The KIR2DL family serves as prognostic biomarkers and correlates with immune infiltrates in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a prevalent haematological malignancy in which various immune and stromal cells in the bone marrow microenvironment have instrumental roles and substantially influence its progression. KIR2DL is a member of the immunoglobulin-like receptor family and a natural killer (NK) cell surface-specific receptor. However, its impact on immune infiltration regarding AML has not been addressed. We aimed to explore molecular markers associated with the immune microenvironment and prognosis of AML with a particular focus on KIR2DL family members. Analysis of data from The Cancer Genome Atlas and Genotype-Tissue Expression databases revealed that KIR2DL1, KIR2DL3 and KIR2DL4 expression were significantly upregulated in AML and associated with decreased overall survival (OS). Moreover, univariate Cox analysis implicated KIR2DL genes as independent prognostic markers of OS. Functional enrichment analysis revealed that KIR2DL genes were associated with immune cells, the immune microenvironment and NK cell-mediated cytotoxicity. Additionally, immune infiltration analyses revealed that KIR2DL upregulation was associated with stronger immune infiltration. Finally, we performed drug sensitivity profiling of KIR2DL genes using the Cellminer database. Collectively, our findings suggest that KIR2DL1, KIR2DL3 and KIR2DL4 have critical roles in AML and may represent novel biomarker genes for disease prognosis and immune infiltration.

The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia / Rol de la MMP-9 en la Regulación de la Degradación de la Membrana Basal Microvascular Esplénica Inducida por Hipoxia de Altura

SUMMARY: To investigate changes of MMP-9 in the rat spleen and hypoxia-induced microvascular basement membrane under high altitude hypoxia. Thirty male specific pathogen-free Sprague Dawley rats were randomly divided into control and hypoxia groups, with 15 rats in each group. The rats in the control group were placed in Dingxi City, Gansu Province (2080 m above sea level) for 30 days. Rats in the hypoxia group were raised in a hypoxic environment in Maduo County, Qinghai Province (4300 m above sea level), for 30 days to establish a hypoxic rat model. Routine blood tests, MMP-9 mRNA, MMP-9 protein, and the spleen microvascular basement membrane were detected. (1) Compared with the control group, the red blood cell count, hemoglobin, and hematocrit levels of the rats in the hypoxia group were all increased; thus, a hypoxia model was successfully established. (2) Compared with the control group, the expression of MMP-9 mRNA and protein was significantly higher in the spleen of rats in the hypoxic group, and the difference was statistically significant (P <0.05). (3) Compared with the control group, the blood vessel basement membrane in the spleen of the hypoxia group was degraded. Under natural low air pressure and high altitude conditions, the expression of MMP-9 in rat spleen tissue increases and participates in the degradation of the microvascular basement membrane.

El objetivo de este trabajo fue investigar los cambios de la MMP-9 en el bazo de la rata y la membrana basal microvascular inducida bajo hipoxia a gran altura. Treinta ratas macho Sprague Dawley, libres de patógenos específicos, se dividieron aleatoriamente en dos grupos de 15 ratas cada uno, un grupo control y un grupo hipoxia. Durante 30 días las ratas del grupo control estuvieron en la ciudad de Dingxi, provincia de Gansu (2080 m sobre el nivel del mar). Las ratas del grupo de hipoxia se criaron en un entorno hipóxico en el condado de Maduo, provincia de Qinghai (4300 m sobre el nivel del mar), durante 30 días para establecer un modelo de rata hipóxica. Se realizaron análisis de sangre de rutina, ARNm de MMP-9, proteína MMP-9 y de la membrana basal microvascular del bazo. En comparación con el grupo control, el recuento de glóbulos rojos, la hemoglobina y los niveles de hematocrito de las ratas del grupo de hipoxia aumentaron; por lo tanto, se estableció con éxito un modelo de hipoxia. En comparación con el grupo control, la expresión de ARNm y proteína de MMP-9 fue significativamente mayor en el bazo de las ratas del grupo hipóxico, siendo la diferencia estadísticamente significativa (P <0,05). En comparación con el grupo control, la membrana basal de los vasos sanguíneos estaba degradada en el bazo del grupo hipoxia. En condiciones naturales de baja presión atmosférica y gran altitud, la expresión de MMP-9 en el tejido del bazo de la rata aumenta y participa en la degradación de la membrana basal microvascular.

The non-coding competing endogenous RNAs in acute myeloid leukemia: biological and clinical implications.

Acute myeloid leukemia (AML) is a hematologic carcinoma that has seen a considerable improvement in patient prognosis because of genetic diagnostics and molecularly-targeted therapies. Nevertheless, recurrence and drug resistance remain significant obstacles to leukemia treatment. It is critical to investigate the underlying molecular mechanisms and find solutions. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), circular RNAs, long non-coding RNAs, and pseudogenes, have been found to be crucial components in driving cancer. The competing endogenous RNA (ceRNA) mechanism has expanded the complexity of miRNA-mediated gene regulation. A great deal of literature has shown that ncRNAs are essential to the biological functions of the ceRNA network (ceRNET). NcRNAs can compete for the same miRNA response elements to influence miRNA-target RNA interactions. Recent evidence suggests that ceRNA might be a potential biomarker and therapeutic strategy. So far, however, there have been no comprehensive studies on ceRNET about AML. What is not yet clear is the clinical application of ceRNA in AML. This study attempts to summarize the development of research on the related ceRNAs in AML and the roles of ncRNAs in ceRNET. We also briefly describe the mechanisms of ceRNA and ceRNET. What's more significant is that we explore the clinical value of ceRNAs to provide accurate diagnostic and prognostic biomarkers as well as therapeutic targets. Finally, limitations and prospects are considered.

Mechanism of salidroside in the treatment of chronic myeloid leukemia based on the network pharmacology and molecular docking.

BACKGROUND: Salidroside is a phenolic natural product, which is a kind of Rhodiola rosea. It has been confirmed that it has inhibitory effects on chronic myeloid leukemia, but the specific performance of its molecular effects is still unclear. OBJECTIVE: To systematically study the pharmacological mechanism of salidroside on chronic myeloid leukemia by means of network pharmacology. METHODS: First, the possible target genes of salidroside were predicted through the Traditional Chinese Medicine Pharmacology Database and Analysis Platform, the target gene names were converted into standardized gene names using the Uniprot website. At the same time, the related target genes of chronic myeloid leukemia were collected from GeneCards and DisGenet; Collect summary data and screen for commonly targeted genes. Then, the above-mentioned intersected genes were imported into the String website to construct the protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. To investigate the overall pharmacological effects of salidroside on chronic myeloid leukemia, we constructed a drug component-target gene-disease (CTD) network. Finally, molecular docking was performed to verify the possible binding conformation between salidroside and the candidate target. RESULTS: A total of 126 salidroside target genes were retrieved, and 106 of them had interactions with chronic myeloid leukemia. The pharmacological effects of salidroside on chronic myeloid leukemia are related to some important oncogenes and signaling pathways. Molecular docking studies confirmed that the main role of salidroside binding to the target genes is hydrogen bonding. CONCLUSIONS: We revealed the potential mechanism of action of salidroside against chronic myeloid leukemia, verified by network pharmacology combined with molecular docking. However, salidroside is a promising drug for the prevention and treatment of chronic myeloid leukemia, and further research is needed to prove it.

Evaluation of Amide Proton Transfer-Weighted Imaging for Risk Factors in Stage I Endometrial Cancer: A Comparison With Diffusion-Weighted Imaging and Diffusion Kurtosis Imaging.

Background: Endometrial cancer (EC) is one of the most common gynecologic malignancies in clinical practice. This study aimed to compare the value of diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), and amide proton transfer-weighted imaging (APTWI) in the assessment of risk stratification factors for stage I EC including histological subtype, grade, stage, and lymphovascular space invasion (LVSI). Methods: A total of 72 patients with stage I EC underwent pelvic MRI. The apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), and magnetization transfer ratio asymmetry (MTRasym at 3.5 ppm) were calculated and compared in risk groups with the Mann-Whitney U test or independent samples t-test. Spearman's rank correlation was applied to depict the correlation of each parameter with risk stratification. The diagnostic efficacy was evaluated with receiver operating characteristic (ROC) curve analysis and compared using the DeLong test. A multivariate logistic regression was conducted to explore the optimal model for risk prediction. Results: There were significantly greater MTRasym (3.5 ppm) and MK and significantly lower ADC and MD in the non-adenocarcinoma, stage IB, LVSI-positive, high-grade, and non-low-risk groups (all p < 0.05). The MK and MTRasym (3.5 ppm) were moderately positively correlated with risk stratification as assessed by the European Society for Medical Oncology (EMSO) clinical practice guidelines (r = 0.640 and 0.502, respectively), while ADC and MD were mildly negatively correlated with risk stratification (r = -0.358 and -0.438, respectively). MTRasym (3.5 ppm), MD, and MK were identified as independent risk predictors in stage I EC, and optimal predictive performance was obtained with their combinations (AUC = 0.906, sensitivity = 70.97%, specificity = 92.68%). The results of the validation model were consistent with the above results, and the calibration curve showed good accuracy and consistency. Conclusions: Although similar performance was obtained with each individual parameter of APTWI, DWI, and DKI for the noninvasive assessment of aggressive behavior in stage I EC, the combination of MD, MK, and MTRasym (3.5 ppm) provided improved predictive power for non-low-risk stage I EC and may serve as a superior imaging marker.

The Healthy Taiwanese Eating Approach is inversely associated with all-cause and cause-specific mortality: A prospective study on the Nutrition and Health Survey in Taiwan, 1993-1996.

BACKGROUND: Few longitudinal studies have investigated the association between foods/dietary pattern and mortality risk in the Asian population. We investigated the prospective association between foods/dietary pattern and risk of death among ethnic Chinese adults in Taiwan. METHODS: The study population included 2475 young and middle-aged adults (aged 18-65 years at baseline) who completed the questionnaires and physical examinations in the Nutrition and Health Survey in Taiwan from 1993 to 1996. A food frequency questionnaire was administered to assess food consumption habits in a face-to-face interview. With survey data linked to the Taiwanese Death Registry, Cox proportional hazard model was used to identify the foods associated with all-cause mortality(followed until 2012), which were then tallied to calculate a dietary pattern score called Taiwanese Eating Approach(TEA) score. The TEA scores were then associated with various kinds of mortality outcomes. In addition, data from 431 elders (aged≥65 yrs) with 288 death endpoints were used to conduct a sensitivity analysis. RESULTS: A total of 385(15.6%) participants died (111 cardiovascular related deaths and 122 cancer related deaths) during the 17.8-year follow-up period(41274 person-years). Twelve foods (9 inverse [vegetables/fish/milk/tea](+1) and 3 positive[fatty meats/fermented vegetables/sweet drinks](-1)) were significantly associated with all-cause mortality risk. All adults were grouped by their cumulative food score into three diet groups: poor diet(29.3% of all subjects), average diet(44.0%), and healthy diet(26.70%). The better the diet, the lower the total, cardiovascular, and other cause mortality outcomes (trend-p < .001). The hazard ratio for the healthy diet was 0.64 (95% confidence interval:0.47-0.87) for total mortality, and 0.52(0.28-0.95) for cardiovascular death, compared with the poor diet in the multivariable models. This phenomenon was also seen in older adults for all-cause, cancer, and other cause mortalities. CONCLUSION: Consuming a healthy Taiwanese Eating Approach (TEA) diet is negatively associated with all-cause, cardiovascular, and other-cause mortalities in Taiwan.

Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway.

Chronic hypoxia (CH) is characterized by long-term hypoxia that is associated with microvessel proliferation and basal membrane (BM) degradation in tissues. The IL-6/JAK2/STAT3/MMP-9 pathway has been described in a variety of human cancers and plays an essential role in microvessel proliferation and BM degradation. Therefore, this study investigated the role of the IL-6/JAK2/STAT3/MMP-9 pathway in hypoxia-mediated microvessel proliferation and BM degradation in the rat bone marrow. Eighty pathogen-free Sprague Dawley male rats were randomly divided into four groups (20 per group)-control group, CH group (exposed to hypoxia in a hypobaric chamber at a simulated altitude of 5000 m for 28 d), CH + STAT3 inhibitor group (7.5 mg/kg/d), and CH + DMSO group. Microvessel density (MVD) and BM degradation in the bone marrow were determined by immunofluorescence staining and transmission electron microscopy. Serum IL-6 levels were assessed by enzyme-linked immunosorbent assay (ELISA), and the levels of P-JAK2, P-STAT3, and MMP-9 were assessed by western blot analysis and real-time reverse transcription PCR (RT-PCR). Hypoxia increased serum IL-6 levels, which in turn increased JAK2 and STAT3 phosphorylation, which subsequently upregulated MMP-9. Overexpression of MMP-9 significantly promoted the elevation of MVD and BM degradation. Inhibition of STAT3 using an inhibitor, SH-4-54, significantly downregulated MMP-9 expression and decreased MVD and BM degradation. Surprisingly, STAT3 inhibition also decreased serum IL-6 levels and JAK2 phosphorylation. Our results suggest that the IL-6/JAK2/STAT3/MMP-9 pathway might be related to CH-induced microvessel proliferation and BM degradation in the bone marrow.

The Role of Autophagy in Cancer Radiotherapy.

BACKGROUND: Autophagy, a pathway for lysosomal-mediated cellular degradation, is a catabolic process that recycles intracellular components to maintain metabolism and survival. It is classified into three major types: macroautophagy, microautophagy, and the chaperone-mediated autophagy (CMA). Autophagy is a dynamic and multistep process that includes four stages: nucleation, elongation, autophagosome formation, and fusion. Interestingly, the influence of autophagy in cancer development is complex and paradoxical, suppressive, or promotive in different contexts. Autophagy in cancer has been demonstrated to serve as both a tumour suppressor and promoter. Radiotherapy is a powerful and common strategy for many different types of cancer and can induce autophagy, which has been shown to modulate sensitivity of cancer to radiotherapy. However, the role of autophagy in radiation treatment is controversial. Some reports showed that the upregulation of autophagy was cytoprotective for cancer cells. Others, in contrast, showed that the induction of autophagy was advantageous. Here, we reviewed recent studies and attempted to discuss the various aspects of autophagy in response to radiotherapy of cancer. Thus, we could decrease the viability of cancer cell and increase the sensibility of cancer cells to radiation, providing a new basis for the application of autophagy in clinical tumor radiotherapy.

Cryptotanshinone inhibits lung cancer invasion via microRNA-133a/matrix metalloproteinase 14 regulation.

Cryptotanshinone inhibits the proliferative and colony formation abilities of human non-small cell lung cancer cells (NSCLCs). The present study reported that signal transducer and activator of transcription 3 is not the only target of cryptotanshinone during the inhibition of human NSCLCs. It was identified that cryptotanshinone upregulates the expression levels of microRNA (miR)-30d-5p, miR-126-3p, miR-133a, miR-338-3p and miR-451a, and downregulates miR-21-5p, miR-96-5p, miR-182-5p and miR-205-5p. Among these, miR-133a was the most significantly upregulated. miR-133a targets and downregulates the expression of matrix metalloproteinase (MMP)14; however, MMP15, MMP16 and MMP24 were determined to be unaffected. This process was identified to be independent of tissue inhibitor of metalloproteinases 2. Cryptotanshinone also suppresses the invasion of human NSCLCs, which may be due to the inhibited expression of MMP14. In conclusion, cryptotanshinone may serve as a potential therapeutic agent in the treatment of lung cancer.

Using amide proton transfer to identify cervical squamous carcinoma/adenocarcinoma and evaluate its differentiation grade.

PURPOSE: To explore the possibility of using amide proton transfer-weighted imaging (APTWI) for the identification and diagnosis of cervical squamous carcinoma (CSC), cervical adenocarcinoma (CA) and different levels of CSC. MATERIALS AND METHODS: Seventy-six patients with newly diagnosed uterine cervical cancer (UCC) were studied prior to treatment, including 20 with poorly differentiated (Grade 3) CSC, 23 with moderately differentiated (Grade 2) CSC, 17 with well-differentiated (Grade 1) CSC, and 16 with CA (13 with poorly differentiated (Grade 3) CA and 3 with moderately differentiated (Grade 2) CA). Differences in the magnetization transfer ratio at 3.5 ppm (MTRasym (3.5 ppm)) were identified between CSC and CA and between high-level (Grade 3) CSC and low-level (Grade 2 and Grade 1) CSC, as well as among all three grades of CSC differentiation. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic thresholds and performance of the parameters. Spearman correlation analysis was used to examine the correlation between the MTRasym (3.5 ppm) and histological grade. RESULTS: The MTRasym (3.5 ppm) in CA was higher than that in CSC (P = 0.001). The MTRasym (3.5 ppm) in high-level CSC was higher than that in low-level CSC (P = 0.001). The MTRasym (3.5 ppm) was positively correlated with the grade of CSC differentiation (r = 0.498, P = 0.001). The MTRasym (3.5 ppm) in Grade 3 CSC was higher than that in Grade 2 and Grade 1 CSC (P = 0.02/0.01). No significant difference in the MTRasym (3.5 ppm) was found between Grade 2 CSC and Grade 1 CSC (P = 0.173). The area under the ROC curve (AUC) for the MTRasym (3.5 ppm) in distinguishing CSC and CA was 0.779, with a cut-off, sensitivity, and specificity of 2.97%, 60.0% and 82.5%, respectively. The AUC for distinguishing high-/low-level CSC was 0.756, with a cut-off, sensitivity, and specificity of 3.29%, 68.8% and 83.3%, respectively. CONCLUSION: APTWI may be a useful technique for the identification and diagnosis of CSC, CA and different levels of CSC, which may have an important impact on clinical strategies for treating patients with UCC.

Comparative analysis of the value of diffusion kurtosis imaging and diffusion-weighted imaging in evaluating the histological features of endometrial cancer.

PURPOSE: This study evaluated and compared the performances of diffusion kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) for diagnosing and histologically grading endometrial cancer. MATERIALS AND METHODS: In this retrospective study, DKI and DWI data for 61 patients with endometrial cancer and 30 patients with a normal endometrium were analyzed, and the mean kurtosis (MK), mean diffusion coefficient (MD) and apparent diffusion coefficient (ADC) values for the endometrial cancer tissue and normal endometrial tissue were acquired. The parameters for the normal endometrium group (G0) and the endometrial cancer groups (G1, G2 and G3) were compared and analyzed. The receiver operating characteristic (ROC) curve was used to evaluate each parameter's diagnostic accuracy and threshold. Spearman correlation analysis was used to analyze the correlations between all parameters and histological grades. RESULTS: The MK values for the G0, G1, G2 and G3 groups increased gradually, while the MD and ADC values decreased gradually. Except for the differences in the ADC values between G0 and G1, the differences among the groups were statistically significant (P < 0.05). The MK values had the highest diagnostic accuracy in differentiating G0 and (G1 + G2 + G3), G0 and G1, G1 and G2, and G2 and G3 (AUC = 0.93, 0.76, 0.91, 0.91, P < 0.05). MK was maximally correlated with histological grade, followed by MD and ADC (MK > MD > ADC; r = - 0.85, + 0.82, + 0.76, P < 0.01). CONCLUSION: Both DKI and DWI can be used to evaluate the diagnosis and histological grading of endometrial cancer. Compared with DWI, the DKI model is a more complete mathematical model with more sensitive parameters, which can more effectively evaluate the pathological and physiological characteristics of endometrial cancer.

Practice of cervical end-esophageal exteriorization in patients with severe intrathoracic anastomotic leakage after esophagectomy.

OBJECTIVE: This study aimed to summarize the clinical experience of severe intrathoracic anastomotic leakage encountered in clinical practice by using cervical end-esophageal exteriorization. METHODS: We undertook a retrospective review of four patients who developed severe anastomotic leakage after subtotal esophagectomy at our department. Four patients with a life-threatening condition and failed conservative management were re-operated on from the original incision using an exteriorized cervical end-esophageal gastric conduit. We returned the gastric conduit to the abdomen and placed a feeding jejunostomy or gastrostomy catheter. Until inflammation was controlled, we re-established intestinal continuity with the gastric or colon conduit, pulled up to the neck by a retrosternal channel. RESULTS: Four patients with esophagectomy and severe intrathoracic anastomotic leakage underwent re-operation. The gastric conduit was returned to the abdomen and cervical end-esophageal exteriorization was performed. Inflammation was rapidly controlled after surgery. Three patients received a second re-operation to re-establish intestinal continuity on days 63, 63, and 16 after the first re-operation. One patient refused re-operation to re-establish intestinal continuity. All four patients survived. CONCLUSION: Cervical end-esophageal exteriorization in patients with severe intrathoracic anastomotic leakage results in rapid control of inflammation. This creates an opportunity to re-establish gastrointestinal continuity, leading to survival of patients.

[The clinical analysis of plakophilin-2 gene mutation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia].

OBJECTIVE: The purpose of this study was to screen genetic variations in plakophilin-2 (PKP2) gene in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and investigate the differences in clinical features between mutation and no-mutation groups. METHODS: Thirty unrelated Chinese patients clinically diagnosed with ARVC/D and 50 healthy controls were included. Genomic DNA was isolated from peripheral blood samples. PCR and direct sequencing were used to detect variations in PKP2 gene. RESULTS: Eight PKP2 mutant variants were identified in 10 ARVC/D patients (8 men, 2 women). Among the eight mutation, three (c.2194C>T, c. 1170+ 1G>A and c. 810_813delGGTC) were novel mutation. Clinical features of the PKP2 mutation group were similar to those of the non-mutation group. CONCLUSIONS: The rate of PKP2 mutation is 33.3% (10/30) in ARVC/D patients. The penetrance of PKP2 mutation for ARVC/D tends to be higher in man patients. No significant differences could be detected in phenotype characteristics between patients with and without PKP2 mutation.

Management trajectories in the type 2 diabetes Integrated Delivery System project in Taiwan: accounting for behavioral therapy, nutrition education and therapeutics.

BACKGROUND AND AIM: Glycated hemoglobin (HbA1c) assessment is basic to diabetes management. Little is done to describe the whole spectrum of the trajectory, its related temporal patterns of metabolic indices, and comorbidities. METHODS AND RESULTS: This was a longitudinal study. In the Diabetes Management through Integrated Delivery System project in Taiwan, enrollees had diabetes, but no major comorbidities. They were randomized into intensive or conventional education (health, diet and exercise) groups. HbA1c was classified by a groupbased trajectory model on the basis of repeated six-monthly measurements. We analyzed data from 1091 subjects who had at least two measurements on HbA1c. HbA1c exhibited three distinct ranges of low (42-53 mmol/mol), intermediate (64-75 mmol/mol) and high (97 mmol/mol), all of which persisted for 4.5 years regardless of receiving intensive education or not. Temporal changes and a time-group interaction were found for triglycerides, total cholesterol, HDL-C and LDL-C. The high trajectory was associated with the major co-morbidities of retinopathy, nephropathy, neuropathy, stroke, hypoglycemia, and ketoacidosis. Patients in the intensive education group (62.4%), which were equally distributed in the three trajectories, had significantly lower HbA1cs (-0.14%= -1.5 mmol/mol, p=0.026). The intermediate trajectory patients with intensive education had HbA1cs higher than the low trajectory patients with conventional education (ß=0.189, p=0.033). Though not significant, a similar pattern was found for DM education in the high group (ß=0.223, p=0.154). CONCLUSIONS: Novel strategies beyond current education and pharmacotherapeutic regimens are needed to lower HbA1c at least 11 mmol/mol for the high HbA1c group to minimize comorbidities.

[Types and risk factors of arrhythmia on young patients with acute coronary syndrome in Henan province].

OBJECTIVE: The types and risk factors of arrhythmia were analyzed on acute coronary syndrome (ACS) patients under the age of 44 years who were hospitalized in Henan province between September 2009 to June 2012. METHODS: Medical records of eligible patients were obtained from the information system of the First Affiliated Hospital of Zhengzhou University teleconsultation information center. Middle aged and elderly ACS patients who were hospitalized at the same period served as controls. Data on arrhythmia types, blood pressure, thyroid disease, respiratory sleep apnea syndrome, smoking history, history of alcohol consumption, eating habits, family history of early-onset arrhythmia, laboratory tests were analyzed. RESULTS: (1) Arrhythmia was detected in 110 out of young ACS patients (55%), which was significantly lower than that in the elderly ACS patients (71.05%, P < 0.01). (2) The top three arrhythmias in young ACS patients were: sinus tachycardia (30.50%), the premature ventricular contractions (19.00%), atrial flutter/atrial fibrillation (16.50%). Incidence of sinus tachycardia, atrial flutter/atrial fibrillation were significantly higher while incidence of ventricular tachycardia, ventricular fibrillation, paroxysmal supraventricular tachycardia were significantly lower in young ACS patients than in middle-aged ACS patients (all P < 0.05). The incidence of sinus tachycardia was higher while incidence of ventricular premature accelerated ventricular spontaneous cardiac rhythm, ventricular tachycardia, ventricular fibrillation, non-paroxysmal supraventricular tachycardia, atrial flutter/atrial fibrillation, paroxysmal supraventricular tachycardia, sinus bradycardia, nodal escape, atrioventricular block were significantly lower in young ACS patients than in elderly ACS patients (all P < 0.05). (3) Body mass index, incidence of smoking, coronary three-vessel disease, drinking, eating salty foods, thyroid dysfunction, sleep apnea were significantly higher in youth ACS patients with arrhythmia than in young ACS patients without arrhythmia (all P < 0. 05). (4) Logistic regression analysis found that number of diseased coronary vessels (OR = 24.293), smoking (OR = 1.112) and alcohol consumption (OR = 1.039) were independent risk factor for developing arrhythmia in young ACS patients from Henan province. CONCLUSIONS: The main types of arrhythmia are sinus tachycardia, premature ventricular contractions, atrial flutter/atrial fibrillation and the major risk factors related to the arrhythmia are number of diseased coronary vessels, smoking and alcohol consumption in young ACS patients from Henan province.

[Population characteristics and impact on heart rate variability, heart rate and blood pressure of passive smoking].

OBJECTIVE: To investigate the basic characteristics of passive smoking population, and the impact of passive smoking on heart rate variability, heart rate and blood pressure. METHODS: Eighty-six passive smokers [mean age: (52.4 ± 7.6) years] were recruited from patients and their relatives who visited cardiovascular outpatient department and excluded structural heart disease between June 2010 and June 2012, 80 normal subjects who were not exposed to smoking served as controls. Questionnaire survey, 24 hours ambulatory electrocardiogram examination and blood pressure measurement were performed in all recruited subjects. RESULTS: (1) Non-marriage rate [18.60% (16/86) vs. 3.75% (3/80), P < 0.01] was significantly higher while education level were significantly lower in passive smoking group than in control group. Passive smokers were more likely service industry workers [29.07% (25/86) vs. 15.00% (12/80), P < 0.05] and had longer daily working time [(7.56 ± 1.24) h vs. (6.02 ± 0.96) h, P < 0.01], and were less likely to be professional technology industry employers [20.93% (18/86) vs. 36.25% (29/80), P < 0.05] and managers [13.95% (12/86) vs. 38.75% (31/80), P < 0.01] compared to controls. The main place of passive smoking was workplace (67.44%, 58/86), entertainment venues (63.95%,55/86), restaurants (48.84%, 42/86). (2) Standard of the normal sinus RR intervals (SDNN), the normal consecutive sinus RR interval difference between the root-mean-square (rMSSD) and adjacent the difference between the RR interval>50 ms the number of share the percentage (PNN50) were significantly lower in passive smoking group than in the control group (all P < 0.05). Every 5 min average of the standard deviation of sinus RR cycle (SDNN index) and 24 h every 5 min sinus RR interval mean standard deviation (SDANN) were similar between the 2 groups (all P > 0.05). Ultra-low-frequency power (VLF), low frequency power (LF), high frequency power (HF) and LF/HF were significantly lower in passive smoking group than in the control group (all P < 0.01). (3) Heart rate and diastolic blood pressure were significantly higher in passive smoking group than in control group (all P < 0.05) while systolic blood pressure was similar between the 2 groups (P > 0.05). CONCLUSIONS: Marriage status, education level, profession and daily working time are independent determinants for passive smoking. Passive smoking mainly occurred in the workplace, entertainment venues and restaurants. Passive smoking is linked with reduced heart rate variability, increased 24 h average heart rate and diastolic blood pressure.

Mutation spectrum in a large cohort of unrelated Chinese patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HC) is a hereditary heterogeneous cardiovascular disorder. Existing data have been of predominantly Caucasian samples, and a large study is needed in Chinese population. The present study was intended to explore the genetic basis and clinical characteristics correlated with different genotypes in a large cohort of Chinese patients. Direct gene sequencing of ß-myosin heavy chain (MYH7), myosin binding protein-C (MYBPC3), and cardiac troponin T (TNNT2) was performed in 136 unrelated Chinese HC patients. Clinical evaluations were conducted. In total, 32 mutations were identified in 36 patients (27%), including 10 novel ones. Distribution of mutations was 56% (MYBPC3), 31% (MYH7), and 13% (TNNT2), respectively. Double mutations were identified in 3% patients. The occurrence of HC-associated sarcomeric mutations was associated with an earlier age of onset, increased left ventricular hypertrophy, a higher incidence of syncope, previous family history, and sudden cardiac death. No statistical difference was identified in patients carrying MYBPC3 and MYH7 mutations with regard to clinical characteristics and outcomes. Patients with double mutations were associated with malignant progression in the study. In conclusion, MYBPC3 is the most predominant gene in HC. Multiple mutations are common in MYH7, MYBPC3, and TNNT2. The present study suggests a large diversity of HC and a prognostic role of genotype.

[Effect of the smoking cessation services in the out-patient department for patients with coronary heart disease].

OBJECTIVE: To evaluate the effects and clinical prognosis of out-patient department-based smoking cessation services for coronary heart disease (CHD) patients. METHODS: A total of 140 smoking patients diagnosed with coronary heart disease in our cardiovascular department were randomly divided into the intensive smoking cessation clinic follow-up group (intervention group, patients were informed on the importance and methods to quit smoking at the first visit and reminded for that at months interval for 6 months, n = 70) and the conventional treatment group (control group, n = 70). After 6 months, the smoking status, cardiovascular event rates, drug usage, out-patient medical costs and quality of life were compared between the two groups. RESULTS: Age, gender, concomitant diseases, drug usage were similar between the two groups at baseline (all P > 0.05). After 6 months, smoking quit rate [34.2% (24/70) vs. 5.7% (4/70), P < 0.01], drug use rates: lipid-lowering drugs [95.3% (67/70) vs. 80.4% (56/70)], ß blockers [82.4% (57/70) vs. 41.3% (28/70)], and ACEI/ARB [61.4% (43/70) vs. 34.4% (24/70)] were significantly higher in the intervention group than in the control group, while total cardiovascular event rates [21.4% (15/70) vs. 47.1% (33/70), P < 0.01] and out-patient medical costs (3789.3 RMB vs. 4984.2 RMB, P < 0.01) were significantly lower in the intervention group than in the control group. The quality of life scores derived from MYO health survey questionnaire was significantly higher in the intervention group than in the control group (P < 0.01). The top three reasons responsible for continuous smoking for all patients failed to quit smoking were: (1) others smoked more than me and still alive and healthy [90.3% (56/62)]; (2) smoking helped me to keep relaxed and reduce trouble in daily work and life [70.9% (44/62)]; (3) smoking was essential while chatting and drinking with friends [66.1% (41/62)]. The overall satisfactory rate to this smoking cessation program was 42.8% and the satisfactory rate was up to 50.0% by patients. CONCLUSIONS: Intensive outpatient smoking cessation follow-up program can significantly improve the smoking cessation rates, the guideline drug use rate and the quality of life while reduce medical costs for coronary heart disease patients.

Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study.

OBJECTIVE: Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown. RESEARCH DESIGN AND METHODS: The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998-2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization. RESULTS: There were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63-2.67]), all-cause hospitalization (2.51 [2.00-3.16]), and total mortality (2.48 [1.41-4.38]). CONCLUSIONS: Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.

Calcium channel blockers and modulation of innate immunity.

PURPOSE OF REVIEW: Researchers and physicians are gaining more understanding of the utility of calcium channel blockers (CCBs) especially in modulation of innate immunity, and choose suitable ones in clinical practice. This review summarizes the recent related research findings. RECENT FINDINGS: Sustained and/or dysregulated expression of pro-inflammatory cytokines is sufficient to produce tissue injury and provoke overt cardiac decompensation. The important question that remains to be addressed is whether or not it will be possible to modulate the inappropriate or maladaptive consequences of innate immune activation and pro-inflammatory cytokine expression in the mammalian heart. CCBs, such as nifedipine, amlodipine, diltiazem, and verapamil, promote the relaxation of cardiac and smooth muscle cells by inhibiting calcium influx through calcium channels and calcium release from intracellular stores, and are commonly used in the treatment of cardiovascular disorders. Recently, several in-vitro studies have shown that, besides the effects they exert on muscle cells, CCBs also suppress the activation of various participants in immune reactions, including T cells, mast cells and macrophages, suggesting that they can be immunosuppressant. SUMMARY: CCBs maybe suppress the activation of various participants in immune reactions.