The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway.

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

Comprehensive Analysis of the Immunosuppressive Function of Regulatory T Cells in Human Hepatocellular Carcinoma Tissues.

BACKGROUND: Immune-based therapies are commonly employed to combat hepatocellular carcinoma (HCC). However, the presence of immune-regulating elements, especially regulatory T cells (Tregs), can dramatically impact the treatment efficacy. A deeper examination of the immune-regulation mechanisms linked to these inhibitory factors and their impact on HCC patient outcomes is warranted. METHODS: We employed multicolor fluorescence immunohistochemistry (mIHC) to stain Foxp3, cytokeratin, and nuclei on an HCC tissue microarray (TMA). Leveraging liver cancer transcriptome data from TCGA, we built a prognostic model focused on Treg-associated gene sets and represented it with a nomogram. We then sourced liver cancer single-cell RNA sequencing data (GSE140228) from the GEO database, selectively focusing on Treg subsets, and conducted further analyses, including cell-to-cell communication and pseudo-time trajectory examination. RESULTS: Our mIHC results revealed a more substantial presence of Foxp3+Tregs in HCC samples than in adjacent normal tissue samples (P < .001). An increased presence of Foxp3+Tregs in HCC samples correlated with unfavorable patient outcomes (HR = 1.722, 95% CI:1.023-2.899, P = .041). The multi-factorial prognosis model we built from TCGA liver cancer data highlighted Tregs as a standalone risk determinant for predicting outcomes (HR = 3.84, 95% CI:2.52-5.83, P < .001). Re-analyzing the scRNA-seq dataset (GSE140228) showcased distinctive gene expression patterns in Tregs from varying tissues. Interactions between Tregs and other CD4+T cell types were predominantly governed by the CXCL13/CXCR3 signaling pathway. Communication pathways between Tregs and macrophages primarily involved MIF-CD74/CXCR4, LGALS9/CD45, and PTPRC/MRC1. Additionally, macrophages could influence Tregs via HLA-class II and CD4 interactions. CONCLUSION: An elevated presence of Tregs in HCC samples correlated with negative patient outcomes. Elucidating the interplay between Tregs and other immune cells in HCC could provide insights into the modulatory role of Tregs within HCC tissues.

A multifunctional ionic liquid coating on 3D-Printed prostheses: Combating infection, promoting osseointegration.

Periprosthetic infection and mechanical loosening are two leading causes of implant failure in orthopedic surgery that have devastating consequences for patients both physically and financially. Hence, advanced prostheses to simultaneously prevent periprosthetic infection and promote osseointegration are highly desired to achieve long-term success in orthopedics. In this study, we proposed a multifunctional three-dimensional printed porous titanium alloy prosthesis coated with imidazolium ionic liquid. The imidazolium ionic liquid coating exhibited excellent bacterial recruitment property and near-infrared (NIR) triggered photothermal bactericidal activity, enabling the prosthesis to effectively trap bacteria in its vicinity and kill them remotely via tissue-penetrating NIR irradiation. In vivo anti-infection and osseointegration investigations in infected animal models confirmed that our antibacterial prosthesis could provide long-term and sustainable prevention against periprosthetic infection, while promoting osseointegration simultaneously. It is expected to accelerate the development of next-generation prostheses and improve patient outcomes after prosthesis implantation.

The correlations between parental warmth and children's approaches to learning: a moderated mediation model of self-efficacy and teacher-child closeness.

Researchers have increasingly considered approaches to learning (ATL) a key indicator of school readiness. Our study purposed to examine the impacts of parental warmth on children's approaches to learning, and the mediating role of self-efficacy, as well as the moderating role of teacher-child closeness in this relationship. Using a whole-group sampling method, 414 Chinese children aged 5-6 years participated this research together with their parents and teachers. Parents of those children were asked to fill out in person questionnaires on parental warmth, children's approaches to learning, and self-efficacy. Children's teachers completed the questionnaire regarding teacher-child closeness. Results indicated that children with high parental warmth were more likely to get high approaches to learning and their self-efficacy played a partial mediating role in this link. In addition, teacher-child closeness moderated the correlation between parental warmth and children's self-efficacy. Specifically, the association between parental warmth and children's self-efficacy was stronger for children with high teacher-child closeness than those with low teacher-child closeness. The results extend our understanding of how parental warmth affects children's approaches to learning, revealing that strategies that could enhance self-efficacy would be effective in improving children's approaches to learning.

Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer.

Background: Uterine corpus endometrial cancer (UCEC) exhibit heterogeneity in their DNA repair capacity, which can impact their response to radiotherapy. Our study aimed to identify potential DNA repair-related biomarkers for predicting radiation response in UCEC. Methods: We conducted a thorough analysis of 497 UCEC samples obtained from TCGA database. Using LASSO-COX regression analysis, we constructed a radiosensitivity signature and subsequently divided patients into the radiosensitive (RS) and the radioresistant (RR) groups based on their radiosensitivity index. The GSVA and GSEA were performed to explore functional annotations. The CIBERSORT and ESTIMATE algorithms were utilized to investigate the immune infiltration status of the two groups. Additionally, we utilized the Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenotype Score (IPS), and pRRophetic algorithms to predict the effectiveness of different treatment modalities. Results: We constructed a radiosensitivity index consists of four DNA repair-related genes. Patients in the RS group demonstrated significantly improved prognosis compared to patients in the RR group when treated with radiotherapy. We observed that the RS group exhibited a higher proportion of the POLE ultra-mutated subtype, while the RR group had a higher proportion of the copy number high subtype. GSVA enrichment analysis revealed that the RS group exhibited enrichment in DNA damage repair pathways. Notably, the RS group demonstrated a higher proportion of naïve B cells and follicular helper T cells, while regulatory T cells (Tregs) and memory B cells were more abundant in the RR group. Furthermore, patients in the RS-PD-L1-high subgroup exhibited enrichment in immune-related pathways and increased sensitivity to immunotherapy, which is likely to contribute to their improved prognosis. Additionally, we conducted in vitro experiments to validate the expression of radiosensitivity genes in non-radioresistant (AN3CA) and radioresistant (AN3CA/IR) endometrial cancer cells. Conclusions: In conclusion, our research successfully constructed a radiosensitivity signature with robust predictive capacity. These findings shed light on the association between immune activation, PD-L1 expression, and the response to immunotherapy in the context of radiotherapy.

Effectiveness of nirmatrelvir-ritonavir versus azvudine for adult inpatients with severe or critical COVID-19.

BACKGROUND: In China, both nirmatrelvir-ritonavir (Paxlovid) and azvudine have been granted approval to treat adult SARS-CoV-2-infected patients with moderate symptoms. Information about the clinical effect of the two available agents among inpatients with severe or critical COVID-19 is scarce. PURPOSE: To compare the clinical outcomes of Paxlovid and azvudine among adult inpatients with severe or critical COVID-19. METHOD: We conducted a retrospective cohort study in two large medical centres after the epidemic control measures were lifted in China. A new propensity score matched-inverse probability of treatment weighting cohort was constructed to evaluate the in-hospital all-cause mortality, hospital length of stay, Sequential Organ Failure Assessment (SOFA) score and safety. RESULTS: A total of 955 individuals were in the cohort. The antiviral therapy strategies were decided by the senior physician and the supplies of the pharmacy. A total of 451 patients were in the Paxlovid group, and 504 patients were in the azvudine group. Compared with Paxlovid, the effects of azvudine on in-hospital all-cause mortality were not significantly different, and the OR (95% CI) was 1.084 (0.822 to 1.430), and the average hospital length of stay of patients discharged alive was also similar in the azvudine group, and the difference (day) and (95% CI) was 0.530 (-0.334 to 1.393). After 7 days of therapy, the degree of decline in the SOFA score was greater in the Paxlovid group than in the azvudine group (p<0.001). The change in glomerular filtration rate was not significantly different (p=0.824). CONCLUSION: Paxlovid and azvudine had similar effectiveness on in-hospital all-cause mortality and hospital length of stay. Compared with the azvudine group, after 7 days of therapy, the degree of decline in SOFA score was significantly higher in the Paxlovid group. These findings need to be verified in larger prospective studies or randomised controlled trials.

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer.

OBJECTIVE: The clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE). METHODS: 92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments. RESULTS: the DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05). CONCLUSION: SMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.

Anomaly Detection of Permanent Magnet Synchronous Motor Based on Improved DWT-CNN Multi-Current Fusion.

The Permanent Magnet Synchronous Motor (PMSM) is the power source maintaining the stable and efficient operation of various pieces of equipment; hence, its reliability is crucial to the safety of public equipment. Convolutional Neural Network (CNN) models face challenges in extracting features from PMSM current data. A new Discrete Wavelet Transform Convolutional Neural Networks (DW-CNN) feature with fusion weight updating Long Short-Term Memory (LSTM) anomaly detection is proposed in this paper. This approach combines Discrete Wavelet Transform (DWT) with high and low-frequency separation processing and LSTM. The anomaly detection method adopts DWT and CNN by separating high and low-frequency processing. Moreover, this method combines the hybrid attention mechanism to extract the multi-current signal features and detects anomalies based on weight updating the LSTM network. Experiments on the motor bearing real fault dataset and the PMSM stator fault dataset prove the method's strong capability in fusing current features and detecting anomalies.

Precursor exhausted CD8+T cells in colorectal cancer tissues associated with patient's survival and immunotherapy responsiveness.

Exhausted CD8+T cells represent a distinct cellular lineage that emerges during both chronic infections and cancers. Recent studies have shown that persistent antigen exposure can drive the differentiation of precursor exhausted CD8+T cells, termed Tpex cells, which are characterized as TCF-1+PD-1+CD8+T cells. Elevated Tpex cell frequencies in the tumor microenvironment (TME) are associated with improved overall survival (OS) in cancer patients and heightened responsiveness to anti-PD-1 therapy. In our present study, we utilized multi-color immunohistochemistry (mIHC) to determine the localization and clinical implications of tumor-infiltrating Tpex cells within the TME of human colorectal cancer (CRC) tissues. We also conducted a multi-omics integrative analysis using single-cell RNA sequencing (scRNA-seq) data derived from both the murine MC38 tumor model and human CRC tissues. This analysis helped delineate the transcriptional and functional attributes of Tpex cells within the CRC TME. Furthermore, we employed spatial transcriptome sequencing data from CRC patients to investigate the interactions between Tpex cells and other immune cell subsets within the TME. In conclusion, our study not only established a method for Tpex cell detection using mIHC technology but also confirmed that assessing Tpex cells within the CRC TME could be indicative of patients' survival. We further uncovered the transcriptional and functional characteristics of Tpex cells in the TME and ascertained their pivotal role in the efficacy of immunotherapy against CRC.

Aerobic Oxidative Carboxylation of Styrene Over Cobalt Catalysts: Integrated CO2 Capture and Conversion.

The direct synthesis of cyclic carbonates through oxidative carboxylation of alkenes using CO2 and O2 offers a sustainable and carbon-neutral method for CO2 utilization, which is, however, still a largely unexplored field. Here we develop a single-atom catalyst (SAC) Co-N/O-C as the earth-abundant metal catalyst for the oxidative carboxylation of styrene with CO2 and O2. Remarkably, even using the flue gas as an impure CO2 and O2 source, desired cyclic carbonate could be obtained with moderate productivity, which shows the potential for integrated CO2 capture and conversion, leveraging the high CO2 adsorption capacity of Co-N/O-C. In addition, the catalyst can be reused five times without an obvious decline in activity. Detailed characterizations and theoretical calculations elucidate the crucial role of single Co atoms in activating O2 and CO2, as well as controlling selectivity.

Water-stable boroxine structure with dynamic covalent bonds.

Boroxines are significant structures in the production of covalent organic frameworks, anion receptors, self-healing materials, and others. However, their utilization in aqueous media is a formidable task due to hydrolytic instability. Here we report a water-stable boroxine structure discovered from 2-hydroxyphenylboronic acid. We find that, under ambient environments, 2-hydroxyphenylboronic acid undergoes spontaneous dehydration to form a dimer with dynamic covalent bonds and aggregation-induced enhanced emission activity. Intriguingly, upon exposure to water, the dimer rapidly transforms into a boroxine structure with excellent pH stability and water-compatible dynamic covalent bonds. Building upon these discoveries, we report the strong binding capacity of boroxines toward fluoride ions in aqueous media, and develop a boroxine-based hydrogel with high acid-base stability and reversible gel-sol transition. This discovery of the water-stable boroxine structure breaks the constraint of boroxines not being applicable in aqueous environments, opening a new era of researches in boroxine chemistry.

Efficient Alkene Hydroformylation by Co-C Symmetry-Breaking Sites.

Alkene hydroformylation is one of the largest industrial reactions on an industrial scale; however, the development of nonnoble heterogeneous catalysts is usually limited by their low activities and stabilities. Herein, we constructed a 1% Co2C/SiO2 catalyst featuring Co-Cvacancy-Co-C symmetry-breaking sites, which generated a polar surface exhibiting a moderate charge density gradient at the localized Co atoms. Comparatively, this catalyst exhibited notable enhancements in the adsorption and activation of the reactants, as well as in the polarity between intermediates. Significantly, the spatial distance between the adsorption sites of intermediates was reduced, thereby effectively decreasing the energy barrier of reaction processes. As the density of the symmetry-breaking sites increased, the turnover number for propene hydroformylation soared to 18 363, exceeding the activity of heterogeneous Co-based catalysts reported thus far by 1 or 2 orders of magnitude, and the catalyst exhibited high stability during the reaction. This study provides a methodology for constructing atomically active sites, which holds great potential for the design and development of highly efficient catalysts.

The neuroprotective effect of near infrared light therapy in aged mice with postoperative neurocognitive disorder by upregulating IRF7.

BACKGROUND: Postoperative neurocognitive disorder (PND) is a common central nervous system complication after undergoing surgery and anesthesia especially in elderly patients, while the therapeutic options are very limited. This study was carried out to investigate the beneficial effects of transcranial near infrared light (NIRL) which was employed to the treatment of PND and propose the involved mechanisms. METHODS: The PND mice were established through left carotid artery exposure under isoflurane anesthesia and received transcranial NIRL treatment. Behavioral testing was performed to evaluate the cognitive function of PND mice after transcranial NIRL therapy. Changes in the transcriptomic profiles of prefrontal cortex (PFC) and hippocampus (HP) were identified by next generation sequencing (NGS), and the molecular mechanisms involved were examined by both in vivo mouse model and in vitro cell culture studies. RESULTS: We found that transcranial NIRL therapy effectively ameliorated learning and memory deficit induced by anesthesia and surgery in aged mice. Specifically, we identified down-regulation of interferon regulatory factor 7 (IRF7) in the brains of PND mice that was mechanistically associated with increased pro-inflammatory M1 phenotype of microglia and elevated neuroinflammatory. NIRL treatment produced protective effects through the upregulation of IRF7 expression and reversing microglial phenotypes from pro-inflammatory to neuroprotective, resulting in reduced brain damage and improved cognitive function in PND mice. CONCLUSION: Our results indicate that transcranial NIRL is an effective and safe therapy for PND via alleviating neuroinflammation, and IRF7 plays a key transcription factor in regulating the M1-to-M2 switch of microglia.

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection in regulating apoptosis in osteosarcoma.

OBJECTIVE: The main objectives of this study were to identify the active components of Tongguanteng injection (TGT) and investigate the preclinical efficacy and mechanism of TGT on osteosarcoma using a combination of network pharmacology and experimental validation. METHODS: To identify the active constituents and targets of TGT against osteosarcoma using network pharmacology, we constructed a network consisting of an 'active ingredient-disease-target-pathway' and a protein-protein interaction (PPI) network. The target organ network was utilized to investigate the distribution of core targets in tissues. Afterwards, the core targets underwent Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The binding energy between receptors and ligands was compared using molecular docking. In addition, SwissADME was employed to forecast the pharmacokinetic characteristics of the substances. Finally, real-time polymerase chain reaction (RT-PCR), cell proliferation assay, morphological analysis, apoptosis assay, mitochondrial membrane potential (MMP) detection, and Western blotting were utilized to confirm the potential mechanisms of TGT treatment in osteosarcoma cell lines 143B and SAOS2. RESULTS: A total of 54 chemical constituents of TGT and 71 targets associated with osteosarcoma were acquired. Through the molecular docking technology, Tenacigenin B, Marsdekoiside, Taraxasterol, Tenacissoside G, Tenacissoside L, and Tenacissoside J were identified as the primary active components of TGT among the various compounds. Analysis of target organs suggests that TGT may play an anti-osteosarcoma role through immune regulation. The GO and KEGG enrichment analysis revealed that TGT could trigger osteosarcoma cell apoptosis by inhibiting the HIF-1 signalling pathway and modulating PD-1 expression and the PD-1 checkpoint pathway in cancer. SwissADME database predicted that Tenacigenin B and Taraxasterol had the best drug-likeness. In vitro studies also demonstrated that TGT suppressed the activity and induced alterations in the morphology of osteosarcoma cells. It decreased MMP levels, triggered apoptosis by increasing Bax expression and Caspase-3 activity, and decreased Bcl-2 expression, thereby exerting an anti-osteosarcoma effect. In the meantime, RT-PCR tests demonstrated that TGT could control immune response against tumors and hinder the proliferation and spread of cancerous cells by impacting the levels of critical factors, including JUN, HSP90AA1, HDAC1, and CDK1. CONCLUSION: The study accurately anticipated the active components, targets, and pathways of TGT in the management of osteosarcoma. The molecular mechanism of TGT-induced apoptosis in osteosarcoma cells was demonstrated by in vitro experiments. These results provide theoretical and technical support for TGT as a clinical adjuvant drug for osteosarcoma.

The application of nanopore targeted sequencing for pathogen diagnosis in bronchoalveolar lavage fluid of patients with pneumonia: a prospective multicenter study.

OBJECTIVE: To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens. METHODS: This large-scale multicentre prospective study performed in 8 hospitals across China from April to October 2022. Hospitalised patients with a diagnosis of pneumonia at admission were included. Complete clinical data were collected, and bronchoalveolar lavage fluid were obtained from each patient. These samples underwent simultaneous testing using conventional microbial testing, metagenomic next-generation sequencing, and nanopore targeted sequencing. RESULTS: A total of 218 patients were included. Among the 168 cases of pulmonary infection, 246 strains of pathogens were confirmed. Nanopore targeted sequencing outperformed conventional microbial testing, identifying more pathogens with a sensitivity increase of 47.9% (77.2% vs. 29.3%). Metagenomic next-generation sequencing had a sensitivity of 82.9%. Total of 70.1% patients had consistent results in both metagenomic next-generation sequencing and nanopore targeted sequencing. Nanopore targeted sequencing exhibited significantly higher sensitivity in detecting Pneumocystis jiroveci, cytomegalovirus, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Streptococcus pneumoniae, and Mycoplasma pneumoniae compared to conventional microbial testing. However, metagenomic next-generation sequencing demonstrated higher sensitivity than nanopore targeted sequencing for Aspergillus (88.5% vs. 53.8%). Regarding the detection of co-infections, nanopore targeted sequencing displayed significantly higher sensitivity than conventional microbial testing (76.7% vs. 28.7%) and was on par with metagenomic next-generation sequencing (76.7% vs. 82.9%). CONCLUSION: Nanopore targeted sequencing performs equally well as metagenomic next-generation sequencing in bronchoalveolar lavage fluid for pathogen diagnosis in pneumonia, both methods showing higher sensitivity than conventional microbial testing. Nanopore targeted sequencing can be considered a reliable method for diagnosing pathogens in pneumonia.

Prophylatic use of IV nalmefene to prevent epidural opioid-induced pruritus: A multicenter, randomized clinical trial.

STUDY OBJECTIVE: The incidence of pruritus from neuraxial opioids is about 60%. Pruritus causes discomfort and decreases the quality of recovery. This randomized double-blinded clinical trial was aimed to evaluate the prophylactic effects of a single dose IV nalmefene on the incidence and severity of epidural opioid-induced pruritus within 24 h after surgeries. DESIGN: A two-center, randomized, double blinded, controlled clinical trial. SETTING: The study was conducted from March 2022 to February 2023 at two tertiary care hospitals in China. PATIENTS: Patients aged between 18 and 80 years-old who underwent elective surgeries and received epidural analgesia intra- and post-operatively were screened for study enrollment. A total of 306 patients were enrolled, 302 patients underwent randomization and 296 patients were included in the final analysis. INTERVENTIONS: The nalmefene group was prophylactically given 0.5 µg/kg nalmefene intravenously while the control group was given the same volume of saline. MEASUREMENTS: The primary endpoint was the incidence of pruritus within 24 h after surgeries. The secondary endpoints included time of the first patient-reported pruritus, severity of pruritus after surgeries, severity of acute pain scores after surgeries and other anesthesia/analgesia related side effects. MAIN RESULTS: Pruritus occurred in 51 of the 147 (34.69%) patients in the control group and 35 of the 149 (23.49%) patients in the nalmefene group (odds ratio, 0.58; 95% CI, 0.35 to 0.96; P = 0.034) within 24 h postoperatively. Nalmefene group demonstrated delayed onset of pruritus, reduced severity of pruritus and decreased vomiting within 24 h after surgery. There were no significant differences in postoperative analgesia and the incidence of other anesthesia/analgesia associated side effects. CONCLUSIONS: A single dose of 0.5 µg/kg nalmefene intravenously significantly reduced the incidence and severity of epidural-opioid induced pruritus within 24 h after surgery without affecting the efficacy of epidural analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn) and the registration number is ChiCTR2100050463. Registered on August 27th, 2021.

The incidence of asthma attributable to temperature variability: An ecological study based on 1990-2019 GBD data.

BACKGROUND: Asthma, the second leading cause of death from chronic respiratory diseases, is associated with climate change, especially temperature changes. It is currently unclear about the relationship between long-term temperature variability and the incidence of asthma on a global scale. METHODS: We used asthma incidence, demographic and socioeconomic data from the Global Burden of Disease (GBD) Results Database, and environmental and geographical statistics from TerraClimate between 1990 and 2019 to determine the association between maximum temperature variability and asthma incidence. We also predicted the incidence of heat-related asthma in the future (2020-2100) under four shared socioeconomic pathways (SSPs: 126, 245, 370, and 585). RESULTS: Between 1990 and 2019, the global median incidence of asthma was 402.0 per 100,000 with a higher incidence (median: 1380.3 per 100,000) in children under 10 years old. We found that every 1 °C increase in maximum temperature variability increased the risk of asthma globally by 5.0 %, and the effect was robust for individuals living in high-latitude areas or aged from 50 to 70 years. By 2100, the average incidence of asthma is estimated to be reduced by 95.55 %, 79.32 %, and 40.02 % under the SSP126, SSP245, and SSP370 scenarios, respectively, compared to the SSP585 at latitudes >60°. CONCLUSION: Our study provides evidence that maximum temperature variability is associated with asthma incidence. These findings suggest that implementing stricter mitigation and adaptation strategies may be importment in reducing asthma cases caused by climate change.