Insight on Efficacy of Renal Artery Denervation for Refractory Hypertension with Chronic Kidney Diseases: A Long-Term Follow-Up of 24-Hour Ambulatory Blood Pressure.

Aims: To explore the long-term efficacy and safety of renal denervation in patients with RHT and CKD, a post hoc analysis of eGFR subgroups was completed. Methods: Fifty-four patients with refractory hypertension with chronic kidney disease were treated with RDN and enrolled in the study. Patients were divided into three groups according to eGFR: eGFR 46-90 ml/min group, eGFR 15-45 ml/min group, and eGFR <15 ml/min group. The planned follow-up period was 48 months to assess 24 h ambulatory blood pressure, renal function, type of antihypertensive medication, and RDN complications. Results: The ablation sites of the GFR 46-90 ml/min group and GFR 15-45 ml/min group were 32.57 ± 2.99 and 29.53 ± 5.47, respectively. No complications occurred in the GFR 46-90 ml/min group. The GFR<15 ml/min group was treated with 27.07 ± 5.59 ablation. Renal artery dissection occurred in each group of GFR 15-45 ml/min and GFR <15 ml/min. And renal stent implantation artery was performed on these two patients. No severe renal artery stenosis occurred. There were no significant differences in Scr and eGFR between the three groups at each follow-up point. Compared with baseline, SBP was significantly of each group decreased to varying degrees at each follow-up time point. SBP decreased most in the GFR 46-90 ml/min group. Compared with baseline, the type of antihypertensive drugs used in the GFR46-90 ml/min group decreased significantly except for 36 and 48 months. At 48 months' postadmission, there was a significant decrease in the type of antihypertensive medication used in the GFR15-45 ml/min group, and there was no significant decrease in the type of antihypertensive medication used in the GFR<15 ml/min group. Conclusions: RDN can safely reduce SBP in CKD patients combined with RHT for 48 months, with the most pronounced reduction in the GFR15-45 ml/min group. The variety of antihypertensive drugs was significantly reduced after RDN. This was particularly evident in patients with GFR 15-45 ml/min.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with hypertrophic cardiomyopathy with non-valvular atrial fibrillation.

Hypertrophic cardiomyopathy (HCM) patients with nonvalvular atrial fibrillation (AF) have an increased risk of suffering thromboembolic events. Vitamin K antagonists (VKA) are recommended as therapy but there is still limited data regarding the efficacy of prescribing non-vitamin K antagonist oral anticoagulants (NOACs). This retrospective study investigates the effectiveness and safety of NOAC administration in patients with HCM and AF. A total of 124 patients with HCM and AF on an oral anticoagulant therapy were recruited between January 2015 and December 2019; these patients were followed up until March 31, 2020. Kaplan-Meier analysis was used to compare the clinical outcomes in patients treated with NOACs versus warfarin. The Cox model was used to estimate the risk of clinically relevant bleeding. Our study included 124 patients, of which 48 (38.7%) received warfarin and 76 (61.3%) received NOACs. Survival analysis showed the patients undergoing NOACs had a lower risk of clinically relevant bleeding (log-rank P = 0.039) over a period of 53.6 months. The median time in therapeutic range (TTR) score was 50% (interquartile range: 40.43 to 57.08%). A total of nine patients (18.75%) had a good TTR with a median score of 66.35% (interquartile range: 64.58 to 77.75%). The incidence of death by all causes, cardiovascular death and thromboembolism were similar between NOAC and warfarin-treated patients (log-rank P = 0.239, log-rank P = 0.386, and log-rank P = 0.257, respectively). Patients treated with NOACs showed a significant reduction in the risk of clinical (P = 0.011) and gastrointestinal bleeding (P = 0.032). Cox multiple regression analysis showed age (HR 1.13, 95% CI 1.03-1.24; P = 0.013) and warfarin therapy (HR 7.37, 95% CI 1.63-33.36; P = 0.010) were independent predictors of clinically relevant bleeding. Compared to warfarin, NOACs were associated with a lower incidence of clinically relevant bleeding in HCM patients with AF, as demonstrated by the similar incidence of death by all causes, cardiovascular death and thromboembolic events.

Lysine glycation of apolipoprotein A-I impairs its anti-inflammatory function in type 2 diabetes mellitus.

Apolipoprotein A-I (apoA-I), the major protein compontent of high-density lipoprotein (HDL), exerts many anti-atherogenic functions. This study aimed to reveal whether nonenzymatic glycation of specific sites of apoA-I impaired its anti-inflammatory effects in type 2 diabetes mellitus (T2DM). LC-MS/MS was used to analyze the specific sites and the extent of apoA-I glycation either modified by glucose in vitro or isolated from T2DM patients. Cytokine release in THP-1 monocyte-derived macrophages was tested by ELISA. Activation of NF-kappa B pathway was detected by western blot. The binding affinity of apoA-I to THP-1 cells was measured using 125I-labeled apoA-I. We identified seven specific lysine (Lys, K) residues of apoA-I (K12, K23, K40, K96, K106, K107 and K238) that were susceptible to be glycated either in vitro or in vivo. Glycation of apoA-I impaired its abilities to inhibit the release of TNF-α and IL-1ß against lipopolysaccharide (LPS) in THP-1 cells. Besides, the glycation levels of these seven K sites in apoA-I were inversely correlated with its anti-inflammatory abilities. Furthermore, glycated apoA-I had a lower affinity to THP-1 cells than native apoA-I had. We generated mutant apoA-I (K107E, M-apoA-I) with a substitution of glutamic acid (Glu, E) for lysine at the 107th site, and found that compared to wild type apoA-I (WT-apoA-I), M-apoA-I decreased its anti-inflammatory effects in THP-1 cells. We also modeled the location of these seven K residues on apoA-I which allowed us to infer the conformational alteration of glycated apoA-I and HDL. In summary, glycation of these seven K residues altered the conformation of apoA-I and consequently impaired the protective effects of apoA-I, which may partly account for the increased risk of cardiovascular disease (CVD) in diabetic subjects.

Impact of renin-angiotensin-aldosterone system-blocking agents on the risk of contrast-induced acute kidney injury: a prospective study and meta-analysis.

OBJECTIVE: We sought to assess the impact of the pretreatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for coronary intervention on the risk of contrast-induced acute kidney injury (CI-AKI) after 72-hour postcontrast administration, together with a comprehensive meta-analysis in this aspect. METHODS AND RESULTS: In this prospective study, 401 patients referred for percutaneous coronary intervention were enrolled with 134 patients in non-renin-angiotensin-aldosterone system group, 204 patients in ACEIs group and 63 patients in ARBs group. For further meta-analysis, articles were identified through PubMed, EMBASE, Wanfang, and VIP. Data extraction and study quality were assessed in duplicate. Altogether, 14 qualified trials (including this prospective study) with 1960 patients taking ACEIs or ARBs and 1457 patients receiving no renin-angiotensin-aldosterone system blockers were analyzed. There was an overall 1.28-fold increased risk for CI-AKI in patients taking ACEIs or ARBs (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.79-2.09; P = 0.315). Overall changes in serum creatinine, estimated GFR, and blood urea nitrogen were also nonsignificant. Subgroup analyses identified a significantly increased risk for CI-AKI in patients taking ARBs (OR = 3.31; 95% CI, 1.89-5.78; P < 0.0005), and no significance was observed for patients taking ACEIs (OR = 0.86; 95% CI, 043-1.72; P = 0.664). Also, patients taking ARBs had serum creatinine markedly increased by 0.05 mg/dL (95% CI, 0.02-0.09; P = 0.005). CONCLUSIONS: The findings of this meta-analysis provide clear evidence for a deleterious impact of ARBs on the development of CI-AKI.

Efficacy and safety of 3D reconstruction and basket multi-electrode renal denervation (RDN) for refractory hypertensive patients with chronic kidney disease.

Renal Artery Sympathetic Denervation (RDN) can lower blood pressure. Different ablation catheters (single electrode, multi-electrode) have different scopes of ablation (renal artery main stem and branches). Few studies have compared the advantages and disadvantages of different ablation catheters and different procedures in terms of antihypertensive efficacy. To compare the efficacy and safety of 3D reconstruction radiofrequency ablation (3DRA) and basket multi-electrode radiofrequency ablation (BMRA) in Renal Artery Sympathetic Denervation. Fifty-three patients with Refractory hypertension (RHT) were divided into BMRA, (n = 28) and 3DRA(n = 25). BMRA group used a stereobasket multi-electrode ablation catheter with a controlled ablation temperature of 60°C and an ablation time of 120 s per site. 3DRA group used a NavStar pressure-monitored perfusion monopolar ablation catheter with a controlled ablation temperature of 40°C, an ablation time of 40 s per site, and an ablation energy of 12 W. Baseline and RDN parameters and complications were compared in both groups. Home and 24 h ambulatory blood pressure, type of anti-hypertensive medication taken, and serum creatinine were followed up at 1, 3, 6, 12, and 24 months after the RDN. There were no differences in baseline characteristics between the two groups. (23.14 ± 2.00)months of follow-up in the BMRA group resulted in a total of (25.86 ± 8.61) loci ablation. (19.28 ± 7.40)months of follow-up in the 3DRA group resulted in a total of (21.04 ± 6.47)loci ablation. Home SBP was significantly lower in both groups at 1 month after RDN treatment compared to baseline(H-SBP/mmHg: BMRA 149.9 ± 10.59 vs. baseline 168.36 ± 12.76; 3DRA 152.6 ± 14.91 vs. 164.89 ± 12.96, both p < .05). The proportion of people with 24 h ambulatory SBP attainment was significantly higher in both groups and was maintained for 24 months. At each follow-up time point, there were no differences in home and 24-h flow SBP, DBP, or Scr between the two groups. There were two cases of severe renal artery complications from implanted vascular stents and one case of femoral artery pseudoaneurysm in the 3DRA group. At follow-up, 1 (1.9%) patient in the 3DRA group died of unexplained death and 1 (1.9%) patient developed heart failure, and 1 (1.9%) patient in the BMRA group died of unexplained death. Basket multi-electrode radiofrequency ablation and 3D reconstruction radiofrequency ablation of the renal artery applied to RDN have comparable efficacy in reducing systolic blood pressure.

Afferent Renal Denervation Attenuates Sympathetic Overactivation From the Paraventricular Nucleus in Spontaneously Hypertensive Rats.

BACKGROUND: The effectiveness of renal denervation (RDN) in reducing blood pressure and systemic sympathetic activity in hypertensive patients has been established. However, the underlying central mechanism remains unknown. This study aimed to investigate the role of RDN in regulating cardiovascular function via the central renin-angiotensin system (RAS) pathway. METHODS: Ten-week-old spontaneously hypertensive rats (SHR) were subjected to selective afferent renal denervation (ADN) using capsaicin solution. We hypothesized that ADN would effectively reduce blood pressure and rebalance the RAS component of the paraventricular nucleus (PVN) in SHR. RESULTS: The experimental results show that the ADN group exhibited significantly lower blood pressure, reduced systemic sympathetic activity, decreased chronic neuronal activation marker C-FOS expression in the PVN, and improved arterial baroreflex function, compared with the Sham group. Furthermore, ACE and AT1 protein expression was reduced while ACE2 and MAS protein expression was increased in the PVN of SHR after ADN. CONCLUSIONS: These findings suggest that RDN may exert these beneficial effects through modulating the central RAS pathway.

Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity.

AIMS/HYPOTHESIS: In type 2 diabetes mellitus (T2DM), the abnormal protein and lipid composition of diabetic high-density lipoprotein (HDL) could impair its anti-inflammatory functions. Whether nonenzymatic glycation directly impaired the anti-inflammatory effects of HDL in innate immunity remained unclear. METHODS: Human acute monocytic leukemia cell line (THP-1) cells, mouse RAW 264.7 macrophages and primary human monocytes derived macrophages were pre-incubated with native HDL, diabetic HDL isolated from T2DM patients or HDL glycated with different doses of d-glucose in vitro and then challenged with lipopolysaccharide (LPS). The release of tumor necrosis factor (TNF)-α and IL-1ß was assayed by enzyme-linked immunosorbent assay (ELISA). Phosphorylation of Iκ-Bα in cytoplasm and nuclear translocation of NF-κB were detected by western blot. Glycation levels of native HDL, glycated HDL and diabetic HDL were determined using LC-MS/MS. RESULTS: The potency of diabetic HDL to inhibit the release of TNF-α (p < 0.05) and IL-1ß (p < 0.001) was dramatically attenuated compared with that of native HDL. Similarly, glycation of HDL in vitro impaired its ability to inhibit TNF-α and IL-1ß release in a glucose dose-dependent manner. Moreover, apoHDL still effectively inhibited the release of TNF-α and IL-1ß induced by LPS, but glycated apoHDL partly lost such abilities. Nonenzymatic glycation levels of glycated HDL and diabetic HDL increased 28 fold (p < 0.001) and 4 fold (p < 0.001), respectively compared with that of native HDL. CONCLUSIONS: In this study, we observed that diabetic HDL and HDL glycated in vitro both partly lose their protective effects to inhibit cytokines release induced by LPS in macrophages, and nonenzymatic glycation of the protein components of HDL plays key roles in these impairments.

Effects of renal denervation on the expression profile of circular RNA in the serum of patients with resistant hypertension.

OBJECTIVE: Renal denervation (RDN) is a new treatment option for resistant hypertension (RH), although it has been shown that reduced sympathetic nerve activity after RDN is the main cause of blood pressure decline. In view of the possible correlation between circRNA and hypertension and the metabolic state of the body after RDN, we investigated the potential role of circRNA in RDN treatment of RH. METHODS: Serum samples of patients with RH were collected before and 48 h after RDN. We explored the mechanism underlying RDN with high-throughput integration of circRNA data. RESULTS: There were 338 circRNAs that were differentiated before and after RDN; 170 were upregulated and 168 were downregulated (≥1.2-fold, P < 0.05), and the expression of five of them changed significantly (≥1.5-fold, P < 0.05). We used reverse transcription-quantitative polymerase chain reaction to confirm these results in 13 other patients with RH. hsa_circRNA_000367 was upregulated and hsa_circRNA_405119 was downregulated after RDN. We predicted their downstream miRNA-mRNA network and analyzed their putative function via the circRNA-miRNA-mRNA pathway. GO/KEGG analysis showed that their functional annotation may be related to nerve injury and hypertension. We used the Venn Diagram Generator to obtain the intersection of predicted target and sympathetic nerve-related genes (from GeneCards website). CONCLUSION: The mechanism underlying RDN may be closely related to upregulated hsa_circRNA_000367 or downregulated hsa_circRNA_405119 and involve regulated multiple pathways and multiple cellular and molecular biological processes. These circRNAs may potentially be used as treatment effect biomarkers in RDN.

[Association between high sensitivity C-reactive protein and contrast induced acute kidney injury in patients with acute coronary syndrome undergoing percutaneous coronary intervention: impact of atorvastatin].

OBJECTIVE: To observe the association between preprocedural high sensitivity C-reactive protein (hs-CRP) level and incidence of contrast induced acute kidney injury (CI-AKI) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and the impact of atorvastatin pretreatment on CI-AKI. METHODS: According to the level of preprocedural hs-CRP, 270 ACS patients were divided into three groups: high hs-CRP group (hs-CRP ≥ 3 mg/L, n = 176), moderate hs-CRP group (hs-CRP 1-3 mg/L, n = 60) and normal hs-CRP group (hs-CRP < 1 mg/L, n = 34). According to the dosage of preprocedural atorvastatin, the high hs-CRP group was further divided into 10 mg group (n = 49), 20 mg group (n = 66) and 40 mg group (n = 61). Serum creatinine (Scr), blood urea nitrogen (BUN), cystatin C (Cys C), hs-CRP were measured at before and 24 hours, 48 hours after PCI. CCr and GFR were calculated according to Scr and Cys C. Risk factors for CI-AKI were determined by multivariate logistic regression analysis. RESULTS: (1) Cys C was significantly increased and GFR after PCI significantly reduced in high and moderate hs-CRP groups compared with normal hs-CRP group (P < 0.05). (2) Incidence of CI-AKI was 43.18%, 38.33%, 20.59% in high, moderate and normal hs-CRP groups, respectively (P < 0.05). (3) In high hs-CRP group, postprocedural GFR was significantly higher while postprocedural Cys C and hs-CRP were significantly lower in 40 mg statin subgroup than 10 mg and 20 mg statin subgroups (P < 0.05), similar trends were documented when comparing 20 mg statin subgroup with 10 mg statin subgroup (P < 0.05). (4) Multivariate logistic regression analysis showed that pretreatment with high dose atorvastatin was a protective factor for post CI-AKI (20 mg atorvastatin: OR = 0.15, 95%CI 0.06 - 0.33, P = 0.001; 40 mg atorvastatin: OR = 0.10, 95%CI 0.04 - 0.23, P = 0.001), while high levels of preprocedural hs-CRP (OR = 2.06, 95%CI 1.01 - 4.23, P = 0.048), diabetes mellitus (OR = 10.71, 95%CI 5.29 - 21.70, P = 0.001), advanced age (OR = 2.64, 95%CI 1.05 - 6.63, P = 0.038) and renal failure (OR = 5.14, 95%CI 1.13 - 23.39, P = 0.034) were independent risk factors of CI-AKI. CONCLUSION: High hs-CRP level is linked with the development of CI-AKI in ACS patients undergoing PCI and pretreatment with 40 mg atorvastatin is associated with lower incidence CI-AKI, possibly by reducing the postprocedural inflammation responses.

Effect of Exercise Prescription Implementation Rate on Cardiovascular Events.

BACKGROUND: Exercise prescription of cardiac rehabilitation (CR) is vital in patients with cardiovascular diseases (CVDs) and those carrying high risk for CVDs. However, the relation between the implementation rate of exercise prescription and cardiovascular events (CVEs) is unclear. DESIGN AND METHODS: In this retrospective study, using the administration data from the Rehabilitation Center in a hospital, patients aged ≥18 years with CVDs were consecutively enrolled from November 2018 to May 2021. Patients were divided into the high execution group (HEG) and low execution group (LEG) depending on whether they completed more than half the time of the exercise prescriptions. Baseline characteristics, ultrasonic cardiogram, cardiopulmonary exercise test, follow-up data, and CVEs were collected. RESULTS: The mean age of the 197 CR patients was 61.8 ± 13.7 years and the mean follow-up duration was 10.9 ± 4.2 months. Among them, 15 patients suffered CVEs: 4 in the HEG and 11 in the LEG. The incidence of CVEs showed significant differences between HEG and LEG (chi-square test). Free-event survival analysis using Kaplan-Meier survival plots showed that patients in LEG had poor survival. Cox proportional hazards regression analysis revealed that the prescription implementation rate was an independent predictor of CVEs. CONCLUSIONS: Our study suggested a significant effect of exercise prescription execution rate on the occurrence of CVEs. Further, the HEG of exercise prescription was associated with lower CVDs.

[Atorvastatin attenuated contrast induced renal function damage].

OBJECTIVE: To study the effects of atorvastatin on contrast induced renal function change and plasma hsCRP in patients undergoing coronary angiography. METHODS: 120 patients who underwent coronary angiography were randomized to receive atorvastatin (20 mg/qn, n = 60) or no atorvastatin (n = 60) treatment 2 to 3 days before coronary angiography. Urinary alpha1-MG, TRF and mALB were checked for evidence of tubular or glomerular damage at start, 1 day and 2 days after the administration of a radiocontrast agent. Serum creatinine, BUN, cystatin C and hsCRP levels were also assessed at the same time. Ccr and GFR were calculated according to Cockcroft-Gault and GFR (ml/min) = 74.835/Cys C(1.333) formulas basing on serum creatinine or cystatin C concentration. RESULTS: (1) In control group, comparison with the value before coronary angiography, urinary alpha1-MG, TRF and mALB or serum cystatin C and hsCRP significantly increased at day 1 after angiography (P < 0.01). In comparison to the levels at day 1 after angiography, urinary alpha1-MG, TRF, mALB, serum cystatin C significantly decreased at day 2 after angiography (P < 0.01), but alpha1-MG, cystatin C still exceeded the values before coronary angiography, TRF and mALB levels at day 2 after angiography had no significant change compared to baseline (P > 0.05), hsCRP level at day 2 after angiography had no significant change compared to that at day 1 after angiography (P > 0.05) too. (2) In comparison with the value before coronary angiography in atorvastatin-treated group, the levels of urinary alpha1-MG, TRF and mALB or serum cystatin C at day 1 and day 2 after angiography had no significant change compared to baseline (P > 0.05).Serum hsCRP significantly increased at day 1 after angiography compared to baseline (P < 0.01), but it had no significant change compared to day 2 after angiography (P > 0.05). (3) To compare to the atorvastatin-treated group, the values of urinary alpha1-MG, TRF and mALB or Cys C and hsCRP significantly increased at day 1 after angiography in control group (P < 0.01), the values of urinary alpha1-MG, cystatin C and hsCRP still significantly increased at day 2 (P < 0.01)too, but those of TRF and mALB had no significantly change at day 1 or day 2 after angiography between the two groups (P > 0.05). There was no significant change in BUN, Cr, Ccr levels before and after angiography between the two groups. CONCLUSIONS: Low dose contrast induces light renal function damage. Pretreatment with atorvastatin 20 mg/qn for 2 to 3 days could significantly reduce procedural inflammatory reaction, attenuate urinary protein and the effect of degrading GFR in coronary angiography patients.

Effects of leptin on endothelial function with OB-Rb gene transfer in Zucker fatty rats.

The metabolic syndrome in association with obesity is a major clinical problem inducing hypertension, diabetes mellitus, and atherosclerosis. Leptin induces angiogenesis by its proliferative effects on endothelial cells (ECs) via OB receptor (OB-Rb) gene. We evaluated the growth of ECs and intracellular signalings in response to leptin in vitro and the angiogenic effects of leptin in the cornea in vivo with and without adenovirus-mediated transfer of the OB-Rb gene in Zucker fatty (ZF) rats as a model for the metabolic syndrome. Recombinant adenovirus vector encoding rat OB-Rb (Ad.OB-Rb) or Escherichia coli. LacZ (Ad.LacZ) was transfected into cultured ECs from Zucker lean (ZL) rats and ZF rats. Leptin increased DNA synthesis dose-dependently in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb, but not with Ad.LacZ, improved the growth effects of leptin in ECs from ZF rats. Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb restored phosphorylation of JAK2 and STAT3 in ECs from ZF rats. Leptin induced angiogenesis in cornea from ZL rats, but not from ZF rats. Coadministration of leptin and Ad.OB-Rb induced angiogenesis in cornea from ZF rats. Ad.LacZ did not influence the angiogenic effects of leptin. The impaired endothelial function with the leptin resistance may be one of causes of the atherosclerosis in the metabolic syndrome.

Novel mechanisms of the antiproliferative effects of amlodipine in vascular smooth muscle cells from spontaneously hypertensive rats.

The calcium channel blocker amlodipine continues to be of interest due to its potential proven ability to hinder the progression of atherosclerosis and reduce the number of clinical ischemic events. Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) are useful in the study of atherosclerosis because they show exaggerated growth with production of angiotensin II (Ang II) by conversion to the synthetic phenotype. To clarify mechanisms of the antiproliferative effects of amlodipine, we evaluated effects of the expression of growth factors, the changes in phenotype, and the proliferation of VSMC from SHR. Amlodipine significantly inhibited basal DNA synthesis and proliferation of VSMC from SHR. Amlodipine also inhibited expression of platelet-derived growth factor (PDGF) A-chain, transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) mRNAs in VSMC from SHR. Decreases in levels of PDGF A-chain and bFGF mRNAs in VSMC from SHR were greater with amlodipine than with nifedipine. Amlodipine significantly inhibited expression of the synthetic phenotype markers osteopontin and matrix Gla mRNAs, indicating that it inhibited the exaggerated growth of VSMC from SHR and suppressed the change from the contractile phenotype to the synthetic phenotype. Thus, amlodipine may be a beneficial therapeutic agent for patients with hypertensive vascular diseases.

The comparison between robotic and manual ablations in the treatment of atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: To examine in what aspects and to what extent robotic ablation is superior over manual ablation, we sought to design a meta-analysis to compare clinical outcomes between the two ablations in the treatment of atrial fibrillation. METHODS AND RESULTS: A literature search was conducted of PubMed and EMBASE databases before December 1, 2013. Data were extracted independently and in duplicate from 8 clinical articles and 792 patients. Effect estimates were expressed as weighted mean difference (WMD) or odds ratio (OR) and the accompanied 95% confidence interval (95% CI). Pooling the results of all qualified trials found significant reductions in fluoroscopic time (minutes) (WMD; 95% CI; P: -8.9; -12.54 to -5.26; <0.0005) and dose-area product (Gy×cm2) (WMD; 95% CI; P: -1065.66; -1714.36 to -416.96; 0.001) for robotic ablation relative to manual ablation, with evident heterogeneity (P<0.0005) and a low probability of publication bias. In subgroup analysis, great improvement of fluoroscopic time in patients with robotic ablation was consistently presented in both randomized and nonrandomized clinical trials, particularly in the former (WMD; 95% CI; P: -12.61; -15.13 to -10.09; <0.0005). Success rate of catheter ablation was relatively higher in patients with robotic ablation than with manual ablation (OR; 95% CI; P: 3.45; 0.24 to 49.0; 0.36), the difference yet exhibiting no statistical significance. CONCLUSIONS: This study confirmed and extended previous observations by quantifying great reductions of fluoroscopic time and dose-area product in patients referred for robotic ablation than for manual ablation in the treatment of atrial fibrillation, especially in randomized clinical trials.

Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of Rho-kinase pathway.

Contrast medium-induced acute kidney injury (CI-AKI) remains a leading cause of iatrogenic, drug-induced acute renal failure. This study aimed to investigate the protective effects of atorvastatin against renal tubular cell apoptosis in diabetic rats and the related mechanisms. CI-AKI was induced by intravenous administration of iopromide (12ml/kg) in streptozotocin-induced diabetic rats. Atorvastatin (ATO) was administered intragastrically at the dose of 5, 10 and 30mg/kg/d in different groups, respectively, for 5 days before iopromide injection. Renal function parameters, kidney histology, renal tubular cell apoptosis, the expression of apoptosis regulatory proteins, caspase-3 and Rho-associated protein kinase 1 (ROCK-1), and the phosphorylation of myosin phosphatase target subunit -1 (MYPT-1), were determined. Atorvastatin was shown to notably ameliorate contrast medium induced medullary damage, restore renal function, and suppress renal tubular apoptosis. Meanwhile, atorvastatin up-regulated the expression of Bcl-2, down-regulated the expression of Bax, caspase-3 and ROCK-1, restored the ratio of Bcl-2/Bax, and suppressed the phosphorylation of MYPT-1 in a dose-dependent manner. Thus, atorvastatin pretreatment could dose-dependently ameliorate the development of CI-AKI, which was partly attributed to its suppression of renal tubular cell apoptosis by inhibiting the Rho/ROCK pathway.

Left radial access is preferable to right radial access for the diagnostic or interventional coronary procedures: a meta-analysis involving 22 randomized clinical trials and 10287 patients.

OBJECTIVE: The transradial approach has been used extensively for both diagnostic and interventional coronary procedures; however, there is no universal consensus hitherto on the optimal choice of radial access from either the left or the right artery. We therefore sought to meta-analyze available randomized clinical trials to compare the left with the right radial access for the diagnostic or interventional coronary procedures. METHODS AND RESULTS: Four electronic databases including the PubMed, EMBASE, Wanfang, and CNKI were searched up to April 2013. In total, there were 22 qualified randomized trials involving 5317 and 4970 patients assigned to the left and the right radial accesses, respectively. Data were extracted independently by two investigators. Analyses of the full data set indicated significant reductions in fluoroscopy time (seconds) (weighted mean difference; 95% confidence interval; P: -36.18; -53.28 to -18.53; <0.0005) and contrast use (mL) (-2.88; -5.41 to -0.34; 0.026) in patients with the left radial access compared to those with the right radial access, and there was strong evidence of heterogeneity but low probability of publication bias. The failure rate of radial access from the left was relatively lower than that from the right (odds ratio: 0.83; 95% confidence interval: 0.68-1.01; P = 0.064). Further in meta-regression analyses, body mass index was found to be a potential source of heterogeneity for both fluoroscopy time (regression coefficient: 35.85; P = 0.025) and catheter number (regression coefficient: 0.35; P = 0.018). CONCLUSIONS: Our findings demonstrate that left radial access is preferable to right radial access in terms of fluoroscopy time and contrast use for the diagnostic or interventional coronary procedures. The import of this study lies in its great shock to the concept of convenient radial access from the right artery.

[Arresting effect of p16 and dll4 transfection on cell cycle of K562 cells].

This study was purposed to investigate the expression and role of eukaryotic expression vector containing p16, dll4 genes in leukemia K562 cells. A vector pBudCE4.1-16-dll4 containing wild type p16cDNA and dll4cDNA was designed and constructed, then this vector was transfected into leukemia K562 cells by using lipofectamine 2000. The expression of p16 and dll4 genes was detected by Western blot, the cell growth curve and cell cycle were determined by CCK-8 kit and flow cytometry respectively. The results showed that the recombinant plasmid pBudCE4.1-16-dll4 was constructed and transfected into K562 cells in vitro successfully. The expression of exogenous P16 and Dll4 proteins could be detected in K562 cells. After transfection for 48 hours, the K562 cells were arrested in G(1) phase, the cell count increased in G(0)/G(1) phase and reduced in S phase, the cell proliferation decreased as compared with control. It is concluded that the p16 and dll4 genes can simultaneously express in K562 cells transfected with recombinant plasmid pBudCE4.1-16-dll4 in vitro which results in G(0)/G(1) arrest and reduces cell proliferation.

[Inhibitory effect of p16, p53 transfection on leukemic cell lines K562 and HL-60].

This study was purposed to construct a vector containing human suppressor gene p53 and p16, and to investigate their expression and effect on K562 and HL-60 cells. pBudCE4.1-53-16 is a vector designed for simultaneous expression of human suppressor gene p53 and p16 in mammalian cell line. After transfection into K562 cells with lipofectamine(TM) 2000, the expression of p53 and p16 genes was detected by Western blot and immunocytochemical method. The growth curve, apoptosis, cell cycle were assayed by CCK-8 and flow cytometry. The results showed that the recombinant plasmid pBudCE4.1-53-16 was constructed successfully and were verified by PCR and restriction analysis. The expression of P53 and P16 protein could be detected after transfection into leukemia cells (K562 and HL-60) for 48 hours. As compared with control group, the cell proliferation in experimental group was inhibited, the cells were arrested in G0 phase and apoptotic cells increased (p<0.001). It is concluded that the recombinant plasmid pBudCE4.1-53-16 has been established. p16 and p53 in the recombinant plasmid pBudCE4.1-53-16 synchronously express in leukemic cells after transfection in vitro for 2 days and results in reduced proliferation, G0 arrest and apoptosis increase.

[Transplantation of mesenchymal stem cells transfected with hepatocyte growth factor gene improves heart function in rats with heart failure].

AIM: To investigate the effects of hepatocyte growth factor gene transfected MSCs transplantation on cardiac function and fibrosis in rats heart failure model induced by adriamycin. METHODS: MSCs were isolated from SD rats by density gradient centrifugation, purified, and transfected with Ad-hHGF. ELISA were used to detect the protein expression of hHGF in these MSCs. Forty SD rats underwent intraperitoneal injection with adriamycin to induce heart failure model. 8 healthy rats served as control, 24 survival rats were randomly divided into 3 groups (n = 8): Rats in Ad-hHGF transfected MSCs group were injected with Ad-hHGF transfected MSCs 2 weeks after the establishment of the model, rats in MSC group injected with suspension of MSCs only, and model group was injected with cold culture fluid. Heart function was evaluated by a physiological recorder 4 weeks after cell transplantation. Myocardial cell morphology and interstitial collagen were studied by electron microscope and were stained by Sirus red. TGF-beta1 was detected by immunohistochemical method. RESULTS: (1) MSCs could be transfected efficiently by Ad-hHGF, manifested by a higher level of expression in vitro, persisting 14 days at least. (2) Four weeks after the cells transplantion, cardiac necrosis in MSC-hHGF rats was improved when compared with those in the MSCs (P < 0.05) and Model group (P < 0.01). The heart function of the MSC-hHGF rats was greatly improved with an significant increase in LVSP and + dp/dt(max), although LVEDP still highter than that of normal rats. (3) MSC-Ad-hHGF decreased Myocardial collagen content and the level of TGFbeta1 compaired with MSCs transplanted rats (P < 0.01). CONCLUSION: Transplantation of HGF gene transfected MSCs improved heart function, decreased myocardial collagen and the level of TGFbeta1.

Co-transfection of p16(INK4a) and p53 genes into the K562 cell line inhibits cell proliferation.

BACKGROUND AND OBJECTIVES: The tumor suppressor genes p53 and p16(INK4a), both of which act in tumor surveillance, are homozygously deleted in the human leukemia cell line K562. This study was performed to assess whether co-transfection of the p16(INK4a) and p53 genes could inhibit K562 cell proliferation. DESIGN AND METHODS: p16(INK4a) and p53 genes were co-transfected into K562 cells with liposome, and the expression of the transfected genes was detected by Western-immunoblotting and immunocytochemistry. The effect of the p16(INK4a) and p53 transfected cell culture was quantified by trypan blue staining, and the number of recovered viable cells was assessed every day after transfection. Cells were analyzed for expression of annexin V in order to detect apoptosis. Differentiation of transfected K562 cells was measured by the benzidine oxidation test, and the cell cycle was analyzed by flow cytometry. RESULTS: After co-transfection, there were 23% and 28% p53 and p16(INK4a) positive cells respectively. Co-transfection with p16(INK4a) and p53 genes significantly inhibited cell proliferation when compared to transfection with either p16(INK4a) or p53 gene. The percentage of cells expressing the apoptosis-related cell surface antigen annexin V was significantly higher in p53 and p16(INK4a) transfected cells than in p53 or p16(INK4a) transfected cells (6.24+/-0.37% vs 4.88+/- 0.17%, p<0.05 and vs 2.78+/-0.26%, p<0.05, respectively). p16(INK4a) and p53 co-transfection significantly increased the number of cells in G1 phase and decreased that in S phase. INTERPRETATION AND CONCLUSIONS: Expression of wild-type p16(INK4a) and p53 genes in K562 cells results in reduced proliferation and apoptosis. Introduction of exogenous p16(INK4a) and p53 genes into K562 cells might contribute to the clinical treatment of leukemia.