Impact of main vessel calcification on procedural and clinical outcomes of bifurcation lesion undergoing provisional single-stenting intervention: a multicenter, prospective, observational study.

BACKGROUND: Few data on the combined effects of bifurcation and calcification on coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) are available. This study evaluated the impact of main vessel (MV) calcification on the procedural and long-term outcomes in patients with CAD who underwent provisional single stent PCI. METHODS: This is a multicenter, prospective, observational study. Patients with bifurcation lesions were enrolled at 10 PCI centers in China from January 2015 to December 2017. Intravascular ultrasound or optical coherence tomography was performed in all patients to evaluate the MV calcification. Patients were treated with provisional single stent strategy using drug eluting stents and followed-up at 1 month, 6 months and 12 months after discharge by telephone contact or outpatient visit. Repeated coronary imaging was performed within one year. We compared the procedural success rates in MV and in side branch (SB), and target lesion failure (TLF), defined as a composite of cardiac death, non-fatal myocardial infarction, definite or possible stent thrombosis and target lesion revascularization between patients with and without MV calcification. RESULTS: A total of 185 subjects were enrolled according to the inclusion and exclusion criteria of this study. MV calcification was detected in 119 (64.3%, calcification group) and not found in 66 (35.7%, non-calcification group) patients. The angiographic success rate of MV was 95.8% in the calcification group and 97.0% in the non-calcification group (P = 0.91); the angiographic success rate of SB was 32.8% in the calcification group and 53.0% in the non-calcification group (P < 0.05). During the one-year follow-up period, TLF occurred in 14 (11.8%) patients in the calcification group and in 13 (19.7%) in the non-calcification group (P = 0.31). Multivariate regression analysis showed the same result (HR = 1.23, 95% CI: 0.76-1.52, P = 0.47). Calcification on group had higher recurrent angina than non-calcification group (13.51% vs. 17.65%, P < 0.05). CONCLUSIONS: In patients with coronary bifurcation lesion treated with provisional one stent approach, calcification of MV is associated with lower SB procedural success rate, it could increase recurrence of angina; however, it was not associated with an increased risk of TLF.

Effects of hepatitis C virus core protein and nonstructural protein 4B on the Wnt/ß-catenin pathway.

BACKGROUND: Hepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/ß-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/ß-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis. RESULTS: Compared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced ß-catenin/Tcf-dependent transcriptional activity (F = 40.87, P < 0.01); increased nuclear translocation of ß-catenin (F = 165.26, P < 0.01); upregulated nuclear ß-catenin, cytoplasmic ß-catenin, Wnt1, c-myc, and cyclin D1 protein expression (P < 0.01); and promoted proliferation of Huh7 cells (P < 0.01 or P < 0.05). Neither protein enhanced ß-catenin/Tcf-dependent transcriptional activity in the LO2 cells (F = 0.65, P > 0.05), but they did significantly enhance Wnt3a-induced ß-catenin/Tcf-dependent transcriptional activity (F = 64.25, P < 0.01), and promoted the nuclear translocation of ß-catenin (F = 66.54, P < 0.01) and the Wnt3a-induced proliferation of LO2 cells (P < 0.01 or P < 0.05). Moreover, activation of the Wnt/ß-catenin signaling pathway was greater with the core protein than with NS4B (P < 0.01 or P < 0.05). CONCLUSIONS: HCV core protein and NS4B directly activate the Wnt/ß-catenin signaling pathway in Huh7 cells and LO2 cells induced by Wnt3a. These data suggest that HCV core protein and NS4B contribute to HCV-associated hepatocellular carcinogenesis.

Inhibition of expression of hepatitis C virus 1b genotype core and NS4B genes in HepG2 cells using artificial microRNAs.

The present study aimed to evaluate the silencing effect of artificial microRNAs (amiRNAs) against the hepatitis C virus (HCV) 1b (HCV1b) genotype core (C) and non-structural protein 4B (NS4B) genes. pDsRed-monomer-Core and pDsRed-monomer-NS4B plasmids, containing the target genes were constructed. A total of eight artificial micro RNA (amiRNA)-expressing plasmids, namely, pmiRE-C-mi1 to -mi4 and pmiRE-NS4B-mi1 to -mi4, were designed and constructed to interfere with various sites of the core and NS4B genes, and the amiRNA interfering plasmid and the corresponding target gene-expressing plasmid were co-transfected into HepG2 cells. At 48 h after transfection, HCV core and NS4B gene expression levels were detected using fluorescence microscopy, flow cytometry, reverse transcription quantitative polymerase chain reaction and western blot analysis. Fluorescence microscopy revealed that the target gene-transfected cells expressed red fluorescent protein, whereas the interfering plasmid-transfected cells exhibited expression of green fluorescent protein. The percentage of red fluorescent proteins and mean fluorescence intensity, as well as protein expression levels of the core and NS4B genes within the cells, which were co-transfected by the amiRNA interfering plasmid and the target gene, were significantly decreased. The results of the present study confirmed that amiRNAs may effectively and specifically inhibit the expression of HCV1b core and NS4B genes in HepG2 cells, potentially providing a novel therapeutic strategy for the treatment of HCV.

Randomized controlled study of plasma exchange combined with molecular adsorbent re-circulating system for the treatment of liver failure complicated with hepatic encephalopathy.

BACKGROUND/AIMS: To evaluate the use of plasma exchange (PE) combined with the molecular adsorbent re-circulating system (MARS) for the treatment of liver failure complicated with hepatic encephalopathy. METHODOLOGY: A prospective randomized controlled study was conducted to compare the therapeutic effect of MARS treatment (MARS group, n=60) with that of PE combined with MARS treatment (PE+MARS group, n=60) in patients with liver failure complicated with hepatic encephalopathy. RESULTS: The serum total bilirubin and blood ammonia levels were significantly decreased compared with pretreatment levels after 3 days of both the MARS treatment (p=0.0001, p<0.001) and PE+MARS treatment (both p<0.0001) and the Glasgow coma scale score was significantly increased (both p<0.0001). The 30-day mortality rate was 10.0% (6/60) in the MARS group and 11.7% (7/60) in the PE + MARS group. The per capita cost of treatment was significantly lower in the PE + MARS group than in the MARS group (p=0.0003). CONCLUSIONS: Both MARS and PE + MARS therapy can safely and effectively be used to treat liver failure complicated with hepatic encephalopathy, but PE + MARS therapy reduces serum total bilirubin level more effectively and is more cost-effective.

A facile chemical approach for preparing a SERS active silver substrate.

This communication describes a new surface-enhanced Raman scattering (SERS) active silver substrate prepared by iodination of the evaporated silver foil. After iodination, the morphology of the silver substrate undergoes a self-evolution process in which it displays accordingly the UV-vis absorption shift as well as the AFM topological test. Rhodamine 6G (R6G) is used as the probe molecule to evaluate the enhancement efficiency of the silver substrate at different self-evolution time intervals. The SERS intensity of R6G increases up to ∼29-fold and reaches a maximum after the substrate evolved for 24 h. This method is feasible for the production of an efficient SERS silver substrate.

A bulky bis-pocket manganese(V)-oxo corrole complex: observation of oxygen atom transfer between triply bonded Mn(V)[triple bond]O and alkene.

The highly bulky bis-pocket corrole 5,10,15-tris(2,4,6-triphenylphenyl)corrole (H(3)TTPPC) has been synthesized. Resonance Raman spectroscopy revealed a triply bonded Mn[triple bond]O moiety in its manganese(V)-oxo complex. Direct oxygen atom transfer from (TTPPC)Mn[triple bond]O to styrene was confirmed by an (18)O-labeling experiment. The (TTPPC)Mn(III) complex also exhibits significant shape selectivity in the catalytic epoxidation of nonconjugated dienes.

Mycophenolate mofetil prevents lethal acute liver failure in mice induced by bacille Calmette-Guérin and lipopolysaccharide.

BACKGROUND/AIMS: To investigate the effect of mycophenolate mofetil (MMF) on acute liver injury induced by bacille Calmette-Guérin (BCG) and lipopolysaccharide (LPS). METHODS: Acute liver failure was induced in male Kunming strain mice by injecting the animals with BCG 2.5 mg per mouse, and LPS 10 microg per mouse 10 days later. The mice in the treatment groups were given MMF 2 h before, simultaneous with, or 2 h after administration of LPS, and the mice in the control group were given the same dose of saline. The 24-h survival rate, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were compared. Serum levels of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 6 (IL-6) were measured and the expressions of TNF-alpha, IFN-gamma, and IL-6 mRNA in the liver tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). Concanavalin A (Con A)-induced splenocyte proliferation were determined by methods of methyl thiazolyl tetrazolium. RESULTS: Injecting a small dose of LPS into BCG-primed mice caused a lethal hepatic injury mimicking acute hepatitis, from which 16 of the 20 mice died within 24 h (20% survival rate). Massive necrosis of parenchymal hepatocytes with marked inflammatory cell infiltration was observed by histological examination. In parallel, serum ALT and TNF-alpha, IFN-gamma, and IL-6 levels were increased. Expression of TNF-alpha, IFN-gamma, and IL-6 mRNA in the liver were significantly increased also. Treatment with MMF markedly reduced the death rate in a dose-dependent manner. It reached its maximal effect at the dosage of 150 mg per kg of body weight when pretreated 2 h before LPS injection, with improvement of histological feather and survival rate (84.2%, 16/19). MMF significantly inhibited serum levels of TNF-alpha, IFN-gamma, and IL-6, and significantly reduced TNF-alpha, IFN-gamma, and IL-6 expression in the liver, which increased after BCG and LPS injection. Moreover, splenocyte proliferation response induced by Con A was also inhibited by MMF treatment. CONCLUSIONS: Treatment with MMF has a protective effect on endotoxin-induced fatal liver failure by regulating the production of inflammatory cytokines and T-cell proliferation.

Dendritic nanostructures of silver: facile synthesis, structural characterizations, and sensing applications.

Silver nanodendrites are synthesized by a simple surfactant-free method using a suspension of zinc microparticles as a heterogeneous reducing agent. Structural characterizations suggest the preferential growth along 100 and 111 directions by oriented attachment of silver nanocrystals in the diffusion limit, leading to the formation of silver nanodendrites 20-30 nm in stem and branch diameter and 5-50 microm in length. Surface-enhanced Raman scattering studies show that the silver nanodentrites give an intensive and enhanced Raman scattering when pyridine was used as a probing molecule. We have also demonstrated that the silver nanodendrites increase the sensitivity of an electrochemical glucose biosensor by as much as 1-2 orders of magnitude.

[Role of platelet activating factor in hepatorenal syndrome].

OBJECTIVE: To investigate the relationship between platelet activating factor (PAF) and occurrence of hepatorenal syndrome (HRS). METHODS: A total of 57 cases of patients with liver cirrhosis or hepatitis gravis were enrolled. The serum concentrations of PAF, lipopolysaccharide (LPS) and prothrombin activity (PTA), total bilirubin, and serum creatinine were detected in patients combined with HRS and in patients without HRS in hospital at the term. The correlations among the PAF, LPS, and the function of liver and kidney were analyzed. RESULTS: The concentrations of PAF and LPS in the patients combined with HRS were significantly higher than those patients without HRS. There were linear correlations between the PAF and LPS level, the total bilirubin level and PAF level, the PAF level and serum creatinine level. CONCLUSION: The PAF associates with the occurrence of HRS. The PAF may mediate the occurrence of HRS induced by LPS. The PAF level may forecast whether patients with liver failure will take place HRS.

[Study on the influencing factors of thrombocytopenia in viral hepatitis].

OBJECTIVE: To explore the pathogenesis of thrombocytopenia in viral hepatitis. METHODS: 84 viral hepatitis patients and 20 healthy controls were divided into three groups: Group A: 48 viral hepatitis patients with thrombocytopenia; Group B: 36 viral hepatitis patients with normal platelet count; and Group C: 20 healthy controls. Serum thrombopoietin (TPO) levels were measured in all subjects by enzyme linked immunosorbent assay. The levels of PAIg, PAIgG, PAIgA, PAIgM were detected in all subjects by flow cytometry. Spleen size was assessed in all subjects by abdominal color ultrasound B Scan. Bone marrow cells were examined in 74 subjects with bone marrow punctures. RESULTS: Serum thrombopoietin level was lower in group A than in group C and in group B. Serum TPO levels were correlated with platelet counts in the patients with advanced liver diseases. PAIg, PAIgG levels were significantly higher in group A than in group B and in group C. An inverse correlation was found between platelet counts and PAIg levels. An inverse correlation was also observed between platelet counts and PAIgG levels. The incidence of splenomegaly was significantly higher in group A (77.1%) than in group B (47.2%), while group C had no splenomegaly. An inverse correlation between spleen size and platelet count was observed (r = -0.581). There were 4 patients in group A with hypoplasia of bone marrow karyocytes, but there were no such cases in groups B and C. CONCLUSIONS: TPO level decreasing in patients with severe liver function impairments correlates with thrombocytopenia in advanced liver diseases. Autoimmune mechanism mediated by PAIg may play an important role in thrombocytopenia associated with viral hepatitis. Splenomegaly is the influencing factor leading to thrombocytopenia in viral hepatitis. Patients with chronic liver diseases had bone marrow depression, which may be a factor inducing thrombocytopenia in patients with viral hepatitis.

[Platelet associated immunoglobulin in the pathogenesis of thrombocytopenia in patients with chronic liver disease].

OBJECTIVE: To explore the role of platelet associated immunoglobulin (PAIg) in the mechanism of thrombocytopenia associated with chronic liver disease. METHODS: The levels of PAIg, PAIgG, PAIgA, and PAIgM were detected in 48 viral hepatitis patients with thrombocytopenia, 36 viral hepatitis patients with normal platelet count and 20 healthy subjects by flow cytometry. RESULTS: PAIg and PAIgG levels (34.54 +/- 14.54%, 28.98 +/- 14.77%, respectively) in the 48 viral hepatitis with thrombocytopenia were significantly higher than those [(21.12 +/- 10.88)%, (16.60 +/- 7.83)%, respectively, P < 0.001)] in the 36 viral hepatitis with normal platelet count and those [(21.15 +/- 16.15) %, (14.89 +/- 9.57)% , respectively, P < 0.01)] in the 20 healthy controls. An inverse correlation was found between the platelet count and PAIg levels (r = -0.446, P < 0.01), and an inverse correlation was also observed between the platelet count and PAIgG levels (r = -0.462, P < 0.01). CONCLUSION: Autoimmune mechanism mediated by PAIg may play an important role in thrombocytopenia associated with viral hepatitis.

[Structure and regulative function of the 5' end flanking sequence of gene CCR5].

OBJECTIVE: To construct the pCAT reporter genes containing the 5'-end flanking of CC chemokine receptor 5(CCR5) gene in different sequence lengths and identify the sequence, which regulates the gene expression of CCR5 by the CAT analysis system. METHODS: The target sequences were amplified by pyrobest DNA polymerase, and were inserted into the upstream of CAT gene located in the pCAT enhancer vector by the directional clone technique respectively; the regulative sequence was identified by analyzing the CAT activities of reconstructed plasmid in Hela cells. RESULTS: The region, containing 486 bp upstreaming from exon 1, stimulated the reporter gene activity which was about 3 times that of the pCAT enhancer vector in transfected cells. CONCLUSION: There is an up-regulative element of gene transcription in the region of -1(-)-486 bp in CCR5 gene upstream.