LncRNA MALAT1 suppresses monocyte-endothelial cell interactions by targeting miR-30b-5p and enhancing ATG5-mediated autophagy.

Background: Monocyte-endothelial cell (EC) interactions are one of the earliest events in the development of atherosclerosis and play a crucial role in atherosclerotic plaque formation. Although attempts have been made to modulate this interaction, the underlying molecular signalling mechanisms remain unclear. This study aimed to investigate the role of long non-coding RNA MALAT1 in monocyte-EC interactions. Methods: The expression of MALAT1, ICAM-1, VCAM-1, P-selectin, CCL2 and CXCL1 was evaluated in ApoE-/- mouse aortic tissues and inflamed human umbilical vein endothelial cells (HUVECs). The regulatory impact of MALAT1 on cell adhesion molecules, monocyte-EC adhesion, and autophagy was assessed. The interactions between MALAT1 and microRNAs (miRNAs) were evaluated using dual-luciferase reporter and RNA pull-down assays. Results: MALAT1 expression decreased in ApoE-/- mouse aortic tissues and inflammatory HUVECs. MALAT1 overexpression suppressed the expression of ICAM-1, VCAM-1 and CXCL1, and reduced the migration and adhesion of monocytes to ECs. Inhibition of MALAT1 promoted cell adhesion molecule expression and monocyte-EC interactions. Mechanistically, MALAT1 binds directly to miR-30b-5p and decreases its effective expression by functioning as an endogenous sponge, thereby increasing the expression of autophagy-related gene 5 (ATG5) and stimulates endothelial autophagy. Conclusions: Our findings suggest that MALAT1 suppresses monocyte-EC interactions by targeting miR-30b-5p and enhancing ATG5-mediated endothelial autophagy. These data imply that MALAT1 may play a protective role at the early stages of the atherosclerotic process.

Prevalence of risk factors associated with rupture of abdominal aortic aneurysm (AAA): a single center retrospective study.

Background: Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease. The mortality rate for an AAA rupture is very high. Understanding the risk factors for AAA rupture would help AAA management, but little is known about these risk factors in the Chinese population. Methods: This retrospective study included patients that were diagnosed with AAA during the last 5 years in a large national hospital in southern China. AAA patients were divided into a rupture and non-rupture group. Clinical data were extracted from the hospital medical record system. Clinical features were compared between the rupture and non-rupture groups. The associations between potential risk factors and rupture risk were evaluated using a multivariate logistic regression analysis. Results: A total of 337 AAA patients were included for analysis in the present study. AAA diameter was significantly larger, and high-sensitivity C-reactive protein (hs-CRP) and serum creatinine levels were both significantly higher in AAA rupture patients. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels were significantly lower in AAA rupture patients. After adjustment, the multivariate logistic analysis found that AAA diameter and hs-CRP were independently positively associated with AAA rupture, and HDL-C level was adversely associated with AAA rupture. Conclusions: Our data suggests that larger AAA diameter and higher hs-CRP level are associated with a higher risk of AAA rupture, and higher HDL-C level is associated with a lower risk of AAA rupture. The results of this study may be helpful for the management of AAA patients in southern China.

USP10 regulates macrophage inflammation responses via stabilizing NEMO in LPS-induced sepsis.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome characterized by persistent inflammation and immunosuppression, leading to septic shock and multiple organ dysfunctions. Ubiquitin-specific peptidase 10 (USP10), a deubiquitinase enzyme, plays a vital role in cancer and arterial restenosis, but its involvement in sepsis is unknown. OBJECTIVE: In this study, we investigated the significance of USP10 in lipopolysaccharide (LPS)-stimulated macrophages and its biological roles in LPS-induced sepsis. METHODS: Lipopolysaccharides (LPS) were used to establish sepsis models in vivo and in vitro. We use western blot to identify USP10 expression in macrophages. Spautin-1 and USP10-siRNA were utilized for USP10 inhibition. ELISA assays were used to assess for TNF-α and IL-6 in vitro and in vivo. Nuclear and cytoplasmic protein extraction and Confocal microscopy were applied to verify the translocation of NF-κB. Mechanically, co-immunoprecipitation and rescue experiments were used to validate the regulation of USP10 and NEMO. RESULTS: In macrophages, we found that LPS induced USP10 upregulation. The inhibition or knockdown of USP10 reduced the pro-inflammatory cytokines TNF-α and IL-6 and suppressed LPS-induced NF-κB activation by regulating the translocation of NF-κB. Furthermore, we found that NEMO, the regulatory subunit NF-κB essential modulator, was essential for the regulation of LPS-induced inflammation by USP10 in macrophages. NEMO protein evidently interacted with USP10, whereby USP10 inhibition accelerated the degradation of NEMO. Suppressing USP10 significantly attenuated inflammatory responses and improved the survival rate in LPS-induced sepsis mice. CONCLUSIONS: Overall, USP10 was shown to regulate inflammatory responses by stabilizing the NEMO protein, which may be a potential therapeutic target for sepsis-induced lung injury.

Endothelial miR-199a-3p regulating cell adhesion molecules by targeting mTOR signaling during inflammation.

BACKGROUND: Adherence of monocytes to endothelial cells is the initial stage for development of coronary artery disease (CAD). MiRNAs have been reported to participate in this process by regulating the expression of cell adhesion molecules. This study aimed to explore the function of miR-199a-3p in endothelial inflammation and adhesion. METHODS: We assessed the expression of miR-199a-3p in CAD patients and ApoE-/- mice. The relationship between miR-199a-3p level and endothelial inflammation and adhesion was examined. ELISA was used to test the level of IL-6 and IL-8. Dual luciferase reporter assay was used to evaluate the binding between miR-199a-3p and mTOR. RESULTS: A decreased expression of miR-199a-3p was observed in the PBMCs and plasma of CAD patients, aorta of ApoE-/- mice and inflammatory HUVECs. MiR-199a-3p significantly suppressed the expression levels of pro-inflammatory cytokine (IL-6, IL-8), endothelial adhesion molecules (ICAM-1, VCAM-1) and monocyte-endothelial cells interaction. MiR-199a-3p directly targeted and repressed mTOR, and its suppression effect on ICAM-1 and VCAM-1 was abolished by mTOR inhibitor rapamycin, and rescued by mTOR activator MHY1485. Overexpression of miR-199a-3p promoted autophagy in HUVECs and inhibiting autophagy by chloroquine attenuated the effect of miR-199a-3p on ICAM-1 and VCAM-1 expression. Inhibition of autophagy promoted endothelial adhesion molecule expression and monocyte-EC interaction. CONCLUSIONS: Our results suggested that miR-199a-3p suppressed endothelial inflammation and adhesion by targeting mTOR signaling and increasing autophagy. Our findings point to an important role for miR-199a-3p in the early stage of cardiovascular disease.

Incidence and risk factors of in-stent restenosis after percutaneous coronary intervention in patients from southern China.

BACKGROUND: In-stent restenosis (ISR) remains a challenge for coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI) with stents, and risk factors for ISR are controversial. This study aimed to investigate the incidence and risk factors of ISR in patients from southern China. METHODS: In this retrospective study, patients diagnosed as acute coronary syndromes (ACS) and underwent successful PCI with drug-eluting stent (DES) and conducted a follow-up coronary angiography in Center for Cardiovascular Diseases of Meizhou People's Hospital at the period of January 1st, 2016 to January 1st, 2021 were included for analysis. The clinical and angiographic factors were compared between patients in ISR ( +) and ISR (-) groups. The association between variables and ISR was evaluated by multivariate logistic regression model. RESULT: A total of 341 ACS patients who had been installed at least 1 stent were included in this study. The follow-up time was 34.2 ± 17.2 months. During the follow-up period, 62 (18.2%) patients experienced ISR, and the average time for ISR was 32.8 months; the incidence of ISR for left main coronary artery, left anterior descending coronary artery, left circumflex artery coronary artery and right coronary artery were 6.7%, 20.9%, 19.4% and 14.4%, respectively; left ventricular ejection fraction (LVEF), stent number, stent type, statin therapy, antiplatelet therapy were significantly different between patients in ISR ( +) and ISR (-) group. Multivariate logistic analysis suggested that LVEF and stent number were significantly correlated with ISR. CONCLUSION: Our study revealed the incidence and risk factors of ISR in patients from southern China. Our data suggested that LVEF and stent number were independent risk factors associated with ISR.

Characterization of the B cell receptor repertoire of patients with acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is a complex cardiovascular disease whose development involves the dysregulation of adaptive immune responses. Though it has been proven that T cells associate with inflammation in the development of ACS, the function of B cells in disease remains unclear. OBJECTIVE: The aim of this study was to reveal the diversity of the B cell receptor (BCR) repertoire of patients with ACS. METHODS: We conducted a pilot study to sequence the immune repertoire of peripheral blood mononuclear cells (PBMCs) from patients with ACS, including acute myocardial infarction (AMI) and unstable angina (UA), and quantitatively characterized BCR repertoires by bioinformatics analysis. RESULTS: We found that patients with AMI and UA had lower BCR repertoire diversity compared with controls with normal coronary arteries (NCA). Lower percentages of productive unique BCR nt sequences and higher percentages of top 200 unique BCR sequences were identified in AMI and UA patients than NCA controls. Patients had various preferential usage of V and J genes from B cell clones in accordance with the disease severity of coronary arteries. AMI patients had distinct CDR3 amino acids, and their frequency differed among patients with ACS. CONCLUSIONS: Our results indicate that differential BCR signatures represent an imprint of distinct repertoires among ACS patients. This study thereby opens up the prospect of studying disease-relevant B cells to better understand and treat ACS.

Association between apolipoprotein E gene polymorphism and nonalcoholic fatty liver disease in Southern China: A case-control study.

BACKGROUND: Apolipoprotein E (ApoE) polymorphisms have been reported to be associated with nonalcoholic fatty liver disease (NAFLD), but the conclusions of studies are inconsistent in different regions. The present study aims to investigate the role of ApoE genotypes on NAFLD in southern China. METHODS: A total of 1064 subjects including 372 NAFLD patients and 692 controls who attended Meizhou People's Hospital located in southern China from March 1, 2016 to April 30, 2020 were enrolled in this study. The ApoE genotypes were detected and the laboratory parameters were examined. RESULTS: Significant differences were observed between NAFLD patients and controls in the prevalence of ε3/ε3 (p < 0.001) and ε3/ε4 (p = 0.004). NAFLD patients presented higher frequency of ε4 allele than controls (p = 0.013). Logistic regression analysis suggested that ε3/ε3 was an independent risk factor (OR: 1.435, 95% CI: 1.084-1.891, p = 0.010), while ε3/ε4 was an independent protective factor (OR: 0.578, 95% CI: 0.404-0.828, p = 0.003) for development of NAFLD. In addition, allele ε4 showed a protective effect on NAFLD with an adjusted OR of 0.588 (95% CI: 0.420-0.824, p = 0.002). CONCLUSION: Our results suggested that ApoE genotype was associated with the development of NAFLD in the population of southern China. Individuals carrying ε3/ε3 were at higher risk of NAFLD, while those carrying ε3/ε4 were at lower risk of NAFLD.

Characterization of LncRNA expression profile and identification of functional LncRNAs associated with unstable angina.

BACKGROUND: Increasing evidences suggest that long noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of coronary artery disease (CAD). However, the association between lncRNAs expression profiles and unstable angina (UA) remained poorly known. Thus, the present study aims to investigate expression patterns, biological functions, and diagnostic value of lncRNAs in UA. METHODS: The present study explored the lncRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of UA patients and normal coronary artery (NCA) controls using RNA-seq. The biological function of differentially expressed lncRNAs was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of the selected lncRNAs was validated in another 44 UA patients and 46 NCA controls. Receiver operating characteristic curve (ROC) was performed to evaluate the diagnostic value of lncRNAs for UA. RESULTS: A total of 98 lncRNAs and 615 mRNAs were observed differentially expressed in PBMCs of UA patients as compared to NCA controls. The 10 most upregulated lncRNAs were LNC_000226, DANCR, RP1-167A14.2, LNC_002091, LNC_001526, LNC_001165, LNC_002772, LNC_000088, LNC_001226, and FAM157C, and the 10 most downregulated lncRNAs were RP11-734I18.1, RP11-185E8.1, RP11-360I2.1, LNC_001302, LNC_001287, RN7SL471P, LNC_000914, LINC01506, RP11-160E2.6, and LNC_000995. LNC_000226 and MALAT1 have high area under the curve values (AUC) for distinguishing UA from NCA patients (0.810 and 0.799, respectively), and the combination of MALAT1 and LNC_000226 increased the AUC value to 0.878. CONCLUSIONS: The present study added our understanding about the lncRNA expression profile in UA patients and provided potential biomarkers for the diagnosis of UA.

Clonal diversity of the B cell receptor repertoire in patients with coronary in-stent restenosis and type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is known as a risk factor for coronary in-stent restenosis (ISR) in patients with coronary artery disease (CAD). Evidence suggests that B cells play a functional role in the progression of atherosclerotic lesions. However, the B cell receptor (BCR) repertoire in patients with ISR remains unclear. This study aims to profile the BCR repertoire in patients with coronary ISR/T2DM. A total of 21 CAD patients with or without ISR/T2DM were enrolled. PBMCs were isolated and examined for BCR repertoire profiles using DNA-seq. Our results showed that the diversity of amino acid sequences in ISR DM patients was higher than that in ISR -DM patients. The frequencies of 21 V/J paired genes differed between ISR DM and -ISR DM patients, while frequencies of 5 V/J paired genes differed between ISR DM and ISR -DM. The -ISR -DM group presented the highest clonotype overlap rate, while ISR DM patients presented the lowest overlap rate. Our study presented the BCR repertoires in patients with ISR/T2DM. The data suggested different BCR signatures between patients with ISR and T2DM. Further analysis of BCR profiles would enhance understanding of ISR.

Clinical effect of lymphocyte immunotherapy on patients with unexplained recurrent spontaneous abortion.

INTRODUCTION: Lymphocyte immunotherapy (LIT) is believed to be a viable treatment for unexplained recurrent spontaneous abortion (URSA), but its effect remains controversial. This study aims to investigate the clinical effect of LIT in patients with URSA and clarify the factors that may influence the outcome of LIT. METHODS: This study included a total of 704 URSA patients, of which 444 patients accepted LIT treatment. URSA patients that did not accept LIT served as control group. Clinical characteristics were collected and analyzed between LIT and control group. The blocking antibody was tested before and after LIT. The outcome of LIT treatment was recorded. Logistic regression analysis was applied to evaluate the independent predictors of LIT success. RESULTS: After LIT treatment, 77.9% (346/444) of USRA patients turned to BA positive, and the conversion rate elevated with increased LIT (p < .001). LIT significantly improved the pregnancy rate and live birth rate in USRA patients (65.3% vs. 29.6%, p < .001; 80.3% vs. 50.6%, p < .001). Multivariate regression analysis suggested that younger maternal age and positive BA were independent predictors of LIT success. CONCLUSION: LIT effectively induced the production of BA, and improved pregnancy rate and live birth rate in URSA patients. Our findings supported LIT as a beneficial treatment for URSA.

Circulating Exosomal microRNAs as Biomarkers of Systemic Lupus Erythematosus.

OBJECTIVES: Many studies indicate that microRNAs (miRNAs) could be potential biomarkers for various diseases. The purpose of this study was to investigate the clinical value of serum exosomal miRNAs in systemic lupus erythematosus (SLE). METHODS: Serum exosomes were isolated from 38 patients with SLE and 18 healthy controls (HCs). The expression of miR-21, miR-146a and miR-155 within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using receiver operating characteristic (ROC) curves, we evaluated the diagnostic value of exosomal miRNAs. RESULTS: Exosomal miR-21 and miR-155 were upregulated (p<0.01), whereas miR-146a expression (p<0.05) was downregulated in patients with SLE, compared to that in HCs. The expression of miR-21 (p<0.01) and miR-155 (p<0.05) was higher in SLE patients with lupus nephritis (LN) than in those without LN (non-LN). The analysis of ROC curves revealed that the expression of miR-21 and miR-155 showed a potential diagnostic value for LN. Furthermore, miR-21 (R=0.44, p<0.05) and miR-155 (R=0.33, p<0.05) were positively correlated with proteinuria. The expression of miR-21 was negatively associated with anti-SSA/Ro antibodies (R=-0.38, p<0.05), and that of miR-146a was negatively associated with anti-dsDNA antibodies (R=-0.39, p<0.05). CONCLUSIONS: These findings suggested that exosomal miR-21 and miR-155 expression levels may serve as potential biomarkers for the diagnosis of SLE and LN.

Elevated serum triglyceride predicts recurrence of colorectal polyps in patients with advanced adenomas.

BACKGROUND: Recurrence of colorectal polyps is common and impacted by various factors. This study was performed to explore the association between lipid profiles and recurrence of colorectal polyps. METHODS: This study retrospectively analyzed the lipid profiles of 435 patients who underwent colonoscopy with removal of colorectal polyps and assessed recurrence of polyps by follow-up colonoscopy. Multivariate regression logistic analysis was used to evaluate the association between lipid profiles and polyp recurrence. RESULTS: During the 1.5-year follow-up, recurrence of colorectal polyps was observed in 135 of 435 patients (30.34%). Patients with recurrent polyps showed a higher level of triglycerides (P = 0.006) and lower levels of high-density lipoprotein cholesterol (P = 0.008) and apolipoprotein A1 (P = 0.033). The multivariate regression logistic model suggested that an elevated triglyceride level was an independent risk factor for polyp recurrence (odds ratio, 1.55; 95% confidence interval, 1.02-2.35; P = 0.039) in patients with advanced adenoma. CONCLUSIONS: Lipid profiles are associated with recurrence of colorectal polyps. An elevated triglyceride level is an independent risk predictor of polyp recurrence in patients with advanced adenoma.

Circulating MicroRNA Expression Profiles in Patients with Stable and Unstable Angina.

OBJECTIVES: High incidence and case fatality of unstable angina (UA) is, to a large extent, a consequence of the lack of highly sensitive and specific non-invasive markers. Circulating microRNAs (miRNAs) have been widely recommended as potential biomarkers for numerous diseases. In the present study, we characterized distinctive miRNA expression profiles in patients with stable angina (SA), UA, and normal coronary arteries (NCA), and identified promising candidates for UA diagnosis. METHODS: Serum was collected from patients with SA, UA, and NCA who visited the Department of Cardiovascular Diseases of the Meizhou People's Hospital. Small RNA sequencing was carried out on an Illumina HiSeq 2500 platform. miRNA expression in different groups of patients was profiled and then confirmed based on that in an independent set of patients. Functions of differentially expressed miRNAs were predicted using gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis. RESULTS: Our results indicated that circulating miRNA expression profiles differed between SA, UA, and NCA patients. A total of 36 and 161 miRNAs were dysregulated in SA and UA patients, respectively. miRNA expression was validated by reverse transcription quantitative polymerase chain reaction. CONCLUSION: The results suggest that circulating miRNAs are potential biomarkers of UA.

Comprehensive analysis of T-cell receptor repertoire in patients with acute coronary syndrome by high-throughput sequencing.

BACKGROUND: This study aims to investigate the T-cell receptor (TCR) repertoire in patients with acute coronary syndrome (ACS). METHODS: The TCR repertoires of 9 unstable angina patients (UA), 14 acute myocardial infarction patients (AMI) and 9 normal coronary artery (NCA) patients were profiled using high-throughput sequencing (HTS). The clonal diversity of the TCR repertoires in different groups was analyzed, as well as the frequencies of variable (V), diversity (D) and joining(J) gene segments. RESULTS: ACS patients including UA and AMI, showed reduced TCRß diversity than NCA patients. ACS patients presented higher levels of clonal expansion. The clonotype overlap of complementarity determining region 3(CDR3) was significantly varied between different groups. A total of 10 V genes and 1 J gene were differently utilized between ACS and NCA patients. We identified some shared CDR3 amino acid sequences that were presented in ACS but not in NCA patients. CONCLUSIONS: This study revealed the distinct TCR repertoires in patients with ACS and demonstrated the presence of disease associated T-cell clonotypes. These findings suggested a role of T cells in ACS and provided a new way to explore the mechanisms of ACS.

Epidemiological investigation and antimicrobial susceptibility analysis of mycoplasma in patients with genital manifestations.

BACKGROUND: The aim of this study was to investigate the infection and antimicrobial resistance of Ureaplasma urealyticum and Mycoplasma hominis in patients with genitourinary symptoms among Hakka population in Meizhou, China. METHODS: A total of 12 633 females and 3315 males who presented urogenital symptoms and were subjected to mycoplasma tests from 2014 to 2018 were enrolled in this study. The mycoplasma detection and antimicrobial susceptibility were tested using the Mycoplasma ID/AST kit. RESULTS: The total incidence of mycoplasma infection, as well as the incidence of U urealyticum in Hakka population was annually increasing from 2014 to 2018. The total incidences and U urealyticum infection were more prevalent in females than males. Higher positive rate of mycoplasmas infection was observed in women aged 16-20 (50.9%) and men aged 26-30 (25.4%). The occurrence of antimicrobial resistance of mycoplasma to antibacterial agents remained relatively similar in the past five years. Ureaplasma urealyticum infection, M hominis infection, and co-infection of resistance to levofloxacin, erythromycin, ciprofloxacin, ofloxacin, roxithromycin, azithromycin, clarithromycin, and sparfloxacin were dramatically higher in females than in males. CONCLUSION: Our findings indicate a high burden of mycoplasmas infection and antimicrobial resistance of mycoplasmas infection among females, and josamycin and minocycline may be recommended as the primary choice in clinical treatment of anti-mycoplasmas.

Circulating microrna expression profiles in patients with stable and unstable angina

OBJECTIVES: High incidence and case fatality of unstable angina (UA) is, to a large extent, a consequence of the lack of highly sensitive and specific non-invasive markers. Circulating microRNAs (miRNAs) have been widely recommended as potential biomarkers for numerous diseases. In the present study, we characterized distinctive miRNA expression profiles in patients with stable angina (SA), UA, and normal coronary arteries (NCA), and identified promising candidates for UA diagnosis. METHODS: Serum was collected from patients with SA, UA, and NCA who visited the Department of Cardiovascular Diseases of the Meizhou People's Hospital. Small RNA sequencing was carried out on an Illumina HiSeq 2500 platform. miRNA expression in different groups of patients was profiled and then confirmed based on that in an independent set of patients. Functions of differentially expressed miRNAs were predicted using gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis. RESULTS: Our results indicated that circulating miRNA expression profiles differed between SA, UA, and NCA patients. A total of 36 and 161 miRNAs were dysregulated in SA and UA patients, respectively. miRNA expression was validated by reverse transcription quantitative polymerase chain reaction. CONCLUSION: The results suggest that circulating miRNAs are potential biomarkers of UA.

Circulating exosomal micrornas as biomarkers of systemic lupus erythematosus

OBJECTIVES: Many studies indicate that microRNAs (miRNAs) could be potential biomarkers for various diseases. The purpose of this study was to investigate the clinical value of serum exosomal miRNAs in systemic lupus erythematosus (SLE). METHODS: Serum exosomes were isolated from 38 patients with SLE and 18 healthy controls (HCs). The expression of miR-21, miR-146a and miR-155 within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using receiver operating characteristic (ROC) curves, we evaluated the diagnostic value of exosomal miRNAs. RESULTS: Exosomal miR-21 and miR-155 were upregulated (p<0.01), whereas miR-146a expression (p<0.05) was downregulated in patients with SLE, compared to that in HCs. The expression of miR-21 (p<0.01) and miR-155 (p<0.05) was higher in SLE patients with lupus nephritis (LN) than in those without LN (non-LN). The analysis of ROC curves revealed that the expression of miR-21 and miR-155 showed a potential diagnostic value for LN. Furthermore, miR-21 (R=0.44, p<0.05) and miR-155 (R=0.33, p<0.05) were positively correlated with proteinuria. The expression of miR-21 was negatively associated with anti-SSA/Ro antibodies (R=−0.38, p<0.05), and that of miR-146a was negatively associated with anti-dsDNA antibodies (R=−0.39, p<0.05). CONCLUSIONS: These findings suggested that exosomal miR-21 and miR-155 expression levels may serve as potential biomarkers for the diagnosis of SLE and LN.

Apolipoprotein E gene polymorphism and the risk of cardiovascular disease and type 2 diabetes.

BACKGROUND: The role of apolipoprotein E gene (APOE) in lipid metabolism has been well established, and APOE is associated with the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). However, the relationship between APOE polymorphisms and type 2 diabetes (T2DM) with or without CVD remains unclear. METHODS: In this cross-sectional study, a total of 924 participants including 211 controls (CVD-T2DM-), 247 T2DM patients with CVD (CVD-T2DM+), 232 CVD patients without T2DM (CVD + T2DM-) and 234 T2DM patients with CVD (CVD + T2DM+), were genotyped using chip platform. The association between APOE polymorphisms and T2DM patients with or without CVD was analyzed by univariable and multivariable logistic analysis. RESULTS: The present study showed that the frequency of E3/E4 increased in T2DM patients with CVD (p < 0.01). The ε4 allele was higher in CVD patients without T2DM (p < 0.01) and T2DM patients with CVD (p < 0.01) as compared with the controls. CONCLUSIONS: The subjects carrying ε4 allele have increased risk of CVD and T2DM, and exhibit higher level of lipid profiles.

Molecular analysis of hemoglobinopathies in a large ethnic Hakka population in southern China.

Thalassemia is an inherited autosomal recessive disorder with microcytic hypochromic anemia resulting from reduced or absent synthesis of 1 or more of the globin chains of hemoglobin. This study provided the insight into prevalence and molecular characterization of thalassemia in Hakka population. 14,524 unrelated subjects were included in our study from January 2015 to November 2017. All the subjects were detected by hematological analysis, hemoglobin electrophoresis analysis, and molecular diagnosis (gap-polymerase chain reaction and flow-through hybridization technology). Data analysis was used to compare allele frequencies between the Hakka populations. Seven thousand four hundred twenty-two cases of microcytosis were found. The percentage of microcytosis in Meizhou, Ganzhou, and Heyuan was 50.91% (6738/13,236), 51.27% (445/868), and 56.90% (239/420), respectively. A total of 5516 mutant chromosomes were identified, including 3775 α-thalassemia and 1741 ß-thalassemia. --/αα was the most common α-thalassemia genotype, followed by -α/αα and -α/αα, accounted for 84.92% of α-thalassemia genotypes. Twelve kinds of mutations and 26 genotypes in ß-thalassemia were found. IVS-II-654(C→T), CD41-42(-TCTT), -28(A→G), and CD17(A→T) alleles accounted for 92.65% of these mutations. IVS-II-654/N, CD41-42/N, -28/N, CD17/N genotypes accounted for 91.53% of ß-thalassemia genotypes. 27 fetuses with at-risk pregnancies were subjected to prenatal diagnosis. Five fetuses were Bart's hydrops syndrome and 2 fetuses with ß-thalassemia major. There were some differences in molecular characterization of thalassemia among Hakka people in different areas of southern China. Our results enriched the related information of thalassemia in the region, which provided valuable references for the prevention and control of thalassemia.