Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.
Angiotensin I ; antagonists & inhibitors ; metabolism ; Animals ; Antioxidants ; pharmacology ; Blood Pressure ; drug effects ; Hypertension ; chemically induced ; drug therapy ; Male ; Oxidative Stress ; drug effects ; Paraventricular Hypothalamic Nucleus ; drug effects ; Peptide Fragments ; antagonists & inhibitors ; metabolism ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Sodium Chloride, Dietary ; pharmacology

ABSTRACT:OBJECTIVE To study the effect of isoliquiritigenin on cell proliferation,apoptosis induction,mRNA expression of endoplasmic reticulum stress related gene ATF4,DDIT3 and TNFRSF10B in NCI-H1 57 human lung cancer cell line. METHODS NCI-H1 57 cells were cultured and treated with various concentrations isoliquiritigenin.The cell proliferation was analyzed by MTT and the occurrence of cell apoptosis was examined by flow cytometry.ATF4,DDIT3 and TNFRSF10B gene mRNA expression were detected by real-time fluorescence quantitative polymerase chain reaction.RESULTS Isoliquiritigenin significantly inhibited NCI-H1 57 cell proliferation in a dose and time dependent manner.The results of flow cytometry revealed that isoliquiritigenin could induce apoptosis in NCI-H1 57 cells.Real-time quantitative RT-PCR showed that isoliquiritigenin up-regulated mRNA expression of ATF4,DDIT3 and TNFRSF10B(P <0.05 ~0.01).CONCLUSION Isoliquiritigenin can in-hibit NCI-H1 57 cell proliferation,induce cell apoptosis by activating the endoplasmic reticulum stress response.

ABSTRACT:OBJECTIVE To explore the effect of Baicalin in vivo of the expression of NF-κB and cytokines in ulcerative coli-tis rats.METHODS The colitis model of mice were established with TNBS methord.Mice were randomly divided into control group,model group,Baicalin group,and SASP group.After continuous administration for 10 days,observed the colon gross morphological changes,the colon tissue level of TNF-α,IL-8 and IL-1 were detected using ELISA,and the protein expression of NF-κB in the colon tissues of mice were detected using Western Blot.RESULTS Compared with the model group,Baicalin(100 mg∕kg) group could significantly improve the colon gross morphological form,the Baicalin(25,50,100 mg∕kg)groups could in-hibit the secretion of inflammatory factors dose-dependently,the high dose group could reduce IL-1,IL-8 and TNF-αexpression (P <0.05),no significant difference occured between the SASP group.Compared with the model group,.Baicalin high dose group could reduce NF-kB levels,promote IkBαlevel(P <0.05) .CONCLUSION Baicalin can inhibit NF-κB activation,and thus play its anti-inflammatory effect in ulcerative colitis mice.

OBJECTIVE To develop a sensitive and selective ultra performance liquid chromatography-triple quadrupole mass spectrometer(UPLC-MS/MS) method for quantification of eight components(chrysin,baicalein,apigenin,orohylin A, wogonin,baicalin,wogonoside,oroxin A) in Schisandra chinensis Georgi.METHODS The separation was performed on a Thermo BDS Hypersil C1 8(2.1 mm×100 mm,2.3 μm) column.The mobile consisted of acetonitrile (A) and 0.1% formic acid aqueous with a gradient elution at a flow-rate of 0.25 mL/min.The detection was acquired by MRM.The column temper-ature was 40 ℃.RESULTS The linear ranges of chrysin,baicalein,apigenin,orohylin A,wogonin,baicalin,wogonoside, oroxin A were 0.975~62.5 ng/mL(r 2 =0.999 8),4.875~2 500 ng/mL(r 2 =0.999 7),0.975~62.5 ng/mL(r 2 =0.999 4), 0.097 5~12.5 ng/mL(r 2 =0.999 6),0.048 83~6.25 ng/mL(r 2 =0.999 9),4.875~2 500 ng/mL(r 2 =0.999 8),0.488 3~250 ng/mL(r 2 =0.999 9),0.488 3 ~ 250 ng/mL(r 2 = 0.999 8),respectively.The recoveries were 98.75%,96.44%, 101.13%,99.41%,102.26%,98.45%,96.75%,99.42%.CONCLUSION The proposed method enables quantification for the study of the compounds of chrysin,baicalein,apigenin,orohylin A,wogonin,baicalin,wogonoside,oroxin A in Schisan-dra chinensis Georgi.

BACKGROUNDPatients with multivessel coronary artery disease and depressed left ventricular ejection fraction (LVEF) represent a high risk group of patients for coronary revascularization. There are limited data on percutaneous coronary intervention treatment in this population.

METHODSAmong a cohort of 4335 patients with three-vessel disease with or without left main disease undergoing percutaneous coronary intervention, 191 patients had LVEF < 40% (low ejection fraction (EF)) and 4144 patients had LVEF ≥ 40%. In-hospital and long-term outcomes were examined according to LVEF.

RESULTSThe estimated two-year rates of major adverse cardiac events, cardiac death, and myocardial infarction were significantly higher in the low EF group (19.64% vs. 8.73%, Log-rank test: P < 0.01; 10.30% vs. 1.33%, Log-rank test: P < 0.01, and 10.32% vs. 2.28%, Log-rank test: P < 0.01 respectively), but there was no difference in the rates of target vessel revascularization (6.18% vs. 6.11%, Log-rank test: P = 0.96). Using the Cox proportional hazard models, LVEF < 40% was a significant risk factor for cardiac death, myocardial infarction, and major adverse cardiac events (OR (95%CI): 4.779 (2.369 - 9.637), 2.673 (1.353 - 5.282), and 1.827 (1.187 - 2.813) respectively), but was not a statistically significant risk factor for target vessel revascularization (OR (95%CI): 1.094 (0.558 - 2.147)).

CONCLUSIONAmong patients undergoing percutaneous coronary intervention for multivessel coronary artery disease, left ventricular dysfunction remains associated with further risk of cardiac death in-hospital and during long-term follow-up.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Disease ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Ventricular Function, Left ; physiology

Influenza virus is the causative agent of the seasonal and occasional pandemic flu. The current H1N1 influenza pandemic, announced by the WHO in June 2009, is highly contagious and responsible for global economic losses and fatalities. Although the H1N1 gene segments have three origins in terms of host species, the virus has been named swine-origin influenza virus (S-OIV) due to a predominant swine origin. 2009 S-OIV has been shown to highly resemble the 1918 pandemic virus in many aspects. Hemagglutinin is responsible for the host range and receptor binding of the virus and is therefore a primary indicator for the potential of infection. Primary sequence analysis of the 2009 S-OIV hemagglutinin (HA) reveals its closest relationship to that of the 1918 pandemic influenza virus, however, analysis at the structural level is necessary to critically assess the functional significance. In this report, we report the crystal structure of soluble hemagglutinin H1 (09H1) at 2.9 Å, illustrating that the 09H1 is very similar to the 1918 pandemic HA (18H1) in overall structure and the structural modules, including the five defined antiboby (Ab)-binding epitopes. Our results provide an explanation as to why sera from the survivors of the 1918 pandemics can neutralize the 2009 S-OIV, and people born around the 1918 are resistant to the current pandemic, yet younger generations are more susceptible to the 2009 pandemic.
Animals ; Cloning, Molecular ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus ; chemistry ; genetics ; immunology ; isolation & purification ; Influenza A Virus, H1N1 Subtype ; chemistry ; genetics ; immunology ; Models, Molecular ; Protein Conformation ; Swine ; virology

Seven steroids and two cumarins were isolated from the petroleum ether extract of the specie Cacalia tangutica of the family Compositae which were collected in Minhe county, Qinhai province of China. The structures were identified as Stigmast4-en-3beta, 6beta-diol (1), 24-ethyl-5alpha-cholestane-3beta, 5, 6beta-triol (2), 7beta- methoxy-stigmast-5-en-3beta-ol (3), Schleicherastatin 1 (4), Stigmast-5-en-3beta, 7alpha-diol (5), umbelliferone (6) and hydrangetin (7) by the means of chemical and modern spectroscopic analysis (MS, 1H-NMR, 13C-NMR, DEPT). The compounds 1-5 were isolated from Cacalia tangutica for the first time.
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Molecular Structure ; Plants, Medicinal ; chemistry ; Steroids ; chemistry

BACKGROUNDThe baseline characteristics of patients in a multinational trial are possibly related to cardiovascular outcome. This study compared the baseline characteristics of patients recruited in China with those recruited in other countries.

METHODSA total of 508 Chinese hypertensive men and 728 women over the age of 80 years who entered the Hypertension in the Very Elderly Trial (HYVET) were compared with those in 860 men and 1348 women who entered the trial in other countries.

RESULTSThe Chinese subjects were slightly younger, had less previous hypertension but more previous strokes than the subjects from other countries. The Chinese subjects smoked more than those from other countries, but drank less alcohol. They had less previous episodes of myocardial infarction and were, on average, lighter and shorter. The Chinese had lower mean concentrations of blood urea, uric acid and creatinine as well as higher concentrations of high density lipoprotein (HDL) cholesterol. The concentration of total cholesterol was, on average, lower in the Chinese subjects as was blood glucose. The levels of serum sodium and potassium, blood hematocrit and hemoglobin were all, on average, lower in the Chinese subjects.

CONCLUSIONSCalorie restriction, compared with the rest of the world, may have resulted in lower stature and weight, and recent increases in calorie intake have not changed the metabolic profile of the very elderly hypertensive patients in China. Some of these biochemical differences may reflect different dietary lifestyle in the Chinese.

Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Double-Blind Method ; Female ; Humans ; Hypertension ; blood ; drug therapy ; Male

OBJECTIVETo describe the design and application of cluster randomized controlled method on typhoid Vi vaccine trial, and to assess the effect of implementation.

METHODSSimple size calculation of cluster-randomized trial was used to determine the sample size of the two groups and a vaccination campaign was conducted. The study group was given typhoid Vi vaccine and the control group was given meningococcal A vaccine.

RESULTSAccording to sample size calculation, a total sample of 96,121 participants was required and the study areas were divided into 108 clusters. In practice, 53 study clusters with 44,054 participants and 54 control clusters with 48,422 participants were stratified and matched according to size, location (urban or rural), characteristics (school, department, factory, demography) were randomized respectively. Confounding factors of two groups including age, sex, resident area, income, level of education were compared. It was found that the ratio of all confounding factors between the two groups were comparable and balanced.

CONCLUSIONConfounding factors can be better controlled between study group and the control group by applying cluster-randomized method on vaccine trail which enabled the intervention to be more scientifically evaluated; The implementation of cluster randomization trial was simple and easy to be accepted.

Adolescent ; Adult ; Child ; Child, Preschool ; China ; Cluster Analysis ; Female ; Humans ; Male ; Mass Vaccination ; organization & administration ; Middle Aged ; Polysaccharides, Bacterial ; immunology ; Typhoid Fever ; prevention & control ; Typhoid-Paratyphoid Vaccines ; immunology ; Vaccination