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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.
Subject(s)
Humans , Female , Blood Platelets/pathology , Biomarkers, Tumor/genetics , Ovarian Neoplasms/pathology , ChinaABSTRACT
@#Aquaporins(AQPs)is a family of transmembrane channins with low activation energy, high selectivity and rapid transport of water molecules, widely expressed in eye tissues. It was found that AQPs has physiological functions in eye tissue including maintaining the internal lens circulation homeostasis, participating in atrial aqueous circulation, mediating retinal signaling and promoting damage repair. Mutations or abnormal function of AQPs can lead to the occurrence of various ophthalmic diseases. If the expression and function of AQPs can be changed by using certain drugs or technical means, it is expected to become a new target for the treatment of ophthalmic diseases in the future.
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Objective To screen the targets of traditional Chinese medicine-derived potential plant molluscicides based on network pharmacology and explore the mechanisms of molluscicidal actions. Methods The traditional Chinese medicines with molluscicidal actions were screened based on retrospective literature reviews, and their molluscicidal efficiency was summarized. The active ingredients and potential targets of traditional Chinese medicines were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Unified Protein Database and literature mining using network pharmacology. The drug-active ingredient-target network was created using the software Cytoscape 3.7.2, and the key targets were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the Metascape software. Results A total of 27 types of snail control drugs derived from traditional Chinese medicines were screened from publications and classified into 14 categories. Network pharmacology identified 190 active ingredients, and the active ingredients with a high degree in the drug-active ingredient-target network included quercetin, linoleyl acetate, luteolin, beta-carotene, (24S)-ethylcholesta-5,22,25-trans-3beta-ol, fumarine and arctiin, with 181 corresponding potential targets screened. KEGG pathway enrichment analysis revealed that these targets were mainly located in 16 pathways, including the neuroactive ligand-receptor interactions, regulation of adipocyte lipolysis and adrenergic signal in myocardial cells. Conclusions This study preliminarily demonstrates the multi-ingredient, multi-target and multi-pathway mechanisms of action of 27 molluscicides. The screened key ingredient may provide the basis for isolation, purification and pharmacological studies of molluscicides, and the screened key targets and key pathways may facilitate the illustration of mechanisms of actions of traditional Chinese medicine-derived molluscicides and development of novel green molluscicides.
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Objective:To discuss the clinical efficacy of Qingfei Xiegantang on chronic inflammation and endothelial function of people of Taiyin constitution with metabolic syndrome （MS）. Method:Patients （162 cases） were divided into control group （80 cases） and observation group （82 cases）. Both groups got lifestyle intervention and treatment with lipid regulation， blood pressure reduction and hypoglycemia according to MS. Patients in observation group got Qingfei Xiegantang， 1 dose/day. Patients in control group got placebo granules of Qingfei Xiegantang. The treatment lasted for 4 months. Before and after treatment， weight， height， waist （WC）， hip， body mass index （BMI） and waist hip ratio （WHR） were calculated. Levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （2 hPG）， glycosylated hemoglobin （HbA1c） and fasting insulin （FINS） were measured. Insulin resistance index （HOMA-IR）， insulin sensitivity index （ISI） and islet beta cell function index （HOMA-<italic>β</italic>）， systolic blood pressure （SBD）， diastolic blood pressure （DBP）， tumor necrosis factor-α （TNF-<italic>α</italic>）， interleukin-6 （IL-6）， leptin （LP）， adiponectin （ADP）， nitric oxide （NO）， endothelin-1 （ET-1）， endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were detected and recorded. Then the safety was evaluated. Result:Levels of body mass， BMI， WHR， TG， TC， LDL-C， FBG， 2 hPG， HbA1c， HOMA-IR， SBD， DBP， TNF-<italic>α</italic>， IL-6， LP， ET-1 and iNOS were all lower than those in control group. Levels of HDL-C， InISI， HOMA-<italic>β</italic>， ADP， NO and eNOS were higher than those in control group （<italic>P</italic><0.01）. And score of syndrome differentiation of Taiyin people was lower than that in control group （<italic>P</italic><0.01）. The compliance rate of BMI in observation group was 70.27% （52/74）， which was higher than 53.42% （39/73） in control group （<italic>χ</italic><sup>2</sup>=4.421， <italic>P</italic><0.05）. The compliance rate of blood pressure was 95.95% （71/74）， was higher than 84.93% （62/73） in control group （<italic>χ</italic><sup>2</sup>=5.171， <italic>P</italic><0.05）. The compliance rate of blood fat was 87.84% （65/74）， which was higher than 72.60% （53/73） （<italic>χ</italic><sup>2</sup>=5.386， <italic>P</italic><0.05）. Conclusion:Qingfei Xiegantang can regulate the obesity， blood pressure， blood glucose and blood lipid components of MS， relieve clinical symptoms， improve IR， insulin sensitivity and islet <italic>β</italic> cell function， reduce inflammatory reaction， and increase vascular endothelial function of people of taiyin constitution with metabolic Syndrome.
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To discuss the characteristics of symptoms improvement based on the follow-up evaluation of Eustachian tube balloon dilation medium to long-term efficacy in patients with symptomatic Eustachian tube dysfunction (SETD). Patients from 2015 to 2017 were followed up after Eustachian tube balloon dilation (with the sense of aural fullness, or tinnitus and hearing ambiguity). All participants had been done ETDQ-7 before surgery and were re-evaluated with ETDQ-7 in follow-up. The improvement of overall and individual symptoms scores in ETDQ-7, the effects of gender and the difference of scores at different stages (12-18 months, 18-24 months and 24-30 months) after the operation were analyzed. There were 29 patients, including 16 males and 13 females, whose age ranged from 20 to 62 years old. The medium to long-term score of ETDQ-7 significantly declined after surgery (27.0±7.9 . 14.1±7.5, 0.05). Among all symptoms, symptoms like "blockage feeling in ear or being like under the water, constriction feeling" , "sound of blisters or explosions in the ear" decreased obviously (0.05). Comparing different stages after surgery, the scores of ETDQ-7 existed no difference (0.05). And the difference of gender showed no significant influence on surgery effects. The subjective symptoms of patients with Eustachian tube dysfunction diagnosed with SETD can be significantly improved in the medium to long-term follow-up after Eustachian tube balloon dilation, and the degree of improvement is not linearly related to the postoperative time.
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Objective To investigate the dose and time kinetics of induction of apoptosis induced by doxorubicin in J urkat leukemiacells, and to explore its pertinent molecular mechanisms. Methods Human Jurkat leukemia T - cells were treated with doxorubicin at theconcentration of 0.1 mg/L, 0.2 mg/L, 0.5 mg/L and 1.0 mg/L for 6,12,24 and 36 hours, respectively, of which one sample was pre-treated with zVAD- fmk (benzyloxycarbonyl - Val -Ala - Asp - fluoromethylketone) prior to addition of doxorubicin 0.2 mg/L. Apop-tosis was detected with both annexin V - FITC and propidium iodide ( PI ) staining and annexin V FITC and PI double positive cellswere analyzed by flow cytometry. Western blot was used to evaluate the level of Fas ligand (FasL) and FADD (Fas - associated death do-main) expression. Results The differences of apoptotic cells induced by all dose of doxorubicin were not significant (P＞0.05 ) at 6hour;at 12 hour, only the highest dose, 1 mg/L, significantly induced cell apoptosis;while the lowest dose,0.1 mg/L, did not significantlycaused cell apoptosis for all time points. After exposure to the doses of 0.2 and 0.5 mg/L for 24 or 36 hours,a significant increase in per-centage of apoptotic cells was observed (P ＜ 0.001 ). Apoptosis induced by doxorubicin was completely inhibited when the cells were incu-bated with doxorubicin in the presence of zVAD - fmk (P ＜ 0. 001 ). The level of FasL and FADD expression correspondingly increasedwith exposure time to doxorubicin. Conclusions Doxorubicin induces apoptosis in a dose - and time - dependent manner; upregulatedFasL may initiate the activation of the Fas signaling pathway and caspases are the ultimate executioner in the induction of leukemia cellapoptosis by doxorubicin.
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Objective To observe the protection of Caspase inhibitor(zVAD-fmk,benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) on neonatal rat with hypoxic-ischemic brain damage(HIBD).Methods Thirty-six neonatal rats,7 days old,were randomly divided into hypoxic-ischemic(HI) control group(A),zVAD-fmk treated group(B) and sham group(C).Before HI insult,a pan-Caspase inhibitor,zVAD-fmk or normal buffer solution was injected into the cerebral ventricle.The water content of cerebral hemisphere was measured and the percentage of apoptofic cells in hippocampal neurons was measured by Flow cytometer(Annexin V/PI) at 24 hours after HI insult.The effect on body weights(percentage of increased weight,WIP) and macroscopical changes(percentage of cortox and hippocampal dead neurons) were assessed at 14 days.Results Compared with group A,the water content of ischemic hemisphere and apoptosis percentage of hippocampal neurons in group B reduced significantly.The difference of percentage of increased weight at 14 days in group B was not significantly.Microscopic examination showed that cortox and hippocampus neural death rate in group B was proved significantly reduced compared with that in group A.Conclusion Intracerebral administration of zVAD-fmk has protective effects on hypoxic-ischemic brain damage in neonatal rat.
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0.05) at 6 hour;at 12 hour,only the highest dose,1 mg/L,significantly induced cell apoptosis;while the lowest dose,0.1 mg/L,did not significantly caused cell apoptosis for all time points.After exposure to the doses of 0.2 and 0.5 mg/L for 24 or 36 hours,a significant increase in percentage of apoptotic cells was observed(P