This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

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 establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was mean_CIMT=0.324 7+0.006 9×age and SD_CIMT=0.076 9+0.001 2×age. For women, the regression was mean_CIMT=0.354 9+0.005 4×age and SD_CIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.
Male ; Humans ; Adult ; Female ; Carotid Intima-Media Thickness ; Cardiovascular Diseases ; Reference Values ; Carotid Arteries/diagnostic imaging* ; Ultrasonography, Carotid Arteries ; Risk Factors ; Carotid Artery Diseases

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL^-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.

Objective: To explore the predictive values of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score on the death risk of severe burn patients. Methods: A retrospective case series study was conducted. From February 2018 to November 2019, 260 severe burn patients who met the inclusion criteria were admitted to the Department of Burns of the First Affiliated Hospital of Nanchang University, including 158 males and 102 females, aged 36 (3, 53) years. According to the final outcome, the patients were divided into survival group (n=229) and death group (n=31). Data of patients were compared and statistically analyzed with chi-square test or Mann-Whitney U test between the two groups, including the gender, age, cause of burn, site of burn, total burn area, depth of burn, combined inhalation injury, and combined underlying diseases on admission, and the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score calculated based on part of the aforementioned data. The Kendall tau-b coefficient method was used to analyze the consistency of the above-mentioned three scores in 260 severe burn patients. The receiver operating characteristic (ROC) curves of the above-mentioned three scores predicting the death risk of 260 severe burn patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of AUC of the above-mentioned three scores was compared by Delong test. Results: The gender, site of burn, and depth of burn of patients between the two groups were all similar (P>0.05). The age, total burn area, proportion of flame burn, proportion of combined inhalation injury, and proportion of combined underlying diseases of patients in death group were significantly higher than those in survival group (with Z values of 5.53 and 17.78, respectively, χ² values of 16.23, 15.89, and 17.78, respectively, P<0.01); the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score of patients in death group were 142 (115, 155), 7 (5, 7), 2 (2, 3), all significantly higher than 64 (27, 87), 1 (0, 3), 0 (0, 1) in survival group (with Z values of 7.91, 7.64, and 7.61, respectively, P<0.01). In 260 severe burn patients, the results between the modified Baux score and Ryan score, modified Baux score and Belgian Outcome in Burn Injury score, Ryan score and Belgian Outcome in Burn Injury score were significantly consistent (with Kendall tau-b coefficients of 0.75, 0.71, and 0.86, respectively, P<0.01). The AUCs of ROC curves of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score for predicting the death risk of 260 severe burn patients were 0.92, 0.89, and 0.85, respectively (with 95% confidence intervals of 0.86-0.98, 0.83-0.95, and 0.78-0.93, respectively, P<0.01); the optimal thresholds were 106.5, 4.5, and 1.5 points, respectively; the sensitivity under the optimal threshold were 88.5%, 76.9%, and 73.1%, respectively, and the specificity under the optimal threshold were 88.5%, 87.2%, and 86.3%, respectively. The modified Baux score was similar to Belgian Outcome in Burn Injury score in the AUC quality (z=1.25, P>0.05), which were both significantly better than the AUC quality of Ryan score (with z values of 2.35 and 2.11, respectively, P<0.05). Conclusions: The modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score have good ability in predicting the death risk of severe burn patients. From the perspective of clinical practice, the modified Baux score is more suitable as a predictive tool for the prognosis of severe burn patients.
Adult ; Burns ; Female ; Hospitalization ; Humans ; Male ; Prognosis ; ROC Curve ; Retrospective Studies

Objective: Involuntary admission to psychiatric inpatient care can protect both patients with severe mental illnesses and individuals around them. This study analyzed annual healthcare costs per person for involuntary psychiatric admission and examined categories of mental disorders and other factors associated with mortality. Methods: This retrospective cohort study collected 1 million randomly sampled beneficiaries from the National Health Insurance Database for 2002–2013. It identified and matched 181 patients with involuntary psychiatric admissions (research group) with 724 patients with voluntary psychiatric admissions (control group) through 1:4 propensity-score matching for sex, age, comorbidities, mental disorder category, and index year of diagnosis. Results: Mean life expectancy of patients with involuntary psychiatric admissions was 33.13 years less than the general population. Average annual healthcare costs per person for involuntary psychiatric admissions were 3.94 times higher compared with voluntary admissions. The general linear model demonstrated that average annual medical costs per person per compulsory hospitalization were 5.8 times that of voluntary hospitalization. Survival analysis using the Cox proportional hazards model found no significant association between type of psychiatric admission (involuntary or voluntary) and death. Conclusion This study revealed no significant difference in mortality between involuntary and voluntary psychiatric admissions, indicating involuntary treatment’s effectiveness.

ObjectiveTo study the effect of isoflavones from Sojae Semen Praeparatum （ISSP） on lipid metabolism in atherosclerotic mice， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 （PPARγ/LXRα/ABCA1） signaling pathway. MethodFifty ApoE^-/- mice were randomly assigned into the model group， western medicine （atorvastatin calcium， 3.03 mg·kg^-1） group， and low-， medium-， and high-dose ISSP （2.5， 5， 10 mg·kg^-1， respectively） groups， with 10 rats in each group. Atherosclerosis model mice were established by bilateral ovariectomy and feeding high-fat diet. Another 10 ApoE^-/- mice receiving ovariectomy and high-fat diet were taken as the sham group. Some mice died of postoperative infection， and finally 6 mice were included in each group. One week after operation， each group was administrated with corresponding drugs or equivalent amount of normal saline. After 12 weeks， the levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and non-esterified fatty acids （NEFAs） in serum and liver tissue were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining and oil red O staining were used for observation of aortic plaque formation and liver lipid deposition. The mRNA and protein levels of PPARγ， LXRα， ABCA1， and ATP-binding cassette transporter G1 （ABCG1） in liver were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the sham group， the modeling of atherosclerosis increased the aortic plaque area （P<0.01）， elevated the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the level of HDL-C （P<0.01）， increased the liver index （P<0.05） and the levels of TC， TG， and NEFAs in liver （P<0.01）， and caused obvious hepatic fat vacuoles and lipid deposition. In addition， the modeling down-regulated the mRNA levels of PPARγ， LXRα， ABCA1 in liver （P<0.05， P<0.01），and regulated the mRNA and protein levels of ABCG1（P<0.05， P<0.01）. Compared with the model group， atorvastatin calcium and middle-， high-dose ISSP reduced the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the liver index （P<0.01）， alleviated the liver fat vacuoles and lipid deposition， and increased the levels of TC， TG， and NEFAs in the liver （P<0.05， P<0.01）. Furthermore， they up-regulated the mRNA and protein levels of PPARγ， LXRα， ABCA1， and ABCG1 in the liver （P<0.05， P<0.01）. ConclusionISSP may regulate lipid metabolism through PPARγ/LXRα/ABCA1 signaling pathway to down-regulate the expression of inflammatory cytokines in serum and alleviate liver lipid deposition， thereby suppressing the formation of atherosclerotic plaque.

Objective To explore the mechanism of tetramethylpyrazine (TMP) in preventing and treating inflammation and cell apoptosis in rats. Methods Totally 180 healthy male SD rats were selected and randomly divided into sham operation group (sham), cerebral ischemia reperfusion injury(CIRI) group, nimodipine group (nimodipine, N), and TMP subdivided into low-dose group (low). There were three subgroups: low-dose(L), medium dose (M), and high dose (H). In CIRI group a modified suture method was used to prepare the CIRI model; each TMP group was given tail injection 30 minutes before surgery. Intervention was given by intravenous injection of 5 mg/kg, 10 mg/kg, and 30 mg/kg TMP. N group was given tail vein injection of nimodipine (1 mg/kg), sham group and CIRI group were given the same dose of normal saline. SD rats in each group were scored for neurological deficits immediately after the CIRI model was constructed. At the same time, after 24 hours of reperfusion in each group,2,3,5-triphenyltetrazole chloride (TTC) staining, HE staining and Nissl staining were performed to detect the morphological changes of the parietal cortex ischemic penumbra; ELISA to detect the expression of IL-1β and IL-8 in the parietal cortex, TUNEL detects neuronal cell apoptosis in the parietal cortex, immunofluorescence detected the expression of β-catenin positive cells in the parietal cortex, and Western blotting detected the expression of Bax and Bcl-2 in the parietal cortex. Results Compared with the sham group, the neurological deficit score in the CIRI group was significantly higher(P<0.01). The HE and Nissl staining showed neuronal swelling and degeneration, some of which showed vacuole-like changes, pyknosis and deep staining of the nucleus, and a decrease in the number of neurons(P<0.01), the number of Nissl bodies was significantly reduced(P<0.01);the concentrations of inflammatory factors IL-1β and IL-8 increased significantly(P<0.01), apoptotic cells and β-catenin-positive cells and their average absorbance values both increased significantly(P<0.01);the expression of Bcl-2 protein decreased, while the expression of Bax protein increased significantly(P<0.01). Compared with the CIRI group, the neurological deficit scores of the rats in the N group and the TMP intervention group were reduced (P<0.01), HE and Nissl staining revealed that the edema of large neurons was reduced, a few nerve cells were destroyed, and the number of neurons increased(P<0.01), the number of Nissl bodies ncreased (P<0.01);the concentration of inflammatory factors IL-1β and IL-8 decreased significantly(P<0.01), apoptotic cells and β-catenin-positive cells and the average absorbance value decreased significantly (P<0.01)the expression of Bcl-2 protein increased, while the expression of Bax protein decreased significantly(P<0.01);compared with group N, as the concentration of TMP increased, nerve function, inflammatory response, and neuronal pathological changes showed dose-effects relationship (P<0.05). Conclusion TMP intervention treatment can alleviate the neurological deficit, neuronal damage, tissue edema, inflammatory factors and cell apoptosis after CIRI in rats. The mechanism may be related to the inhibition of the expression of β-catenin protein in the parietal cortex of rats.

Background::Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.Methods::From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA 2DS 2-VA score (excluding female sex from the CHA 2DS 2-VASc score). Results::Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA 2DS 2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA 2DS 2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). Conclusion::In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA 2DS 2- VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration::www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).