Targeted exome sequencing strategy (NeoEXOME) for Chinese newborns using a pilot study with 3423 neonates.

BACKGROUND: Newborn screening (NBS) aims to detect congenital anomalies, and next-generation sequencing (NGS) has shown promise in this aspect. However, the NBS strategy for monogenic inherited diseases in China remains insufficient. METHODS: We developed a NeoEXOME panel comprising 601 genes that are relevant to the Chinese population found through extensive research on available databases. An interpretation system to grade the results into positive (high-risk, moderate-risk, and low-risk genotypes), negative, and carrier according to the American College of Medical Genetics (ACMG) guidelines was also developed. We validated the panel to evaluate its efficacy by using data from the "1000 Genomes Project" and conducted a pilot multicenter study involving 3423 neonates. RESULTS: The NGS positive rate in the 1000 Genomes Project was 7.6% (23/301), whereas the rate was 12.0% in the multicenter study, including 3249 recruited neonates. Notably, in 200 neonates, positive per conventional NBS, 58.5% (69/118) showed results consistent with NGS. In the remaining 3049 neonates showing negative results in conventional NBS, 271 (8.9%) were positive per NGS, and nine of them were clinically diagnosed with diseases in the follow-up. CONCLUSION: We successfully designed a NeoEXOME panel for targeted sequencing of monogenic inherited diseases in NBS. The panel demonstrated high performance in the Chinese population, particularly for the early detection of diseases with no biochemical markers.

A three-in-one versatile sensor for concise detecting biogenic amines and beef freshness.

Biogenic amines (BAs), as important indicators for evaluating food spoilage caused by fermentation processes or microbial activities, present significant risks of food safety. Consequently, the development of a simple, sensitive, and selective detection method for amines is of great importance. In this study, we proposed a three-in-one sensor 3,6-bis(dimethylamino)-9-(ethylthio)xanthylium (PSE) for high sensitivity and selectivity detecting BAs with multimodal responses, including olfactory, colorimetric, and fluorescent signals, thus facilitating convenient real-time detection of BAs. Mechanism study indicated that the nucleophilic substitution of PSE with BAs induced such rapid multi-responses with a low detection limit (LOD = 0.03 µM). We further fabricated PSE loaded paper for portable detection of BAs vapors. And the accurate determination of BAs levels is achieved through analyzing the RGB color mode. Finally, we successfully applied these test strips for non-destructive assessing meat beef freshness with the assistance of a smartphone in on-site scenarios.

Guest-Stimulated Nonplanar Porphyrins in Flexible Metal-Organic Frameworks.

Nonplanar porphyrins with out-of-plane distortions play crucial roles in many biological functions and chemical applications. The artificial construction of nonplanar porphyrins usually involves organic synthesis and modification, which is a highly comprehensive approach. However, incorporating porphyrins into guest-stimulated flexible systems allows to manipulate the porphyrin distortion through simple ad/desorption of guest molecules. Here, a series of porphyrinic zirconium metal-organic frameworks (MOFs) is reported that exhibit guest-stimulated breathing behavior. X-Ray diffraction analysis and skeleton deviation plots confirm that the material suffers from porphyrin distortion to form a ruffled geometry under the desorption of guest molecules. Further investigation reveals that not only the degree of nonplanarity can be precisely manipulated but also the partial distortion of porphyrin in a single crystal grain can be readily achieved. As Lewis acidic catalyst, the MOF with nonplanar Co-porphyrin exhibits active properties in catalyzing CO2 /propylene oxide coupling reactions. This porphyrin distortion system provides a powerful tool for manipulating nonplanar porphyrins in MOFs with individual distortion profiles for various advanced applications.

Differences of genomic alterations and heavy metals in non-small cell lung cancer with different histological subtypes.

PURPOSE: This study aimed to explore the correlations among heavy metals concentration, histologic subtypes and molecular characteristics in patients with non-small cell lung cancer (NSCLC). METHODS: In this study, an NGS panel of 82 tumor-associated genes was used to identify genomic alternations in 180 newly diagnosed patients with NSCLC. The concentrations of 18 heavy metals in the serum samples were detected by inductively coupled plasma emission spectrometry (ICP-MS). RESULTS: A total of 243 somatic mutations of 25 mutant genes were identified in 115 of 148 patients with LUAD and 45 somatic mutations of 15 mutant genes were found in 24 of 32 patients with LUSC. The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were markedly different between patients with LUAD and LUSC. Moreover, patients with LUSC were significantly positively correlated with Ba, but not LUAD. Lastly, patients with EGFR mutations presented significant negative correlations with Cd and Sr, whereas patients with TP53 mutations showed a significant positive correlation with Pb. CONCLUSION: The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were different between patients with LUAC and LUSC, and heavy metals (e.g., Ba, Pb, and Cd) may contribute to the tumorigenesis of NSCLC with different histological and molecular subtypes.

Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling.

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 µM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor ß-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.

Molecular Correlates of Early Onset of Diabetic Cardiomyopathy: Possible Therapeutic Targets.

Diabetes mellitus (DM) is associated with mitochondrial dysfunction and oxidative stress that can lead to diabetic cardiomyopathy (DCM), which can often remain undetected until late stages of the disease. However, myocardial injury occurs before the onset of measurable cardiac dysfunction, although its molecular correlates are poorly understood. In this study, we made a DM rat induced by a high-fat diet combined with low and high doses of streptozotocin (STZ) to emulate pre and early DCM. RNA-sequencing analysis of ventricular tissue revealed a differential transcriptome profile and abnormal activation of pathways involved in fatty acid metabolism, oxidative phosphorylation, cardiac structure and function, insulin resistance, calcium signalling, apoptosis, and TNF signalling. Moreover, using high glucose-treated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), we recapitulated the cardiac cellular phenotype of DM and identified several molecular correlates that may promote the development of DCM. In conclusion, we have developed an experimental framework to target pathways underlying the progression of DCM.

Untargeted metabolomic analysis of urine samples for diagnosis of inherited metabolic disorders.

Metabolomics has become an important tool for clinical research, especially for analyzing inherited metabolic disorders (IMDs). The purpose of this study was to explore the performance of metabolomics in diagnosing IMDs using an untargeted metabolomic approach. A total of 40 urine samples were collected: 20 samples from healthy children and 20 from pediatric patients, of whom 13 had confirmed IMDs and seven had suspected IMDs. Samples were analyzed by Orbitrap mass spectrometry in positive and negative mode alternately, coupled with ultra-high liquid chromatography. Raw data were processed using Compound Discovery 2.0 ™ and then exported for partial least squares discriminant analysis (PLS-DA) by SIMCA-P 14.1. After comparing with m/zCloud and chemSpider libraries, compounds with similarity above 80% were selected and normalized for subsequent relative quantification analysis. The uncommon compounds discovered were analyzed based on the Kyoto Encyclopedia of Genes and Genomes to explore their possible metabolic pathways. All IMDs patients were successfully distinguished from controls in the PLS-DA. Untargeted metabolomics revealed a broader metabolic spectrum in patients than what is observed using routine chromatographic methods for detecting IMDs. Higher levels of certain compounds were found in all 13 confirmed IMD patients and 5 of 7 suspected IMD patients. Several potential novel markers emerged after relative quantification. Untargeted metabolomics may be able to diagnose IMDs from urine and may deepen insights into the disease by revealing changes in various compounds such as amino acids, acylcarnitines, organic acids, and nucleosides. Such analyses may identify biomarkers to improve the study and treatment of IMDs.

Outcomes of non-left bundle branch block conduction abnormalities after transcatheter aortic valve replacement.

Transcatheteraortic valve replacement (TAVR) is a revolutionized treatment for severe aortic valve stenosis. Although new and improved TAVR devices are constantly being developed, cardiac conduction abnormalities post-TAVR requiring permanent pace14353maker implantation (PPMI) still occur frequently. Previously, pre-existing right bundle branch block (RBBB) has been shown to be predictive of PPMI after TAVR compared with patients without RBBB, while occurrence of new left bundle branch block (LBBB) was associated with a higher rate of PPMI. However, less attention has been paid to the clinical values of new onset non-LBBB conduction disturbances such as RBBB, left anterior fascicular block (LAFB) or atrioventricular block (AVB). To our knowledge, this is the first report focus on the association of new-onset non-LBBB and PPMI after TAVR. The study was approved by the Ethics Committee of HwaMei Hospital, University of Chinese Academy of Sciences.

Association of stent diameter and target vessel revascularization in patients undergoing percutaneous coronary intervention: a secondary retrospective analysis based on a Chinese cohort study.

BACKGROUND: In the treatment of coronary heart disease, target vessel revascularization (TVR) has attracted increasing attention as an efficient means of percutaneous coronary intervention (PCI). The purpose of this study was to explore the association between stent diameter and TVR in patients undergoing PCI. METHODS: This was a secondary retrospective analysis involving patients with PCI with at least one stent implanted. Information was obtained from the Dryad Digital Repository. Multivariable logistic regression models, interaction analyses, subgroup analyses and piecewise linear regression models were used to evaluate the association between stent diameter and TVR. RESULTS: A total of 2522 patients were eventually enrolled in this study, of which 122 (4.8%) had undergone TVR. Significant positive associations were observed between stent diameter and TVR (continuous: odds ratio [OR] 0.485, 95% confidence interval [CI] 0.305-0.773, P = 0.002; categorical variable: T2 vs. T1, OR 0.541, 95% CI 0.348-0.843; T3 vs. T1, OR 0.520, 95% CI 0.334-0.809; P for trend = 0.005). The association remained stable in the fully adjusted model (continuous: OR 0.526, 95% CI 0.306-0.902, P = 0.020; categorical variable: T2 vs. T1, OR 0.510, 95% CI 0.310-0.839; T3 vs. T1, OR 0.585, 95% CI 0.352-0.973; P for trend = 0.042). Among the subgroups of differing clinical presentations, stent diameter was a powerful protective factor for TVR, especially in the delayed PCI group (P for interaction = 0.002). The association was highly consistent across all the other subgroups studied (all P for interaction > 0.05). In the piecewise linear regression model, the need for TVR decreased with an increase in stent diameter when this ranged between 2.5 and 2.9 mm (OR 0.01, 95% CI: 0.01-0.13, P < 0.001). CONCLUSIONS: A large stent diameter is a powerful protective factor for TVR in PCI patients, especially in the delayed PCI group. This "bigger-is-better" protective effect is remarkable in stents with diameter 2.5-2.9 mm.

Increasing Fracture Risk Associates With Plasma Circulating MicroRNAs in Aging People's Sarcopenia.

Aging generally coincides with a gradual decline in mass and strength of muscles and bone mineral density (BMD). Sarcopenia is closely linked to osteoporosis in the elderly, which can lead to abnormal gait, balance disorders, and dysfunctions, as well as increase in the risks of falls, fractures, weakness, and death. MicroRNAs (miRNAs, miRs) are a kind of short and non-coding RNA molecules but can regulate posttranscriptional protein expression. However, we have known little about their participation in age-associated osteoporosis and sarcopenia. The current study aims to confirm those miRNAs as biomarkers for age-related reduction in muscular atrophy associated with human blood fractures. In our study, 10 fracture-risk-related miRNAs (miR-637, miR-148a-3p, miR-125b-5p, miR-124-3p, miR-122-5p, miR-100-5p, miR-93-5p, miR-21-5p, miR-23a-3p, and miR-24-3p) were analyzed. For the initial screening, we determined the abundance of fracture-risk-associated miRNAs by RT-PCR most frequently detected in enrolled 93 elderly with sarcopenia and non-sarcopenia, respectively. Statistically, the relative expression levels of plasma miR-23a-3p, miR-93-5p, and miR-637 in the sarcopenia group were significantly lower than that in the non-sarcopenia group, while the levels of other miRNAs did not change significantly. Moreover, we showed that the levels of ASM/height2, handgrip strength, and 4-m velocity in the sarcopenia group were significantly lower than in the non-sarcopenia group. Whereafter, we expanded the sample for further detection and analysis and revealed that the levels of plasma miR-23a-3p, miR-93-5p, and miR-637 in the sarcopenia group were significantly lower than that in the non-sarcopenia group, which is consistent with the initial screening experiment. From our analysis, changes in levels of plasma miR-93-5p and miR-637 were dramatically related to ASM/height2. Furthermore, changes in miR-23a and miR-93-5p were significantly affected by ASM/height2 in female individuals, with no significant correlations between miRNAs changes and these diagnostic indexes in male individuals after adjusting sex. The study showed that plasma miRNAs changed in an aging-related sarcopenia manner and were associated with increased fracture risk. In aging patients, plasma miR-23a-3p, miR-93-5p, and miR-637 have the potential as biomarkers of sarcopenia, which can affect the development of physiological dysfunction and may be also used in the fracture risk assessment of these patients.

Simultaneous quantification of fat-soluble vitamins A, 25-hydroxylvitamin D and vitamin E in plasma from children using liquid chromatography coupled to Orbitrap mass spectrometry.

The fat-soluble vitamins A, D, E and K are micronutrients essential for physiological activity, metabolism and growth. Accurate and sensitive analytical methods are needed to support growing research into fat-soluble vitamins and their impact on children's growth and health. Here we report the first method for simultaneous quantification of fat-soluble vitamins A (retinol), 25-hydroxylvitamin D2, 25-hydroxylvitamin D3, and vitamin E (α-tocopherol) using a Q-Exactive Orbitrap mass spectrometer in high-resolution, parallel reaction monitoring mode. This method can select desired ions with high efficiency, potentially making it superior to triple-quadrupole mass spectrometers that employ multiple reaction monitoring. The proposed method offers excellent accuracy, specificity, and sensitivity, as demonstrated with plasma samples from healthy children.

C4OH is a potential newborn screening marker-a multicenter retrospective study of patients with beta-ketothiolase deficiency in China.

BACKGROUND: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China. RESULTS: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel. CONCLUSION: This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.

Integrative identification of the pathogenic role of a novel G6PD missense mutation c.697G>C.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a hereditary disease caused by pathogenic mutations of G6PD. While most of the pathogenic variants of G6PD have been annotated, hemolysis of unknown etiology but analogous to that in G6PD deficiency persists, implying the existence of undocumented pathogenic variants. In our previous study, we reported four novel G6PD variants in China, for which the pathogenicity remains to be verified. METHODS: The variants were verified by exogenous expression in HEK-293 cells, and their functions were predicted by PolyPhen-2 and SIFT. The CRISPR/Cas9 system was exploited to edit the G6PD c.697G>C variant in HEK-293 cells and K562 cells. The expression of G6PD was detected by quantitative PCR (qPCR) and western blotting. The cell growth capacity was detected by the CCK-8 assay and crystal violet staining. The G6PD enzyme activity was reflected by the G6P/6PG ratio test. The apoptosis of cells was detected by Annexin V-APC/7-AAD staining. The secondary and crystallographic structures were denoted according to the literature and PyMOL software. The G6PD protein was purified from lysis of transformed Escherichia coli (E. coli) cell with Ni-charged Resin Column. The enzymatic activity was detected at different temperatures. RESULTS: The G6PD activity of exogenous G6PD c.697G>C in HEK-293 cells was significantly lower than that of wild type (WT) G6PD, a finding that was consistent with the observation in clinical samples. The functional predictions conducted by different algorithms indicated the damage role of the G6PD c.697G>C variant in its enzymatic activity. We recapitulated the G6PD c.697G>C variant both in HEK-293 cells and K562 cells by adapting the CRISPR/Cas9 strategy. Using distinct cell lines expressing the G6PD c.697G>C variant endogenously, we confirmed the deteriorative role of the G6PD c.697G>C variant in its enzymatic activity. Regarding the secondary and crystallographic structure, we found a mutated amino acid approaching the structural NADP+ binding site. Finally, we demonstrated the c.697G>C variant compromised the thermal stability of G6PD protein. CONCLUSIONS: Our data delineated the pathogenic role of G6PD c.697G>C variant for G6PD deficiency, implying the wide usage of CRISPR/Cas9 for genetic disease research.

Association between sleep disturbance with motoric cognitive risk syndrome in Chinese older adults.

BACKGROUND AND PURPOSE: Sleep disturbance and cognitive impairment are common and related in the elderly population worldwide. The aim of the present study was to explore the association between sleep disturbance and motoric cognitive risk (MCR) syndrome, which is characterized by subjective cognitive complaints and objective slow gait in older individuals without dementia or any mobility disability in the community-dwelling elderly Chinese population. METHODS: We recruited 940 participants aged ≥65 years from November 2016 to March 2017 in the Ningbo Community Study on Aging (NCSA). Self-reported sleep duration and sleep-quality variables, comprehensive geriatric evaluation, as well as indicators for diagnosing MCR syndrome were evaluated in this cross-sectional study. RESULTS: Multiple logistic regression analysis showed that a 1-SD increase in night (1.1 h) and 24-h sleep duration (1.3 h) was associated, respectively, with a 21% (95% confidence interval [CI], 1%-47%; p = 0.04) and 30% (95% CI, 3%-64%; p = 0.03) higher odds of having MCR syndrome. Considering sleep duration as a categorical variable, longer night-sleep duration (>8.5 h) was associated with MCR syndrome (OR, 2.03; p = 0.02) compared to shorter night-sleep duration (<8 h). For sleep-quality factors, increasing frequency of trouble falling asleep, waking early or easily, nightmares, and taking sleep drugs were significantly associated with MCR syndrome after adjusting for potential covariables (all p for trend < 0.05), but not for self-perceived sleep quality (p for trend = 0.10). CONCLUSIONS: Long sleep duration, poor sleep quality, and taking sleep drugs were associated with higher odds of having MCR syndrome in the community-dwelling elderly Chinese population. Further research is needed to explore the underlying mechanisms.

The Landscape of Actionable Genomic Alterations by Next-Generation Sequencing in Tumor Tissue Versus Circulating Tumor DNA in Chinese Patients With Non-Small Cell Lung Cancer.

Background: Circulating tumor DNA (ctDNA) sequence analysis shows great potential in the management of non-small cell lung cancer (NSCLC) and the prediction of drug sensitivity or resistance in many cancers. Here, we drew and compared the somatic mutational profile using ctDNA and tumor tissue sequence analysis in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), and assess its potential clinical value. Methods: In this study, 221 tumor tissues and 174 plasma samples from NSCLC patients were analyzed by hybridization capture-based next-generation sequencing (NGS) panel including 95 cancer-associated genes. Tumor response assessments were applied to 137 patients with advanced-stage (III and IV) NSCLC who first received targeted agents. Results: Twenty significantly mutated genes were identified such as TP53, EGFR, RB1, KRAS, PIK3CA, CD3EAP, CTNNB1, ERBB2, APC, BRAF, TERT, FBXW7, and HRAS. Among them, TP53 was the most frequently mutated gene and had a higher mutation probability in male (p = 0.00124) and smoking (p < 0.0001) patients. A total of 48.35% (191/395) of NSCLC patients possessed at least one actionable alteration according to the OncoKB database. Although the sensitivity of genomic profiling from ctDNA was lower than that from tumor tissue DNA, the mutational landscape of target genes from ctDNA is similar to that from tumor tissue DNA, which led to 61.22% (30/49) of mutational concordance in NSCLC. Additionally, the mutational concordance between tissue DNA and ctDNA in LUAD differs from that in LUSC, which is 63.83% versus 46.67%, indicating that NSCLC subtypes influence the specificity of mutation detection in plasma-derived ctDNA. Lastly, patients with EGFR and TP53 co-alterations showed similar responses to Gefitinib and Icotinib, and the co-occurring TP53 mutation was most likely to be a poor prognostic factor for patients receiving Gefitinib, indicating that the distributions and types of TP53 mutations may contribute to the efficacy and prognosis of molecular targeted therapy. Conclusions: As a promising alternative for tumor genomic profiling, ctDNA analysis is more credible in LUAD than in LUSC. Genomic subtyping has strong potential in prognostication and therapeutic decision-making for NSCLC patients, which indicated the necessity for the utility of target NGS in guiding clinical management.

Chinese expert brief consensus on newborn screening of inherited metabolic disorders during the novel coronavirus infection epidemic.

Novel coronavirus (2019-nCov) infection (COVID-19) rapidly spread across China and 25 countries in the worldwide, which infected not only adults but also children, even neonates. Each year, about 15 million newborns are delivered in China. Newborn screening (NBS) helps effectively prevent some mental retardation, premature death, and adverse outcomes in the early stage of baby, which could detect some inherited metabolic disorders (IMDs). During this COVID-19 epidemic, how to balance the risk of infected 2019-nCov and the risk of disability and teratogenesis of IMDs. Expert members of NBS extra quality assessment in National Clinical Center of Laboratory (NCCL) give a brief consensus for NBS of IMDs in the COVID-2019 epidemic, hoping that the brief consensus could be reference for NBS of IMDs in the other epidemic areas or periods all over the world.

Exosomes: Cell-Free Therapy for Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are an important cause of death and disease worldwide. Because injured cardiac tissue cannot be repaired itself, it is urgent to develop other alternate therapies. Stem cells can be differentiated into cardiomyocytes, endothelial cells, and vascular smooth muscle cells for the treatment of CVDs. Therefore, cell therapy has recently been considered a viable treatment option that can significantly improve cardiac function. Nonetheless, implanted stem cells rarely survive in the recipient heart, suggesting that the benefits of stem cell therapy may involve other mechanisms. Exosomes derived from stem cells have a myocardial protection function after myocardial injury, and may be a promising and effective therapy for CVDs. Here, we discuss the application and mechanism of exosomes derived from stem cells in the diagnosis and treatment of CVDs and provide evidence for the application of exosomes in CVDs. Graphical Abstract.

Circulating MicroRNAs in Plasma Decrease in Response to Sarcopenia in the Elderly.

sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is a major cause of morbidity and mortality in elders. Current diagnostic criteria of sarcopenia have not been agreed internationally, and the clinical diagnostic biomarkers for sarcopenia have not been identified. Circulating miRNAs (miRNAs, miRs) have recently been characterized as novel biomarkers for sarcopenia. However, the change of circulating miRNAs in response to sarcopenia are still not fully understood. Here, we enrolled a total of 93 elderly patients clinically diagnosed with sarcopenia and matching 93 non-sarcopenia elderly in this study. Specifically, levels of candidate circulating miRNAs which were involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were detected in these two groups. In small-sample screening experiments, plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels were significantly down-regulated in sarcopenia compared to those who non-sarcopenia. In contrast, miR-1, mir-133a, miR-133b, miR-21, miR-146a, miR-126, miR-221, and miR-20a were not changed significantly. Subsequently, we expanded the sample size to further detection and verification, and found that plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels in the sarcopenia group were significantly reduced compared to the non-sarcoma group, which is consistent with the results of the small-sample screening experiment. In addition, we showed that ASM/Height2, handgrip strength, knee extension and 4-meter velocity in sarcopenia group were significantly lower than those in non-sarcopenia group. Here we correlated the decrease of miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 in sarcopenia group and non-sarcopenia group with diagnostic indexes of sarcopenia (ASM/Height2, Handgrip strength and 4-meter velocity) after adjusting sex. The results showed that miR-208b and miR-155 changes were significantly correlated with handgrip strength in woman, miR-208b, miR-499, and miR-222 changes were significantly correlated with ASM/Height2 in man, while other miRNAs changes did not show a strong correlation with these diagnostic indexes. In conclusion, plasma miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 decrease in response to sarcopenia in the elderly. Although further studies are needed to clarify the potential use of circulating miRNAs as biomarkers of sarcopenia, present findings set the stage for defining circulating miRNAs as biomarkers and suggesting their physiological roles in elderly with sarcopenia.