Objective:To analyze therapeutic effect of amiodarone combined RAS inhibitors on hypertensive patients with atrial fibrillation(AF),and its influence on serum levels of uric acid(SUA)and silent information regulator 2-related enzymes 1(SIRT1).Methods:A total of 186 hypertensive patients with AF were selected from our hospital. They were randomly and equally divided into amiodarone group(group A),amiodarone + telmisartan group(A+T group)and amiodarone + ramipril group(A+ R group).Left atrial diameter(LAD),P wave dispersion(Pd),lev-els of high sensitive C reactive protein(hsCRP),brain natriuretic peptide(BNP)and SUA,SIRT1 mRNA and pro-tein expression and blood pressure variability(BPV)were observed and compared among three groups before and 45d after treatment.Results:Compared with before treatment,there were significant improvement in all index ex-cept SUA after treatment in three groups,P=0.001 all;compared with group A after treatment,there were signif-icant reductions in 24hSBPV[(0.112 ± 0.022)vs.(0.092 ± 0.020)vs.(0.091 ± 0.021)],24hDBPV[(0.143 ±0.031)vs.(0.130 ± 0.040)vs.(0.129 ± 0.039)],levels of hsCRP[(8.3 ± 0.3)mg/L vs.(5.3 ± 0.6)mg/L vs. (3.6 ± 0.4)mg/L],BNP[(64.9 ± 9.4)ng/dl vs.(61.1 ± 7.6)ng/dl vs.(58.2 ± 8.3)ng/dl]and SUA[(498.85 ± 89.54)μmol/L vs.(298.54 ± 56.12)μmol/L vs.(278.32 ± 54.09)μmol/L],SIRT1 mRNA[(2.20 ± 0.34)%vs.(1.87 ± 0.30)% vs.(1.76 ± 0.31)%]and protein[(29.54 ± 8.12)% vs.(26.31 ± 7.43)% vs.(23.21 ± 6.90)%]expression in A+T group and A+ R group,P<0.05 or <0.01. Compared with group A,there were sig-nificant rise in Pd[(39.3 ± 4.2)ms vs.(40.9 ± 4.1)ms,(41.2 ± 5.1)ms],and significant reduction in LAD [(37.8 ± 3.4)mm vs.(35.1 ± 4.6)mm,(35.7 ± 4.5)mm]in A+T group and A+R group,P<0.05 or <0.01. Conclusion:Amiodarone combined RAS inhibitors can significantly improve blood pressure variability,and reduce inflammatory factor,SUA and serum SIRT1 level in hypertensive patients with AF.

OBJECTIVETo identify the relationship between coagulation factor V (FV) gene single nucleotide polymorphisms (SNPs) and venous thromboembolism (VTE).

METHODSThe FV clotting activity (FV: C) and FV antigen (FV: Ag) in plasma of VTE group (111 patients) and normal control (110 patients) were detected using one-stage clotting assay and ELISA, respectively. Five pairs of primers of the F V polymorphisms including Asp79His, Arg306The, Arg306Gly, Arg506Gln and Ile359The/His1299 Arg were synthesized and amplified by PCR. The PCR products were digested by restriction enzyme using PCR-RFLP. The detected polymorphisms were confirmed by direct sequencing. The samples containing the polymorphisms were screened for coding regions of all F V exons with direct sequencing.

RESULTSThe plasma levels of F V: C and F V: Ag of VTE group and normal control were (106.9 +/- 28.0)%, (110.4 +/- 33.3)% and (102.4 +/- 30.9)%, (102.1 +/- 24.1)%, respectively. The plasma level of FV: Ag was significantly different between VTE group and normal control. However, there was no difference in F V: C levels. Polymorphisms for the fore mentioned 5 primer pairs were not found in either patients or normal controls. Polymorphism of His1299Arg was identified in 5 patients with VTE and 3 normal controls. And these 5 cases also combined Met1736Val polymorphism, 3 of them combined another Asp2194Gly polymorphism.

CONCLUSIONThe higher plasma level of F V: Ag contribute to venous thromboembolism. There is no relationship between polymorphisms of Asp79His, Arg306The, Arg306Gly, Arg506Gln, Ile359The and venous thromboembolism in Chinese studied. Polymorphism His1299Arg is higher in VTE group than in normal control, but has no statistical difference. Polymorphisms of His1299Arg, Met1736Val and Asp2194Gly are linked disequilibrium in Chinese Han population.

Factor V ; genetics ; Female ; Gene Frequency ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Venous Thromboembolism ; genetics

Objective To explore whether the expression level of heparanase (HPA) and its coagulation proteins on leukemic blast membrane could determine the hemostatic balance on the surface of leukemia cells.Methods Forty patients of leukemia were studied,and 20 patients with iron dificient anemia as the control group.Expression of tissue factor (TF),heparanase (HPA),tissue factor pathway inhibitor (TFPI),and urokinase plasminogen activator receptor (UPAR) on leukemic blast surfaces were analyzed by flowcytometry.Results The expression of TF,UPAR,and HPA in AML,ALL,CML,CLL and CRAL groups were significantly higher compared with the control group (t =.3.289,3.507,2.701,P ＜0.05; t =2.498,0.802,3.090,P ＜0.05; t =2.642,3.308,2.696,P ＜0.05; t =3.417,3.434,2.382,P ＜0.05; t =2.193,2.272,2.263,P ＜0.05).There were no significantly differences between the leukemic cell expression of TFPI and the control group (P ＞0.05).Expression of TF,UPAR,HPA in AML patients were significantly higher than ALL,CML and CLL groups (t =2.463,2.179,2.276,P ＜0.05; t =2.637,2.402,2.095,P ＜0.05; t =2.548,2.425,2.412,P ＜0.05).The levels of TF,UPAR and HPA in M3,M4 and M5 patients were higher than that of M1,M2 groups (P ＜0.05).There were no significantly differences among M3,M4 and M5 (P ＞0.05).Conclusions These results suggest that TF,UPAR and HPA are predominately expressed on leukemic blast surface,particularly in M3and M4,5 subtypes.The expression of coagulation proteins on blast membrane might determine the hemostatic balance on the surface of leukemia cells.

The study was aimed to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in bone marrow (BM) of leukemia patients and investigate the interaction of CYR61, CTGF, VEGF-C, VEGFR-2 proteins in occurrence, development, infiltration and metastasis of leukemia and its clinical significance, to find a new tumor marker for diagnosis and treatment of leukemia with some new directions. 74 patients with leukemia were enrolled in this study, 38 out of them were males and 36 were females, aged from 6 to 77 years old with the median age of 45 years old. In the control group, 7 males and 5 females, aged from 16 to 78 years old with the median age of 46. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA. The results showed that the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in BM of newly diagnosed patients with acute and chronic leukemia of each group were significantly higher as compared with the control group (p < 0.05). The levels of CYR61, CTGF mRNA in acute leukemia remission group were significantly higher than those in control group (p = 0.039, 0.025). The level of CTGF mRNA was highest in B-ALL group, and was higher than that in AML, CML, CLL, T-ALL groups (p = 0.002, 0.034, 0.002, 0.010). In AML group, mRNA expressions of CYR61 and CTGF, CYR61 and VEGF-C, CTGF and VEGFR-2 were positively correlated (r = 0.452, 0.466, 0.464; p = 0.045, 0.038, 0.039), and in CML group mRNA expression of CYR61 and VEGF-C was positively correlated (r = 0.882, p = 0.000). The expression levels of VEGF-C, VEGFR-2 mRNA in acute leukemia patients with extramedullary infiltration were higher than those in acute leukemia patients without extramedullary infiltration (p = 0.028, 0.047). VEGF-C mRNA expression and the original cell counts in AML group were positively correlated (r = 0.418, p = 0.034). It is concluded that CYR61, CTGF, VEGF-C and VEGFR-2 interact each other in the pathogenesis of leukemia, promote the development, metastasis and infiltration of leukemia; and these factors in different types of leukemia and extramedullary infiltration are different, which may become tumor markers of leukemia; and blocking VEGF-C and VEGFR-2 may block tumor growth and metastasis.
Adolescent ; Adult ; Aged ; Bone Marrow ; metabolism ; Case-Control Studies ; Child ; Connective Tissue Growth Factor ; metabolism ; Cysteine-Rich Protein 61 ; metabolism ; Female ; Humans ; Leukemia ; metabolism ; pathology ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Vascular Endothelial Growth Factor C ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of long pulse 1064 nm Nd:YAG laser therapy in the treatment of onychomycosis of the toenails.

METHODSA total of 104 patients with onychomycosis (461 toenails) were divided by age into ≥60 years group and <60 years group, and each group was further divided into subgroups according to Scoring Clinical Index of Onychomycosis (SCIO) scoring and the location of the compromised toenails. All the toenails were treated with 10 to12 sessions of long pulse 1064 nm Nd:YAG laser therapy at the interval of 1 week. All the patients were followed up for 48 weeks after the initial treatment to assess the clinical efficacy and adverse reactions.

RESULTSThe overall clinical response rate in these patients was 72.5% by the end of the 48-week follow-up. In patients aged <60 years, the clinical response rate and mycological cure rate were significantly higher than the rates in patients aged ≥60 years (P<0.05). No significant differences were observed in the response rates between different SCIO subgroups (P>0.05); the 2nd to 4th toenails showed better outcomes after the therapy than the 1st and 5th toenails (P<0.05). No adverse reactions related with the therapy were recorded in these patients.

CONCLUSIONLong pulse 1064 nm Nd:YAG laser is an effective and safe approach for treatment of onychomycosis of the toenails.

Humans ; Lasers, Solid-State ; Middle Aged ; Nails ; microbiology ; Onychomycosis ; therapy ; Treatment Outcome

The study was aimed to investigate the factor V coagulation activity (FV:C), and to evaluate FVgene polymorphisms and activated protein C resistance (APCR) in the patients with venous thromboembolism (VTE). 95 patients with VTE and 95 normal controls were investigated for FV gene polymorphisms. FV Leiden, FVCambridge, and FVHong Kong were detected by PCR, MnlI and BstNI digestion respectively. FVAsp79His and FVI359T were detected by MassARRAY. FV:C and APCR in 65 patients with VTE and 60 normal controls were determined by a one-stage clotting method and the APTT-based assays respectively. The results showed that the mean levels of plasma FV:C were significantly higher in VTE group than that in controls (108.03% +/- 28.29% vs 95.17% +/- 29.75%) (P = 0.008), the incidence of APCR were 20.0% (13 of 65 cases) in patients with VTE and 5.0% (3 of 60 cases) in normal controls (P = 0.012). FV Leiden, FVCambridge, FVHong Kong, FVAsp79His and FVI359T mutations were not found in two groups. It is concluded that the increased plasma level of FV:C is a risk factor for VTE. There is APCR in both groups, APCR is also a risk factor to VTE. APCR may not be associated with mutations of FV Leiden, FVCambridge, FVHong Kong, FVAsp79His and FV I359T polymorphisms, other factors need to study further in APCR.
Activated Protein C Resistance ; complications ; genetics ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Factor V ; genetics ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Protein C ; metabolism ; Venous Thromboembolism ; blood ; complications ; genetics ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of 0.9-ms 1064-nm Nd:YAG laser alone or combined with itraconazole for treatment of toenail onychomycosis.

METHODSA total of 37 patients with onychomycosis (178 toenails) were randomly assigned to groups A and B, and each group was further divided into different subgroups according to the Scoring Clinical Index of Onychomycosis (SCIO) and Onychomycosis Severity Index (OSI) scoring. All the patients were treated with 0.9-ms Nd:YAG laser once a week for 8 times. The patients in group A were treated with laser alone, and those in group B were treated with laser combined with itraconazole. The clinical effect, clinical scores, appearance of the toenails and adverse reactions in the two groups were analyzed, and the patients' satisfaction rate was also investigated.

RESULTSAt the 12th months of follow-up, the clinical response rate and mycological cure rate in group A were 31.33% and 30.00%, respectively, similar to the rates in group B (35.79% and 41.18%, respectively) (P>0.05). After the treatments, the SCIO and OSI scores showed no significant changes in group A (P>0.05) but both increased significantly in group B (P<0.05). The response rates did not differ significantly among the subgroups with SCIO<12 or with OSI<16 (P>0.05), but showed significant differences among the subgroups with SCIO≥12 or with OSI≥16 (P<0.05). Of the total of 178 toenails, 33.71%, 74.72% and 70.79% toenails showed improvements in terms of clear nail growth, shape and color, respectively. The overall patients' satisfaction rate was 62.16%, and no adverse reactions related with the therapy were recorded in these patients.

CONCLUSIONFor treatment of toenail onychomycosis, 0.9-ms 1064-nm Nd:YAG laser can effectively improve the aesthetic appearance of the toenails, and a combined treatment with Nd:YAG laser and itraconazole can be better option in severe cases of onychomycosis.

INTRODUCTION: Hospital-based resuscitation interventions, such as therapeutic temperature management (TTM), emergency percutaneous coronary intervention (PCI) and extracorporeal membrane oxygenation (ECMO) can improve outcomes in out-of-hospital cardiac arrest (OHCA). We investigated post-resuscitation interventions and hospital characteristics on OHCA outcomes across public hospitals in Singapore over a 9-year period. METHODS: This was a prospective cohort study of all OHCA cases that presented to 6 hospitals in Singapore from 2010 to 2018. Data were extracted from the Pan-Asian Resuscitation Outcomes Study Clinical Research Network (PAROS CRN) registry. We excluded patients younger than 18 years or were dead on arrival at the emergency department. The outcomes were 30-day survival post-arrest, survival to admission, and neurological outcome. RESULTS: The study analysed 17,735 cases. There was an increasing rate of provision of TTM, emergency PCI and ECMO (P<0.001) in hospitals, and a positive trend of survival outcomes (P<0.001). Relative to hospital F, hospitals B and C had lower provision rates of TTM (≤5.2%). ECMO rate was consistently <1% in all hospitals except hospital F. Hospitals A, B, C, E had <6.5% rates of provision of emergency PCI. Relative to hospital F, OHCA cases from hospitals A, B and C had lower odds of 30-day survival (adjusted odds ratio [aOR]<1; P<0.05 for hospitals A-C) and lower odds of good neurological outcomes (aOR<1; P<0.05 for hospitals A-C). OHCA cases from academic hospitals had higher odds ratio (OR) of 30-day survival (OR 1.3, 95% CI 1.1-1.5) than cases from hospitals without an academic status. CONCLUSION Post-resuscitation interventions for OHCA increased across all hospitals in Singapore from 2010 to 2018, correlating with survival rates. The academic status of hospitals was associated with improved survival.
Hospitals, Public ; Humans ; Out-of-Hospital Cardiac Arrest/therapy* ; Percutaneous Coronary Intervention ; Prospective Studies ; Singapore/epidemiology*

Ferroptosis is a novel type of cell death which induced by iron-dependent lipid peroxidation accumulation. This type of cell death is significantly different from other cell death in terms of morphology, genetics and biochemistry. It has been reported that ferroptosis is involved in a variety of human diseases, particularly in liver diseases. Therefore, screening and studying of inhibitors or activators of ferroptosis may provide novel strategies for prevention and treatment of liver diseases. This review provides the biological characteristics and regulatory signaling pathways of ferroptosis, as well as the relationship between ferroptosis and liver diseases, which will contribute to new insight into the pathogenesis of liver diseases.

This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; metabolism ; pathology ; Case-Control Studies ; Child ; Child, Preschool ; Connective Tissue Growth Factor ; metabolism ; Cysteine-Rich Protein 61 ; metabolism ; Female ; Humans ; Leukemia ; metabolism ; pathology ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Vascular Endothelial Growth Factor C ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Young Adult