BackgroundChronic atrophic gastritis and gastric precancerous lesions are associated with increased gastric cancer risk. Chinese herbal medicine is widely used as an adjunct to conventional therapy, but the certainty and clinical interpretation of its effects remain unclear.ObjectiveTo evaluate the efficacy and safety of Chinese herbal medicine added to the same conventional therapy for chronic atrophic gastritis and gastric precancerous lesions.MethodsEight international and Chinese databases and three trial registries were searched from inception to 31 March 2026 and updated to 16 August 2026. Randomised controlled trials comparing Chinese herbal medicine plus the same conventional therapy with conventional therapy alone and reporting extractable pathological outcomes were included. Random-effects models used restricted maximum likelihood estimation and Hartung-Knapp inference. Additional sensitivity analyses examined clinically comparable histopathology, baseline balance based on auditable pretreatment data, and exclusion of high-risk-of-bias results. Risk of bias was assessed using RoB 2 and certainty using GRADE.ResultsSixty-nine randomised trials comprising 6,983 participants in eligible comparisons were included. Exploratory Broad end-of-treatment analyses favoured combined treatment for gastric mucosal atrophy (30 studies; SMD −1.63, 95% CI −2.03 to −1.24), intestinal metaplasia (29 studies; SMD −1.48, 95% CI −1.90 to −1.06), and dysplasia or intraepithelial neoplasia (21 studies; SMD −1.25, 95% CI −1.51 to −0.99). Heterogeneity was substantial (I2 82.4%–92.7%); prediction intervals crossed the null for atrophy and intestinal metaplasia but not for dysplasia/intraepithelial neoplasia. Sensitivity analyses restricted to clinically comparable histopathological assessments included only three to four studies and were imprecise, with confidence intervals crossing the null. Helicobacter pylori clearance/negative conversion among baseline-positive participants was higher with combined treatment (15 studies; RR 1.25, 95% CI 1.15–1.37), whereas the strict test-of-cure sensitivity was imprecise (3 studies; RR 1.19, 95% CI 0.91–1.56). There was no clear evidence of a difference in reported adverse events (14-study evidence set; RR-contributing studies = 12; RR 0.93, 95% CI 0.58–1.50), which should not be interpreted as evidence of equivalent safety. Certainty was low for all five principal outcomes.ConclusionChinese herbal medicine added to conventional therapy may be associated with lower short-term pathological scores on average, but the magnitude and clinical meaning of these effects remain uncertain because of trial limitations, marked heterogeneity, and imprecision in clinically comparable analyses. The findings do not establish durable histological regression or gastric cancer prevention, and the pooled estimates should not be interpreted as a class-wide effect applicable to all Chinese herbal medicines.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261442138, identifier CRD420261442138.
PurposeChemotherapy-induced peripheral neuropathy (CIPN) is a heterogeneous, treatment-limiting adverse event of cytotoxic chemotherapy that impairs sensory, motor, autonomic and balance function, and substantially reduces cancer patients’ quality of life. Current pharmacotherapy options are limited: duloxetine is the only guideline-recommended agent for established painful CIPN, while no drugs are approved for primary prevention. Non-pharmacological interventions have emerged as promising adjunctive strategies, yet evidence strength varies widely across modalities and patient subgroups. This narrative review aimed to synthesize contemporary clinical evidence of non-pharmacological interventions for CIPN prevention, symptom treatment and functional rehabilitation, to deliver stratified, chemotherapy-specific clinical guidance and identify gaps for future research.MethodA narrative review design was adopted, without pre-registration or standardized systematic review screening protocols. Targeted manual literature retrieval was conducted across PubMed, Web of Science, CNKI and Wanfang Data for peer-reviewed human clinical studies published between January 2018 and March 2025. We focused on four core non-pharmacological modalities for CIPN: multimodal exercise therapy, physical therapy incorporating cryotherapy, acupuncture-based complementary therapies, and behavioral self-management interventions. High-certainty evidence was defined as consistent results from large multicenter randomized controlled trials and network meta-analyses; moderate/low-certainty evidence was derived from small single-center trials and observational studies.ResultsCumulative stratified evidence demonstrates clear heterogeneity in intervention efficacy and clinical applicability. Multimodal supervised exercise and physical rehabilitation carry the most consistent high-certainty evidence for both primary CIPN prevention and functional recovery, with significant improvements in numbness, neuropathic pain, balance and muscle strength. Cryotherapy shows robust preventive efficacy exclusively in patients receiving taxane chemotherapy, with insufficient supportive data for platinum or vinca alkaloid regimens. Acupuncture, including warm needle acupuncture, TEAS and electroacupuncture, provides moderate-to-low certainty adjunctive relief for refractory established CIPN symptoms but is not recommended as first-line therapy. Behavioral interventions exert limited direct therapeutic effects on nerve injury, yet effectively improve symptom coping, treatment adherence and long-term self-management. All interventions exhibit favorable safety profiles with minimal severe adverse events when individualized to patient fitness, comorbidities and chemotherapy regimens.ConclusionNon-pharmacological interventions cannot be considered uniformly effective for all CIPN populations; evidence strength and clinical indications differ markedly by modality. Supervised multimodal exercise and physical rehabilitation represent first-line adjunctive strategies for broad CIPN prevention and functional recovery. Cryotherapy is a targeted preventive option limited to taxane-treated patients. Acupuncture serves as secondary adjunctive care for persistent symptoms, while behavioral interventions function as supportive self-management tools. Clinical implementation requires agent-specific patient stratification, individualized intervention prescription, standardized validated CIPN assessment tools, and integrated multidisciplinary oncology rehabilitation pathways. Further large, stratified randomized controlled trials with long-term follow-up are required to standardize intervention protocols and validate sustained clinical benefits.
Breast cancer cells encounter heterogeneous oxygen conditions arising from abnormal vasculature, impaired perfusion, rapid proliferation, and fluctuating blood flow. Adaptation to oxygen stress is increasingly recognized as a major driver of tumor progression and therapeutic resistance. This review integrates current evidence on the mechanisms through which breast cancer cells adapt to oxygen stress and identifies opportunities for precision therapeutic intervention. Oxygen stress activates hypoxia-inducible factors and interconnected signaling networks that coordinate metabolic reprogramming, mitochondrial adaptation, reactive oxygen species generation, and redox homeostasis. These responses are reinforced by autophagy, unfolded protein response, epithelial–mesenchymal plasticity, cancer stemness, extracellular-matrix remodeling, angiogenesis, and immune suppression. Together, these mechanisms sustain cellular survival, facilitate invasion and metastasis, and promote resistance to chemotherapy, radiotherapy, endocrine therapy, HER2-directed treatment, and other targeted approaches. Oxygen-stress responses vary across breast cancer subtypes, emphasizing the need for biologically informed therapeutic strategies. Potential precision approaches include targeting hypoxia signaling, glycolytic and mitochondrial dependencies, lactate metabolism, antioxidant systems, autophagy, proteostasis, hypoxia-activated pathways, and hypoxia-associated immune suppression. Integrating molecular biomarkers, metabolic profiling, spatial technologies, and functional imaging may improve identification of tumors with actionable oxygen-stress dependencies. Oxygen-stress adaptation represents an interconnected survival network rather than a single hypoxia pathway. Therapeutically exploiting tumor-specific adaptive dependencies, while accounting for subtype and spatial heterogeneity, may provide new opportunities to overcome treatment resistance and improve precision management of breast cancer.
Treatment-resistant breast cancer remains a major clinical challenge because conventional clinicopathological and molecular biomarkers incompletely capture the dynamic interactions between tumour cells, immunity, inflammation, and the systemic host response. Next-generation inflammatory signatures offer an opportunity to expand the diagnostic–prognostic landscape by integrating cellular, molecular, immune, and thromboinflammatory indicators with established tumour characteristics. This narrative review critically examines emerging evidence for neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, C-reactive protein, cytokines, tumour-associated macrophages, myeloid-derived suppressor cells, neutrophil extracellular traps, coagulation biomarkers, and liquid-biopsy-derived measures in treatment-resistant breast cancer. Particular attention is given to sources of heterogeneity, including population characteristics, tumour subtype, treatment exposure, comorbid inflammation, sampling time, specimen processing, analytical platforms, and inconsistent biomarker thresholds. The review further evaluates the transition from biomarker discovery to clinical decision support, highlighting the need for prospective multicentre validation, standardised analytical procedures, external validation of computational models, and integration with molecular subtyping, circulating tumour DNA, imaging, and immune profiling. Rather than interpreting inflammation as a static prognostic variable, longitudinal inflammatory trajectories may provide earlier signals of biological treatment resistance and complement conventional measures of disease progression. Future research should establish clinically actionable inflammatory combinations and evaluate biomarker-guided anti-inflammatory strategies alongside standard therapies. Ultimately, integrating inflammatory phenotypes with tumour molecular characteristics may facilitate earlier recognition of resistance and more precise, dynamic, and equitable breast cancer management.
Bone metastases constitute one of the most severe complications in patients with advanced malignancies. Conventional treatment approaches face significant limitations: surgical intervention carries a high risk of recurrence; radiotherapy and chemotherapy often cause myelosuppression; and anti-resorptive agents provide only limited control over tumor progression. Although immunotherapy has achieved remarkable success in various solid tumors in recent years, its therapeutic impact on bone metastases remains limited. This limitation is largely attributed to the distinct immunosuppressive microenvironment within bone lesions, which is marked by (1) a substantial decline in both the quantity and functional activity of effector immune cells, coupled with an abnormal accumulation of immunosuppressive cell populations, and (2) the formation of a vicious cycle of “tumor growth-bone metabolic imbalance-immune suppression,” driven by complex signaling interactions among osteoblasts, osteoclasts, and tumor cells. Recently, nanomaterials have emerged as promising therapeutic platforms due to their precise targeting and delivery capacity, inherent immune-stimulatory properties, and potential to restore bone homeostasis. Nonetheless, translating nanoplatforms into clinical practice for skeletal lesions remains a formidable challenge. This review highlights how specialized organic-inorganic hybrids and biomimetic nanoplatforms have achieved the most significant microenvironment remodeling and osteolytic inhibition within intraosseous murine models. Ultimately, we provide an actionable roadmap detailing how integrating multi-omics precision profiles and temporal programmable delivery can bridge the gap between preclinical nanomedicine and clinical oncological translation.
