Disordered gut microbiota and alterations in the serum metabolome are associated with venous thromboembolism.

INTRODUCTION: The gut microbiome plays a crucial role in various diseases, and its regulation is a potential treatment option for these conditions. However, the relationship between the gut microbiome and venous thromboembolism (VTE) remains poorly explored. METHODS: In this study, we collected feces and serum samples from 8 VTE patients and 7 healthy controls. The gut microbiota and serum metabolites were analyzed using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Additionally, a combined analysis of microbiota and metabolome was performed. RESULTS: The alpha and beta diversity between the VTE and control groups were significantly different. Patients with VTE exhibited an overgrowth of Blautia, Roseburia, Coprococcus, and Ruminococcus. Moreover, serum metabolomics analysis revealed altered levels of choline and lithocholic acid. Pathway enrichment analysis indicated a significant upregulation of bile secretion pathways. In addition, a positive correlation was observed between the levels of serum choline and lithocholic acid and the abundance of gut flora enriched in the VTE group. CONCLUSION: This study provided novel insights into the disordered gut microbiota and serum metabolome associated with VTE, suggesting potential common pathological mechanisms between VTE and arterial thrombosis. Targeted modulation of the gut microbiome may hold promise as a preventive and therapeutic approach for VTE.

Oxidative stress in acute pulmonary embolism: emerging roles and therapeutic implications.

Oxidative stress is an imbalance between the body's reactive oxygen species and antioxidant defense mechanisms. Oxidative stress is involved in the development of several cardiovascular diseases, such as pulmonary hypertension, atherosclerosis, and diabetes mellitus. A growing number of studies have suggested the potential role of oxidative stress in the pathogenesis of pulmonary embolism. Biomarkers of oxidative stress in pulmonary embolism have also been explored, such as matrix metalloproteinases, asymmetric dimethylarginine, and neutrophil/lymphocyte ratio. Here, we comprehensively summarize some oxidative stress mechanisms and biomarkers in the development of acute pulmonary embolism and summarize related treatments based on antioxidant stress to explore effective treatment strategies for acute pulmonary embolism.

Tracheal microbiome and metabolome profiling in iatrogenic subglottic tracheal stenosis.

BACKGROUND: To study the role of microecology and metabolism in iatrogenic tracheal injury and cicatricial stenosis, we investigated the tracheal microbiome and metabolome in patients with tracheal stenosis after endotracheal intubation. METHODS: We collected 16 protected specimen brush (PSB) and 8 broncho-alveolar lavage (BAL) samples from 8 iatrogenic subglottic tracheal stenosis patients, including 8 PSB samples from tracheal scar sites, 8 PSB samples from scar-free sites and 8 BAL samples, by lavaging the subsegmental bronchi of the right-middle lobe. Metagenomic sequencing was performed to characterize the microbiome profiling of 16 PSB and 8 BAL samples. Untargeted metabolomics was performed in 6 PSB samples (3 from tracheal scar PSB and 3 from tracheal scar-free PSB) using high-performance liquid chromatography‒mass spectrometry (LC‒MS). RESULTS: At the species level, the top four bacterial species were Neisseria subflava, Streptococcus oralis, Capnocytophaga gingivals, and Haemophilus aegyptius. The alpha and beta diversity among tracheal scar PSB, scar-free PSB and BAL samples were compared, and no significant differences were found. Untargeted metabolomics was performed in 6 PSB samples using LC‒MS, and only one statistically significant metabolite, carnitine, was identified. Pathway enrichment analysis of carnitine revealed significant enrichment in fatty acid oxidation. CONCLUSION: Our study found that carnitine levels in tracheal scar tissue were significantly lower than those in scar-free tissue, which might be a new target for the prevention and treatment of iatrogenic tracheal stenosis in the future.

Circular RNAs Regulate Vascular Remodelling in Pulmonary Hypertension.

Circular RNAs (circRNAs) are a newly identified type of noncoding RNA molecule with a unique closed-loop structure. circRNAs are widely expressed in different tissues and developmental stages of many species, participating in many important pathophysiological processes and playing an important role in the occurrence and development of diseases. This article reviews the discovery, characteristics, formation, and biological function of circRNAs. The relationship between circRNAs and vascular remodelling, as well as the current status of research and potential application value in pulmonary hypertension (PH), is discussed to promote a better understanding of the role of circRNAs in PH. circRNAs are closely related to the remodelling of vascular endothelial cells and vascular smooth muscle cells. circRNAs have potential application prospects for in-depth research on the possible pathogenesis and mechanism of PH. Future research on the role of circRNAs in the pathogenesis and mechanism of PH will provide new insights and promote screening, diagnosis, prevention, and treatment of this disease.

Construction and analysis of the abnormal lncRNA-miRNA-mRNA network in hypoxic pulmonary hypertension.

The incidence of hypoxic pulmonary hypertension (HPH) is increasing. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in HPH, but the functions and mechanism have yet to be fully elucidated. In the present study, we established a HPH rat model with 8 h of hypoxia exposure (10% O2) per day for 21 days. High-throughput sequencing identified 60 differentially expressed (DE) lncRNAs, 20 DE miRNAs and 695 DE mRNAs in rat lung tissue. qRT-PCR verified the accuracy of the results. The DE mRNAs were significantly enriched in immune response, inflammatory response, leukocyte migration, cell cycle, cellular response to interleukin-1, IL-17 signalling pathway, cytokine-cytokine receptor interaction and Toll-like receptor signalling pathway. According to the theory of competing endogenous RNA (ceRNA) networks, lncRNA-miRNA-mRNA network was constructed by Cytoscape software, 16 miRNAs and 144 mRNAs. The results suggested that seven DE lncRNAs (Ly6l, AABR07038849.2, AABR07069008.2, AABR07064873.1, AABR07001382.1, AABR07068161.1 and AABR07060341.2) may serve as molecular sponges of the corresponding miRNAs and play a major role in HPH.

Independent association of severity of obstructive sleep apnea with lipid metabolism of atherogenic index of plasma (AIP) and apoB/apoAI ratio.

BACKGROUND: Cardiovascular diseases (CVDs) are highly prevalent in obstructive sleep apnea (OSA), and dyslipidemia is an important factor. Atherogenic index of plasma (AIP, log[TG/HDL-C]) and apolipoproteinB to apolipoproteinAI ratio (apoB/apoAI ratio) are considered high quality predictors of cardiovascular risk. However, the associations between OSA severity and AIP and apoB/apoAI ratio remained unclear. METHODS: A retrospective study was performed in 284 patients. Subjects were assessed with polysomnography (PSG) test, and OSA severity was defined by AHI. Data collected included anthropometric measurements, medical history, sleep parameters, fasting plasma lipids, fasting blood glucose, and insulin. RESULTS: Participants were classified based on AHI into the following groups: control group (n = 28), mild group (n = 52), moderate group (n = 53), and severe group (n = 151). Triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), apoAI, AIP, apoB/apoAI ratio (low-density lipoprotein cholesterol), LDL-C/HDL-C ratio, and HDL-C/apoAI ratio showed statistical significance among AHI subgroups (P < 0.05). The Pearson correlation analysis revealed that AIP (r = 0.32, P < 0.001) and apoB/apoAI ratio (r = 0.24, P < 0.001) were positively related to AHI. By multivariate linear regression analysis, we found that AHI was independently related to AIP (ß = 0.24, P = 0.001), apoB/apoAI ratio (ß = 0.24, P<0.001). CONCLUSION: AHI was independently correlated with AIP and apoB/apoAI ratio in OSA. Our findings suggested that AIP and apoB/apoAI ratio increased with OSA severity, which might be partly responsible for the high risk of CVDs in OSA.

Independent association of vitamin D and insulin resistance in obstructive sleep apnea.

BACKGROUND: Vitamin D insufficiency and/or high levels of parathyroid hormone (PTH) seem to be associated with abnormal glucose metabolism, which is frequent in obstructive sleep apnea (OSA). The purpose of this study was to investigate vitamin D and PTH concentrations in OSA, and to explore potential links between vitamin D, PTH and insulin resistance (IR). METHODS: A total of 112 subjects with suspected OSA were recruited consecutively, and evaluated by polysomnography (PSG) to determine the number of apnea and hypopnea episodes per hour of sleep (apnea/hypopnea index: AHI). OSA was diagnosed for AHI≥5. Average (APO2) and minimum pulse oxygen saturation (MPO2) were assessed during PSG as indices of nocturnal hypoxemia. After overnight fasting, a standard 75g oral glucose tolerance test was performed. Serum 25-hydroxyvitamin D, PTH, fasting glucose and fasting insulin were also measured. Homeostasis model assessment (HOMA) was used to evaluate IR: HOMA-IR=fasting plasma insulin×fasting plasma glucose/22.5, with "insulin resistance" defined as HOMA-IR>2.7. RESULTS: Patients were classified into 4 groups according to AHI: control group (AHI<5, n=8), mild OSA (5≤AHI<15, n=18), moderate OSA (15≤AHI<30, n=33), and severe OSA (AHI≥30, n=53). They were also classified, according to HOMA-IR, as insulin-resistant (HOMA-IR>2.7, n=59) or non-insulin-resistant (HOMA-IR≤2.7, n=45). There were no significant differences in vitamin D or PTH levels between AHI groups. HOMA-IR was significantly higher in severe OSA than in controls (P=0.019). Vitamin D concentration correlated negatively with AHI (r=-0.242, P=0.01) and with HOMA-IR (r=-0.338, P<0.001). PTH concentration correlated negatively with vitamin D concentration (P<0.001), but not with AHI or HOMA-IR. HOMA-IR correlated positively with AHI (r=0.368, P<0.001) and negatively with MPO2 (r=-0.414, P<0.001). Finally, stepwise linear multivariate regression showed that vitamin D concentration (ß=-0.209, P=0.014) and MPO2 (ß=-0.221, P=0.011) were independently associated with HOMA-IR. CONCLUSION: Subjects with severe OSA may have a low vitamin D level associated with increased risk of IR. Vitamin D was independently associated with IR in OSA. Vitamin D insufficiency may play a role in the pathogenesis of IR in OSA.

The association of hemocyte profile and obstructive sleep apnea.

BACKGROUND: The hemocyte profile is one of the most frequently requested clinical laboratory tests. However, the analysis of blood cell indexes of obstructive sleep apnea (OSA) patients in previous studies was not comprehensive. And, this study aimed to fully analyze the blood routine in OSA patients. METHODS: A retrospective study was conducted on 1087 male patients, who were admitted to the sleep center of Nanfang Hospital from May 2013 to February 2018. According to the apnea hypopnea index (AHI), patients were divided into four groups: control group (AHI < 5, n = 135), mild OSA (5 ≦ AHI < 15, n = 185), moderate OSA (15 ≦ AHI < 30, n = 171), and severe OSA (AHI ≧ 30, n = 596). Data collected included sleep parameters, complete blood routine, body mass index (BMI), age, and comorbidities. RESULTS: In our study, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, erythrocytes, hemoglobin, hematocrit, platelets, MPV, and PDW-SD were statistically significant among the four groups based on AHI (P < 0.05), but no significant differences were found in MCV, RDW-SD, N/L, and P/L ratio (P > 0.05). Neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, platelets, and MPV were significantly correlated with AHI. Moreover, multiple linear regression analysis demonstrated that hematocrit (ß = 73.254, P = 0.001), neutrophils (ß = 1.414, P = 0.012), and lymphocytes (ß = 4.228, P < 0.001) were independently associated with AHI. CONCLUSION: Neutrophils, lymphocytes, and hematocrit were independently associated with OSA severity. And combining these three blood cell indicators could contribute to the diagnosis of OSA.