Hongtao Jin

The widespread assumption that “natural” equals “safe” has been repeatedly challenged by adverse events associated with medicinal plant-derived products. Unlike synthetic pharmaceuticals, these natural products present distinct safety concerns because of their compositional complexity, inherent variability, and batch-to-batch inconsistency. Consequently, a one-size-fits-all approach to toxicological assessment is insufficient. In this narrative review, we propose a pragmatic “classify-then-evaluate” framework that stratifies natural products into three operational categories according to compositional complexity and degree of chemical characterization—TCM compound formulae, active fractions/extracts, and purified single compounds. This framework enables safety evaluations to be tailored to product complexity by integrating conventional toxicological assays with emerging new approach methodologies. By linking chemical characterization, hazard identification, quality control, and risk assessment within a tiered system, this framework bridges the gap between evidence generation and regulatory decision-making, offering a scientifically grounded and proportionate pathway for evaluating the safety of natural products used in integrative medicine, with a primary focus on herbal and TCM-related products. The review does not aim to provide a comprehensive systematic evidence map; further validation of the proposed framework is required

Background: Olanzapine is an atypical antipsychotic used to treat schizophrenia and manic episodes. Its potential thromboembolic risk has been reported, but the evidence remains controversial. This study aimed to comprehensively evaluate the association between olanzapine and pulmonary embolism (PE) and venous thromboembolism (VTE). Methods: This study combined meta-analysis and signal mining from the FDA Adverse Event Reporting System (FAERS) database to assess the association between olanzapine and pulmonary embolism (PE) and venous thromboembolism (VTE). Results: From 55,905 olanzapine-related adverse event reports in the Faers database, 1,233 significant signals were identified, including serious adverse events not fully documented on the drug label, such as pulmonary embolism and venous embolism. A meta-analysis of eight studies showed that olanzapine use significantly increased the risk of VTE and pulmonary embolism (OR = 2.07, 95% CI: 1.37–3.14, P = 0.0006). Conclusion: These findings suggest that olanzapine is associated with an increased risk of thromboembolic events; therefore, enhanced clinical surveillance and further investigation into its safety are necessary. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD420251003254.

Cancer remains a major global health challenge, and although immunotherapy has achieved remarkable breakthroughs, its efficacy is often limited by tumor-induced immunosuppression within the tumor microenvironment (TME). Emerging evidence indicates that metabolic reprogramming plays a pivotal role in shaping the TME and regulating antitumor immune responses. Targeting tumor and immune cell metabolism has therefore become a promising strategy to enhance the effectiveness of cancer immunotherapy. This review first summarizes the metabolic reprogramming that occurs within the TME, including alterations in glucose, lipid, and amino acid metabolism in tumor cells, as well as the metabolic adaptation of immune cells. We then highlight recent advances in natural products that modulate key metabolic pathways and their potential to reshape the immunosuppressive TME. Special emphasis is placed on natural compounds that not only inhibit tumor cell metabolism but also restore the metabolic fitness of immune cells, thereby improving antitumor immunity. In addition, advances in delivery strategies, including nanocarrier-based and stimuli-responsive systems, are reviewed for their roles in improving the bioavailability, stability, and tumor targeting of natural metabolism-regulating agents. Finally, we discuss the current status and challenges of translating natural metabolism-regulating agents into clinical applications, including issues of dose optimization, safety evaluation, and patient selection. Despite these hurdles, precision targeting of metabolic pathways, interdisciplinary collaboration, and the discovery of novel compounds—particularly immune-sensitizing agents derived from traditional medicine—are expected to accelerate progress. Collectively, natural products represent promising adjuvant strategies for cancer immunotherapy, with great potential to overcome current therapeutic limitations and improve clinical outcomes.

The relationship between allergies and cancer has been a topic of debate for decades. This study conducted a systematic review and meta-analysis of 53 studies to evaluate the association between allergies and cancers. Case–control and cohort studies were analyzed, focusing on cancer incidence. The results showed significant negative correlations between allergies and cancers such as colorectal cancer, lymphoma, pancreatic cancer, leukemia, and brain cancers. For colorectal cancer, the pooled odds ratio (OR) for any allergy was 0.77 (95% CI 0.67–0.87). Asthma was associated with a reduced risk of lymphoma (OR 0.81, 95% CI 0.70–0.94) and gynecological cancers (OR 0.72, 95% CI 0.53–0.97). For Pancreatic cancer, any allergy was associated with an OR of 0.68 (95% CI 0.59–0.77). Hay fever showed a strong inverse association with brain cancer risk (OR 0.66, 95% CI 0.58–0.76). However, atopic allergy was positively linked to an increased risk of lymphoma (OR 2.02, 95%CI 1.10–3.70). The study highlighted significant variations in the effects of different allergy types on cancer risks. These findings suggest that allergies may act as protective factors against certain cancers, while atopic allergy may increase the risk of certain cancers. However, the certainty of evidence, assessed using the GRADE framework, was low to very low, and results should be interpreted with caution. In particular, associations for lung cancer, leukemia, and gastrointestinal cancers were supported by very low-certainty evidence, primarily due to reliance on observational designs, heterogeneity among studies. These findings underscore the complex and heterogeneous relationship between allergies and cancer, and highlight the need for further high-quality research to elucidate the underlying mechanisms and assess clinical implications.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death and disability worldwide. Its complex etiology involves factors such as smoking, air pollution, genetic susceptibility, and social environment. With the accelerating global aging population and urbanization, the incidence and burden of COPD continue to rise. Current treatment strategies for COPD are relatively conservative, primarily focusing on bronchodilators, inhaled corticosteroids, and long‐term oxygen therapy. Although these approaches can alleviate symptoms and slow disease progression to some extent, they fail to effectively target the underlying mechanisms of the disease, leaving an unmet clinical need for more‐effective therapies. This highlights the urgency of developing innovative drugs that are both safe and efficacious to address the challenges in COPD treatment. As a traditional Chinese medicine with a long history, Colla corii asini has garnered significant attention for its diverse pharmacological effects and favorable safety profile. Research has shown that Colla corii asini possesses multiple biological activities, including hematopoiesis, nourishing the lungs, enhancing immunity, anti‐infection, antiaging, antitumor, and antifatigue effects. Moreover, it has demonstrated potential in regulating oxidative stress, immune imbalance, and inflammatory responses. Recent evidence suggests that Colla corii asini may play a protective role in lung function through multitarget and multipathway mechanisms. Based on previous research findings, this paper explores the potential therapeutic value of Colla corii asini in COPD treatment by addressing the current clinical management challenges and identifying potential therapeutic targets. It also integrates the pharmacological effects of Colla corii asini into a broader treatment context, providing new perspectives for comprehensive COPD management and laying the theoretical foundation for its modernization and innovative application.

Organoids are derived from self-organizing stem cells and form three-dimensional structures that are structurally and functionally similar to in vivo tissues. With the ability to replicate the in vivo microenvironment and maintain genetic stability, organoids have become a powerful tool for elucidating developmental mechanisms, accurately modeling disease processes, and efficiently screening drug candidates, and have also demonstrated significant value in the field of traditional Chinese medicine (TCM)-including applications in screening active components of TCM, studying TCM pharmacodynamic mechanisms, evaluating TCM safety, and verifying the effects of traditional non-pharmacological therapies such as acupuncture and yoga. Organoids can be cultured using air-liquid interface systems, bioreactors, and vascularization techniques. They are widely used in drug screening, disease modeling, precision medicine, and toxicity assessment. However, current limitations include high costs, difficulty in accurately replicating the microenvironment, and ethical concerns. In this review, we systematically retrieve, synthesize, and analyze relevant literature to elucidate the culture methods of organoid technology, its diverse applications across various fields, and the challenges it faces. In the future, integration with artificial intelligence may provide new insights and strategies for drug development and disease research and the modernization of TCM.

The prevalence of herbal medicines has gained widespread, particularly among cancer patients seeking adjunctive therapies. Co-administered with anticancer drugs (ACDs) frequently, herbal medicines result in increasing cases of herb-drug interactions (HDIs), following the serious clinical consequences. While herbal medicines pose negative impacts, such as limiting efficacy and increasing toxicity of ACDs, they also offer potential benefits, including enhancing bioavailability, reducing adverse reactions, and reversing tumor drug resistance. This review is the first to systematically characterize HDI molecular mechanisms at both pharmacodynamic (PD) and pharmacokinetic (PK) levels, elucidating how herbal medicines modulate ACDs efficacy and safety through antagonism/synergy/detoxification target, metabolic enzymes, and transporters. In particular, emerging risk prediction methodologies are proposed to assess the clinical occurrence of potential PD/PK-mediated HDIs. We provide a novel insight for promoting the mechanism study of HDIs, facilitating the safe and effective integration of herbal medicines into cancer treatment. Graphical Abstract