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The efficacy of a low-protein diet (LPD) on diabetic nephropathy is controversial. We aimed to investigate the renoprotective effects of an LPD and the underlying molecular mechanism in a rat model of type 2 diabetes and obesity.Diabetic male Wistar fatty (fa/fa) rats (WFRs) were treated with a standard diet (23.84% protein) or an LPD (5.77% protein) for 20 weeks from 24 weeks of age. We investigated the effect of the LPD on renal function, fibrosis, tubular cell damage, inflammation, mitochondrial morphology of proximal tubular cells (PTCs), apoptosis, autophagy and activation of mammalian target of rapamycin complex 1 (mTORC1).Kidney weight, albuminuria, excretion of urinary liver-type fatty acid binding protein, levels of plasma cystatin C and changes in renal histology, including fibrosis, tubular cell damage and inflammation, were aggravated in WFRs compared with non-diabetic Wistar lean rats (WLRs). Fragmented and swelling mitochondria accumulated in PTCs and apoptosis were enhanced in the kidney of WFRs. Immunohistochemical staining of p62 and p-S6 ribosomal protein (p-S6RP) in the tubular lesions of WFRs was increased compared with WLRs. The LPD intervention clearly ameliorated damage as shown by the assessment of renal function and histology, particularly tubulointerstitial damage in diabetic kidneys. Additionally, the 5.77% LPD, but not the 11.46% LPD, significantly suppressed p-S6RP levels and increased microtubule-associated protein light chain 3-II levels in the renal cortex. The LPD intervention partially decreased HbA1c levels in WFRs, and no differences in mean BP were observed among any of the groups.A very-low-protein diet improved advanced diabetic renal injuries, including tubulointerstitial damage, by restoring autophagy through the suppression of the mTORC1 pathway.

Background. Myocardial bridging (MB), a common benign coronary anomaly, may bring about some unwanted complications such as angina-like chest pain. The only way of MB detection is coronary arteriography or coronary computed tomographic angiography, which is costly and invasive. This study intended to profile a panel of circulating microRNAs (miRNAs) as potential biomarkers for the diagnosis of MB. Methods. Using TaqMan Low-Density Array followed by quantitative reverse transcriptase PCR (qRT-PCR) validation, we analyzed the expression of miRNAs in serum samples from 90 MB patients and 50 non-MB controls. Results. The Low-Density Array data showed that 196 miRNAs were differentially expressed in MB patient sera in comparison with controls. After qRT-PCR validation and receiver operating characteristic (ROC) analysis, a list of five miRNAs (miR-29b, miR-151-3p, miR-126, miR-503-3p and miR-645) showed the ability to distinguish MB patients from controls. The area under curve (AUC) values range from 0.722–0.938. Conclusions. We have demonstrated that this panel of five serum miRNAs is expected to become potential non-invasive biomarkers for detection of MB.

Background Coronary atherosclerosis, the most common form of coronary artery disease (CAD), is characterized by accumulation of lipid in the walls of coronary arteries. Recent data from clinical trials have showed that high-density lipoprotein cholesterol (HDL-C) has causal role in the pathogenesis and development of coronary atherosclerosis. Cholesteryl ester transfer protein (CETP) is an important regulator of plasma HDL-C. Several genetic mutations in the CETP gene were found to be associated with HDL-C levels. The aim of the present study is to evaluate the association of HDL-C-related CETP polymorphisms and risk of coronary atherosclerosis. Methods We investigated the association of seven single nucleotide polymorphisms (SNP) (rs1800775, rs708272, rs5882, rs1532624, rs1864163, rs7499892, and rs9989419) in the CETP gene with the risk of coronary atherosclerosis and levels of HDL-C in a case–control study in China. Included in the study were 420 patients with coronary atherosclerosis and 424 healthy controls. SNP genotyping was performed by TaqMan allelic discrimination assay and serum lipid levels were measured by standard laboratory methods. Results Carriers of the AA and GA + AA genotypes of rs708272 had significant lower risks of coronary atherosclerosis (OR = 0.55, 95% CI: 0.36-0.85, p = 0.003; OR = 0.67, 95% CI: 0.50-0.90, p = 0.007, respectively) compared to those with GG genotype. These relations remained significant after adjustment for confounding effects of age, smoking, diabetes and hypertension. The rs1800775 polymorphism was significantly associated with serum levels of HDL-C in healthy controls (p = 0.04). Besides, rs708272 was in close linkage disequilibrium (LD) with rs1800775 in this study. Conclusions Our findings indicated that CETP rs708272 may be associated with the risk of coronary atherosclerosis and rs1800775 may influence serum HDL-C levels in healthy controls in Chinese.

Purpose: This study was to investigate whether high pericardial adipose tissue (PAT) volume is related to the presence and severity of coronary artery disease (CAD). Methods: Consecutive patients (310 patients) who underwent both dual-source 64-slice CT and percutaneous coronary angiography were recruited into this study. Waist circumference (WC), body mass index (BMI), blood biochemical variables, coronary artery calcium (CAC) score and Gensini score were measured. Pericardial adipose tissue (PAT) volume was determined by dual-source CT. Results: PAT volume was positively correlated with BMI, WC, gender (male), hypertension, diabetes, age, total cholesterol and low-density lipoprotein-cholesterol. PAT volume in CAD patients was significantly higher than that in patients without CAD (238.36 ± 81.21 cm3 vs. 200.13±72.34 cm3). PAT volumes in patients with multi-vessel lesions were significantly higher than those with one-vessel lesions (P < 0.001). A significant correlation between PAT volume and CAC score (r=0.305, P < 0.001) was found. PAT volume was an independent factor affecting Gensini score. Conclusion: PAT volume was significantly correlated with traditional cardiovascular risk factors, the severity of coronary atherosclerosis and the number of stenotic coronary vessels. Thus, PAT volume may be a reliable marker to evaluate the presence and severity of CAD.

Objective: To describe a case with acute myocardial infarction caused by gastric carcinoma-associated thrombotic thrombocytopenic purpura. Clinical Presentation and Intervention: A 79-year-old man was admitted with abdominal pain and pyrexia. He later developed cardiac complications and microangiopathy that indicated worsening progression. Manifold evidence confirmed the diagnosis of myocardial infarction caused by thrombotic thrombocytopenic purpura. The patient was treated mainly with plasma transfusion incorporated with steroids. Conclusion: This case should remind physicians to consider microangiopathy as a differential diagnosis in patients with unexplained cardiac symptoms or atypical presentation. Early diagnosis and treatment are helpful in decreasing the sequelae of this syndrome.

Suicide attempts constitute a serious clinical problem. People who have attempted suicide are at an elevated risk for additional suicide attempts, but there is limited evidence regarding the predictors of suicidality of suicide attempters following case management services. In the present study the indicators of suicidality after case management were examined. A total of 1,056 subjects who had recently attempted suicide were recruited from January 1, 2011, to June 30, 2011. The suicide prevention center of Kaohsiung City in Taiwan provided case management services and followed up on suicide attempt cases for 6 months. The salient factors for repeat suicide attempts were estimated using a logistic regression analysis. The results showed that multiple factors, including a "willingness to receive mental health services during a crisis," "social support," "a history of mental disorders," and "a history of suicide," could predict repeat suicide attempts with hazard ratios (0.58, 0.54, 3.84, 1.51) and 95% confidence interval (0.39-0.86, 0.36-0.83, 2.41-6.10, 1.03-2.21). The four factors mentioned above were the most accurate predictors of subsequent suicidality when case management services were utilized after 6 months of follow-up. The findings of our study could help clarify future strategies for suicide prevention. Language: en

Background Suicide attempts constitute a serious clinical problem and have important implications for healthcare resources. The aim of the present study was to evaluate the effectiveness of case management using crisis postcards over a 6-month follow-up period. Method A randomised controlled trial was conducted in Kaohsiung, Taiwan. Prevention of further suicide attempts was compared between two groups with and without the postcard intervention. The intervention group consisted of 373 participants (139 males, 234 females; age: 39.8 ± 14.0 yrs.). The control group consisted of 388 participants (113 males, 275 females; age: 40.0 ± 16.0 yrs.). A survival analysis was used to test the effectiveness of the crisis postcard intervention for the prevention of suicide reattempts. Per-protocol and intention-to-treat analyses were conducted. Results The intention-to-treat analysis indicated that the crisis postcard had no effect (hazard ratio = 0.84; 95% CI = 0.56 – 1.29), whereas the per-protocol analysis showed a strong benefit for the crisis postcard (hazard ratio = 0.39; 95% CI = 0.21 – 0.72). Conclusion Although the results of the present study indicated that the postcard intervention did not reduce subsequent suicide behaviour, our study provides an alteration to the postcard intervention. Further studies need to be conducted to clarify whether this type of intervention can reduce subsequent suicidal behaviour, with a particular focus on reducing the rate of loss to follow-up.

1. The aim of the present study was to determine whether ligustrazine (2,3,5,6-tetramethylpyrazine; TMP) exerts a cardioprotective effect during myocardial ischaemia reperfusion (IR), and to investigate the underlying mechanisms and the role of endothelial nitric oxide synthase (eNOS) in cardioprotection. 2. Sprague-Dawley rats were divided into a sham group and five IR groups: IR control, TMP pretreated, TMP + wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor), N(G) -nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) and TMP + L-NAME. IR was produced by 35 min of regional ischaemia followed by 120 min of reperfusion. Myocardial infarct size, oxidative stress, myocardial apoptosis, nitric oxide (NO) production, and expression of phosphorylated protein kinase B (Akt) and eNOS were measured. 3. TMP markedly decreased infarct size and attenuated myocardial apoptosis, as evidenced by a decrease in the apoptotic index and reduced caspase-3 activity. TMP treatment caused a marked increase in NO production. Cotreatment with wortmannin or L-NAME completely blocked the TMP-induced NO increase. TMP induced phosphorylation of Akt at Ser 473 (1.61 ± 0.18 vs 0.79 ± 0.10 in the IR control group) and phosphorylation of eNOS at Ser1177 (1.87 ± 0.33 vs 0.94 ± 0.22 in the IR control group). Wortmannin abrogated the phosphorylation of Akt and eNOS induced by TMP. 4. These data suggest that ligustrazine has anti-apoptotic and cardioprotective effects against myocardial IR injury and that it acts through the PI3K/Akt pathway. In addition, the phosphorylation of eNOS with subsequent NO production was found to be an important downstream effector that contributes significantly to the cardioprotective effect of TMP.

Background: Dual-source CT coronary angiography (CTCA) has been used to detect coronary artery disease; however, the factors with potential to affect its diagnostic accuracy remain to be defined. Purpose: To prospectively evaluate the accuracy of dual-source CTCA in diagnosing coronary artery stenosis according to conventional coronary angiography (CAG), and the effect of average heart rate, heart rate variability, and calcium score on the accuracy of CTCA. Material and Methods: A total of 113 patients underwent both dual-source CTCA and CAG. The results were used to evaluate the findings in dual-source CTCA to assess the accuracy in the diagnosis of ≥50% (significant stenosis) and >75% (severe stenosis) of coronary artery according to those by CAG. Patients were divided into subgroups according to their heart rate (HR), HR variability (HRV), and calcium score, and the accuracy of CTCA was further evaluated. The chi-square test was used to analyze the difference in sensitivity and specificity for the detection of ≥50% and >75% coronary stenosis among subgroups. The generalized estimation equation method was used in per-vessel analysis to adjust for within-patient correlation. Results: In all, 113 patients had 338 vessels and 1661 segments evaluated by CAG. Dual-source CTCA displayed 1527 segments (91.9%). Among them, 1468 segments (calcium score by CAG score 1, n=1018; score 2, n=270; score 3, n=180) were assessable in CTCA. On a per-patient analysis, the sensitivity and specificity of CTCA were 93.9% and 93.5% for significant stenosis and 86.9% and 98.1% for severe stenosis. On a per-vessel basis, the sensitivity and specificity were 90.2% and 97.1% for significant and 83.3% and 98.1% for severe stenosis. On a per-segment analysis, the sensitivity and specificity were 90.2% and 97.1% for significant and 83.3% and 98.1% for severe stenosis. Average HR had no effect on the sensitivity and specificity of CTCA ( P>0.05); whereas HRV and calcium score had some effect on the sensitivity and specificity of CTCA ( P Conclusion: On a per-patient, per-vessel, and per-segment basis, dual-source CTCA has a high sensitivity and specificity for the diagnosis of coronary artery stenosis. Average HR has no effect on the diagnostic accuracy of CTCA, while HRV and calcium score have a statistically significant effect on the sensitivity and specificity of CTCA.

To determine the presence of membrane testosterone receptors in cultured vascular smooth muscle cells (VSMC), and investigate their relationship with classical intracellular androgen receptors (iAR).VSMCs were cultured from the thoracic aorta of male Sprague-Dawley rats by the explant method. Subconfluent VSMCs were incubated with serum-free medium for 24 h to obtain quiescent non-dividing cells, and then treated with the indicated agents. The aliquots of VSMCs were labeled with testosterone-BSA-FITC (T-BSA-FITC) and analyzed by flow cytometry. Classical iARs in intact- and permeabilized-cells were detected with anti-iAR antibodies and FITC-labeled secondary antibodies by immunofluorescence, followed by flow cytometry analysis.Incubation of VSMCs with T-BSA-FITC obviously increased their relative fluorescence intensity at 10 sec as compared with the untreated controls (P0.01), and so did it at 10 min in comparison with the treatment with BSA-FITC alone or together with free testosterone (P0.01). Pretreatment with iAR antagonist flutamide exhibited no significant influence on the relative fluorescence intensity of VSMCs (P = 0.318). Traditional iARs were not detectable on the surface of intact VSMCs, although permeabilized cells contained iARs.VSMCs contain testosterone receptors in the plasma membrane, and these membrane receptors are not identical to classical iARs.

Clinical studies have shown decreased levels of sexual hormones, particularly testosterone deficiency, in men with chronic heart failure (CHF). The authors aimed to investigate the effect of testosterone on cardiac function and the possible mechanism of androgen protecting the heart in male rats.Forty-three male SD rats were randomly divided into 3 groups: right heart failure (RHF, n = 15), physiologic testosterone treatment (TT, n = 15) and control (n = 13). The RHF group was given intraperitoneal injection of monocrotaline at 60 mg/kg to make RHF models; the TT group was injected with testosterone at 5 mg/kg 3 days after monocrotaline administration; and the control group received equal volume of saline. The CD34+ cells in the peripheral blood of each rat were counted by flow cytometry. The levels of serum testosterone and tumor necrosis factor alpha (TNF-alpha) were measured by chemiluminescence immunoassay and enzyme linked immunosorbent assay, respectively. The hearts, lungs and livers of all the surviving rats were excised at 6 weeks for pathological and immunohistochemical examinations.The level of serum testosterone was gradually decreased, while that of TNF-alpha obviously increased in the RHF group. After testosterone treatment, the TT group showed a remarkable improvement of cardiac performance and a significant decrease in the level of serum TNF-alpha as compared with the RHF group. Statistically significant differences were observed neither in the CD34+ cell count in the peripheral blood nor in the CD34+ expression of the myocardial cells between the TT and RHF groups.Physiological supplementation of testosterone can improve the cardiac function of RHF male rats, probably through its inhibition of TNF-alpha rather than by autologous mobilization of bone marrow stem cells.

To explore the acute effects of testosterone at the physiological level on PGF2alpha-induced increase in intracellular Ca2+ in cultured vascular smooth muscle cells (VSMCs).VSMCs from the thoracic aorta of male Sprague-Dawley rats were cultured using the explant method. The subconfluent VSMCs were incubated with serum-free medium for 24 hours to obtain quiescent non-dividing cells and then treated with the indicated agents. For the measurement of [Ca2+]i, the VSMCs were loaded with fura-2. Changes of [Ca2+]i were determined ratiometrically with a Nikon TE-2000E system.The resting level of [Ca2+]i was around 100 nmol/L in the VSMCs. Exposing cells to perfusate containing 10 micromol/L PGF2alpha triggered an immediate and transient peak in [Ca2+]i, which gradually decreased afterwards. Interference at the peak with the physiological concentration (40 nmol/L) of testosterone significantly decreased the peak-to-baseline time of [Ca2+]i, compared with ethanol vehicle (104.9 +/- 27.0 s vs 153.5 +/- 40.4 s, P0.01). Pretreatment with testosterone at 40 nmol/L for 2 minutes also reduced the peak-to-baseline time of [Ca2+]i significantly in comparison with the ethanol control (120.6 +/- 32.0 s vs 151.4 +/- 27.4 s, P0.01), but it had no significant effect on the peak level of PGF2alpha-induced intracellular Ca2+ (390.0 +/- 126.0 nmol/L vs 403.4 +/- 160.7 nmol/L, P0.05).Testosterone at physiological concentration inhibits PGF2alpha-induced Ca2+ fluxes, probably via receptor-operated calcium channels by a non-genomic mechanism in VSMCs, which may be involved in the vasodilatory effect of testosterone.

To compare coronary lesion characteristics by coronary angiography (CAG) between yellows and whites.CAG results of 3021 Chinese patients, defined as yellows, from Nanjing and 3230 Australian patients, defined as whites, from Sydney were analyzed. The coronary artery lesion was evaluated by the number and location of coronary lesion and Gensini scores.(1) Coronary stenosis was diagnosed in 69.4% Chinese patients and 75.5% in Australians. The involved coronary arteries were left anterior descending branch, right coronary artery, left circumflex branch and left main coronary artery in a descending order in both Chinese and Australians. (2) The incidences of three-vessel disease and left main disease of yellows were significantly lower than that of whites in both male (29.8% vs. 34.0% and 9.6% vs. 14.2%) and female patients (15.8% vs. 26.2% and 4.9% vs. 11.6%) respectively, all P0.05. (3) There was an age-dependent Gensini scores increase in both yellows and whites patients and Gensini scores at age 40 and more of whites were significantly higher than those of yellows in comparable age groups.The incidences of three-vessel disease and left main disease as well as Gensini score were significantly higher in Australian patients than those of Chinese patients.

To investigate the efficacy of adaptive pressure support servo-ventilation (APSSV) on Cheyne-Stokes respiration (CSR) in congestive heart failure (CHF).14 patients with CHF and CSR were recruited. During sleep, oxygen therapy and APSSV were separately performed. Comparison before and after each treatment was made for the following items: a) parameters of sleep respiration, sleep structure and quality; b) cardiac function index such as left ventricle ejection fraction (LVEF) and 6 minutes' walking distance; c) plasma endothelin-1 (ET-1) levels.Compared with the baseline level before treatment, the apnea hypopnea index significantly decreased during oxygen therapy (P0.05) and further declined during APSSV (P0.01); on the contrary, the lowest pulse oxygen saturation increased during oxygen therapy (P0.05) and further elevated during APSSV (P0.01). Compared with arousal index before treatment, it was significantly lower during oxygen therapy (P0.05) and the lowest during APSSV (P0.01). Compared with both during oxygen therapy and before treatment, during APSSV the percentage ofI + II stage sleep time/total sleep time was significantly lower while the percentage of III + IV stage sleep time/total sleep time was significantly higher. The above percentages during oxygen therapy and before treatment showed no significant difference (P0.05). LVEF was significantly higher during APSSV than during oxygen therapy and before treatment (P0.05). Six minutes' walking distance was the shortest before treatment and the longest during APSSV. There was a significant difference among that before treatment, during oxygen therapy and APSSV (all P0.01). The plasma ET-1 level showed significantly lower during APSSV than that before and during oxygen treatment (P0.05), but no significant difference between the levels before and during oxygen treatment (P0.05).APSSV, more effective than oxygen therapy, is of great clinical significance in improvement of CHF and its prognosis by a better sleep and breathing.

To investigate the effects of testosterone exposure on androgen receptor (AR) mRNA expression in cultured vascular smooth muscle cells (VSMCs).VSMCs were cultured from the thoracic aorta of male SD rats using explant method. The total RNA was extracted by one-step guanidine isothiocyanate method and subjected to Northern blotting analysis for determining AR mRNA level. The effect of testosterone on the viability and growth of VSMCs were studied by means of cell counting and tritiated thymidine incorporation assay.Testosterone treatment of the synchronized VSMCs for 24 h increased intracellular AR mRNA expression in a dose-dependent manner, with relative mRNA level of 97.67+/-7.22, 98.00+/-13.58, 143.33+/-10.99, 177.67+/-14.62 and 185.67+/-19.97 corresponding to testosterone doses of 0, 4 nmol/L, 40 nmol/L, 400 nmol/L and 4 micromol/L, respectively. Incubation of synchronized VSMCs with testosterone at a physiological level of 40 nmol/L for 24 h resulted in a mean of 30% up-regulation of AR mRNA level, compared with that of untreated cells. During AR up-regulation, testosterone had no significant effects on the cell number and DNA synthesis of VSMCs as measured by cell counting and tritiated thymidine incorporation assay.Self-initiated up-regulation of AR mRNA expression occurs in synchronized VSMCs, which is independent of testosterone that influences apoptosis or growth rate of the cells, suggesting the involvement of AR in androgen regulational at the transcription level in VSMCs.