Lentivirus-mediated silencing of the PTC1 and PTC2 genes promotes recovery from spinal cord injury by activating the Hedgehog signaling pathway in a rat model

This study aimed to investigate the effect of Patched-1 (PTC1) and PTC2 silencing in a rat model, on Hedgehog (Hh) pathway-mediated recovery from spinal cord injury (SCI). An analytical emphasis on the relationship between the sonic hedgehog (Shh) pathway and nerve regeneration was explored. A total of 126 rats were divided into normal, sham, SCI, negative control (NC), PTC1-RNAi, PTC2-RNAi and PTC1/PTC2-RNAi groups. The Basso, Beattie and Bresnahan (BBB) scale was employed to assess hind limb motor function. Quantitative real-time polymerase chain reaction and western blotting were performed to examine the mRNA and protein levels of PTC1, PTC2, Shh, glioma-associated oncogene homolog 1 (Gli-1), Smo and Nestin. Tissue morphology was analyzed using immunohistochemistry, and immunofluorescent staining was conducted to detect neurofilament protein 200 (NF-200) and glial fibrillary acidic protein (GFAP). The PTC1/PTC2-RNAi group displayed higher BBB scores than the SCI and NC groups. Shh, Gli-1, Smo and Nestin expression levels were elevated in the PTC1/PTC2-RNAi group. PTC1 and PTC2 mRNA and protein expression was lower in the PTC1/PTC2-RNAi group than in the normal, sham and SCI groups. Among the seven groups, the PTC1/PTC2-RNAi group had the largest positive area of NF-200 staining, whereas the SCI group exhibited a larger GFAP-positive area than both the normal and the sham groups. The Shh pathway may provide new insights into therapeutic indications and regenerative recovery tools for the treatment of SCI. Activation of the Hh signaling pathway by silencing PTC1 and PTC2 may reduce inflammation and may ultimately promote SCI recovery.

Effects of rosuvastatin on atherosclerosis and LOX-1, NF-κb p65 expression in the aorta of apoe-deficient mice / 解放军医学杂志

Objective To investigate the effects of HMG-CoA reductase inhibitor rosuvastatin on atherosclerosis and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and nuclear factor (NF)-kB p65 expressions in apolipoprotein E (ApoE)-deficient mice. Methods Twenty six-week-old ApoE-deficient male mice were randomly divided into hyperlipidemia model group (n=10) and rosuvastatin group (n=10), and they were fed high-fat diet for 13 weeks. Ten six-week-old C57BL/6J (wild type, WT) male mice were selected as normal control group, and were fed normal diet for 13 weeks. After 13 weeks, blood was drawn from the mice to determine serum levels of total cholesterol (TCH), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C). These mice were sacrificed, and their aortas were obtained and examined with HE staining; Western blotting and RT-PCR were used to analyze LOX-1, NF-kB p65 expression intensity in aorta tissue quantitatively. Results The serum level of TCH, TG and LDL-C in rosuvastatin group were lower than those in hyperlipidemia model group (P<0.05). Pathological observation showed that atherosclerotic lesions of the aortas were aggravated significantly in hyperlipidemia model group but alleviated in rosuvastatin group compared with normal control group. Compared with normal control group, LOX-1, NF-kB p65 protein and mRNA expressions significantly increased in hyperlipidemia model group (P<0.05) and reduced in rosuvastatin group (P<0.05). Conclusions Rosuvastatin may lower blood lipid significantly, alleviate the degree of atherosclerotic lesions, and inhibit LOX-1, NF-kB p65 protein and mRNA expressions in the aortic tissue of ApoE-deficient mice. Its anti-athrosclerosis effect is related to down regulation of LOX-1 and NF-kB p65 expressions.

Clinical outcomes after recanalization of a chronic total occluded vessel with bifurcation lesions: results from single-center, prospective, chronic total occlusion registry study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Stenting strategies and clinical outcomes of bifurcation lesions in a chronic total occlusion (CTO) vessel after successful recanalization remain to be unknown.</p><p><b>METHODS</b>Between January 2001 and December 2009, 195 (41.1%) patients with 254 (47.0%) bifurcation lesions in CTO vessels from a pool of 564 patients with 659 CTO lesions were included and divided into proximal (n = 134) and distal (n = 120) groups, according to the location of the bifurcation lesions. The primary endpoint was the occurrence of major adverse cardiac events (MACE) at the end of clinical follow-up, including cardiac death, myocardial infarction, or target vessel revascularization (TVR).</p><p><b>RESULTS</b>Collaterals with Rentrop class 3 were seen more in distal group (100% and 68.3%), compared to proximal group (76.9% and 45.6%). Two-stent technique for proximal bifurcation lesions was used in 24.6%, significantly different from the distal group (6.7%, P < 0.001), without significant difference in composite MACE between proximal and distal groups, or between one- and two-stent subgroups in proximal group. The composite MACE after 1-year in complete revascularization subgroup was 17.9% relative to 29.6% in the incomplete revascularization group (P = 0.044). Stents in long false lumen in main vessel were mainly attributive to decreased TIMI grade flow, with resultant increased in-stent restenosis, total occlusion, TVR and coronary aneurysms. Imcomplete revasculzarization (HR 2.028, P = 0.049, 95%CI 1.002 - 4.105) and post-stenting TIMI flow (HR 6.122, P = 0.020, 95%CI 1.334 - 28.092) were two independent predictors of composite MACE at the 1-year follow-up.</p><p><b>CONCLUSIONS</b>Two-stent was more used for proximal bifurcation lesions. No significant difference was observed in MACE between proximal and distal, or between one- and two-stent subgroups in the proximal group. Placement of a safety wire was critical for proximal bifurcation lesions. Complete revascularization was mandatory to improve clinical outcomes.</p>

Hemodynamic changes of fractional flow reserve after double kissing crush and provisional stenting technique for true bifurcation lesions / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is associated with fewer unfavorable events. However, the hemodynamic change in FFR after different stenting approaches for bifurcation lesions is still not fully studied. The aim of this study was to analyze the hemodynamic changes in FFR after double kissing (DK) crush and provisional side branch (SB) stenting (PS) for true coronary bifurcation lesions.</p><p><b>METHODS</b>Seventy-five patients with true bifurcated lesions were randomly divided into DK (n = 38) and PS (n = 37) groups. Additional SB stenting in the PS group was required if there was any pinched SB ostium > 70% stenosis, or ≥ type B dissection, or TIMI flow < grade 3. FFR at hyperemia in the main vessel (MV) and SB was measured prior- and post-stenting, and at 8 months follow-up.</p><p><b>RESULTS</b>Baseline clinical, angiographic and lesion characteristics were matched well between the two groups, with the exception of the final kissing balloon inflation (FKBI, 100.0% in the DK vs. 83.8% in the PS group, P < 0.001). Baseline FFR was comparable between the DK and the PS groups, however, the acute gain and late loss of SB FFR at 8-month follow-up in the DK group were 0.18 ± 0.15 and -0.06 ± 0.11, compared to 0.12 ± 0.18 (P = 0.044) and -0.002 ± 0.07 (P = 0.037) in the PS group, respectively. MV FFR post-stenting > 0.94 was seen in about 40% of patients. There was no significant difference in the clinical events at 1-year follow-up between the two groups.</p><p><b>CONCLUSIONS</b>DK crush was associated with improved acute gain and late loss of SB FFR. The lower rate of FFR > 0.94 after stenting underscored the further improvement of stenting quality.</p>

Clinical outcomes of percutaneous coronary intervention for chronic total occlusion lesions in remote hospitals without on-site surgical support / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The safety of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions in remote hospitals without surgical facilities remains unknown. This study aimed to evaluate three-year outcomes after CTO for PCI in ten centers around China where no on-site coronary artery bypass grafting (CABG) support was available.</p><p><b>METHODS</b>A total of 152 patients from 10 Chinese hospitals without on-site surgical facilities were prospectively studied. Intra-procedural and in-hospital events were assessed. Angiographic follow-up was indexed eight months after the initial procedure. Clinical follow-up was extended to three years. The primary outcome was the rate of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction and target-vessel revascularization (TVR).</p><p><b>RESULTS</b>The incidence of CTO was 7.9% in patients who underwent PCI. Successful recanalization was achieved in 132 patients (86.8%). Compared with patients in the PCI success group, patients with PCI procedural failure had longer lesion lengths ((42.32 +/- 22.08) mm vs (27.61 +/- 22.85) mm, P = 0.023), a higher rate of perforation (25.0% vs 0, P = 0.014), and a greater need for pericardial puncture. There were significant differences in MACE in-hospital and at one year and three years between the failure (10.0%, 30.0% and 35.0%) and the success (3.0%, 12.1% and 14.4%) groups (P = 0.037, 0.034 and 0.040, respectively). These led to a significant decrease in the MACE-free survival rate at one and three years in the failure group, compared with the success group (P = 0.031 and 0.023, respectively). Stump was the only predictor of recanalization success (HR 0.158, 95% CI 0.041-0.612, P = 0.008), whereas procedural failure (OR 13.023, 95% CI 6.67-13.69, P = 0.002), incomplete revascularization (OR 9.71, 95% CI 2.93-5.59, P = 0.005), and total stent length (OR 6.02, 95% CI 1.55-11.93, P = 0.027) were three independent predictors of MACE.</p><p><b>CONCLUSIONS</b>PCI for CTO was unsafe in remote hospitals without CABG facilities. Paying attention to coronary perforation is important for successful procedures.</p>

Crush stenting in treating coronary bifurcate lesions: paclitaxel eluting stents versus sirolimus eluting stents / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Because no data regarding the comparison of crush stenting with paclitaxel (PES) or sirolimus eluting stents (SES) for coronary bifurcate lesions have been reported, we compared the clinical outcomes of these two types of stents.</p><p><b>METHODS</b>Two hundred and thirty patients with 242 bifurcate lesions were enrolled in a prospective, nonrandomized trial. Primary endpoints included myocardial infarction, cardiac death and target vessel revascularization at 8 months.</p><p><b>RESULTS</b>All patients were followed up clinically and 82% angiographically at 8 months. Final kissing balloon inflation was performed in 72% in the PES and 75% in the SES groups (P>0.05). Compared to the SES group, PES group had a higher late loss and incidence of restenosis (P=0.04) in the prebifurcation vessel segment. The postbifurcation vessel segment in the PES group had a greater late loss ((0.7+/-0.6) mm vs (0.3+/-0.4) mm, P<0.001) and higher restenosis in the side branch (25.5% vs 15.6%, P=0.04) when compared to the SES group. There was significant difference of insegment restenosis in the entire main vessel between PES and SES groups (P=0.004). Target lesion revascularization was more frequently seen in the PES group as compared to the SES group (P=0.01). There was significant difference in the accumulative MACE between these two groups (P=0.01). The survival rate free from target lesion revascularization was significantly higher in the SES group when compared to the PES group (P<0.001).</p><p><b>CONCLUSION</b>SES is superior to PES in reducing restenosis and target lesion revascularization by 8-month follow-up after crush stenting for bifurcate lesions.</p>

Comparison of DK crush with classical crush technique with drug-eluting stents for the treatment of coronary bifurcation lesions from DKCRUSH-1 study / 中华心血管病杂志

<p><b>OBJECTIVE</b>To determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions.</p><p><b>METHODS</b>311 patients with bifurcation lesions were randomized to classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation group. The primary endpoints included major adverse cardiac events (MACE).</p><p><b>RESULTS</b>Final kissing balloon inflation (FKBI) success rate was 76% in C and 100% in DK groups (P < 0.001). DK crush procedure was characterized by lower unsatisfactory FKBI rate (27.6% vs.6.3%, P < 0.01). Clinical follow-up was available in 100% and angiographic follow-up in 82% patients. The overall restenosis rate was 32.3% in C and 20.3% in DK groups (P = 0.01), respectively. Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub-groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was 3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P > 0.05). The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique.</p><p><b>CONCLUSION</b>DK crush technique is an alternative of double stenting techniques in terms of improvement of restenosis and clinical outcomes.</p>

Left ventricular endocardial pacing predicts the reduction of left ventricular outflow tract pressure gradient immediately after percutaneous transseptal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy refractory to medication / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertrophic obstructive cardiomyopathy (HOCM) carries an increased risk for sudden cardiac death. No data regarding the percutaneous transseptal myocardial ablation (PTSMA) and epicardial left ventricular pacing (LVP) were reported.</p><p><b>METHODS</b>Seven patients with recurrent symptoms and increased resting left ventricular outflow tract pressure gradient (LVOTG) after PTSMA and another 14 patients with HOCM without history of PTSMA were studied. Both resting and dobutamine stress echocardiography, PTSMA and LVP were routinely performed.</p><p><b>RESULTS</b>In patients without previous PTSMA procedure, mild reduction of resting LVOTG was detected at 5 minutes after left ventricular pacing, and this reduction became significant at 10 minutes. All patients were divided into successful and unsuccessful groups according to their response to LVP. In contrary to patients in unsuccessful group, resting and R-S2 stimuli-induced LVOTG during PTSMA procedure were decreased dramatically ((9 +/- 5) mmHg vs (58 +/- 12) mmHg, (12 +/- 2) mmHg vs (113 +/- 27) mmHg, P < 0.001). Analysis of Logistic regression demonstrated that only LVOTG level during left ventricular pacing was an independent factor predicting the reduction of LVOTG immediately after PTSMA (odds ratio (OR), 0.59; 95% CI 2.67 to 5.82; P = 0.0002).</p><p><b>CONCLUSION</b>Left ventricular endocardial temporary pacing plays a critical role in predicting acute effect on the reduction of LVOTG immediately after PTSMA procedure.</p>