1.Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy.
Siqin HE ; Lulu WANG ; Dongxu WU ; Fan TONG ; Huan ZHAO ; Hanmei LI ; Tao GONG ; Huile GAO ; Yang ZHOU
Acta Pharmaceutica Sinica B 2024;14(2):765-780
A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.
2.Establishment of HPLC fingerprint and content determination of multiple index components in Xiao’er resuqing oral liquid
Junfeng CUI ; Shuai CUI ; Xiukun LIANG ; Dongxu LI ; Xinrui WANG ; Peng GAO
China Pharmacy 2024;35(7):801-806
OBJECTIVE To establish an HPLC fingerprint of Xiao’er resuqing oral liquid, and to determine the contents of twelve index components. METHODS HPLC method was adopted. The determination was performed on Venusil MP C18 column with mobile phase consisting of acetonitrile-0.1% phosphate aqueous solution (gradient elution) at a flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm, the column temperature was 30 ℃, the injection volume was 10 μL. HPLC fingerprint of Xiao’er resuqing oral liquid was established by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM (2012 edition) to evaluate the similarity. The contents of 12 components were determined, including (R, S)-goitrin, 3,5-O-dicaffeoyl quinic acid, puerarin, forsythin, forsythoside A, chlorogenic acid, baicalin, saikosaponins d, wogonoside, baicalein, emodin and chrysophanol. RESULTS The similarity of HPLC fingerprints of 13 batches of Xiao’er resuqing oral liquid was greater than 0.97, and 14 common peaks were confirmed. The contents of the above 12 index components in 13 batches of Xiao’er resuqing oral liquid were as follows: 0.078-0.172, 1.564-2.736, 1.338-2.578, 0.426-0.872, 1.477-2.628, 1.396-2.447, 4.052-9.146, 0.367- 0.692, 1.974-4.674, 1.274-2.969, 0.085-0.167 and 0.155-0.307 mg/mL. CONCLUSIONS The established HPLC fingerprint and content determination methods have high accuracy and high specificity, which can be used for the quality evaluation of Xiao’er resuqing oral liquid.
3.Systemic therapy for advanced hepatocellular carcinoma
Jiahao XU ; Dongxu YIN ; Yuchen LI ; Fujie CHEN ; Mingda WANG ; Tian YANG
Journal of Clinical Hepatology 2024;40(11):2306-2314
Hepatocellular carcinoma(HCC)is one of the most common malignancies with high morbidity and mortality rates worldwide.With the advances in molecular biology and tumor immunology,molecular-targeted agents represented by tyrosine kinase inhibitors(such as sorafenib and lenvatinib)and immunotherapy represented by PD-1/PD-L1 monoclonal antibodies have brought hope for patients with advanced HCC.The combination of immunotherapy and anti-angiogenic therapy can further improve the treatment outcome of patients.In addition,the optimization and integration of stereotactic body radiotherapy,local treatment,and systemic treatment may maximize the benefits of patients.In the future,through a deep understanding of the heterogeneity of HCC,the development of precision molecular subtyping and individualized treatment,and the establishment of a multidisciplinary collaborative diagnosis and treatment system,systemic therapy is expected to achieve long-term management of advanced HCC.This article reviews the current status and advances in systemic therapy for advanced HCC.
4.Analysis of loss to follow-up status and influencing factors of children born to pregnant women with HIV infection in China in 2019
Ya GAO ; Xiaoyan WANG ; Qun GAO ; Dongxu HUANG ; Qian WANG ; Yu WANG ; Hongqiao ZHENG ; Xinwei LI ; Caiyun FU ; Ziqi ZHANG ; Ailing WANG
Chinese Journal of Epidemiology 2024;45(6):833-838
Objective:To understand the loss to follow-up of children born to pregnant women with HIV infection (HIV-exposed children) and analyze its influencing factors in China in 2019.Methods:The data were collected from the follow-up records of pregnant women with HIV infection and their children reported by the national "Management Information System for the Prevention of HIV, syphilis and Hepatitis B Mother-to-Child Transmission" in 2019. HIV-exposed children were defined as those who were not followed up after birth or who were not followed up at 18 months of age and who were not followed up at 21 months of age. The univariate and multivariate influencing factors of loss to follow-up of children born to HIV-infected pregnant women were analyzed by χ2 test and logistic regression model. SPSS 25.0 software was used for statistical analysis. Results:The number of HIV-infected pregnant women was 5 039, the number of live-born children was 5 035, the number of loss to follow-up children within 18 months of age was 283, and the loss to follow-up rate children was 5.62%(283/5 035). The results of multivariate logistic regression analysis showed that the rate of loss to follow-up of exposed children born to pregnant women who worked as farmers (animal husbandry and fishery) (a OR=0.34, 95% CI: 0.22-0.53), unmarried (a OR=0.47, 95% CI: 0.24-0.93), first marriage (a OR=0.38, 95% CI: 0.22-0.67), remarriage (a OR=0.36, 95% CI: 0.20-0.67) and cohabiting (a OR=0.47, 95% CI: 0.23-0.97), and knew they had HIV infection before this pregnancy (a OR=0.53, 95% CI: 0.40-0.70) was lower. Han nationality (a OR=1.52, 95% CI: 1.09-2.13), primary school (a OR=2.06, 95% CI: 1.10-3.89) and junior middle school (a OR=1.81, 95% CI: 1.03-3.17) educational level, non-use of antiviral drugs (a OR=6.21, 95% CI: 4.32-8.93) and delivery in township (street) level midwifery institutions (a OR=5.72, 95% CI: 1.61-20.27) had higher rates of loss to follow-up among infants born to HIV-infected pregnant women. Conclusions:HIV-exposed children still have a specific rate of loss to follow-up in China in 2019. In order to further reduce the rate of loss to follow-up, it is of great significance to improve the detection rate of HIV before pregnancy and the rate of antiviral drugs used in pregnant women with HIV infection, which is of great significance for the effective implementation of comprehensive intervention measures of prevention of mother-to-child transmission of HIV.
5.Effect of Sample Solvent on Chromatographic Retention Performance of Traditional Chinese Medicine Components in RP-HPLC
Dongxu ZHANG ; Tong ZHANG ; Yue DING ; Yong ZHANG ; Zhengyan YANG ; Shenshu WANG ; Xinhua ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):1017-1027
Objective To explore the solvent effect on the chromatographic retention performance by RP-HPLC in traditional Chinese medicine analysis.Methods Five traditional Chinese medicines were selected to determin by HPLC according to the requirements of each medicinal content determination item in Chinese pharmacopoeia(Vol.Ⅰ,2020),they were gentiopicroside-Radix gentianae,syringin-Acanthopanax enticosus,rosin diglucoside-Eucommia ulmoides,aesculin-Fraxinus Cortex,and adenosine-Cordyceps sinensis respectively.The effect of sample solvent in RP-HPLC was explored preliminarily on the chromatographic peak abnormalities and some solutions were proposed.Results The abnormal chromatographic retention behavior of the five traditional Chinese medicine components were characterized by retention time drift,peak broadening,extending and splitting,the fundamental reason for the above abnormal phenomenons was that there was a certain mismatch between the sample solvent and the mobile phase,leading to different existing forms of the sample between the sample solvent and the mobile phase(Solvent Effect).The results showed that the mobile phase or similar to mobile phase solution was a preferred method to reduce and eliminate solvent effect.In addition,reducing the injection volume or using the solvent effect eliminator can also be used as auxiliary means.Conclusion Solvent effect can cause abnormal peak shape,and had an influence on the accuracy of qualitative and quantitative results,it should be taken seriously in daily Chinese medicine analysis work.
6.Research progress of hyperandrogenism affecting liver function in polycystic ovary syndrome
Chen NAN ; Hongmin QI ; Dongxu WANG
Clinical Medicine of China 2024;40(6):477-480
Polycystic ovary syndrome (PCOS) is a common disease among women of childbearing age, and hyperandrogenism (HA) is a typical clinical feature of PCOS patients. In recent years, research has found that HA is closely related to the liver function of PCOS patients, in addition to causing reproductive, endocrine, and metabolic disorders. This article provides a review from four aspects: the relationship between PCOS and HA, the impact of HA on liver function in PCOS patients, the mechanism of HA affecting liver function in PCOS, and the intervention of HA on improving liver function in PCOS. The aim is to further raise awareness of the multi system effects of HA on PCOS patients and provide a basis and approach for improving liver function and clinical prognosis in PCOS patients.
7.Research Progress in Chinese Materia Medica Regulation of Glucose Metabolism Reprogramming Intervention in Gastric Precancerous Lesions Based on Hypoxia Microenvironment
Xiaolong WANG ; Ruiping SONG ; Pengcheng DOU ; Zhuangzhuang FENG ; Xiaowei SUN ; Dongxu LEI ; Jing YANG ; Qingshan NAN ; Jin SHU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):179-184
Precancerous lesions of gastric cancer is a key stage in the development of gastric cancer.The reprogramming of glucose metabolism is a prominent feature of precancerous lesions of gastric cancer.Hypoxic microenvironment and hypoxia-inducible factors are important factors influencing the occurrence of glucose metabolic reprogramming.This article summarized the relationship between hypoxic microenvironment and the reprogramming of glucose metabolism in precancerous lesions of gastric cancer,and concluded the relevant research on TCM compounds and effective components to improve hypoxic microenvironment and further regulate glycolysis for the treatment of this disease.It was concluded that the mechanism may be the inhibition of angiogenesis,regulation of signaling pathways and key proteins of glycolysis,expression of multiple enzymes,reduction of lactate secretion,inhibition of cell malignant proliferation and invasion.It explored the mechanism of Chinese materia medica in improving hypoxic microenvironment and regulating glycolysis,so as to provide reference for the prevention and treatment of precancerous lesions of gastric cancer.
8.Epidemiological analysis of the current prevalence of hepatitis B virus infection among pregnant and postpartum women in China from 2021 to 2023
Dongxu HUANG ; Xiaoyan WANG ; Qian WANG ; Ya GAO ; Yu WANG ; Changhe WANG ; Ailing WANG
Chinese Journal of Hepatology 2024;32(5):449-452
Objective:To analyze hepatitis B serologic tests and the current prevalence of hepatitis B virus (HBV) infection among pregnant and postpartum women in China from 2021 to 2023.Methods:Data on managing the prevention of mother-to-child transmission of HIV, syphilis, and hepatitis were retrieved from the National Information System. A positive serum HBsAg test was used to define HBV infection. The χ2 test was used to compare the coverage rate of the hepatitis B serologic test across different years, in early-stage pregnancy, and the current HBV infection in pregnant and postpartum women. A two-sided P value of <0.05 was considered a statistically significant difference. Results:The coverage rate for hepatitis B serological detection in pregnant (including intrapartum) and postpartum women and early-stage pregnancy rose from 99.68% (10?463?059/10?496?883) and 82.96% (8?707?765/10?496?883) to 99.94% (8?678?777/8?684?387, P ?0.001) and 88.87% (7?717?857/8?684?387, P ?0.001) in China between 2021 and 2023. The current prevalence rate of HBV infection decreased from 4.98% (521?479/10?463?059) in 2021 to 4.56% (396?148/8?678?777) in 2023 among pregnant and postpartum women ( P ?0.001). The current prevalence rate of HBV infection ranged from 1.53% to 10.39% among pregnant and postpartum women in various provinces of China in 2023. Conclusion:The coverage rate for hepatitis B serologic tests in China increased significantly between 2021 and 2023 in pregnant and postpartum women. Therefore, the current prevalence rate of HBV infection has decreased significantly in pregnant and postpartum women, but a regional difference still exists.
9.Application of post competency-oriented "TECK" teaching model in clinical pathology internship teaching
Wei DOU ; Dongxu WANG ; Zhongwei AI ; Fan YANG ; Yonghong HUANG ; Dandan CUI ; Haiying DONG
Chinese Journal of Medical Education Research 2024;23(10):1384-1389
Objective:To investigate the effects of the "TECK" (theoretical class, experimental course, case discussion, and knowledge reinforcement) teaching model oriented by post competency in clinical pathology internship teaching.Methods:The intern students from 2015 to 2019 in the pathology direction of clinical medicine in the School of Pathology, Qiqihar Medical College, who were enrolled in the internship from 2019 to 2023, were selected as the research objects.We enrolled 32 medical students from grades 2017, 2018, and 2019 (research group) and 24 medical students from grades 2015 and 2016 (control group) who would participate in pathology internships. The control group adopted the traditional internship mode, while the research group adopted the competency-oriented "TECK" teaching mode. After the internship, the two groups were compared for internship assessment score and surveyed for post competency. With the use of SPSS 18.0 statistical software. Continuous data were presented as (mean±standard deviation) and t-test was used for comparison between groups. Count data were expressed in the number of cases, and chi-square test was used for comparison between groups.The significance level α was 0.05. Results:The research group showed significantly higher scores of skill assessment (82.81±4.20 vs. 79.58±5.09) and pathological diagnosis assessment (80.28±4.23 vs. 76.21±4.58) than the control group (both P<0.05), with no significant difference in the score of theoretical knowledge ( P>0.05). In terms of post competency, the research group was superior to the control group in clinical skills and medical care ability (12.38±0.94 vs. 11.35±0.76), disease prevention and health promotion ability (6.28±0.92 vs. 4.48±0.93), interpersonal communication and information management ability (19.81±1.09 vs. 17.00±1.28), and teamwork and scientific research ability (11.44±1.27 vs. 9.25±0.87; all P<0.05). There were no significant differences between the two groups in core values and professional literacy and medical knowledge and lifelong learning (both P>0.05). Conclusions:In undergraduate internships, the competency-oriented "TECK"teaching mode can significantly improve students' clinical operation and pathological diagnosis ability, and effectively cultivate their abilities of clinical skills and medical care, disease prevention and health promotion, interpersonal communication and information management, teamwork and scientific research.
10.Effects of miR-451 on glycolysis and apoptosis of breast cancer cells by regulating Rho/ROCK1 pathway
Dongxu FENG ; Wei WU ; Pingfa GAO ; Jun WANG ; Lijuan SHI ; Dawei CHEN ; Wenbing LI ; Meifeng ZHANG
Journal of International Oncology 2023;50(8):449-456
Objective:To explore the effects of miR-451 on glycolysis and apoptosis of breast cancer cells by regulating the Rho/ROCK1 pathway.Methods:Breast cancer MCF7 cells were divided into breast cancer cells (BC) group, breast cancer cells + miR-451-NC (MN) group, breast cancer cells + miR-451 inhibitor (MI) group, breast cancer cells + miR-451 mimic (MM) group, breast cancer cells + lysophosphatidic acid (BL) group, breast cancer cells + fasudil (BF) group, and breast cancer cells + miR-451 mimic + fasudil (MF) group. Glucose uptake detection kit and lactate detection kit were used to detect cell glycolysis, DAPI staining was used to detect cell apoptosis, Western blotting was used to detect Rho/ROCK1 pathway protein expression, and double luciferase reporting assay was used to confirm the interaction between miR-451 and Rho/ROCK1.Results:The glucose intake of cells in the BC group, MN group, MI group and MM group were (14.22±2.36) ×10 5 mg/h, (14.20±2.37) ×10 5 mg/h, (21.55±2.43) ×10 5 mg/h, (6.19±1.34) ×10 5 mg/h ( F=5.30, P<0.001), respectively, and lactic acid production were (1.52±0.21) ×10 5 μg/h, (1.53±0.22) ×10 5 μg/h, (2.05±0.32) ×10 5 μg/h, (0.54±0.12) ×10 5 μg/h ( F=3.28, P=0.008), respectively. The apoptosis rates were (10.13±1.35) %, (10.16±1.37) %, (5.36±1.24) %, (28.47±2.56) % ( F=6.36, P<0.001), respectively. The expressions of Rho protein were 2.31±0.46, 2.32±0.41, 2.95±0.35, 1.05±0.25 ( F=2.86, P=0.017), respectively. The expressions of ROCK1 protein were 2.51±0.41, 2.52±0.42, 3.05±0.33, 1.15±0.13 ( F=2.43, P=0.035), and there were statistically significant differences between the MN and MI groups, MN and MM groups, MI and MM groups (all P<0.05). The glucose intake in the BC group, BL group and BF group were (14.22±2.36) ×10 5 mg/h, (21.54±2.40) ×10 5 mg/h, (6.20±1.35) ×10 5 mg/h ( F=5.33, P<0.001), respectively. Lactic acid production were (1.52±0.21) ×10 5 μg/h, (2.01±0.30) ×10 5 μg/h, (0.55±0.12) ×10 5 μg/h ( F=3.28, P=0.008), respectively. The apoptosis rates were (10.13±1.35) %, (5.34±1.22) %, (28.44±2.54) % ( F=6.45, P<0.001). The expressions of Rho protein were 2.31±0.46, 2.94±0.45, 1.01±0.24 ( F=2.40, P=0.037), respectively, and the expressions of ROCK1 protein were 2.51±0.41, 3.08±0.42 and 1.13±0.12, respectively ( F=2.38, P=0.039). The pairwise comparisons among the three groups were statistically significant (all P<0.05). In the MF group, glucose intake was (3.21±0.89) ×10 5 mg/h, lactic acid production was (0.33±0.04) ×10 5 μg/h, apoptosis rate was (38.01±2.87) %, Rho protein expression was 0.55±0.14, and ROCK1 protein expression was 0.51±0.10. There were statistically significant differences among the MM group, BF group and MF group ( F=4.53, P=0.001; F=4.26, P=0.002; F=6.12, P<0.001; F=4.06, P=0.002; F=9.72, P<0.001), and there were statistically significant differences between the MF group and BF group (all P<0.05). Dual luciferase report showed that miR-451 transfection significantly decreased the luciferase activity of ROCK1-3'-UTR-WT (0.59±0.03 vs. 1.01±0.05, t=17.64, P<0.001), but had no significant effect on mutated genes (1.01±0.07 vs. 1.02±0.04, t=0.30, P=0.767) . Conclusion:Overexpression of miR-451 can significantly inhibit glycolysis of breast cancer cells and promote apoptosis of breast cancer cells, the mechanism of which may be related to inhibition of Rho/ROCK1 pathway.

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