Genetic deletion of the apoptosis associated speck like protein containing a card in LysM+ macrophages attenuates spinal cord injury by regulating M1/M2 polarization through ASC-dependent inflammasome signaling axis.

Apoptosis associated speck like protein containing a card (ASC), the key adaptor protein of the assembly and activation of canonical inflammasomes, has been found to play a significant role in neuroinflammation after spinal cord injury (SCI). The previous studies indicated that widely block or knockout ASC can ameliorate SCI. However, ASC is ubiquitously expressed in infiltrated macrophages and local microglia, so further exploration is needed on which type of cell playing the key role. In this study, using the LysMcre;Ascflox/flox mice with macrophage-specifc ASC conditional knockout (CKO) and contusive SCI model, we focus on evaluating the specific role of ASC in lysozyme 2 (LysM)+ myeloid cells (mainly infiltrated macrophages) in this pathology. The results revealed that macrophage-specifc Asc CKO exhibited the follow effects: (1) A significant reduction in the numbers of infiltrated macrophages in the all phases of SCI, and activated microglia in the acute and subacute phases. (2) A significant reduction in ASC, caspase-1, interleukin (IL)-1ß, and IL-18 compared to control mice. (3) In the acute and subacute phases of SCI, M1 subset differentiation was inhibited, and M2 differentiation was increased. (4) Histology and hindlimb motor recoveries were improved. In conclusion, this study elucidates that macrophage-specific ASC CKO can improve nerve function recovery after SCI by regulating M1/M2 polarization through inhibiting ASC-dependent inflammasome signaling axis. This indicates that ASC in peripheral infiltrated macrophages may play an important role in SCI pathology, at least in mice, could be a potential target for treatment.

Patterns of intrinsic capacity trajectory and onset of activities of daily living disability among community-dwelling older adults.

Background: Global population ageing has brought about new challenges for elderly care. Exploring intrinsic capacity (IC) over time, which is designed as a composite measure of an individual's physical and mental capabilities, is essential for promoting healthy ageing and preventing dependency, such as that emerging from disability in activities of daily living (ADL). We aimed to identify and examine the differences between classes of IC trajectory and onset of ADL disability. Methods: We conducted an observational study using data from three waves (2011-15) of the China Health and Retirement Longitudinal Study, comprising 2609 participants with 6034 observations. IC was measured by five domains, including locomotion, cognition, psychological, sensory capacities, and vitality. We used joint latent class modelling to identify distinct classes with similar patterns of IC trajectory and onset of ADL disability, as well as to explore the variation in IC trajectory and predict five-year risks of ADL disability considering the heterogeneity in the elderly population. Results: The average baseline IC score was 7.15 (range: 0-15). We observed that IC scores slowly decreased with age, with 17.25% of participants developing ADL disability. We identified three classes of IC, which could be described as moderate health (class 1: n = 1634, 62.63%), at-risk (class 2: n = 716, 27.44%; had the highest risk of ADL disability), and optimal health (class 3: n = 259, 9.93%; had the lowest baseline risk of ADL disability). The probability of being in the moderate health class was decreased the most by emotional problems (odds ratio (OR) = 0.219; P < 0.001). Having a self-rated poor standard of living substantially reduced the chances of moderate (OR = 0.308; P = 0.001) and optimal health (OR = 0.110; P < 0.001). Conclusions: Observing IC trajectories and the onset of ADL disability can stratify the elderly into heterogeneous groups, as well as provide data for implementing person-centred care plans to reverse the trend and delay the adverse outcomes in clinical practice.

Epidemiological characteristics of human rabies cases reported by sites in China from 2006 to 2022.

BACKGROUND: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. METHODS: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. RESULTS: During 2006-2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. CONCLUSIONS: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.

Synthesis and biological evaluation of sulfonamide derivatives containing imidazole moiety as ALK5 inhibitors.

Four series of sulfonamide derivatives (13a-b, 14a-d, 15a-b, and 16a-d) were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) inhibitory activities. Of these, compounds 13b (IC50 = 0.130 µM) and 15a (IC50 = 0.130 µM) showed the highest inhibitory activities against ALK5 kinase, with activities similar to the positive control LY-2157299. Notably, we discovered that introduction of sulfonamide group at the 2-position of the central imidazole ring significantly increased ALK5 inhibitory activity. Compounds 13b and 15a did not show toxicity in A549 cells up to the maximum concentration of 50 µM, and effectively inhibited TGF-ß1-induced Smad-signaling and cell motility in A549 cells. The results indicate that compounds 13b and 15a are worth of further development as anticancer agents.

Application of in vivo reflectance confocal microscopy in the diagnosis of Bowen's disease.

Bowen's disease (BD) is a relatively rare early-stage squamous cell carcinoma in situ, most commonly affecting the middle-aged and elderly, and occurring on the skin or mucous membranes of various parts of the body. Its onset is concealed, the course of the disease is chronic, and some patients have malignant tumors outside the skin; therefore, it is necessary to diagnose and evaluate the disease at an early stage. This study aimed to investigate the application of reflectance confocal microscopy (RCM) in the diagnosis of BD. We performed RCM imaging on the lesion site and underwent skin biopsy for histological diagnosis of 92 patients initially diagnosed with BD in clinic. A retrospective analysis of the RCM result as well as the histological examination revealed that after analyzing RCM images, out of 92 biopsy lesions, 61 were diagnosed with BD, of which 54 were consistent with RCM diagnosis. Among the 59 cases diagnosed with BD by RCM, 54 cases were consistent with the histological diagnosis. Afterwards, we analyzed the RCM characteristics in patients with BD verified by biopsy, and compared the RCM images of two different lesions, classic Bowen's disease and pigmented Bowen's disease, and further summarized the key points of BD under RCM. Finally, we focused on the differential characteristics between BD and other skin diseases in RCM. RCM is of great value in the diagnosis of BD. RESEARCH HIGHLIGHTS: A retrospective study of RCM and histological diagnosis in patients with clinical diagnosis of BD. Analyze the RCM characteristics of skin lesions verified by biopsy. RCM is of great value in the diagnosis and differentiation of BD.

Odontogenic Keratocyst in Maxillary Sinus with Ectopic Third Molar: A Case Report.

BACKGROUND Odontogenic keratocyst (OKC) is a common odontogenic cyst, and it occurs more frequently in the mandible, with the posterior region of the dental arch, the angle, or the ramus being the most commonly affected sites. Odontogenic keratocyst occurring within the maxillary sinus is extremely rare, accounting for only about 1% of cases. CASE REPORT A 20-year-old female patient without any clinical symptoms underwent an oral examination, during which a dense dental shadow was identified within the maxillary sinus, surrounded by a low-density shadow. Physical examination revealed absence of the left maxillary third molar, with intact mucosa. The patient reported no history of tooth extraction. X-ray and cone-beam computed tomography revealed a high-density image within the left maxillary sinus, resembling a tooth and surrounded by a soft-tissue shadow, which exhibited a greater density in comparison to conventional odontogenic cysts. The initial diagnosis was odontogenic keratocyst in the maxillary sinus with an ectopic maxillary third molar. Surgical enucleation of the cyst and extraction of the impacted tooth were carried out utilizing the Caldwell-Luc approach. Histopathological analysis confirmed the presence of OKC. No significant recurrence was noted during the 6 months of follow-up. CONCLUSIONS Odontogenic keratocysts in the maxillary sinus with ectopic third molar are rare and may not have any symptoms in the early stage. Surgery can be performed using the Caroler-Luke approach to achieve ideal treatment results. In view of the high recurrence rate of OKC, close follow-up should be conducted after surgery.

Evaluation of Confocal Laser Scanning Microscopy in Histological Classification and Photodynamic Therapy of Low-risk Basal Cell Carcinoma.

BACKGROUND: Confocal laser scanning microscopy (CLSM) is noninvasive technique utilized for identification and analysis skin malignancies. Several studies have applied CLSM in monitoring the therapeutic effects of basal cell carcinoma (BCC). OBJECTIVE: To investigate the diagnostic value of CLSM in low-risk BCC and the evaluation of photodynamic therapy (PDT). METHODS: We have diagnosed 149 patients with BCC using CLSM and histopathological examination. Based on histopathology, we summarized the classification information of low-risk BCC along with imaging features observed through CLSM. Thirty-four low-risk BCC patients underwent PDT treatment, and we used CLSM to evaluate its efficacy. RESULTS: Out of 149 participants were diagnosed with BCC by CLSM, 52 were pigmented type, 87 were nodular type and 10 were superficial type. After histopathological examination, 44 out of 52 were pigmented type, five were nodular type and three were superficial type. The results of CLSM were consistent with those of 87 nodular type and 10 superficial type. The CLSM features of nodular were observed in the tissue fissures around the tumor, the pigment mass was the CLSM characteristic of pigmented type. The simultaneous occurrence of inflammation and increased vasculature were characteristics of superficial. The effective rate of PDT was 100%, and the cure rate was 67.6%. At 12 months follow up, the recurrence rate of PDT was 11.8%, 15.0% for nodule type, 10.0% for pigmented type and 0% for superficial type. CONCLUSION: The tissue classification of CLSM for low-risk BCC was consistent with histopathology. CLSM can be used to monitor the efficacy of PDT for low-risk BCC.

[Efficacy of a Daltuzumab-containing Regimen in Patients with mSMART High-Risk Multiple Myeloma].

OBJECTIVE: To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM) with mSMART 3.0 score. METHODS: Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023, all of whom received daltezumab-based regimen (regimen drugs including dexamethasone, isazomib, bortezomib, lenalidomide). The efficacy and safety of the treatment were retrospectively analyzed. RESULTS: The median age of 16 patients was 63.5 (47-70) years old, including 10 cases of IgG type, 2 cases of IgA type, and 4 cases of light chain type. The curative efficacy was judged in all 16 patients, with an overall response rate of 93.75% (15/16), including 4 cases of strict complete remission (sCR), 1 case of complete remission (CR), 2 case of very good partial remission (VGPR), partial remission (PR) in 5 cases, and minor remission (MR) in 3 cases. The median follow-up time was 11(2-30) months, and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period. The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia, and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections. CONCLUSION: Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

Associations between postoperative cognitive dysfunction, serum interleukin-6 and postoperative delirium among patients after coronary artery bypass grafting: A mediation analysis.

BACKGROUND: POCD is a common complication among patients who underwent coronary artery bypass graft (CABG), it is linked to loss of independence and reduced quality of life. AIMS AND OBJECTIVES: To examine the association between postoperative cognitive dysfunction (POCD), postoperative delirium (POD) and interleukin-6 (IL-6). DESIGN: A prospective cohort study. METHODS: Patients who underwent elective isolated CABG were enrolled. POCD was assessed by a set of cognitive function tools. Delirium was assessed using the CAM-ICU. The logistic regression analyses were used to identify the predictive value of POD or IL-6 on POCD. The path analysis was used to analyse the relationship among POD, IL-6 and POCD. RESULTS: A total of 212 patients were enrolled, with 25.0% of patients developing POD and 32.5% developing POCD. The multiple logistic regression analysis revealed that patients with POD had a four-fold increased hazard of POCD (OR = 3.655), and patients with IL-6 ≥ 830.50 pg/mL at the 6th hours after surgery had a 5-fold increased risk of experiencing POCD (OR = 5.042). However, the mediation effect of POD between IL-6 and POCD was not statistically significant (ß = 0.059, p = .392). CONCLUSIONS: POD and IL-6 at the 6th hour after surgery (≥830.50 pg/mL) are two potent predictors for POCD, while POD did not play a mediation effect between IL-6 and POCD. RELEVANCE TO CLINICAL PRACTICE: Early identification of risk factors (e.g., delirium assessment and testing for serum IL-6 levels) by clinical nurses for POCD may contribute to the clinical practice for the targeted prevention nursing strategies.

Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice.

Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1ß, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization.

A cluster-randomized controlled trial of a nurse-led artificial intelligence assisted prevention and management for delirium (AI-AntiDelirium) on delirium in intensive care unit: Study protocol.

BACKGROUND: Delirium is a common complication among intensive care unit (ICU) patients that is linked to negative clinical outcomes. However, adherence to the Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS guidelines), which recommend the use of the ABCDEF bundle, is sub-optimal in routine clinical care. To address this issue, AI-AntiDelirium, a nurse-led artificial intelligence-assisted prevention and management tool for delirium, was developed by our research team. Our pilot study yielded positive findings regarding the use of AI-AntiDelirium in preventing patient ICU delirium and improving activities of daily living and increasing intervention adherence by health care staff. METHODS: The proposed large-scale pragmatic, open-label, parallel-group, cluster randomized controlled study will assess the impact of AI-AntiDelirium on the incidence of ICU delirium and delirium-related outcomes. Six ICUs in two tertiary hospitals in China will be randomized in a 1:1 ratio to an AI-AntiDelirium or a PADIS guidelines group. A target sample size of 1,452 ICU patients aged 50 years and older treated in the ICU for at least 24 hours will be included. The primary outcome evaluated will be the incidence of ICU delirium and the secondary outcomes will be the duration of ICU delirium, length of ICU and hospital stay, ICU and in-hospital mortality rates, patient cognitive function, patient activities of daily living, and ICU nurse adherence to the ABCDEF bundle. DISCUSSION: If this large-scale trial provides evidence of the effectiveness of AI-AntiDelirium, an artificial intelligence-assisted system tool, in decreasing the incidence of ICU delirium, length of ICU and hospital stay, ICU and in-hospital mortality rates, patient cognitive function, and patient activities of daily living while increasing ICU nurse adherence to the ABCDEF bundle, it will have a profound impact on the management of ICU delirium in both research and clinical practice. CLINICAL TRIAL REGISTRATION: ChiCTR1900023711 (Chinese Clinical Trial Registry).

Virome diversity shaped by genetic evolution and ecological landscape of Haemaphysalis longicornis.

BACKGROUND: Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. RESULTS: We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. CONCLUSIONS: These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.

Changes in Cytokine Levels in Patients with Severe Fever with Thrombocytopenia Syndrome Virus.

Purpose: To characterize the cytokine profile of patients with severe fever with thrombocytopenia syndrome (SFTS) in relation to disease severity. Patients and Methods: 60 laboratory-confirmed SFTS patients and 12 healthy individuals from multi-centers in Shandong Province of China were included, and all patients were divided into fatal patients (9) and recovered patients (51) due to their final outcomes. Multiplex-microbead immunoassays were conducted to estimate levels of 27 cytokines in the sera of patients and controls. Results: The results showed that levels of IL-2, IL-4, IL-6, IL-7, IL-8, IL-15, IL-1RA, G-CSF, GM-CSF, IFN-γ, TNF-α, basic FGF, PDGF-BB, RANTES, IP-10, MIP-1α, MIP-1ß, MCP-1, and Eotaxin differed significantly among the SFTS fatal patients, recovered patients, and the healthy controls (all p<0.05). Compared to the healthy controls, the fatal patients and recovered patients had reduced levels of IL-2, IL-4, IL-7, PDGF-BB, RANTES, and Eotaxin, while the levels of PDGF-BB and RANTES were significantly lower in fatal patients compared to recovered patients. The increasing levels of IL-6, IL-8, IL-15, IL-1RA, G-CSF, GM-CSF, IFN-γ, TNF-α, basic FGF, IP-10, MIP-1α, MIP-1ß, and MCP-1 were observed in fatal patients (all p<0.05), and the levels of IL-6, IP-10, MIP-1α, and MCP-1 were significantly higher than other two groups. The Spearman correlation analysis indicated a positive correlation between platelet count and PDGF-BB levels (p<0.05), while the white blood cell count had a negative correlation with MIP-1 level (p<0.05). Conclusion: The research exhibited that the SFTS virus (SFTSV) caused an atypical manifestation of cytokines. The levels of IL-6, IP-10, MIP-1α, and MCP-1 had been observed a positive association with the severity of the illness.

An Ex Vivo Aorta Culture Model to Study Vascular Cellular Senescence.

Animal studies on vascular aging pose a few limitations. One of the most important reasons for this is the absence of a fast and efficient model of vascular tissue aging. In this study, ex vivo aortic culture and Matrigel subcutaneous implantation are combined to develop a new model for studying vascular cellular senescence. Eight-week-old C57BL/6J mice are used to obtain aortas. Bleomycin is used to induce aortas senescence in vitro. Then, aortas are transplanted to the acceptor mice with Matrigel. Senescence is evaluated using western blotting, quantitative polymerase chain reaction, and senescence-associated beta-galactosidase activity. Inflammatory cytokines are detected using Luminex Liquid Suspension Chip. RNA levels are analyzed by transcriptome sequencing. The results revealed that vessels in the bleomycin group exhibited significant senescence than those in the control group that can be enhanced by stripping vessel adventitia. The levels of cytokines such as interleukin (IL-2, IL-1ß, and IL-6 increased significantly in the ex vivo model. Furthermore, transcriptome sequencing revealed 56 significantly differentially expressed genes (DEGs) in ex vivo model vessels compared with those in naturally aging aortas. In conclusion, this study introduces a cost-effective and time-saving vessel senescence model for vascular cellular senescence.

A comprehensive study of oxidative stress-related effects on the prognosis and drug therapy of cervical cancer.

BACKGROUND: Cervical cancer (CC) is a serious global disease with poor prognoses and a significant recurrence rate in patients with advanced disease. Oxidative stress (OS) greatly influences many types of human cancers, making it crucial to understand the functional mechanisms of OS-related genes in CC. METHODS: The transcriptome and clinical data of three normal samples and 306 patients with CC were obtained from The Cancer Genome Atlas dataset. The GSE44001 dataset was acquired from the Gene Expression Omnibus database. OS-related subtypes in the cohort with CC were identified using unsupervised hierarchical clustering, univariate Cox analysis, gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator regression analysis. Additionally, molecular pathways that differ across subtypes were determined and OS-related genes linked to the prognosis of patients of CC were determined. Finally, a clinical prognostic gene signature was developed and validated. The relative infiltration level of immune cell subpopulations in different risk groups and subtypes was evaluated using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERPORT) algorithm and single-sample GSEA (ssGSEA) techniques. RESULTS: The present study established two distinct OS subtypes (OS clusters A and B). Analysis using ssGSEA and CIBERSPORT revealed that OS cluster B exhibited a significant level of immune infiltration. A clinical prognostic gene signature was established using OS-related characteristic genes identified by examining the differentially expressed genes across both subtypes. Furthermore, patients with CC were grouped into high- and low-risk groups, with the low-risk group showing higher survival rates. Additionally, these individuals exhibited significant advantages in terms of survival and immunotherapy. Receiver operating characteristic curve analysis demonstrated the higher predictive value of the clinical prognostic gene signature. The outcomes of the validation group depicted congruence with those recorded in the training group. CONCLUSIONS: A new model was constructed based on eight OS-related characteristic genes to aid the prediction of the survival rates of individuals with CC. The present study contributes to the existing literature on the mechanisms of OS genes in CC and offers a fresh perspective for future advancements in immunotherapy for such individuals.

Impact of Clinical Decision Support System Assisted prevention and management for Delirium on guideline adherence and cognitive load among Intensive Care Unit nurses (CDSSD-ICU): Protocol of a multicentre, cluster randomized trial.

BACKGROUND: Adherence to the delirium bundle intervention is sub-optimal in routine practice, and inappropriate use of the instructional design of interventions may result in higher cognitive load among nurses. It remains unclear whether the Clinical Decision Support System (CDSS) Assisted Prevention and Management for Delirium (CDSS-AntiDelirium) results in the improvement of adherence to delirium intervention and the reduction of extraneous cognitive load, as well as improving adherence to delirium intervention, among nurses in the intensive care unit (ICU). METHODS: This study (named the CDSSD-ICU) is a multicentre, prospective, cluster randomized controlled clinical trial. A total of six ICUs in two hospitals will be randomized in a 1:1 ratio to receive either the CDSS-AntiDelirium group or the delirium guidelines group. The CDSS-AntiDelirium consists of four modules: delirium assessment tools, risk factor assessment, a nursing care plan, and a nursing checklist module. Each day, nurses will assess ICU patients with the assistance of the CDSS-AntiDelirium. A total of 78 ICU nurses are needed to ensure statistical power. Outcome assessments will be conducted by investigators who are blinded to group assignments. The primary endpoint will be adherence to delirium intervention, the secondary endpoint will be nurses' cognitive load measured using an instrument to assess different types of cognitive load. Repeated measures analysis of variance will be used to detect group differences. A structural equation model will be used to clarify the mechanism of improvement in adherence. DISCUSSION: Although the CDSS has been widely used in hospitals for disease assessment, management, and recording, the applications thereof in the area of delirium are still in infancy. This study could provide scientific evidence regarding the impact of a CDSS on nurses' adherence and cognitive load and promote its further development in future studies. CLINICAL TRIAL REGISTRATION: ChiCTR1900023711 (Chinese Clinical Trial Registry).

EMNPD: a comprehensive endophytic microorganism natural products database for prompt the discovery of new bioactive substances.

The discovery and utilization of natural products derived from endophytic microorganisms have garnered significant attention in pharmaceutical research. While remarkable progress has been made in this field each year, the absence of dedicated open-access databases for endophytic microorganism natural products research is evident. To address the increasing demand for mining and sharing of data resources related to endophytic microorganism natural products, this study introduces EMNPD, a comprehensive endophytic microorganism natural products database comprising manually curated data. Currently, EMNPD offers 6632 natural products from 1017 endophytic microorganisms, targeting 1286 entities (including 94 proteins, 282 cell lines, and 910 species) with 91 diverse bioactivities. It encompasses the physico-chemical properties of natural products, ADMET information, quantitative activity data with their potency, natural products contents with diverse fermentation conditions, systematic taxonomy, and links to various well-established databases. EMNPD aims to function as an open-access knowledge repository for the study of endophytic microorganisms and their natural products, thereby facilitating drug discovery research and exploration of bioactive substances. The database can be accessed at http://emnpd.idrblab.cn/ without the need for registration, enabling researchers to freely download the data. EMNPD is expected to become a valuable resource in the field of endophytic microorganism natural products and contribute to future drug development endeavors.

Impact of delirium intervention on cognitive load among nurses in the intensive care unit: A multi-centre cluster randomized controlled trial.

BACKGROUND: High cognitive load in nurses is a common problem in the intensive care unit (ICU). However, it remains unclear what different types of cognitive load the ICU nurses have experienced during the implementation of delirium interventions. AIM: To describe the characteristics and explore the effect of implementing a delirium intervention on the cognitive load of nurses working in the ICU. METHODS: A cluster-randomized controlled clinical trial was conducted. Six ICUs were randomized in a 1:1 ratio, and eligible nurses from these units provided either a delirium bundle intervention in addition to usual care (27 nurses) or usual care alone. An instrument was used to measure different types of cognitive load (MDT-CL), assessing intrinsic, extraneous and germane cognitive load. The repeated measures analysis of variance was used to detect between-group differences. RESULTS: Among these nurses, significant between-group differences were identified in terms of their overall (P < 0.001), intrinsic (P < 0.001) and extraneous (P < 0.001) cognitive load. There was no significant change observed in the germane cognitive load (P = 0.489) in the delirium intervention group. CONCLUSION: It is important to understand how the implementation of a delirium intervention affects different types of cognitive load in nurses, in order that tailored strategies can be applied to reduce cognitive load in ICU nurses.

The polarization of microglia and infiltrated macrophages in the injured mice spinal cords: a dynamic analysis.

Background: Following spinal cord injury (SCI), a large number of peripheral monocytes infiltrate into the lesion area and differentiate into macrophages (Mø). These monocyte-derived Mø are very difficult to distinguish from the local activated microglia (MG). Therefore, the term Mø/MG are often used to define the infiltrated Mø and/or activated MG. It has been recognized that pro-inflammatory M1-type Mø/MG play "bad" roles in the SCI pathology. Our recent research showed that local M1 cells are mainly CD45-/lowCD68+CD11b+ in the subacute stage of SCI. Thus, we speculated that the M1 cells in injured spinal cords mainly derived from MG rather than infiltrating Mø. So far, their dynamics following SCI are not yet entirely clear. Methods: Female C57BL/6 mice were used to establish SCI model, using an Infinite Horizon impactor with a 1.3 mm diameter rod and a 50 Kdynes force. Sham-operated (sham) mice only underwent laminectomy without contusion. Flow cytometry and immunohistofluorescence were combined to analyze the dynamic changes of polarized Mø and MG in the acute (1 day), subacute (3, 7 and 14 days) and chronic (21 and 28 days) phases of SCI. Results: The total Mø/MG gradually increased and peaked at 7 days post-injury (dpi), and maintained at high levels 14, 21 and 28 dpi. Most of the Mø/MG were activated, and the Mø increased significantly at 1 and 3 dpi. However, with the pathological process, activated MG increased nearly to 90% at 7, 14, 21 and 28 dpi. Both M1 and M2 Mø were increased significantly at 1 and 3 dpi. However, they decreased to very low levels from 7 to 28 dpi. On the contrary, the M2-type MG decreased significantly following SCI and maintained at a low level during the pathological process.

Metavirome of 31 tick species provides a compendium of 1,801 RNA virus genomes.

The increasing prevalence and expanding distribution of tick-borne viruses globally have raised health concerns, but the full repertoire of the tick virome has not been assessed. We sequenced the meta-transcriptomes of 31 different tick species in the Ixodidae and Argasidae families from across mainland China, and identified 724 RNA viruses with distinctive virome compositions among genera. A total of 1,801 assembled and complete or nearly complete viral genomes revealed an extensive diversity of genome architectures of tick-associated viruses, highlighting ticks as a reservoir of RNA viruses. We examined the phylogenies of different virus families to investigate virome evolution and found that the most diverse tick-associated viruses are positive-strand RNA virus families that demonstrate more ancient divergence than other arboviruses. Tick-specific viruses are often associated with only a few tick species, whereas virus clades that can infect vertebrates are found in a wider range of tick species. We hypothesize that tick viruses can exhibit both 'specialist' and 'generalist' evolutionary trends. We hope that our virome dataset will enable much-needed research on vertebrate-pathogenic tick-associated viruses.