Selective effect of winter weather on a songbird's morphology depends on individual sex and winter condition.

Knowledge of the effect of harsh weather on the phenotypic traits of organisms is essential for understanding the environmental influence on phenotype evolution and holds implications for predicting how species respond to current climate change. For many birds, harsh weather in winter often imposes a strong selective effect on their survival, and only the individuals with certain phenotypes may survive. However, whether the selective effect on phenotype varies with winter weather conditions has been poorly investigated. Here, we explored the selective effect of winter weather on black-throated tit's (Aegithalos concinnus) morphological traits under winters with and without severe snowstorms. We found that for males, the sizes of their bills, heads and wings significantly affected their overwinter survival, but the effects varied with winter conditions. In relatively benign winters, males with smaller bill depths, smaller bill surface areas, and greater head lengths survived better; whereas, in winters with severe snowstorms, a reverse pattern was found. This phenomenon was likely driven by selection pressures from heat retention and foraging requirements, with their relative importance depending on winter conditions. Additionally, wing length was positively correlated with male survival and the relationship was stronger in harsher winters, which was probably due to longer wings' higher flight efficiency in adverse weather. By contrast, we found no correlation between morphological traits and survival in females. These results suggest a sex-specific and condition-dependent selective effect of environment on bird phenotypes, implying complicated interactions between different selection pressures and phenotype evolution.

Efficacy of revascularization in CTO patients based on hibernating myocardium therapy.

BACKGROUND: The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single-photon emission computed tomography (SPECT) and 18F-FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). METHODS: A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). RESULTS: After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008-1.052, p = .007). The cut-off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p = .035). A sensitivity analysis restricting patients with single-vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008-1.043, p = .005). CONCLUSION: HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO-PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large-scale studies.

A pseudo-targeted metabolomics for discovery of potential biomarkers of cardiac hypertrophy in rats.

Cardiac hypertrophy (CH) is one of the stages in the occurrence and development of severe cardiovascular diseases, and exploring its biomarkers is beneficial for delaying the progression of severe cardiovascular diseases. In this research, we established a comprehensive and highly efficient pseudotargeted metabolomics method, which demonstrated a superior capacity to identify differential metabolites when compared to traditionaluntargeted metabolomics. The intra/inter-day precision and reproducibility results proved the method is reliable and precise. The established method was then applied to seek the potential differentiated metabolic biomarkers of cardiac hypertrophy (CH) rats, and oxylipins, phosphorylcholine (PC), lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), Krebs cycle intermediates, carnitines, amino acids, and bile acids were disclosed to be the possible differentiate components. Their metabolic pathway analysis revealed that the potential metabolic alterations in CH rats were mainly associated with phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, citrate cycle, glyoxylate and dicarboxylate metabolism, and tyrosine metabolism. In sum, this research provided a comprehensiveand reliable LC-MS/MS MRM platform for pseudo-targeted metabolomics investigation of disease condition, and some interesting potential biomarkers were disclosed for CH, which merit further exploration in the future.

Development and validation of a predicting nomogram for in-hospital mortality of COVID-19 Omicron variant: A cohort study of 1324 cases in Beijing Anzhen Hospital.

Coronavirus disease 2019 (COVID-19) is continuously posing high global public health concerns due to its high morbidity and mortality. This study aimed to construct a convenient risk model for predicting in-hospital mortality of COVID-19 Omicron variant. A total of 1324 hospitalized patients with Omicron variant were enrolled from Beijing Anzhen Hospital. During hospitalization, the Omicron variant mortality rate was found to be 24.4%. Using the datasets of clinical demographics and laboratory tests, three machine learning algorithms, including best subset selection, stepwise selection, and least absolute shrinkage and selection operator regression analyses were employed to identify the potential predictors of in-hospital mortality. The results found that a panel of twenty-four clinical variables (including age, hyperlipemia, stroke, tumor, and several cardiovascular markers) identified by stepwise selection model exhibited significant performances in predicting the in-hospital mortality of COVID-19. The resultant nomogram showed good discrimination, highlighted by the areas under the curve values of 0.88 for 10 days, 0.81 for 20 days, and 0.82 for 30 days, respectively. Furthermore, decision curve analysis showed a significant reliability and precision for the established stepwise selection model. Collectively, this study developed an accurate and convenience risk model for predicting the in-hospital mortality of COVID-19 Omicron.

MF-MNER: Multi-models Fusion for MNER in Chinese Clinical Electronic Medical Records.

To address the problem of poor entity recognition performance caused by the lack of Chinese annotation in clinical electronic medical records, this paper proposes a multi-medical entity recognition method F-MNER using a fusion technique combining BART, Bi-LSTM, and CRF. First, after cleaning, encoding, and segmenting the electronic medical records, the obtained semantic representations are dynamically fused using a bidirectional autoregressive transformer (BART) model. Then, sequential information is captured using a bidirectional long short-term memory (Bi-LSTM) network. Finally, the conditional random field (CRF) is used to decode and output multi-task entity recognition. Experiments are performed on the CCKS2019 dataset, with micro avg Precision, macro avg Recall, weighted avg Precision reaching 0.880, 0.887, and 0.883, and micro avg F1-score, macro avg F1-score, weighted avg F1-score reaching 0.875, 0.876, and 0.876 respectively. Compared with existing models, our method outperforms the existing literature in three evaluation metrics (micro average, macro average, weighted average) under the same dataset conditions. In the case of weighted average, the Precision, Recall, and F1-score are 19.64%, 15.67%, and 17.58% higher than the existing BERT-BiLSTM-CRF model respectively. Experiments are performed on the actual clinical dataset with our MF-MNER, the Precision, Recall, and F1-score are 0.638, 0.825, and 0.719 under the micro-avg evaluation mechanism. The Precision, Recall, and F1-score are 0.685, 0.800, and 0.733 under the macro-avg evaluation mechanism. The Precision, Recall, and F1-score are 0.647, 0.825, and 0.722 under the weighted avg evaluation mechanism. The above results show that our method MF-MNER can integrate the advantages of BART, Bi-LSTM, and CRF layers, significantly improving the performance of downstream named entity recognition tasks with a small amount of annotation, and achieving excellent performance in terms of recall score, which has certain practical significance. Source code and datasets to reproduce the results in this paper are available at https://github.com/xfwang1969/MF-MNER .

Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Microplastics in three types of human arteries detected by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS).

Microplastics are ubiquitous in the environment. Human body can be exposed to microplastics through inhalation and ingestion and some microplastics can enter the blood and accumulate in various tissues and organs throughout the body. Animal experiments have suggested that microplastics may promote atherosclerosis. However, data on microplastics in human arteries and clinical evidence supporting a link between microplastics and atherosclerosis are currently lacking. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was used in this study to detect microplastics in three types of human arteries: coronary and carotid arteries with atherosclerotic plaques, as well as the aorta without plaques. Microplastics were detected in all 17 arterial samples, with an average concentration of 118.66 ± 53.87 µg/g tissue. Four types of microplastics were identified: polyethylene terephthalate (PET, 73.70%), polyamide-66 (PA-66, 15.54%), polyvinyl chloride (PVC, 9.69%), and polyethylene (PE, 1.07%). Most importantly, the concentration of microplastics in arteries containing atherosclerotic plaques, both coronary arteries (156.50 ± 42.14 vs. 76.26 ± 14.86 µg/g tissue, P = 0.039), and carotid arteries (133.37 ± 60.52 vs. 76.26 ± 14.86 µg/g tissue, P = 0.015), was significantly higher than that in aortas which did not contain atherosclerotic plaques, suggesting that microplastics might be associated with atherosclerosis in humans. This study provides valuable data for further hazard assessments of microplastics on human cardiovascular health.

Excessive daytime sleepiness is associated with increased residual cardiovascular risks among coronary artery disease patients with obstructive sleep apnea.

OBJECTIVE: Excessive daytime sleepiness (EDS) frequently accompanies obstructive sleep apnea (OSA) and may increase cardiovascular risks. The majority of coronary artery disease (CAD) patients receive understandard treatments, it is not clear whether EDS is associated with increased residual cardiovascular risks in CAD patients with OSA. METHOD: This study is a prospective cohort study that included 1215 consecutive CAD patients underwent overnight sleep study with a 3.7 year follow-up. Sleepiness was is determined by the Epworth Sleepiness Scale questionnaire. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, stroke, and heart failure. Kaplan-Meier model and Cox proportional hazards models were used to explore the relationship between residual cardiovascular risks and EDS. RESULT: 1027 cases were eventually enrolled, and a total of 129 patients experienced cardiovascular and cerebrovascular events. Participants with EDS had a higher risk of MACCE compared to those without EDS (17.02% vs. 9.58%, P = 0.005). The presence of EDS is associated with higher incidence of MACCE compared to non-EDS patients (HR 2.833; 95%CI:1.394-5.762; P < 0.001). EDS was significantly associated with increased incidence of MACCE in OSA patients (HR 1.765; 95%CI:1.276-2.543; P = 0.193), while there was no significant association between EDS and cardiovascular risks in non-OSA patients (HR 1.233; 95%CI: 0.893-2.755; P = 0.127). CONCLUSIONS: The existence of EDS may lead to increased cardiovascular risks, EDS is associated with increased cardiovascular risks in CAD patients, especially in patients with OSA.

Altitude explains insignificant autumn phenological changes across regions with large topography relief in the Tibetan Plateau.

The start of the growing season (SGS) and the end of the growing season (EGS) are widely employed in global change studies to represent the spring and autumn phenology, respectively. Despite the Tibetan Plateau (TP) experiencing significant warming in recent decades, EGS has exhibited only slight changes. Previous studies have concentrated on exploring the environmental regulation of phenology, ignoring the distinctive influences of elevation. Therefore, a more in-depth investigation into the underlying mechanism is warranted. In this study, we investigate the variability of EGS among alpine vegetation regions at different elevations and conduct an analysis based on satellite data. Phenology data of alpine vegetation are extracted from SPOT NDVI dataset spanning from 1999 to 2018, using a piecewise-logistic-maximum-ratio method. We analyze the factors influencing EGS trends at different elevations. The results show that the overall insignificant variation in EGS is mainly attributed to altitude. With the altitude increasing, the annual mean EGS experiences a delay of 0.28 days/100 m below 3500 m, while it advances by 0.2 days/100 m above 3500 m. The opposing shift in elevation below and above 3500 m leads to this counteraction. Elevation emerges as the predominant factor influencing EGS trends, explaining the highest variations (38 %), followed by SGS (22 %) and precipitation (22 %). The elevation effect is most pronounced in areas with substantial topography fluctuations. Moreover, the elevation lapse rate of EGS (ELR_EGS) exhibits an opposite trend with growing season (GS) temperature and a similar trend with GS precipitation between the regions below and above 3500 m, ultimately linking to this counteraction. This study underscores elevation is a critical regulator of vegetation EGS responses to climatic changes over the TP, revealing significant spatial heterogeneities in these responses.

Impact of Metabolic Syndrome on Post-Operative Infection in Patients Undergoing Flexible Ureteroscopy Lithotripsy.

Background: To investigate retrospectively whether metabolic syndrome (MetS) of flexible ureteroscopy (fURS) lithotripsy can be used to predict post-operative infection. Patients and Methods: After screening, 1,110 patients who received fURS lithotripsy for upper urinary tract stones in our center between January 2015 and December 2022 were analyzed retrospectively. Patients were divided into MetS-positive group and MetS-negative group. Post-operative infection was divided into fever, urosepsis, and septic shock. Relevant data during the peri-operative period were collected. Univariable and multivariable logistic regression analyses were adopted to estimate the impact of metabolic syndrome on post-operative infection in patients undergoing fURS lithotripsy. Results: Among the 1,110 patients, 427 tested positive for MetS, whereas 683 tested negative. Eighty-eight patients suffered from fever (67 patients in the MetS-positive group and 21 in the MetS-negative group). Forty-nine patients had urosepsis (29 patients in the MetS-positive group and 20 in the MetS-negative group), of whom seven patients developed septic shock. No patient developed multiple organ failure or died because of infection. The prevalence of post-operative infections in the MetS-positive group was higher than that in the MetS-negative group (p < 0.001). Multivariable logistic regression analyses showed that diabetes mellitus, MetS-positive, positive urine culture, and longer operation time were positively correlated with post-operative fever. Positive MetS, positive urine culture, and longer operation time were strongly correlated with post-operative urosepsis. Conclusions: Metabolic syndrome was found to be associated with post-operative infection in patients undergoing fURS lithotripsy, suggesting it can serve as a predictive factor.

Chiral Nanomaterials for Cancer Vaccines.

Chirality is a fundamental characteristic of living organisms and is commonly observed at the biomolecule, cellular, and tissue levels. Chiral nanomaterials play an irreplaceable role in nanomedicine and nanobiology because of their unique enantioselectivity with biological components. Here, research progress relating to chiral nanomaterials in the field of vaccines is reviewed, including antigen presenting systems, immune adjuvants, and cancer vaccines. First, the common synthesis methods are outlined for different types of chiral nanomaterials, as well as their chiral sources, optical properties, and potential biological applications. Then, the application of chiral nanomaterials are discussed in the field of vaccines with reference to the promotion of antigen presentation and activation of the immune system for tumor immunotherapy. Finally, the current obstacles and future research directions of chiral nanomaterials are revealed with regard to regulating the immune system.

The impact of negative pressure wound therapy on surgical wound infection, hospital stay and postoperative complications after spinal surgery: A meta-analysis.

To systematically assess the effect of negative pressure wound therapy (NPWT) on postoperative surgical wound infection, length of hospital stay and postoperative complications after spinal surgery. Relevant studies on the application of NPWT in spinal surgery were conducted via a computerised database search, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang, from inception to June 2023. The identified literature was rigorously screened and data extraction was performed by two investigators independently. The quality of the relevant studies was evaluated using the Newcastle-Ottawa scale (NOS). The effect size for count data was determined by the odds ratio (OR), while the impact size for measurement data was expressed as the standardised mean difference (SMD). The 95% confidence interval (CI) was calculated for each effect magnitude. Stata 17.0 software was used for the meta-analysis. Ten papers, totalling 1448 patients, were finally included. This study demonstrated that NPWT led to a statistically significant reduction in the occurrence of postoperative surgical wound infections (OR: 0.377, 95% CI: 0.238-0.598, p < 0.001), fewer postoperative complications (OR: 0.526, 95% CI: 0.360-0.770, p = 0.001) and a shortened hospital stay (SMD: -0.678, 95%CI: -1.324 to -0.031, p = 0.040) after spinal surgery compared with the control group. When compared with other treatment approaches, NPWT also demonstrated a substantial reduction in surgical wound infections and postoperative complications, as well as a shorter duration of hospitalisation after spinal surgery.

Ahdc1 is a potent regulator of obesity and energy metabolism.

AT-hook DNA-binding motif-containing protein 1 (AHDC1) is a causal gene of intellectual disability/developmental delay in humans. The biological role of AHDC1 is unclear. Recently, some clues from AHDC1 mutation carriers hinted that AHDC1 may participate in body-weight regulation. In this first metabolic phenotype study of Ahdc1 deficiency, we generated a Ahdc1-deficienct mouse line and found that Ahdc1 deficiency in both male and female mice led to adiposity from weaning and obesity characterized by reduced energy expenditure and respiratory quotient, with progressive development of hyperleptinemia, insulin resistance, abnormal glycolipid metabolism, and fatty liver. Our findings show that Ahdc1 is a novel key regulator of obesity and energy metabolism, which provides new insight into the physiological mechanisms of obesity.NEW & NOTEWORTHY In this first metabolic phenotype study of Ahdc1 deficiency, we generated a survivable Ahdc1-deficient mouse line. We found that Ahdc1 deficiency in both male and female mice resulted in adiposity from weaning and obesity characterized by reduced energy expenditure and respiratory quotient. Additionally, there was a progressive development of hyperleptinemia, insulin resistance, abnormal glycolipid metabolism, and fatty liver. These findings demonstrate that Ahdc1 is a novel key regulator of obesity and energy metabolism.

Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. METHODS: Two independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients (n = 184) from heterozygous FH (HeFH, n = 376) and non-FH (n = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients. RESULTS: Beyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients. CONCLUSIONS: Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.

Detection of Various Microplastics in Patients Undergoing Cardiac Surgery.

Microplastics have been detected in human stool, lungs, and placentas, which have direct exposure to the external environment through various body cavities, including the oral/anal cavity and uterine/vaginal cavity. Crucial data on microplastic exposure in completely enclosed human organs are still lacking. Herein, we used a laser direct infrared chemical imaging system and scanning electron microscopy to investigate whether microplastics exist in the human heart and its surrounding tissues. Microplastic specimens were collected from 15 cardiac surgery patients, including 6 pericardia, 6 epicardial adipose tissues, 11 pericardial adipose tissues, 3 myocardia, 5 left atrial appendages, and 7 pairs of pre- and postoperative venous blood samples. Microplastics were not universally present in all tissue samples, but nine types were found across five types of tissue with the largest measuring 469 µm in diameter. Nine types of microplastics were also detected in pre- and postoperative blood samples with a maximum diameter of 184 µm, and the type and diameter distribution of microplastics in the blood showed alterations following the surgical procedure. Moreover, the presence of poly(methyl methacrylate) in the left atrial appendage, epicardial adipose tissue, and pericardial adipose tissue cannot be attributed to accidental exposure during surgery, providing direct evidence of microplastics in patients undergoing cardiac surgery. Further research is needed to examine the impact of surgery on microplastic introduction and the potential effects of microplastics in internal organs on human health.

Comparison of computed tomography and magnetic resonance imaging findings and histopathological features of macrotrabecular-massive hepatocellular carcinoma.

Background: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel subtype of HCC, one of eight distinct subtypes, that accounts for 5% of all cases of HCC and is associated with a worse prognosis. Preoperative diagnosis of MTM-HCCs using imaging findings can facilitate patient treatment decision-making. The purpose of this study was to describe computed tomography (CT) and magnetic resonance imaging (MRI) findings of MTM-HCCs and compare these findings with histopathological features. Methods: This retrospective case-control study was performed at Shenzhen People's Hospital. The cohort included 17 patients with surgically confirmed MTM-HCCs and 232 patients with surgically confirmed non-MTM-HCCs who were enrolled by searching the pathological database from January 2018 to June 2022. CT and MRI findings were retrospectively analyzed and compared with pathological features. Student's t-test or Mann-Whitney U test for continuous variables and χ2 test or Fisher's exact test for categorical variables were implemented to compare imaging manifestations between MTM-HCCs and non-MTM-HCCs, as appropriate. Results: Seventeen tumors with a mean diameter of 8.58±2.83 cm were identified in the 17 patients. In addition to the typical findings of hepatocellular carcinomas (HCCs), such as arterial phase hyperenhancement (APHE), wash out, restricted diffusion, capsule and non-uptake at the hepatobiliary phase (HBP), the most common findings in MTM-HCCs were necrosis in 11 patients (64.7%, 11/17), followed by intratumoral arteries in 6 patients (35.3%, 6/17), peritumoral arterial transitive enhancement in 3 patients (17.6%, 3/17) and peritumoral hypointensive areas at the HBP in 3 of 8 patients (37.5%, 3/8) who received gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) enhancement. The tumor size of non-MTM-HCCs was 5.26±1.94 cm, which was smaller than the 8.58±2.83 cm of MTM-HCCs (P<0.001). The frequency of necrosis and intratumoral arteries was significantly higher in MTM-HCCs than in non-MTM-HCCs (necrosis: 64.7% vs. 34.6%, P=0.012; intratumoral arteries: 47.1% vs. 19.7%, P=0.008). Conclusions: MTM-HCCs tend to be large in size with intratumoral artery and intratumoral necrosis, which are characteristics that may distinguish them from non-MTM-HCCs.

Vascular smooth muscle cells specific deletion of angiopoietin-like protein 8 prevents angiotensin II-promoted hypertension and cardiovascular hypertrophy.

AIMS: Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 concentrations are increased in patients with hypertension and positively associated with blood pressure. ANGPTL8 deficiency ameliorates blood pressure in mice treated with chronic intermittent hypoxia. Currently, little is known regarding the pathophysiological role of the vascular smooth muscle cell (VSMC)-derived ANGPTL8 in hypertension and hypertensive cardiovascular remodelling. METHODS AND RESULTS: Circulating ANGPTL8 concentrations, as determined by enzyme-linked immunosorbent assay, were significantly higher in hypertensive patients than in controls (524.51 ± 26.97 vs. 962.92 ± 15.91 pg/mL; P < 0.001). In hypertensive mice [angiotensin II (AngII) treatment for 14 days] and spontaneously hypertensive rats, ANGPTL8 expression was increased and predominantly located in VSMCs. In AngII-treated mice, systolic and diastolic blood pressure in Tagln-Cre-ANGPTL8fl/fl mice were approximately 15-25 mmHg lower than that in ANGPTL8fl/fl mice. AngII-induced vascular remodelling, vascular constriction, and increased expression of cell markers of proliferation (PCNA and Ki67) and migration (MMP-2 and MMP-9) were strikingly attenuated in Tagln-Cre-ANGPTL8fl/fl mice compared with ANGPTL8fl/fl mice. Furthermore, the AngII-induced increase in the heart size, heart weight, heart/body weight ratio, cardiomyocyte cross-sectional area, and collagen deposition was ameliorated in Tagln-Cre-ANGPTL8fl/fl mice compared with ANGPTL8fl/fl mice. In rat artery smooth muscle cells, ANGPTL8-short hairpin RNA decreased intracellular calcium levels and prevented AngII-induced proliferation and migration through the PI3K-Akt pathway, as shown using LY294002 (inhibitor of PI3K) and Akt inhibitor VIII. CONCLUSION: This study suggests that ANGPTL8 in VSMCs plays an important role in AngII-induced hypertension and associated cardiovascular remodelling. ANGPTL8 may be a novel therapeutic target against pathological hypertension and hypertensive cardiovascular hypertrophy.

ANGPTL8 deletion attenuates abdominal aortic aneurysm formation in ApoE-/- mice.

Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 levels are increased in patients with thoracic aortic dissection (TAD). TAD shares several risk factors with abdominal aortic aneurysm (AAA). However, the role of ANGPTL8 in AAA pathogenesis has never been investigated. Here, we investigated the effect of ANGPTL8 knockout on AAA in ApoE-/- mice. ApoE-/-ANGPTL8-/- mice were generated by crossing ANGPTL8-/- and ApoE-/- mice. AAA was induced in ApoE-/- using perfusion of angiotensin II (AngII). ANGPTL8 was significantly up-regulated in AAA tissues of human and experimental mice. Knockout of ANGPTL8 significantly reduced AngII-induced AAA formation, elastin breaks, aortic inflammatory cytokines, matrix metalloproteinase expression, and smooth muscle cell apoptosis in ApoE-/- mice. Similarly, ANGPTL8 sh-RNA significantly reduced AngII-induced AAA formation in ApoE-/- mice. ANGPTL8 deficiency inhibited AAA formation, and ANGPTL8 may therefore be a potential therapeutic target for AAA.

Metabolomics and network analysis uncovered profound inflammation-associated alterations in hepatitis B virus-related cirrhosis patients with early hepatocellular carcinoma.

Patients with hepatitis B virus (HBV)-related liver cirrhosis (LC) are at high risk for hepatocellular carcinoma (HCC). Limitations in the early detection of HCC give rise to poor survival in this high-risk population. Here, we performed comprehensive metabolomics on health individuals and HBV-related LC patients with and without early HCC. Compared to non-HCC patients (N = 108) and health controls (N = 80), we found that patients with early HCC (N = 224) exhibited a specific plasma metabolome map dominated by lipid alterations, including lysophosphatidylcholines, lysophosphatidic acids and bile acids. Pathway and function network analyses indicated that these metabolite alterations were closely associated with inflammation responses. Using multivariate regression and machine learning approaches, we identified a five-metabolite combination that showed significant performances in differentiating early-HCC from non-HCC than α-fetoprotein (area under the curve values, 0.981 versus 0.613). At metabolomic levels, this work provides additional insights of metabolic dysfunction related to HCC progressions and demonstrates the plasma metabolites might be measured to identify early HCC in patients with HBV-related LC.