1.Lysosomes as Regulators of Cancer Stemness and Drug Resistance
Fa-Xiao ZHOU ; Di-Ping YU ; Si-Qi TAN ; Hong-Yu DUAN ; Xiao-Ming WU
Progress in Biochemistry and Biophysics 2026;53(4):951-967
Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.
2.Construction and Application of a Real-World Cohort of Community-Acquired Pneumonia Based on a Multimodal Large-Scale Traditional Chinese Medicine Big Data Platform
Zhichao WANG ; Xianmei ZHOU ; Fanchao FENG ; Mengqi WANG ; Xin WANG ; Bin KANG ; Xiaofan YU ; Xiaoxiao WANG ; Lei XIAO ; Juan LI ; Zhichao ZHANG ; Ye MA ; Yeqing JI ; Xin TONG ; Zhuoyue WU ; Jia LIU
Journal of Traditional Chinese Medicine 2026;67(9):961-965
This paper introduces a real-world cohort research model for community-acquired pneumonia (CAP) based on the Jiangsu Traditional Chinese Medicine (TCM) Dominant Diseases Diagnosis and Treatment Data Platform. Firstly, data cleaning is performed by standardizing diagnosis, symptoms, treatment and imaging, intelligently extracting unstructured information, and cleaning and constructing a standardized database. Secondly, for cohort establishment, CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly, in terms of protocol design, the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria, estimate sample size, define interventions, outcomes and economic evaluations, providing a reference for real-world TCM research on CAP.
3.Construction and Application of a Real-World Cohort of Community-Acquired Pneumonia Based on a Multimodal Large-Scale Traditional Chinese Medicine Big Data Platform
Zhichao WANG ; Xianmei ZHOU ; Fanchao FENG ; Mengqi WANG ; Xin WANG ; Bin KANG ; Xiaofan YU ; Xiaoxiao WANG ; Lei XIAO ; Juan LI ; Zhichao ZHANG ; Ye MA ; Yeqing JI ; Xin TONG ; Zhuoyue WU ; Jia LIU
Journal of Traditional Chinese Medicine 2026;67(9):961-965
This paper introduces a real-world cohort research model for community-acquired pneumonia (CAP) based on the Jiangsu Traditional Chinese Medicine (TCM) Dominant Diseases Diagnosis and Treatment Data Platform. Firstly, data cleaning is performed by standardizing diagnosis, symptoms, treatment and imaging, intelligently extracting unstructured information, and cleaning and constructing a standardized database. Secondly, for cohort establishment, CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly, in terms of protocol design, the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria, estimate sample size, define interventions, outcomes and economic evaluations, providing a reference for real-world TCM research on CAP.
4.Epidemiological characteristics of foodborne disease outbreaks in Wuhan, Hubei Province from 2006 to 2023
Yue ZHOU ; Mengdie SHI ; Xiao WANG ; Xiaomin WU ; Yating WU
Shanghai Journal of Preventive Medicine 2025;37(7):549-555
ObjectiveTo analyze the epidemiological characteristics of foodborne disease outbreaks in Wuhan from 2006 to 2023, and to provide a scientific basis for the development of foodborne disease prevention and control measures. MethodsDescriptive statistical analyses were performed on foodborne disease outbreaks confirmed by the district and municipal center for disease control and prevention (CDC) in Wuhan from 2006 to 2023, and the attack rate and case fatality rate were calculated as well. ResultsA total of 182 foodborne disease outbreaks were reported in Wuhan from 2006 to 2023, with a cumulative of 2 820 cases. Among which, 3 cases were dead, with an annual average attack rate of 1.22% and a case fatality rate of 0.11%. The highest number of outbreaks occurred in collective canteens (43.96%, 80/182), the highest attack rate was observed in catering facilities (11.03%), and the highest case fatality rate was found in households (1.45%). Among the foodborne disease outbreaks with identified etiologies, microbial factors were the leading causes (36.26%, 66/182), with the main pathogens being norovirus, Bacillus cereus, and other unspecified bacteria. Fungal factors were mainly attributed to poisonous mushrooms, with a relatively high fatality rate of 2.22% (2/90). Outbreaks caused by bacterial factors were more common in the central urban area (30.28%, 33/109), while fungal-related outbreaks were more frequent in the outlying urban areas (24.66%, 18/73). ConclusionCollective canteens are the main venues for foodborne disease outbreaks in Wuhan. Microbial factors are the main pathogenic factors, and poisonous mushrooms are the leading causes to death. It is necessary to strengthen the supervision on collective canteens, carry out various forms of public awareness campaigns on poisonous mushroom poisoning, and, if required, cooperate with the gardening department to eradicate wild poisonous mushrooms in the green belts. A collaborative cooperation involving multiple departments is essential to reduce the occurrence of foodborne disease outbreaks.
5.Analyzing the influencing factors of occupational burnout among disease control and prevention staffs in Sichuan Province
Chaoxue WU ; Shuang DONG ; Liang WANG ; Xunbo DU ; Lin ZHAO ; Dan SHAO ; Quanquan XIAO ; Lijun ZHOU ; Chongkun XIAO ; Heng YUAN
China Occupational Medicine 2025;52(3):288-292
Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.
6.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.
7.Genome-wide DNA methylation and mRNA transcription analysis revealed aberrant gene regulation pathways in patients with dermatomyositis and polymyositis.
Hui LUO ; Honglin ZHU ; Ding BAO ; Yizhi XIAO ; Bin ZHOU ; Gong XIAO ; Lihua ZHANG ; Siming GAO ; Liya LI ; Yangtengyu LIU ; Di LIU ; Junjiao WU ; Qiming MENG ; Meng MENG ; Tao CHEN ; Xiaoxia ZUO ; Quanzhen LI ; Huali ZHANG
Chinese Medical Journal 2025;138(1):120-122
8.Quality changes of volatile oil and chlorogenic acid compounds during extraction process of Artemisiae Argyi Folium: process analysis based on chemical composition, physicochemical properties, and biological activity.
Dan-Dan YANG ; Hao-Zhou HUANG ; Xin-Ming CHEN ; Lin HUANG ; Ya-Nan HE ; Zhen-Feng WU ; Xiao-Ming BAO ; Ding-Kun ZHANG ; Ming YANG
China Journal of Chinese Materia Medica 2025;50(11):3001-3012
To explore the variation laws of volatile oil during the extraction process of Artemisiae Argyi Folium and its impact on the quality of the medicinal solution, as well as to achieve precise control of the extraction process, this study employed headspace solid phase microextraction gas chromatography-mass spectrometry(HS-SPME-GC-MS) in combination with multiple light scattering techniques to conduct a comprehensive analysis, identification, and characterization of the changes in volatile components and the physical properties of the medicinal solution during the extraction process. A total of 82 volatile compounds were identified using the HS-SPME-GC-MS technique, including 21 alcohols, 15 alkenes, 14 ketones, 9 acids, 6 aldehydes, 5 phenols, 3 esters, and 9 other types of compounds. At different extraction time points(15, 30, 45, and 60 min), 71, 72, 64, and 44 compounds were identified in the medicinal solution, respectively. It was observed that the content of volatile components gradually decreased with the extension of extraction time. Through multivariate statistical analysis, four compounds with significant differences during different extraction time intervals were identified, namely 1,8-cineole, terpinen-4-ol, 3-octanone, and camphor. RESULTS:: from multiple light scattering techniques indicated that at 15 minutes of extraction, the transmittance of the medicinal solution was the lowest(25%), the particle size was the largest(0.325-0.350 nm), and the stability index(turbiscan stability index, TSI) was the highest(0-2.5). With the extension of extraction time, the light transmittance of the medicinal solution improved, stability was enhanced, and the particle size decreased. These laws of physicochemical property changes provide important basis for the control of Artemisiae Argyi Folium extraction process. In addition, the changes in the bioactivity of Artemisiae Argyi Folium extracts during the extraction process were investigated through mouse writhing tests and antimicrobial assays. The results indicated that the analgesic and antimicrobial effects of the medicinal solution were strongest at the 15-minute extracting point. In summary, the findings of this study demonstrate that the content of volatile oil in Artemisiae Argyi Folium extracts gradually decreases with the extension of extraction time, and the variation in volatile oil content directly influences the physicochemical properties and pharmacological efficacy of the medicinal solution. This discovery provides important scientific reference for the optimization of Artemisiae Argyi Folium extraction processes and the development and application of process analytical technologies.
Oils, Volatile/pharmacology*
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Artemisia/chemistry*
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Gas Chromatography-Mass Spectrometry
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Drugs, Chinese Herbal/pharmacology*
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Chlorogenic Acid/pharmacology*
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Solid Phase Microextraction
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Quality Control
9.Studies on pharmacological effects and chemical components of different extracts from Bawei Chenxiang Pills.
Jia-Tong WANG ; Lu-Lu KANG ; Feng ZHOU ; Luo-Bu GESANG ; Ya-Na LIANG ; Guo-Dong YANG ; Xiao-Li GAO ; Hui-Chao WU ; Xing-Yun CHAI
China Journal of Chinese Materia Medica 2025;50(11):3035-3042
The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals
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Drugs, Chinese Herbal/isolation & purification*
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Mice
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Male
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Sleep Initiation and Maintenance Disorders/physiopathology*
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Humans
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Myocardial Infarction/drug therapy*
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Myocardial Ischemia/drug therapy*
10.Polarized light microscopic mineral phase authentication and health risk assessment of raw and calcined fossil mineral Chinese medicinal material Draconis Os.
Yan-Qiong PAN ; Zheng LIU ; Li-Wen ZHENG ; Ying ZHANG ; Liu ZHOU ; Xi-Long QIAN ; Fang FANG ; Xiao WU ; Sheng-Jin LIU
China Journal of Chinese Materia Medica 2025;50(15):4238-4247
This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis*
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Risk Assessment
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Minerals/chemistry*
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Fossils
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Humans
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Drug Contamination
;
Mass Spectrometry


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