ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Objective To develop a method for accurate identification of multiscale carotid plaques in ultrasound images.Methods We proposed a two-stage carotid plaque detection method based on deep convolutional neural network(SM-YOLO).A series of algorithms such as median filtering,histogram equalization,and Gamma transformation were used to preprocess the dataset to improve image quality.In the first stage of the model construction,a candidate plaque set was built based on the YOLOX_l target detection network,using multiscale image training and multiscale image prediction strategies to accommodate carotid artery plaques of different shapes and sizes.In the second stage,the Histogram of Oriented Gradient(HOG)features and Local Binary Pattern(LBP)features were extracted and fused,and a Support Vector Machine(SVM)classifier was used to screen the candidate plaque set to obtain the final detection results.This model was compared quantitatively and visually with several target detection models(YOLOX_l,SSD,EfficientDet,YOLOV5_l,Faster R-CNN).Results SM-YOLO achieved a recall of 89.44%,an accuracy of 90.96%,a F1-Score of 90.19%,and an AP of 92.70%on the test set,outperforming other models in all performance indicators and visual effects.The constructed model had a much shorter detection time than the Faster R-CNN model(only one third of that of the latter),thus meeting the requirements of real-time detection.Conclusion The proposed carotid artery plaque detection method has good performance for accurate identification of carotid plaques in ultrasound images.

Objective To develop a method for accurate identification of multiscale carotid plaques in ultrasound images.Methods We proposed a two-stage carotid plaque detection method based on deep convolutional neural network(SM-YOLO).A series of algorithms such as median filtering,histogram equalization,and Gamma transformation were used to preprocess the dataset to improve image quality.In the first stage of the model construction,a candidate plaque set was built based on the YOLOX_l target detection network,using multiscale image training and multiscale image prediction strategies to accommodate carotid artery plaques of different shapes and sizes.In the second stage,the Histogram of Oriented Gradient(HOG)features and Local Binary Pattern(LBP)features were extracted and fused,and a Support Vector Machine(SVM)classifier was used to screen the candidate plaque set to obtain the final detection results.This model was compared quantitatively and visually with several target detection models(YOLOX_l,SSD,EfficientDet,YOLOV5_l,Faster R-CNN).Results SM-YOLO achieved a recall of 89.44%,an accuracy of 90.96%,a F1-Score of 90.19%,and an AP of 92.70%on the test set,outperforming other models in all performance indicators and visual effects.The constructed model had a much shorter detection time than the Faster R-CNN model(only one third of that of the latter),thus meeting the requirements of real-time detection.Conclusion The proposed carotid artery plaque detection method has good performance for accurate identification of carotid plaques in ultrasound images.

BACKGROUND: The therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCsExo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood.This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function. METHODS: Bioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCsExo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess b-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry.Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot. RESULTS: hsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers. CONCLUSION This study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.

OBJECTIVE: To develop a noninvasive method for prediction of 1p/19q codeletion in diffuse lower-grade glioma (DLGG) based on multimodal magnetic resonance imaging (MRI) radiomics. METHODS: We collected MRI data from 104 patients with pathologically confirmed DLGG between October, 2015 and September, 2022. A total of 535 radiomics features were extracted from T₂WI, T₁WI, FLAIR, CE-T₁WI and DWI, including 70 morphological features, 90 first order features, and 375 texture features. We constructed logistic regression (LR), logistic regression least absolute shrinkage and selection operator (LRlasso), support vector machine (SVM) and Linear Discriminant Analysis (LDA) radiomics models and compared their predictive performance after 10-fold cross validation. The MRI images were reviewed by two radiologists independently for predicting the 1p/19q status. Receiver operating characteristic curves were used to evaluate classification performance of the radiomics models and the radiologists. RESULTS: The 4 radiomics models (LR, LRlasso, SVM and LDA) achieved similar area under the curve (AUC) in the validation dataset (0.833, 0.819, 0.824 and 0.819, respectively; P>0.1), and their predictive performance was all superior to that of resident physicians of radiology (AUC=0.645, P=0.011, 0.022, 0.016, 0.030, respectively) and similar to that of attending physicians of radiology (AUC=0.838, P>0.05). CONCLUSION Multiparametric MRI radiomics models show good performance for noninvasive prediction of 1p/19q codeletion status in patients with in diffuse lower-grade glioma.
Humans ; Magnetic Resonance Imaging ; Chromosome Aberrations ; Area Under Curve ; Glioma/genetics* ; ROC Curve

OBJECTIVE To study the effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute myocardial infarction. METHODS The model of heart failure after acute myocardial infarction was established by ligaturing the anterior descending branch of the left coronary artery in rats. The model rats were divided into model group，Shenfu yixin granule low-dose and high-dose groups （1.76，8.8 g/kg），Fosinopril sodium tablets group （positive control ，4 mg/kg），sham operation group was set up （only threading without ligation at the same position ），with 8 rats in each group. After 4 weeks of drug intervention ，the hemodynamic indexes of rats in each group were measured by physiological recorder. The pathological changes of myocardial tissue were observed in each group. The level of oxidative stress in cardiomyocytes ， mitochondrial membrane potential ，protein expression of PTEN-induced putative kinase 1（PINK1），E3 ubiquitin ligase Parkin and ubiquitin binding protein P 62 in myocardial tissue of rats in each group were detected. RESULTS Compared with sham operation group ，the pathological injuries such as myocardial fiber morphology disorder and inflammatory cell infiltration were serious. The left ventricular end systolic pressure （LVESP），maximum rate of rise of left ventricular internal pressure （+dp/dtmax）， maximun rate of decrease of left ventricular internal pressure （－dp/dtmax），total antioxidant capacity ，mitochondrial membrane potential，PINK1，Parkin and P 62 protein expression were significantly decreased in model group （P＜0.01）. The left ventricular end diastolic pressure （LVEDP），the level of reactive oxygen species and the activity of reduced nicotinamide adenine dinucleotide phosphate in left ventricular ischemic cardiomyocytes were significantly increased （P＜0.01）. Compared with model group ，the pathological injuries of myocardial tissue in intervention groups were alleviated ，and above indexes were improved in varying degrees（P＜0.01 or P＜0.05）. CONCLUSIONS Shenfu y ixin granule can reduce the level of oxidative stress and alleviate heart failure after acute myocardial infarction ，which may be related to the activation of Parkin-dependent pathway to strengthen mitochondrial autophagy and reduce mitochondrial dysfunction.

Objective To investigate the value of multiplex bead-based flow fluorescent immunoassay (MBFFI) in the diagnosis of primary biliary cholangitis (PBC) by analyzing its results in detecting antimitochondrial antibody M2 subtype (AMA-M2), gp210 antibody, and sp100 antibody. Methods A total of 340 patients who attended The Affiliated Hospital of Qingdao University from August 2018 to June 2020 and were diagnosed with PBC were enrolled as PBC group, and 143 patients with other diseases and 117 individuals undergoing physical examination were also enrolled. MBFFI and immunoblotting test (IBT) were used to detect AMA-M2, gp210, and sp100 autoantibodies in serum, and the Kappa-test was used to compare the consistency of the two methods in detecting the same autoantibody; the receiver operating characteristic (ROC) curve was used to evaluate the value of MBFFI detection of three antibodies in the diagnosis of PBC; the chi-square test was used to compare positive. Results In the PBC group, the two methods showed the best consistency in detecting AMA-M2(Kappa=0.874) and showed relatively good consistency in detecting gp210 and sp100 antibodies (Kappa=0.713 and 0.749). MBFFI had the highest sensitivity of 72.06% in detecting AMA-M2; it had a sensitivity of 44.71% in the combined detection of gp210 and sp100 antibodies, which was higher than its sensitivity in detecting each antibody alone; it had a sensitivity of 82.65% in the combined detection of AMA-M2, gp210, and sp100 antibodies, which was higher than its sensitivity in detecting each antibody alone. Combined detection of the three antibodies had the largest area under the ROC curve of 0.907 0 in the diagnosis of PBC. Conclusion MBFFI has good consistency with IBT in detecting autoantibodies associated with PBC, and the combined detection of AMA-M2, gp210, and sp100 antibodies by MBFFI has higher sensitivity and value in the diagnosis of PBC.

Background: Dietary fiber is strongly recommended as the basic treatment for functional constipation according to global guidelines. However, a complete evaluation standard for the laxative functional food remains to be improved in China. Aims: To evaluate the efficacy and safety of the laxative function of a compound fructose-oligosaccharide fiber granule, so as to provide evidence-based medical basis for the evaluation of laxative functional food. Methods: In a randomized, double-blind, parallel and controlled trial with placebo as control, 120 subjects with functional constipation were enrolled in 2 clinical research centers in Beijing, and randomly divided into experimental group and control group (60 cases in each group). Subjects in experimental group were given a compound fructose-oligosaccharide fiber granule dissolved in 50 mL water orally, 1 bag (9 g) per day for 2 weeks; while those in control group were given a placebo granule with the same appearance, specification and dosage as the experimental group. The bowel movement frequency per week, defecation status and stool consistency were recorded before and after the test, and the safety tests were completed. Results: After 2 weeks of treatment, the bowel movement frequency in experimental group increased by (1.63±1.57) times per week, the stool consistency assessed by Bristol stool form scale and the difficulty in defecation were also improved as compared with the baseline (all P<0.05). Furthermore, improvements in experimental group were superior to those in control group (all P<0.05). No allergic and other adverse events were reported during the test, and there were no significant changes in blood, urine, stool routine and blood biochemical indices before and after the test. Conclusions: The compound fructose-oligosaccharide fiber granule tested in this study is proved to have laxative effect and is safety for functional constipation. The testing program is scientific and of feasibility, and may provide a methodology basis for human oral administration trials of laxative functional food.

Objective To evaluate the clinical application value of serum high sensitive α-fetoprotein variant ratio (hs-AFP-L3％) in the diagnosis and treatment of hepatocellular carcinoma.Methods From October 2016 to March 2018,at Affiliated Hospital of Qingdao University,160 patients diagnosed with hepatocellular carcinoma,32 patients with intrahepatic cholangiocarcinoma (ICC),52 patients with post-hepatitis B liver cirrhosis,53 patients with chronic hepatitis B and 50 healthy controls were enrolled.The serum levels of hs-AFP-L3％ and α-fetoprotein were measured.Mann-Whitney U test,Spearman correlation analysis,Wilcoxon signed rank test and chi-square test were performed for statistical analysis.Results The serum levels of hs-AFP-L3％ and α-fetoprotein in hepatocellular carcinoma group were 24.90％ (4.68％ to 61.85％) and 113.45 μg/L (11.18 μg/L to 1 803.48 μg/L),respectively,which were higher than those in ICC group (0.50％,0.50％ to 0.50％;and 2.79 μg/L,1.72 μg/L to 4.04 μg/L),cirrhosis group (0.50％,0.50％ to 5.25％;and 18.35 μg/L,3.95 μg/L to 31.93 μg/L),chronic hepatitis group (0.50％,0.50％ to 4.25％;and 2.70 μg/L,1.80 μg/L to 17.00 μg/L),and healthy control group (0.50％,0.50％ to 0.50％;and 1.94 μg/L,1.46 μg/L to 2.63 μg/L),and the differences were statistically significant (U =461.00,1 485.50,1 141.00,625.00;401.50,2 207.00,1 254.00,266.00;all P ＜0.01).The sensitivity of hs-AFP-L3％ and α-fetoprotein in the diagnosis of hepatocellular carcinoma was 66.3％ and 70.0％,respectively;and the difference was not statistically significant (x2 =0.54,P ＞ 0.05).The sensitivity of the combined detection was 82.5％,which was higher than that of the separate detection,and the differences were statistically significant (x2 =24.04 and 18.05,both P ＜0.01).The specificity of hs-AFP-L3％ was 95.2％,which was higher than that of α-fetoprotein (68.6％),and the difference was statistically significant (x2 =26.04,P ＜ 0.01).The specificity of the combined detection of these two markers was 68.6％,which was lower than that of hs-AFP-L3％ alone (95.2％),and the difference was statistically significant (x2 =26.04,P ＜ 0.01).There was no statistically significant difference in the specificity between the combined detection and α-fetoprotein detection alone (68.6％,P ＞ 0.05).The sensitivity of hs-AFP-L3％ in the diagnosis of patients with α-fetoprotein-negative (α-fetoprotein ＜ 20 μg/L) hepatocellular carcinoma was 41.7％.The serum levels of hs-AFP-L3％ and α-fetoprotein were both positively correlated with tumor size and clinical stage (hs-AFP-L3％ r =0.272 and 0.436;α-fetoprotein r =0.375 and 0.458;all P ＜ 0.01).The reduction of serum hs-AFP-L3％ in 38 patients with hepatocellular carcinoma after operation was 82.2％,which was higher than that of oα-fetoprotein (69.2％),and the difference was statistically significant (U =532.50,P =0.049).There was no correlation between serum level of hs-AFP-L3％ and α-fetoprotein level (r =0.077,P ＞ 0.05).Conclusions The sensitivity of hs-AFP-L3％ is similar to that of α-fetoprotein in the diagnosis of hepatocellular carcinoma,while the specificity of hs-AFP-L3％ is higher than that of α-fetoprotein.The combined detection of the two markers can improve the diagnostic rate of hepatocellular carcinoma.The hs-AFP-L3％ has a high diagnostic value in α-fetoprotein-negative hepatocellular carcinoma.

OBJECTIVE： To observe the effects of Shenfu yixin decoction on reactive oxygen species （ROS） and energy metabolism in primary hypoxic cardiomyocytes. METHODS： After isolation， culture and identification， primary cardiomyocytes of neonatal SD rats were randomly divided into normal group， model group， positive control group （coenzyme Q10， 0.1 mmol/L） and Shenfu yixin decoction low-dose and high-dose groups （0.25， 0.5 mg/mL）. Except for normal group， other groups were cultured with 5％O2， 5％CO2 and 90％N2 for 6 h to induce hypoxic injury model. After 6 hours of hypoxia， ROS contents in cardiomyocytes and mitochondria of each group were detected by ROS probe and flow cytometry. Luciferase luminescence and Western blotting were used to detect ATP content and CK protein expression of each group. Transmission electron microscope was used to observe ultrastructure of cardiomyocytes in each group. RESULTS： Compared with normal group， the expression of ROS in primary hypoxic cardiomyocytes and mitochondria as well as the content of ROS were increased significantly， while the content of ATP and expression levels of CK protein were decreased significantly （P＜0.05）； there were swelling of endoplasmic reticulum and mitochondria， dissolution or even disappearance of mitochondrial ridge， obvious cardiomyocytes injury. Compared with model group， the expression of ROS in primary hypoxic cardiomyocytes and mitochondria of administration groups， the contents of ROS in primary hypoxic cardiomyocytes of positive control group and Shenfu yixin decoction high-dose group as well as the content of ROS in primary hypoxic cardiomyocytes mitochondria of administration groups were all decreased significantly， while ATP contents in primary hypoxic cardiomyocytes of positive control group and Shenfu yixin decoction high-dose group as well as expression levels of CK protein in primary hypoxic cardiomyocytes of administration groups were all increased significantly （P＜0.05）. The primary hypoxic cardiomyocytes injury was relieved significantly in positive control group and Shenfu yixin decoction high-dose group. CONCLUSIONS： Shenfu yixin decoction can improve primary hypoxic cardiomyocytes， down-regulate the expression of ROS in cardiomyocytes and mitochondria and also improve its energy metabolism.