Objective To investigate the changes of cardiac structure and function in type 2 diabetes mellitus (T2DM), analyze the related risk factors of heart failure, and improve the awareness of the effect of diabetes on the heart. Methods Randomly selected 170 cases of T2DM patients As the object of study, 170 cases of non diabetic patients as con-trol group, according to whether complicated with heart failure were divided into heart failure patients and non heart failure patients.Comparison of each group left ventricular posterior wall thickness, left ventricular end diastolic diameter, left ven-tricular end systolic diameter, left ventricular ejection fraction, E/A ratio Differences, analysis of the related risk factors of heart failure by logistic regressive.Results T2DM group left ventricular posterior wall thickness, left ventricular end diastolic diameter and left ventricular end systolic diameter increased , Left ventricular ejection fraction decreased, E/A ratio de-creased, were statistically significant difference compared with the control group (p <0.05).These differences are mainly come from non heart failure patients.Logistic regression showed that factors in patients with diabetes duration, HbA1c, com-pliance and complications of hypertension, coronary heart disease, is a risk factor for heart failure complicated with T2DM (all p<0.01).These may be the risk factor for diabetic patients with heart failure.Conclusion Diabetes can cause cardiac remodeling, systolic and diastolic dysfunction maybe some T2DM patients.They did not show symptoms of heart failure in the clinical, but their Cardiac structure and function are abnormal.We should pay attention to the cardiac function examination and early evaluation, prevention of risk factors, to avoid the occurrence of heart failure.

Adult ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Phenotype ; Thrombophilia ; genetics ; Thrombosis ; Young Adult

Objective To investigate the effect of progressive neurological deterioration ( PND) of cerebral watershed infarction on early prognosis. Methods The consecutive patients with cerebral watershed infarction admitted in the Department of Neurology,Jinling Hospital,Nanjing University School of Medicine and their cerebral watershed infarctions confirmed by the imaging examination from March 2009 to March 2014 were enrolled. The clinical features, laboratory indicators and imaging features of internal watershed infarction,cortical-type watershed infarction,and mixed watershed infarction were identified and analyzed. The National Institutes of Health Stroke Scale was used to score neurological deficit. The modified Rankin scale ( mRS) was used to score the prognosis of patients. Single factor analysis was used to compare the differences between the groups. At the same time,the correlation between PND and poor prognosis of cerebral watershed infarction at day 90 was analyzed by multivariable Logistic regression analysis. Results A total of 89 patients with cerebral watershed infarction were enrolled,including 43 cortical-type watershed infarctions,36 internal watershed infarctions, and 10 mixed watershed infarctions. Single factor analysis indicated that the incidences of PND of internal watershed infarction and mixed watershed infarction were significantly higher than the cortical-type watershed infarction (36. 1% [n=13],50. 0% [n=5], and 16. 3% [n=7],respectively;P=0. 018). At day 90,28 patients had poor prognosis,and mRS was (3.4±1. 0) scores at day 90. There was significant difference in the types of infarction between the patients with poor prognosis and patients with good prognosis (P<0. 05). In patients with poor prognosis, most of them were internal watershed infarctions,accounting for 50. 0% (14/28),while in patients with good prognosis,most of them were cortical-type watershed infarctions(57. 4% [35/61]). The incidence of PND in patients with poor prognosis was significantly higher than that in patients with good prognosis (57.1% [16/28] vs. 14. 8% [9/61];P<0. 05). The result of multivariate Logistic regression analysis showed that after adjustment for confounding factor, PND was independently associated with the poor prognosis of cerebral watershed infarction at day 90 (OR 6. 969,95%CI 2. 451-19. 869;P<0. 01). Conclusion Compared with the cortical-type watershed infarction, the patients with internal watershed infarction is more prone to have PND, and PND is independently correlate with the poor prognosis at day 90.

Objective To explore the changes of deceleration capacity of rate (DC) and analyze its correlation with heart rate variability (HRV) and other factors in patients with coronary heart disease. Methods One hundred and twenty-nine patients with coronary heart disease (coronary heart disease group) and 109 healthy people (control group) were enrolled in this study. DC and HRV parameters were measured by using digitized 24 h Holter. The correlation between DC and HRV parameters, other factors were analyzed. Results The levels of DC, SDNN, SDANN, SDNNi, PNN50, TP, LF, HF, AC in coronary heart disease group were significantly lower than those in control group:(5.64±1.67) ms vs. (6.71±1.47) ms, (106.60±20.53) ms vs. (138.82±31.22) ms, (96.94±20.06) ms vs. (127.47±31.87) ms,(28.53±14.75) ms vs. (52.24±14.65) ms, 87.72%vs. 103.86%,(1 967.10±966.16) ms2/Hz vs. (2 846.70±1 443.41) ms2/Hz,(326.43±195.35) ms2/Hz vs.(457.64±254.30) ms2/Hz, 85.88 vs. 106.39, (-6.18±2.15) ms vs. (-7.00±2.51) ms, P<0.05 or<0.01. DC was correlated with SDNNi, PNN50,TP,LF, HF, AC both in total population or in coronary heart disease group and control group by using multiple linear correlation analysis ( r=0.586, 0.356, 0.531, 0.563, 0.435,-0.433, P<0.01). After removing confounders, DC was correlated with age, SDNNi, rMSSD, PNN50 and AC (P<0.01). Conclusions DC decreases in patients with coronary heart disease and is strong correlativity with HRV parameters. DC could be used for quantitative detection of autonomic nervous function.

Objective To explore the genetic mechanism of Yang-deficiency constitution by detecting genomic copy number variations (CNVs). Methods Thirty cases of Yang-deficiency constitution and 30 cases of balanced constitution were included according to the standards of Classification and Determination of Constitution in Traditional Chinese Medicine. DNA was extracted from white blood cells in peripheral blood. A genome-wide association study was conducted by using Affymetrix SNP 6.0 platform. CNVs of each sample were analyzed using PennyCNV software. The Yang-deficiency constitution-specific copy number variation regions (CNVRs) of each autosome were identified. CNVR-related genes and their annotations were searched at online Human Genome Browser. Results The mean number of CNVs in balanced constitution group was 12.63±3.39, ranging from 8 to 20. After stepwise elimination of two Yang-deficiency constitution subjects, the mean number of CNVs in Yang-deficiency constitution group was 15.04±8.95, ranging from 2 to 38. A total of 26 CNVRs were identified from 28 Yang-deficiency constitution subjects, including 19 duplicated CNVRs, 6 deleted CNVRs, and 1 mixed type CNVR. Most CNVRs were shared by a few Yang-deficiency constitution subjects, and only 7 CNVRs were shared by more than 5 Yang-deficiency constitution subjects. The functions of representative genes in Yang-deficiency constitution-specific CNVRs were related with extracellular and intracellular signal transduction, metabolic regulation, and immune response, etc. Conclusion Yang-deficiency constitution subjects have some specific genomic CNVs, which might result in Yang-deficiency constitution phenotypes by influencing the expression of genes associated with extracellular and intracellular signal transduction, material metabolism (energy metabolism), and immune response, etc.

OBJECTIVETo explore effect of iron overload on the proliferation and apoptosis of mesenchymal stem cell(MSCs) and the possible mechanism.

METHODSIron overload model of MSCs was established by adding ferric ammonium citrae (FAC) into the culture medium at different concentrations (100, 200, 400 Μmol/L) and incubated for different lengths of time (12, 24, 48 h). The levels of labile iron pool (LIP) and reactive oxygen species (ROS) were measured to confirm oxidative stress state in the model. Changes in cell proliferation and apoptosis after iron overload were measured through population double time(DT)and annexin V-PI assay. Finally, the expressions of phosphorylated p38 mitogen activated protein kinase (P-p38MAPK), p38MAPK, protein kinase B (AKT), and p53 were determined through Western blot analysis to investigate which ROS-mediated signaling pathway was involved in this process.

RESULTSThe LIP level of MSCs was significantly increased by FAC treatment at 400 Μmol/L (mean fluorescence intensity 482.49±20.96 vs. 303.88±23.37, P<0.05). The level of intracellular ROS was positively correlated with the concentration of FAC and reached a peak level when cultured with 400 Μmol/L FAC (P<0.05).After treatment with 400 Μmol/L FAC at different time points (12 h, 24 h, and 48 h), the DT of MSCs was (1.47± 0.11) d, (1.80±0.13) d, and (2.04±0.14) d, respectively, which was signifcantly longer than that of the control, which was(1.20±0.05)d (P<0.05).The apoptosis rate was also significantly higher in iron overload group[(3.51±1.17)% vs.(0.66±0.62)%, P<0.05]with consequent increase in the expressions of P-p38MAPK, p38MAPK, and p53 proteins in iron overload group, while no significant difference was found in the expression of AKT.

CONCLUSIONIron overload can inhibit the proliferation of MSCs and induce their apoptosis through the generation of ROS, which is probably due to the stimulation of p38MAPK- p53 signaling pathway.

Apoptosis ; drug effects ; Bone Marrow Cells ; drug effects ; metabolism ; Cell Proliferation ; drug effects ; Cells, Cultured ; Humans ; Iron ; pharmacology ; Mesenchymal Stromal Cells ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Tumor Suppressor Protein p53 ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

OBJECTIVE: To examine the serum levels of S100 calcium-binding protein A8/A9 complex (S100A8/ A9) in patients with acute coronary syndrome (ACS) and to explore the relation between the serum levels of S100A8/A9 and the degree of coronary lesion. METHODS: A total of 126 patients with coronary heart disease were enrolled from Xiangya Hospital of Central South University between September 2010 and January 2011, which included 51 patients with unstable angina pectoris (UAP group, n=51), 50 patients with acute myocardial infarction (AMI group, n=50), and 25 patients with stable angina pectoris (SAP group, n=25). Twenty-five healthy volunteers were served as a normal control group (NC group, n=25). According to the coronary artery lesion area, ACS patients were also divided into a single-branch group, a double-branch group and a triple-branch group. Serum levels of S100A8/A9 were measured by enzyme-linked immunosorbent assay on the day when the patients admitted to the hospital and on the day after one-week treatment (UAP group + AMI group). The serum levels were compared among the various branch groups. The short-term prognosis in patients with ACS was investigated by phone follow-up after 3 months. RESULTS: 1) The S100A8/A9 level in the SAP group was significantly higher than that in the normal control group (P<0.05). The serum levels of S100A8/A9 in the UAP group and the AMI group were significantly higher than that in the SAP group (all P<0.05); There was no significant difference in the S100A8/A9 level between the UAP group and the AMI group (P>0.05); 2) After one-week standard treatment, the serum levels of S100A8/A9 in patients with ACS were significantly reduced compared with that at the admission (P<0.01), but it was still elevated compared with that in the normal control group (P<0.01); 3) The serum level of S100A8/A9 in the triple-branch group was significantly higher than that in the single-branch group and the double-branch group (both P<0.05); 4) The short-term prognosis in patients with ACS was not correlated with the serum level of S100A8/A9 (r=0.012, P> 0.05). CONCLUSION The serum level of S100A8/A9 is significantly elevated in patients with ACS, which might be positively correlated with the number of the coronary lesion branches.
Acute Coronary Syndrome ; blood ; pathology ; Angina Pectoris ; Angina, Unstable ; Coronary Artery Disease ; Enzyme-Linked Immunosorbent Assay ; Humans ; Leukocyte L1 Antigen Complex ; blood ; Prognosis

OBJECTIVETo explore susceptibility genes associated with yang-deficiency constitution using single nucleotide polymorphism (SNP) genotyping.

METHODSBased on an epidemiological survey, 30 volunteers with yang-deficiency constitution and 30 volunteers with a balanced constitution were included according to the Classification and Determination Standards of Constitutions in Traditional Chinese Medicine. Peripheral blood was collected and DNA was extracted from white blood cells. A genome-wide association study (GWAS) was conducted by SNP 6.0 genotyping at the Beijing CapitalBio Corporation Ltd. A minimum association P-value (Fisher's exact value) of less than 10(-4) in the allele, genotype, dominant, and recessive models served as the standard for significant association of SNP with yang-deficiency constitution.

RESULTSAmong the four genetic models, a total of 42 SNPs were significantly associated with yang-deficiency constitution (Fisher's exact P-values P<10(-4)). These SNPs were adjacent to more than 20 genes, including RGS6, mGluR5, GAPDHL19, and IKZF1.

CONCLUSIONYang-deficiency constitution exhibits the characteristics of polygenic inheritance. This pilot study suggests that the polymorphisms in RGS6, mGluR5, GAPDHL19, and IKZF1 are associated with changes in cyclic adenosine monophosphate and cyclic guanosine monophosphate levels, memory, metabolic energy status, and immune function, respectively in people with yang-deficiency constitution.

Adolescent ; Adult ; Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide ; Yang Deficiency ; genetics ; Young Adult

Objective To explore the effect of pattern-specific physical therapy based on functional impair-ment on chronic neck pain ( CNP ) . Methods Ninety-three CNP patients treated in the outpatient department of our hospital between March 2016 and November 2017 were randomly divided into a study group ( n=46) and a control group ( n=47) . The control group received routine physical treatment, while the study group was treated with pattern-specific physical therapy involving local pain management, traction, soft tissue relaxation, mobilization, strength training, posture control training and active exercise as well as health education. Each was based on a physical exami-nation and pattern classification by doctors and therapists. The subjects in both groups were required to complete 3 to 6 ninety-minute sessions of outpatient treatment and 6 thirty-minute sessions of self-training at home over 2 weeks. Pain intensity and cervical dysfunction were rated using a visual analogue scale ( VAS) and a neck disability index ( NDI) before and after the two-week intervention and one month later. Before the intervention and during the follow-up, postural analyses for the head and neck in a standing position were performed. The cranial vertebral angle ( CVA) , protracted shoulder angle ( PSA) and sagittal head elevation were measured. Results Eighty-seven par-ticipants completed the treatments and follow-up. After the 2-week intervention, the average VAS rating at the end of cervical anteflection in the study group was significantly lower than that in the control group ( P≤0.05) . Significantly greater improvement in the NDI scores was observed in the study group than the control group ( P≤0.05) . During the follow-up, it was found that the average CVA score had improved more significantly in the study group than with the control group ( P≤0.01) , but there were no significant differences in the other measurements between the two groups.Conclusion This pattern-specific physical therapy process is more effective for relieving the end pain during cervical anteflection quickly. It can improve functioning and ability in daily activities to some degree, as well as correct head and neck posture in the long term. It may be helpful in regulating physical therapy for neck pain and for developing a standardized treatment protocol for CNP .