Association of IL-6 Gene (-174 and -572 G/C) Polymorphisms with Proliferative Diabetic Retinopathy of Type 2 Diabetes in a Chinese Population.

PURPOSE: To investigate the association of interleukin (IL)-6 with proliferative diabetic retinopathy (PDR) of type 2 diabetes (T2D) in a Chinese population. METHODS: Two subtypes of the IL-6 promoter (-174 and -572 G/C) were genotyped in 215 T2D patients with PDR and 207 T2D patients with a normal retinal function (controls) using the PCR-RFLP method. The mRNA and protein expression of IL-6 was examined by real-time PCR. RESULTS: T2D patients with PDR had a significantly higher frequency of IL-6 -174 GC (OR 0.58; 95% CI 0.34-0.99; p = 0.011) and IL-6 -572 GG (OR 0.53; 95% CI 0.24-1.14; p = 0.016) than T2D controls. The mRNA expressions of the rs1800795 GC and rs1800796 GG genotype were significantly increased compared to other cases (Fsig = 0.002, p = 0.001, respectively), followed by a relative increase in IL-6 in protein. CONCLUSIONS: IL-6 genotypes of rs1800795 GC and rs1800796 GG might point to a relatively high risk for T2D patients suffering from PDR in a Chinese population and they were associated with elevation of IL-6 expression in both mRNA and protein.

[Cilostazol inhibits proliferation and induces apoptosis in rat vascular smooth muscle cells through Rb-p53-p21 pathways].

OBJECTIVE: To explore the effects and related mechanisms of cilostazol on rat vascular smooth muscle cells (VSMCs)proliferation. METHODS: VSMCs were treated with DMEM (control) and various doses of cilostazol (1.0×10(-7), 2.5×10(-7), 5.0×10(-7), 7.5×10(-7) and 1.0×10(-6) mol/L) for 13 d (cell counting) or 72 h. Proliferation of VSMCs was investigated by cell-counting, MTT and flow cytometry analysis. Cell apoptosis was determined by TUNEL staining. mRNA and protein expressions of cell cycle regulatory proteins, such as Rb, p53 and p21 were detected by RT-PCR and Western blot, respectively. RESULTS: Cilostazol inhibited VSMCs proliferation and induced VSMCs arrest at G1 phase in a dose-dependent manner. High dose of cilostazol (7.5×10(-7) and 1.0×10(-6) mol/L) induced VSMCs apoptosis. p53 mRNA expression in 2.5×10(-7) mol/L to 7.5×10(-7) mol/L groups as well as 1.0×10(-6) mol/L group (3.22 ± 0.45 vs. 1.75 ± 0.32) and p53 protein expression in 7.5×10(-7) mol/L group and 1.0×10(-6) mol/L group (0.53 ± 0.11 vs. 0.18 ± 0.06) were significantly upregulated after 72 h culture (all P < 0.05 vs. control). Low dose of cilostazol (1.0×10(-7), 2.5×10(-7) and 5.0×10(-7) mol/L) significantly upregulated p21 mRNA expression compared to control group (1.86 ± 0.19, 2.20 ± 0.24 and 2.10 ± 0.18 vs. 1.210 ± 0.18, all P < 0.05). Similarly, Rb mRNA expression was significantly upregulated in 1.0×10(-7), 2.5×10(-7) and 5.0×10(-7) mol/L groups (0.89 ± 0.07 vs. 0.38 ± 0.04)compared with control group (all P < 0.05). However, high dose cilostazol (7.5×10(-7) and 1.0×10(-6) mol/L) significantly downregulated p21 mRNA expression (0.81 ± 0.09 vs. 1.21 ± 0.18, 0.36 ± 0.10 vs. 1.21 ± 0.18, all P < 0.05 vs. control) and Rb mRNA expression (0.12 ± 0.02 and 0.11 ± 0.02 vs. 0.38 ± 0.04, all P < 0.05 vs. control). p21 and Rb protein expressions also upregulated at low concentrations of cilostazol and downregulated at high concentrations of cilostazol. CONCLUSION: Cilostazol could inhibit the proliferation of rat VSMCs through modulating Rb-p53-p21 pathway and induce VSMCs apoptosis through upregulating p53.

[Clinical efficacy of intra-aortic balloon pumping in treating patients with acute myocardial infarction with left main coronary artery disease].

OBJECTIVE: To evaluate the efficacy and safety of intra-aortic balloon pump (IABP) counter pulsation in the treatment of ST-segment elevation myocardial infarction (STEMI) with concurrent left main coronary artery (LMCA) disease. METHODS: A retrospective analysis was performed on 305 patients with confirmed STEMI due to LMCA occlusion (≥ 50%) by coronary angiography. They were divided into IABP and non-IABP groups according to the application of IABP or not. Two groups were further divided into 2 subgroups according to the treatment with percutaneous coronary intervention (PCI) or drug alone. Short and long-term clinical efficacies and the incidence of complications caused by the application of IABP were analyzed in all groups and subgroups. RESULTS: (1) PCI procedure: Successful rate of immediate post-procedure was 100%. No death, major cardiovascular event and cerebrovascular accident occurred during the procedure. The average number of stents per patient was 2.1 ± 0.7 and the average diameter and length of stent were (3.9 ± 0.6) and (24.2 ± 7.1) mm respectively. (2) SAFETY: No significant difference existed between the IABP and non-IABP groups in in-hospital massive bleeding rate (0.94% vs 1.00%, P > 0.05). However, the IABP group had a higher prevalence of mild in-hospital bleeding than the non-IABP group. (3) In-hospital and long-term major adverse cardiac event (MACE) rate: (1) IABP group had a lower MACE rate (25.3% (24/95) vs 38.5% (57/148), P < 0.05). (2) In spite of IABP implantation, the PCI subgroup had significantly a lower mortality rate than the drug subgroup (7.2% (6/83) vs 25.0% (6/24), P < 0.05). (3) The combined use of PCI and IABP was superior to other regimens with regards to decreasing short and long-term mortality (11.2% (12/107) and 25.3% (50/198), P < 0.01). CONCLUSION: PCI is feasible and safe for the STEMI patients with LMCA and better short and long-term efficacies may be achieved. The use of IABP in the treatment of LMCA-related STEMI reduces MACE rate and improves survival rate.

[Effects of intensive antiplatelet therapy for patients with high on-treatment platelet reactivity after coronary stent implantation].

OBJECTIVE: To explore the effects of intensive antiplatelet therapy for patients with high on-treatment platelet reactivity (HPR) after coronary stent implantation. METHODS: Between March 2009 and February 2011, a total of 3316 consecutive acute coronary syndrome patients undergoing drug-eluting stent implanting from 3 hospitals were enrolled. Among them, 840 patients (25.3%) were identified as HPR (defined as 20 µmol/L adenosine diphosphate induced platelet aggregation of ≥ 55% at 24 hours after administration of 300 mg clopidogrel loading dose and 300 mg aspirin). The HPR patients were randomly assigned to receive standard (aspirin 300 mg/d and clopidogrel 75 mg/d, n = 280) or intensified (n = 560) antiplatelet therapy by the ratio of 1:2. Patients in the intensive group were initially treated with a double maintenance dose of clopidogrel (150 mg/d) and aspirin (300 mg/d). After 3 days, patients with unsolved HPR received additional cilostazol treatment (50 - 100 mg, bid). The reversion rate of HPR and clinical events were observed. RESULTS: In the intensive group, HPR reversed in 304 out of 560 patients (54.3%) at 3 days post therapy and the remaining 256 patients with HPR were treated with additional cilostazol regimen for another 3 days and the total reversion rate of HPR was 81.1% (454/560). The reversion rate of HPR at 30 days in the intensified group was significantly higher than that of the standard group (69.9% vs. 55.7%, P = 0.000). At 30 days after percutaneous coronary intervention, 1 patient suffered from subacute stent thrombosis (0.2%) in intensified group and no stent thrombosis was observed in standard group (P = 1.000). There were no death, major or minor bleeding in both two groups. Minimal bleeding was also similar in the two groups (intensive: 4.28% vs. standard: 2.14%, P = 0.166). CONCLUSIONS: The intensified antiplatelet therapy regimens could significantly increase the reversion rate of HPR in acute coronary syndrome patients undergoing coronary stenting without increasing the risk of bleeding. The clinic impact of this strategy needs to be elucidated by long term follow-up outcome studies.

HPV-Related Promoter Methylation-Based Gene Signature Predicts Clinical Prognosis of Patients With Cervical Cancer.

Persistent high-risk HPV infection drives tumorigenesis in various human malignancies, including cervical, oropharyngeal, anal, and vulvar carcinomas. Although HPV-related tumors arise in several different sites, they share many common genetic and epigenetic events. Complex and heterogeneous genomic aberrations and mutations induced by high-risk HPV contribute to the initiation and progression of cervical cancer (CC). However, the associations between high-risk HPV infection and DNA methylation have not been clearly investigated. In the present study, HPV-related gene promoter methylation signature was comprehensively analyzed using multiple interactive platforms. CC patients were successfully classified into high-risk and low-risk groups with significant differences in clinical outcomes based on the HPV-related gene promoter methylation signature. Moreover, the protein levels of ALDH1A2 and clinical prognostic value were confirmed in the CC patients cohort. In summary, our study provides compelling evidence that HPV-related gene promoter methylation signature serves as a strong prognostic signature for CC patients. Clinical investigations in large CC patient cohorts are greatly needed to pave the way to implement epigenetic biomarkers into better clinical management.

TGF-ß1-regulated miR-3691-3p targets E2F3 and PRDM1 to inhibit prostate cancer progression.

Transforming growth factor-ß1 (TGF-ß1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-ß1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-ß1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA. miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue, and its expression level correlated inversely with aggressive clinical pathological features. Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation, migration, and invasion, and promoted apoptosis. The miR-3691-3p target genes E2F transcription factor 3 (E2F3) and PR domain containing 1, with ZNF domain (PRDM1) were upregulated in miR-3691-3p-overexpressing PCa cells, and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation, migration, and invasion. Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis. Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p, both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue. Our results indicate that TGF-ß1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1. These results provide novel insights into the mechanisms by which TGF-ß1 contributes to the progression of PCa.

[Therapeutic effect and safety of drug eluting stent for patients with acute ST-elevation anterior wall myocardial infarction by left anterior descending artery occluded abruptly].

OBJECTIVE: To assess the therapeutic effect and safety of drug eluting stent for the patients with anterior wall myocardial infarction by left anterior descending artery occluded abruptly. METHODS: From January 2004 to December 2008, 302 patients with anterior wall myocardial infarction in 12 hours from chest pain to treatment were treated. But only 189 patients were recruited and randomly divided into drug eluting stent group (n = 95) and bare metal stent group (n = 94). The occurrence of cardiac death, stent thrombosis, reinfarction, target vessel revascularization and re-hospitalization because of heart function failure was compared. RESULTS: There was no difference in cardiac death [3/95 (3%) vs 7/94 (7%), P = 0.206], reinfarction [1/95 (1%) vs 5/94 (5%), P = 0.112] and re-hospitalization because of heart function failure [8 (8%) vs 5 (5%), P = 0.434]. Compared with those in bare metal stent group, the patients in drug eluting stent group has a lower rate of target vessel revascularization [2 (2%) vs 13 (14%), P = 0.009] and composite therapeutic effect endpoints [12 (13%) vs 25 (27%), P = 0.011]. There was no difference in safety endpoint or stent thrombosis [1 (1%) vs 4 (4%), P = 0.204]. CONCLUSION: In patients with anterior wall myocardial infarction by left anterior descending artery occluded abruptly, drug eluting stent decreases the rate of target vessel revascularization. But it has no increased stent thrombosis.

[Effect of percutaneous coronary intervention timing and cilostazol use on left ventricular remodeling in patients with non-ST elevation myocardial infarction].

OBJECTIVE: To observe the dynamic changes of plasma matrix metalloproteinases (MMPs) and investigate the effect of early or delayed percutaneous coronary intervention (PCI) in the presence or absence cilostazol on left ventricle (LV) remodeling in patients with non-ST elevation myocardial infarction (NSTEMI). METHODS: One hundred and sixty-four patients undergoing PCI with NSTEMI were randomized to early PCI (PCI within 24 h) group or delayed PCI group (PCI after 36 h), and patients in both group were further assigned to cilostazol or no cilostazol group. Plasma MMP-2 and MMP-9 concentrations were measured at 2, 4 days and 2 and 4 weeks after PCI. Left ventricular end-diastolic volume (LVEDV), left ventricle ejection fraction (LVEF), left ventricle posterior wall (LVPW) and interventricular septum (IVS) were measured by echocardiography at baseline and 1 year after PCI. RESULTS: MMP-2 concentration at 2 weeks after PCI is higher than that at 2, 4 days and 4 weeks after PCI. MMP-9 concentration at 4 days is higher than that at 2 days, 2 weeks and 4 weeks after PCI. MMP-2 and MMP-9 were significantly lower in cilostazol group compared with that in non-cilostazol group at 4 days, 2 weeks and 4 weeks after NSTEMI (all P < 0.05). Changes of LVEDV and LVEF were significantly less in cilostazol group and early PCI group than that in no cilostazol group and delay PCI group (P < 0.05 or P < 0.01) at 1 year after NSTEMI. CONCLUSIONS: Early PCI and Cilostazol use are associated with less LV remodeling in patients with NSTEMI. Cilostazol attenuated LV remodeling possibly by reducing concentration of MMP-2 and MMP-9 after PCI.

[Anatomy variation of coronary vein system in patients with ischemic heart disease and non-ischemic].

OBJECTIVE: The purpose of this study was to analyze the anatomy variation of coronary vein system in patients with ischemic heart disease (IHD) and non-ischemic heart disease (NIHD). METHOD: Forty-one patients with IHD and 87 patients with NIHD [101 men, mean age (63.5 +/- 10.6) years] were included in this study. RESULTS: Coronary sinuses were successfully cannulated and venographies were obtained in 127 cases. Transvenous LV pacing leads were successfully placed in optimal coronary vein in 123 cases (96.09%). The majority (76.38%) patients had at least one or more vessel abnormalities (thinness, stenosis, tortuousity, lack of lateral marginal vein or postero-lateral vein). The incidence of thin and tortuousity was significantly higher in lateral marginal vein than that in postero-lateral vein (P < 0.05-0.01). The incidence of lack of postero-lateral marginal vein was more frequent than the lack of lateral vein (P < 0.05). The rate of abnormality in both vessels was 25.2%. Incidence of vein lack in male was more frequent than in female (P < 0.05). The thin and tortuousity of vessels in female were more frequent than in male (P < 0.05). The incidence of thin and tortuousity of postero-lateral and abnormality of both vessels was significantly higher in IHD than in NIHD patients (P < 0.05). All coronary sinus myocardial bridges occurred in NIHD. Stenoses of left anterior descending (LAD) and left circumflex (LCX) were mostly associated with abnormality of lateral vessels. CONCLUSIONS: The anatomic variations of lateral and postero-lateral coronary vein were more frequent in this patient cohort. Vein lack in male was more frequent and the thin and tortuousity of vessels were less in male than in female patients. The ratio of vessel abnormality is higher in patients with IHD. Coronary arteries stenosis and position of infarction are associated with anatomic variations of coronary vein system.

Ubiquitin Carboxyl-Terminal Hydrolases and Human Malignancies: The Novel Prognostic and Therapeutic Implications for Head and Neck Cancer.

Ubiquitin C-terminal hydrolases (UCHs), a subfamily of deubiquitinating enzymes (DUBs), have been found in a variety of tumor entities and play distinct roles in the pathogenesis and development of various cancers including head and neck cancer (HNC). HNC is a heterogeneous disease arising from the mucosal epithelia of the upper aerodigestive tract, including different anatomic sites, distinct histopathologic types, as well as human papillomavirus (HPV)-positive and negative subgroups. Despite advances in multi-disciplinary treatment for HNC, the long-term survival rate of patients with HNC remains low. Emerging evidence has revealed the members of UCHs are associated with the pathogenesis and clinical prognosis of HNC, which highlights the prognostic and therapeutic implications of UCHs for patients with HNC. In this review, we summarize the physiological and pathological functions of the UCHs family, which provides enlightenment of potential mechanisms of UCHs family in HNC pathogenesis and highlights the potential consideration of UCHs as attractive drug targets.

[Short and medium term follow-up study on the changes of spine pelvic parameters in patients with hip-spine syndrome after total hip arthroplasty].

OBJECTIVE: To investigate the influence of total hip arthroplasty on the changes of spine pelvic parameters in patients with hip spine syndrome. METHODS: From January 2013 to October 2014, 22 patients (26 hips) with hip spine syndrome accompanied by necrosis of femoral head, hip osteoarthritis and congenital dysplasia of hip were treated with total hip arthroplasty. There were 12 males and 10 females with an average age of 58.4 years (range, 45 to 76 years). The course of disease was 1.5 to 25 years with an average of 12.8 years. Before and after the operation, the anteroposterior, full length radiographs of both lower limbs, thoracolumbar spine and pelvis in standing position were routinely taken. The balance parameters of spine pelvis coronal plane and sagittal plane before and after the replacement were measured. Visual analogue scale (VAS), Oswestry Disability Index (ODI) and Harris score were performed before and after the operation. RESULTS: All cases were followed up for 21 to 52 (32±8) months. No infection, prosthesis subsidence, loosening, prosthesis dislocation were found in the last follow up. After total hip arthroplasty, sagittal vertical axis(SVA), thoracic kyphosis(TK), lumbar lordosis(LL), pelvic tilt (PT) were significantly reduced(P<0.05), sacral slope(SS) was significantly increased(P<0.05), there was no significant difference in pelvic incidence(PI)(P>0.05); PT and scoliosis (coronal position) were significantly decreased after operation(P<0.05); VAS score of waist, VAS score of hip joint and ODI score of waist were significantly decreased before and after operation (P<0.05). Harris score of hip joint increased significantly after operation, and thedifference was statistically significant (P<0.05). CONCLUSION: After total hip arthroplasty, the coronal and historical balance parameters of spine and pelvis are significantly improved, and the short term and medium-term effects are satisfactory.

[Strategy of acetabular anteversion in total hip arthroplasty with lumbar degenerative kyphosis].

OBJECTIVE: To investigate how to place the anteversion of acetabular prosthesis more reasonably in patients with lumbar degenerative kyphosis. METHODS: A total of 122 patients with degenerative kyphosis of lumbar spine who underwent total hip arthroplasty from December 2017 to October 2019 were included and divided into experimental group and control group, 61 cases in each group. In experimental group, there were 25 males and 36 females, with a median age of 67.0 years;the median course of disease was 46.0 months;the functional pelvic plane with acetabular anteversion was set according to different types of pelvic anterior plane bracket. In control group, there were 27 males and 34 females, with a median age of 67.0 years;the median course was 42.0 months;in control group, the anteversion was set by the traditional method. The patients were followed up for 3 months. The operation time and blood loss were recorded. The incidence of infection and dislocation within 3 months was counted. Harris score before and 3 months after operation was recorded. Functional anteversion angle of standing position was measured 3 months after operation. RESULTS: Compared with control group, there was no difference in operation time and blood loss between the two groups (P=0.918, 0.381);there was no infection between two groups within 3 months after operation;there was 1 case of hip joint dislocation in the control group and no dislocation in experimental group. There was no significant difference in Harris score before and after operation. Three months later, reexamination of pelvic standing radiographs showed that the number of patients with functional anteversion of acetabular prosthesis outside the safe area was less in experimental group thanin control group (P=0.048), and the functional anteversion angle of acetabular prosthesis was more concentrated in the range of 15 ° to 20 ° in experimental group (P<0.001). CONCLUSION: According to the preoperative evaluation and classification of patients, better functional anteversion of acetabular prosthesis can be obtained with the help of pelvic anterior plane reference bracket in hip arthroplasty with lumbar degenerative kyphosis.

Bone Marrow Mesenchymal Stem Cells Ameliorate Cisplatin-Induced Renal Fibrosis via miR-146a-5p/Tfdp2 Axis in Renal Tubular Epithelial Cells.

Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury (AKI). However, the potential function of MSCs in chronic kidney disease remains elusive. Renal fibrosis is the common endpoint of chronic progressive kidney diseases and causes a considerable health burden worldwide. In this study, the protective effects of bone marrow mesenchymal stem cells (BM-MSCs) were assessed in repeated administration of low-dose cisplatin-induced renal fibrosis mouse model in vivo as well as a TGF-ß1-induced fibrotic model in vitro. Differentially expressed miRNAs in mouse renal tubular epithelial cells (mRTECs) regulated by BM-MSCs were screened by high-throughput sequencing. We found microRNA (miR)-146a-5p was the most significant up-regulated miRNA in mRTECs. In addition, the gene Tfdp2 was identified as one target gene of miR-146a-5p by bioinformatics analysis. The expression of Tfdp2 in the treatment of BM-MSCs on cisplatin-induced renal injury was evaluated by immunohistochemistry analysis. Our results indicate that BM-MSC attenuates cisplatin-induced renal fibrosis by regulating the miR-146a-5p/Tfdp2 axis in mRTECs.

[Comparison on long-term effects of atorvastatin or pravastatin combined with clopidogrel for patients undergoing coronary stenting: a randomized controlled trial].

OBJECTIVE: To evaluate the long-term therapeutic effects of atorvastatin via cytochrome P450 (CYP)3A4 pathway or a non-CYP 3A4 pathway statin, pravastatin, combined with clopidogrel for the patients undergoing coronary stenting. METHODS: Between February 2006 and March 2007, a total of 1275 patients undergoing successful coronary stenting were randomly assigned to receive atorvastatin 20 mg/d (n = 638) or pravastatin 20 mg/d (n = 637). All patients received standard clopidogrel therapy. The primary end point was cardiac and cerebral ischemic events at 12 months, defined as a composite of cardiac death, non-fatal myocardial infarction (MI) or stroke. The secondary end points were major adverse cardiac and cerebral events (MACCE), stent thrombosis and TIMI hemorrhagic events at 12 months. RESULTS: The baseline clinical characteristics, angiographic and PCI result were comparable between two groups. At 12 month follow-up, no significant difference was observed in cardiac and cerebral ischemic events between two groups (4.7% vs 5.5%, P > 0.05). Also no significant difference existed in rate of cardiac death (1.9% vs 2.5%, P > 0.05), non-fatal MI (0.5% vs 0.3% , P > 0.05), stroke (2.4% vs 2.7%, P > 0.05) and TVR (7.7% vs 5.5%, P > 0.05) between two groups. The rates of MACCE (12.4% vs 11.0%, P > 0.05), stent thrombosis (2.0% vs 2.5%, P > 0.05) and hemorrhagic events (13.0% vs 12.2%, P > 0. 05) were similar between two groups. CONCLUSION: The 12 month clinical outcomes were similar between patients receiving atorvastatin 20 mg/d or pravastatin 20 mg/d combined with clopidogrel after coronary stenting. It confirmed the efficacy and safety of the combination of clopidogrel with statins via different metabolic pathways.

[Long-term clinical outcomes of patients undergoing successful or failed percutaneous coronary intervention for chronic total occlusions of coronary arteries].

OBJECTIVE: To evaluate the long-term outcomes of successful or failed revascularization in patients with chronic total occlusions (CTO). METHODS: The clinical data of 1332 consecutive patients underwent percutaneous coronary intervention (PCI) for CTO between June 1993 and December 2006 in our hospital were analyzed. These patients were divided into two groups according to the procedural success (n = 1202) or failure (n = 130). RESULTS: Overall success rate of procedure was 90.2% (1202/1332). The patients in CTO success group experienced a superior 10-year survival rate (76.9% vs. 64.6%, log rank P = 0.012) and a significantly higher no major adverse cardiovascular event (MACE) survival rate (41.8% vs. 27.6%, log rank P < 0.001) compared to the patients in CTO failure group. During the long-term follow-up, the proportion of patients who accepted coronary artery bypass grafting (CABG) was significantly lower in CTO success group than that in the CTO failure group (4.3% vs. 14.6%, P < 0.001). CONCLUSION: Successful PCI procedure leads to increased long-term survival and MACE-free survival and the reduced need for CABG for patients with CTO lesions.

[Outcome of percutaneous coronary intervention of graft occlusion post coronary artery bypass graft].

OBJECTIVE: To evaluate the feasibility and efficacy of percutaneous coronary intervention (PCI) for graft occlusion post coronary artery bypass graft (CABG). METHODS: The clinical data of 135 post-CABG patients with bypass graft occlusion and angina pectoris symptoms admitted to our department between June 2003 and June 2007 were analyzed. The mean interval from CABG to index angiography was 33.8 +/- 23.5 months. Among 318 grafts, 29 left internal mammary artery (LIMA, 29/128, 22.7%) and 117 saphenous vein bypass grafts (117/188, 62.2%) were occluded. A total of 158 target lesions from these 146 vessels were treated with PCI. All target lesions were B2/C type lesion with 29.7% (47/158) chronic total occlusions. RESULTS: A total of 310 DES were implanted. The total success rate of PCI procedure was 96. 3% (130/135), and lesion success rate was 96.8% (153/158). No major clinical complications occurred during peri-intervention period. All patients underwent PCI were followed at 12 month. Angiographic follow-up was obtained in 89 patients and the angiographic restenosis rate was 5.6% (5/89) in these patients. The major adverse cardiac events and target vessel revascularization rates were 5.4% (7/130) and 6.2% (8/130), respectively. CONCLUSION: This study demonstrates that PCI procedure for graft occlusion post-CABG is feasible and safe and associated with a high procedure success rate and favorable long-term clinical and angiographic outcomes.

Sex Differences Associated With Circulating PCSK9 in Patients Presenting With Acute Myocardial Infarction.

A limited number of studies have explored whether the role of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathogenesis of acute myocardial infarction (AMI) is sex specific. The purpose of the present study was to examine sex differences in plasma PCSK9 in Chinese patients with AMI. In this study, a total of 281 records from patients presenting with AMI were analyzed.We compared hospital data and plasma PCSK9 levels by sex difference for inpatients presenting with AMI. After 1 year of follow-up, major adverse cardiac events(MACE) were recorded. A Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. We found that, compared with male groups, PCSK9 levels were higher in female patients not only for overall patients with AMI but also for patients with ST-elevation myocardial infarction (STEMI) (median: 273.6 [215.6-366.8] vs. 325.1 [247.5-445.3] ng/ml, P = 0.0136; 273.4 [215.6-369.7] vs. 317.1 [249.6-450.1], P = 0.0275, respectively). The cumulative incidence of cardiac death and 1-year MACE were significantly higher in the female group compared with male group (10% vs. 2.74%, P = 0.025; 15% vs. 4.11%, P = 0.0054, respectively). On multivariate Cox regression analysis, female sex, total triglyceride, glycosylated hemoglobin A, and homocysteic acid were independent risk factors of 1-year MACE. There was no significant correlation between PCSK9 and 1-year MACE in total AMI patients. In conclusion, PCSK9 levels and 1-year MACE were higher in women with AMI than in men with AMI, however, female sex but not PCSK9 were significant correlated with the 1-year MACE. The clinical implications of this finding are worthy of further investigations and must be confirmed in larger cohorts.

Multi-wire plaque crushing as a novel technique in treating chronic total occlusions.

BACKGROUND: Failure of balloon catheter passing through the occluded segment accounts for 10% - 15% of all procedures during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). We sought to investigate an original technique for facilitating balloon catheter passing by multi-wire plaque crushing. METHODS: Between July 2000 and October 2007, 152 patients with 164 CTO lesions who had failed balloon passing were treated by multi-wire plaque crushing technique. The main process of this technique was to insert 1 or 2 wires along with the original wire located in the true lumen of CTO lesions after balloon failure for plaque crushing and then to withdraw the crushing wires to get an enlarged lumen inside of the occlusion segment, thus facilitating the balloon passing. RESULTS: Both overall lesion and technique success rates were 91.5% (150/164). A total of 211 crushing wires were used during PCI, including 1 crushing wire for 117 (71.3%) lesions and 2 crushing wires for 47 (28.7%) lesions. Approximately 57.3% (121/211) of all crushing wires were those already used in the same procedure. Technique failure occurred in 14 lesions (8.5%). Technique failure was due to crushing wires entering false lumen (92.9%, 13/14) and coronary perforation (7.1%, 1/14). Major procedural complications included coronary perforation (1 case) and severe coronary dissection (2 cases), all of which were successfully treated. CONCLUSIONS: Multi-wire plaque crushing technique is effective in facilitating balloon catheter passing during CTO PCI. It is feasible, economical and relatively safe with a low rate of procedural complications.

[Acute angiographic and clinical outcomes of patients with calcified chronic total occlusion underwent percutaneous coronary intervention].

OBJECTIVE: To evaluate the in-hospital outcome of patients with calcified chronic total occlusion (CTO) lesion underwent percutaneous coronary intervention (PCI). METHODS: The clinic and lesion characteristics as well as acute PCI outcome were analyzed in 726 patients with calcified CTO [624 detected by coronary angiography (CAG) and 102 detected by intravascular ultrasound (IVUS)] and received PCI therapy from June 1995 to February 2007 in our department. RESULTS: There were 728 diseased vessels with 732 lesions in these patients. Total procedure success rate (80.6% vs. 89.2%, P < 0.05) and the lesion success rate (80.2% vs. 88.2%, P < 0.05) were significantly lower in calcified CTO detected by CAG compared to that detected by IVUS. The causes of procedure failures in CAG detected patients were as follows: 87 guide failure, 21 balloon failure, 8 procedure related complications and 5 low TIMI blood flow (grade 2) at the end of PCI procedure. The causes of procedure failures in IVUS detected patients were as follows: 7 guide wire failure, 2 balloon failure, 1 procedure related complications and 1 patient with low TIMI blood flow (grade 2). The in-hospital major adverse cardiac events (MACE) rate was 1.1% in CAG detected calcified CTO and 1.0% in IVUS detected calcified CTO (P > 0.05). CONCLUSION: PCI therapy resulted in satisfactory procedure success rate and in-hospital outcome for patients with calcified CTO and IVUS is helpful for further increasing the PCI procedure success rate in patients with calcified CTO.

Smad4 and ERK2 stimulated by transforming growth factor beta1 in rhabdomyosarcoma.

BACKGROUND: Transforming growth factor beta (TGF-beta) plays an essential role in the regulation of normal physiologic processes of cells. TGF-beta has been shown to regulate several mitogen-activated protein kinases (MAPK) pathways in several epithelial cells. However, the effects of TGF-beta on soft tissue sarcoma are seldom reported. Our previous studies suggested that there should be some other signal transduction pathways besides Smads, which are important to regulate the growth of human embryonal rhabdomyosarcoma (RMS) cells. In the present study, we examined the expression and functional relations of extracellular signal-regulated kinase 2 (ERK2) and Smad4 in human RMS tissue and a RMS cell line, RD. METHODS: RD cells and normal human primary skeletal myoblasts (Mb) were treated with TGF-beta1 to establish the expression profile of ERK2 at the mRNA and protein levels detected by RT-PCR and immunofluorescence. Immunohistochemistry was used to detect the expression of ERK2 and Smad4 in 50 tissue specimens of human RMS and 23 specimens of normal skeletal muscles. Follow-up of specimens was performed 6 months to 70 months later. RESULTS: RD cells and human RMS tissues showed the higher expression of ERK2 and Smad4 than the normal control, either the protein level or the mRNA level. And, exogenous TGF-beta1 stimulation can lead to higher expression of ERK2 and its nuclear translocation, so TGF-beta1 can also activated MAPK (ERK2) pathway, resulting in a sustained activation of ERK2 for at least 2 hours. Immunohistochemistry analysis, however, showed that there was no correlation between ERK2 and Smad4 protein. The overexpression of ERK2 and Smad4 had no indicative effects on histological subtypes, histological grading, gender, age, and prognosis. CONCLUSIONS: In RMS, signaling of TGF-beta1 from cell surface to nucleus can also be directed through the MAPK (ERK2) pathway besides the TGF-beta1/Smads pathway. The activation of ERK2 by TGF-beta1 may be Smad4 independent. Moreover, there may be some other tanglesome relationships between the TGF-beta1/Smads pathway and the MAPK pathway which takes part in the development, invasion and metastasis of tumor cells.