. Furthermore, the effect of partial blockade of the p38 MAPK signaling pathway by SB202190 on the levels of lncRNA-PVT1 was explored. RESULTS: Following treatment of THP-1-derived macrophages with different concentrations of LPS, the levels of lncRNA-PVT1 and IL-1ß, TNF-α mRNA were increased in a dose-dependent manner. Silencing of lncRNA-PVT1 reduced the expressions of IL-1ß and TNF-α mRNA via inhibition of the p38 MAPK signaling pathway. Specifically, inhibiting the p38 MAPK pathway significantly decreased the LPS-induced lncRNA-PVT1 elevation. CONCLUSIONS: Our observations suggest that lncRNA-PVT1 can be silenced to ameliorate LPS-induced inflammation in macrophages via inhibition of the p38 MAPK pathway. Further, the p38 MAPK pathway can regulate the expression of lncRNA-PVT1 via a positive feedback loop.

Prognostic Value of the Red Cell Distribution Width in Patients with Sepsis-Induced Acute Respiratory Distress Syndrome: A Retrospective Cohort Study.

OBJECTIVE: The prognostic value of the red cell distribution width (RDW) in patients with sepsis-induced acute respiratory distress syndrome (ARDS) is still elusive. This study is aimed at determining whether RDW is a prognostic indicator of sepsis-induced ARDS. METHODS: This retrospective cohort study included 1161 patients with sepsis-induced ARDS. The datasets were acquired from the Medical Information Mart for Intensive Care III database. The locally weighted scatter-plot smoothing technique, Cox regression, Kaplan-Meier estimator, and subgroup analysis were carried out to evaluate the association between RDW and 90-day mortality. RESULTS: The RDW and mortality had a roughly linear increasing relationship. The Cox regression model results were as follows: for level 2 (14.5% < RDW < 16.2%), hazard ratio (HR) = 1.35, 95% confidence interval (CI) = 1.03-1.77, and for level 3 (RDW ≥ 16.2%), HR = 2.07, 95% CI = 1.59-2.69. The following results were obtained when RDW was treated as a continuous variable: HR = 1.11, 95%CI = 1.06-1.15. The P values of the interaction between the RDW and covariates were greater than 0.05. CONCLUSION: RDW is a new independent prognostic marker for patients with sepsis-induced ARDS.