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

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.
Humans ; Middle Aged ; Aged ; Insulin Resistance ; Blood Glucose/metabolism* ; Biomarkers ; Diabetes Mellitus ; Hypertension ; Glucose ; Triglycerides ; Cholesterol, HDL

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.
Animals ; Rats ; Arachidonic Acid ; Biomarkers/blood* ; Blood Proteins ; Chromatography, High Pressure Liquid ; Creatinine ; Drugs, Chinese Herbal/therapeutic use* ; Glomerulonephritis/metabolism* ; Metabolomics ; Urea ; Chronic Disease ; Disease Models, Animal ; Complex Mixtures/therapeutic use*

OBJECTIVES: To study the changes of protein levels in peripheral blood after it dried. METHODS: The proteins from whole blood and bloodstains were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and normalized by the label-free quantification (LFQ) method. The differential proteins were analyzed by using R 4.2.1 software, limma and edgeR package. The analysis of biological function, signaling pathway and subcellular localization for the differential proteins was then performed. RESULTS: A total of 623 and 596 proteins were detected in whole blood and bloodstains, respectively, of which 31 were statistically significant in the quantitative results, including 10 up-regulated and 21 down-regulated proteins in bloodstains. CONCLUSIONS The protein abundances in whole blood and bloodstains are highly correlated, and the variation of protein abundances may be related to the changes of endogenous and structural proteins in cells. The application of proteomics technology can assist the screening and identification of protein biomarkers, thereby introducing new biomarkers for forensic research.
Chromatography, Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Proteomics/methods* ; Blood Stains ; Biomarkers

Objective: To explore the trend and influencing factors of serum lipoprotein (a) (Lp(a)) concentration over time in Chinese community populations. Methods: This study is a prospective cohort study. The participants were enrolled from Chinese Multi-provincial Cohort Study- Beijing projects, completed the cardiovascular disease risk factor surveys in 2002 and 2007, and the serum Lp (a) concentration were measured. Based on the Lp(a) concentration at baseline (2002) and follow-up (2007), the participants were classified into subgroups of <30.0 mg/dl (1 mg/dl=0.01 g/L) group, 30.0 to 49.9 mg/dl group, and ≥50.0 mg/dl group, respectively. Multivariable logistic regression analysis was used to identify influencing factors associated with Lp (a) absolute change (≥20 mg/dl) and relative change (≥20%) within 5 years. Results: Among 1 955 participants with age of (56.5±8.0) years old and 821 male (42.0%) at baseline, there were 1 657 (84.8%), 184 (9.4%) and 114 (5.8%) participants in Lp(a)<30.0 mg/dl group, 30.0 to 49.9 mg/dl group and ≥50.0 mg/dl group, respectively. Among the baseline Lp(a) concentration of 30.0-49.9 mg/dl group, 68 (37.0%) participants progressed to Lp(a) ≥50.0 mg/dl after 5 years follow-up, and 102 (55.4%) remained at this level. Participants with baseline Lp(a)<30.0 mg/dl (92%, 1 524/1 657) or Lp(a)≥50.0 mg/dl (94.7%, 108/114) tended to be maintained at their respective levels. The results of the multivariate logistic regression analysis showed that, in addition to the high level of baseline Lp(a) concentration, family history of cardiovascular disease, elevated fasting blood glucose and usage of oral lipid-lowering drugs were the influencing factors of Lp(a) changes over time (P<0.05). Conclusions: Adults with borderline-high Lp(a) concentrations (30.0 to 49.9 mg/dl) could be considered for repeated testing, especially for those with a family history of cardiovascular disease, elevated fasting blood glucose and usage of statins.
Adult ; Humans ; Male ; Middle Aged ; Lipoprotein(a) ; Cardiovascular Diseases ; Blood Glucose ; Cohort Studies ; Prospective Studies ; Biomarkers ; Risk Factors

Objective: To explore the trend and influencing factors of serum lipoprotein (a) (Lp(a)) concentration over time in Chinese community populations. Methods: This study is a prospective cohort study. The participants were enrolled from Chinese Multi-provincial Cohort Study- Beijing projects, completed the cardiovascular disease risk factor surveys in 2002 and 2007, and the serum Lp (a) concentration were measured. Based on the Lp(a) concentration at baseline (2002) and follow-up (2007), the participants were classified into subgroups of <30.0 mg/dl (1 mg/dl=0.01 g/L) group, 30.0 to 49.9 mg/dl group, and ≥50.0 mg/dl group, respectively. Multivariable logistic regression analysis was used to identify influencing factors associated with Lp (a) absolute change (≥20 mg/dl) and relative change (≥20%) within 5 years. Results: Among 1 955 participants with age of (56.5±8.0) years old and 821 male (42.0%) at baseline, there were 1 657 (84.8%), 184 (9.4%) and 114 (5.8%) participants in Lp(a)<30.0 mg/dl group, 30.0 to 49.9 mg/dl group and ≥50.0 mg/dl group, respectively. Among the baseline Lp(a) concentration of 30.0-49.9 mg/dl group, 68 (37.0%) participants progressed to Lp(a) ≥50.0 mg/dl after 5 years follow-up, and 102 (55.4%) remained at this level. Participants with baseline Lp(a)<30.0 mg/dl (92%, 1 524/1 657) or Lp(a)≥50.0 mg/dl (94.7%, 108/114) tended to be maintained at their respective levels. The results of the multivariate logistic regression analysis showed that, in addition to the high level of baseline Lp(a) concentration, family history of cardiovascular disease, elevated fasting blood glucose and usage of oral lipid-lowering drugs were the influencing factors of Lp(a) changes over time (P<0.05). Conclusions: Adults with borderline-high Lp(a) concentrations (30.0 to 49.9 mg/dl) could be considered for repeated testing, especially for those with a family history of cardiovascular disease, elevated fasting blood glucose and usage of statins.
Adult ; Humans ; Male ; Middle Aged ; Lipoprotein(a) ; Cardiovascular Diseases ; Blood Glucose ; Cohort Studies ; Prospective Studies ; Biomarkers ; Risk Factors

Objective: To explore the reentry rate of reactive blood donors in the bloodborne pathogen infection screening in Hangzhou City, and analyze the donation behavior of those who successfully returned. Methods: A retrospective analysis of the return data of blood donors with reactive bloodborne pathogen screening markers was conducted at Zhejiang Provincial Blood Center from June 2017 to May 2022. The reentry process for blood donors with reactive bloodborne pathogen screening markers in Hangzhou City is as follows: after the initial screening period of 6 months, donors can voluntarily apply for return to the blood center. Samples are collected and subjected to routine enzyme-linked immunosorbent assay (ELISA) screening for HBsAg, anti-HCV, HIV Ab/Ag, and anti-TP, as well as a single nucleic acid (HIV/HCV/HBV) test. For samples that show non-reactivity in both ELISA and nucleic acid tests, serum biomarker testing for the reasons of exclusion is performed using chemiluminescence immunoassay (CLIA), and those with non-reactivity are allowed to return. Results: A total of 4 583 reactive blood donors who met the criteria for re-entry applied for reentry, out of which 475 applications were received from donors in the Hangzhou area. Among these, 279 donors were successfully readmitted, resulting in a success rate of 58.74% (279/475). By the end of December 2021, out of the 174 donors who successfully returned, 114 donors chose to donate again. They collectively donated 39 530 ml of whole blood and 1 147.2 therapeutic doses of platelets. Among these, 21 donors once again showed reactivity for pathogen infection biomarkers, accounting for 18.42% (21/114). Conclusion: The reentry strategy has somewhat mitigated the attrition of blood donors. Nevertheless, there are instances where donors who were successfully readmitted show reactivity once more in the screening for pathogen infection biomarkers.
Humans ; Blood Donors ; Blood-Borne Pathogens ; Retrospective Studies ; Mass Screening/methods* ; Biomarkers ; HIV Infections ; Nucleic Acids ; Hepatitis B virus

Objective: To explore the reentry rate of reactive blood donors in the bloodborne pathogen infection screening in Hangzhou City, and analyze the donation behavior of those who successfully returned. Methods: A retrospective analysis of the return data of blood donors with reactive bloodborne pathogen screening markers was conducted at Zhejiang Provincial Blood Center from June 2017 to May 2022. The reentry process for blood donors with reactive bloodborne pathogen screening markers in Hangzhou City is as follows: after the initial screening period of 6 months, donors can voluntarily apply for return to the blood center. Samples are collected and subjected to routine enzyme-linked immunosorbent assay (ELISA) screening for HBsAg, anti-HCV, HIV Ab/Ag, and anti-TP, as well as a single nucleic acid (HIV/HCV/HBV) test. For samples that show non-reactivity in both ELISA and nucleic acid tests, serum biomarker testing for the reasons of exclusion is performed using chemiluminescence immunoassay (CLIA), and those with non-reactivity are allowed to return. Results: A total of 4 583 reactive blood donors who met the criteria for re-entry applied for reentry, out of which 475 applications were received from donors in the Hangzhou area. Among these, 279 donors were successfully readmitted, resulting in a success rate of 58.74% (279/475). By the end of December 2021, out of the 174 donors who successfully returned, 114 donors chose to donate again. They collectively donated 39 530 ml of whole blood and 1 147.2 therapeutic doses of platelets. Among these, 21 donors once again showed reactivity for pathogen infection biomarkers, accounting for 18.42% (21/114). Conclusion: The reentry strategy has somewhat mitigated the attrition of blood donors. Nevertheless, there are instances where donors who were successfully readmitted show reactivity once more in the screening for pathogen infection biomarkers.
Humans ; Blood Donors ; Blood-Borne Pathogens ; Retrospective Studies ; Mass Screening/methods* ; Biomarkers ; HIV Infections ; Nucleic Acids ; Hepatitis B virus

OBJECTIVES: There is a high coagulation state in pregnant women, which is prone to coagulation and fibrinolysis system dysfunction. This study aims to explore the latest coagulation markers-thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator/plasminogen activator inhibitor compound (tPAI-C) in different stages of pregnancy, establish reference intervals (RIs) for healthy pregnant women of Chinese population, and to provide an effective and reliable reference for clinicians. METHODS: A total of 492 healthy pregnant women, who underwent pregnancy examination and delivery in the Department of Obstetrics, Second Xiangya Hospital of Central South University from October 2019 to October 2020, were enrolled for this study. They were assigned into the first trimester group, the second trimester group, the third trimester group, and the puerperium group according to the pregnancy period, and 123 healthy non-pregnant women were selected as the controls. Plasma levels of TM, TAT, PIC and tPAI-C were analyzed by automatic chemiluminescence immunoassay analyzer. The RIs for TM, TAT, PIC, and tPAI-C were defined using non-parametric 95% intervals, determined following Clinical and Laboratory Standards Institute Document C28-A3c (CLSI C28-A3c), and Formulation of Reference Intervals for the Clinical Laboratory Test Items (WS/T402-2012). RESULTS: TM and TAT levels increased gradually in the first, second, and third trimester women and decreased in the puerperium women (P<0.05 or P<0.01). PIC level of healthy non-pregnant women was lower than that of pregnant women (P<0.05 or P<0.01), but PIC level of pregnant and puerperium women did not differ significantly (P>0.05). tPAI-C level in healthy non-pregnant women was lower than that of pregnant women (P<0.05 or P<0.01), and tPAI-C level was significantly decreases in the puerperium women (P<0.01). The RIs for TM were as follows: Healthy non-pregnant women at 3.20-4.60 TU/mL, the first and second trimester at 3.12-7.90 TU/mL, the third trimester at 3.42-8.29 TU/mL, puerperium at 2.70-6.40 TU/mL. The RIs for TAT were as follows: Healthy non-pregnant women at 0.50-1.64 ng/mL, the first and second trimester at 0.52-6.91 ng/mL, the third trimester at 0.96-12.92 ng/mL, puerperium at 0.82-3.75 ng/mL. The RIs for PIC were as follows: Healthy non-pregnant women at 0.160-0.519 ng/mL, pregnant women at 0.162-0.770 μg/mL. The RIs for tPAI-C were as follows: Healthy non-pregnant women at 1.90-4.80 ng/mL, the first and second trimester at 2.03-9.33 ng/mL, the third trimester at 2.80-14.20 ng/mL, puerperium at 1.10-8.40 ng/mL. CONCLUSIONS The levels of 4 new coagulation markers TM, TAT, PIC, and tPAI-C in pregnant women are increased significantly during pregnancy and gradually return to normal after delivery. The RIs for TM, TAT, PIC, and tPAI-C in pregnant women by trimester are established according to CLSI C28-A3c, thus providing a clinical reference for clinician in judgement of thrombotic risk.
Biomarkers/blood* ; Blood Coagulation ; Female ; Humans ; Postpartum Period ; Pregnancy ; Reference Values

INTRODUCTION: Contrast-induced nephropathy (CIN) is a serious complication of percutaneous coronary intervention (PCI). The most important predictor of CIN is renal function before PCI. Serum creatinine (SCr) is a commonly used biomarker of renal function, but an elevation in SCr lags behind the onset of kidney injury and is not viable for early detection of CIN after PCI. Our primary objective was to investigate whether preoperative cystatin C (CysC) before PCI was an early predictor of postoperative CIN. The secondary objective was to evaluate associations between preoperative CysC and renal biomarkers. METHODS: From December 2014 to December 2015, 341 patients with normal renal function were enrolled into the study at our medical centre. All patients were apportioned to normal CysC (≤1.03 mg/L) or high CysC (>1.03 mg/L) groups before PCI and were hydrated from four hours prior to PCI to 24 hours after it. Renal function was monitored at 48 hours after PCI. Clinical parameters were recorded before and after PCI. RESULTS: There was no significant difference in preoperative SCr between the CIN and non-CIN groups. However, preoperative CysC demonstrated significant difference between the two groups (p <0.01). Logistic regression analysis showed that elevated CysC before PCI was a risk factor for CIN (p = 0.013). Furthermore, the linear regression models identified an association between CysC before PCI and renal function after PCI. CONCLUSION CysC before PCI was viable as a biomarker of renal function after PCI and high preoperative CysC was able to predict CIN earlier than SCr.
Humans ; Biomarkers/blood* ; Contrast Media/adverse effects* ; Coronary Angiography ; Creatinine/blood* ; Cystatin C/blood* ; Kidney Diseases/diagnosis* ; Percutaneous Coronary Intervention ; Risk Factors