Probing the interaction between the metallo-ß-lactamase SMB-1 and ampicillin by multispectral approaches combined with molecular dynamics.

Metallo-ß-lactamases (MßLs) hydrolyze and inactivate ß-lactam antibiotics, are a pivotal mechanism conferring resistance against bacterial infections. SMB-1, a novel B3 subclass of MßLs from Serratia marcescens could deactivate almost all ß-lactam antibiotics including ampicillin (AMP), which has posed a serious threat to public health. To illuminate the mechanism of recognition and interaction between SMB-1 and AMP, various fluorescence spectroscopy techniques and molecular dynamics simulation were employed. The results of quenching spectroscopy unraveled that AMP could make SMB-1 fluorescence quenching that mechanism was the static quenching; the synchronous and three-dimensional fluorescence spectra validated that the microenvironment and conformation of SMB-1 were altered after interaction with AMP. The molecular dynamics results demonstrated that the whole AMP enters the binding pocket of SMB-1, even though with a relatively bulky R1 side chain. Loop1 and loop2 in SMB-1 undergo significant fluctuations, and α2 (71-73) and local α5 (186-188) were turned into random coils, promoting zinc ion exposure consistent with circular dichroism spectroscopy results. The binding between them was driven by a combination of enthalpy and entropy changes, which was dominated by electrostatic force in agreement with the fluorescence observations. The present study brings structural insights and solid foundations for the design of new substrates for ß-lactamases and the development of effective antibiotics that are resistant to superbugs.

Impact of Heating Conventional Cigarettes with a Novel Device on Health-related Biomarkers and Cigarette Use Patterns among Chinese Adult Smokers Unwilling to Quit: A Pilot Randomized Controlled Trial.

INTRODUCTION: We evaluated the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on biomarkers and cigarette use patterns in Chinese adult smokers unwilling to quit smoking. METHODS: In this pilot randomized controlled trial, 50 eligible participants were allocated to either Control group (smoking conventional cigarettes) or HTP device group (switching to using heated conventional cigarettes by the HTP device). Participants in the HTP device group went through a 2-day run-in period then used heated conventional cigarettes exclusively for 5 days, followed by flexible use for 14 days. Five biomarkers of exposure (BoEs) were measured at baseline and on Day 7. Thirteen biomarkers of biological effect (BoBEs) were measured at baseline and on Day 21. Safety, daily cigarette consumption, craving, withdrawal symptoms, and device acceptability, were assessed. RESULTS: BoE levels decreased by 26.4 % to 71.4% from baseline in the HTP device group, while BoBE levels did not significantly change in either group. In the HTP group, 56% exclusively used heated conventional cigarettes during the flexible use period, experiencing reduced cravings and withdrawal symptoms, while dual users consumed more cigarettes. Mild to moderate device-related reactions were reported in 36% of users. Satisfaction, taste, and harm reduction belief scores averaged 7.4, 6.6, and 8.7 (out of 10), respectively. CONCLUSIONS: Switching to heated cigarettes with the HTP device may reduce short-term exposure to smoke toxicants. However, it can lead to increased tobacco use among dual users. Further investigation is needed to confirm these preliminary findings. IMPLICATIONS: This study is the first to evaluate the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on health-related biomarkers and cigarette use patterns among Chinese adult smokers. This novel HTP device can directly heat conventional cigarettes without the necessity for specifically designed tobacco products, avoiding potential additive risks of traditional HTPs. If the results of this study could be further verified by randomized controlled clinical trials with larger sample sizes, this novel HTP device could serve as a short-term harm reduction alternative for smokers unwilling to quit.

BSE@GW Prediction of Charge Transfer Exciton in Molecular Complexes: Assessment of Self-Energy and Exchange-Correlation Dependence.

The Bethe-Salpeter equation using the GW approximation to the self-energy (BSE@GW) is a computationally attractive method for studying electronic excitation from first principles within the many-body Green's function theory framework. We examine its dependence on the underlying exchange-correlation (XC) approximation as well as on the GW approximation for predicting the charge transfer exciton formation at representative type-II interfaces between molecular systems of tetrachloro-1,2-benzoquinone (TCBQ) and acene derivatives. For the XC approximation, we consider several widely used generalized gradient approximation (GGA) and hybrid GGA functionals. For the GW self-energy approximation, we examine the recently proposed renormalized singles approach by Yang and coauthors [J. Phys. Chem. Lett. 2019, 10 (3), 447-452; J. Chem. Theory Comput. 2022, 18, 7570-7585] in addition to other commonly employed approximated GW schemes. We demonstrate a reliable prediction of the charge transfer exciton within the BSE@GW level of theory.

Switchable and Tunable Radiative Cooling: Mechanisms, Applications, and Perspectives.

The cost of annual energy consumption in buildings in the United States exceeds 430 billion dollars ( Science 2019, 364 (6442), 760-763), of which about 48% is used for space thermal management (https://www.iea.org/reports/global-status-report-for-buildings-and-construction-2019), revealing the urgent need for efficient thermal management of buildings and dwellings. Radiative cooling technologies, combined with the booming photonic and microfabrication technologies ( Nature 2014, 515 (7528), 540-544), enable energy-free cooling by radiative heat transfer to outer space through the atmospheric transparent window ( Nat. Commun. 2024, 15 (1), 815). To pursue all-season energy savings in climates with large temperature variations, switchable and tunable radiative coolers (STRC) have emerged in recent years and quickly gained broad attention. This Perspective introduces the existing STRC technologies and analyzes their benefits and challenges in future large-scale applications, suggesting ways for the development of future STRCs.

Ion diffusion retarded by diverging chemical susceptibility.

For first-order phase transitions, the second derivatives of Gibbs free energy (specific heat and compressibility) diverge at the transition point, resulting in an effect known as super-elasticity along the pressure axis, or super-thermicity along the temperature axis. Here we report a chemical analogy of these singularity effects along the atomic doping axis, where the second derivative of Gibbs free energy (chemical susceptibility) diverges at the transition point, leading to an anomalously high energy barrier for dopant diffusion in co-existing phases, an effect we coin as super-susceptibility. The effect is realized in hydrogen diffusion in vanadium dioxide (VO2) with a metal-insulator transition (MIT). We show that hydrogen faces three times higher energy barrier and over one order of magnitude lower diffusivity when it diffuses across a metal-insulator domain wall in VO2. The additional energy barrier is attributed to a volumetric energy penalty that the diffusers need to pay for the reduction of latent heat. The super-susceptibility and resultant retarded atomic diffusion are expected to exist universally in all phase transformations where the transformation temperature is coupled to chemical composition, and inspires new ways to engineer dopant diffusion in phase-coexisting material systems.

Tracking COPD exacerbation patterns and forecasting readmission risks utilizing electronic medical records.

INTRODUCTION: Accurate evaluation of exacerbation frequency is an essential part of COPD assessment. But relying on just the prior-year exacerbation history may not capture the full picture of risk given the inherent year-to-year fluctuations in exacerbation rates. This study aimed to evaluate the predictive performance of models incorporating the 3-year exacerbation history based on electronic medical record. MATERIALS AND METHODS: This retrospective cohort study included 86,501 COPD hospitalized patients in Beijing from 2008 to 2014. The annual frequency of COPD exacerbation hospitalizations over a 3-year period after the index hospitalization was calculated, with patients segmented into seven distinct exacerbation trajectory groups. Logistic regression was used to evaluate the predictive capability of the 3-year exacerbation history for exacerbation readmission in the fourth year. Predictors included age, sex, comorbidities, and exacerbation hospitalization in previous 1-3 years. Model performance was evaluated using area under the receiver operating characteristic curve (AUC). RESULTS: Of the studied patients, 56.5% were men, and the mean age (SD) was 73.8 (10.3) years. The overall readmission rate for COPD exacerbation was 0.31 per person-year, with only 3.8% of patients persistently readmitted over three consecutive years. The 3-year trajectory of exacerbation frequency was associated with exacerbation risk in the fourth year. Compared to just the prior year, the inclusion of a 3-year exacerbation hospitalization history notably improved prediction accuracy, with AUC elevating from 0.731 (0.724-0.739) to 0.786 (0.779-0.792). CONCLUSION: These results unveil the fluctuating nature of COPD exacerbation hospitalization frequency across years and demonstrate that integrating a more comprehensive 3-year exacerbation history significantly refines the prediction model for future risk, thus providing a more nuanced and actionable insight for clinical care.

Global Trends in mHealth and Medical Education Research: Bibliometrics and Knowledge Graph Analysis.

Background: Mobile health (mHealth) is an emerging mobile communication and networking technology for health care systems. The integration of mHealth in medical education is growing extremely rapidly, bringing new changes to the field. However, no study has analyzed the publication and research trends occurring in both mHealth and medical education. Objective: The aim of this study was to summarize the current application and development trends of mHealth in medical education by searching and analyzing published articles related to both mHealth and medical education. Methods: The literature related to mHealth and medical education published from 2003 to 2023 was searched in the Web of Science core database, and 790 articles were screened according to the search strategy. The HistCite Pro 2.0 tool was used to analyze bibliometric indicators. VOSviewer, Pajek64, and SCImago Graphica software were used to visualize research trends and identify hot spots in the field. Results: In the past two decades, the number of published papers on mHealth in medical education has gradually increased, from only 3 papers in 2003 to 130 in 2022; this increase became particularly evident in 2007. The global citation score was determined to be 10,600, with an average of 13.42 citations per article. The local citation score was 96. The United States is the country with the most widespread application of mHealth in medical education, and most of the institutions conducting in-depth research in this field are also located in the United States, closely followed by China and the United Kingdom. Based on current trends, global coauthorship and research exchange will likely continue to expand. Among the research journals publishing in this joint field, journals published by JMIR Publications have an absolute advantage. A total of 105 keywords were identified, which were divided into five categories pointing to different research directions. Conclusions: Under the influence of COVID-19, along with the popularization of smartphones and modern communication technology, the field of combining mHealth and medical education has become a more popular research direction. The concept and application of digital health will be promoted in future developments of medical education.

Chemical Potentials and the One-Electron Hamiltonian of the Second-Order Perturbation Theory from the Functional Derivative Approach.

We develop a functional derivative approach to calculate the chemical potentials of second-order perturbation theory (MP2). In the functional derivative approach, the correlation part of the MP2 chemical potential, which is the derivative of the MP2 correlation energy with respect to the occupation number of frontier orbitals, is obtained from the chain rule via the noninteracting Green's function. First, the MP2 correlation energy is expressed in terms of the noninteracting Green's function, and its functional derivative to the noninteracting Green's function is the second-order self-energy. Then, the derivative of the noninteracting Green's function to the occupation number is obtained by including the orbital relaxation effect. We show that the MP2 chemical potentials obtained from the functional derivative approach agree with that obtained from the finite difference approach. The one-electron Hamiltonian, defined as the derivative of the MP2 energy with respect to the one particle density matrix, is also derived using the functional derivative approach, which can be used in the self-consistent calculations of MP2 and double-hybrid density functionals. The developed functional derivative approach is promising for calculating the chemical potentials and the one-electron Hamiltonian of approximate functionals and many-body perturbation approaches dependent explicitly on the noninteracting Green's function.

Qualitative and Quantitative Analysis of Three-Dimensional Fluorescence Spectra by Improved Parallel Factor Analysis with Internal Standard Sample Embedding.

The strategy of parallel factor analysis, combined with the internal standard method, has been increasingly applied to the qualitative and quantitative analysis of three-dimensional fluorescence spectra of unknown mixed fluorophores. Nevertheless, the disparity in the number of fluorophores included in the internal standard sample set and the number included in test samples may impact the qualitative and quantitative outcomes of parallel factor analysis. In this work, we systematically established the framework of the parallel factor analysis with internal standard sample embedding (ISSE-PARAFAC) strategy. We applied this framework to six datasets representing two scenarios and a real dataset and conducted a detailed discussion on the effects of the disparity between the number of fluorophores in the internal standard sample set and the number in the test set on both qualitative and quantitative results. Additionally, we introduced an enhancement to PARAFAC by aggregating fluorophores with similar emission wavelengths, corresponding to the peaks of emission loadings (spectra) obtained from PARAFAC, as a single fluorophore. This aggregation aimed to mitigate the strong correlation between similar fluorophores. The results imply that the presence of irrelevant fluorophores in the internal standard sample set, whether increased or decreased, does not significantly affect the qualitative and quantitative analysis of target fluorophores in the test set. Moreover, we demonstrated that the improved parallel factor analysis with internal standard sample embedding not only fully decomposes the uncorrelated mixed fluorophores for qualitative analysis but also allows the established linear concentration model for fluorescent components to predict the corresponding fluorophore concentration of test samples, enabling quantitative analysis at the ppm level (mg/L).

Assessment of the reversibility of resistance in the absence of antibiotics and its relationship with the resistance gene's fitness cost: a genetic study with mcr-1.

BACKGROUND: The intensive use of antibiotics has resulted in strong natural selection for the evolution of antimicrobial resistance (AMR), but whether, and under what circumstances, the removal of antibiotics would result in a rapid reduction in AMR has been insufficiently explored. We aimed to test the hypothesis that in the simple, yet common, case of AMR conferred by a single gene, removing antibiotics would quickly reduce the prevalence of resistance if the AMR gene imposes a high fitness cost and costless resistance is extremely rare among its proximal mutants. METHODS: In this genetic study, to test our hypothesis, we used the mcr-1 gene in Escherichia coli, which confers resistance to the last-resort antibiotic colistin, as a model. A high-throughput reverse genetics approach was used to evaluate mcr-1 variants for their fitness cost and resistance levels relative to a non-functional construct, by measuring relative growth rates in colistin-free media and at 2 µg/mL and 4 µg/mL colistin. We identified costless resistant mcr-1 mutants, and examined their properties within the context of the sequential organisation of mcr-1's functional domains as well as the evolutionary accessibility of these mutations. Finally, a simple population genetic model incorporating the measured fitness cost was constructed and tested against previously published real-world data of mcr-1 prevalence in colonised inpatients in China since the 2017 colistin ban in fodder additives. FINDINGS: We estimated the relative growth rates of 14 742 mcr-1 E coli variants (including the wild type), 3449 of which were single-nucleotide mutants. E coli showed 73·8% less growth per 24 h when carrying wild-type mcr-1 compared with the non-functional construct. 6252 (42·4%) of 14 741 mcr-1 mutants showed colistin resistance accompanied by significant fitness costs, when grown under 4 µg/mL colistin selection. 43 (0·3%) mcr-1 mutants exhibited costless resistance, most of which contained multiple mutations. Among the 3449 single mutants of mcr-1, 3433 (99·5%) had a fitness cost when grown in colistin-free media, with a mean relative growth of 0·305 (SD 0·193) compared with the non-functional variant. 3059 (88·7%) and 1833 (53·1%) of 3449 single mutants outgrew the non-functional mcr-1 in the presence of 2 µg/mL and 4 µg/mL colistin, respectively. Single mutations that gave rise to costless mutants were rare in all three domains of mcr-1 (transmembrane domain, flexible linker, and catalytic domain), but the linker domain was enriched with cost-reducing and resistance-enhancing mutations and depleted with cost-increasing mutations. The population genetics model based on the experimental data accurately predicts the rapid decline in mcr-1 prevalence in real-world data. INTERPRETATION: Many identified costless resistant variants that consist of multiple mutations are unlikely to evolve easily in nature. These findings for colistin and mcr-1 might be applicable to other cases in which AMR entails a substantial fitness cost that cannot be mitigated in proximal mutants. FUNDING: National Natural Science Foundation of China, and National Key Research and Development Program of China.

Inhibition and transport mechanisms of the ABC transporter hMRP5.

Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters.

Utilizing EMR Data for Smoking Behavior Surveillance in Hospitalized Patients With Chronic Respiratory Diseases and Its Impact on Clinical Outcomes - Beijing Municipality, China, 2014-2023.

What is already known on this topic?: Smoking is the primary risk factor for a poor prognosis in chronic respiratory disease (CRD). Current tobacco surveillance efforts in China focus on the general population and do not adequately cover CRD patients. What is added by this report?: We employed electronic medical records (EMR) to track smoking habits in 28,334 hospitalized CRD patients at Beijing Chao-Yang Hospital. The rates of former and current smokers were 30.7% and 18.0%, respectively. Both former and current smokers exhibited an increased risk of respiratory symptoms and extended hospital stays. What are the implications for public health practice?: These results underscore the importance of implementing smoking monitoring and targeted cessation interventions for hospitalized patients with CRDs.

Reconfigurable multi-channel microwave photonic receiver for a multi-band signal based on cascaded microring resonator banks.

What we believe to be a novel reconfigurable multi-channel microwave photonic (MWP) receiver for multi-band RF signal is demonstrated for the first time, to the best of our knowledge. A reconfigurable MWP signal processing chip based on two cascaded microring filter banks is employed in the proposed receiver, which slices the multi-band RF input into several narrow band signals and selects optical frequency comb lines for frequency converting of each channel. Due to the significant reconfigurability of the signal processing chip, the proposed receiver can flexibly choose the output frequency band of each channel, and thus different frequency components of the multi-band RF input can be down converted to the intermediate frequency (IF) band for receiving or converted to other frequency band for forwarding. A multi-band RF signal composed of a linear frequency modulation (LFM) signal with 2 GHz bandwidth and a quad-phase shift keyed (QPSK) signal with 100 Mbit/s rate is experimentally received and reconstructed by the proposed receiver, where the reconstructed LFM component exhibits a signal to noise ratio (SNR) of 10.2 dB, and the reconstructed QPSK component reaches a high SNR of 26.1 dB and a great error vector magnitude (EVM) of 11.73%. On the other hand, the QPSK component of the multi-band RF signal centered at 13.5 GHz is successfully converted to 3.1 GHz.

STAT3 phosphorylation at Tyr705 affects DRP1 (dynamin-related protein 1) controlled-mitochondrial fission during the development of apoptotic-resistance in pulmonary arterial endothelial cells.

BACKGROUND: The apoptosis-resistant pulmonary arterial endothelial cells (PAECs) are known to be major players in the pulmonary remodeling of pulmonary arterial hypertension (PAH) and exhibit an abnormal metabolic profile with mitochondrial dysfunction. Mitochondrial fission has been shown to regulate the apoptosis of several cell types, but this is largely unexplored in the PAECs. OBJECTIVE: The roles of mitochondrial fission control by Dynamin related protein-1 (DRP1) in the development of PAECs apoptosis suppression were investigated in present study and the potential mechanisms behind this were furtherly explored. METHODS: The mitochondrial morphology was investigated in PAECs from PAH rats with the pulmonary plexiform lesions, and the relations of it with DRP1 expression and apoptosis were furtherly identified in apoptosis-resistant PAECs induced by hypoxia. PAECs were isolated from rats with severe PAH and from normal subjects, the apoptotic-resistant PAECs were induced by hypoxia. DRP1 gene knockdown was achieved via DRP1-siRNA, DRP1 and STAT3 phosphorylation were blocked using its inhibitors, respectively. Apoptosis was analyzed by flow cytometry, and mitochondrial morphology was investigated by transmission electron microscope and confocal microscopy. RESULTS: The PAECs isolated from PAH rats with the pulmonary plexiform-like lesions and displayed lower apoptotic rate with increased DRP1 expression and mitochondrial fragmentation. In addition, similar observations were achieved in apoptosis-resistant PAECs induced by hypoxia. Targeting DRP1 using siRNA and pharmacologic blockade prevented the mitochondrial fission and subsequent apoptotic resistance in PAECs under hypoxia. Mechanistically, STAT3 phosphorylation at Tyr705 was shown to be activated in both PAH and hypoxia-treated PAECs, leading to the regulation of DRP1 expression. Of importance, targeting STAT3Tyr705 phosphorylation prevented DRP1 disruption on apoptosis in PAECs under hypoxia. CONCLUSIONS: These data indicated that STAT3 phosphorylation at Tyr705 impacted DRP1-controlled mitochondrial fission during the development of apoptosis-resistance in PAECs, suggesting mitochondrial dynamics may represent a therapeutic target for PAH.

Intramolecular Hydrogen Bonding Rigidifying Flexible Bridge for Solution- and Vacuum-Processed TSCT-TADF Emitters.

To realize strong donor-acceptor face-to-face stacking for efficient through-space charge transfer-type thermally activated delayed fluorescence, a conceptually new design strategy is proposed to couple flexible bridges with adequate rigidity via built-in intramolecular hydrogen bonds (IHBs). The resulting emitter ACE-CN has a planarized benzyl methyl ether bridge self-anchored by the C-H···O IHB and shows a high photoluminescence quantum efficiency of 93%. The solution- and vacuum-processed devices exhibited high external quantum efficiencies of 11.8% and 24.7%, respectively.

Advances in Microfluidic-Based Core@Shell Nanoparticles Fabrication for Cancer Applications.

Current research in cancer therapy focuses on personalized therapies, through nanotechnology-based targeted drug delivery systems. Particularly, controlled drug release with nanoparticles (NPs) can be designed to safely transport various active agents, optimizing delivery to specific organs and tumors, minimizing side effects. The use of microfluidics (MFs) in this field has stood out against conventional methods by allowing precise control over parameters like size, structure, composition, and mechanical/biological properties of nanoscale carriers. This review compiles applications of microfluidics in the production of core-shell NPs (CSNPs) for cancer therapy, discussing the versatility inherent in various microchannel and/or micromixer setups and showcasing how these setups can be utilized individually or in combination, as well as how this technology allows the development of new advances in more efficient and controlled fabrication of core-shell nanoformulations. Recent biological studies have achieved an effective, safe, and controlled delivery of otherwise unreliable encapsulants such as small interfering RNA (siRNA), plasmid DNA (pDNA), and cisplatin as a result of precisely tuned fabrication of nanocarriers, showing that this technology is paving the way for innovative strategies in cancer therapy nanofabrication, characterized by continuous production and high reproducibility. Finally, this review analyzes the technical, biological, and technological limitations that currently prevent this technology from becoming the standard.

Survival outcomes of neoadjuvant immunochemotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. METHODS: This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). RESULTS: Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. CONCLUSION: This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.

Remnant cholesterol and risk of major adverse cardiovascular events: a systematic review and dose-response meta-analysis of cohort studies.

Emerging evidence indicates a significant role of remnant cholesterol in contributing to the residual risk associated with major adverse cardiovascular events (MACE). This study aims to evaluate the dose-response relationship between remnant cholesterol and the risk of MACE. PubMed, Embase and Cochrane databases were reviewed to identify cohort studies published in English up to 1 August 2023. Twenty-eight articles were selected. Pooled hazard ratios (HR) and their 95% confidence intervals (CIs) were calculated using fixed or random-effects models to evaluate the association between remnant cholesterol and the risk of MACE. The dose-response relationship between remnant cholesterol levels and the risk of MACE was analyzed using the linear model and restricted cubic spline regression models. For calculated remnant cholesterol levels, the pooled HR (95% CI) of MACE for per 1-SD increase was 1.13 (1.08, 1.17); HR (95% CI) for the second quartile (Q2), the third quartile (Q3) and the highest quartile (Q4) of remnant cholesterol levels were 1.14 (1.03, 1.25), 1.43 (1.23, 1.68) and 1.68 (1.44, 1.97), respectively, compared with the lowest quartile (Q1). For measured remnant cholesterol levels, the pooled HR (95% CI) of MACE per 1-SD increase was 1.67 (1.39, 2.01). The dose-response meta-analysis showed a dose-response relationship between remnant cholesterol levels and the risk of MACE, both on a linear trend (P < 0.0001) and a nonlinear trend (P < 0.0001). The risk of MACE is associated with increased levels of remnant cholesterol, and the dose-response relationship between remnant cholesterol levels and the risk of MACE showed both linear and nonlinear trends.

Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD.

BACKGROUND: Recent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been shown to affect corticosteroid response. Whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking has not been fully investigated so far. OBJECTIVES: This study aimed to assess whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking. METHODS: We included 3402 inpatients with AECOPD treated with corticosteroids at Beijing Chao-Yang Hospital from July 2013 to June 2021. Blood eosinophil counts were measured within 24 hours of admission. An eosinophil percentage ≥2% was considered as high eosinophilic. Smokers in this study were defined as current or former smokers. Treatment failure was defined as a worsening of AECOPD that led to adverse clinical outcomes or required further treatment or an extended hospital stay or hospitalisation following the exacerbation. Multivariate-adjusted logistic models were used to estimate the OR and 95% CI associated with treatment failure. RESULTS: There were 958 (28.2%) treatment failure events occurring. Patients with high eosinophils had a lower risk of treatment failure (OR 0.74, 95% CI 0.63 to 0.87) than patients with low eosinophils. Compared with never smoking and low eosinophilic group, the ORs for treatment failure were 0.70 (95% CI 0.52 to 0.96) for never smoking and high eosinophilic group, 0.82 (95% CI 0.64 to 1.05) for smoking and low eosinophilic group and 0.62 (95% CI 0.47 to 0.81) for smoking and high eosinophilic group. Furthermore, there was no significant interaction between eosinophils and smoking status in relation to treatment failure (p for interaction=0.73). Similar results were obtained from multiple secondary outcomes and subgroup analyses. CONCLUSION: Elevated blood eosinophils are associated with a lower rate of corticosteroid treatment failure, regardless of smoking status. Smoking does not modify the association between blood eosinophil level and corticosteroid treatment failure among inpatients with AECOPD.

[A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies].

OBJECTIVE: To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies (IIMs) patients receiving conventional treatment. METHODS: Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were included. The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics, laboratory features, peripheral blood lymphocytes, immunological indicators, and therapeutic drugs. RESULTS: Among the 635 patients included, 518 patients finished the follow-up, with an average time of 36.8 months. The total complete clinical response rate of IIMs was 50.0% (259/518). The complete clinical response rate of dermatomyositis (DM), anti-synthetase syndrome (ASS) and immune-mediated necrotizing myopathy (IMNM) were 53.5%, 48.9% and 39.0%, respectively. Fever (P=0.002) and rapid progressive interstitial lung disease (RP-ILD) (P=0.014) were observed much more frequently in non-complete clinical response group than in complete clinical response group. The aspartate transaminase (AST), lactate dehydrogenase (LDH), D-dimer, erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group. As for the treatment, the percentage of glucocorticoid received and intravenous immunoglobin (IVIG) were significantly higher in non-complete clinical response group than in complete clinical response group. Risk factor analysis showed that IMNM subtype (P=0.007), interstitial lung disease (ILD) (P=0.001), eleva-ted AST (P=0.012), elevated serum ferritin (P=0.016) and decreased count of CD4+T cells in peripheral blood (P=0.004) might be the risk factors for IIMs non-complete clinical response. CONCLUSION: The total complete clinical response rate of IIMs is low, especially for IMNM subtype. More effective intervention should be administered to patients with ILD, elevated AST, elevated serum ferritin or decreased count of CD4+T cells at disease onset.