Relationship between depression and burnout among nurses in Intensive Care units at the late stage of COVID-19: a network analysis.

BACKGROUND: Mental health problems are critical and common in medical staff working in Intensive Care Units (ICU) even at the late stage of COVID-19, particularly for nurses. There is little research to explore the inner relationships between common syndromes, such as depression and burnout. Network analysis (NA) was a novel approach to quantified the correlations between mental variables from the perspective of mathematics. This study was to investigate the interactions between burnout and depression symptoms through NA among ICU nurses. METHOD: A cross-sectional study with a total of 616 Chinese nurses in ICU were carried out by convenience sampling from December 19, 2022 to January19, 2023 via online survey. Burnout symptoms were measured by Maslach Burnout Inventory-General Survey (MBI-GS) (Chinese version), and depressive symptoms were assessed by the 9-item Patient Health Questionnaire (PHQ-9). NA was applied to build interactions between burnout and depression symptoms. We identified central and bridge symptoms by R package qgraph in the network model. R package bootnet was used to examined the stability of network structure. RESULTS: The prevalence of burnout and depressive symptoms were 48.2% and 64.1%, respectively. Within depression-burnout network, PHQ4(Fatigue)-MBI2(Used up) and PHQ4(Fatigue)-MBI5(Breakdown) showed stronger associations. MBI2(Used up) had the strongest expected influence central symptoms, followed by MBI4(Stressed) and MBI7 (Less enthusiastic). For bridge symptoms. PHQ4(Fatigue), MBI5(Breakdown) and MBI2(Used up) weighed highest. Both correlation stability coefficients of central and bridge symptoms in the network structure were 0.68, showing a high excellent level of stability. CONCLUSION: The symptom of PHQ4(Fatigue) was the bridge to connect the emotion exhaustion and depression. Targeting this symptom will be effective to detect mental disorders and relieve mental syndromes of ICU nurses at the late stage of COVID-19 pandemic.

Development and validation of an assessment index for quantifying cognitive task load in pilots under simulated flight conditions using heart rate variability and principal component analysis.

To investigate whether high cognitive task load (CTL) for aircraft pilots can be identified by analysing heart-rate variability, electrocardiograms were recorded while cadet pilots (n = 68) performed the plane tracking, anti-gravity pedalling, and reaction tasks during simulated flight missions. Data for standard electrocardiogram parameters were extracted from the R-R-interval series. In the research phase, low frequency power (LF), high frequency power (HF), normalised HF, and LF/HF differed significantly between high and low CTL conditions (p < .05 for all). A principal component analysis identified three components contributing 90.62% of cumulative heart-rate variance. These principal components were incorporated into a composite index. Validation in a separate group of cadet pilots (n = 139) under similar conditions showed that the index value significantly increased with increasing CTL (p < .05). The heart-rate variability index can be used to objectively identify high CTL flight conditions.Practitioner summary: We used principal component analysis of electrocardiogram data to construct a composite index for identifying high cognitive task load in pilots during simulated flight. We validated the index in a separate group of pilots under similar conditions. The index can be used to improve cadet training and flight safety.Abbreviations: ANOVA: a one-way analysis of variance; AP: anti-gravity pedaling task; CTL: cognitive task load; ECG: electrocardiograms; HR: heart rate; HRV: heart-rate variability; HRVI: heart-rate variability index; PT: plane-tracking task; RMSSD: root-mean square of differences between consecutive R-R intervals; RT: reaction task; SDNN: standard deviation of R-R intervals; HF: high frequency power; HFnu: normalized HF; LF: low frequency power; LFnu: normalized LF; PCA: principal component analysis.

Stat3 shRNA delivery with folate receptor-modified multi-functionalized graphene oxide particles for combined infrared radiation and gene therapy in hepatocellular carcinoma.

As a vital oncogene, a variety of inhibitors targeting Stat3 and its various upstream signaling pathways has been explored. Since small molecules, peptidomimetics and other peptide inhibitors usually lead to side effects and difficult administration, gene therapeutics that have characteristics of low toxicity and high targeting, make them an attractive alternative for targeting Stat3. A major challenge to this approach is the lack of safe delivery systems for in-vivo applications. Among the various siRNA delivery systems, nanoparticles emerge as a new tool for gene delivery with high biocompatibility, low cost, and minimal toxicity. In this study, we developed a graphene oxide (GO)-based nanocarrier, GO-polyethyleneimine (PEI)-polyethylene glycol (PEG)-folic acid (FA), as a tool targeting for Stat3-specific shRNA to mouse hepatoma cells in vitro and in vivo . Infrared photothermal therapy was combined in vivo since GO has the characteristic of infrared absorbability. Our results suggest a significant tumor growth inhibition after treatment with GO-PEI-PEG-FA- sh-Stat3 combined with infrared photothermal therapy. Thus, GO-PEI-PEG-FA appears to be a novel nano-transformer that could be used in the clinics in future.

Effects of novel microimplant-assisted rapid palatal expanders manufactured by 3-dimensional printing technology: A finite element study.

INTRODUCTION: The expansion effects of several new microimplant-assisted rapid palatal expanders (MARPEs) manufactured by 3-dimensional printing technology were evaluated by finite element analysis (FEA). The aim was to identify a novel MARPE suitable for treating maxillary transverse deficiency. METHODS: The finite element model was established using MIMICS software (version 19.0; Materialise, Leuven, Belgium). First, the appropriate microimplant insertion characteristics were identified via FEA, and several MARPEs with the above insertion patterns were manufactured by 3-dimensional printing technology. Then, the stress distribution and displacement prediction of the 4 MARPEs and hyrax expander (model E) were evaluated via FEA: bone-borne (model A), bone-tooth-borne (model B), bone-mucous-borne (model C), bone-tooth-mucous-borne (model D). RESULTS: Monocortical microimplants perpendicular to the cortical bone on the coronal plane resulted in better expansion effects. Compared with a conventional hyrax expander, the orthopedic expansion of each of the 4 MARPEs was far larger, the parallelism was greater, and the posterior teeth tipping rate was lower. Among them, the expansion effects of models C and D were the best; the von Mises peak values on the surfaces of the microimplants were smaller than those of models A and B. CONCLUSIONS: This study may demonstrate that the 4 MARPEs obtained more advantageous orthopedic expansion effects than a hyrax expander. Models C and D obtained better biomechanical effects and had better primary stability. Overall, model D is the recommended expander for treating maxillary transverse deficiency because its structure acts like an implant guide and is beneficial for the accurate insertion of the microimplant.

A photodynamically sensitized dendritic cell vaccine that promotes the anti-tumor effects of anti-PD-L1 monoclonal antibody in a murine model of head and neck squamous cell carcinoma.

BACKGROUND: Immune checkpoint inhibitors are promising tools in combating several cancers, including head and neck squamous cell carcinoma (HNSCC). However, a substantial portion of HNSCC patients do not respond to PD-L1 antibody. Here we describe a photodynamic therapeutic (PDT) approach to enhance anti-tumor effects of the anti-PD-L1 antibody. METHODS: Phototoxicity of PDT was confirmed using fluorescence microscopy, Cell Counting Kit-8 (CCK-8), Enzyme Linked Immunosorbent Assay (ELISA) and flow cytometry analyses. Phenotypic and functional maturation of immature DCs (imDCs) induced by PDT were measured using flow cytometry and ELISA. A mouse model was established using the HNSCC line, SCC7, and was used to evaluate therapeutic effects of PDT-DC vaccine in facilitating anti-tumor immunity of PD-L1 antibody. RESULTS: Immunogenic cell death (ICD) of SCC7 cells was induced by PDT with 0.5 µM of m-THPC and the 5 J/cm2 of light dose. ICD of SCC7 cells stimulated imDCs maturation. In vivo assays suggested that PDT-DC vaccine and anti-PD-L1 mAb synergistically induced anti-tumor immunity and suppressed tumor progression. CONCLUSION: PDT-DC vaccine enhances therapeutic effects of PD-L1 antibody, which might provide a novel approach for HNSCC immunotherapy.

High-efficiency treatment with the use of traditional anchorage control for a patient with Class II malocclusion and severe overjet.

Patients with Class II malocclusion and severe overjet are often dissatisfied with their facial disharmony. Although temporary skeletal anchorage devices (TSADs) are now widely used in orthodontic treatment, traditional anchorage devices should not be overlooked as a treatment option. Proper design of traditional anchorage can achieve 3-dimensional control of incisors and molars as efficiently as TSADs in some patients with severe malocclusion. We used traditional anchorage devices, including a transpalatal arch and a Nance palatal arch, combined with a utility arch to treat an 11-year-old Chinese girl with a skeletal Class II malocclusion and severe overjet. The space was closed in 2 steps to protect molar anchorage. Facial improvement, especially smile esthetics, and Class I molar relationship and overjet correction were achieved in 17 months of treatment. Follow-up records 22 months after treatment show that the results remained stable.

Inhibitory Effect of Low-Intensity Pulsed Ultrasound on the Expression of Lipopolysaccharide-Induced Inflammatory Factors in U937 Cells.

OBJECTIVES: Low-intensity pulsed ultrasound (US) has been reported to promote periodontal tissue regeneration and reduce inflammation in soft tissues and in bone infectious diseases. Here we investigated the effect of low-intensity pulsed US on the expression of lipopolysaccharide (LPS)-induced inflammatory factors in U937 macrophage cells. METHODS: U937 cells were stimulated with different concentrations of LPS and exposed to different intensities of low-intensity pulsed US. Cell viability and apoptosis of U937 cells were determined by cell-counting kit assays and flow cytometry. A real-time polymerase chain reaction and an enzyme-linked immunosorbent assay were used to test the expression of inflammatory factors. The expression levels of toll-like receptor 4, p65, p-IκBα, and IκBα were assessed by western blots. RESULTS: Tumor necrosis factor α began to increase in U937 cells on induction with 1-µg/mL LPS. Low-intensity pulsed US at the intensity of 60 mW/cm2 was more effective in reducing interleukin 8 (IL-8) expression. Furthermore, LPS inhibited the viability and increased apoptosis of U937 cells, whereas low-intensity pulsed US significantly reversed these effects (P < .05). Low-intensity pulsed US reduced the protein expression of IL-6 and IL-8 at both gene and protein levels in U937 cells. The western blot and immunofluorescence showed that low-intensity pulsed US primarily suppressed the degradation and phosphorylation of IκBα and the translocation of p65 into the nuclei. CONCLUSIONS: Low-intensity pulsed US alleviated the expression of inflammatory factors induced by LPS in U937 cells. This process was modulated by suppressing the toll-like receptor 4-nuclear factor κB signaling pathway. Therefore, low-intensity pulsed US might be a potential immunomodulatory therapy for the treatment of periodontitis.

3D reconstruction images of cone beam computed tomography in dental medicine application: A case study and mini-review.

Dental cone beam computed tomography (CBCT) is a new approach in diagnosis and predication of various dental diseases, including trauma, congenital defects, tumors and inflammatory. In this study, we reported the outcome of CBCT for a complicated case of malocclusion, accompanied with tooth loss and periodontitis. A combined application of CBCT with 3D-static images and rotated reconstruction images is reviewed as a systematic model in diagnosis, treatment and progonsis of a complex malocclusion.

[Influence of healing process of extraction on related growth factors in microscrew-bone interface of implanted titanium microscrews near the extraction wounds].

OBJECTIVE: To detect the expression of growth factors relating to bone reconstructions in microscrew-bone interface of implanted titanium microscrews near the extraction wounds, and to determine the influence of healing process on the growth factors. METHODS: Eight male Beagle dogs (age 18 months) were divided into experimental and control groups. Titanium microscrews were implanted near an extraction wound in the dogs in the experimental group, while the controls had implantation without extraction wounds. The dogs were sacrificed at 1, 3, 8, 12 weeks, respectively. Immunohistochemistry and in situ hybridization sections were performed to detect the expression of TGF-beta, TNF-alpha, osteocalcin (OC) protein and Cbfal mRNA. RESULTS: The experimental group had higher levels of expression of TGF-beta, TNF-alpha protein and Cbfa1 mRNA than the controls, with significant differences appearing at week one for TNF-alpha (P<0.05), week three for TGF-beta and TNF-alpha (P<0.05), and week eight for Cbfa1 mRNA (P<0.05). The expression of OC increased over time and reached peak at week eight (P<0.05). CONCLUSION: Microscrews implanted near extraction wounds can maintain stability. Severe inflammation occurs in the early stage of healing, but does not sustain. Bone remodeling remains active over the healing process. But prolonged healing phase without force loading could weaken the remodeling.

Taxifolin inhibits melanoma proliferation/migration impeding USP18/Rac1/JNK/ß-catenin oncogenic signaling.

BACKGROUND: Metastatic melanoma is a fatal cancer. Despite the advances in targeted therapy and immunotherapy for patients with melanoma, drug resistance and low response rates pose a considerable challenge. Taxifolin is a multifunctional natural compound with emerging antitumor potentials. However, its utility in melanoma treatment remains unclear. PURPOSE: The study aimed to investigate the effect of purified Taxifolin from Larix olgensis roots (Changbai Mountain, China) on melanoma and explore the underlying mechanism. METHODS: Purified Taxifolin from Larix olgensis roots was evaluated for its antimelanoma effects in vitro and in vivo settings. RNA-seq analysis was performed to explore the underlying mechanism. RESULTS: Purified Taxifolin (> 99 %) from Larix olgensis roots inhibited the proliferation and migration of B16F10 melanoma cells at 200 and 400 µM, and of A375 cells at 100 and 200 µM. Taxifolin administered at 60 mg/kg suppressed tumor growth and metastasis in mouse models without causing significant toxicity. Taxifolin modulated USP18/Rac1/JNK/ß-catenin axis to exert its antitumor effect. CONCLUSION: These findings indicate that Taxifolin derived from Larix olgensis roots may be a promising antimelanoma therapy.

Enhancing emotion regulation: investigating the efficacy of transcutaneous electrical acupoint stimulation at PC6 in reducing fear of heights.

This study investigated the impact of transcutaneous electrical acupoint stimulation (TEAS) at Neiguan acupoint (PC6) on the physiological and behavioral responses of participants exposed in virtual height. 40 participants were included in the study and were randomly assigned to either a control group or an intervention group. Participants had an immersive experience with a VR interactive platform that provided somatosensory interaction in height stimulation scenes. Psychological scores, behavioral and cognitive performance, and physiological responses were recorded and analyzed. The results indicated that the intervention group had significantly lower fear scores compared to the control group. Analysis of heart rate variability revealed that the intervention group exhibited improved heart rate variability, indicating enhanced cardiovascular function and emotion regulation. The behavioral and cognitive results demonstrated that the intervention group exhibited higher left eye openness, faster reaction times, and greater movement distance, suggesting enhanced attentional focus, cognitive processing, and reduced avoidance behaviors. These findings suggest that TEAS at PC6 can effectively reduce fear and improve the regulation of physiological and behavioral responses to negative emotional stimuli.

STING in tumors: a focus on non-innate immune pathways.

Cyclic GMP-AMP synthase (cGAS) and downstream stimulator of interferon genes (STING) are involved in mediating innate immunity by promoting the release of interferon and other inflammatory factors. Mitochondrial DNA (mtDNA) with a double-stranded structure has greater efficiency and sensitivity in being detected by DNA sensors and thus has an important role in the activation of the cGAS-STING pathway. Many previous findings suggest that the cGAS-STING pathway-mediated innate immune regulation is the most important aspect affecting tumor survival, not only in its anti-tumor role but also in shaping the immunosuppressive tumor microenvironment (TME) through a variety of pathways. However, recent studies have shown that STING regulation of non-immune pathways is equally profound and also involved in tumor cell progression. In this paper, we will focus on the non-innate immune system pathways, in which the cGAS-STING pathway also plays an important role in cancer.

Efficacy and safety of innate and adaptive immunotherapy combined with standard of care in high-grade gliomas: a systematic review and meta-analysis.

Background: Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival. Method: Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356). Results: We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; Z = -2.00, P = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; Z = -1.99, P = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; P = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; Z = -3.53; P = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; Z = -2.23; P = 0.0256). Conclusion: Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.

Metal-organic framework modified carbon cloth for electric field enhanced thin film microextraction of sulfonamides in animal-derived food.

Sulfonamides (SAs) were widespread in animal-derived food at trace level, which could trigger hazards to human health. Herein, electric field enhanced thin-film microextraction (EE-TFME) was developed based on carbon cloth (CC) modified with metal-organic frameworks (MOFs) for extraction of SAs (sulfadiazine, sulfathiazole, sulfamerazine, sulfadimidine, sulfamethoxazole and sulfisoxazole), which were a series of polar analytes. MIL-101(Cr) was in situ synthesized on CC via hydrothermal reaction and then was used as positive electrode in EE-TFME for adsorption of SAs. Compared with traditional TFME, EE-TFME shortened extraction equilibrium time from 30 min to 15 min. Coupled with high-performance liquid chromatography (HPLC), the limits of detection (LODs) were 2.5-4.5 µg/L, while the repeatability and intermediate precision was lower than 9.1%. Quantitative determination of SAs in extracts of animal-derived samples, such as honey, pork, chicken and milk, was achieved with recoveries from 81.7% to 114.2%. The developed MOF/CC-based EE-TFME has a great potential in rapid extraction of similar polar or ionic analytes from complex food matrices.

Roles for the methyltransferase SETD8 in DNA damage repair.

Epigenetic posttranslational modifications are critical for fine-tuning gene expression in various biological processes. SETD8 is so far the only known lysyl methyltransferase in mammalian cells to produce mono-methylation of histone H4 at lysine 20 (H4K20me1), a prerequisite for di- and tri-methylation. Importantly, SETD8 is related to a number of cellular activities, impinging upon tissue development, senescence and tumorigenesis. The double-strand breaks (DSBs) are cytotoxic DNA damages with deleterious consequences, such as genomic instability and cancer origin, if unrepaired. The homology-directed repair and canonical nonhomologous end-joining are two most prominent DSB repair pathways evolved to eliminate such aberrations. Emerging evidence implies that SETD8 and its corresponding H4K20 methylation are relevant to establishment of DSB repair pathway choice. Understanding how SETD8 functions in DSB repair pathway choice will shed light on the molecular basis of SETD8-deficiency related disorders and will be valuable for the development of new treatments. In this review, we discuss the progress made to date in roles for the lysine mono-methyltransferase SETD8 in DNA damage repair and its therapeutic relevance, in particular illuminating its involvement in establishment of DSB repair pathway choice, which is crucial for the timely elimination of DSBs.

Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation.

Purpose: There is a bidirectional relationship between periodontitis and type 2 diabetes mellitus (T2DM). The aim of this study was to further explore the pathogenesis of this comorbidity, screen out ferroptosis-related genes involved in the pathological process, and predict potential drug targets to develop new therapeutic strategies. Methods: Common cross-talk genes were identified from periodontitis datasets (GSE16134, GSE10334 and GSE106090) and T2DM databases (DisGeNET and GeneCard). Then, GO and KEGG enrichment analyses, PPI network analysis and hub gene identification were performed. The association between ferroptosis and periodontitis with T2DM was investigated by Pearson correlation analysis. Core ferroptosis-related cross-talk genes were identified and verified by qRT-PCR. Potential drugs targeting these core genes were predicted via DGIDB. Results: In total, 67 cross-talk genes and two main signalling pathways (immuno-inflammatory pathway and AGE-RAGE signalling pathway) were identified. Pearson correlation analysis indicated that ferroptosis served as a crucial target in the pathological mechanism and treatment of periodontitis with T2DM. IL-1ß, IL-6, NFE2L2 and ALOX5 were identified as core ferroptosis-related genes and the qRT-PCR detection results were statistically different. In total, 13 potential drugs were screened out, among which, Echinacea and Ibudilast should be developed first. Conclusions: This study contributes to a deeper understanding of the common pathogenesis of periodontitis and T2DM and provides new insights into the role of ferroptosis in this comorbidity. In addition, two drugs with potential clinical application value were identified. The potential utility of these drugs requires further experimental investigation.

Epigenetic regulation of cancer stem cells: Shedding light on the refractory/relapsed cancers.

The resistance to drugs, ability to enter quiescence and generate heterogeneous cancer cells, and enhancement of aggressiveness, make cancer stem cells (CSCs) integral part of tumor progression, metastasis and recurrence after treatment. The epigenetic modification machinery is crucial for the viability of CSCs and evolution of aggressive forms of a tumor. These mechanisms can also be targeted by specific drugs, providing a promising approach for blocking CSCs. In this review, we summarize the epigenetic regulatory mechanisms in CSCs which contribute to drug resistance, quiescence and tumor heterogeneity. We also discuss the drugs that can potentially target these processes and data from experimental and clinical studies.