[Cross sectional study of familial hypercholesterolemia in dyslipidemia patients receiving lipid-lowering therapy: DYSIS-China subgroup analysis].

Objectives: To analyze the incidence, blood lipid levels and cardiovascular disease of familial hypercholesterolemia (FH) in dyslipidemia patients receiving lipid-lowing therapy from the DYSIS-China. Methods: Dyslipidemia International Study-China (DYSIS-China) database was re-analyzed according to the criteria of "Chinese guidelines for prevention and treatment of dyslipidemia in adults-2016 version". DYSIS-China database included 25 317 dyslipidemia out-patients who received at least one lipid-lowering drug for at least three months. All the patients were divided into three groups: unlikely HF, possible FH and definite FH according to the Dutch Lipid Clinic Network diagnostic criteria. Age, gender, lipids levels, drug use and complications were compared among the three groups. Factors were compared between Possible FH group and definite FH group in terms of age stratification. Results: A total of 23 973 patients with dyslipidemia were included. The average age was (64.8±9.9) years, 11 757 patients were females (49.0%). The proportion of unlikely FH in the total population was 20 561 (85.7%), possible FH was 3294 (13.7%), and the definite FH was 118(0.5%). Patients in the definite FH group (58.3±8.5 years) was younger than in unlikely HF(65.3±9.8 years) and possible FH(61.8±9.9 years) group. LDL-C ((5.6±1.9) mmol/L) levels were significantly higher in definite FH group than in unlikely HF ((2.5±0.9) mmol/L) and possible FH ((4.3±1.0) mmol/L) group. TC ((7.4±1.8) mmol/L) levels were also significantly higher in definite FH group than in unlikely HF ((4.3±1.0) mmol/L) and possible FH ((6.0±1.0) mmol/L) group. Percent of female sex, sedentary lifestyle and systolic blood pressure value were significantly higher in definite FH group than in other two groups (all P<0.05). Statin use was similar among the 3 groups. Prevalence of ischemic cardiomyopathy (70(59.3%)) was significantly higher in the definite FH group than in unlikely FH group7519 (36.6%) and possible FH group1149 (34.9%). The rate of hypertension (82 (69.5%)) was also significantly higher in the definite FH group than in unlikely FH group (2 063 (62.6%) and in possible FH group (13 928 (67.7%)). The possible FH group had the highest proportion of patients aged 55-64 years (1 146 (34.8%)), and the prevalence of hypertension 358 (76.8%), diabetes 189 (40.6%), ischemic heart disease 186 (39.9%), cerebrovascular disease 149 (32.0%) and heart failure 28 (6.0%) was the highest in patients over 75 years old. The definite FH group had the highest proportion of patients aged 55-64 years (49 (41.52%)), and the prevalence of ischemic heart disease (70 (59.3%)) was the highest in patients aged 45-54 years old group, there was no significant difference in the prevalence of diabetes,hypertension,heart failure,peripheral artery disease and cerebrovascular disease among different age groups. Conclusion: The detection rate of FH in Chinese patients with dyslipidemia is not low, the blood lipid level is poorly controlled, and the risk of cardiovascular disease is high in Chinses FH patients.

Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta-analysis.

BACKGROUND AND PURPOSE: Migraine has greatly impacted the quality of life for migraineurs and was ranked as the seventh highest specific cause of disability worldwide in 2012. Because of the role of serotonin in migraine mechanisms, antidepressants have been used in the prevention of migraine. However, the role of antidepressants for migraine prophylaxis in adults has not been completely established. Our aim was systematically to assess the efficacy and feasibility of antidepressants for the prevention of migraine in adults based on currently available literature. METHODS: A comprehensive search of databases was conducted including the Cochrane, PubMed, Web of Science and Embase databases from inception to July 2016. Randomized controlled trials that assigned adults with a clinical diagnosis of migraine to antidepressant or placebo treatment were included. The primary outcome was the reduction of migraine frequency or index. RESULTS: Overall, 16 randomized controlled trials including 1082 participants were identified. Antidepressants had a significant advantage over placebo in reducing the migraine frequency or index of adults with a standardized mean difference of -0.79 [95% confidence interval (CI) -1.13 to -0.45, P < 0.00001]. Patients receiving antidepressant therapy were more likely to experience an at least 50% reduction of headache burden than those receiving placebo (28.9% vs. 20.2%; risk ratio 1.40; 95% CI 0.97-2.02; P = 0.07). However, antidepressants were less well tolerated than placebo because of some adverse events (risk ratio 1.74, 95% CI 1.05-2.89, P = 0.03). CONCLUSIONS: Antidepressants are effective in the prophylaxis of migraine in adults, but the level of evidence for antidepressants except for amitriptyline seems to be quite shaky.

[Status of cholesterol goal attainment for the primary and secondary prevention of atherosclerotic cardiovascular disease in dyslipidemia patients receiving lipid-lowering therapy: DYSIS-China subgroup analysis].

OBJECTIVE: To analyze the current status of cholesterol goal attainment for the primary and secondary prevention of cardiovascular disease in dyslipidemia patients using data from the DYSIS-China study. METHODS: Based on criteria defined in the 2014 China Cholesterol Education Program (CCEP) and the 2007 Chinese guidelines for the prevention and treatment of dyslipidemia in adults, 25 317 dyslipidemia patients enrolled in the DYSIS-China study (from March 2012 to October 2012) were stratified to the atherosclerotic cardiovascular disease(ASCVD) primary prevention and secondary prevention groups. The total cholesterol (TC) target goals were <3.11, 4.14, 5.18, and 6.22 mmol/L, respectively, and the low-density lipoprotein cholesterol (LDL-C) therapeutic goals were less than 1.8, 2.6, 3.4, and 4.1 mmol/L, respectively, for the very high-risk, high-risk, moderate-risk, and low-risk patients in the primary prevention group. The TC targets for the very high-risk and high-risk patients were <3.11 and <4.14 mmol/L, respectively, and the LDL-C targets were <1.8 and <2.6 mmol/L, respectively, in the secondary prevention group. The TC and LDL-C goal attainment rates were calculated for the different risk groups according to the targets values. RESULTS: Totally, 71.09% (n=18 000) of the dyslipidemia patients were grouped into very high and high risk groups, 51.76% (n=13 104) and 48.24% (n=12 213) patients were stratified to primary and secondary prevention of ASCVD. The LDL-C and TC goal attainment rates for the secondary prevention group were 33.09%(4 041 cases) and 21.05% (2 571 cases), respectively. The LDL-C and TC goal attainment rates for the primary prevention group were 52.40% (6 866 cases) and 42.06% (5 511 cases), respectively. Multivariate logistic regression analysis showed that diabetes mellitus(OR=5.75, 4.15, P<0.05), coronary heart disease(OR=5.70, 3.58, P<0.001), and peripheral arterial disease(OR=2.42, 1.49, P<0.05) were risk factors for failure to achieve TC and LDL-C goals, respectively. CONCLUSIONS: Despite the widespread application of the 2014 CCEP and 2007 Chinese dyslipidemia guidelines, LDL-C goal attainment among secondary and primary prevention patients remains suboptimal in China. More rigorous guideline adherence is therefore required to increase the LDL-C and TC goal attainment rates and improve the long-term cardiovascular outcomes in Chinese dyslipidemia patients.

UV-induced CYP1A1 gene expression in human cells is mediated by tryptophan.

Induction of cytochrome P-4501A1 (CYP1A1) activity by UV has been observed earlier in animal studies via a mechanism that has not yet been resolved. Our previous data have indicated that formylated indolocarbazoles which are formed by UV irradiation of tryptophan solutions are very potent Ah-receptor agonists. To evaluate the effect of UV light on cytochrome P4501A1 gene expression, we studied the induction of CYP1A1 mRNA by UV irradiation of cultured human keratinocytes (HaCaT cell line), primary human blood lymphocytes and mouse Hepa-1 cells. The cells were exposed to UV light delivered by a bank of 6 Philips TL20/12RS sun lamps emitting primarily in the UVB range in the absence and presence of tryptophan. A semiquantitative reverse transcriptase-linked polymerase chain reaction (RT-PCR) was used for analysis of gene expression in the treated cells. The results show that the CYP1A1 mRNA level induced by UV in the presence of tryptophan was higher than that induced by UV alone in both HaCaT cells and lymphocytes after 3 h of incubation post-UV irradiation. To find out if the induction by UV light is caused by the formation of an Ah receptor ligand, Hepa-1 wild-type and Ah receptor deficient c12 cell lines were applied. Wild-type (wt) cells were inducible either by the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) or by UV-irradiation but very low or undetectable levels were observed in the c12 cells. This shows that the induction of gene expression by FICZ and UV is Ah receptor dependent. Together, these results indicate that UV-induced CYP1A1 gene expression in mammalian cells is mediated by an Ah receptor ligand formed from tryptophan. Thus, the photoproducts of tryptophan are suggested to be mediators of light via binding to the Ah receptor and as such also could have a role in light-regulated biological rhythms.

Rapid and transient induction of CYP1A1 gene expression in human cells by the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole.

Studies to assess the induction of CYP1A1 gene expression by tryptophan derived oxidation products which are suggested as endogenous ligands for the Ah receptor are described. For the two high affinity Ah receptor ligands produced from tryptophan, the chemical structure was recently identified as 6-formylindolo[3,2-b]carbazole (FICZ) and 6,12-diformylindolo[3,2-b]carbazole (dFICZ), respectively. Therefore these two compounds show a close similarity to the indolecarbinol-derived condensation product indolo[3,2-b]carbazole (ICZ). Incubation of cells from a human keratinocyte (HaCaT) cell line together with ICZ, FICZ, dFICZ and some structurally related indole compounds was performed. The compound with the highest affinity to the Ah receptor, FICZ, was found to be the most efficient inducer of CYP1A1 gene expression in short time incubation (0.5 h) experiments. With longer incubation times (24 h) ICZ was the most efficient inducer. The two most active compounds, FICZ and ICZ, caused increased mRNA levels already at a concentration of 100 pM. FICZ was also shown to increase CYP1A1 mRNA levels in fresh human peripheral blood cells at the same low concentration. FICZ and ICZ were furthermore compared with regard to their capacity to inhibit cDNA-expressed human CYP1A1 enzyme and FICZ was found to be the most potent inhibitor. The inhibition was, however, transient in character indicating that FICZ is also an exceptionally good substrate for the CYP1A1 enzyme. The results showing the potent and transient effect of these formylindolocarbazoles, thus emphasize their important properties as signal substances in the Ah receptor pathway. This makes the most potent compound, FICZ, a good candidate for the endogenous ligand of the Ah receptor necessary for normal development and for the basal expression of Ah receptor-dependent genes.

A nine-year prospective study on the incidence of childhood type 1 diabetes mellitus in China.

To investigate the epidemiological characteristics of childhood type 1 diabetes mellitus in China, newly diagnosed cases of type 1 diabetes with an onset age under 15 years were retrospectively registered by 23 local centers in China following a standardized protocol on the basis of the nationwide registry established by the WHO DiaMond Project China Participating Center, Chinese Academy of Preventive Medicine (CAPM). A population of about 24 million children were covered in the defined areas. A two-sample capture-recapture method was used to estimate case ascertainment. Between 1988 and 1996, 903 diabetic cases were registered in 9 ethnic groups. The overall ascertainment corrected incidence rate (IR) was 0.59 per 100,000 person-year. The IR was 0.52/100,000 (95% CI: 0.50-0.54) for males and 0.66/100,000 (95% CI: 0.64-0.68) for females. The standardized ascertainment corrected IR by the national age-specific population in 1990 was 0.57 per 100,000 person-year. The incidence among various ethnic groups ranged from 0.25/100,000 to 3. 06/100,000. The IRs increased with northern latitude, and the IR of Han population was significantly higher in North China compared with South China (0.67 versus 0.53 per 100,000 respectively, P < 0.01). A correlation model of incidence and calendar time showed that the IR increased significantly between 1988 and 1996 (r = 0.86, P = 0.0027). The relative risk (RR) of type 1 diabetes mellitus for different age-groups estimated by a Poisson regression model showed that taking RR as 1.00 for age-group from 0 to 4 years, the RR for age-group from 5 to 9 year and from 10 to 14 year was 2.30 and 3.60 respectively. The standardized ascertainment corrected IR of childhood type 1 diabetes mellitus in China in much lower than in other countries. The geographic and ethnic variability of the incidence suggests that both genetic and environmental factors play a role in the development of childhood diabetes in China.

Regulation of CYP1A1 transcription via the metabolism of the tryptophan-derived 6-formylindolo[3,2-b]carbazole.

A functional cytochrome P4501A1 (CYP1A1) enzyme has been suggested to metabolize endogenous substrates and to autoregulate its own transcription in mouse hepatoma cells. In the present study, the regulation of CYP1A1 gene transcription by 6-formylindolo[3,2-b]carbazole (FICZ), a suggested endogenous ligand for the aryl hydrocarbon receptor (AhR), has been studied in mouse Hepa-1 cell lines. The tryptophan photoproduct, FICZ, has previously been characterized to possess very high AhR binding affinity and to transiently induce CYP1A1 gene expression in cultured cells at picomolar concentrations. The results from this study show that a transient induction of CYP1A1 mRNA at a low concentration of FICZ was only seen in wild-type cells. In c37 cells, deficient in CYP1A1, FICZ caused a sustained induction. Interestingly, we found that a higher amount of tryptophan in culture medium increased the constitutive level of CYP1A1 mRNA expression in the c37 cells but not in the wild-type cells. This suggests that a tryptophan-derived AhR ligand in the medium regulates the basal CYP1A1 expression. In metabolism studies performed with S9 prepared from c37 cells no metabolites were formed from FICZ and no loss of FICZ was observed, while with wild-type cells FICZ was rapidly metabolized. HPLC analysis revealed that at least three metabolites were formed in an NADPH-dependent manner from FICZ when incubated with rat liver S9. The CYP1A1 inhibitor ellipticine totally blocked the metabolism of FICZ. Ellipticine also enhanced both basal and FICZ-induced CYP1A1 mRNA expression. Taken together, these results indicate that tryptophan is a precursor of the endogenous ligand and that the suggested tryptophan-derived ligand FICZ is a substrate for the CYP1A1 enzyme and is involved in autoregulation of CYP1A1 transcription.

Characterization of the transcript of a new class of retroposon-type repetitive element cloned from the powdery mildew fungus, Erysiphe graminis.

The putative master transcript of a novel class of repetitive element has been cloned from the fungus erysiphe graminis f.sp. hordei. Sequence analysis of the cDNA revealed that the element, designated Eg-R1, is a member of the retroposon superfamily with properties in common with SINEs and LINEs (short or long interspersed elements). SINE-like properties include the transcript size (approximately 700 bp), and the lack of major open reading frames. In contrast, the fact that the transcript is polyadenylated and is most probably transcribed by RNA polymerase II, suggests a functional relationship to LINEs. Except for a short, but striking, sequence identity to a published SINE from the same fungus, no similar sequence was found in database searches. A constitutively high transcript level is found throughout the asexual life cycle of the fungus. Small differences in band patterns of Southern blots were observed between two isolates of E. graminis f.sp. hordei, while the band patterns in an isolate of the very close relative E. graminis f.sp. tritici in general appear dissimilar. This may imply that the element is currently active. Recent dispersal is confirmed by the observation that an approximately 550 bp internal hinfI fragment is conserved in the majority of the copies in all three isolates. Approximately 50 copies are present in E. graminis f.sp. hordei.

Cardiovascular effects of total soyasaponin in central nervous system and its relationship with monoamine transmitters.

AIM: To study the cardiovascular effect of total soyabeans saponins (TS) in brain and its relationship with monoamines. METHODS: After injection of TS (75 micrograms) into ventriculus lateralis cerebri (VLC) the changes of blood pressure (BP) and heart rate (HR) were observed and the contents of monoamines both in peripheral blood and brain (telencephalon, diencephalon, brainstem) were measured respectively by HPLC-ECD and fluorophotometry. RESULTS: After injection of TS into VLC, BP rise from 11.59 +/- 0.84 to 14.59 +/- 0.69 kPa; HR increased from 411 +/- 21 to 465 +/- 14 bpm; the contents of NE and E in peripheral blood increased from 6 +/- 3 to 64 +/- 44, from 6 +/- 2 to 38 +/- 34 nmol/L plasma, respectively, NE in brainstem increased from 14 +/- 0 to 18 +/- 3 nmol/g wet tissue respectively, but the contents of 5-HT in the 3 areas measured in the experiment decreased: in telecephalon from 9 +/- 1 to 5 +/- 1, in diencephalon from 14 +/- 2 to 7 +/- 2, in brainstem from 14 +/- 3 to 6 +/- 1 nmol/g wet tissue. CONCLUSIONS: The cardiovascular effects of TS in CNS were involved in the monoamine transmitters.