Objective: To identify risk factors for progression to sepsis in patients with non-ventilator hospital-acquired pneumonia (NV-HAP) and develop a practical and accurate nomogram to improve clinical outcomes. Methods: We retrospectively enrolled 408 hospitalized patients diagnosed with hospital-acquired pneumonia at Peking University Third Hospital between January 2017 and December 2021. Clinical and laboratory data were collected, and patients were randomly assigned to a training cohort and a validation cohort. Univariate and multivariate logistic regression analyses were performed in the training cohort to identify independent risk factors associated with progression to sepsis. A predictive nomogram was then constructed based on these independent predictors and validated using the validation cohort. Results: A total of 368 patients were ultimately included. Multivariate logistic regression analysis identified male sex (OR = 2.22, 95% CI: 1.09–4.51), coagulation dysfunction (OR = 2.35, 95% CI: 1.04–5.30), acute myocardial infarction (OR = 8.58, 95% CI: 2.10–35.04), chronic kidney disease (OR = 2.73, 95% CI: 1.15–6.51), underlying respiratory disease (OR = 0.31, 95% CI: 0.12–0.79), oxygenation index (OR = 0.99, 95% CI: 0.99–1.00), platelet count (OR = 0.99, 95% CI: 0.98–0.99), and total bilirubin (OR = 1.03, 95% CI: 1.01–1.06) as independent predictors for progression to sepsis in NV-HAP patients. The nomogram demonstrated good predictive performance, with C-index values of 0.73 in the training cohort and 0.64 in the validation cohort. Calibration curves indicated acceptable agreement between predicted and actual outcomes, and decision curve analysis confirmed favorable clinical utility in both cohorts. Conclusion: In patients with NV-HAP, clinicians should pay particular attention to specific independent risk factors identified in this study, such as male sex, coagulation dysfunction, acute myocardial infarction, chronic kidney disease, underlying respiratory diseases, decreased oxygenation index, thrombocytopenia, and elevated total bilirubin. The developed nomogram effectively predicts the risk of progression to sepsis, providing clinicians with a practical tool for timely intervention and potentially improving patient outcomes.

Objective: This study aimed to investigate the factors influencing weaning failure from invasive mechanical ventilation (IMV) in critically ill older patients with coronavirus disease 2019 (COVID-19). Methods: We enrolled critically ill older patients with COVID-19 who were admitted to the medical intensive care unit (ICU) and received IMV between December 2022 and June 2023. Results: We included 68 critically ill older patients with COVID-19 (52 male [76.5 %] and 16 female individuals [23.5 %]). The patients’ median age (interquartile range) was 75.5 (70.3–82.8) years. The median length of ICU stay was 11.5 (7.0–17.8) days; 34 cases (50.0 %) were successfully weaned from IMV. The successfully weaned group had a higher proportion of underlying chronic obstructive pulmonary disease [6 (17.6 %) vs. 0, P = 0.033] and fewer cases of diabetes [7 (20.6 %) vs. 16 (47.1 %), P = 0.021] compared with the weaning failure group. Serum lactate levels [1.5 (1.2–2.3) vs. 2.6 (1.9–3.1) mmol/L, P < 0.001], blood urea nitrogen [8.2 (6.3–14.4) vs. 11.4 (8.0–21.3) mmol/L, P = 0.033], Acute Physiology and Chronic Health Evaluation (APACHE) II score [19.0 (12.0–23.3) vs. 22.5 (16.0–29.3), P = 0.014], and hospitalization days before endotracheal intubation [1.0 (0.0–5.0) vs. 3.0 (0.0–11.0), P = 0.023] were significantly decreased in the successfully weaned group, whereas PaO2/FiO2 [148.3 (94.6–200.3) vs. 101.1 (67.0–165.1), P = 0.038] and blood lymphocyte levels [0.6 (0.4–1.0) vs. 0.5 (0.2–0.6) 109/L, P = 0.048] were significantly increased, compared with the weaning failure group. Multivariate logistic regression analysis showed that diabetes (OR= 3.413, 95 %CI 1.029−11.326), P = 0.045), APACHE II Score (OR = 1.089, 95 % CI 1.008−1.175), P = 0.030), and hospitalization days before endotracheal intubation (OR = 1.137, 95 % CI 1.023−1.264), P = 0.017) were independent risk factors for weaning failure. Conclusion: In critically ill older patients with COVID-19 with diabetes, higher APACHE II Score, and longer hospitalization days before endotracheal intubation, weaning from IMV was more challenging. The study could help develop strategies for improving COVID-19 treatment.

Cellular quiescence is a dormant, non-dividing cell state characterized by significant shifts in physiology and metabolism. Quiescence plays essential roles in a wide variety of biological processes, ranging from microbial sporulation to human reproduction and wound repair. Moreover, when the regulation of quiescence is disrupted, it can drive cancer growth and compromise tissue regeneration after injury. In this Review, we examine the dynamic changes in metabolism that drive and support dormant and transiently quiescent cells, including spores, oocytes and adult stem cells. We begin by defining quiescent cells and discussing their roles in key biological processes. We then examine metabolic factors that influence cellular quiescence in both healthy and disease contexts, and how these could be leveraged in the treatment of cancer.

患者在使用两性霉素B胆固醇硫酸酯复合物治疗毛霉菌感染过程中出现发热,临床药师进行不良反应关联性评价后考虑为使用两性霉素B胆固醇硫酸酯复合物引起的药物热,建议停用可疑药品.医师采纳临床药师意见,患者停用相关药物后体温降至正常.临床药师协助医师及时识别和处理药物热,避免严重药源性损害的发生,为两性霉素B胆固醇硫酸酯复合物的临床合理应用及不良反应预警提供参考.

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.

Protein posttranslational modifications play important roles in cardiovascular diseases. The authors’ previous report showed that the abundance of succinylated and glutarylated proteins was significantly lower in the serum of patients with acute myocardial infarction (AMI) than in that of healthy volunteers, suggesting a potential relationship between protein acylation and AMI. Sirtuin 5 (SIRT5) facilitates the removal of malonyl, succinyl, and glutaryl modification; however, its effects on AMI remain unknown. In this study, the levels of SIRT5 in AMI mouse model was compared. Results showed elevated hepatic SIRT5 after myocardial infarction. Hepatocyte-specific SIRT5 overexpressing mice (liver SIRT5 OE) were generated to address the possible involvement of hepatic SIRT5 in AMI. The areas of myocardial infarction, myocardial fibrosis, and cardiac function in a model of experimental myocardial infarction were compared between liver SIRT5 OE mice and wild-type (WT) mice. The liver SIRT5 OE mice showed a significantly smaller area of myocardial infarction and myocardial fibrosis than the WT mice. The fibroblast growth factor 21 (FGF21) in the blood and myocardium of liver SIRT5 OE mice after AMI was markedly elevated compared with that in WT mice. The results of mass spectrometry showed increased levels of proteins regulating tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid β-oxidation pathways in the liver mitochondria of liver SIRT5 OE mice. These findings showed that SIRT5 may exhibit a cardioprotective effect in response to acute ischemia through a liver-cardiac crosstalk mechanism, probably by increasing the secretion of FGF21 and the improvement of energy metabolism.

This paper presents a deep learningbased classification model, referred to as InceptionSSVEP, for the steady-state visual evoked potential (SSVEP) based braincomputer interface (BCI). InceptionSSVEP adopts the main concept of Inception network, which is a deep learning model performing well in image classification tasks, to improve the performance of SSVEP classification. A multi-scale convolution structure is utilized in InceptionSSVEP to extract both long-term and short-term features of SSVEP signals, for the purpose of ensuring the comprehensiveness of high-dimensional features in extracted SSVEPs. Moreover, a data enhancement scheme is proposed to overcome the impact of SSVEP data amount limitation on classifier training. Results show that the proposed InceptionSSVEP outperforms other existing methods significantly, and validate that Inception networks have good transferability on SSVEP signals. Reasons for the good performance of InceptionSSVEP are analyzed using deep learning interpretability tools.

In this paper, the practical performance of space-frequency block code (SFBC)-based multiple-input multiple-output (MIMO) orthogonal frequency division multiplexing (OFDM) system in the presence of nonlinear power amplifier with imperfect channel state information (CSI) over two-wave with diffuse power (TWDP) channel is analyzed. In the performance analysis, we first introduce the equivalent single-input single-output (SISO) scalar model with nonlinear power amplifier and then the SISO model is used to construct a model for the nonlinear MIMO-OFDM system. Considering the channel estimation error at the receiver, we study the effects of MMSE channel estimation error on the channel capacity. What is more, based on inter modulation product (IMP) analysis, we study the BER performance of nonlinear SFBC MIMO-OFDM systems, considering M-ary phase shift keying (MPSK) and M-ary quadrature amplitude modulation (MQAM). And the effects of channel estimation error on the BER performance are studied. Finally, this paper also derives the closed-form expressions of the system optimal operating point. The numerical results and comparisons are provided for several forms of SFBC MIMO-OFDM. From these analysis results, it is found that the analytical interpretation of the observed behavior in the simulation can be advanced, and the actual analysis of the performance optimization of the nonlinear MIMO-OFDM system is also provided.

Digital predistortion (DPD) is a major linearization technique for nonlinear power amplifier (PA). While DPD requires the measurement of PA instantaneous behavior for calculating PA inverse characteristic. In designing system-level DPD, it is necessary to develop a correlation algorithm for measuring the instantaneous behaviour of remote PAs when the local PA testbed is lacked. This paper proposes a novel correlation algorithm to measure the instantaneous behavior of PAs. In this proposed algorithm, the influence of PA nonlinearity and memory effects on PN sequence is modeled and compensated, and this is followed by the conventional compensation of the carrier offset. In the real measurement of a solid state PA (SSPA).

PurposeTo identify protein malonylation, succinylation, and glutarylation in human and rat serum.Experimental designImmunoprecipitation coupled with MS/MS is employed to compare the relative abundance of malonylation, succinylation, and glutarylation of serum protein in acute myocardial infarction human and rat.ResultsOne hundred thirty and 48 unique malonylated, succinylated, or glutarylated peptides are found in human and rat serum, respectively. Succinylation is the most predominant modification. The most modified protein is albumin. Abundance of serum protein succinylation and glutarylation is significantly (p < 0.05) lower in the peripheral serum of ST‐segment elevation myocardial infarction patients compared with healthy volunteers, which is also observed in acute myocardial infarction rats.Conclusions and clinical relevanceMalonylation, succinylation, and glutarylation widely exist in mammalian serum proteins, and may reveal novel mechanism of acute myocardial infarction.

Background:The role of airway microbiota in COPD is highly debated. Symptomology assessment is vital for the management of clinically stable COPD patients; however, the link between symp toms and the airway microbiome is currently unknown.Purpose:The present study aimed to evaluate the relationship among stable COPD patients.Patients and methods:We conducted pyrosequencing of bacterial 16S rRNA using induced sputum samples in a Han Chinese cohort that included 40 clinically stable COPD patients and 19 healthy controls.Results:Alterations in community composition and core bacte rial taxa (Neisseria subflava, etc.) were observed in patients with severe symptoms compared with controls. The co-occurrence network indicated that the key microbiota enriched in COPD patients showed higher expression in patients with severe symptoms. The association pattern of symptoms with the sputum microbiome was obviously different from that of lung function in COPD patients.Conclusion:These findings broaden our insights into the relationship between the sputum microbiota and the symptom severity in COPD patients, emphasizing the role of symptoms in the airway microbiome, independent of lung function.

Sirtuin 5 (SIRT5) is a NAD - dependent lysine deacylase. To investigate the potential role of SIRT5 and acylation in obesity and Type 2 Diabetes (T2D), we established and characterized the hepatic SIRT5 - overexpressing ob/ob mice (ob/ob - SIRT5 OE). The ob/ob - SIRT5 OE mice showed decreased malonylation and succinylation, improved cellular glycolysis, suppressed glyconeogenesis, enhanced fatty acid oxidation, and attenuated hepatic steatosis. A total of 955 malonylation sites on 434 proteins and 1,377 succinylation sites on 429 proteins were identified and quantitated. Further analysis revealed that malonylation was the major SIRT5 target in the glycolysis/gluconeogenesis pathway, while succinylation was the preferred SIRT5 target in the oxidative phosphorylation pathway. Our data suggested that hepatic overexpression of SIRT5 ameliorated the metabolic abnormalities of ob/ob mice, probably through demalonylating and desuccinylating proteins in the main met abolic pathways.Declaration of Interests: The authors declare no competing interests.Funding: This work was supported by the National Natural Science Foundation of China (31671175, 31771257, 61773025), the Strategic Priority Research Programs (Category A) of the Chinese Academy of Sciences (XDA12030207), the National Key R&D Program of China (2017YFA0205501), the interdisciplinary medicine Seed Fund of Peking University (BMU2017MB001) and the National Laboratory of Biomacromolecules.The study design was approved by the appropriate ethics review boards.

Background: Adverse cardiovascular effects associated with air pollution exposure have been widely demonstrated. However, inconsistent cardiovascular responses were observed from reducing indoor air pollution exposure. We aimed to assess whether short-term air filtration intervention could benefit cardiovascular health in elderly living in high pollution area. Methods: A randomized crossover intervention study of short-term indoor air filtration intervention on cardiovascular health was conducted among 35 non-smoking elderly participants living in Beijing in the winter of 2013, as part of Beijing Indoor Air Purifier StudY (BIAPSY). Portable air filtration units were randomly allocated to active filtration for 2 weeks and sham filtration for 2 weeks in the households. Twelve-hour daytime ambulatory heart rate variability (HRV) and blood pressure (ABP) were measured during active and sham filtration. Concurrently, real-time indoor and outdoor particulate matter with diameter less than 2.5 mu m (PM2.5) and indoor black carbon (BC) concentrations were measured. We applied generalized additive mixed models to evaluate the associations of 1- to 10-h moving average (MA) exposures of indoor PM2.5 and BC with HRV and ABP indices, and to explore whether these associations could be modified by air filtration. Results: We observed decreases of 34.8% in indoor PM2.5 and 35.3% in indoor BC concentrations during active filtration. Indoor PM2.5 and BC exposures were significantly associated with reduced HRV and increased ABP indices, and greater changes were observed during sham filtration. In specific, each 10 mu g/m(3) increase in indoor PM2.5 at MA8-h was associated with a significant reduction of 1.34% (95% CI: -2.42, -0.26) in SDNN during sham filtration, compared with a non-significant reduction of 0.81% (95% CI: -6.00, 4.68) during active filtration (P-inter, < 0.001). Each 1 mu g/m(3) increase in indoor BC at MA8-h was associated with a significant increase of 2.41% (95% CI: 0.38, 4.47) in SBP during sham filtration, compared with a non-significant increase of -1.09% (95% CI: -4.06, 1.96) during active filtration (P-inter = 0.135). Nonlinear inverse exposure-response relationships of indoor air pollution exposures with predicted HRV and ABP indices also confirmed some cardiovascular benefits of short-term air filtration intervention. Conclusions: Our results suggested that short-term indoor air filtration intervention can be of some cardiovascular benefits in elderly living with high pollution episodes.

BACKGROUND:Sirtuin 5 (SIRT5) is a NAD+-dependent lysine deacylase. The SIRT5 deficiency mouse model shows that it is dispensable for metabolic homeostasis under normal conditions. However, the biological role of SIRT5 and acylation in pathological states such as obesity and type 2 diabetes (T2D) remains elusive.METHODS:The hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) was established by CRISPR/Cas9 gene editing tool Protein malonylation and succinylation lysine sites were identified by immunoprecipitation coupled lipid chromatography - tandem mass spectrometry (LC-MS/MS) methods.FINDINGS:The ob/ob-SIRT5 OE mice showed decreased malonylation and succinylation, improved cellular glycolysis, suppressed gluconeogenesis, enhanced fatty acid oxidation, and attenuated hepatic steatosis. A total of 955 malonylation sites on 434 proteins and 1377 succinylation sites on 429 proteins were identified and quantitated. Bioinformatics analysis revealed that malonylation was the major SIRT5 target in the glycolysis/gluconeogenesis pathway, whereas succinylation was the preferred SIRT5 target in the oxidative phosphorylation pathway.INTERPRETATION:Hepatic overexpression of SIRT5 ameliorated the metabolic abnormalities of ob/ob mice, probably through demalonylating and desuccinylating proteins in the main metabolic pathways. SIRT5 and related acylation might be potential targets for metabolic disorders. FUND: National Key R&D Program of China, the National Natural Science Foundation of China, the Strategic Priority Research Programs (Category A) of the Chinese Academy of Sciences, the Interdisciplinary Medicine Seed Fund of Peking University and the National Laboratory of Biomacromolecules.

Biomarkers for the management of chronic obstructive pulmonary disease (COPD) are limited. The aim of this study was to explore new plasma biomarkers in patients with COPD. Thyroxine-binding globulin (THBG) was initially identified by proteomics in a discovery panel and subsequently verified by enzyme-linked immunosorbent assay in another verification panel with a 1-year follow-up. THBG levels were elevated in patients with COPD (9.2±2.3 μg/mL) compared to those of the controls (6.6±2.0 μg/mL). Receiver operating characteristic curves suggested that THBG was able to slightly differentiate between patients with COPD and controls (area under the curve [AUC]: 0.814) and performed better if combined with fibrinogen (AUC: 0.858). THBG was more capable of distinguishing Global Initiative for Obstructive Lung Disease stages I-III and IV (AUC: 0.851) compared with fibrinogen (AUC 0.582). THBG levels were negatively associated with predicted percentage forced expiratory volume in 1 s and positively related to predicted percentage residual volume, RV/percentage total lung capacity, and percentage low-attenuation area. COPD patients with higher baseline THBG levels had a greater risk of acute exacerbation (AE) than those with lower THBG levels (P=0.014, by Kaplan-Meier curve; hazard ratio: 4.229, by Cox proportional hazards model). In summary, THBG is a potential plasma biomarker of COPD and can assist in the management of stable stage and AEs in COPD patients.

In this Beijing Indoor Air Purifier StudY (BIAPSY), we conducted a randomized crossover intervention trial in a panel of 35 non-smoking senior participants with free-living, with and without chronic obstructive pulmonary disease (COPD). Portable air filtration units were randomly allocated to active-(filter in) for 2weeks and sham-mode (filter out) for 2weeks in the households. We examined the differences in indoor air pollutant concentrations in 20 study homes and a suite of cardio-respiratory biomarker levels in study participants between filtration modes, with and without adjustment for potential confounders. Following active filtration, we observed significant reductions from 60±45 to 24±15μg/m3 in ten-day averages of indoor PM2.5 and reductions from 3.87±1.65 to 1.81±1.19m-1.10-5 in ten-day averages of indoor BC, compared to sham-mode filtration. The major components of indoor PM2.5, including water soluble organics, NO3-, SO42-, Zn2+, Pb2+ and K+, were also reduced significantly by 42% to 63%. However, following active filtration, we only observed significant reductions on systemic inflammation measured as of IL-8 at 58.59% (95% CI: -76.31, -27.64) in the total group of participants and 70.04% (95% CI: -83.05, -47.05) in the subset of COPD patients, with adjustments. We were not able to detect improvements on lung function, blood pressure, and heart rate variability, following short-term intervention of two-week active air filtration. In conclusion, our results showed that indoor air filtration produced clear improvement on indoor air quality, but no demonstrable changes in the cardio-respiratory outcomes of study interest observed in the seniors living with real-world air pollution exposures.

The study aimed to determine the relationship between throat microbiome and COPD. Sixty-five Chinese males (n=20, smokers without COPD; n=45 smokers with COPD) were included. Nonmetric multidimensional scaling indicated differences of microbiome between COPD and controls, but no difference was observed between COPD patients with differing degrees of lung function or disease severity. Rarefaction analyses suggested that operational taxonomic units (OTUs, species-level) richness decreased in COPD. The dominant taxa between COPD and controls were similar, but the proportions of taxonomic distribution were different. The dominant phyla were Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria. The dominant genera were Haemophilus, Leptotrichia, Porphyromonas, Fusobacterium, Veillonella, Streptococcus, Neisseria and Prevotella. Two dominant OTUs, otu3 (Veillonella_dispar) and otu4 (Streptococcus_unclassified), were identified. Otu3 and its father-level taxa, which were negatively correlated with predicted percent of forced expiratory volume in a second (FEV1%pred), were increased in COPD. By contrast, otu4 and its father-level taxa, which were positively correlated with FEV1%pred, were decreased in COPD. Otu4 also showed a slight potential as a COPD biomarker. To conclude, the throat microbiome was different between smokers with or without COPD, which is similar to findings from the lower respiratory tract. This study may strengthen our understanding of the relationship between microbiomes of different airway sites and COPD.

Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs. This mechanism facilitates homologous recombination (HR) and cell survival. We confirmed the interaction between RPA and G9a to be critical for RPA foci formation and HR upon DNA damage. Collectively, our findings demonstrate a regulatory pathway based on CK2-G9a-RPA that permits HR in cancer cells and provide further rationale for the use of G9a inhibitors as a cancer therapeutic.