Diagnostic, predictive and prognostic molecular biomarkers in clear cell renal cell carcinoma: A retrospective study.

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of kidney cancer. Many patients are diagnosed at advanced stages, making early detection crucial. Unfortunately, there are currently no noninvasive tests for ccRCC, emphasizing the need for new biomarkers. Additionally, ccRCC often develops resistance to treatments like radiotherapy and chemotherapy. Identifying biomarkers that predict treatment outcomes is vital for personalized care. The integration of artificial intelligence (AI), multi-omics analysis, and computational biology holds promise in bolstering detection precision and resilience, opening avenues for future investigations. The amalgamation of radiogenomics and biomaterial-basedimmunomodulation signifies a revolutionary breakthrough in diagnostic medicine. This review summarizes existing literature and highlights emerging biomarkers that enhance diagnostic, predictive, and prognostic capabilities for ccRCC, setting the stage for future clinical research.

SC-Net: Symmetrical conical network for colorectal pathology image segmentation.

BACKGROUND AND OBJECTIVE: Image segmentation of histopathology of colorectal cancer is a core task of computer aided medical image diagnosis system. Existing convolutional neural networks generally extract multi-scale information in linear flow structures by inserting multi-branch modules, which is difficult to extract heterogeneous semantic information under multi-level and different receptive field and tough to establish context dependency among different receptive field features. METHODS: To address these issues, we propose a symmetric spiral progressive feature fusion encoder-decoder network called the Symmetric Conical Network (SC-Net). First, we design a Multi-scale Feature Extraction Block (MFEB) matching with the Symmetric Conical Network to obtain multi-branch heterogeneous semantic information under different receptive fields, so as to enrich the diversity of extracted feature information. The encoder is composed of MFEB through spiral and multi-branch arrangement to enhance context dependence between different information flow. Secondly, the information loss of contour, color and others in high-level semantic information through causally stacking MFEB, the Feature Mapping Layer (FML) is designed to map low-level features to high-level semantic features along the down-sampling branch and solve the problem of insufficient global feature extraction in deep levels. RESULTS: The SC-Net was evaluated on our self-constructed colorectal cancer dataset, a publicly available breast cancer dataset and a polyp dataset. The results revealed that the mDice of segmentation reached 0.8611, 0.7259 and 0.7144. We compare our model with the state-of-art semantic segmentation UNet++, PSPNet, Attention U-Net, R2U-Net and other advanced segmentation networks. The experimental results demonstrate that we achieve the most advanced performance. CONCLUSIONS: The results indicate that the proposed SC-Net excels in segmenting H&E stained pathology images, effectively preserving morphological features and spatial information even in scenarios with weak texture, poor contrast, and variations in appearance.

From Short- to Long-Range Chiral Recognition on Surfaces: Chiral Assembly and Synthesis.

Research on chiral behaviors of small organic molecules at solid surfaces, including chiral assembly and synthesis, can not only help unravel the origin of the chiral phenomenon in biological/chemical systems but also provide promising strategies to build up unprecedented chiral surfaces or nanoarchitectures with advanced applications in novel nanomaterials/nanodevices. Understanding how molecular chirality is recognized is considered to be a mandatory basis for such studies. In this review, a series of recent studies in chiral assembly and synthesis at well-defined metal surfaces under ultra-high vacuum conditions are outlined. More importantly, the intrinsic mechanisms of chiral recognition are highlighted, including short/long-range chiral recognition in chiral assembly and two main strategies to steer the reaction pathways and modulate selective synthesis of specific chiral products on surfaces.

Novel SCN5A frame­shift mutation underlying in patient with idiopathic ventricular fibrillation manifested with J wave in inferior lead and prolonged S­wave in precordial lead.

Mutations in the SCN5A gene has been recognized as resulting in a series of life-threatening arrhythmias. However, it also causes idiopathic ventricular fibrillation (IVF) with J wave in inferior leads and prolonged S-wave upstroke in precordial leads, which has not been previously reported. The present study aimed to study the mechanisms of a patient with IVF manifested with J wave in inferior leads and prolonged S-wave upstroke in precordial leads. The electrocardiograms (ECG) of the proband were recorded and genetic testing was conducted. Patch-clamp and immunocytochemical studies were performed in heterologously transfected 293 cells. The VF attacks was documented in a 55-year-old male proband with syncope episodes. 12-lead ECG shown the transient J wave in the inferior leads and prolonged S-wave upstroke in precordial V1-V3 leads in the same timeframe. Genetic analysis revealed a novel 1 base deletion (G) at position 839 in exon 2 in SCN5A gene (C280S*fs61), which causes a severe truncation of the sodium channel. The functional study revealed that in 293 cells transfected with mutant channel, no sodium current could be recorded even though the immunocytochemical experiment confirmed the truncated sodium channel existed in cytosol. The kinetics of the wild-type (WT) channel were not altered when co-transfected with C280S*fs61 mutant which suggested a haploinsufficiency effect of sodium channel in the cells. The present study identified a novel C280Sfs*61 mutation that caused the 'loss of function' of the sodium channel by haploinsufficiency mechanism. The reduced sodium channel function in the heart may cause conduction delay that may underlie the manifestation of J wave and prolonged S-wave upstroke associated with IVF.

TaSPL14-7A is a conserved regulator controlling plant architecture and yield traits in common wheat (Triticum aestivum L.).

Plant architecture is a crucial influencing factor of wheat yield and adaptation. In this study, we cloned and characterized TaSPL14, a homologous gene of the rice ideal plant architecture gene OsSPL14 in wheat. TaSPL14 homoeologs (TaSPL14-7A, TaSPL14-7B and TaSPL14-7D) exhibited similar expression patterns, and they were all preferentially expressed in stems at the elongation stage and in young spikes. Moreover, the expression level of TaSPL14-7A was higher than that of TaSPL14-7B and TaSPL14-7D. Overexpression of TaSPL14-7A in wheat resulted in significant changes in plant architecture and yield traits, including decreased tiller number and increased kernel size and weight. Three TaSPL14-7A haplotypes were identified in Chinese wheat core collection, and haplotype-based association analysis showed that TaSPL14-7A-Hap1/2 were significantly correlated with fewer tillers, larger kernels and higher kernel weights in modern cultivars. The haplotype effect resulted from a difference in TaSPL14-7A expression levels among genotypes, with TaSPL14-7A-Hap1/2 leading to higher expression levels than TaSPL14-7A-Hap3. As favorable haplotypes, TaSPL14-7A-Hap1/2 underwent positive selection during global wheat breeding over the last century. Together, the findings of our study provide insight into the function and genetic effects of TaSPL14 and provide a useful molecular marker for wheat breeding.

Molecular characterization and clinical investigation of patients with heritable thoracic aortic aneurysm and dissection.

OBJECTIVES: Thoracic aortic aneurysm and dissection has a genetic predisposition and a variety of clinical manifestations. This study aimed to investigate the clinical and molecular characterizations of patients with thoracic aortic aneurysm and dissection and further explore the relationship between the genotype and phenotype, as well as their postoperative outcomes. METHODS: A total of 1095 individuals with thoracic aortic aneurysm and dissection admitted to our hospital between 2013 and 2022 were included. Next-generation sequencing and multiplex ligation-dependent probe amplification were performed, and mosaicism analysis was additionally implemented to identify the genetic causes. RESULTS: A total of 376 causative variants were identified in 83.5% of patients with syndromic thoracic aortic aneurysm and dissection and 18.7% of patients with nonsyndromic thoracic aortic aneurysm and dissection, including 8 copy number variations and 2 mosaic variants. Patients in the "pathogenic" and "variant of uncertain significance" groups had younger ages of aortic events and higher aortic reintervention risks compared with genetically negative cases. In addition, patients with FBN1 haploinsufficiency variants had shorter reintervention-free survival than those with FBN1 dominant negative variants. CONCLUSIONS: Our data expanded the genetic spectrum of heritable thoracic aortic aneurysm and dissection and indicated that copy number variations and mosaic variants contributed to a small proportion of the disease-causing alterations. Moreover, positive genetic results might have a possible predictive value for aortic event severity and postoperative risk stratification.

Improved in situ analysis of lead isotopes in low-Pb melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry.

RATIONALE: In situ Pb isotope analyses of tiny melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS) are crucial for exploring the origins of mafic lavas. However, quantitative use of this technique with low-Pb (<10 ppm) melt inclusions is difficult due to their low 204 Pb content and 204 Hg interference. METHODS: Pb isotopic ratios of various reference glasses and olivine-hosted melt inclusions were determined using LA-MC-ICP-MS. Multiple ion counters were used to simultaneously determine signal intensities of all Pb isotopes and 202 Hg. An Hg signal-removal smoothing device reduced its signal in the gas blank by >80%. Instrumental mass bias was corrected using the standard-sample bracketing method. RESULTS: With 24-90 µm diameter laser spots, 2-4 Hz repetition rates, and 2.5-4 J cm-2 energy fluence, the analytical precisions of 20x Pb/204 Pb ratios (x = 6, 7, 8) for standards BHVO-2G, ML3B-G, NIST 614, NKT-1G, T1-G, GOR132-G, and StHs6/80-G were <1.0% (2RSD) when 208 Pb signals >100 000 cps. The Wangjiadashan melt inclusions have 206 Pb/204 Pb = 17.14-18.44, 207 Pb/204 Pb = 15.28-15.66, and 208 Pb/204 Pb = 37.12-38.68. CONCLUSIONS: The described method improves the precision and accuracy of in situ Pb isotope analysis in low-Pb melt inclusions using LA-MC-ICP-MS. The Pb isotopic compositions of the Wangjiadashan melt inclusions indicate the coexistence of LoMu and EMII+young HIMU components in the mantle source of weakly alkaline basalts.

Metabolomic Profile Reveals That Ceramide Metabolic Disturbance Plays an Important Role in Thoracic Aortic Dissection.

AIMS: Thoracic aortic dissection (TAD) is a life-threatening disease with no effective drug therapy thus far. New therapeutic targets and indications for timely surgical intervention are urgently needed. Our aim is to investigate new pathological mechanisms and potential biomarkers of TAD through global metabolomic profiling of aortic aneurysm and dissection patients. METHODS AND RESULTS: We performed untargeted metabolomics to determine plasma metabolite concentrations in an aortic disease cohort, including 70 thoracic aortic aneurysm (TAA) and 70 TAD patients, as well as 70 healthy controls. Comparative analysis revealed that sphingolipid, especially its core metabolite C18-ceramide, was significantly distinguished in TAD patients but not in TAA patients, which was confirmed by subsequent quantitative analysis of C18-ceramide in a validation cohort. By analyzing our existing multiomics data in aortic tissue in a murine TAD model and TAD patients, we found that an enhanced ceramide de novo synthesis pathway in macrophages might contribute to the elevated ceramide. Inhibition of the ceramide de novo synthesis pathway by myriocin markedly alleviated BAPN-induced aortic inflammation and dissection in mice. In vitro studies demonstrated that exogenous C18-ceramide promoted macrophage inflammation and matrix metalloprotein (MMP) expression through the NLRP3-caspase 1 pathway. In contrast, inhibition of endogenous ceramide synthesis by myriocin attenuated lipopolysaccharide (LPS)-induced macrophage inflammation. CONCLUSIONS: Our findings demonstrated that ceramide metabolism disturbance might play a vital role in TAD development by aggravating aortic inflammation through the NLRP3 pathway, possibly providing a new target for pharmacological therapy and a potential biomarker of TAD.

A systematic study of mosaicism in heritable thoracic aortic aneurysm and dissection.

Mosaicisms are often overlooked in routine molecular diagnosis. Although not common, they are of great significance for accurate diagnosis and genetic counseling. In this study, we systematically evaluated the frequency of mosaicisms in both asymptomatic parents and affected patients with thoracic aortic aneurysm and dissection (TAAD). Next-generation sequencing (NGS) data from 1085 patients was reanalyzed with a more lenient allele frequency to detect potential mosaic variants. In addition, parental mosaicisms were investigated in 80 TAAD families. Finally, a total of six mosaic variants were detected in our cohort. Three of them were identified in symptomatic patients and three were in asymptomatic parents. Notably, a low-level mosaic variant in TGFB2 was detected combined with a causative FBN1 variant in patient AD2001, which might partially explain the clinical heterogeneity in his family. Our study hinted that it is necessary and feasible to implement mosaicism analysis in routine molecular diagnosis.

Metabolomic Characterization of Fatty Acids in Patients With Coronary Artery Ectasias.

Background: We used a targeted metabolomics approach to identify fatty acid (FA) metabolites that distinguished patients with coronary artery ectasia (CAE) from healthy Controls and patients with coronary artery disease (CAD). Materials and methods: Two hundred fifty-two human subjects were enrolled in our study, such as patients with CAE, patients with CAD, and Controls. All the subjects were diagnosed by coronary angiography. Plasma metabolomic profiles of FAs were determined by an ultra-high-performance liquid chromatography coupled to triple quadrupole mass spectrometric (UPLC-QqQ-MS/MS). Results: Ninety-nine plasma metabolites were profiled in the discovery sets (n = 72), such as 35 metabolites of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), 10 FAs, and 54 phospholipids. Among these metabolites, 36 metabolites of AA, EPA, and DHA showed the largest difference between CAE and Controls or CAD. 12-hydroxyeicosatetraenoic acid (12-HETE), 17(S)-hydroxydocosahexaenoic acid (17-HDoHE), EPA, AA, and 5-HETE were defined as a biomarker panel in peripheral blood to distinguish CAE from CAD and Controls in a discovery set (n = 72) and a validation set (n = 180). This biomarker panel had a better diagnostic performance than metabolite alone in differentiating CAE from Controls and CAD. The areas under the ROC curve of the biomarker panel were 0.991 and 0.836 for CAE versus Controls and 1.00 and 0.904 for CAE versus CAD in the discovery and validation sets, respectively. Conclusions: Our findings revealed that the metabolic profiles of FAs in the plasma from patients with CAE can be distinguished from those of Controls and CAD. Differences in FAs metabolites may help to interpret pathological mechanisms of CAE.

Novel LTBP3 mutations associated with thoracic aortic aneurysms and dissections.

BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a hidden-onset but life-threatening disorder with high clinical variability and genetic heterogeneity. In recent years, an increasing number of genes have been identified to be related to TAAD. However, some genes remain uncertain because of limited case reports and/or functional studies. LTBP3 was such an ambiguous gene that was previously known for dental and skeletal dysplasia and then noted to be associated with TAAD. More research on individuals or families harboring variants in this gene would be helpful to obtain full knowledge of the disease and clarify its association with TAAD. METHODS: A total of 266 TAAD probands with no causative mutations in known genes had been performed wholeexome sequencing (WES) to identify potentially pathogenic variants. In this study, rare LTBP3 variants were the focus of analysis. RESULTS: Two compound heterozygous mutations, c.625dup (p.Leu209fs) and c.1965del (p.Arg656fs), in LTBP3 were identified in a TAAD patient along with short stature and dental problems, which was the first TAAD case with biallelic LTBP3 null mutations in an Asian population. Additionally, several rare heterozygous LTBP3 variants were also detected in other sporadic TAAD patients. CONCLUSION: The identification of LTBP3 mutations in TAAD patients in our study provided more clinical evidence to support its association with TAAD, which broadens the gene spectrum of LTBP3. LTBP3 should be considered to be incorporated into the routine genetic analysis of heritable aortopathy, which might help to fully understand its phenotypic spectrum and improve the diagnostic rate of TAAD.

Analysis of Intestinal Flora and Levels of Epidermal Growth Factor Receptor, Interleukin-32, and Gastrin 17 in Patients with Gastric Cancer via Carbon Nanoparticle Laparoscopy.

In order to explore the changes of intestinal flora and serum levels of relevant substances in patients with gastric cancer before and after surgery with carbon nanoparticle laparoscopy, a total of 180 patients with early distal gastric cancer who adopted laparoscopic radical gastrectomy for distal gastric cancer in the general surgery department of TCM Hospital of Shi Jia Zhuang City from January 2018 to January 2020 were selected and randomly divided into two groups: traditional laparoscopic operation (control group) and carbon nanoparticle laparoscopic operation (experimental group) were adopted for treatment for the two groups, respectively. Postoperative evaluation included the difference between the two groups in the operative time, the efficiency of intraoperative lymph node dissection, and the number of lymph node detection. The adverse reactions, changes of intestinal flora before and after surgery in the two groups, and the serum levels of epidermal growth factor receptor (EGFR), interleukin-32 (IL-32), and gastrin 17 were evaluated. In the experimental group, the success rate of carbon nanoparticle tracer black staining reached 100%, and the operation time of the experimental group was significantly shorter than that of the control group (P < 0.05). The lymph node detection rate of the experimental group was higher than that of the control group (P < 0.05), but there was no significant difference in the lymph node metastasis rate between the two groups (P > 0.05). The sentinel lymph node sensitivity of the experimental group reached 92.3%, and the specificity, accuracy, and positive and negative prediction rates reached 100%; the experimental group patients were with an obviously higher incidence of level I-II gastrointestinal reaction (P < 0.05). Postoperative increases in Bifidobacteria and Lactobacillus were observed in both groups, while decreases in Enterococcus and Escherichia coli were observed in both groups (P < 0.05). Moreover, the degree of increase and decrease in the experimental group was greater than that in the control group (P < 0.05). The serum levels of EGFR, IL-32, and gastrin 17 in the two groups were significantly lower than those in the control group on 3 d, 7 d, and 15 d after surgery (P < 0.05). In the radical gastrectomy for distal gastric cancer, carbon nanoparticle laparoscopy was not only helpful for the localization of small tumors but also for the thorough dissection of lymph nodes after the surgery, and the postoperative adverse reactions of carbon nanoparticle laparoscopy were also less, which was of great significance for the improvement of intestinal flora and the reduction of serum levels of EGFR, IL-32, and gastrin 17 in gastric cancer patients.

Research on Rainfall Monitoring Based on E-Band Millimeter Wave Link in East China.

Accurate rainfall observation data with high temporal and spatial resolution are essential for national disaster prevention and mitigation as well as climate response decisions. This paper introduces a field experiment using an E-band millimeter-wave link to obtain rainfall rate information in Nanjing city, which is situated in the east of China. The link is 3 km long and operates at 71 and 81 GHz. We first distinguish between the wet and the dry periods, and then determine the classification threshold for calculating attenuation baseline in real time. We correct the influence of the wet antenna attenuation and finally calculate the rainfall rate through the power law relationship between the rainfall rate and the rain-induced attenuation. The experimental results show that the correlation between the rainfall rate retrieved from the 71 GHz link and the rainfall rate measured by the raindrop spectrometer is up to 0.9. The correlation at 81 GHz is up to 0.91. The mean relative errors are all below 5%. By comparing with the rainfall rate measured by the laser raindrop spectrometer set up at the experimental site, we verified the reliability and accuracy of monitoring rainfall using the E-band millimeter-wave link.

A novel point-of-care test of respiratory syncytial viral RNA based on cellulose-based purification and convective PCR.

BACKGROUND: Respiratory syncytial virus (RSV) infection is a global public-health problem. Timely diagnostics are needed for high-risk patients. Several methods have been used for RSV detection but not suitable for on-site detection due to the requirement of specialized laboratories and expensive equipment. METHODS: We developed a convenient, rapid and low-cost method of nucleic acids (NA) extraction based on cellulose paper, which could extract NA from nasopharyngeal swabs (NPSs) within 1 min. This extraction method was integrated with fluorescence convection polymerase chain reaction (CPCR), which easily affordable and easy-to-use NA detection of the RSV in 33 min. RESULTS: The developed cellulose-based NA purification combine with CPCR (CP-CPCR) reliably detected as little as 0.01 TCID50/mL of RSV cultures. CP-CPCR performance was tested further using NPSs: it showed sensitivity of 100% and a specificity of 100% compared with traditional extraction and amplification methods. CONCLUSIONS: Our evaluation confirmed high specificity, sensitivity and efficient of the CP-CPCR, which can be used widely for RSV testing in resource-limited settings.

Glucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype-phenotype association throughout an activity distribution.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common hereditary disorder in China. The existing prevalence and molecular epidemiology of G6PD deficiency in China were geographically limited. In this study, the spectrum of G6PD gene mutations was well characterized in a large and diverse population all over the country; and the correlation of genotype and enzyme activity phenotype was explored for the first time. The results showed that the overall prevalence of G6PD deficiency in China was 2.10% at the national level. The top six common mutations were c.1388 G>A, c.1376 G>T, c.95 A>G, c.392 G>T, c.871 G>A and c.1024 C>T, accounting for more than 90% of G6PD deficient alleles. Compound mutation patterns were frequently observed in females with severe deficiency. The distribution of G6PD activities depended on the type of mutation patterns and genders. Hemizygote, homozygote, and compound heterozygote were predominantly associated with severe G6PD deficiency, whereas heterozygotes with single mutation mainly presented moderate enzyme deficiency. A significant gap between G6PD activities in hemizygous and normal males was observed, and yet, the overall distribution of that in females carrying missense mutations was a continuum from G6PD severely deficient to normal. This is the first report of discussing the association between G6PD genetic variants in the Chinese and enzyme activity phenotypes.

Targeted Genetic Analysis in a Chinese Cohort of 208 Patients Related to Familial Hypercholesterolemia.

AIM: Familial hypercholesterolemia (FH) is the most commonly encountered genetic condition that predisposes individuals to severe autosomal dominant lipid metabolism dysfunction. Although more than 75% of the European population has been scrutinized for FH-causing mutations, the genetic diagnosis proportion among Chinese people remains very low (less than 0.5%). The aim of this study was to identify genetic mutations and help make a precise diagnosis in Chinese FH patients. METHODS: We designed a gene panel containing 20 genes responsible for FH and tested 208 unrelated Chinese possible/probable or definite FH probands. In addition, we called LDLR copy number variation (CNVs) with the panel data by panelcn.MOPS, and multiple ligation-dependent probe amplification (MLPA) was used to search for CNVs in LDLR, APOB, and PCSK9. RESULTS: A total of 79 probands (38.0%) tested positive for a (likely) pathogenic mutation, most of which were LDLR mutations, and three LDLR CNVs called from the panel data were all successfully confirmed by MLPA analysis. In total, 48 different mutations were identified, including 45 LDLR mutations, 1 APOB mutation, 1 ABCG5 mutation, and 1 APOE mutation. Among them, the five most frequent mutations (LDLR c.1879G＞A, c.1747C＞T, c.313＋1G＞A, c.400T＞C, and APOB c.10579C＞T) were detected. Moreover, we also found that patients with LDLR variants of CNVs and splicing and nonsense had increased low-density lipoprotein cholesterol levels when compared with those who carried missense variants. CONCLUSIONS: The spectrum of FH-causing mutations in the Chinese population is refined and expanded. Analyses of FH causal genes have been a great help in clinical diagnosis and have deep implications in disease treatment. These data can serve as a considerable dataset for next-generation sequencing analysis of the Chinese population with FH and contribute to the genetic diagnosis and counseling of FH patients.

Alterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms.

Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.

Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis.

Intracerebral hemorrhage (ICH) is a catastrophic stroke with high mortality, and the mechanism underlying ICH is largely unknown. Previous studies have shown that high serum uric acid (SUA) levels are an independent risk factor for hypertension, cardiovascular disease (CVD), and ischemic stroke. However, our metabolomics data showed that SUA levels were lower in recurrent intracerebral hemorrhage (R-ICH) patients than in ICH patients, indicating that lower SUA might contribute to ICH. In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II)-induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is the first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrovascular rupture during the ICH process.

Comparison of electrolyte and glucose levels measured by a blood gas analyzer and an automated biochemistry analyzer among hospitalized patients.

BACKGROUND: Blood gas analyzers are capable of delivering results on electrolytes and metabolites within a few minutes and facilitate clinical decision-making. However, whether the results can be used interchangeably with values measured by chemistry analyzers remains controversial. Blood gas analyzers are capable of delivering results on electrolytes and metabolites within a few minutes and facilitate clinical decision-making. However, whether the results can be used interchangeably with values measured by chemistry analyzers remains controversial. METHODS: In total, arterial and matched venous blood samples were collected from 200 hospitalized patients. Arterial blood samples were evaluated using a RAPIDPOINT 500 to test electrolyte and glucose levels, then the samples were centrifuged and the same parameters were measured with an AU5800. Venous blood samples were processed and tested in accordance with standard operation procedures. Data were compared by using a paired t test, the agreement between the two analyzers was evaluated by using the Bland-Altman test, and sensitivity and specificity were calculated. RESULTS: Paired t tests showed that all parameters tested were significantly different between the two analyzers except chloride. The biases calculated indicated that blood gas analyzers tend to underestimate the parameters, and the linear regression showed a strong correlation between the two analyzers. The sensitivity, specificity and kappa values demonstrated that the diagnostic performance of blood gas analyzers is not satisfactory. CONCLUSION: The significant reduction in parameter estimation and diagnostic performance we observed suggested that clinicians should interpret results from blood gas analyzers more cautiously. The reference interval of blood gas analyzers should be adjusted accordingly, given that values are underestimated.

Oleic Acid Attenuates Ang II (Angiotensin II)-Induced Cardiac Remodeling by Inhibiting FGF23 (Fibroblast Growth Factor 23) Expression in Mice.

Plasma metabolic profiles were compared between patients with hypertension with and without left ventricular hypertrophy and significantly decreased oleic acid (OA) levels were observed in the peripheral blood of patients with hypertension with left ventricular hypertrophy. We sought to determine the effect and underlying mechanisms of OA on cardiac remodeling. In vitro studies with isolated neonatal mouse cardiomyocytes and cardiac fibroblasts revealed that OA significantly attenuated Ang II (angiotensin II)-induced cardiomyocyte growth and cardiac fibroblast collagen expression. In vivo, cardiac function, hypertrophic growth of cardiomyocytes, and fibrosis were analyzed after an Ang II (1000 ng/kg/minute) pump was implanted for 14 days. We found that OA could significantly prevent Ang II-induced cardiac remodeling in mice. RNA sequencing served as a gene expression roadmap highlighting gene expression changes in the hearts of Ang II-induced mice and OA-treated mice. The results revealed that FGF23 (fibroblast growth factor 23) expression was significantly upregulated in mouse hearts in response to Ang II infusion, which was significantly suppressed in the hearts of OA-treated mice. Furthermore, overexpression of FGF23 in the heart by injection of an AAV-9 vector aggravated Ang II-induced cardiac remodeling and impaired the protective effect of OA on cardiac remodeling. Further study found that OA could suppress Ang II-induced FGF23 expression by inhibiting the translocation of Nurr1 (nuclear receptor-related 1 protein) from the cytoplasm to the nucleus. Our findings suggest a novel role of OA in preventing Ang II-induced cardiac remodeling via suppression of FGF23 expression.