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IntroductionSepsis represents a critical medical condition that arises due to an imbalanced host reaction to infection. Central to its pathophysiology are cytokines. However, observational investigations that explore the interrelationships between circulating cytokines and susceptibility to sepsis frequently encounter challenges pertaining to confounding variables and reverse causality.MethodsTo elucidate the potential causal impact of cytokines on the risk of sepsis, we conducted two-sample Mendelian randomization (MR) analyses. Genetic instruments tied to circulating cytokine concentrations were sourced from genome-wide association studies encompassing 8,293 Finnish participants. We then evaluated their links with sepsis and related outcomes using summary-level data acquired from the UK Biobank, a vast multicenter cohort study involving over 500,000 European participants. Specifically, our data spanned 11,643 sepsis cases and 474,841 controls, with subsets including specific age groups, 28-day mortality, and ICU-related outcomes.Results and DiscussionMR insights intimated that reduced genetically-predicted interleukin-10 (IL-10) levels causally correlated with a heightened sepsis risk (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.52-0.90, P=0.006). An inverse relationship emerged between monocyte chemoattractant protein-1 (MCP-1) and sepsis-induced mortality. Conversely, elevated macrophage inflammatory protein 1 beta (MIP1B) concentrations were positively linked with both sepsis incidence and associated mortality. These revelations underscore the causal impact of certain circulating cytokines on sepsis susceptibility and its prognosis, hinting at the therapeutic potential of modulating these cytokine levels. Additional research is essential to corroborate these connections.

Abstract To establish a pre-test probability model of coronary heart disease (CHD) combined with cardiopulmonary exercise test (CPET) indexes and to compare the clinical effectiveness with Duke clinical score (DCS) and updated Diamond-Forrester model (UDFM), thus further explore the predictive value. 342 cases were used to establish the prediction model equation and another 80 cases were used to verify the effectiveness. The patients were divided into CHD group (n = 157) and non-CHD group (n = 185) according to coronary artery stenosis degree >50% or not. Combining DCS and UDFM as reference models with CPET indexes, a multivariate logistic regression model was established. The area under the ROC curve of the three models were calculated to compare the predictive effectiveness. There were significant differences in gender, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave and ST-T change between two groups (P

Abstract The PI3K/AKT pathway plays an essential role in tumour development. NOD-like receptors (NLRs) regulate innate immunity and are implicated in cancer, but whether they are involved in PI3K/AKT pathway regulation is poorly understood. Here, we report that NLRP6 potentiates the PI3K/AKT pathway by binding and destabilizing p85α, the regulatory subunit of PI3K. Mechanistically, NLRP6 recruits the E3 ligase RBX1 to p85α and ubiquitinates lysine 256 on p85α, which is recognized by the autophagy cargo receptor OPTN, causing selective autophagic degradation of p85α and subsequent activation of the PI3K/AKT pathway by reducing PTEN stability. We further show that loss of NLRP6 suppresses cell proliferation, colony formation, cell migration, and tumour growth in glioblastoma cells in vitro and in vivo. Disruption of the NLRP6/p85α interaction using the Pep9 peptide inhibits the PI3K/AKT pathway and generates potent antitumour effects. Collectively, our results suggest that NLRP6 promotes p85α degradation via selective autophagy to drive tumorigenesis, and the interaction between NLRP6 and p85α can be a promising therapeutic target for tumour treatment.

Metal hydride hydrogen storage has the advantages of high hydrogen storage volume density, high safety, and high hydrogen purity, which can meet the hydrogen storage and supply needs of fuel cells in both mobile and fixed scenarios. It has become one of the most promising hydrogen storage methods. This work studies the dynamic performance of metal hydride hydrogen storage systems under absorption and desorption process by establishing dynamic models and heat exchange models. The dynamic properties of metal hydride hydrogen storage system are analyzed in different reaction process with the experimental test. Results show that when the ambient temperature is within a certain range, low temperatures are conducive to hydrogen absorption, while high temperatures can improve hydrogen release dynamics. Besides, raising the flow rate of hydrogen and reducing the volume fraction of hydrogen storage materials can help to improve the efficiency of hydrogen absorption and desorption reaction.

Based on the single-machine infinite bus system， the validity of trajectory sensitivity calculation by convolution method is deeply analyzed， which provides support for using wide area measurement system to calculate the trajectory sensitivity and improves the level of dynamic safety analysis in power system. Theoretical analysis shows that， the relationship between the track sensitivity and the track will not change by changing generator models. Dynamic simulation is carried out on the basis of theoretical analysis. The simulation results show that different models can simulate the almost consistent dynamic track. The above research shows that the convolution method for calculating the track sensitivity is not affected by the system model. An index is established to evaluate the accuracy of the convolution method for calculating the trajectory sensitivity. By changing the generator model， the disturbance amount and the initial operation state， the dynamic simulation trajectory is traversed. The results show that the convolution method for calculating the trajectory sensitivity in the single-machine infinite bus system has high reliability， the results of convolution method for calculating the trajectory sensitivity in the actual engineering are of high reference value.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging global epidemic. The intention of this study was to explore the risk model and validation of CRKP infection in patients with cerebrovascular disease in the intensive care unit (ICU). The data of patients with cerebrovascular disease and Klebsiella pneumoniae infection were retrospectively collected. The patients were divided into the CRKP group and the carbapenem-susceptible Klebsiella pneumoniae (CSKP) group. There were significant differences (P < 0.05) between the CRKP group and the CSKP group for many variables. Multivariate binary logistic regression analysis showed that the number of types of antibiotics used, history of glucocorticoid use, and duration of mechanical ventilation before the occurrence of infectious bacteria are the independent risk factors for CRKP infection in patients with cerebrovascular disease in the ICU, and a nomogram risk model was constructed accordingly. The area under the ROC curve of the risk model was 0.868 (95% CI: 0.803–0.934).

Abstract Background Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. Methods We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0–4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. Discussion Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. Trial registration ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020–9-24, version 1.0).