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.Herbal Textual Research on Bambusae Succus in Famous Classical Formulas
Yu SHI ; Feng ZHOU ; Yihan WANG ; Yanmeng LIU ; Ming YANG ; Zhiping CHEN ; Jiangshan ZHANG ; Conglong XU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):231-239
This article systematically reviews and examines the historical evolution of Bambusae Succus as a medicinal material, covering aspects such as nomenclature, origin, geographical distribution, harvesting and processing methods, quality assessment, therapeutic effects and indications, by consulting ancient herbal texts, medical compendia, and modern literature. The aim is to provide a reference for the development and utilization of famous classical formulas containing this herb. Research indicated that Bambusae Succus was first documented in the Shennong Bencaojing during the Han dynasty, with Zhuli being the standard name used throughout history, alongside aliases like Zhuzhi, Zhuyou and Huoquan. Historically, the primary source of Bambusae Succus has been Phyllostachys nigra var. henonis(Danzhu), although other species such as Pleioblastus amarus and Bambusa emeiensis have also been used medicinally. Ancient records predominantly noted its origin in Yizhou(present-day Chengdu and surrounding areas in Sichuan) and the Wuling region(between present-day Hunan, Guangdong, Guangxi and Jiangxi provinces), while contemporary sources are mainly from regions south of the Yangtze River and southwestern China. Traditionally, Bambusae Succus was harvested from bamboo that had grown for exactly one year, today, it can be collected year-round without strict age requirements. Ancient preparation methods included direct fire roasting or dry distillation, whereas modern industrial production employs dry distillation, reflux extraction, and percolation. In terms of quality evaluation, ancient texts considered a sweet taste to be superior, while today, clarity and transparency are prioritized. Historically, Bambusae Succus was characterized as sweet and cold nature, targeting the lung and stomach meridians, with uses evolving from clearing heat and resolving phlegm to nourishing Yin, moistening dryness, and relaxing tendons and unblocking meridians. Modern descriptions classify it as sweet, bitter, and cold in nature, affecting the heart, liver, and lung meridians, with functions including clearing heat, resolving phlegm, and facilitating orifices. It is indicated for conditions such as stroke with phlegm confusion, lung heat with phlegm congestion, convulsions, epilepsy, excessive phlegm in febrile diseases, high fever with thirst, irritability during pregnancy, and tetanus, with more clearly defined applications. Based on the results of the research, it is recommended that when developing and utilizing famous classical formulas containing Bambusae Succus, the one-year-old Phyllostachys nigra var. Henonis, which has been highly praised throughout history, should be selected as the source material. Industrial production should adopt the dry distillation method. Furthermore, in-depth research should be conducted on the modern technological characterization of the traditional quality control indicator of sweet taste, and reasonable modern quality control standards should be established.
3.Research Progress on the Application of Novel Functional Materials for Rapid Detection of New Psychoactive Substances
Yi-Ming TIAN ; Yi-Bo YAN ; Di WEN ; Yan SHI
Journal of Forensic Medicine 2025;41(4):314-325
New psychoactive substances(NPS)have the characteristics of rapid turnover,wide varieties,and high abuse potential.It has become a major threat to global public safety.Currently,the forensic identification of NPS faces certain challenges in detection methods for effectiveness,sensitivity,accu-racy and resistance to matrix interference.Novel functional materials(NFM),with their high specific surface area,designability,specific recognition capability and signal amplification effects,provide a new path for advancing rapid detection techniques for NPS.This paper systematically reviews the innova-tive applications of NFM in the rapid detection of NPS over the past decade.By summarizing and analyzing the research and applications of NFM in laboratory detection and on-site rapid screening,it outlines the characteristics and advantages of different types of materials.Combined with the develop-ment trends of NFM in intelligent material design,interdisciplinary integration and portable integrated devices,it provides theoretical references for the development of rapid detection methods for NPS,which is conducive to improving the rapid detection ability of NPS in"anti-drug combat".
4.Clinical prognosis analysis of 177 cases bladder adenocarcinoma in a single center in China and comparison with SEER database
Tianxiang ZHANG ; Lu ZHANG ; Guoliang YANG ; Lianhua ZHANG ; Ming CAO ; Di JIN ; Ruiyun ZHANG ; Guanglei ZHUANG ; Yiran HUANG ; Wei XUE ; Haige CHEN
Chinese Journal of Urology 2025;46(3):166-172
Objective:To investigate the clinical and pathological characteristics, prognostic factors, and treatment outcomes of bladder adenocarcinoma.Methods:The data of 177 bladder adenocarcinoma patients treated at Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2003 to December 2023, and 2 687 bladder adenocarcinoma patients from the SEER database (2000—2021) were reviewed retrospectively. The clinicopathological and prognostic characteristics were compared between the two cohorts. Patients with urachal adenocarcinoma or primary bladder adenocarcinoma were included, while metastatic bladder adenocarcinoma from other sites and urothelial carcinoma with glandular components were excluded. The Chi-square test was used for comparison of categorical data, and propensity score matching (1∶1) was applied to match baseline data between the Renji and SEER cohorts. Kaplan-Meier survival curves were generated, and log-rank tests were used for comparisons. Univariate and multivariate Cox regression analyses were performed using the survival R package, with P-values calculated via Wald tests. Results:The proportion of localized bladder adenocarcinoma was significantly higher in the Renji cohort than in the SEER cohort [61.0% (108/177) vs. 19.4% (521/2 687), P<0.001], and mucinous adenocarcinoma was more common in Renji cohort [33.3% (59/177) vs. 22.6% (607/2 687), P<0.001]. After matching for baseline factors, including SEER stage and pathological grade, survival analysis revealed that the Renji cohort patients had slightly better survival compared to the SEER cohort [median survival: 55.4 (24.1, 196.2) months vs. 39.2 (13.6, 137.4)months, P=0.033]. Multivariate Cox analysis identified SEER stage [Renji cohort: HR=3.83 (95% CI 1.62-9.07), P=0.002; SEER cohort: HR=3.67 (95% CI 3.13-4.31), P<0.001] and pathological grade [Renji cohort: HR = 2.76 (95% CI 1.54-4.95), P=0.001; SEER cohort: HR=1.46 (95% CI 1.29-1.65), P<0.001] as independent prognostic factors. In the Renji cohort, no significant differences were observed in the median progression-free survival [40.1 (19.5, 91.6) months vs. 40.9 (12.8, not reached)months, P=0.976] and overall survival [79.3 (37.1, 195.8) months vs. 53.9 (16.4, 129.5)months, P=0.374] between patients receiving adjuvant chemotherapy and those not receiving it. However, among patients with lymph node-positive bladder adenocarcinoma, adjuvant chemotherapy significantly improved both progression-free survival [40.1 (38.2, 75.4) months vs. 12.2 (3.1, 12.2)months, P=0.004] and overall survival [68.2 (46.2, 84.5)months vs. 28.1 (4.3, 28.3)months, P=0.006]. Conclusions:Bladder adenocarcinoma is rare and associated with poor prognosis. Compared to the SEER cohort, Renji cohort patients had more localized disease, with no significant differences in other features. SEER stage and pathological grade were independent prognostic factors in both cohorts. Lymph node-positive bladder adenocarcinoma patients in the Renji cohort benefited significantly from adjuvant chemotherapy.
5.A hierarchical deep learning model based on whole slide imaging of cerebrospinal fluid cells for rapid diagnosis of meningeal carcinomatosis
Kun CHEN ; Xiangyu LI ; Qianqian XU ; Zhiyu XU ; Di WANG ; Huanhuan QIN ; Guangjie JIANG ; Haoqin JIANG ; Qiong ZHAN ; Mengxi GE ; Xin LI ; Chun XU ; Ming GUAN
Chinese Journal of Laboratory Medicine 2025;48(12):1558-1564
Objective:To develop a convolutional neural network model of whole slide imaging of cerebrospinal fluid cells for rapid and accurate identification and classification of tumor cells in cerebrospinal fluid.Methods:A total of 8 692 cerebrospinal fluid cytology smears from Huashan Hospital Affiliated to Fudan University from January 2nd, 2019, to December 27th, 2024. As randomly assigned, the training set included 4 941 benign and 1 745 malignant samples, while the validation set comprised of 1 368 benign and 638 malignant samples. Whole-slide digital images were acquired using a cytopathology scanner, cells (clusters) were annotated for classification, and a deep learning model was constructed via tiled image patches for cell detection and classification. Model performance was evaluated using accuracy, sensitivity, specificity, and other indicators. The classification efficiency of manual microscopy was compared.Results:The model achieved a mean precision of 96.75% for cerebrospinal fluid cell classification. For malignant tumor cells, the classification accuracy was 96.61% (mAP=98.36%, AUC=0.97). Subtype classification accuracies for epithelial/epithelioid tumors and small round cell tumors were 97.13% (AUC=0.98) and 95.58% (AUC=0.93), respectively. Compared with manual microscopy, which took (9.70±0.82) minutes for classifying 200 cells, (18.27±1.21) minutes for 500 cells, and often exceeded 60 minutes or infeasible for full slides, the AI model took (3.46±0.49) seconds for 200 cells, (6.76±0.82) seconds for 500 cells, and a median of 48.57 seconds for full slides ( P<0.001), representing an efficiency improvement of approximately 161-170 times, significantly enhancing diagnostic efficiency. Conclusion:This fully automated hierarchical deep learning model enables efficient and accurate tumor cell identification and classification in CSF, providing an effective auxiliary tool for the rapid diagnosis of meningeal carcinomatosis.
6.Risk factors and their predictive efficacy for early postoperative complications in elderly patients with hip fracture
Deen WAN ; Yongzhou YAN ; Feng SHUANG ; Hao LI ; Zhi ZENG ; Mudan HUANG ; Lu HAN ; Xiang PENG ; Di YANG ; Ming CHEN ; Qixin LIU
Chinese Journal of Trauma 2025;41(3):274-281
Objective:To investigate the risk factors and their predictive efficacy for early postoperative complications in elderly patients with hip fracture.Methods:A retrospective cohort study was conducted on the clinical data of 203 elderly patients with hip fracture admitted to the 908th Hospital of the Joint Logistics Support Force of the PLA and the First Affiliated Hospital of Nanchang University from January 2022 to December 2023, including 54 males and 149 females, aged 65-100 years [(80.5±7.7)years]. There were 96 patients with femoral neck fracture and 107 patients with intertrochanteric fracture. According to the AO/OTA classification, the fracture was classified as type 31A in 107 patients and type 31B in 96. Among them, 81 patients were treated with proximal femoral nail antirotation (PFNA), 65 with semi-hip arthroplasty, 52 with total hip arthroplasty (THA), and 5 with closed reduction and cannulated nail internal fixation. The patients were divided into complication group ( n=65) and non-complication group ( n=138) according to whether complications (mainly including delirium, lung infection, stress ulcer, and deep vein thrombosis of the lower limbs) occurred within 15 days after surgery. The gender, age, age stage, educational level, cause of injury, associated underlying diseases before surgery, AO/OTA classification, American Society of Anesthesiologists (ASA) classification, 5-factor modified frailty index (mFI-5) score, prognostic nutritional index (PNI), anesthesia method, operation method, operation time, intraoperative blood loss, length of hospital stay, etc., were recorded in the two groups. Univariate analysis and multivariate binary logistic regression analysis were used to evaluate the correlation between the above indexes and the occurrence of early postoperative complications in elderly patients with hip fracture and to determine their independent risk factors. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the predictive efficacy of each risk factor for the occurrence of early postoperative complications in elderly patients with hip fracture. Results:Univariate analysis showed a certain correlation between age, age stage, associated underlying diseases before surgery, AO/OTA classification, ASA classification, mFI-5 score, PNI, operation method, and length of hospital stay and the occurrence of early postoperative complications in elderly patients with hip fracture ( P<0.05), while gender, educational level, cause of injury, anesthesia method, operation time, and intraoperative blood loss were not correlated with the occurrence of early postoperative complications in elderly patients with hip fracture ( P>0.05). The results of multivariate binary logistic regression analysis showed that the associated underlying diseases before surgery ( OR=5.46, 95% CI 1.33, 22.39, P<0.05), mFI-5 score ( OR=15.90, 95% CI 5.36, 47.15, P<0.01), and PNI ( OR=0.70, 95% CI 0.60, 0.81, P<0.01) were significantly correlated with the occurrence of early postoperative complications in elderly patients with hip fracture. The results of ROC curve analysis showed that mFI-5 score (AUC=0.85, 95% CI 0.80, 0.91) and PNI (AUC=0.87, 95% CI 0.82, 0.93) had moderate predictive efficacy, while the early warning efficacy of associated underlying diseases was low (AUC=0.54, 95% CI 0.45, 0.62). The combination of the above risk factors was more effective in predicting early postoperative complications in elderly patients with hip fracture (AUC=0.95, 95% CI 0.92, 0.98). Conclusions:The mFI-5 score, PNI, and associated underlying diseases before surgery are independent risk factors for early postoperative complications in elderly patients with hip fracture. The mFI-5 score and PNI have a higher predictive efficacy than associated diseases before surgery on the occurrence of early postoperative complications in elderly patients with hip fracture, while the combination of the above risk factors provides a significantly better predictive performance.
7.Transzonal Projections and Follicular Development Abnormalities in Polycystic Ovary Syndrome
Di CHENG ; Yu-Hua CHEN ; Xia-Ping JIANG ; Lan-Yu LI ; Yi TAN ; Ming LI ; Zhong-Cheng MO
Progress in Biochemistry and Biophysics 2025;52(10):2499-2511
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.
8.Study on accumulation of polysaccharide and steroid components in Polyporus umbellatus infected by Armillaria spp.
Ming-shu YANG ; Yi-fei YIN ; Juan CHEN ; Bing LI ; Meng-yan HOU ; Chun-yan LENG ; Yong-mei XING ; Shun-xing GUO
Acta Pharmaceutica Sinica 2025;60(1):232-238
In view of the few studies on the influence of
9.Methods and Strategies Employed in Compatibility and Formulation of New Chinese Medicinal Material Resources
Wenhua MING ; Qingqing LI ; Caifeng LI ; Yeran WANG ; Lan WANG ; Yanwen LI ; Zhiyong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):248-256
Chinese medicinal materials serve as the material foundation of traditional Chinese medicine (TCM) culture. The sustainable development of Chinese medicinal material resources is a focal point in the modernization of TCM. With the increasing scarcity of Chinese medicinal material resources, the expansion of new Chinese medicinal material resources has become a crucial means for the sustainable utilization of these resources. New Chinese medicinal material resources refer to natural resources that have been newly discovered or developed, possessing potential medicinal value or healthcare functions, which fall outside the traditional application scope of herbal medicines. These resources have not yet been widely recognized or applied within the framework of traditional TCM theory. They specifically include artificial substitutes for endangered medicinal materials, new medicinal parts of medicinal plants, medicinal materials with expanded clinical applications, and foreign medicinal resources. The rational compatability and formulation of new Chinese medicinal material resources are essential pathways for integrating them into the TCM system. Due to the weak foundational research on new Chinese medicinal material resources in China, the characteristics of these resources that align with the TCM theory are not yet fully understood, posing numerous constraints on formulating prescriptions based on the traditional compatibility principles of TCM. This paper integrates the traditional formulation theory of TCM with modern data integration methods, proposing four formulation models for new TCM resources: synergistic compatibility, substitutive compatibility, symptom-based compatibility, and efficacy semantic compatibility. These models provide new insights for the application of new Chinese medicinal material resources, not only facilitating their rational use in clinical practice but also offering theoretical support for the development and compatibility research of these resources.
10.Methods and Strategies Employed in Compatibility and Formulation of New Chinese Medicinal Material Resources
Wenhua MING ; Qingqing LI ; Caifeng LI ; Yeran WANG ; Lan WANG ; Yanwen LI ; Zhiyong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):248-256
Chinese medicinal materials serve as the material foundation of traditional Chinese medicine (TCM) culture. The sustainable development of Chinese medicinal material resources is a focal point in the modernization of TCM. With the increasing scarcity of Chinese medicinal material resources, the expansion of new Chinese medicinal material resources has become a crucial means for the sustainable utilization of these resources. New Chinese medicinal material resources refer to natural resources that have been newly discovered or developed, possessing potential medicinal value or healthcare functions, which fall outside the traditional application scope of herbal medicines. These resources have not yet been widely recognized or applied within the framework of traditional TCM theory. They specifically include artificial substitutes for endangered medicinal materials, new medicinal parts of medicinal plants, medicinal materials with expanded clinical applications, and foreign medicinal resources. The rational compatability and formulation of new Chinese medicinal material resources are essential pathways for integrating them into the TCM system. Due to the weak foundational research on new Chinese medicinal material resources in China, the characteristics of these resources that align with the TCM theory are not yet fully understood, posing numerous constraints on formulating prescriptions based on the traditional compatibility principles of TCM. This paper integrates the traditional formulation theory of TCM with modern data integration methods, proposing four formulation models for new TCM resources: synergistic compatibility, substitutive compatibility, symptom-based compatibility, and efficacy semantic compatibility. These models provide new insights for the application of new Chinese medicinal material resources, not only facilitating their rational use in clinical practice but also offering theoretical support for the development and compatibility research of these resources.

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