七叶一枝花甾体皂苷种类及含量差异研究进展＊

重楼是我国传统的名贵中药，七叶一枝花为历版《中国药典》收载的重楼药材两个基原植物之一，具有清热解毒、消肿止痛、活血化瘀等功效，其主要活性成分为甾体皂苷类物质。由于重楼市场需求量剧增和七叶一枝花成药时间较长，导致大量依靠人工种植。然而，人工种植过程中产地、采收年限和采收月份都会影响七叶一枝花的甾体皂苷含量。本文系统地总结了七叶一枝花中主要活性成分甾体皂苷的种类，以及不同产地、不同生长年限及不同采收月份的七叶一枝花根茎中甾体皂苷含量差异的研究现状，以期为进一步研究七叶一枝花品质差异、野生资源驯化及规范化种植提供参考。     

DEep learning-based rapid Spiral Image REconstruction (DESIRE) for high-resolution spiral first-pass myocardial perfusion imaging

The objective of the current study was to develop and evaluate a DEep learning-based rapid Spiral Image REconstruction (DESIRE) technique for high-resolution spiral first-pass myocardial perfusion imaging with whole-heart coverage, to provide fast and accurate image reconstruction for both single-slice (SS) and simultaneous multislice (SMS) acquisitions. Three-dimensional U-Net–based image enhancement architectures were evaluated for high-resolution spiral perfusion imaging at 3 T. The SS and SMS MB = 2 networks were trained on SS perfusion images from 156 slices from 20 subjects. Structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and normalized root mean square error (NRMSE) were assessed, and prospective images were blindly graded by two experienced cardiologists (5: excellent; 1: poor). Excellent performance was demonstrated for the proposed technique. For SS, SSIM, PSNR, and NRMSE were 0.977 [0.972, 0.982], 42.113 [40.174, 43.493] dB, and 0.102 [0.080, 0.125], respectively, for the best network. For SMS MB = 2 retrospective data, SSIM, PSNR, and NRMSE were 0.961 [0.950, 0.969], 40.834 [39.619, 42.004] dB, and 0.107 [0.086, 0.133], respectively, for the best network. The image quality scores were 4.5 [4.1, 4.8], 4.5 [4.3, 4.6], 3.5 [3.3, 4], and 3.5 [3.3, 3.8] for SS DESIRE, SS L1-SPIRiT, MB = 2 DESIRE, and MB = 2 SMS-slice-L1-SPIRiT, respectively, showing no statistically significant difference (p = 1 and p = 1 for SS and SMS, respectively) between L1-SPIRiT and the proposed DESIRE technique. The network inference time was ~100 ms per dynamic perfusion series with DESIRE, while the reconstruction time of L1-SPIRiT with GPU acceleration was ~ 30 min. It was concluded that DESIRE enabled fast and high-quality image reconstruction for both SS and SMS MB = 2 whole-heart high-resolution spiral perfusion imaging.     

Future perspectives: Novel Frontiers in Cancer Metastasis

Clinical & Experimental Metastasis -     

The social vulnerability metric (SVM) as a new tool for public health

Objective

To derive and validate a new ecological measure of the social determinants of health (SDoH), calculable at the zip code or county level.

Data Sources and Study Setting

The most recent releases of secondary, publicly available data were collected from national U.S. health agencies as well as state and city public health departments.

Study Design

The Social Vulnerability Metric (SVM) was constructed from U.S. zip-code level measures (2018) from survey data using multidimensional Item Response Theory and validated using outcomes including all-cause mortality (2016), COVID-19 vaccination (2021), and emergency department visits for asthma (2018). The SVM was also compared with the existing Centers for Disease Control and Prevention's Social Vulnerability Index (SVI) to determine convergent validity and differential predictive validity.

Data Collection/Extraction Methods

The data were collected directly from published files available to the public online from national U.S. health agencies as well as state and city public health departments.

Principal Findings

The correlation between SVM scores and national age-adjusted county all-cause mortality was r = 0.68. This correlation demonstrated the SVM's robust validity and outperformed the SVI with an almost four-fold increase in explained variance (46% vs. 12%). The SVM was also highly correlated (r ≥ 0.60) to zip-code level health outcomes for the state of California and city of Chicago.

Conclusions

The SVM offers a measurement tool improving upon the performance of existing SDoH composite measures and has broad applicability to public health that may help in directing future policies and interventions. The SVM provides a single measure of SDoH that better quantifies associations with health outcomes.     

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40 , 59–74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51 , 789–808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.     

Proteomics analysis of lysine crotonylation and 2-hydroxyisobutyrylation reveals significant features of systemic lupus erythematosus

Introduction/objectives

To seek significant features of systemic lupus erythematosus (SLE) by utilizing bioinformatics analysis.

Method

Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to quantify lysine crotonylation (Kcr) and lysine 2-hydroxyisobutyrylation (Khib) in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients and normal controls.

Results

Seventy-six differentially modified proteins (DMPs) dually modified by Kcr and Khib were identified between SLE patients and healthy people. GO enrichment analysis prompted significant enrichment of seventy-six DMPs in MHC class II protein complex binding and leukocyte migration. KEGG pathways were enriched in antigen processing and presentation pathway and leukocyte transendothelial migration pathway. Six DMPs (CLTC, HSPA1B, HSPA8, HSP90AB1, HSPD1, and PDIA3) were identified in antigen processing and presentation pathway, of which HSPA8 was the core protein. Significant changes of Kcr and Khib in HSPA8 may increase ATP hydrolysis and promote antigen binding to MHC II molecule. In leukocyte transendothelial migration pathway, 7 DMPs (ACTN1, ACTN4, EZR, MSN, RAC1, RHOA, and VCL) were identified. MSN was the protein with the most modification sites in this pathway. In amino terminal ferm region of MSN, Kcr and Khib expression change may lead to the adhesion between leukocytes and endothelial cells, which was an important step of leukocyte migration.

Conclusion

Kcr and Khib may promote the antigen presentation and jointly regulate the tissue damage mediated by leukocyte migration in SLE patients, which may play key roles in the pathogenesis of SLE probably.

The role of inflammation in the pathogenesis and treatment of arrhythmias

The pathogenesis of arrhythmias is complex and multifactorial. The role of inflammation in the pathogenesis of both atrial and ventricular arrhythmias (VA) has been explored. However, developing successful pharmacotherapy regimens based on those pathways has proven more of a challenge. This narrative review provides an overview of five common arrhythmias impacted by inflammation, including atrial fibrillation (AF), myocardial infarction, arrhythmogenic cardiomyopathy, cardiac sarcoidosis, and QT prolongation, and the potential role for anti-inflammatory therapy in their management. We identified arrhythmias and arrhythmogenic disease states with the most evidence linking pathogenesis to inflammation and conducted comprehensive searches of United States National Library of Medicine MEDLINE^® and PubMed databases. Although a variety of agents have been studied for the management of AF, primarily in an effort to reduce postoperative AF following cardiac surgery, no standard anti-inflammatory agents are used in clinical practice at this time. Although inflammation following myocardial infarction may contribute to the development of VA, there is no clear benefit with the use of anti-inflammatory agents at this time. Similarly, although inflammation is clearly linked to the development of arrhythmias in arrhythmogenic cardiomyopathy, data demonstrating a benefit with anti-inflammatory agents are limited. Cardiac sarcoidosis, an infiltrative disease eliciting an immune response, is primarily treated by immunosuppressive therapy and steroids, despite a lack of primary literature to support such regimens. In this case, anti-inflammatory agents are frequently used in clinical practice. The pathophysiology of arrhythmias is complex, and inflammation likely plays a role in both onset and duration, however, for most arrhythmias the role of pharmacotherapy targeting inflammation remains unclear.