Colorectal cancer (CRC) is a common malignancy of the digestive tract, and its initiation and progression are closely associated with dysregulation of the tumor immune microenvironment. The CRC immune microenvironment consists of effector immune cells, immunosuppressive cells, inflammatory mediators, immune checkpoint pathways, stromal cells, the extracellular matrix, the gut microbiota, and microbial metabolites. Its pathological features include impaired immune recognition and effector immunity, enhanced immunosuppression, extracellular matrix remodeling-mediated immune exclusion, dysregulated inflammatory and immune checkpoint signaling, and disturbances in gut microbiota and metabolism. Traditional Chinese medicine (TCM), characterized by multicomponent, multitarget, and multilevel regulation, has shown potential value in research on the CRC immune microenvironment. Current preclinical studies suggest that TCM-derived isolated compounds and bioactive constituents, single herbs, Chinese herbal formulas, and Chinese patent medicines may improve immune recognition and effector immune function by restoring antigen presentation, promoting dendritic cell maturation and enhancing effector T-cell responses and natural killer cell activity. These interventions may also inhibit immunosuppressive cells, modulate immune checkpoint and inflammation-related signaling, and enhance antitumor immunity by inducing immunogenic forms of tumor cell death. In addition, TCM may alleviate immunosuppression and immune exclusion by modulating stromal remodeling mediated by cancer-associated fibroblasts and regulating the gut microbiota, microbial metabolites, and tumor immunometabolism. In some preclinical models, these effects enhanced the antitumor efficacy of immune checkpoint blockade and provided experimental support for further mechanistic validation and clinical studies of TCM combined with immunotherapy. However, current evidence remains predominantly preclinical, and further clinical validation and assessment of bioavailability, safety, and drug interactions are needed. This review summarizes the composition and pathological features of the CRC immune microenvironment and discusses recent advances in TCM-mediated immune modulation. It also examines current mechanistic evidence and its limitations to inform further mechanistic validation, clinical study design, and translational research.

BACKGROUND:Oxaliplatin-induced peripheral neuropathy (OIPN) affects up to 80% of patients receiving oxaliplatin-based chemotherapy, and effective preventive strategies remain limited. Huangqi Guizhi Wuwu Decoction (HQGZWWD), a traditional Chinese herbal formula included in China's National Classic Famous Formulas, is widely used for OIPN in clinical practice, but high-quality clinical evidence remains lacking. PURPOSE:This study evaluated the efficacy and safety of HQGZWWD for OIPN prevention and explored its neuroprotective mechanisms. METHODS:We conducted a multicenter, randomized, double-blind, placebo-controlled trial at 12 tertiary hospitals in China. Adults with colorectal cancer scheduled to receive XELOX chemotherapy were randomly assigned (1:1) to oral HQGZWWD granules or placebo (47.5 g per sachet, twice daily) throughout chemotherapy. Participants, outcome assessors, and statisticians were blinded. The primary outcome was the incidence of grade ≥2 chronic OIPN in the modified intention-to-treat population, analyzed using logistic regression with multiple imputation for missing data. RESULTS:A total of 360 participants were enrolled, and 354 were included in the modified intention-to-treat analysis. Grade ≥2 chronic OIPN occurred in 21.3% of patients receiving HQGZWWD group and 38.6% in the placebo group (OR, 0.43; 95% CI, 0.27-0.69; P<0.001). Adverse events were comparable between groups (OR, 1.27; 95% CI, 0.68-2.39; P=0.524). In animal models, HQGZWWD increased pain thresholds, preserved dorsal root ganglia, reduced IL-1β, MCP-1, and MDA levels, and enhanced SOD activity. Consistently, clinical serum enzyme-linked immunosorbent assay (ELISA) analyses further validated these mechanisms, demonstrating that HQGZWWD significantly attenuated chemotherapy-induced elevations of pro-inflammatory cytokines (IL-1β, MCP-1) and oxidative stress marker (MDA), while preserving antioxidant enzyme (SOD) activity in CRC patients receiving XELOX chemotherapy. CONCLUSION:HQGZWWD significantly reduced the incidence of OIPN without increasing toxicity. Preclinical findings suggest that these effects may involve reduced oxidative stress and improved mitophagy. These findings support HQGZWWD as a promising preventive strategy for OIPN. TRIAL REGISTRATION:The trial is registered with ClinicalTrials.gov (NCT04913376).

Cancer-associated fibroblasts (CAFs) are one of the most abundant stromal components in tumor microenvironment (TME), which participate in key processes such as extracellular matrix remodeling, immune regulation, metabolic support and treatment tolerance. In recent years, with the development of single-cell sequencing and spatial omics technology, people's understanding of CAFs has gradually changed from unified cancer cell population to a dynamic cell collection with diverse sources, continuous states and heterogeneous functions. Numerous studies have shown that CAFs have a high degree of dynamic plasticity, and their phenotype can undergo reversible or semi-reversible transformation driven by different microenvironmental signals. The plasticity of CAFs not only explains the functional heterogeneity of CAFs across studies, but also provides a theoretical basis for changing the therapeutic strategy of targeting CAFs from removal to reprogramming. Among them, it is a significant advantage of traditional Chinese medicine (TCM) to reprogram CAFs through network regulation. This article systematically reviews the source and classification system of CAFs. In addition, aiming at the off-target and drug resistance problems in tumor treatment, this article focuses on the unique mechanism of traditional Chinese medicine monomers and compounds reprogramming CAF phenotype with the synergistic advantages of multi-component, multi-target and multi-pathway. This paper aims to provide a new theoretical basis and strategic direction for breaking through the bottleneck of tumor treatment.

Preoperative assessment of lymph node metastasis (LNM) risk is needed to support risk stratification and individualized treatment planning in patients with colorectal cancer (CRC). However, imaging-based nodal staging may be affected by image quality and readers’ experience, and its ability to detect microscopic metastatic disease remains limited. Machine learning models based on routinely available clinical data may provide an accessible and interpretable approach to support individualized preoperative decision-making. This study aimed to establish an interpretable machine learning–based model to estimate the preoperative risk of LNM risk in patients with CRC. The model incorporated preoperative variables that are routinely obtained in clinical practice and was further evaluated in an independent external validation set. We retrospectively analyzed data from 2725 patients diagnosed with CRC at two independent hospitals. The internal cohort was randomly split at a 7:3 ratio for model training and testing. The second-center cohort served as the independent external validation set. The outcome was pathologically confirmed regional LNM. Candidate variables included demographic characteristics, laboratory indicators, tumor markers, and tumor-related clinicopathological features available before surgery. Variables independently associated with LNM were identified using logistic regression analyses. Seven machine learning models were constructed using LightGBM, random forest, support vector machine, logistic regression, decision tree, XGBoost, and naive Bayes. Model performance was checked by discrimination, calibration, clinical utility, and classification metrics. We used the area under the receiver operating characteristic curve (AUC) to assess discrimination. Accuracy, sensitivity, specificity, F1 score, positive predictive value (PPV), and negative predictive value (NPV) described classification performance. Calibration curves compared predicted risks with observed outcomes. Decision curve analysis estimated the model’s net clinical benefit. SHapley Additive exPlanations (SHAP) analysis interpreted the selected model and assessed predictor contributions. The final cohort included 2725 patients. There were 753 patients for model training, 321 for testing, and 1651 for external validation. In multivariable logistic regression, body mass index, preoperative carcinoembryonic antigen level, primary tumor site, clinical T stage, histological type, and tumor differentiation were independently associated with LNM. Among the seven models, random forest showed the most balanced performance. In the test set, this model had an AUC of 0.806. Its accuracy was 0.735, sensitivity was 0.737, and specificity was 0.734. In the external validation set, the AUC was 0.782. Accuracy, sensitivity, and specificity were 0.690, 0.661, and 0.708. An interpretable machine learning model estimated LNM risk in CRC with acceptable performance. Random forest showed stable discrimination in the independent external validation set. It may support individualized preoperative risk stratification, but prospective validation and implementation studies are still needed. Not applicable

Pancreatic cancer is known as the "king of cancers", mainly due to its aggressive metastatic potential and significant heterogeneity. The liver represents the most frequent site of distant metastasis in pancreatic ductal adenocarcinoma (PDAC). Currently, effective treatment options remain critically limited for patients diagnosed with PDAC-derived hepatic metastases. In our research, we integrated single-cell transcriptomic data from multiple samples to delve into the heterogeneity of epithelial cells. We identified a subtype of malignant metastatic epithelial cells and identified CYBA, which encodes the p22phox protein, as a key molecular target promoting hepatic metastasis in PDAC. Through experimental validation, we confirmed that p22phox was highly expressed in pancreatic cancer samples with hepatic metastasis, and its knockdown inhibited the migration of pancreatic cancer cells and metastasis to the liver. Mechanistically, p22phox activated the PI3K-AKT signaling pathway and increased MLC2 phosphorylation, facilitating the polymerization of motor proteins in pancreatic cancer cells and promoting tumor metastasis. NOX inhibitors were found to suppress PI3K-AKT and p-MLC2 pathways, as well as inhibit the migration of pancreatic cancer cells and metastasis to the liver. Therefore, targeting the activity of p22phox in pancreatic cancer may emerge as an effective therapeutic strategy for treating hepatic metastasis in PDAC patients.

Pantothenic acid (PA), or vitamin B5, can be synthesized by gut commensals, but the contribution of microbial PA to metabolic health remains unclear. Here, we find that microbial PA supply is reduced in individuals with metabolic syndrome (MetS) and is associated with impaired gut barrier function and disease severity. Tracing microbial PA identifies Bacteroides fragilis as a key contributor, with panC required for PA biosynthesis, as confirmed by isotope tracing, bacterial culture, and germ-free colonization. In MetS models, colonization with wild-type, but not ΔpanC B. fragilis, restores PA, preserves gut barrier integrity, reduces endotoxemia, and improves metabolic dysfunction. Mechanistically, microbial PA requires host pantothenate kinase activity, as silencing pantothenate kinase 2/3 (PANK2/3) in colonic organoids and in vivo reduces coenzyme A (CoA)/acetyl-CoA metabolism, suppresses Krüppel-like factor 4 (KLF4)-associated differentiation programs, and blunts the protective effects of microbial PA. Finally, a plant-derived polysaccharide enriches PA-producing Bacteroides and restores colonic PA, highlighting a strategy for colonic homeostasis and metabolic health.

Sepsis, a dysregulated host response to infection causing life-threatening organ dysfunction, remains a leading cause of mortality worldwide with death rates exceeding 30%. Current therapeutic approaches inadequately address the complex pathophysiology involving uncontrolled cytokine release, oxidative stress, and persistent infection. Here we report cerium-based nanomodulators (CBB NPs) that integrate antioxidant, anti-inflammatory, and antimicrobial functions for synergistic therapy. The nanoplatform comprises hollow mesoporous cerium oxide nanoparticles (CeO₂ NPs) as catalytic cores, exploiting Ce3+/Ce4+ redox cycling to mimic superoxide dismutase (SOD) and catalase (CAT) enzymes for reactive oxygen species (ROS) scavenging. Bilirubin (BR) provides additional antioxidant protection, while antimicrobial peptide Buforin IIb confers antimicrobial activity. In cecal ligation and puncture (CLP) sepsis model, CBB NPs treatment improved 7-day survival from 0% to 60%, reduced pro-inflammatory cytokine release, and effectively cleared pathogen burden. Notably, CBB NPs ameliorated sepsis-related encephalopathy (SAE) by maintaining blood-brain barrier (BBB) integrity, promoting hippocampal neurogenesis, and improving cognitive dysfunction. This synergistic approach exhibits considerable therapeutic promise for sepsis and related neurological consequences, providing a model for addressing complex disorders via integrated nanomedicine techniques.

Colorectal cancer (CRC) remains a persistent major global health burden, with traditional diagnostic methods like colonoscopy suffering from suboptimal patient compliance rates. This study develops an intelligent diagnostic model based on tongue images to assist in CRC diagnosis, leveraging the integrative potential of traditional tongue diagnosis and modern machine learning. Between June 2023 and July 2024, we collected and processed 1,389 tongue images from CRC patients and 1,543 from non-colorectal cancer (NCRC) participants. Our methodology combines innovative image segmentation using the Segment Anything Model (SAM) with Grounding DINO, extracts both hand-crafted features (color, texture, shape) and deep learning features via Swin-Transformer, and employs feature fusion and selection techniques. The diagnostic model achieves an accuracy of 87.93% (F1-score: 0.9072) in internal validation. In an independent external cohort of 119 CRC patients and 221 NCRC participants, it demonstrates 85.18% precision (recall: 85%, F1-score: 0.8507). This noninvasive, cost-effective approach demonstrates significant potential as a complementary screening tool for CRC, particularly in regions with limited access to conventional diagnostic resources.

Colorectal cancer liver metastasis (CCLM) is a common and serious complication of colorectal cancer and is one of the main causes of patient death. This study examines the trend of CCLM research using bibliometric and visualization analysis to provide a reference for further research. We searched for publications related to CCLM published between 2015 and March 2025 in the Web of Science and PubMed databases and visualized and analyzed data using R (version 4.4.2), VOSviewer (version 1.6.20), and CiteSpace (version 6.3.R1) software. A total of 8656 relevant publications were included. The number of CCLM publications has shown a steady upward trend from 2015 to 2025, with articles being the predominant type. The field has developed a larger number of core authors, with Pawlik, Timothy M. scholar having the highest cumulative number of publications. “Cancers” contributed the most publications. China is the country contributing the most publications in the field, but American scholars have the highest average number of citations per publicaton. “colorectal cancer”, “survival”, “cancer”, “chemotherapy”, “liver metastases”, “hepatic resection”, “surgery” and so on are the keywords that appear with high frequency in this field. The most frequently cited journal is “Annals of Surgery”. The most cited publication is “Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer—Analysis of 1001 consecutive cases”. The citing journals are mainly in the fields of oncology, surgery, and imaging, while the cited journals also include some journals in other basic disciplines. Clinical research on CCLM has mainly focused on prospective studies, with an emphasis on gender, age, treatment outcomes, and disease-free survival. This study comprehensively analyzes the current research status and hotspots in the field of CCLM, which can provide valuable references for future research and help other scholars grasp the dynamics of research in this field and discover potential research directions.

Colorectal cancer poses a significant clinical challenge, with an alarming annual incidence of nearly 1.88 million new cases and limited therapeutic strategies, especially for advanced stages. The tumor microenvironment represents a complex ecosystem encompassing tumor cells, immune cells, cancer-associated fibroblasts, and extracellular matrix. This ecosystem is pivotal in orchestrating the trajectory of colorectal cancer evolution and can be divided into six microenvironments: acidic, hypoxic, metabolic, immune, microbiota, and stromal. The tumor microenvironment has increasingly garnered attention in oncological research, as modulating these environments presents novel therapeutic avenues for colorectal cancer. This review provides a comprehensive evaluation of the capacity of natural products to modulate the tumor microenvironment and augment colorectal cancer therapeutic outcomes. Additionally, this review underscores seminal clinical and preclinical studies, providing valuable insights to unlock the full potential of natural products in the development of novel drugs to effectively address the challenges posed by colorectal cancer.

Liver cancer is a common malignancy with high lethality,and its development is closely associated with liver Qi stagnation,impaired blood circulation,and the long-term accumulation of stasis generating toxin,in which toxin arising from stasis represents a key pathogenic driver.The core mechanism of liver cancer is characterized by stasis-toxin interlocking,and the therapeutic approach of dispelling stasis and detoxifying-guided by the principle of promoting circulation to resolve stasis and clearing toxin at its root-has become a major strategy in prevention and treatment.Through distinct methods such as moving Qi to dispel stasis and remove toxin,clearing heat to eliminate stasis and remove toxin,softening hardness to resolve stasis and remove toxin,and tonifying Qi to dispel stasis and expel toxin,this approach exerts important benefits in liver cancer management.The approach of moving Qi focuses on soothing the liver,promoting Qi movement,and alleviating stasis obstruction,exemplified by formulas such as Gexia Zhuyu Decoction,with Chuanxiong Rhizoma,Curcumae Rhizoma,and Curcumae Radix commonly used.The heat-clearing strategy emphasizes clearing heat,detoxifying,dissipating mass,and dispersing stasis,represented by Longdan Xiegan Decoction,and often incorporates Forsythiae Fructus,Polygoni Cuspidati Rhizoma et Radix,and Moutan Cortex.The softening-hardness approach aims to soften hardness,dissipate mass,eliminate toxin,and resolve stasis,with representative formulas such as Biejiajian Pills and key TCMs including Scolopendra,Gleditsiae Spina,and Prunellae Spica.The Qi-tonifying approach highlights reinforcing healthy Qi,consolidating root,and promoting stasis resolution,represented by formulas such as the Yiqi Huayu Jiedu Prescription,commonly combining Astragali Radix,Notoginseng Radix et Rhizoma,and Agrimoniae Herba.Modern pharmacological studies demonstrate that these stasis-removing and detoxifying TCMs exert anti-liver cancer effects through mechanisms such as cell-cycle arrest,enhancement of mitochondrial-dependent apoptosis,inhibition of tumor angiogenesis,and suppression of proliferation,migration,and invasion of tumor cells,as well as partial reversal of chemoresistance.Their actions involve the coordinated regulation of multiple cancer-related signaling networks,including inhibition of STAT3,NF-κB,PI3K/Akt,TGF-β/Smad pathways,attenuation of pro-inflammatory and pro-proliferative signaling,modulation of the tumor immune microenvironment,alleviation of chronic inflammation,suppression of HIF-1α-mediated and VEGF-mediated angiogenesis,regulation of oxidative stress,and influence on epigenetic processes such as histone acetylation.By systematically summarizing the multi-target and multi-layered action characteristics and potential regulatory mechanisms of these TCM strategies,this study provides a theoretical foundation and therapeutic perspective for understanding and applying stasis-removing and detoxifying TCMs in the management of liver cancer.

Ethnopharmacological relevance The processing of Panax notoginseng (PN) is a quintessential example of the traditional Chinese medicine principle of "different uses for raw and processed products", embodied in the theory of "raw for dispersing while processed for tonifying". However, few studies are available summarizing the corresponding chemical transformations and pharmacological shifts. Aim This review aims to synthesize current research to elucidate the processing-driven chemical transformations and pharmacological shifts in PN. Methods Focused on the core topic of chemical transformations and pharmacological shifts in PN driven by processing, a systematic search of eligible literature published since 2015 was conducted across several databases, including Scopus, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the WanFang Database, and the Chinese Science and Technology Journals Database. Results Key findings indicate that heat-based processing significantly reduces hemostatic components like dencichine while converting native saponins (e.g., ginsenoside Rg1, Rb1, Rd, Re, notoginsenoside R1) into rare saponins (e.g., ginsenoside Rg3, Rg5, Rk1, Rk3, Rh4). This compositional remodeling underpins the efficacy transition that raw PN excels in hemostasis and blood activation, whereas the processed form exhibits enhanced blood-nourishing, immunomodulatory, and anti-tumor activities. However, critical gaps persist, including the lack of dedicated quality standards for processed products, non-standardized processing protocols reliant on empirical judgment, and a fragmented understanding of the systemic mechanisms linking compositional changes to holistic efficacy. Conclusion This review summarizes critical advances in understanding the inherent chemical transformations and pharmacological shifts in PN driven by processing. To advance the field, future research must focus on processing standardization through objective chemical endpoints, establishing quality markers based on multiple rare saponins, investigating processing-chemistry-efficacy-mechanism relationships, and translating laboratory findings into clinical evidence. These further studies are essential for transforming traditional wisdom into precision science, ensuring clinical efficacy and facilitating the global recognition of PN.

Background Colorectal cancer often develops from adenomas over years, necessitating early intervention. Myeloid-derived suppressor cells (MDSCs) are major immune suppressive cell types in colon cancer development from adenomas through early inflammation-induced emergency myelopoiesis. Cannabidiol (CBD) is reported to function in psychosis, coronavirus infection and some cancers through immune regulation. However, its target and underlying mechanisms in colorectal adenomas are unknown.Methods The antitumor effect of CBD was validated in two classical colorectal adenomas models including azoxymethane (AOM)/dextran sulfate sodium salt (DSS) induced mice model and high-fat fed Apcmin/+ mice model. Single-cell RNA sequencing was used to identified the immune environment change after CBD treatment in mice colorectal adenomas. Target responsive accessibility profiling was used to find the target of CBD in MDSCs. Subsequently, multiple immunology assays and molecular biology experiment were employed to explore the adenomas prevention mechanisms of CBD.Results Here, we found that CBD prevented the incidence of colorectal adenomas in AOM/DSS model and high-fat diet fed Apcmin/+ mice model. Our single-cell RNA sequencing data and the results of immunofluorescence revealed that CBD treatment significantly decreased the number of MDSCs in both two colon adenomas models. Mechanistically, CBD bound to the guanine nucleotide exchange factor domain of EEF1B2, inhibiting its function in translational elongation and subsequent C/EBPβ synthesis. This disruption suppressed the differentiation and generation of MDSCs, leading to enhanced T-cell activation and prevention of colorectal adenoma progression.Conclusion Our findings reveal EEF1B2-mediated C/EBPβ protein synthesis as a crucial pathway in MDSC generation and highlight the potential of CBD as an early intervention strategy for colorectal adenomas.

ABSTRACT Colorectal cancer (CRC) is one of the most common and lethal cancers globally, with early detection of precancerous lesions being crucial for reducing its incidence and mortality. Colorectal precancerous lesions, including adenomas, serrated lesions, and dysplasias associated with inflammatory bowel disease (IBD), represent key targets for preventive strategies. Despite advancements in screening and therapeutic options, medicinal natural products clinical application is frequently challenged by low bioavailability, complex in vivo metabolism, unclear adverse effects and side‐effect profiles, and a strong reliance on empirical standards in clinical use. This review provides a comprehensive overview of the definition, classification, and molecular mechanisms underlying colorectal precancerous lesions, epigenetic modifications, and genetic factors. It also highlights the application of multi‐omics technologies in understanding lesion heterogeneity. In addition, the review evaluates cutting‐edge research models such as organoids, 3D co‐culture systems, and various in vivo models, offering insights into their potential for studying CRC precursors. This review summarizes current mechanistic insights into early colorectal carcinogenesis and highlights three major translational directions: therapeutic strategies targeting key genomic alterations; immunologic modulation relevant to inflammation‐driven tumor initiation; and multi‐omics stratification optimizing dosing and patient selection. These perspectives outline emerging opportunities for developing more precise and clinically actionable preventive interventions.

Objective:This study endeavors to develop an intelligent diagnosis and treatment model for Traditional Chinese Medicine (TCM) syndrome differentiation and treatment, characterized by robust reasoning capabilities and exceptional reliability. This is achieved by harnessing clinical case data, employing knowledge distillation methodologies, and integrating Direct Policy Optimization (DPO) reinforcement learning techniques. Methods:GPT-4o was employed as the teacher model to perform knowledge distillation on TCM clinical case data, thereby generating a high-quality instruction dataset for syndrome differentiation and treatment. The distilled data was subsequently fine-tuned by Low-Rank Adaptation (LoRA) method grounded in the Qwen2.5-7B model to improve its abilities of diagnosis and treatment, together with competencies of personalized syndrome differentiation and treatment. Furthermore, an additional dataset of clinical cases was leveraged to emulate the diagnosis and treatment preferences of TCM experts, with the DPO reinforcement learning technique being applied for ongoing refinement and enhancement. Results:The recommended knowledge distillation approach maintained prescription recommendation performance comparable to direct training upon the reinforcement of the model's interpretability and generalization on external data. Aside from that, the DPO method ameliorated the stability of prediction results on the external dataset. Conclusion:The TCM Large Language Model constructed with knowledge distillation and reinforcement learning strategies effectively enhances diagnosis and treatment reasoning and personalized syndrome differentiation and treatment competencies. This approach provides new research directions and technical support for intelligent TCM clinical decision-making.

Huachansu, derived from the dried skin glands of the Chinese toad (Bufo bufo gargarizans), has been used in traditional Chinese medicine for its anti-tumor properties, particularly in hepatocellular carcinoma (HCC). However, its molecular mechanisms remain unclear. This study investigates Huachansu’s therapeutic potential by focusing on mitochondrial apoptosis and endoplasmic reticulum (ER) stress pathways. In vitro studies on HepG2 cells revealed that Huachansu (48–96 mg/mL for 24 h) disrupted mitochondrial function by elevating reactive oxygen species (ROS) generation ( 83

ETHNOPHARMACOLOGICAL RELEVANCE:Gastric precancerous lesions (GPL), the inflammation-driven precursors of gastric cancer (GC), may be propelled by neutrophil extracellular traps (NETs). Jianpi Fuzheng Xiaoji formula (JPFZXJ) is a standardized herbal formulation that translates the ancient "reinforce healthy qi to eliminate pathogenic factors" doctrine of the Huangdi Neijing into modern practice. It is pharmacologically optimized from the classical Han-dynasty pair Lizhong Wan and Banxia Xiexin Tang for targeted intervention against GPL and has been clinically used for its management. Nevertheless, the molecular mechanisms underlying its protective effects remain incompletely defined. AIM OF THE STUDY:To determine whether NET drives GPL and to elucidate how JPFZXJ interrupts this process. MATERIALS AND METHODS:JPFZXJ was chemically profiled by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). The transcriptomic dataset GSE191275 was analysed to quantify immune infiltration in non-atrophic gastritis (NAG), intestinal metaplasia (IM) and GC. In vitro, normal gastric epithelial cell-neutrophil co-cultures were employed to dissect reciprocal signalling. In vivo, a mouse GPL model induced by cyclic N-methyl-N-nitrosourea (MNU) administration was used to map neutrophil dynamics. Ablation of neutrophils or macrophages subsequently identified the principal cellular source of NET release. GPL mice were orally administered JPFZXJ for 10 weeks; infiltrating neutrophils were quantified by flow cytometry, and the capacity of JPFZXJ to attenuate GPL progression through NET inhibition was then evaluated. RESULTS:JPFZXJ significantly attenuated gastric mucosal pathological injury, ameliorated IM and dysplasia (Dys), down-regulated pro-inflammatory cytokines and chemokines, and suppressed neutrophil chemotaxis from peripheral blood to the gastric mucosa, thereby reducing neutrophil recruitment in GPL mucosa. Additionally, JPFZXJ directly inhibited NET formation in GPL mucosa. CONCLUSION:JPFZXJ alleviates GPL through dual mechanisms: curtailing neutrophil recruitment to limit NET sources and directly suppressing NET formation, underscoring its potential as an immunomodulatory approach against gastric carcinogenesis.

Background: Liver cancer remains a persistent global health challenge due to its high occurrence and fatality rates, critically impacting health outcomes and quality of life. The disease burden in East Asia, considering China, Japan, South Korea, and Mongolia, is among the highest globally. This study aims to examine the patterns and trends of liver cancer in selected East Asian countries from 1990 to 2021. Methods: This study employed data from the Global Burden of Disease Study 2021 pertaining to key burden metrics-prevalence, incidence, mortality, years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs)-for selected East Asian countries from 1990 to 2021. Furthermore, the epidemiological trends and patterns were analyzed using decomposition analysis, Joinpoint regression, and age-period-cohort methods. Projections of the cancer burden through 2036 were generated using the Bayesian age-period-cohort model. Results: For all key indicators (incidence, prevalence, mortality, YLDs, YLLs, and DALYs), China had the highest values in both 1990 and 2021. The highest age-standardized rates for incidence (ASIR), mortality (ASMR), prevalence (ASPR), YLDs, YLLs, and DALYs (ASDR) were recorded in Mongolia. For all measured indicators of disease burden, the peak rates in each of the selected East Asian nations were consistently concentrated in the population aged 50 and above. Mongolia is forecasted to maintain the top-ranking ASIR values among the selected East Asian nations considered up to 2036. Conclusions: Over the past three decades, liver cancer has imposed a heavy disease burden on all selected East Asian nations, with rates being notably higher in the elderly population. These insights will provide policy-makers with evidence to guide public health strategies for disease prevention.

1.Introduction A great physician values absolute sincerity,aiming to save lives.The evolving practice of medicine encompasses both ancient tradi-tions and modern innovations,bringing together the East and West.Shanghai is a vibrant city where history meets modernity.Over a century ago,this city witnessed the collision of Chinese medicine and Western medicine.With the aspiration to"inherit ancient wisdom and explore new knowledge,"generations of med-ical pioneers started to pursue the dialogue between and integra-tion of Chinese and Western medicines.After 1949,Shanghai took the lead in responding to the policy of"Uniting Chinese Med-icine and Western Medicine."The efforts in establishing disci-plines,setting up wards,and nurturing talent laid a solid foundation for a systemized development of integrative medicine.

Objectives: Colorectal cancer (CRC) is common, with the adenoma-carcinoma sequence being crucial, but the roles of the PTEN/PI3K/AKT pathway and miRNAs in it are unclear. This study aimed to observe the expression of related miRNAs and pathway molecules in this sequence, explore their role in adenoma carcinogenesis, and offer new ideas for CRC early diagnosis and treatment. Methods: In this study, we observed the expression of miRNA-519 alpha, miRNA-454, miRNA-222-3p, and related molecules of the downstream PTEN/PI3K/AKT/beta-catenin pathway in colorectal adenoma-carcinoma sequence, and used Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), transcriptomic analysis, and immunohistochemistry (IHC) to examine the expression of these miRNAs and molecules in colorectal adenoma and adenocarcinoma tissues. Results: Clinical specimens showed miRNA-222-3p (Ct:17-31) was significantly higher than miRNA-519 alpha (Ct: 37-45) and miRNA-454 (Ct: 31-39) in adenoma and adenocarcinoma; compared with normal tissues, it was upregulated in colorectal adenocarcinoma (p=0.040) and tubular adenoma (p<0.001, higher than tubular adenocarcinoma, p<0.001), and gradually increased in ascending colon villous tubular adenoma (2 L), early carcinoma (3 E Ca vs. 2 L, p=0.020), and adenocarcinoma (4Ca vs. 2 L, p=0.005). Transcriptomic analysis showed miRNA-222-3p upregulated in high-grade (HTG, p=0.021) and low-grade tumor adenoma (LTG, p=0.123) relative to the normal control group (NCG); plasma exosomal miRNA-222-3p was upregulated in LTG (p<0.001) and HTG (p=0.033; both vs. NCG), and KEGG analysis identified the PI3K-AKT pathway as key in adenoma-to-carcinoma progression. In the Azoxymethane/Dextran sodium sulfate (AOM/DSS) model, serum miRNA-222-3p (p=0.040), spleen weight (p=0.019), and intestinal weight (p=0.004) were higher in the model group. Based on IHC and transcriptomics results, the PTEN/PI3K/AKT pathway plays a role in colorectal adenoma carcinogenesis, with PIK3CA and GSK3B possibly involved in post-transcriptional translation. Conclusions: These results indicated that miRNA-222-3p and the PTEN/PI3K/AKT pathway played an important role in colorectal adenoma-carcinoma sequence, especially in the ascending colon. MiRNA-222-3p may serve as a novel noninvasive diagnostic biomarker and therapeutic target for colorectal adenoma carcinogenesis.