1.Preparation of HA-modified emodin-contained multi-walled carbon nanotubes drug delivery system and its inhi-bitory effect on breast cancer cells
Yuduo LI ; Juan DU ; Yunlong LIU ; Feng GENG ; Xiaobing CHEN
China Pharmacy 2025;36(12):1463-1469
OBJECTIVE To prepare hyaluronic acid (HA)-modified emodin (EMD)-contained multi-walled carbon nanotubes (MWCNTs) drug delivery system (HA-MWCNTs-EMD) and explore its in vitro inhibitory effect on breast cancer cells. METHODS EMD was loaded onto MWCNTs to prepare a drug delivery system MWCNTs-EMD; subsequently, the system was further modified with HA to obtain the drug delivery system HA-MWCNTs-EMD. The two drug delivery systems mentioned above were characterized. With free EMD as the reference, the drug release in vitro of the above two drug delivery systems was investigated; the uptake of EMD by two breast cancer cells (MCF-7, MDA-MB-231 cells) was detected. The impacts of the above two drug delivery systems on the expression of surface glycoprotein differentiation group 44 (CD44), activity, apoptosis and lactate dehydrogenase (LDH) release of two breast cancer cells were detected. RESULTS The encapsulation efficiencies of MWCNTs-EMD and HA-MWCNTs-EMD were both (63.52±2.74)%, with drug loading rates of (25.01±1.83)% and (12.13± 1.96)%, particle sizes of (865.95±2.16) and (351.86±1.68) nm, polydispersity indexes of 0.54±0.02 and 0.23±0.01, and Zeta potentials of (23.87±0.14) and (-42.79±0.39) mV, respectively. The 2, 4, 6, 8, 10, 12 and 24-hour cumulative release rates of EMD in MWCNTs-EMD and HA-MWCNTs-EMD were significantly lower than those in free EMD, while the cumulative release rate of HA-MWCNTs-EMD was significantly higher than that of MWCNTs-EMD (P<0.05); the EMD uptakes of MWCNTs-EMD and HA-MWCNTs-EMD by the two types of breast cancer cells were significantly higher than their uptake of free EMD (P<0.05). Compared with the free EMD group, the MWCNTs-EMD and MWCNTs-EMD groups showed significantly higher apoptosis rate and LDH release, significantly lower surface CD44 expression (except for the MWCNTs-EMD group) and cell viability in both cell types, and the effect of HA-MWCNTs-EMD was more pronounced (P<0.05). CONCLUSIONS A novel drug delivery system HA-MWCNTs- EMD loaded with EMD is developed successfully; the drug delivery system has a certain slow-release effect, which can significantly reduce the activity of breast cancer cells, promote their apoptosis and increase the release of LDH, and the above anti- breast cancer effect is significantly stronger than that of free EMD and MWCNTs-EMD.
2.Predictive value of myocardial perfusion-related parameters measured by echocardiography on the prognosis of patients with coronary artery disease at 90 d after percutaneous coronary intervention
Xiaobing CHEN ; Shanshan HUI ; Yunlong ZHANG ; Hongmei RAN
Chinese Journal of Postgraduates of Medicine 2024;47(10):917-922
Objective:To investigate the predictive value of myocardial perfusion-related parameters measured by echocardiography on the prognosis of patients with coronary artery disease at 90 d after percutaneous coronary intervention (PCI).Methods:Eighty-five patients with coronary artery disease who underwent PCI in Linping Branch of the Second Affiliated Hospital of Zhejiang University from October 2020 to October 2022 were selected retrospectively. Patients were divided into the occurrence myocardial perfusion injury group (40 cases) and the non-occurrence myocardial perfusion injury group (45 cases). The quantitative echocardiographic parameters of left ventricular end-diastolic internal diameter (LVEDD) and left ventricular end-systolic internal diameter (LVESD) were compared between the two groups, and the effects of LVEDD and LVESD on the risk of myocardial perfusion injury after PCI in patients with coronary artery disease were analyzed. Logistic regression was used to analyze the factors influencing the major adverse cardiovascular events (MACE) of patients with coronary artery disease at 90 d after PCI. A line graph model was constructed, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were constructed to verify the predictive efficiency of the line graph model.Results:Compared with the day of admission, the levels of LVEDD and LVESD were increased at 2 and 6 h after PCI, and showed an increasing trend at each time point ( P<0.05). The levels of LVEDD and LVESD at 2 and 6 h after PCI in the occurrence myocardial perfusion injury group were higher than those in the non-occurrence myocardial perfusion injury group: (45.56 ± 2.35) mm vs. (43.27 ± 2.12 ) mm, (47.87 ± 3.56) mm vs. (45.73 ± 2.98) mm; (33.49 ± 2.32) mm vs. (31.29 ± 2.29) mm, (35.62 ± 3.03) mm vs. (33.74 ± 2.12) mm, there were statistical differences ( P<0.05). The risk of myocardial perfusion injury was 4.469 and 6.081 times higher in patients with high levels of LVEDD and LVESD than in patients with low levels. The results of Logistic regression analysis showed that coronary multiple lesions, time from onset to balloon dilation, coronary Gensini score and LVEDD, LVESD were independent influencing factors of MACE at 90 d after PCI in patients with coronary artery disease ( P<0.05). Based on the above five independent influencing factors, a column line graph model was established to predict the risk of poor prognosis at 90 d after PCI. According to the column line graph model, the coronary multiple lesions were scored as 5; the corresponding prognostic adverse risk increased with the increase of time from onset to balloon dilation, coronary Gensini score and quantitative echocardiographic parameters LVEDD and LVESD; the internal validation of the column line graph prediction model was performed, and the C-index of the model was 0.978; the calibration curve showed that the model had good differentiation and accuracy in predicting the risk of MACE at 90 d after PCI. The results of ROC curve showed, the area under the curve (AUC) was 0.955 (95% CI 0.952 - 1.000). The DCA showed that when the line graph model was in the high risk threshold range (0 - 0.9), the prediction of the model had clinical practical value and the net benefit of patients was high. Conclusions:The abnormal increase of LVEDD and LVESD determined by echocardiography is associated with myocardial perfusion injury in patients with coronary heart disease after PCI, and a line graph model based on LVEDD and LVESD can predict the occurrence of MACE at 90 d after PCI, so as to guide early risk assessment and prevention.
3.Prediction of 18F-FDG PET/CT Metabolic Parameters in Axillary Lymph Node Metastasis of Breast Cancer
Dandan CHEN ; Yunlong LOU ; Zheng LIN
Chinese Journal of Medical Imaging 2024;32(10):1027-1031
Purpose To establish a non-invasive model for predicting axillary lymph node metastasis(ALNM)based on breast cancer related metabolic parameters.Materials and Methods A total of 158 patients diagnosed as breast cancer in Meizhou People's Hospital from January 1,2016 to March 30,2023 were selected,and all of them underwent whole-body PET/CT examination in our department before operation.Metabolic parameters of primary breast cancer[maximum standard uptake value(SUVmax),metabolic volume,total glycolysis(TLG)],highest axillary lymph node uptake SUVmax(SUVmaxALN),axillary lymph node short diameter and clinical related indexes[age,maximum tumor diameter,pathological type and tumor location]were obtained.According to the surgical and pathological results,the patients were divided into ALNM positive[ALNM(+)]group and ALNM negative[ALNM(-)]group.The relationship between the parameters of the two groups was analyzed,the best influencing factors were screened out,and binary Logistic regression was used to establish a prediction model to obtain the primary metabolic parameters of breast cancer.Results There were significant differences in TLG,metabolic volume,axillary lymph node short diameter and SUVmaxALN between ALNM(+)group and ALNM(-)group(Z=-3.924--1.812,all P<0.05),but there were no significant differences in age,tumor maximum diameter,pathological type,tumor location,primary focus SUVmax and SUVavg(all P>0.05).Multivariate Logistic regression analysis showed that TLG of breast cancer primary focus and SUVmaxALN could be used as independent risk factors of ALNM of breast cancer,and the regression model established by using these two factors was Logit(P)=0.142+0.443×SUVmaxALN-0.013×TLG.The area under the curve of ALNM prediction model based on TLG and SUVmaxALN was 0.769(95%CI 0.691-0.841,P<0.001).Conclusion TLG of breast cancer primary focus and SUVmaxALN can be used as independent predictors of ALNM of breast cancer,and the prediction model based on these two factors can predict ALNM well.This non-invasive method may have a certain application prospect in clinic.
4.Detection value of double inversion recovery sequence in cerebral white matter hyperintensities in patients with acute ischemic stroke
Jiaqi CHEN ; Yunlong YUE ; Rui FU ; Rui NIU
Chinese Journal of Neuromedicine 2024;23(2):140-145
Objective:To evaluate the detective effect of double inversion recovery (DIR) sequence on cerebral white matter hyperintensities (WMH) in patients with acute ischemic stroke, and compare with those of T2WI and FLAIR sequences.Methods:Seventy-three acute ischemic stroke patients with WMH within 14 d of onset, admitted to Department of Neurology, Beijing Shijitan Hospital, Capital Medical University from November 2018 to March 2021, were chosen. MRI T2WI, FLAIR and DIR sequences were used to detect WMH. According to Fazekas scale, patients with periventricular white matter hyperintensities (PVWMH) or deep white matter hyperintensities (DWMH) were divided into mild group (score of 0-1) and moderate to severe group (scores≥2); the differences in WMH volume detected by T2WI, FLAIR and DIR sequences, and signal intensity, cross-sectional area and contrast of isolated lesions were compared.Results:(1) Seventy-three patients were with PVWMH (36 into the mild group and 37 into the moderate to severe group); in patients from the moderate to severe group, PVWMH volume detected by FLAIR sequence was statistically larger compared with that by DIR sequence, and PVWMH volume detected by T2WI sequence was significantly smaller compared with that by FLAIR sequence ( P<0.05). Fifty-seven patients were with DWMH (44 into the mild group and 13 into the moderate to severe group); the DWMH volume detected by FLAIR and T2WI sequences was significantly larger than that by DIR sequence ( P<0.05). (2) A total of 60 isolated lesions were detected, ranged 5.0-9.1 mm in length; isolated lesions enjoying significantly larger cross-sectional area, higher signal intensity, and lower contrast detected by FLAIR and T2WI sequences compared with those by DIR sequence ( P<0.05); isolated lesions enjoying significantly higher signal intensity and contrast detected by T2WI sequence compared with those by FLAIR sequence ( P<0.05). Conclusion:DIR sequence enjoys better effect in detecting WMH than FLAIR and T2WI sequences; the mismatch area of DIR sequence with FLAIR or T2WI sequences suggests WMH penumbra.
5.Research progress on mesenchymal stem cell products and their exosomes in the treatment of inflammatory bowel disease
Jingwen YANG ; Qian CHEN ; Yunlong SHAN ; Jiali LIU ; Ning WEI ; Jing WANG ; Guangji WANG ; Fang ZHOU
Journal of China Pharmaceutical University 2024;55(1):103-114
Abstract: Inflammatory bowel disease (IBD), whose pathogenesis remains elusive, is a group of autoimmune diseases characterized by chronic, progressive, and lifelong inflammation of the digestive tract. The pathogenesis of IBD remains elusive. Although a number of drugs have been developed to treat IBD, their effects are merely anti-inflammatory. In addition, current treatments for IBD are easily susceptible to resistance in clinical practice. Mesenchymal stem cells (MSCs) have been reported to have the ability to migrate to the site of inflammation, with potent immunoregulatory effects, and to rebalance the immune microenvironment and restore the integrity of the epithelial barrier with significant value of application, particularly for patients who are refractory to classic medicines. In this paper, we reviewed the clinical applications, mechanisms and engineerable properties of MSC products and their exosomes to provide some reference for the use of MSCs and their exosomes in the treatment of IBD.
6.Progress of single-cell protein imaging methods
Chunlu YAO ; Weijie ZHANG ; Yunlong ZHANG ; Zhaoxia DENG ; Mengling WANG ; Zuoling ZHANG ; Chen WANG ; Qinxin SONG ; Bingjie ZOU
Journal of China Pharmaceutical University 2024;55(2):147-157
Abstract: The differential expression and subcellular localization of single-cell proteins are closely related to the physiological state and pathological mechanisms of the body. The development of single-cell protein in situ imaging methods provides powerful tools for spatial single-cell proteomics research and single-cell protein profiling. This article summarizes the single-cell protein imaging methods developed in recent years, including the circulating immunofluorescence imaging methods based on ordered multi-round antibody incubation, mass spectrometry imaging based on metal element labeled antibodies, fluorescence imaging based on DNA-barcoded antibody, gene encoded fluorescence protein imaging and spectral imaging based on Raman spectroscopy or X-ray spectroscopy, with brief explanation of the imaging principles of these methods. It focuses on the multiple performance, imaging resolution and signal amplification performance of these methods, and analyzes their application characteristics in practical scientific research and clinical work, in the hope of providing some reference for the development of more revolutionary single-cell imaging methods, and promoting the development of biomedical and precision medicine.
7.Construction of risk prediction model for predicting death or readmission in acute heart failure patients during vulnerable phase based on machine learning
Jing ZENG ; Xiaolong HE ; Huajuan HU ; Xiaoyu LUO ; Zhinian GUO ; Yunlong CHEN ; Min WANG ; Jiang WANG
Journal of Army Medical University 2024;46(7):738-745
Objective To construct risk prediction models of death or readmission in patients with acute heart failure(AHF)during the vulnerable phase based on machine learning algorithms and screen the optimal model.Methods A total of 651 AHF patients with admitted to Department of Cardiology of the Second Affiliated Hospital of Army Medical University from October 2019 to July 2021 were included.The clinical data consisting of admission vital signs,comorbidities and laboratory results were collected from electronic medical records.The composite endpoint was defined as all-cause death or readmission for worsening heart failure within 3 months after discharge.The patients were divided into a training set(521 patients)and a test set(130 patients)in a ratio of 8:2 through the simple random sampling.Six machine learning models were developed,including logistic regression(LR),random forest(RF),decision tree(DT),light gradient boosting machine(LGBM),extreme gradient boosting(XGBoost)and neural networks(NN).Receiver operating characteristic(ROC)curve and decision curve analysis(DCA)were used to evaluate the predictive performance and clinical benefit of the models.Shapley additive explanation(SHAP)was used to explain and evaluate the effect of different clinical characteristics on the models.Results A total of 651 AHF patients were included,of whom 203 patients(31.2%)died or were readmitted during the vulnerable phase.ROC curve analysis showed that the AUC values of the LR,RF,DT,LGBM,XGBoost and NN model were 0.707,0.756,0.616,0.677,0.768 and 0.681,respectively.The XGBoost model had the highest AUC value.DCA showed that the XGBoost model exhibited greater clinical net benefit compared with other models,with the best predictive performance.SHAP algorithm analysis showed that the clinical features that had the greatest impact on the output of the model were serum uric acid,D-dimer,mean arterial pressure,B-type natriuretic peptide,left atrial diameter,body mass index,and New York Heart Association(NYHA)classification.Conclusion The XGBoost model has the best predictive performance in predicting the risk of death or readmission of AHF patients during the vulnerable phase.
8.Salvage radical surgery in early-stage colorectal cancer patients undergoing non-curative endoscopic resection
Shuo FENG ; Weidong DOU ; Yingchao WU ; Guowei CHEN ; Tao WU ; Yong JIANG ; Pengyuan WANG ; Jixin ZHANG ; Yunlong CAI ; Long RONG ; Junling ZHANG ; Xin WANG
Chinese Journal of General Surgery 2024;39(2):81-85
Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.
9.Antioxidant activity of water extract from bamboo stems and its protective effect on t-BHP induced oxidative damage in Caco-2 cells
Xin YUAN ; Yunlong HUANG ; Xiaomin XIE ; Zihan ZHONG ; Jiarui CHEN ; Cuiyu BAO ; Xu YANG ; Ping MA
Journal of Public Health and Preventive Medicine 2024;35(6):50-54
Objective To investigate the antioxidant activity of bamboo stem extracts and the therapeutic effect of bamboo stem water extract on oxidative inflammation induced by tert butyl hydroperoxide (t-BHP) in human colon adenocarcinoma cells (Caco-2). Methods In this study, ABTS, DPPH, and FRAP assays were used to determine the extracellular antioxidant activity of petroleum ether extract, ethyl acetate extract, n-butanol extract, 95% ethanol extract, and distilled water extract from bamboo stems. The human intestinal Caco-2 cell line was used as the model cell, and t-BHP was selected as the oxidative stress modeling agent. The CCK-8 assay was used to detect cell viability and the optimal oxidative damage concentration of t-BHP. The content of MDA, 8-OHdG, TNF-α and IL-1β were detected to assess antioxidant stress effect. Results The five extracts of bamboo all had certain antioxidant activity, among which the water extract of bamboo stem had the best comprehensive antioxidant activity with high cell viability in Caco-2 cells. The optimal modeling concentration of t-BHP was 200 μMol/L. The water extract of bamboo stem significantly reduced the content of oxidative stress related biomarkers and inflammatory factors in Caco-2 cells induced by t-BHP. Conclusion The stem extracts of bamboo in Xianning City have strong in vitro antioxidant activity. Among them, the water extract of bamboo stem has a protective effect on t-BHP induced oxidative damage in Caco-2 cells, suggesting that the water extract possesses a potential to be developed as new antioxidant products for clinical prevention and treatment of oxidative damage related diseases.
10.Application of quality monitoring indicators of blood testing in blood banks of Shandong province
Xuemei LI ; Weiwei ZHAI ; Zhongsi YANG ; Shuhong ZHAO ; Yuqing WU ; Qun LIU ; Zhe SONG ; Zhiquan RONG ; Shuli SUN ; Xiaojuan FAN ; Wei ZHANG ; Jinyu HAN ; Lin ZHU ; Xianwu AN ; Hui ZHANG ; Junxia REN ; Xuejing LI ; Chenxi YANG ; Bo ZHOU ; Haiyan HUANG ; Guangcai LIU ; Ping CHEN ; Hui YE ; Mingming QIAO ; Hua SHEN ; Dunzhu GONGJUE ; Yunlong ZHUANG
Chinese Journal of Blood Transfusion 2024;37(3):258-266
【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.


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