Colorectal cancer is a common and malignant tumor in the digestive tract. Invasion and metastasis of cancer cells are key factors leading to the high mortality rate and postoperative recurrence of colorectal cancer. Chemotherapy is the main treatment method for preventing recurrence of this disease. However， there are many toxic side effects in clinical application， which seriously hinder the treatment process. Therefore， it is imperative to search for efficient and low-toxicity drugs. Traditional Chinese medicine （TCM） has a long history of treating colorectal cancer and offers advantages such as safety， effectiveness， multiple targets， multiple pathways and minimal toxic side effects， which have made it increasingly popular worldwide. According to TCM， the pathogenesis of colorectal cancer is rooted in both deficiency and excess. TCM formulas mainly focus on tonifying the body to address the invasion and metastasis of colorectal cancer， such as Jianpi compound， Jianpi Xiaoai decoction， and Bushen Jiedu Sanjie decoction. TCM monomers， such as emodin， berberine， and tanshinone， mainly focus on clearing heat and removing toxin， circulating blood and transforming stasis， and resolving swelling and dispersing nodules. Signaling pathways play a crucial role for analyzing invasion and metastasis， and research has shown that pathways such as Wnt/β-catenin， phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt）， Janus kinase 2/signal transduction and transcription activating factor 3 （JAK2/STAT3）， nuclear factors-κB （NF-κB）， vascular endothelial growth factor （VEGF） play important roles in the invasion and metastasis of colorectal cancer. The invasion and metastasis of colorectal cancer can be inhibited via regulating the key proteins and related factors in these pathways. In this review， we searched various literature databases， such as PubMed， China National Knowledge Infrastructure （CNKI）， and VIP， using keywords such as "colorectal cancer"， "signaling pathway"， "invasion and metastasis"， and "traditional Chinese medicine"， to summarize and analyze the relevant pathways of TCM compounds and monomers against invasion and metastasis of colorectal cancer published in the past five years. The review aims to provide new insights and references for in-depth research on the therapy for invasion and metastasis of colorectal cancer and new drug development.

Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

Background Water serves as an indispensable resource for human survival and constitutes one of the primary means through which humans are exposed to environmental chemicals. Consequently, the safety of drinking water is critical to safeguarding public health. Objective To analyze the levels of the 10 metal/metalloid indicators [Al, Fe, Mn, Cu, Zn, As, Cd, Cr(VI), Pb, and Hg] in drinking water from a region of the Fuchun River Basin, and to evaluate the health risks in drinking water through oral ingestion. Methods In accordance with the national Standard Examination Method for Drinking Water – Part 2: Collection and Preservation of Water Samples (GB/T 5750-2006 and GB/T 5750-2023), a total of 2016 drinking water samples were collected from urban and rural water supply systems in a region of the Fuchun Basin from 2017 to 2024. Two batches of water samples were collected annually during the dry and wet seasons, with each batch comprising 72 samples from the urban water supply system and 54 samples from the rural water supply system. These samples were analyzed according to the Standard Examination Method for Drinking Water – Part 6: Metal and Metalloid Indicators (GB/T 5750-2006 and GB/T 5750-2023) and the results were compared with the limits specified in the Standards for Drinking Water Quality (GB 5749-2022). Health risks were evaluated using the U.S. Environmental Protection Agency (EPA) health risk assessment model. Results All tested metal/metalloid elements in the drinking water samples of the area met the national standards. The results of risk assessment showed that the non-carcinogenic risks associated with oral intake of drinking water, ranked from highest to lowest, were as follows: As>Cr(VI)>Pb>Cd>Hg>Mn>Cu>Zn>Fe>Al, with values of 4.55×10⁻², 2.79×10⁻², 2.06×10⁻², 1.20×10⁻², 4.95×10⁻³, 4.58×10⁻³, 2.85×10⁻³, 1.95×10⁻³, 1.52×10⁻³, and 9.21×10⁻⁴, respectively. The non-carcinogenic risk of each indicator was less than 1, which suggested no potential risk to population health. The carcinogenic risks ranked as Cr(VI)>As>Cd>Pb, with values of 4.18×10⁻⁵, 2.05×10⁻⁵, 3.85×10⁻⁶, and 2.45×10⁻⁷, respectively. The carcinogenic risks of Cr(VI), As, and Cd were between 10⁻⁶ and 10⁻⁴, which suggested an acceptable carcinogenic risk, while the carcinogenic risk of Pb was relatively negligible. Children's total non-carcinogenic/total carcinogenic risks were comparable to those of adult males, both higher than those of adult females. Additionally, rural areas exhibited higher non-carcinogenic/carcinogenic risks for Cr(VI), while those risks for As and Pb were lower than those in urban water samples, and those risks for Cd were comparable between the two. Conclusion The concentrations of the 10 metal/metalloid indicators in drinking water from the studied region in the Fuchun River Basin comply with the national standards from 2017 to 2024. There is a certain carcinogenic risk associated with oral intake of drinking water, but it is still within the acceptable range. In terms of non-carcinogenic risk, no potential threat to population health is anticipated.

Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P＞0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.