[Risk factor distribution features and trends of young adults with first acute coronary syndrome].

Objective: To observe the characteristics and trends during the last 11 years of risk factors of young adults with first acute coronary syndrome (ACS). Methods: It was a cross-sectional study. We included young adults (18 to 44 years old) hospitalized for acute coronary syndrome in Beijing Anzhen Hospital for a first time from January 2007 to December 2017. Acute coronary syndromes include ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA). The general information, medical history and laboratory test were recorded. Risk factors of ACS were smoking, dyslipidemia, overweight/obesity, hypertension and diabetes. Results: Data from 7 106 patients were analyzed, mean age was (39.8±4.2) years old and 6 593(92.8%)were men, including 2 254 (31.7%) STEMI, 704 (9.9%) NSTEMI and 4 148 (58.4%) UA. Most patients were male (6 593(92.8%)). Dyslipidemia (85.8%(6 094/7 106)), overweight/obesity (82.3%(5 850/7 106)), and smoking (63.9%(4 545/7 106)) were most prevalent. 98.3% (6 885/7 106) patients had at least 1 risk factor. The prevalence of hypertension, diabetes and overweight/obesity increased from 2007 to 2017. Rates of hypertension increased from 37.1%(111/299) to 48.1%(498/1 035) (Ptrend<0.01), diabetes from 12.0%(36/299) to 19.4%(201/1 035) (Ptrend<0.01), overweight/obesity from 74.2%(222/299) to 83.9%(868/1 035) (Ptrend<0.05), respectively. Conclusions: Dyslipidemia, overweight/obesity and smoking are most prevalent risk factors in young adults with a first ACS and most patients have at least 1 risk factor for ACS. Rates of hypertension, diabetes and overweight/obesity progressively increases over time in this patient cohort.

The effect of exercise on high-intensity focused ultrasound treatment efficacy in uterine fibroids and adenomyosis: a retrospective study.

OBJECTIVE: We conducted a retrospective study to evaluate whether exercise after high-intensity focused ultrasound (HIFU) treatment can improve the absorption of uterine fibroids and the relief of dysmenorrhea caused by adenomyosis. DESIGN: A retrospective study. SETTING: Gynaecological department of a single centre in China. POPULATION: Patients with uterine fibroids and adenomyosis. METHOD: From January 2011 to August 2015,83 MRI-confirmed uterine fibroid patients and 102 adenomyosis patients who received HIFU treatment at Chongqing Haifu Hospital and attended the 1-year and 6-month follow up, respectively, were included in our retrospective study. Among the fibroid patients, 51 were assigned to the 'no exercise group' and 32 to the 'exercise group'. Among the adenomyosis patients, 45 were assigned to the 'no exercise group' and to the 57 'exercise group'. MAIN OUTCOME MEASURES: Symptom improvement, uterine fibroid volume and Visual Analogue Scale (VAS) evaluation. RESULTS: Exercise post-HIFU treatment significantly improved the absorption of uterine fibroids, reduced recurrence rate and increased the rate of pregnancy in uterine fibroid patients. Exercise lead to a more significant reduction in the score of dysmenorrhea. CONCLUSION: Exercise post-HIFU treatment demonstrated an enhancement of the therapeutic efficacy of HIFU for both uterine fibroid patients and adenomyosis patients. Therefore, exercise should be recommended to patients as part of the post-treatment disease management plan. TWEETABLE ABSTRACT: A retrospective study evaluated the effect of exercise after high-intensity focused ultrasound (HIFU) treatment on the therapeutic efficacy of HIFU.

Identification of Ca(2+)-binding residues of a protein from its primary sequence.

Calcium is one of the most abundant minerals in the human body, playing a critical role in many cellular activities by interacting with different calcium ion (Ca(2+))-binding proteins. Therefore, the correct identification of Ca(2+)-binding residues is essential for protein functional research. In this study, a new method was developed to predict Ca2+-binding residues from the primary sequence without using three-dimensional information. Through statistical analysis, four kinds of feature parameters were extracted from amino acid sequences: the increment of diversity values of amino acid composition, the matrix scoring values of position conservation, the autocross covariance of physicochemical properties, and the center motif. These features served as input for a support vector machine to predict Ca(2+)-binding residues. This method was tested on four well-established datasets using a five-fold cross-validation. The accuracies and Matthews correlation coefficients were 75.9% and 0.53 (dataset 1), 79.2% and 0.58 (dataset 2), 77.4% and 0.55 (dataset 3), and 79.1% and 0.58 (dataset 4). Comparative results show that the developed method outperforms previous methods. Based on this study, a web server was developed for predicting Ca(2+)-binding residues from any protein sequence, being publically available at http://202.207.29.245/.

Kinase suppressor of Ras signals through Thr269 of c-Raf-1.

We recently established a two-stage in vitro assay for KSR kinase activity in which KSR never comes in contact with any recombinant kinase other than c-Raf-1 and defined the epidermal growth factor (EGF) as a potent activator of KSR kinase activity (Xing, H. R., Lozano, J., and Kolesnick, R. (2000) J. Biol. Chem. 275, 17276-17280). That study, however, did not address the mechanism of c-Raf-1 stimulation by activated KSR. Here we show that phosphorylation of c-Raf-1 on Thr(269) by KSR is necessary for optimal activation in response to EGF stimulation. In vitro, KSR specifically phosphorylated c-Raf-1 on threonine residues during the first stage of the two-stage kinase assay. Using purified wild-type and mutant c-Raf-1 proteins, we demonstrate that Thr(269) is the major c-Raf-1 site phosphorylated by KSR in vitro and that phosphorylation of this site is essential for c-Raf-1 activation by KSR. KSR acts via transphosphorylation, not by increasing c-Raf-1 autophosphorylation, as kinase-inactive c-Raf-1(K375M) served as an equally effective KSR substrate. In vivo, low physiologic doses of EGF (0.001-0.1 ng/ml) stimulated KSR activation and induced Thr(269) phosphorylation and activation of c-Raf-1. Low dose EGF did not induce serine or tyrosine phosphorylation of c-Raf-1. High dose EGF (10-100 ng/ml) induced no additional Thr(269) phosphorylation, but rather increased c-Raf-1 phosphorylation on serine residues and Tyr(340)/Tyr(341). A Raf-1 mutant with valine substituted for Thr(269) was unresponsive to low dose EGF, but was serine- and Tyr(340)/Tyr(341)-phosphorylated and partially activated at high dose EGF. This study shows that Thr(269) is the major c-Raf-1 site phosphorylated by KSR. Furthermore, phosphorylation of this site is essential for c-Raf-1 activation by KSR in vitro and for optimal c-Raf-1 activation in response to physiologic EGF stimulation in vivo.

Epidermal growth factor treatment enhances the kinase activity of kinase suppressor of Ras.

In Drosophila melanogaster and Caenorhabditis elegans, kinase suppressor of Ras (KSR) functions as a positive modulator of Ras-dependent signaling either upstream of or parallel to Raf. Attempts to characterize the biochemical and biological properties of mammalian KSR, however, have had limited success. Although some studies demonstrated a requirement of KSR kinase activity for its action, others indicated the kinase function of KSR is dispensable and suggested that KSR acts primarily as a scaffold protein. Interpretations of KSR function are further hampered by the lack of a standardized assay for its kinase activity in vitro. To address this issue, we established a two-stage in vitro kinase assay in which KSR never comes in contact with any recombinant kinases other than c-Raf-1. Using this assay, we show that KSR immunoprecipitated from quiescent COS-7 cells overexpressing Flag-tagged KSR was inactive, but its activity was rapidly and markedly induced upon epidermal growth factor treatment. Moreover, KSR-reconstituted mitogen-activated protein kinase activation was detected in KSR immunoprecipitates depleted of all contaminating kinases (c-Raf-1, MEK1, ERK2) by multiple high salt washes. Only full-length kinase-active KSR was capable of signaling c-Raf-1-dependent activity as kinase inactive and C- and N-terminal deletion mutants were without effect. Furthermore, endogenous KSR isolated from A431 cells, which contain high levels of activated EGF receptor, displays constitutively enhanced kinase activity. Hence, KSR kinase activity is not an artifact of overexpression but a property intrinsic to this protein. The recognition of EGF as a potent activator of KSR kinase activity and the availability of a well defined in vitro kinase assay should facilitate the definition of the function of KSR as a Ras-effector molecule.