1.Daurisoline Inhibits Progression of Triple-Negative Breast Cancer by Regulating the γγ-Secretase/Notch Axis
Xiangyi ZHAN ; Xiaoyong CHEN ; Mei FENG ; Kuo YAO ; Kefan YANG ; Hui JIA
Biomolecules & Therapeutics 2025;33(2):331-343
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.
2.Daurisoline Inhibits Progression of Triple-Negative Breast Cancer by Regulating the γγ-Secretase/Notch Axis
Xiangyi ZHAN ; Xiaoyong CHEN ; Mei FENG ; Kuo YAO ; Kefan YANG ; Hui JIA
Biomolecules & Therapeutics 2025;33(2):331-343
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.
3.Daurisoline Inhibits Progression of Triple-Negative Breast Cancer by Regulating the γγ-Secretase/Notch Axis
Xiangyi ZHAN ; Xiaoyong CHEN ; Mei FENG ; Kuo YAO ; Kefan YANG ; Hui JIA
Biomolecules & Therapeutics 2025;33(2):331-343
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.
4.Interpretation and Examples:Key Updates in CONSORT 2025
Zelei DAI ; Renjie ZHAO ; Kefan LI ; Yonggang ZHANG ; Nian LI ; Wenjie YANG ; Lei LIU ; Lingmin CHEN
Journal of Sichuan University (Medical Sciences) 2025;56(3):678-685
Standardized clinical trial reporting is crucial for ensuring the scientific validity,reproducibility,and clinical translational value of reported results.The Consolidated Standards of Reporting Trials(CONSORT)statement,an internationally recognized guideline for randomized controlled trials(RCTs),has become an important reference standard for writing research papers in medicine since the 2010 version of CONSORT was published.With advancements in scientific research methodologies and the emergence of new forms of clinical trials,the CONSORT working group released an updated version in April 2025,published in journals such as The BMJ.Herein,we provide a systematic interpretation of the core revisions of CONSORT 2025,as well as a comparison with CONSORT 2010 to highlight the key differences.By providing practical,example-based recommendations,we aim to help domestic researchers apply the new guidelines efficiently,thereby improving the quality of clinical trial reports authored by domestic researchers.
5.Interpretation and Examples:Key Updates in SPIRIT 2025 Statement
Zelei DAI ; Renjie ZHAO ; Kefan LI ; Yonggang ZHANG ; Nian LI ; Wenjie YANG ; Lei LIU ; Lingmin CHEN
Journal of Sichuan University (Medical Sciences) 2025;56(3):686-696
A high-quality clinical trial protocol is the cornerstone for ensuring the scientific integrity and ethical compliance of a study.The Standard Protocol Items:Recommendations for Interventional Trials(SPIRIT)has become the international benchmark for developing clinical trial protocols since its release in 2013.To adapt to the developing trends of open science and patient-centered principles,the SPIRIT group completed a comprehensive update in 2025.While retaining its core structure,this updated guideline introduces a new open science module and incorporates several new elements,including patient and public involvement,trial monitoring,and data sharing,alongside substantial revisions of five pre-existing items.In this article,we critically examine the core revisions in SPIRIT 2025 and,through analysis of representative case studies,illustrate the practical application of the new reporting guideline in drafting trial protocols.Our goal is to to provide Chinese researchers with a valuable reference for understanding and implementing this new reporting guideline,thereby enhancing the quality and rigor of clinical trial protocols developed in the country.
6.Effects of empathy nursing on negative emotion, sleep quality and health literacy of home treatment patients with pulmonary tuberculosis
Kefan CHEN ; Jing GONG ; Jing XIE ; Jiao ZHENG ; Lijuan ZHU ; Shusheng YUAN
Chinese Journal of Practical Nursing 2022;38(7):506-512
Objective:To explore the effect of empathy nursing intervention on negative emotion, sleep quality and health literacy of patients with pulmonary tuberculosis.Methods:A total of 77 patients in Department of Infectious Diseases of People′s Hospital of Leshan from June 2019 to September 2020 were divided into intervention group ( n=39) and control group ( n=38) by random digits table method. The patients in the control group were given routine nursing, and the patients in the intervention group were given empathy nursing intervention on the basis of routine nursing. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI) and Health Literacy Management Scale (HeLMS) were used before and 12 weeks after intervention to evaluate the effects. Results:There was no significant difference in the total scores of HAMD, HAMA, PSQI and HeLMS between the two groups before intervention ( P>0.05), but after intervention, the scores of HAMD and HAMA in the intervention group were 10.64 ± 1.86, 12.64 ± 2.12, lower than those in the control group (14.63 ± 2.19, 15.11 ± 2.71). The differences were statistically significant ( t=-8.63, -4.46, P<0.05). The total score of PSQI and the scores of daytime dysfunction, use of hypnotic drugs, time of falling asleep, time of sleep, sleep quality, sleep disorder and sleep efficiency in the intervention group were 10.26 ± 1.65, 1.22 ± 0.22, 1.48 ± 0.23, 1.51 ± 0.27, 1.45 ± 0.26, 1.57 ± 0.22, 1.54 ± 0.21,1.49 ± 0.24, lower than those in the control group (13.07 ± 2.14, 1.92 ± 0.31, 1.75 ± 0.34, 1.95 ± 0.29, 2.02 ± 0.33, 1.84 ± 0.31, 1.72 ± 0.27, 1.87 ± 0.29). The differences were statistically significant ( t values were -11.45--3.27, all P<0.05). The total score of HeLMS and the scores of information acquisition, communication and interaction, and health improvement intention in the intervention group were 96.12 ± 14.71, 37.87 ± 5.83, 35.91 ± 5.13, 16.21 ± 2.53, higher than those in the control group (86.35 ± 14.12, 33.17 ± 5.27, 32.87 ± 5.42, 14.16 ± 2.19). The differences were statistically significant ( t values were 2.53-3.80, all P<0.05). Conclusions:Empathy nursing intervention can effectively alleviate the negative emotions of pulmonary tuberculosis patients, improve their sleep quality, and improve their health literacy level.
7.Distribution of 1 775 Strains of Bloodstream Infection Pathogens and Analysis of Drug Resistance in Our Hospital during 2011-2016
Ping'an FANG ; Kefan CHEN ; Bin YI ; Yu ZENG ; Jiameng LI ; Yujiao XIONG ; Shusheng YUAN
China Pharmacy 2017;28(29):4080-4085
OBJECTIVE:To provide reference for rational use of antibiotics in the clinic. METHODS:Blood culture positive specimens were collected from our hospital during Jan. 2011-Dec.2016. Distribution of bloodstream infection(BSI)pathogens and drug resistance were analyzed in our hospital retrospectively. RESULTS:During 2011-2016,26 034 blood culture specimens isolat-ed from inpatients of our hospital were examined,including 1 775 positive specimens with positive rate of 6.82%. The specimens mainly came from tumor hematology department(10.65%),neurosurgery department(8.28%)and pediatric department(8.00%). A total of 1 775 strains of pathogens were detected,including 967 strains of Gram-negative bacteria(54.48%)mainly as Escherich-ia coli,Klebsiella pneumoniae,649 strains of Gram-positive bacteria(36.56%)mainly as Coagulase negative Staphylococci, Staphylococcus aureus and 159 strains of fungus(8.96%)mainly as Candida albicans. E. coli and K. pneumoniae were resistant to common antibiotics to different extents,but sensitive to piperacillin sodium and tazobactam sodium,imipenem,meropenem. Aci-netobacter baumanii was highly resistant to enzyme inhibitors,cephalosporins,aminoglycosides,quinolones. Pseudomonas aerugi-nosa was sensitive to third-generation cephalosporins,aminoglycosides and quinolones. S. aureus was highly resistant to penicil-lins,cephalosporins and aminoglycosides. Resistance rate of Coagulase negative Staphylococci to most commonly used antibiotics was higher than 40%. Above two bacteria were sensitive to linezolid and vancomycin with resistance rate of 0. A total of 205 strains of ESBLs-producing E. coli(42.01%),64 strains of ESBLs-producing K. pneumoniae(30.33%)and 31 strains of Methicil-lin-resistant S.aureus(17.61%)were detected.No vancomycin-resistant Enterococcus or vancomycin-resistant S.aureus was detect-ed. CONCLUSIONS:BSI pathogens mainly distribute in tumor hematology department of our hospital. BSI pathogens mainly in-clude Enterobacteriaceae and Staphylococcus,and also involve fungus. The situation of drug resistance and enzyme production are not optimistic.Antibiotics,which are sensitive to the major pathogens,include carbapenems,linezolid and vancomycin.
8.DSF-Cu induces apoptosis of human nasopharyngeal carcinoma CNE-2 Z cells by affecting function of mitochondria and cytoskeleton
Yaping YANG ; Yawei WANG ; Mengjia LI ; Kefan ZHANG ; Xiaoxue SUN ; Zhihong LIANG ; Lixin CHEN ; Liwei WANG ; Haifeng YANG ; Linyan ZHU
Chinese Pharmacological Bulletin 2016;32(9):1208-1216,1217
Aim To study the mechanism of DSF-Cu induced apoptosis of human nasopharyngeal carcinoma CNE-2 Z cells by affecting the function of mitochondria and cytoskeleton. Methods The cell cycle,the rate of apotosis,the levels of intracellular ROS and MMP in CNE-2 Z cells were tested by flow cytometry after trea-ted with different concentration of DSF-Cu. The chan-ges of the cell surface morphology, ultrastructure, cell height, width and roughness were detected by AFM. The distribution and reorganization of cytoskeleton F-actin were observed by Laser scanning confocal micro-scope. Results Cells were incubated with different concentration of DSF-Cu ( 0 ~200 nmol · L-1 ) for 24 h, the apoptotic ratio increased significantly and the treatment of DSF-Cu resulted in a concentration-de-pendent accumulation of CNE-2Z cells in G2/M phase. Furthermore,the treatment of DSF-Cu was able to in-crease the production of intracellular ROS and decrease the MMP in CNE-2Z cells. In addition,AFM imaging showed that compared to the control group,with the in-crease of DSF-Cu concentration,the CNE-2Z cells be-came smaller, cytoplasm condensed, the height in-creased,and the surface roughness reduced. Moreover, the filopodia became shorter, shrinked and even com-pletely destroyed after treated with different concentra-tion of DSF-Cu. At last,the LSCM image showed that the fluorescence intensity of F-actin networks was de-creased, then the structure was rearranged and de-stroyed obviously by treated with DSF-Cu. Conclusion DSF-Cu can induce apoptosis and arrest cell cycle at G2/M phase in CNE-2Z cell through a mitochondria-dependent pathway. Above findings highlight the appli-cations of AFM at the single cell level for the investiga-tion of antineoplastic drug in nasopharyngeal carcinoma therapy.
9.Clinical observation on oxaliplatin reintroduction combined with raltitrexed as second-line chemotherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients
Lin LAI ; Encun HOU ; Yunxin LU ; Kefan CHEN ; Wenliang ZHU ; Yuanjun MO ; Zhiwei TAN
Chinese Journal of Clinical Oncology 2016;43(5):188-193
Objective:To investigate the efficacy and toxicity of oxaliplatin reintroduction combined with raltitrexed as second-line che-motherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients. Methods:The 48 evaluable pa-tients with advanced colorectal cancer following disease progression prior to the first-line chemotherapy were treated with oxaliplatin and raltitrexed (raltitrexed 3 mg/m2 ivgtt d1, oxaliplatin 100-130 mg/m2 ivgtt d1, q21d). All 48 patients were divided into two groups:Group A, non-oxaliplatin-based regimens as the first-line chemotherapy, 20 cases;Group B, oxaliplatin-based regimens as the first-line chemotherapy, 28 cases. Each group was evaluated every two cycles. Results:The response rates (RR) of Groups A and B were 30.0%(6/20) and 32.1%(9/28), the disease control rates (DCR) were 80.0%(16/20) and 75.0%(21/28), the median progression free survival time (mPFS) was 6.5 and 7.0 months, and the median overall survival time (mOS) was 10 and 13 months, respectively. No statistical sig-nificance was observed between the two groups in their RR, CR, mPFS, and mOS (P=0.264, 0.514, 0.713, 0.788), respectively. The most common adverse effects observed wereⅠ-Ⅱgrades of bone marrow suppression, aminotransferase abnormality, and digestive toxici-ties. The incidence of neurotoxicity (Ⅰ-Ⅱgrades) between the two groups was similar. Conclusion:Instead of irinotecan combined with raltitrexed, oxaliplatin reintroduction combined with raltitrexed for second-line chemotherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients is feasible.
10.Effect of hypothyroxinemia on the emotion in developing rats
Daqing CHEN ; Wei DUAN ; Yan QIAN ; Kefan MIAO ; Yanke ZHU ; Zhenyao DING
International Journal of Pediatrics 2014;41(1):84-87
Objective To investigate the effect of hypothyroxinemia on emotion and hippocampus neurons in developing rats.Methods Sixty-nine healthy postnatal day (PD) 1 rats were randomly divided into control group (n =36) and experimental group (n =33).On PD1,experimental group was bilaterally thyroidectomized to establish hypothyroxinemia model,the control group was only given thyroid exposure operation without thyroid resection.On PD10,21,40,serum triiodothyronine (T3),thyroxine (T4),thyrotropicstimulating hormone (TSH) were detected by radioimmunoassay.Tail suspension test,forced swimming test,the elevated-plus maze and open field were respectively employed to detect the anxiety/depression like behavior on PD30,31,32,33.Nisslg staining was used to determine the survival of neurons at PD10,21,40 in hippocampus CA1,CA3,DG regions.Results Serum T4 levels on PD10,21,40 in experimental group decreased significantly as compared with control group (P <0.01),while there was no significant difference in serum T3 or TSH level (P > 0.05).In the tail suspension test,immobility time of experimental group [(197.00 ± 19.50) s] was longer than control group [(158.33 ± 32.90) s,P <0.05].In the forced swimming test,immobility time of experimental group[(92.11 ± 35.24) s] was longer than control group [(62.00 ± 23.73) s,P < 0.05].In the elevated plus-maze test,total number of arm entries and closed arm entries in experimental group were increased as compared with control group(P < 0.05),percentage of closed arm/total time of experimental group was decreased as compared with control group(P < 0.05).In the open field,there was no obvious difference between the two groups(P > 0.05).On PD10,21,40,the amount of neurons in DG region of experimental group were less than control group(P <0.05),while there was no significant difference in CA1 or CA3 on PD10,21,40(P >0.05).Contusions Hypothyroxinemia can cause depression,hyperactivity and hippocampus neuron damage of developing rats.

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