OBJECTIVE: To explore the mechanism by which inositol-requiring enzyme-1α (IRE1α) regulates autophagy function of chondrocytes through calcium homeostasis endoplasmic reticulum protein (CHERP). METHODS: Cultured human chondrocytes (C28/I2 cells) were treated with tunicamycin, 4μ8c, rapamycin, or both 4μ8c and rapamycin, and the expressions of endoplasmic reticulum (ER) stress- and autophagy-related proteins were detected with Western blotting. Primary chondrocytes from ERN1 knockout (ERN1 CKO) mice and wild-type mice were examined for ATG5 and ATG7 mRNA expressions, IRE1α and p-IRE1α protein expressions, and intracellular calcium ion content using qPCR, Western blotting and flow cytometry. The effect of bafilomycin A1 treatment on LC3 Ⅱ/LC3 Ⅰ ratio in the isolated chondrocytes was assessed with Western blotting. Changes in autophagic flux of the chondrocytes in response to rapamycin treatment were detected using autophagy dual fluorescent virus. The changes in autophagy level in C28/I2 cells overexpressing CHERP and IRE1α were detected using immunofluorescence assay. RESULTS: Tunicamycin treatment significantly up-regulated ER stress-related proteins and LC3 Ⅱ/LC3 Ⅰ ratio and down-regulated the expression of p62 in C28/I2 cells (P < 0.05). Rapamycin obviously up-regulated LC3 Ⅱ/LC3 Ⅰ ratio (P < 0.001) in C28/I2 cells, but this effect was significantly attenuated by co-treatment with 4μ8c (P < 0.05). Compared with the cells from the wild-type mice, the primary chondrocytes from ERN1 knockout mice showed significantly down-regulated mRNA levels of ERN1 (P < 0.01), ATG5 (P < 0.001) and ATG7 (P < 0.001), lowered or even lost expressions of IRE1α and p-IRE1α proteins (PP < 0.01), and increased expression of CHERP (P < 0.05) and intracellular calcium ion content (P < 0.001). Bafilomycin A1 treatment obviously increased LC3 Ⅱ/ LC3 Ⅰ ratio in the chondrocytes from both wild-type and ERN1 knockout mice (P < 0.01 or 0.05), but the increment was more obvious in the wild-type chondrocytes (P < 0.05). Treatment with autophagy dual-fluorescence virus resulted in a significantly greater fluorescence intensity of LC3-GFP in rapamycin-treated ERN1 CKO chondrocytes than in wild-type chondrocytes (P < 0.05). In C28/I2 cells, overexpression of CHERP obviously decreased the fluorescence intensity of LC3, and overexpression of IRE1α enhanced the fluorescence intensity and partially rescued the fluorescence reduction of LC3 caused by CHERP. CONCLUSION IRE1α deficiency impairs autophagy in chondrocytes by upregulating CHERP and increasing intracellular calcium ion content.
Animals ; Autophagy ; Calcium/metabolism* ; Chondrocytes ; Endoplasmic Reticulum/metabolism* ; Endoribonucleases/pharmacology* ; Homeostasis ; Inositol ; Mice ; Mice, Knockout ; Protein Serine-Threonine Kinases ; RNA, Messenger/metabolism* ; Sirolimus/pharmacology* ; Tunicamycin/pharmacology*

BACKGROUND: Stent failure is more likely in the lipid rich and thrombus laden culprit lesions underlying ST-segment elevation myocardial infarction (STEMI). This study assessed the effectiveness of post-dilatation in primary percutaneous coronary intervention (pPCI) for acute STEMI. METHODS: The multi-center POST-STEMI trial enrolled 41 consecutive STEMI patients with symptom onset <12 hours undergoing manual thrombus aspiration and Promus Element stent implantation. Patients were randomly assigned to control group (n=20) or post-dilatation group (n=21) in which a non-compliant balloon was inflated to >16 atm pressure. Strut apposition and coverage were evaluated by optical coherence tomography (OCT) after intracoronary verapamil administration via thrombus aspiration catheter, post pPCI and at 7-month follow-up. The primary endpoint was rate of incomplete strut apposition (ISA) at 7 months after pPCI. RESULTS: There were similar baseline characteristics except for stent length (21.9 [SD 6.5] mm vs. 26.0 [SD 5.8] mm, respectively, P=0.03). In post-dilatation vs. control group, ISA rate was lower (2.5% vs. 4.5%, P=0.04) immediately after pPCI without affecting final TIMI flow 3 rate (95.2% vs. 95.0%, P>0.05) or corrected TIMI frame counts (22.6±9.4 vs. 22.0±9.7, P>0.05); and at 7-month follow-up (0.7% vs. 1.8%, P<0.0001), the primary study endpoint, with similar strut coverage (98.5% vs. 98.4%, P=0.63) and 1-year rate of major adverse cardiovascular events (MACE). CONCLUSION In STEMI patients, post-dilatation after stent implantation and thrombus aspiration improved strut apposition up to 7 months without affecting coronary blood flow or 1-year MACE rate. Larger and longer term studies are warranted to further assess safety (ClinicalTrials.gov identifi er: NCT02121223).

Interfascial plane block is a quick,safe and simple technique that offers effective analgesia for video-assisted thoracotomy.However,the currently described methods still have certain limitations.We explored the application of a novel interfascial plane block method-iliocostal plane block in video-assisted thoracotomy,along with the use of stained cadaveric anatomy,with an attempt to shed new light on the analgesia for video-assisted thoracotomy.
Analgesia ; Humans ; Thoracotomy

BackgroundThe relationship between obstructive sleep apnea (OSA) and platelet reactivity in patients undergoing percutaneous coronary intervention (PCI) has not been defined. The present prospective, single-center study explored the relationship between platelet reactivity and OSA in patients with PCI.

MethodsA total of 242 patients were finally included in the study. OSA was screened overnight by polysomnography. Platelet reactivity was assessed with a sequential platelet counting method, and the platelet maximum aggregation ratio (MAR) and average aggregation ratio were calculated. All patients were assigned per apnea-hypopnea index (AHI) to non-OSA (n = 128) and OSA (n = 114) groups. The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity (HPR) on aspirin and clopidogrel, and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel.

ResultsMedian AHI was significantly higher in the OSA group than in the non-OSA group (34.5 events/h vs. 8.1 events/h, Z = -13.422, P < 0.001). Likewise, median arachidonic acid- and adenosine diphosphate-induced maximum aggregation rate (MAR) in the OSA group was significantly higher than those in the non-OSA group (21.1% vs. 17.7%, Z = -3.525, P < 0.001 and 45.8% vs. 32.2%, Z = -5.708, P < 0.001, respectively). Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin (odds ratio [OR]: 1.055, 95% confidence interval [CI]: 1.033-1.077, P < 0.001) and clopidogrel (OR: 1.036, 95% CI: 1.017-1.056, P < 0.001). The cutoff value of AHI for HPR on aspirin was 45.2 events/h (sensitivity 47.1% and specificity 91.3%), whereas cutoff value of AHI for HPR on clopidogrel was 21.3 events/h (sensitivity 68.3% and specificity 67.7%).

ConclusionPlatelet reactivity appeared to be higher in OSA patients with PCI despite having received a loading dose of aspirin and clopidogrel, and OSA might be an independent predictor of HPR on aspirin and clopidogrel.

Adult ; Aged ; Aged, 80 and over ; Blood Platelets ; physiology ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Percutaneous Coronary Intervention ; Prospective Studies ; Sleep Apnea, Obstructive ; physiopathology ; surgery

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.

Twenty-eight compounds were isolated and purified from Clinopodium chinense by Sephedax LH-20, ODS, MCI and preparative HPLC. Their structures were identified as apigenin (1), apigenin-7-O-β-D-glucopyranoside (2), apigenin-7-O-β-D-glucuronopyranoside (3), thellungianol (4), apigenin-7-O-β-D-rutinoside (5), luteolin (6), luteolin-4'-O-β-D-glucopyranoside (7), apigenin-7-O-β-D-pyranglycuronate butyl ester (8), luteolin-7-O-β-D-rutinoside (9), luteolin-7-O-β-D-noehesperidoside (10), acacetin (11), acacetin-7-O-β-D-glucuronopyranoside (12), buddleoside (13), naringenin (14), pruning (15), nairutin (16), isosakuranetin (17), isosakuranin (18), didymin (19), hesperidin (20), kaempferol (21), quercetin (22), kaempferol-3-O-α-L-rahmnoside (23), p-hydroxycinnamic acid (24), caffeic acid (25), cis-3-[2-[1-(3,4-dihydroxy-phenyl)-1 -hydroxymethyl]-1,3-ben-zodioxol-5-yl]-(E)-2-propenoic acid (26), mesaconic acid (27), gentisic acid 5-O-β-D-(6'-salicylyl)-glucopyranoside (28). Among them, compounds 7, 9-10, 12, 23, 26-28 were isolated from the Clinopodium for the first time. The protective effects of compounds 1-6, 8-17 and 19 against H2O2-induced H9c2 cardiomyocyte injury were tested, compounds 15 exhibited significantly protective effects. Compared with the cell viability of (62.12±6.18)% in the model, pruning exhibited viabilities of (84.25±7.36)% at 25.0 mg•L⁻¹, respectively, using quercetin as a positive control [cell viability of (84.55±8.26)%, 20 mg•L⁻¹].

BACKGROUNDThe double kissing (DK) crush technique is a modified version of the crush technique. It is specifically designed to increase the success rate of the final kissing balloon post-dilatation, but its efficacy and safety remain unclear.

METHODSData were obtained from the DKCRUSH-I trial, a prospective, randomized, multi-center study to evaluate safety and efficacy. Post-procedural and eight-month follow-up intravascular ultrasound (IVUS) analysis was available in 61 cases. Volumetric analysis using Simpson's method within the Taxus stent, and cross-sectional analysis at the five sites of the main vessel (MV) and three sites of the side branch (SB) were performed. Impact of the bifurcation angle on stent expansion at the carina was also evaluated.

RESULTSStent expansion in the SB ostium was significantly less in the classical crush group ((53.81 ± 13.51)%) than in the DK crush group ((72.27 ± 11.46)%) (P = 0.04). For the MV, the incidence of incomplete crush was 41.9% in the DK group and 70.0% in the classical group (P = 0.03). The percentage of neointimal area at the ostium had a tendency to be smaller in the DK group compared with the classical group ((16.4 ± 19.2)% vs. (22.8 ± 27.1)%, P = 0.06). The optimal threshold of post-procedural minimum stent area (MSA) to predict follow-up minimum lumen area (MLA) < 4.0 mm(2) at the SB ostium was 4.55 mm(2), yielding an area under the curve of 0.80 (95% confidence interval: 0.61 to 0.92).

CONCLUSIONOur data suggest that the DK crush technique is associated with improved quality of the final kissing balloon inflation (FKBI) and had smaller optimal cutoff value of post-procedural MSA at the SB ostium.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Disease ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Ultrasonography

Background The double kissing (DK) crush technique is a modified version of the crush technique.It is specifically designed to increase the success rate of the final kissing balloon post-dilatation,but its efficacy and safety remain unclear.Methods Data were obtained from the DKCRUSH-I trial,a prospective,randomized,multi-center study to evaluate safety and efficacy.Post-procedural and eight-month follow-up intravascular ultrasound (IVUS) analysis was available in 61 cases.Volumetric analysis using Simpson's method within the Taxus stent,and cross-sectional analysis at the five sites of the main vessel (MV) and three sites of the side branch (SB) were performed.Impact of the bifurcation angle on stent expansion at the carina was also evaluated.Results Stent expansion in the SB ostium was significantly less in the classical crush group ((53.81±13.51)％) than in the DK crush group ((72.27±11.46)％) (P=-0.04).For the MV,the incidence of incomplete crush was 41.9％ in the DK group and 70.0％ in the classical group (P=-0.03).The percentage of neointimal area at the ostium had a tendency to be smaller in the DK group compared with the classical group ((16.4±19.2)％ vs.(22.8±27.1)％,P=-0.06).The optimal threshold of post-procedural minimum stent area (MSA) to predict follow-up minimum lumen area (MLA) ＜4.0 mm2 at the SB ostium was 4.55 mm2,yielding an area under the curve of 0.80 (95％ confidence interval:0.61 to 0.92).Conclusion Our data suggest that the DK crush technique is associated with improved quality of the final kissing balloon inflation (FKBI) and had smaller optimal cutoff value of post-procedural MSA at the SB ostium.

Objective To evaluate risk factors and clinical outcome of coronary artery aneurysms (CAA) developed after drug-eluting stent implantation evidenced by coronary angiographic followup.Methods This study analyzed 4500 consecutive patient with de novo coronary artery stenosis receiving drug-eluting stent (DES) implantation from January 2004 to May 2009.Seven hundred and sixty patients with angiographic follow-ups at 6-8 months and 28-48 months after the index procedure were enrolled.CAA was defined as a localized dilatation exceeding 1.5 times the diameter of the adjacent artery.The independent risk factors and major adverse cardiac events (MACE) including cardiac death,myocardial infarction,target-vessel revascularization (TVR) and in-stent thrombosis were analyzed.Results CAA was detected in 70 patients with 70 lesions (9.2％,70/760).Logistic analysis showed that lesion in an infarctrelated artery (OR: 5.9,P ＜ 0.01),lesion in the left anterior descending artery (OR: 4.5,P ＜ 0.01),lesion with chronic total occlusion (OR: 3.4,P ＜ 0.05),and lesion length ＞ 33 mm (OR: 2.9,P ＜ 0.05)were independent risk factors for CAA.Follow-up duration was (1131 ±478) days.MACE was found in 19 patients and all received TVR.There were 11 patients with myocardial infarction and 8 patients with evidence of in-stent thrombosis.Mortality was zero during follow-up.Conclusions The risk factors for the development of CAA after DES are lesions in an infarct-related artery,in the left anterior descending artery,with chronic total occlusion,and with lesion length ＞ 33 mm.MACE is not uncommon in patients with CAA and long-ferm clinical follow-up is warranted for patients with CAA.

BACKGROUNDThe correlation between angiographic or intravascular ultrasound (IVUS) variables and fractional flow reserve (FFR) in patients with single left anterior descending artery (LAD) lesion has not been studied. The current study aimed at determining the best cutoff value of angiographic and IVUS parameters for defining FFR < 0.80 in patients with LAD lesion.

METHODSQuantitative coronary analysis, IVUS and FFR measurements were undergone in 169 patients with single LAD lesion. The best angiographic and IVUS cutoff value and their predictive value for FFR < 0.80 were compared using area under the receiver-operator characteristic curve (AUC) in overall patients or in subgroups stratified by lesion sites.

RESULTSFFR < 0.80 was found in 99 lesions (58.6%). Minimal lumen area (MLA), and plaque burden (PB) were two predictors of FFR < 0.80. Lesion length had less value in predicting FFR < 0.80. The cutoff value of PB and MLA for FFR < 0.80 was 75.4% and 3.03 mm(2). MLA and PB had similar high diagnostic value for proximal (cutoff value 3.04 mm(2) and 76.5%) and distal LAD lesion (2.82 mm(2) and 80.6%). Combination of MLA (2.82 mm(2)) and PB (80.6%) had increased diagnostic value for distal LAD lesion.

CONCLUSIONSMLA and plaque burden had equivalent diagnostic value for FFR < 0.80 when lesion localized in LAD. The predictive value of combination of MLA and plaque burden for distal LAD lesion was strengthened.

Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Coronary Vessels ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Plaque, Atherosclerotic ; diagnostic imaging ; Ultrasonography, Interventional ; methods