Outcomes and Risk Factors Associated with Pericardiectomy in Patients with Constrictive Pericarditis: A Retrospective Study from China.

PURPOSE: Pericardiectomy is the definitive treatment option for constrictive pericarditis and is associated with a high prevalence of morbidity and mortality. However, information on the associated outcomes and risk factors is limited. We aimed to report the mid-term outcomes of pericardiectomy from a single center in China. METHODS: We retrospectively reviewed data collected from patients who underwent pericardiectomy at our institute from April 2018 to January 2023. RESULTS: Eighty-six consecutive patients (average age, 46.1 ± 14.7 years; 68.6 men) underwent pericardiectomy through midline sternotomy. The most common etiology was idiopathic (n = 60, 69.8%), and 82 patients (95.3%) were in the New York Heart Association function class III/IV. In all, 32 (37.2%) patients underwent redo sternotomies, 36 (41.9%) underwent a concomitant procedure, and 39 (45.3%) required cardiopulmonary bypass. The 30-day mortality rate was 5.8%, and the 1-year and 5-year survival rates were 88.3% and 83.5%, respectively. Multivariable analysis revealed that preoperative mitral insufficiency (MI) ≥moderate (hazard ratio [HR], 6.435; 95% confidence interval [CI] [1.655-25.009]; p = 0.007) and partial pericardiectomy (HR, 11.410; 95% CI [3.052-42.663]; p = 0.000) were associated with increased 5-year mortality. CONCLUSION: Pericardiectomy remains a safe operation for constrictive pericarditis with optimal mid-term outcomes.

Design, synthesis, and biological evaluation of 2,4-diaminopyrimidine derivatives as potent Hematopoietic Progenitor Kinase 1 (HPK1) inhibitors.

HPK1 also referred to as MAP4K1, belongs to the category of mammalian STE20-like protein serine/threonine kinases. Its physiological function involves the down-regulation of T cell signals, and it is regarded as a new immune checkpoint of tumor immunology. In this study, we commenced our investigation with the hit compounds, focusing the efforts on structural optimization and SAR exploration to identify a novel class of 2,4-diaminopyrimidine HPK1 inhibitors. Notably, compound 14g exhibited a remarkable inhibitory effect on HPK1 kinase (IC50 = 0.15 nM), significantly suppressed the phosphorylation of the downstream adaptor protein SLP76 (pSLP76 IC50 = 27.92 nM), and effectively stimulated the secretion of the T cell activation marker IL-2 (EC50 = 46.64 nM). In vitro microsomal stability assay, compound 14g showed moderate stability in HLMs with T1/2 = 38.2 min and CLint = 36.4 µL·min-1·mg-1 proteins. In vivo pharmacokinetic studies, compound 14g demonstrated heightened plasma exposure (AUC0-inf = 644 ng·h·mL-1), extended half-life (T1/2 = 9.98 h), and reduced plasma clearance (CL = 52.3 mL·min-1·kg-1) compared to the reference compound after a single intravenous dose of 2 mg/kg in rats. These results indicated that compound 14g emerged as a promising inhibitor of HPK1.

Novel biaryloxazolidinone derivatives with broad-spectrum antibacterial activity, favorable drug-like profiles and in vivo efficacy against linezolid-resistant Staphylococcusaureus.

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S. aureus, multidrug resistant S. aureus and Enterococcus faecalis were evaluated. Remarkably, compound 8b was identified with potent antibacterial activity against S. aureus (MIC = 0.06 µg/mL), MSSA (MIC = 0.125 µg/mL), MRSA (MIC = 0.06 µg/mL), LRSA (MIC = 0.125 µg/mL) and LREFa (MIC = 0.5 µg/mL). Compound 8b was demonstrated as a promising candidate through druglikeness evaluation including metabolism in microsomes and plasma, Caco-2 cell permeability, plasma protein binding, cytotoxicity, and inhibition of CYP450 and human monoamine oxidase. Notably, compound 8b displayed excellent PK profile with appropriate T1/2 of 1.49 h, high peak plasma concentration (Cmax = 2320 ng/mL), high plasma exposure (AUC0-t = 8310 h ng/mL), and superior oral bioavailability (F = 68.1 %) in Sprague-Dawley rats. Ultimately, in vivo efficacy of compound 8b in a mouse model of LRSA systemic infection was also demonstrated. Taken together, compound 8b represents a promising drug candidate for the treatment of linezolid-resistant Gram-positive bacterial strains infection.

Discovery and optimization of dihydropteridone derivatives as novel PLK1 and BRD4 dual inhibitor for the treatment of cancer.

In this study, we have designed, synthesized and tested three series of novel dihydropteridone derivatives possessing isoindolin-1-one or isoindoline moieties as potent inhibitors of PLK1/BRD4. Remarkably, most of the compounds showed preferable inhibitory activity against PLK1 and BRD4. Compound SC10 exhibited excellent inhibitory activity with IC50 values of 0.3 nM and 60.8 nM against PLK1 and BRD4, respectively. Meanwhile, it demonstrated significant anti-proliferative activities against three tumor-derived cell lines (MDA-MB-231 IC50 = 17.3 nM, MDA-MB-361 IC50 = 8.4 nM, and MV4-11 IC50 = 5.4 nM). Moreover, SC10 exhibited moderate rat liver microsomal stability (CLint = 21.3 µL·min-1·mg-1), acceptable pharmacokinetic profile (AUC0-t = 657 ng·h·mL-1, oral bioavailability of 21.4 %) in Sprague-Dawley rats, reduced hERG toxicity, acceptable PPB and CYP450 inhibition. Further research indicated that SC10 could induce MV4-11 cell arrest at the S phase and apoptosis in a dose-dependent manner. This investigation provided us with an initial point for developing novel anticancer agents as dual inhibitors of PLK1 and BRD4.

2-Aminopyrimidine derivatives as selective dual inhibitors of JAK2 and FLT3 for the treatment of acute myeloid leukemia.

Dual inhibitors of JAK2 and FLT3 can synergistically control the development of acute myeloid leukemia (AML), and overcome secondary drug resistance of AML that is associated with FLT3 inhibition. We therefore designed and synthesized a series of 4-piperazinyl-2-aminopyrimidines as dual inhibitors of JAK2 and FLT3, and improved their selectivity for JAK2. Screening cascades revealed that compound 11r exhibited inhibitory activity with IC50 values of 2.01, 0.51, and 104.40 nM against JAK2, FLT3, and JAK3, respectively. Compound 11r achieved a high selectivity for JAK2 at a ratio of 51.94, and also showed potent antiproliferative activity in HEL (IC50 = 1.10 µM) and MV4-11 (IC50 = 9.43 nM) cell lines. In an in vitro metabolism assay, 11r exhibited moderate stability in human liver microsomes (HLMs), with a half-life time of 44.4 min, and in rat liver microsomes (RLMs), with a half-life of 143 min. In pharmacokinetic studies, compound 11r showed moderate absorption (Tmax = 5.33 h), with a peak concentration of 38.7 ng/mL and an AUC of 522 ng h/mL in rats, and an oral bioavailability of 25.2%. In addition, 11r induced MV4-11 cell apoptosis in a dose-dependent manner. These results indicate that 11r is a promising selective JAK2/FLT3 dual inhibitor.

Design, synthesis, and biological evaluation of novel dihydropteridone derivatives possessing oxadiazoles moiety as potent inhibitors of PLK1.

Polo like kinase 1 (PLK1) is a serine/threonine kinase that is widely distributed in eukaryotic cells and plays an important role in multiple phases of the cell cycle. Its importance in tumorigenesis has been increasingly recognized in recent years. Herein, we describe the optimization of a series of novel dihydropteridone derivatives (13a-13v and 21g-21l) possessing oxadiazoles moiety as potent inhibitors of PLK1. Compound 21g exhibited improved PLK1 inhibitory capability with an IC50 value of 0.45 nM and significant anti-proliferative activities against four tumor-derived cell lines (MCF-7 IC50 = 8.64 nM, HCT-116 IC50 = 26.0 nM, MDA-MB-231 IC50 = 14.8 nM and MV4-11 IC50 = 47.4 nM) with better pharmacokinetic characteristics than BI2536 in mice (AUC0-t = 11 227 ng h mL-1vs 556 ng h mL-1). Moreover, 21g exhibited moderate liver microsomal stability and excellent pharmacokinetic profile (AUC0-t = 11227 ng h mL-1, oral bioavailability of 77.4%) in Balb/c mice, acceptable PPB, improved PLK1 inhibitory selectivity, and no apparent toxicity was observed in the acute toxicity assay (20 mg/kg). Further investigation showed that 21 g could arrest HCT-116 cells in G2 phase and induce apoptosis in a dose-dependent manner. These results indicate that 21g is a promising PLK1 inhibitor.

A Dual Coverage Monitoring of the Bile Acids Profile in the Liver-Gut Axis throughout the Whole Inflammation-Cancer Transformation Progressive: Reveal Hepatocellular Carcinoma Pathogenesis.

Hepatocellular carcinoma (HCC) is the terminal phase of multiple chronic liver diseases, and evidence supports chronic uncontrollable inflammation being one of the potential mechanisms leading to HCC formation. The dysregulation of bile acid homeostasis in the enterohepatic circulation has become a hot research issue concerning revealing the pathogenesis of the inflammatory-cancerous transformation process. We reproduced the development of HCC through an N-nitrosodiethylamine (DEN)-induced rat model in 20 weeks. We achieved the monitoring of the bile acid profile in the plasma, liver, and intestine during the evolution of "hepatitis-cirrhosis-HCC" by using an ultra-performance liquid chromatography-tandem mass spectrometer for absolute quantification of bile acids. We observed differences in the level of primary and secondary bile acids both in plasma, liver, and intestine when compared to controls, particularly a sustained reduction of intestine taurine-conjugated bile acid level. Moreover, we identified chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, and glycolithocholic acid in plasma as biomarkers for early diagnosis of HCC. We also identified bile acid-CoA:amino acid N-acyltransferase (BAAT) by gene set enrichment analysis, which dominates the final step in the synthesis of conjugated bile acids associated with the inflammatory-cancer transformation process. In conclusion, our study provided comprehensive bile acid metabolic fingerprinting in the liver-gut axis during the inflammation-cancer transformation process, laying the foundation for providing a new perspective for the diagnosis, prevention, and treatment of HCC.

Left atrial subclinical dysfunction in children with Kawasaki disease: a two-dimensional speckle-tracking echocardiography study.

BACKGROUND: Left atrial (LA) function is a very important prognostic indicator for many cardiovascular diseases. In this study, we aimed to determine whether LA function is impaired in children with Kawasaki disease (KD) and to analyze the relationships between LA deformation and conventional echocardiographic parameters and laboratory markers. METHODS: A total of 50 KD patients during different disease phases and 50 age- and sex-matched controls were retrospectively analyzed. Patients in the acute phase based on coronary artery dilation (CAD) were subdivided into Group I (with CAD) and Group II (without CAD) and compared. RESULTS: During the acute phase, KD patients had a lower peak LA longitudinal strain (PLALS), a lower LA strain peak during LA contraction (LASct), and a lower LA strain rate peak during LA contraction (LASRct) than the controls. The PLALS, LASct and LASRct began to increase during the subacute phase, and during the convalescent phase, all LA strains in patients had recovered to normal compared with the control subjects. Subgroup analysis revealed that, compared with Group II, Group I had higher C-reactive protein (CRP) and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; however, there were no significant differences in LA strains. Only the PLALS during the acute phase was negatively correlated with left ventricular mass index, CRP and NT-proBNP. CONCLUSIONS: In patients with KD, LA function is impaired during the acute phase, and this impairment is transient. Two-dimensional speckled tracking echocardiography is a useful tool for detecting subclinical LA dysfunction.

Discovery of novel 7,7-dimethyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidines as ATR inhibitors based on structure-based drug design.

ATR kinase is essential to the viability of replicating cells responding to the accumulation of single-strand breaks in DNA, which is an attractive anticancer drug target based on synthetic lethality. Herein we design, synthesize, and evaluate a novel series of fused pyrimidine derivatives as ATR inhibitors. As a result, compound 48f, with an IC50 value of 0.0030 µM against ATR, displayed strong monotherapy efficacy in ataxia-telangiectasia mutated (ATM) kinase-deficient tumor cells LoVo, SW620, OVCAR-3 cell lines with IC50 values of 0.040 µM, 0.095 µM, 0.098 µM, respectively. More importantly, the combination of 48f with AZD-1390, cisplatin, oxaliplatin, and olaparib respectively resulted in synergistic activity against HT-29, HCT116, A549, MCF-7, MDA-MB-231 cells. Moreover, 48f showed a favorable pharmacokinetic profile with a bioavailability of 30.0% in SD rats, acceptable PPB, high permeability (Papp A to B = 8.23 cm s-1 × 10-6), and low risk of drug-drug interactions. Collectively, compound 48f could be a promising compound for further investigation.

Accurate determination for lipidomics based on LC-tandem-MS parameters modeling, prediction, and database: Monitoring the progression of hepatocellular carcinoma.

The unavailability of adequate lipid reference standards is a major challenge for accurate quantitative analysis of lipidomics. Based on the discovery of regularity and predictability for lipids in chromatography-mass spectrometry behaviors, "target compound-structure correlation-analytical parameter database" protocol and "modeling-prediction" strategy were carried out to calculate the relative coefficients of analytical parameters within each subclass. Then the relevant LC-tandem-MS parameters of unknown lipids were predicted and a quantification parameter database for 4081 lipids was established and validated. Reference standards-independent accurate determination for lipidomics was achieved with the parameter's database and applied to monitor the change of lipid metabolism in the plasma of whole course of health-hepatitis-cirrhosis-hepatocellular carcinoma (HCC). Combined Student's t test, orthogonal partial least squares discrimination analysis (OPLS-DA) and binary logistic regression-ROC analysis, lipid biomarkers for differentiating health from each disease and differentiating different stages of disease were identified and the pathogenesis of HCC was preliminarily clarified. The established methodology would shed light on comprehensive and accurate quantitative lipidomics and exploring the pathomechanism and potential therapeutic targets of HCC.

A convenient and efficient 4-(diethylamino)-butylamine-labeled polarity-response-homodispersed strategy for absolute quantification of carboxyl submetabolome: Monitoring the whole progressive course of hepatocellular carcinoma.

Recent studies have shown that dysregulation of carboxyl submetabolome homeostasis is closely related to the occurrence and development of hepatocellular carcinoma (HCC). However, it is still a challenge to quantify carboxyl metabolites with high efficiency by conventional methods due to their species diversity and nature differences. Moreover, there are few studies on carboxyl submetabolome profiling during the whole progression of HCC. In this study, a convenient and efficient workflow for absolute quantification of carboxyl submetabolome was established based on the 4-(diethylamino)-butylamine (DEABA)-labeled polarity-response-homodispersed strategy. After optimizing derivation conditions with response surface methodology (RSM), the reaction only needed 1 min at room temperature, which radically simplified the labeling process. Compared with nonderivatization, the gaps of polarities and responses of the analytes were narrowed by DEABA labeling, realizing the polarity-response-homodispersion. Then resolution and sensitivity in HPLC-MS/MS were improved significantly. Ultimately, the workflow was applied to monitor carboxyl metabolic profile in human plasma of the whole progressive course of hepatocellular carcinoma. Combined with analysis of variance (ANOVA), orthogonal partial least squares discrimination analysis (OPLS-DA), Bayesian linear discriminant analysis (BLDA) and other data mining methods, the biomarkers of "health-hepatitis-cirrhosis-HCC" were screened out, and the diagnostic model was established. Furthermore, the relevancy between carboxyl submetabolome disorders and the pathogenesis of HCC was investigated. The developed method has the characteristics of high sensitivity, high coverage and high practicability, which is suitable for the study of biomarkers of carboxyl submetabolome in the whole progression of HCC.

A Diuretic Response is Associated with the Early Prognosis of Patients Undergoing Repeat Tricuspid Valve Surgery Due to Severe Tricuspid Regurgitation After Left-Sided Valvular Surgery.

OBJECTIVE: To analyze the factors affecting the early prognosis of patients undergoing repeat tricuspid valve surgery due to severe tricuspid regurgitation after left-sided valvular surgery. METHOD: We retrospectively analyzed 76 patients undergoing repeat tricuspid valve surgery due to severe tricuspid regurgitation after left-sided valvular surgery at Peking University International Hospital between October 2017 and February 2021. Patients were divided into two groups, according to preoperative weight control and whether the adjusted diuretic dose exceeded 40 mg of furosemide (or the equivalent dose). The factors affecting the early prognosis were analyzed through postoperative follow up. RESULTS: Thirty-five male patients (46.1%), aged 57±13 years, were enrolled in the study. For the patients who received a preoperative same dose of furosemide ≥40 mg/day and a same dose of furosemide <40 mg/day, the baseline data basically were the same. There were 76 patients (100%) who were followed up. Endpoint events during the follow up were as follows: Six patients (7.9%) died, two patients (2.6%) were admitted to the hospital or transferred to the intensive care unit due to cardiac insufficiency, and other conditions such as severe tricuspid regurgitation on repeat ultrasound, bilateral lower extremity edema, and inability to reduce or stop diuretics were found in five cases (6.6%). Compared with the group with the same dose of furosemide <40 mg/day group, the ≥40 mg/day group had a higher incidence of endpoints (12, 27.3% vs. 1, 3.1%, P = 0.006). CONCLUSION: In patients undergoing repeat tricuspid valve surgery due to severe tricuspid regurgitation after left-sided valvular surgery, a diuretic response was associated with surgical prognosis. Compared with the low-dose furosemide group, the high-dose group (≥40 mg/) had a significantly increased incidence of early events.

Distribution Pattern and Influencing Factors of Heavy Metal Resistance Genes in the Yellow River Sediments of Henan Section.

The transformation of heavy metal resistance genes (MRGs) in the environment has attracted increasing attention in recent years. However, few studies have reported the MRG content in the Yellow River, one of the main irrigation water sources in the North China Plain. In this study, we quantified MRG abundance by a metagenomic approach, and assessed the influence on MRGs of both bioavailable and total heavy metal (HM) content. The results indicate that Cu-resistant genes are the most common genes, and the prevalence of arsM needs more attention. Comamonadaceae is the dominant family in the Yellow River, and the presence of organic pollutants may contribute to the prevalence of Vicinamibacteraceae, Nocardioidaceae, and Flavobacteriacea. The results of the Mantel test and Spearman analysis indicate that both the bioavailable fractions and total content of HMs could have little influence on MRGs. Network analysis results indicate that some dominant bacteria could be the potential hosts of some prevalent MRGs, which may exert an adverse impact on human health.

Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors.

The elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Herein, we reported the discovery of a series of benzamide derivatives containing urea moiety as sEH inhibitors. Intensive structural modifications led to the identification of compound A34 as a potent sEH inhibitor with good physicochemical properties. Molecular docking revealed an additional hydrogen-bonding interaction between the unique amide scaffold and Phe497, contributing to sEH inhibition potency enhancement. Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC50 value of 0.04 ± 0.01 nM and a Ki value of 0.2 ± 0.1 nM. It also showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies. In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib. Metabolism studies in vivo together with an inflammatory pain evaluation suggest that A34 may be a viable lead compound for the development of highly potent sEH inhibitors.

Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors.

The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC50 value of 0.03 ± 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief.

PM2.5-Induced Programmed Myocardial Cell Death via mPTP Opening Results in Deteriorated Cardiac Function in HFpEF Mice.

PM2.5 exposure can induce or exacerbate heart failure and is associated with an increased risk of heart failure hospitalization and mortality; however, the underlying mechanisms remain unclear. This study focuses on the potential mechanisms underlying PM2.5 induction of cardiomyocyte programmed necrosis as well as its promotion of cardiac function impairment in a mouse model of heart failure with preserved ejection fraction (HFpEF). HFpEF mice were exposed to concentrated ambient PM2.5 (CAP) (CAP group) or filtered air (FA) (FA group) for 6 weeks. Changes in myocardial pathology and cardiac function were documented for comparisons between the two groups. In vitro experiments were performed to measure oxidative stress and mitochondrial permeability transition pore (mPTP) dynamics in H9C2 cells following 24 h exposure to PM2.5. Additionally, co-immunoprecipitation was conducted to detect p53 and cyclophilin D (CypD) interactions. The results showed exposure to CAP promoted cardiac function impairment in HFpEF mice. Myocardial pathology analysis and in vitro experiments demonstrated that PM2.5 led to mitochondrial damage in cardiomyocytes and, eventually, their necrosis. Moreover, our experiments also suggested that PM2.5 increases mitochondrial reactive oxygen species (ROS), induces DNA oxidative damage, and decreases the inner mitochondrial membrane potential (ΔΨm). This indicates the presence of mPTP opening. Co-immunoprecipitation results showed a p53/CypD interaction in the myocardial tissue of HFpEF mice in the CAP group. Inhibition of CypD by cyclosporin A was found to reverse PM2.5-induced mPTP opening and H9C2 cell death. In conclusion, PM2.5 induces mPTP opening to stimulate mitochondria-mediated programmed necrosis of cardiomyocytes, and it might exacerbate cardiac function impairment in HFpEF mice.

An Integrated Mutually Oriented "Chemical Profiling-Pharmaceutical Effect" Strategy for Screening Discriminating Markers of Underlying Hepatoprotective Effects to Distinguish Garden-Cultivated from Mountain-Cultivated Ginseng.

Garden-cultivated Ginseng (GG) and mountain-cultivated Ginseng (MG) both belong to Panax Ginseng C. A. Meyer. However, the effective substances which can be used to distinguish GG from MG remain obscure. Therefore, the purpose of this study was to screen for discriminating markers that can assist in the correct identification of GG and MG. HPLC Q-TOF/MS and various chemometrics methods were used to analyze the chemical profiles of 13 batches of Ginseng and to explore the characteristic constituents of both GG and MG. The hepatocyte-protecting effects of GG and MG were investigated through a paclitaxel-induced liver injury model. Through a combination of correlation analysis and bioinformatic techniques, markers for differentiation between GG and MG were ascertained. A total of 40 and 41 compounds were identified in GG and MG, respectively, and 15 characteristic ingredients contributed significantly to the discrimination of GG from MG. Correlation analysis and network pharmacology were applied and ginsenosides Rg1, Re, Rb1, Rc, Rb2, and Rg3 were found to be discriminating markers of GG and MG. Six markers for the identification of GG and MG were screened out by a step-wise mutually oriented "chemical profiling-pharmaceutical effect" correlation strategy, which is of great significance for future quality assessment of Ginseng products.

Real-time shear wave elastography evaluation of the correlation between brain tissue stiffness and body mass index in premature neonates.

BACKGROUND: Real-time shear wave elastography (SWE) is non-invasive and reliable for quantitatively evaluate stiffness of tissues and organs. Until now, little researches have applied SWE to evaluate brain tissue of premature neonates. This study sought to compare differences in the average brain tissue elasticity modulus (Emean) values of neonates, and explore the factors affecting these differences. METHODS: In total, 159 neonates admitted from December 2019 to February 2021 were taken as the study subjects and divided into 2 groups based on their time of birth. Premature neonates, full-term neonates, and neonates with neonatal pneumonia were included in this study. Of the 159 neonates, 76 were premature and 83 were full-term. SWE was used to quantitatively evaluate the Emean of bilateral paraventricular white matter, thalamus, and choroid, and to analyze the relationship between body mass index (BMI) and Emeans in both groups of neonates. RESULTS: The Emeans of the paraventricular white matter, thalamus, and choroid of the premature neonates were lower than those of the full-term neonates (P<0.001). The BMI of the premature and full-term neonates was positively correlated to the bilateral paraventricular white matter, thalamus, and choroid Emean. CONCLUSIONS: SWE can be used to quantitatively evaluate the brain tissue stiffness of neonates, and as a reference for neonatal brain-related diseases.

Evaluating Lymph Node Stiffness to Differentiate Bacterial Cervical Lymphadenitis and Lymph Node-First Presentation of Kawasaki Disease by Shear Wave Elastography.

OBJECTIVES: The purpose of our study was to evaluate the potential of cervical lymph node shear wave elastography (SWE) to quantify the lymph node stiffness (kilopascals) noninvasively among patients with lymph node-first presentation of Kawasaki disease (NFKD), patients with bacterial cervical lymphadenitis (BCL), and healthy children (HC). We further aimed to investigate the correlation of laboratory data and lymph node stiffness to provide a reference basis for the early diagnosis of NFKD. METHODS: Lymph node stiffness measurements were prospectively performed in 47 patients with NFKD, 56 patients with BCL, and 56 HC using SWE. Cervical SWE was compared in the groups. Factors associated with increased cervical lymph node stiffness were studied. RESULTS: The mean elasticity of the largest cervical lymph nodes was significantly higher in the BCL group than the NFKD and HC groups (mean elasticity ± SD, 16.37 ± 2.45, 12.22 ± 2.64, and 7.81 ± 1.67 kPa, respectively; P < .01), with a cutoff of 14.55 kPa (area under the curve, 0.885; sensitivity, 89%; and specificity, 76%). In patients with NFKD, interleukin 6 (standardized ß = 0.363; P = .01), alanine aminotransferase (standardized ß = 0.253; P = .03), aspartate aminotransaminase (standardized ß = 0.536; P = .047), and total bilirubin (standardized ß = 0.486; P < .01) values were correlated with increased largest cervical lymph node stiffness. CONCLUSIONS: Cervical lymph node stiffness was different between NFKD and BCL. Shear wave elastography is a potential method to identify clinically distinguishable early NFKD.

Assessment of myocardial function by two-dimensional speckle tracking echocardiography in patients with Kawasaki disease: a mid-term follow-up study.

BACKGROUND: Myocardial impairment proved by histological studies persists in late convalescent phase Kawasaki disease patients. Whether Kawasaki disease-induced myocardial lesions can be detected in an earlier time is not well explored. In this study, we aimed to evaluate left ventricular (LV) myocardial function by two dimensional speckle tracking echocardiography (2DSTE) in late convalescent phase Kawasaki disease patients. METHODS: A total of 68 Kawasaki disease patients during mid-term phase including 47 with no coronary artery aneurysm (NCAA) and 21 with coronary artery aneurysm (CAA), and 60 controls with age matched were consecutively enrolled. RESULTS: No significant differences on conventional echocardiographic LV systolic function indices were found among group comparison. Compared with controls, Kawasaki disease patients had lower global longitudinal stain (GLS) and global circumferential stain (GCS). In subgroup analysis, both those with CAA and without CAA had lower GLS, lower GCS, higher amino-terminal propeptide of type III procollagen (PIIINP) and higher carboxyterminal propeptide of procollagen type I (PIPC) than in controls. GLS had significantly negative correlations with PIIINP (r = -0.69, P = 0.002) and PIPC (r = -0.82, P = 0.000). CONCLUSION: Subclinical myocardial dysfunction in mid-term follow-up Kawasaki disease patients existed regardless of coronary artery status despite normal measurements of LV systolic function by routine echocardiography, and myocardial fibrosis may play a contributed role in this subclinical myocardial function impairment. 2DSTE is a valuable imaging modality for detecting regional and global myocardial dysfunction in Kawasaki disease patients in an early time.