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Background: In recent years, two-dimensional speckle tracking echocardiography (2D-STE) has been increasingly used to detect left ventricular myocardial ischemia with high accuracy for a reliable and comprehensive assessment of myocardial function by myocardial strain analysis. The present study aimed to assess whether the longitudinal strain (LS) bull’s eye plot could accurately detect left ventricular myocardial ischemia in homozygous familial hypercholesterolemia (HoFH) patients. Methods: A total of 28 HoHF patients, who underwent 2D-STE and myocardial perfusion imaging (MPI), were classified into two groups as diagnosed by MPI for myocardial ischemia. The myocardial ischemia score by MPI, LS bull’s-eye plot, and strain parameters were analyzed and compared. Results: Among the 28 HoFH patients, MPI detected 30.77% and 2D-STE showed 30.19% ischemic segments in 13 and 15 HoFH patients with myocardial ischemia, respectively. All segmental LSs in the left anterior descending artery (LAD) perfusion territory were significantly decreased in patients with myocardial ischemia. The diagnostic capability of 2D-STE for myocardial ischemia was 85.29%, 95.34%, and 93.91% for sensitivity, specificity and accuracy, respectively. Conclusion: Left ventricular LS bull’s-eye plot can assist rapid and accurate evaluation of myocardial ischemia in HoFH patients. The myocardial ischemia is mainly distributed in the LAD perfusion territory in these patients.

Aim: This study explored new immunoadjuvants with stronger immune activity to enhance therapeutic effects against leukemia. Materials & methods: Whole blood and bone marrow of acute myeloid leukemia (AML) patients and healthy volunteers were collected. Isolated mononuclear cells were treated with two newly designed CpG oligodeoxynucleotides, CpG sequence 13 and 19, and known CpG oligodeoxynucleotides and analyzed via flow cytometry. Results: CpG Seq 13 and 19 possess strong immune activation and enhance the proliferation, degranulation and cytotoxicity of T cells. They also inhibit AML cell proliferation. When CpG Seq 13/19 are combined with anti-OX40 antibodies, the cytotoxicity of T cells on AML cells are further enhanced. Conclusion: CpG Seq 13 and 19 are strong immune adjuvant candidates for AML treatment.

Background This case report describes the clinical process of a shepherd who suffered brucellosis-related endocarditis (BE) and spondylitis (BS) and was infected with Brucella melitensis biovar 3 (B. melitensis biovar 3). Case presentation A 55-year-old male patient was admitted to The First Affiliated Hospital of Shihezi University on October 11, 2018, due to over 3 months of intermittent fever, back pain, and heart trouble. The Rose Bengal Plate test was positive, the standard agglutination test titer for brucellosis was 1/800, and the blood culture was positive for B. melitensis biovar 3. Three instances of transthoracic echocardiography examination at days 1, 25, and 376 after admission to the hospital and magnetic resonance imaging (MRI) and computed tomography (CT) checks at days 5 and 38 revealed that the size of the vegetation on the posterior leaflet of the mitral valve increased from 0.7 × 1.4 cm to 1.2 × 1.5 cm and that the left atrium and ventricle were enlarged. The MRI and CT results showed hyperplasia of the second and third vertebra, a cold abscess formed on both sides of the psoas major muscles, and the vertebra hyperplasia became aggravated at a later time point. The patient’s situation deteriorated, and heart failure was discovered on October 22, 2019. At the moment of submission of this manuscript, the patient remains in bed at home because of severe debility caused by brucellosis. Conclusions This is the first reported case of endocarditis combined with spondylitis caused by B. melitensis biovar 3 in a shepherd. Brucellosis infection can cause work-power losses because of misdiagnosis or a lack of proper treatment. Early diagnosis and treatment are essential for a successful outcome.

The balance between Th17 cells and T regulatory (Treg) cells has emerged as a prominent factor in regulating cancer development. However, the effect of CpG oligodeoxynucleotides (ODNs) on the differentiation of Treg/Th17 cells has not been well studied. We sought here to explore the function of CpG ODNs in the differentiation of Tregs and Th17 cells in vitro and in vivo.Mouse spleen cells were cultured with anti-CD3 monoclonal antibodies in vitro. Tregs and Th17 cell differentiation was induced by transforming growth factor (TGF)-β and interleukin (IL)-2, or TGF-β, IL-6, and IL-23, respectively. Then cells were treated with two CpG ODNs, CpG 1982, or CpG 1826. FBL-3-inoculated C57Bl/6 mice were treated with CpG 1826, tumor vaccine, or combination of CpG 1826 and tumor vaccine. After treatment, spleen cells and serum were isolated, and Tregs/Th17 cells were detected by flow cytometry. The expression of forkhead box P3 (Foxp3), retinoid-related orphan receptor gamma-t (RORγt), IL-10, and IL-17 mRNA was measured by real-time PCR, and protein levels were measured by Western blot and enzyme-linked immunosorbent assay.The frequency of Treg cells increased significantly (p0.05) in the FBL-3-inoculated leukemia mouse model compared with control mice, whereas the frequency of Th17 cells did not change. Median survival of mice after treatment with CpG 1826 and tumor vaccine was significantly prolonged compared with that of control mice (p0.05). The frequency of induced Treg cells decreased after treatment with CpG 1826, whereas the frequency of Th17 cells induced by cytokines in vitro and in the murine leukemia model increased following treatment with CpG 1826. Furthermore, after treatment with CpG 1826, the mRNA and protein levels of Foxp3 and IL-10 decreased significantly both in vitro and in vivo (p0.05), whereas those of RORγt and IL-17 increased significantly (p0.05).CpG 1826 may inhibit the differentiation of Treg cells induced by cytokines, promote the differentiation of Th17 cells in vitro and in murine leukemia models, and prolong the median survival of mice with leukemia.

Coronary artery fistula (CAF) is a rare anomaly of the coronary artery. The draining site of a right coronary artery (RCA) fistula may usually be the right ventricle, right atrium, or pulmonary artery. Here, we present a patient with right coronary artery to coronary sinus fistula (RCACSF) complicated by aneurysmal dilatation of the coronary sinus (CS) and stenosis of CS ostium.

Marfan syndrome (MFS) is an autosomal dominant genetic disorder of the connective tissue, typically characteristic of cardiovascular manifestations, valve prolapse, left ventricle enlargement, and cardiac failure. Fibrillin-1 (FBN1) is the causative gene in the pathogenesis of MFS. Patients with different FBN1 mutations often present more considerable phenotypic variation. In the present study, three affected MFS pedigrees were collected for genetic analysis. Using next-generation sequencing (NGS) technologies, 3 novel frameshift pathogenic mutations which are cosegregated with affected subjects in 3 pedigrees were identified. These novel mutations provide important diagnostic and therapeutic insights for precision medicine in MFS, especially regarding the lethal cardiovascular events.

The current study aimed to verify an miRNA signature in endothelial cells undergoing mechanical stretch stimulation. In the present study, microarray profiling was conducted in order to identify the differential expression of miRNAs in endothelial cells undergoing mechanical stimulation, compared with unstimulated endothelial cells. The microarray data was then validated by reverse transcription‑quantitative polymerase chain reaction. Genes and signaling pathways regulated by the miRNAs were investigated in silico using Gene Ontology and the Kyoto Encyclopedia of Genes or Genomes, which are ontological and network‑mapping algorithms. The microarray data collected demonstrated that 38 miRNAs exhibited significant differential expression in endothelial cells with mechanical stretch stimulation. Of these, 20 were upregulated and 18 were downregulated. The results from the in silico analysis indicated that the miRNAs identified were participants in mechanical stretch‑induced endothelial dysfunction. During the initial stage of vein graft failure, which is induced by endothelial dysfunction, a unique miRNA signature was identified. The identified miRNAs are suggested to be involved in the pathological processes of traumatic injury.

The objective of this study was to determine the characteristic echocardiographic manifestations of Behcet's disease. Ninety-seven Behcet's patients admitted to our hospital from January 2002 to December 2016 were retrospectively analyzed. There were 63 patients (64.9%) with cardiac involvement; these included 47 men (74.6%) and 16 women (25.4%). Of these 63 patients, most (74.6%) exhibited valvular lesions, especially aortic regurgitation. The primary characteristic manifestations of valves were cusp prolapse with aneurysmal changes, vegetation-like lesions and echo-free spaces within the annulus. Second (30.0%) were aortic lesions, including aortic dilation or aneurysm formation, aortic pseudoaneurysm and coronary sinus aneurysm. Other manifestations, such as cardiac thrombosis, coronary arterial pseudoaneurysm, pulmonary aneurysm and pericardial effusion, were rare. Cardiac involvement is not uncommon in Behcet's patients, especially in males, and it is characterized by valvular disease, especially aortic regurgitation. The diagnosis of Behcet's disease should be considered when evaluating patients with these characteristic echocardiographic manifestations.

The aim of the present study was to evaluate the serum levels of interleukin-6 (IL-6), CXC chemokine ligand-10 (CXCL-10) and intercellular adhesion molecule-l (ICAM-1) in patients with Graves' disease (GD) following iodine-131 (131I) therapy. A total of 30 patients with GD participated in the present study. Serum cytokine levels were measured with ELISA, and correlation analyses were performed. Serum levels of IL-6, CXCL-10 and ICAM-1 were significantly higher in patients with GD prior to treatment than those in the control subjects (P

Objective Familial hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipid metabolism, causing premature coronary heart disease (CHD) due to accelerated atherosclerosis from birth, and the study of left ventricular (LV) function of this disease is seldom. The purpose of this study was to explore the value of layer-specific strain on assessing the early damage of LV function in asymptomatic and left ventricular ejection fraction (LVEF) well-preserved patients with heterozygous FH (HeFH). Methods A total of 49 patients aged 38.7±8.7 diagnosed with heterozygous familial hypercholesterolemia and who had undergone transthoracic echocardiography from 2010 to 2016 were included in this study. A total 32 healthy volunteers aged 35.6±10.3 were included as control group. Longitudinal and circumferential strains of the endocardium, myocardium, and epicardium (LSendo, LSmyo, and LSepi and CSendo, CSmyo, and CSepi) were obtained by a software enabling the analysis of strains in three myocardial layers. Results In longitudinal strain (LS), the LS of endocardium (LSendo) and the LS of myocardium (LSmyo) are significantly reduced in patients with HeFH (P

Inflammation is a key event in hypertensive organ damage, and TNF-alpha and IL-1 beta are elevated in hypertension. In this study, we evaluated the effects of TNF-alpha and IL-1 beta elevation on hypertensive cardiac damage by treatment with a bifunctional inflammatory inhibitor, TNF receptor 2-fragment crystalization-IL-1 receptor antagonist (TFI), which can neutralize these 2 cytokines simultaneously. A mouse hypertension model of angiotensin II (Ang II) infusion (1500 ng/kg.min for 7 d) was induced in wild-type mice. TNF-alpha and IL-1 beta were inhibited by TFI administration (5 mg/kg, every other day), the effects of inhibition on cardiac damage were examined, and its mechanism on inflammatory infiltration was further studied in vivo and in vitro. Ang II infusion induced cardiac injury, including increased macrophage infiltration, expression of inflammatory cytokines (IL-12, IL-6, etc), and cardiac fibrosis, such as elevated alpha-smooth muscle actin, collagen I, and TGF-beta expression. Importantly, the Ang II-induced cardiac injury was suppressed by TFI treatment. Moreover, TFI reduced the expression of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and monocyte chemotactic protein-1 expression in Ang II-treated hearts. Additionally, blockade of TNF-alpha and IL-1 beta by TFI reduced monocyte adherence to endothelia cell and macrophage migration. This study demonstrates that blocking TNF-alpha and IL-1 beta by TFI prevents cardiac damage in response to Ang II, and targeting these 2 cytokines simultaneously might be a novel tool to treat hypertensive heart injury.

Continuous subcutaneous insulin infusion (CSII) for type 2 diabetes mellitus (T2DM) is a promising therapy. CSII therapy is flexible, but the required insulin dose for different people may vary. Few studies have investigated the insulin dose and characteristics of CSII for T2DM, and none has focused on an Asian Chinese population.In total, 171 subjects with T2DM were using CSII and divided into different groups according to their body mass index (BMI) and the course of disease, respectively. The basal rate of CSII was set for four periods per day. We preferentially adjusted the basal insulin dose to control fasting and preprandial blood glucose.Good glycemic control was achieved after 4.8±2.5 days. The mean total daily insulin dose was 31.66±9.85 IU, and the dose per unit body weight was 0.48±0.19 IU/kg/day. The total daily basal and bolus doses were 21.14±7.64 IU and 10.38±3.62 IU, respectively (i.e., about 66.7±6.8% and 33.3±6.8% of the total daily dose). We did not observe any significant difference in total dose of insulin or basal and bolus doses of insulin per day among different groups divided by BMI. Only in the group with BMI of23 kg/m(2) was the insulin dose of per kilogram of body weight (0.60±0.25 IU/kg/day) significantly higher than in the other two groups (P=0.0001). There was no relationship between the insulin dose and the course of disease.In individuals with T2DM on CSII short-term intensive therapy, proper increase of basal dose of insulin and preferential adjustment of the basal rate may be the effective method that can achieve good glycemic control with a lower total daily dose.

The aim of the present study was to determine whether the expression levels of interleukin (IL)-2 and IL-10 may be used as biological markers in Graves’ disease (GD) patients. A total of 256 individuals, including 118 GD patients and 138 healthy individuals, were enrolled into the study. Blood samples were collected from each patient and healthy individual, which were then subjected to enzyme-linked immunosorbent assay (ELISA). Total RNA and total proteins were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. In addition, restriction fragment length polymorphism (RFLP) analysis was performed to detect the presence of genetic polymorphisms. The ELISA results indicated that the IL-2 and IL-10 serum levels in the GD patients were increased by ~5.2 and ~7-fold when compared with the levels in the healthy controls. The results of RT-qPCR indicated that the mRNA expression levels of IL-2 and IL-10 were upregulated in the GD patients when compared with the healthy controls. Furthermore, the western blot analysis results revealed that the protein expression levels of IL-2 and IL-10 were significantly increased in the GD patients. RFLP analysis indicated that the increased number of GG single nucleotide polymorphisms (SNPs) in the GD group were detected in the −330 locus of the IL-2 promoter and the −1082 locus of the IL-10 promoter. In addition, the results indicated that the relatively high rates of homozygous GG SNPs (IL-2 −330T/G and IL-10 −1082A/G polymorphisms) on the alleles may be associated with the incidence of GD. The serum, mRNA and protein expression levels of IL-2 and IL-10 were significantly increased in GD patients when compared with the levels in the healthy controls. In conclusion, the expression levels and genetic polymorphisms of IL-2 and IL-10 may be potential biomarkers for the incidence of Graves’ disease in the population studied.

Objective To investigate prospectively the insulin dose requirements of Chinese patients with type 2 diabetes mellitus treated with either multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII) therapy during a 2-week therapeutic intervention. Methods Patients with type 2 diabetes mellitus were randomly assigned to MDI or CSII therapy. The effects of the two treatment methods were determined based on blood glucose parameters, total daily insulin dose and rates of hypoglycaemia. Results A total of 609 patients were enrolled in the study. Glycaemic goals were achieved after a mean ± SD of 6.90 ± 2.10 and 5.44 ± 2.22 days’ treatment in the MDI and CSII groups, respectively. Once stabilized, the mean ± SD total daily insulin doses were 37.12 ± 10.19 IU and 32.58 ± 8.78 IU for the MDI and CSII groups, respectively. Once stabilized, the mean ± SD total basal and bolus doses were 19.46 ± 7.95 IU/day and 17.66 ± 3.53 IU/day for the MDI group, and 22.79 ± 7.55 IU/day and 9.81 ± 2.64 IU/day for the CSII group, respectively. There were significant differences in the total, basal and bolus insulin doses between the two groups. Conclusion CSII therapy may be considered as an effective method to achieve good glycaemic control in Chinese patients with type 2 diabetes mellitus.

The purpose of this study was to evaluate and compare multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine with continuous subcutaneous insulin infusion (CSII) with aspart in patients with type 2 diabetes mellitus (T2DM). It was assessed whether MDI was capable of controlling glycemic index with a higher efficacy than CSII by preferential adjustment of basal insulin with a lower total daily insulin dosage in T2DM. Two hundred patients with T2DM were enrolled in the study and randomly assigned to CSII (n=100) and MDI (n=100; aspart immediately prior to each meal and glargine at bedtime) groups for 12 weeks of therapy. During the last week of each treatment period, the subjects wore a continuous glucose monitoring system for 2-3 days. The dosage of basal insulin was preferentially adjusted to control prior-meal blood glucose levels, and the characteristics of insulin dosage were analyzed. No statistically significant differences were observed between the two groups in hemoglobin A1c (HbA1c), which dropped from 10-11% prior to therapy to 7-7.5% after 12 weeks. After 12 weeks, good glycemic level control was achieved in all patients in the MDI and CSII groups. A statistically significant difference in the dose of insulin between the CSII and MDI groups was observed (P

Objective: There are many reports on associations between spermatogenesis and partial azoospermia factor c (AZFc) deletions as well as duplications; however, results are conflicting, possibly due to differences in methodology and ethnic background. The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population, residents within Yunnan Province, China. Methods: A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population. The study was performed by sequence-tagged site plus/minus (STS+/−) analysis followed by gene dosage and gene copy definition analysis. Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome (Y-SNP) multiplex assays based on single base primer extension technology. Results: The distribution of Y haplotypes was not significantly different between the case and control groups. The frequencies of both gr/gr (7.6% vs. 8.5%) and b2/b3 (6.3% vs. 8.5%) deletions do not show significant differences. Similarly, single nucleotide variant (SNV) analysis shows no significant difference of gene copy definition between the cases and controls. However, the frequency of partial duplications in the infertile group (4.0%) is significantly higher than that in the control group (0.7%). Further, we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes. Conclusions: Our results show that male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.

Medial degeneration and inflammation are features of abdominal aortic aneurysms (AAAs). However, the early inflammatory event initiating aneurysm formation remains to be identified. Activated platelets release abundant proinflammatory cytokines and are involved in initial inflammation in various vascular diseases. We investigated the role of platelets in progression of AAA in vivo and in vitro. Histological studies of tissues of patients with AAA revealed that the number of platelets was increased in aneurysm sites along with the increased infiltration of T lymphocytes and augmented angiogenesis. In a murine model of AAA, apolipoprotein E-knockout mice infused with 1,000 ng/kg/min angiotensin II, treatment with clopidogrel, an inhibitor of platelets, significantly suppressed aneurysm formation (47% decrease, P