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.Research progress on the intervention of energy metabolism disorders in chronic heart failure by active ingredients of traditional Chinese medicine through regulating circadian rhythms
Ruiqi GUO ; Sutong WANG ; Zhaohui LYU ; Yan LI ; Renwei GUAN ; Xiao LI
China Pharmacy 2026;37(5):670-675
The onset and progression of chronic heart failure (CHF) are closely associated with myocardial energy metabolism disorders, and this pathological process significantly affects patient prognosis. Traditional Chinese medicine (TCM), grounded in time-based medical theories such as the correspondence between humans and nature and the theory of circadian flow of meridians (Ziwu Liuzhu), exhibits intrinsic consistency with modern circadian rhythm theory, providing a unique theoretical framework for understanding and intervening in CHF from a temporal perspective. This article systematically explores the impact of circadian rhythms on energy metabolism and the potential mechanisms by which TCM active ingredients intervene in CHF through a review of relevant literature. It is found that various TCM active ingredients, including flavonoids (such as nobiletin), alkaloids (such as berberine), and polyphenols (such as resveratrol), can improve mitochondrial function, promote fatty acid oxidation, enhance glucose uptake and utilization efficiency, maintain metabolic balance, and alleviate oxidative stress and inflammatory responses in myocardial cells by regulating the expression and rhythms of core circadian clock genes such as CLOCK, BMAL1, PER, and CRY. These actions thereby correct energy metabolism disorders and improve cardiac function. Further exploration of the interaction mechanisms between these components and the circadian rhythms holds promise for providing novel theoretical foundations and potential intervention strategies for the prevention and treatment of CHF.
3.Influenza surveillance results in Ordos City in 2017 - 2023
Xiaomin ZHANG ; Hongtao XIAO ; Sheng WANG ; Rong SUN ; Shangwu JIN ; Di ZHANG ; Jiming HAO ; Jialin LYU ; Chunyan YANG
Journal of Public Health and Preventive Medicine 2026;37(2):54-58
Objective To analyze the influenza-like illness (ILI) data in Ordos City from 2017 to 2023 and conduct nucleic acid detection of the virus to understand the local influenza epidemic situation, and to provide a reliable basis for influenza prevention and control in the city. Methods Real-time quantitative polymerase chain reaction (qPCR) was used to identify virus subtypes in ILI throat swab samples. Comparisons of positive rates were conducted using the chi-square test, with a significance level of α=0.05. Results From 2017 to 2023, a total of 3,283,434 outpatient and emergency visits were recorded at the Ordos City Central Hospital, including 74,159 ILI cases, with an ILI proportion of 2.26%. The majority of ILI cases (74.43%) occurred in children aged 0~14 years old. The overall positive rate of influenza virus nucleic acid detection was 10.87%, with the highest proportion being subtype A (seasonal H3) at 43.03%. The highest detection rate was observed in the 5~14 years age group, with statistically significant differences in positive rates across age groups (χ2=155.638, P<0.001). Influenza peaks occurred mainly from November to March of the following year. From January to April, three types of influenza were prevalent alternately or mixed, while from October to December, subtype A (seasonal H3) predominated. Positive rates varied significantly across months (χ2=250.923, P<0.001). The temporal trends of ILI proportions and PCR-positive rates were consistent. Conclusion Influenza in Ordos City exhibits distinct seasonal and age distribution characteristics, with alternating or mixed circulation of three virus types. Continued efforts are needed to strengthen influenza surveillance, especially the prevention and control of influenza in infants and adolescents.
4.MAUP Effect on Spatial Pattern of Pseudostellaria heterophylla Production Regions in China
Leting ZHANG ; Tao ZHOU ; Chengdong XU ; Zhixian JING ; Chenghong XIAO ; Hui WANG ; Tingting SHI ; Jiawei HUANG ; Xiaobo ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):183-191
ObjectiveTo investigate the modifiable areal unit problem (MAUP) in the spatial pattern of Pseudostellaria heterophylla production regions and reveal the impact of statistical scales on the spatial distribution characteristics of this medicinal plant species. MethodsUsing multi-source data (literature records, field surveys, and statistical data), we systematically analyzed the spatial patterns across three administrative levels (provincial, prefectural, and county scales). Spatial autocorrelation (Moran's I) analysis, high-low clustering (Getis-Ord General G), and hot/cold spot analysis (Getis-Ord Gi*) were employed. ResultsThe literature-based analysis showed that the production regions of P. heterophylla presented random distribution on the provincial scale and significant aggregation on the prefectural scale. The field survey data showed that the production regions displayed random distribution on the provincial scale but significant aggregation on both prefectural and county scales. The statistical data revealed that the production regions lacked spatial autocorrelation on the provincial scale but demonstrated significant aggregation on prefectural and county scales. ConclusionMAUP effects have substantive implications for understanding and decision-making in the arrangement of medicinal plant production regions. The county scale proves to be the most sensitive and explanatory level for analyzing the spatial pattern of P. heterophylla production regions, providing a critical foundation for habitat modeling, suitability evaluation, and ecological cultivation planning of medicinal plants.
5.Acupuncture combined with blade needle therapy for knee osteoarthritis:a randomized controlled trial.
Xiao LI ; Yujie CUI ; Wenjin YANG ; Yuanyuan LI ; Xiao GUO ; Di LIU ; Mengyun YU ; Hui HU ; Hua LI
Chinese Acupuncture & Moxibustion 2025;45(11):1571-1576
OBJECTIVE:
To observe the clinical efficacy and safety of acupuncture combined with blade needle therapy for knee osteoarthritis (KOA).
METHODS:
A total of 60 patients with KOA were randomly divided into an observation group and a control group, 30 cases each group. The control group received acupuncture at Neixiyan (EX-LE4),Dubi (ST35), Yinlingquan (SP9), Liangqiu (ST34), Xuehai (SP10), Yanglingquan (GB34) and Zusanli (ST36) on the affected side, once every other day, 3 times a week. The observation group received blade needle therapy on the basis of the treatment in the control group, once every 3 days, 2 times a week. Both groups were treated for 4 weeks. Before treatment, after 2, 4 weeks of treatment, and after 1 month of treatment completion (in follow-up), the scores of pain visual analogue scale (VAS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and Lequesne index were observed in the two groups, and the clinical efficacy and safety were evaluated.
RESULTS:
After 2, 4 weeks of treatment and in follow-up, the pain VAS scores, Lequesne index scores, and pain, stiffness, function scores of WOMAC in both groups were decreased compared with those before treatment (P<0.05), and the VAS scores, Lequesne index scores and pain, function scores of WOMAC in the observation group were lower than those in the control group (P<0.05). The effective response rate in the observation group was 76.7% (23/30), while that in the control group was 70.0% (21/30), there was no statistically significant difference in the effective response rates between the two groups (P>0.05). No adverse reactions were observed in either group.
CONCLUSION
Acupuncture combined with blade needle therapy could alleviate pain and promote functional recovery in KOA patients, and achieve long-lasting improvements.
Humans
;
Osteoarthritis, Knee/physiopathology*
;
Acupuncture Therapy/instrumentation*
;
Male
;
Female
;
Middle Aged
;
Aged
;
Acupuncture Points
;
Treatment Outcome
;
Adult
;
Needles
;
Combined Modality Therapy
6.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
7.Review, revision, and prospect of list of substances with both edible and medicinal values in China.
Xin-Yuan SUN ; Ya-Ping ZHENG ; Kang-Meng SUN ; Chun-Nian HE ; Pei-Gen XIAO
China Journal of Chinese Materia Medica 2025;50(2):346-355
The thought of medicine and food homology and substances with both edible and medicinal values are an important part of China's excellent traditional culture and medicine treasure, playing an important role in human diet and health maintenance for thousands of years. Substances with both edible and medicinal values are a standardized name governed by existing regulations, and many substances with both edible and medicinal values in the list lack important information such as original plants and edible and medicinal parts. Some substances change as the relevant regulations change, which confuses the use and regulation. According to the definition and inclusion conditions of substances with both edible and medicinal values in the Regulation of Substances with Both Edible and Medicinal Values Catalogue, this paper comprehensively reviewed the first batch of 87 substances with both edible and medicinal values published in 2002 by collecting information and investigating the practical application. Some substances supplemented, deleted, and revised were analyzed and discussed, and a complete revised list was compiled, encompassing a total of 90 substances, which were when combined with the 19 substances of the last three batches(published in 2019, 2023, and 2024), amounted to a total of 109 substances. In addition, the substances not currently in the published list but have both edible and medicinal values according to the latest definition were summarized, which revealed at least 27 other substances. Therefore, there were at least 136 substances with both edible and medicinal values. Additionally, the potential substances that could be included in the list of substances with edible and medicinal values were prospected, providing a focus for future expansion of the list. This paper systematically reviewed and revised the list of substances with both edible and medicinal values to lay a foundation for the regulatory authorities to revise the catalog of these substances and provide basic information for promoting the new quality productive forces in the health field and boosting the orderly and rapid development of the big health industry.
China
;
Humans
;
Drugs, Chinese Herbal/standards*
;
Plants, Medicinal/chemistry*
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Medicine, Chinese Traditional
8.Comparison on odor components before and after processing of Cervi Cornu Pantotrichum based on electronic nose, HS-GC-MS, and odor activity value.
Xiao-Yu YAO ; Ke SHEN ; Di WU ; Xiao-Fei SUN ; Chun-Qin MAO ; Li FU ; Xiao-Yan WANG ; Hui XIE ; Tu-Lin LU
China Journal of Chinese Materia Medica 2025;50(2):421-431
Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis*
;
Electronic Nose
;
Gas Chromatography-Mass Spectrometry/methods*
;
Animals
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Volatile Organic Compounds/analysis*
;
Deer
;
Drugs, Chinese Herbal/chemistry*
9.Development goals and strategies of ecological agriculture of Chinese materia medica.
Chuan-Zhi KANG ; Si-Qi LIU ; Bang-Xing HAN ; Tao ZHOU ; Xiao WANG ; Da-Hui LIU ; Ye YANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2025;50(1):42-47
This paper aims to contribute to guaranteeing the stable development and enhancing the understanding of ecological agriculture of Chinese materia medica so that the national strategy and industrial demand can be better served. It first introduces current traditional Chinese medicine(TCM)policy and industrial development status from five aspects, including policy guarantee, theoretical support, technological innovation, standardization system, and brand influence. Then, the paper analyzes the development dilemma of TCM agriculture in production and quality increase and ecological environment protection. It also proposes the development goals of ecological agriculture of Chinese materia medica that meet the current industrial development demand, which are reducing chemical fertilizers, pesticides, and carbon emissions, improving quality, increasing efficiency, and protecting ecological environment. In addition, the new development goals are interpreted through case studies. Finally, this paper proposes four development strategies for ecological agriculture of Chinese materia medica: conducting research on the pattern and spatial and temporal variations of nationwide TCM production areas; studying the internal and external ecological memories of medicinal plant growth from the perspectives of genetic variations and environmental adaptation variations and elucidating their contributions to the formation of quality; carrying out selection and breeding of stress-resistant varieties for ecological agriculture of Chinese materia medica, the optimization of key technologies for soil improvement and restoration and green prevention and control against diseases and pests, and the improvement of quality; carrying out research on the quality assurance and value realization of ecological products made from TCM. This research can provide guidance for policy formulation, theoretical development of the discipline, and the enhancement of industrial technology for ecological agriculture of Chinese materia medica.
Agriculture/methods*
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China
;
Drugs, Chinese Herbal
;
Plants, Medicinal/chemistry*
;
Ecosystem
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Materia Medica
;
Medicine, Chinese Traditional
10.New strategy and method in traditional Chinese medicine compatibility for detoxification based on component-target-effect interaction.
Zhao-Fang BAI ; Wei SHI ; Yuan GAO ; Jia-Bo WANG ; Xiao-He XIAO
China Journal of Chinese Materia Medica 2025;50(4):853-859
The safety of traditional Chinese medicine(TCM) has always been taken very seriously, and rich and valuable theories and experiences have been developed to ensure the safe and precise use of TCM in clinical practices. In recent years, the cognitive theory of toxicity of TCM, has undergone a profound change. TCM is characterized by the existence of intrinsic toxicity, idiosyncratic toxicity, and indirect toxicity related to organic factors. Therefore, the traditional theories and experiences of TCM, which focus on the prevention and control of intrinsic toxicity, fail to be used for the development of risk prevention and control countermeasures for newly discovered TCM with idiosyncratic toxicity and indirect toxicity. Accordingly, based on the toxicity classification and mechanism characteristics of TCM, this paper proposed a new strategy and method in TCM compatibility for detoxification based on componenttarget-effect interaction. The strategy based on component-target-effect interaction is to carry out TCM compatibility for detoxification by blocking the occurrence of drug-mediated damage and promoting damage repair through component interactions, target interactions,and/or effect interactions. Based on this theory, the paper established a strategy for TCM compatibility that aligned with the cognitive theory of toxicity of TCM, so as to achieve safe and precise use of TCM in clinical practices. The strategy based on component-targeteffect interaction has been exemplarily applied to the development of countermeasures to reduce the toxicity of TCM, including Polygonum Multiflorum, Epimedii Folium, and Psoraleae Fructus, and a new mechanism of Glycyrrhizae Radix et Rhizoma to " harmonize various medicines and detoxify myriad poisons" was illustrated, providing a scientific basis for the safe and precise use of TCM in clinical practice. This paper explained the scientific connotation, application forms, and application examples of componenttarget-effect interaction, aiming to provide a theoretical and methodological basis for guaranteeing the precise use of TCM in clinical practice and innovate the theories and methods of TCM compatibility for detoxification.
Drugs, Chinese Herbal/chemistry*
;
Humans
;
Medicine, Chinese Traditional/methods*
;
Animals
;
Drug-Related Side Effects and Adverse Reactions/prevention & control*


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