Sex differences in the association of the uric acid to high-density lipoprotein cholesterol ratio with coronary artery disease risk among Chinese nondialysis patients with CKD stages 3-5.

BACKGROUND AND AIMS: Evidence has indicated that serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with coronary artery disease (CAD). The UA to HDL-C ratio (UHR) has recently drawn attention as a new predictor for metabolic syndrome, inflammation and atherosclerosis. However, the association between the UHR and CAD in nondialysis chronic kidney disease (CKD) patients is still unclear. METHODS AND RESULTS: We retrospectively analysed 733 nondialysis patients with CKD stage 3-5 who received their first coronary artery angiography (CAG), including 510 participants with CAD. All laboratory indicators were collected within one week before CAG. The median UHR of CAD and non-CAD patients was 15.52% and 12.29%, respectively. In multivariate analysis, female patients with a high UHR were 4.7 times more at risk of CAD than those with a lower UHR. Meanwhile, the positive association of the UHR with the severity of coronary artery stenosis (CAS) persisted significantly in female CAD subjects but not in males. In addition, receiver operating characteristic (ROC) curves were constructed for CAD and severe CAS. The area under the curve (AUC) for the UHR was higher than that for UA and HDL-C alone in female patients [UHR (AUC): 0.715 for CAD and 0.716 for severe CAS]. CONCLUSIONS: An elevated UHR was independently related to an increased CAD risk and the severity of CAS in nondialysis female patients with CKD stage 3-5, and was more predictive of the onset of CAD and the severity of CAS than UA or HDL-C alone.

Effects of Sacubitril/Valsartan on resistant hypertension and myocardial work in hemodialysis patients.

Growing evidences have confirmed the effect of Sacubitril/Valsartan (SV) on antihypertension and cardiac protection in general population. However, there was no prospective study about the effect and safety of SV on resistant hypertension and myocardial work in hemodialysis patients. In this single-center, prospective, before-after study, enrolled patients were endured with resistant hypertension for more than 6 months. Participants were initially instructed to take SV 50 mg twice daily, and the dosage was gradually increased up to 100 mg twice daily. The primary outcomes were blood pressure (BP) control, N-terminal pro-B-type natriuretic peptide (NT-proBNP), myocardial work (MW), fatigue and life quality. In addition, the adverse events were also recorded in this cohort. A total of 18 patients (34-64 years old) was finally enrolled and completed in this study. The SV-based regimen provided significantly mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-20.7/-8.3 mm Hg), respectively. The cardiac remodeling parameters were partially improved. Compared to the baseline, NT-proBNP was significantly reduced at week 4 (8119.50 [3710.75, 29300] pg/ml to 7216.50 [4124.75, 17455.00] pg/ml, p = .046), which was much lower at week 12 (3130.50 [2244.50, 9565.70] pg/ml, p = .037). Global MW index was higher at week 12 compared to the baseline (p = .026). MW efficiency was also improved accordingly compared to the baseline, even though the statistical difference was not significant (p = .226). Life quality and fatigue were improved at week 12 compared to the baseline (all p = .000). There was no serious adverse events were observed. SV safely and effectively controlled resistant hypertension and improved MW as well as life quality in hemodialysis patients.

Transient receptor potential melastatin 4 contributes to early-stage endothelial injury induced by arsenic trioxide.

BACKGROUND/AIMS: To investigate the effect of Arsenic Trioxide (ATO) on endothelial cells injury and explore the role of transient receptor potential melastatin 4 channel (TRPM4) in ATO-induced endothelial injury. METHODS: qRT-PCR was used to examine the mRNA expression of TRPM4 in human umbilical vein endothelial cells (HUVECs). The protein levels were measured by Western blot and immunostaining. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, apoptosis, and migration, respectively. The ultrastructural changes were observed by scanning electron microscopy. The membrane potential, cytosolic [Na+]i, cytosolic [Ca2+]i and reactive oxygen species (ROS) levels were detected by fluorescent probes. Isometric tension of mesenteric artery was recorded by using a multiwire myograph system. RESULTS: ATO induced HUVEC cells injury, the significant upregulation of TRPM4 in this process was inhibited by 9-phenanthrol or siRNA. ATO-induced apoptosis and decrease in the cell viability/ migration were all partially reversed upon the treatment with 9-phenanthrol. Whereas, ATO-mediated increase in membrane potential, cytosolic [Na+]i, cytosolic [Ca2+]i and the ROS levels were also abolished by 9-phenanthrol or siRNA, suggesting that oxidative stress may be the potential mechanisms underlying ATO-induced endothelial injury. Additionally, 9-phenanthrol treatment prevented ATO-mediated impairment of acetylcholine-induced endothelium-dependent relaxations. CONCLUSION: TRPM4 is involved in endothelial injury induced by ATO and may be a promising therapeutic target for endothelial injury.

[Effect of Ningdong Granule on the levels of IL-12 and TNF-alpha in children patients with Tourette's syndrome].

OBJECTIVE: To observe the effect of Ningdong Granule (NG) on serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) of children patients with Tourette's syndrome (TS). METHODS: Totally 90 TS children patients were randomly assigned to the NG group, the NG + Tiapride group (abbreviated as the combined treatment group), and the Tiapride group, 30 in each group. Besides,another 30 healthy children were recruited as the healthy control group. Patients in the NG group were treated with NG (consisting of all gastrodia rhizome, Codonopsis pilosula, Ophiopogon japonicus, white peony root, Rhinocerotidae, oyster, earthworm, licorice root, etc.), one dose daily, administered by dissolving it in boiled water, taken in two portions in the morning and in the evening respectively. Patients in the Tiapride group took Tiapride Tablet, 50 -100 mg each time, twice daily. The dosage was adjusted according to individual difference and changes of pathogenic conditions. The maximal dosage was 300 mg per day. Those in the combined treatment group were treated with equal dose of NG and Tiapride Tablet in combination. The treatment course was 3 months for all. Changes of pathogenic condition before and after treatment were assessed by Yale global tic severity scale (YGTSS). Serum levels of IL-12 and TNF-alpha were detected by enzyme-labeled immunosorbent assay (ELISA) before and after treatment. RESULTS: (1) The total effective rate of the NG group, the combined treatment group, and the Tiapride group was 79.3%, 83.3%, and 67.9%, respectively. It was the lowest in the Tiapride group (P < 0.05). It was significantly higher in the combined treatment group than in the NG group (P < 0.05). (2) The post-treatment YGTSS score was obviously lower in each group after treatment than before treatment (P < 0.05). The posttreatment YGTSS score was obviously lower in the NG group and the combined treatment group than in the Tiapride group (P < 0.05), but with no statistical difference between the fromer two groups (P > 0.05).(3) Compared with the healthy control group before treatment, serum levels of IL-12 and TNF-alpha (pg/mL) were 124.95 +/- 22.78 and 209.52 +/- 21.69 in the NG group, 126.14 +/- 25.65 and 208.97 +/- 22.46 in the combined treatment group, 123.00 +/- 24.26 and 205.10 +/- 26.16 in the Tiapride group, being higher than those in the healthy control group (64.56 +/- 27.59 and 78.13 +/- 33.42; P < 0.05). After treatment, serum levels of of IL-12 and TNF-alpha were 104.67 +/- 16.84 and 183.01 +/- 24.95 in the NG group, 109.04 +/- 16.81 and 179.87 +/- 23.45 in the combined treatment group, significantly lower than before treatment (P < 0.05). But there was no statistical difference in serum levels of IL-12 or TNF-alpha in the Tiapride group between before treatment (123.00 +/- 24.26 and 205.10 +/- 26.16) and after treatment (117.75 +/- 16.79 and 199.76 +/- 33.21; P > 0.05). CONCLUSION: NG could modulate abnormal serum levels of IL-12 and TNF-alpha in TS children patients, which might be one of its pharmacodynamic mechanisms for treating TS.

[Effect of ningdong granule on stereotyped behaviors in Tourette syndrome model rats of different Chinese medical syndromes].

OBJECTIVE: To observe the effect of Ningdong Granule (NDG) on stereotyped behaviors in Tourette's syndrome (TS) model rats of different Chinese medical syndromes. METHODS: Thirty-two Wistar rats were used to establish TS models of different Chinese medical syndromes (n =8) induced by TS children patients' sera of 4 syndromes, i.e., Xin-Gan deficiency syndrome (XGDS), Gan-Shen yin deficiency syndrome (GSYDS), sputum-turbid blocking aperture syndrome (STBAS), and Gan hyperactivity Pi deficiency syndrome (GHPDS). Corresponding sera was micro-infused to them while administering NDG (120 mg/kg each time, thrice daily, for 3 successive weeks). Besides, another normal control group (n =8) was set up by injecting sera from healthy children plus intragastric perfusion of normal saline. Stereotyped behaviors were recorded on the 1st, 7th, 14th, and 21st day after administration of NDG. RESULTS: The anti-neural antibody serum concentration in TS children was significantly higher than that in healthy control [(1.28 +/- 0.36) UL vs. (0.52 +/- 0.24) U/L, P < 0.01 ]. It was (1.34 +/- 0.41) U/L in the XGDS group, (1.19 +/- 0.51) U/L in the GSYDS group, (1.29 +/- 0.61) U/L in the STBAS group, and (1. 17 +/- 0.45) U/L in the GHPDS group, showing no statistical difference (P > 0.05). There was no statistical difference in stereotypic behaviors of rats after treatment among the four different Chinese medical syndromes (P > 0.05). At day 7, 14, and 21 after treatment by NDG, the times of stereotyped behaviors were significantly less in the XGDS group than in the other three groups at the same time points except in the GHPDS group at day 14 (P < 0.05, P < 0.01). Meanwhile, the total numbers of stereotyped behaviors in the XGDS group [(42.8 +/- 12.6)] was obviously superior to that in the GSYDS group [(29.3 +/- 13.7)], the STBAS group [(21.9 +/- 10.4)], and the GHPDS group [(30.6 +/- 9.6)], showing statistical difference (P < 0.01, P < 0.05) after treatment by NDG at day 21. CONCLUSIONS: The anti-neural antibody serum concentration in TS children was significantly higher than that in healthy children. Stereotyped behaviors could be induced in rats after intrastriatal micro-infusion of TS sera rich in anti-neural antibody. TS model rats of XGDS were better improved than rats in the other 3 groups after treatment by NDG.