This study is to investigate the influence and the expression of CMTM family of testosterone on spermatogenesis suppression in the male rats treated by gossypol and cyclophosphamide. Gossypol (50 mg kg(-1)) and cyclophosphamide (20 mg kg(-1)) were administered to male rats to induce spermatogenesis suppression. Testosterone propionate was administrated at the dose of 5 mg kg(-1) every other day for 6 times. Sperm was collected from the left caudal epididymis, the count and motility of sperm were analyzed by CASA. Morphological change of testis tissue was observed with HE staining. The expression of CMTM family was examined by Western blotting assay. Gossypol (50 mg kg(-1)) and cyclophosphamide (20 mg kg(-1)) decreased the count and motility of sperm, and the pathological change of testis tissue was also observed. But, testosterone (5 mg kg(-1)) had positive effect. Furthermore, CMTM4 down-expressed remarkably in the gossypol and cyclophosphamide treated rats, the expression of the CMTM4 was up-expressed after testosterone administration. On the contrary, the expression of CMTM2 increased significantly only in gossypol treated male rats, but not in cyclophosphamide treated male rats. The expression of CMTM2 was down-expressed after testosterone administration. However, no obvious change of CMTM2 was observed in cyclophosphamide treated rats. Testosterone did not influence the expression of CKLF1, CMTM3 and CMTM5, the CMTM6, CMTM7 and CMTM8 of CMTM family were not detected in testis tissue. These demonstrated that the spermatogenesis effect of testosterone (5 mg kg(-1)) was associated with the expression of CMTM family, and CMTM2 and CMTM4 may take part in the spermatogenesis process.
Animals ; Cyclophosphamide ; toxicity ; Gene Expression Regulation ; Gossypol ; toxicity ; Male ; Membrane Proteins ; metabolism ; Rats ; Rats, Wistar ; Sperm Count ; Sperm Motility ; drug effects ; Spermatogenesis ; drug effects ; Testis ; metabolism ; pathology ; Testosterone ; pharmacology

OBJECTIVETo evaluate risk factors and clinical outcome of coronary artery aneurysms (CAA) developed after drug-eluting stent implantation evidenced by coronary angiographic follow-up.

METHODSThis 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.

RESULTSCAA was detected in 70 patients with 70 lesions (9.2%, 70/760). Logistic analysis showed that lesion in an infarct-related 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.

CONCLUSIONSThe 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.

Aged ; Coronary Aneurysm ; etiology ; Coronary Restenosis ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Middle Aged ; Prognosis ; Risk Factors

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

Aged ; Angina, Unstable ; pathology ; therapy ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Coronary Disease ; pathology ; therapy ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome

OBJECTIVETo explore the molecular mechanism in the formation of unstable plaques.

METHODSThe cDNA microarray E-MTAB-2055 was downloaded from ArrayExpress database to screen the differentially expressed genes in 24 ruptured plaques against 24 stable plaques. Functional enrichment analysis was conducted to define the biological processes and pathways involved in disease progression. The protein-protein interaction network was constructed to identify the risk modules with close interactions. Five pairs of carotid specimens were used to validate 3 differentially expressed genes of the risk modules by real-time PCR.

RESULTSA total of 439 genes showed differential expression in our analysis, including 232 up-regulated and 207 down-regulated genes according to the data filter criteria. Immune-related biological processes and pathways were greatly enriched. The protein-protein interaction network and module analysis suggested that TYROBP, VCL and CXCR4 might play critical roles in the development of unstable plaques, and differential expressions of CXCR4 and TYROBP in carotid plaques were confirmed by real-time PCR.

CONCLUSIONOur study shows the differential gene expression profile, potential biological processes and signaling pathways involved in the process of plaque rupture. TYROBP may be a new candidate disease gene in the pathogenesis of unstable plaques.

Adaptor Proteins, Signal Transducing ; genetics ; Disease Progression ; Down-Regulation ; Gene Expression Profiling ; Humans ; Membrane Proteins ; genetics ; Oligonucleotide Array Sequence Analysis ; Plaque, Atherosclerotic ; genetics ; Protein Interaction Maps ; Real-Time Polymerase Chain Reaction ; Receptors, CXCR4 ; genetics ; Transcriptome ; Up-Regulation ; Vinculin ; genetics

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

BACKGROUNDStenting strategies and clinical outcomes of bifurcation lesions in a chronic total occlusion (CTO) vessel after successful recanalization remain to be unknown.

METHODSBetween 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).

RESULTSCollaterals 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.

CONCLUSIONSTwo-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.

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; Coronary Stenosis ; therapy ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Registries ; Stents ; adverse effects ; Treatment Outcome

BACKGROUNDFractional 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.

METHODSSeventy-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.

RESULTSBaseline 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.

CONCLUSIONSDK 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.

Adolescent ; Adult ; Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Disease ; therapy ; Coronary Stenosis ; therapy ; Drug-Eluting Stents ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; methods ; Treatment Outcome ; Young Adult

Asthma is a chronic inflammatory respiratory disease accompanied with airway inflammation, airway remodeling and bronchial hyperresponsiveness. Chemokines are important for the recruitment of immune cells to the lung, which play an important role in the formation and development of asthma. Targeting the chemokine receptors to anti-inflammation and anti-asthma is a new strategy and some candidate drugs are discovered recently. This review is focused on the development of chemokine receptor antagonists for anti-asthma, which will promote the compound designations.
Animals ; Anti-Asthmatic Agents ; pharmacology ; therapeutic use ; Asthma ; drug therapy ; Heterocyclic Compounds ; pharmacology ; Humans ; Phenylurea Compounds ; therapeutic use ; Piperidines ; pharmacology ; therapeutic use ; Pyridazines ; pharmacology ; Receptors, CCR1 ; antagonists & inhibitors ; Receptors, CCR3 ; antagonists & inhibitors ; Receptors, CCR4 ; antagonists & inhibitors ; Receptors, CXCR4 ; antagonists & inhibitors ; Receptors, Chemokine ; antagonists & inhibitors

BACKGROUNDThe gender-based differences in adverse events after drug-eluting stent (DES) implantation between Chinese women and men have not been fully studied. The present study aimed to compare the 5-year clinical outcome after DES implantation in Chinese women and men.

METHODSChinese women (n = 298) and men (n = 698) with newly diagnosed de novo coronary lesions were studied after DES implantation. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) over a 5-year follow-up, including myocardial infarction (MI), cardiac death, and target vessel revascularization (TVR). Propensity score matching (PSM) was used to compare the adjusted MACE rates between sexes.

RESULTSWomen differed in body habitus and had increased fasting cholesterol. Fewer women presented with MI, and they had better cardiac function with less complex disease. The unadjusted rate of MI at 3 years (2.1%) and 5 years (5.0%) and MACE (25.2%) at 5 years in men was significantly higher than that of women (0.3%, 1.0% and 17.8%, P = 0.050, P = 0.032, and P = 0.011, respectively). After PSM, the adjusted adverse events between sexes were similar. The stent thrombosis rate rapidly increased after 2 years in men.

CONCLUSIONSThere were significant gender-based differences in baseline characteristics. Chinese men had equivalent outcomes to women after DES after adjustment by PSM. The increased rate of MI in men was attributed to an increased unadjusted rate of MACE.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Prospective Studies ; Treatment Outcome