Guowang Yang

Background: Breast cancer survivors frequently experience fatigue-centered symptom clusters—concurrent, interrelated symptoms including fatigue, pain, and dyspnea—that significantly impair quality of life and functional status. Despite the high prevalence of these symptoms, few interventional trials have targeted symptom clusters as a unified treatment endpoint. Current management relies predominantly on behavioral interventions with inconsistent efficacy, and no pharmacological agent has demonstrated high-quality evidence for cluster-level symptom control in this population. Methods: This multicenter, randomized, double-blind, placebo-controlled trial will enroll 262 postoperative breast cancer survivors (stage I–IIIA) with moderate-to-severe fatigue-centered symptom clusters from 11 hospitals across China. Eligible participants must have completed adjuvant therapy, exhibit an ECOG performance status of 0–1, and present with a MDASI-C fatigue-dyspnea-pain subscale score ≥4. Participants will be randomized 1:1 to receive either Shenqi Shiyiwei Granule or matching placebo for 60 days, with standardized psycho-exercise-dietary guidance provided to all participants throughout a 120-day study period. The primary endpoint is the change from baseline in the fatigue-dyspnea-pain symptom cluster score at 2 months, assessed using the MD Anderson Symptom Inventory-Chinese version (MDASI-C). Secondary endpoints include quality-of-life measures (MFSI-SF, FACT-B, TCM Spleen Qi Deficiency Scale) and cardiopulmonary functional capacity. Exploratory biomarker analyses will evaluate hypothalamic-pituitary-adrenal axis hormones, cytokine profiles, and gonadal hormone concentrations to elucidate potential mechanisms. Efficacy will be analyzed using mixed-effects models for repeated measures (MMRM) with prespecified sensitivity analyses for missing data assumptions. Discussion: This trial represents one of the first rigorous investigations targeting the fatigue-centered symptom cluster as a unified therapeutic endpoint in breast cancer survivors. By combining traditional Chinese herbal medicine with guideline-endorsed behavioral interventions, this study aims to provide high-quality evidence for a novel multi-target treatment strategy. The exploratory biomarker assessments may illuminate the biological mechanisms underlying symptom cluster interrelationships, establishing a foundation for future mechanistic and interventional research in cancer survivorship care. Clinical trial registration: [ https://itmctr.ccebtcm.org.cn/mgt/project/user/user-project-view/0A267E22-1E0A-4A95-99B0-E5964124F203 ], The International Traditional Medicine Clinical Trial Registry [ITMCTR2025001511].

ObjectivesTo evaluate the efficacy and safety of Yiqi Huatan Sanjie (YQHTSJ) Formula in patients with pulmonary nodules and the traditional Chinese medicine pattern of Lung-Spleen Qi deficiency with phlegm-stasis accumulation.MethodsIn this prospective two-center cohort study, 170 patients were enrolled, including 50 in the treatment group and 120 controls. The treatment group received YQHTSJ Formula for 3 months, whereas controls underwent watchful waiting. The primary outcome was change in mean nodule diameter on computed tomography. Secondary outcomes included exploratory artificial intelligence-assisted volumetry, traditional Chinese medicine symptom scores, anxiety and depression scores, and safety. Propensity score matching was performed using 1:1 nearest-neighbor matching with a caliper of 0.2.ResultsOf 170 enrolled patients, 140 completed follow-up. Propensity score matching generated 37 matched pairs, with all standardized mean differences below 0.1. In the matched cohort, the diameter-based response rate was higher with YQHTSJ Formula than with watchful waiting (43.2% vs 0.0%; exact McNemar test, P< 0.001), with 16 discordant pairs favoring treatment and none favoring control. The paired mean difference in diameter change was −2.95 mm favoring treatment (95% CI, −4.62 to −1.29; paired t-test, P = 0.001). Anxiety and traditional Chinese medicine symptom scores improved after treatment (both P < 0.05). Among 14 treated patients with evaluable paired thin-slice DICOM data, the exploratory volumetric response rate was 50.0%. No serious adverse events occurred.ConclusionsYQHTSJ Formula was associated with short-term pulmonary nodule regression or stabilization and was generally well tolerated. Larger randomized multicenter trials are needed.

Background: Huayu Wan (HYW), a Traditional Chinese Medicine (TCM) formulation widely used in the clinical treatment of cancer, has demonstrated anti-tumor activity and augments chemotherapy efficacy by improving intratumoral drug delivery in non-small cell lung cancer. However, its efficacy and role in enhancing the response to immune checkpoint inhibitors (ICIs) for the treatment of triple-negative breast cancer (TNBC) remain unclear. Objective: To study the underlying mechanisms of HYW in enhancing the efficacy of ICIs for TNBC treatment. Materials and methods: In the 4T1 TNBC model, tumor growth, vascular structure/function, immune cell infiltration, angiogenic factors and effector cytokines were evaluated using ultrasound imaging, immunohistochemistry, immunofluorescence, and ELISA. HYW’s effects on angiogenesis were validated via in vitro assays (HUVEC proliferation, tube formation, wound healing and transwell invasion) under normal oxygen/hypoxic conditions. Results: TCGA data and network pharmacology identified VEGFA and the PI3K-Akt/HIF-1 signaling axis as key targets of HYW. HYW significantly enhanced ICIs efficacy, with a tumor inhibition rate of 36.55% (vs. 5.01% for ICIs alone). Mechanistically, HYW: Normalized tumor vasculature: Restored the balance between proangiogenic and antiangiogenic factors (reduced VEGFA/bFGF, increased TSP-1/PF4), enhanced pericyte coverage and improved vascular maturity, and enhanced intratumoral perfusion (ultrasound imaging). Alleviated hypoxia: Inhibited HIF-1α and reduced hypoxic regions (Hypoxyprobe staining). Remodeled the TME: Promoted CD8 ⁺ T cell infiltration, increased effector cytokines (GZMB, IFN-γ, TNF-α), and inhibited CD8 ⁺ T cell exhaustion, downregulated exhaustion markers (Tim3, CD244, CD101, PD-L1). Inhibited PI3K-Akt-mTOR signaling: Reduced downstream HIF-1α/VEGFA expression, breaking the hypoxia-angiogenesis-immunosuppression cycle. Conclusion: HYW enhances ICIs efficacy in TNBC by normalizing tumor vasculature and remodeling the tumor immune microenvironment (TIME), which provides a novel rationale for combining TCM with ICIs to improve TNBC treatment outcomes.

Small cell lung cancer (SCLC) is a heterogeneous disease with different pathogenic mechanisms. A range of molecular classification systems has been propose

Background: Platelet indices (PIs) – including platelet count (PC), plateletcrit (PCT), mean platelet volume, and platelet distribution width (PDW) – are routinely assessed in clinical practice. Although observational studies have reported associations between PIs and lung cancer outcomes, the dose–response relationship and causality remain unestablished. This study aims to determine prognostic thresholds of PIs and elucidate their causal roles in lung cancer. Methods: We systematically reviewed PubMed, Medline, and Web of Science (through December 2024) for studies on PIs and lung cancer prognosis. Hazard ratios (HRs) were pooled via random-effects models. Dose–response thresholds were identified using restricted cubic splines and generalized least squares. Two-sample Mendelian randomization (MR) analyses with inverse variance weighting assessed causality, complemented by sensitivity analyses (MR-Egger, weighted median). Results: In the meta-analysis of 62 studies (N = 38,562 patients), elevated PC (HR = 1.016, 95% CI: 1.009 to 1.024) and PCT (HR = 1.704, 95% CI: 1.040–2.790) independently predicted poorer overall survival. A nonlinear dose–response relationship revealed that each 10 ⁹ /L increase in PC conferred a 4.2% higher risk of adverse prognosis in non-small cell lung cancer (HR = 1.042, 95% CI: 1.029 to 1.056), with a critical threshold at 177.5 × 10 ⁹ /mL. MR analyses demonstrated population-specific causality: a 1-SD increase in PC elevated lung cancer risk by 33% in East Asians (OR = 1.33, P < .001), while in Europeans, equivalent increments in PC and PCT increased small cell lung cancer (SCLC) risk by 17% (OR = 1.17, P = .01) and 19% (OR = 1.19, P < .001), respectively. Additionally, higher PDW was causally linked to a 6% increased lung cancer risk (OR = 1.06, P = .02). Conclusion: This first study integrating dose–response meta-analysis and MR evidence identifies PC and PCT as robust prognostic biomarkers for lung cancer, with population-specific causal effects. The identified PC threshold (177.5 × 10 ⁹ /mL) provides a clinically actionable tool for NSCLC risk stratification, highlighting the translational potential of routine PIs monitoring in oncology practice.

Objective: To serve as a clinical reference, we conducted a meta-analysis to assess and compare the efficacy and safety of combining Chinese herbal injections (CHIs) with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for treating advanced EGFR-mutated non-small cell lung cancer (NSCLC). Methods: Predetermined databases contained randomized controlled studies comparing CHIs + EGFR-TKIs to EGFR-TKIs alone. The Cochrane Reviewer’s Handbook for Systematic Reviews of Interventions was used to evaluate study methodology. To assess the effects of CHIs on patients with NSCLC receiving EGFR-TKIs, R (version 4.4.0) and RevMan (version 5.4) were used to conduct a meta-analysis using the Mantel–Haenszel or Inverse Variance method. The quality of results was evaluated using the Grade of Recommendations Assessment, Development and Evaluation (GRADE) method. Results: The 13 qualifying trials included 899 subjects. The objective response rate (ORR) was significantly increased by Kanglaite injection (RR = 1.52, 95% confidence interval [CI]: 1.07–2.15, p = 0.02). The disease control rate (DCR) was influenced by Kanglaite injection (RR = 1.14, 95% CI: 1.01–1.29, p = 0.04) and Aidi injection (RR = 1.23, 95% CI: 1.02–1.48, p = 0.03). Shenmai injection + EGFR-TKIs reduced dermatologic toxicities (RR = 0.35, 95% CI: 0.18–0.69, p = 0.002). The combination of CHIs with EGFR-TKIs improved the expression of CD3 ⁺ (standardized mean difference [SMD] = 1.38, 95% CI: 0.46–2.30, p = 0.003), CD4 ⁺ (SMD = 1.08, 95% CI: 0.51–1.65, p = 0.0002), and the CD4 ⁺ /CD8 ⁺ ratio (SMD = 0.96, 95% CI: 0.54–1.38, p < 0.00001) compared to EGFR-TKIs alone. The GRADE method revealed that most outcomes exhibited low certainty evidence. Conclusion: The combination of CHIs and EGFR-TKIs improved ORR, DCR, adverse effects, and immune function in patients with NSCLC. Due to limitations in the assessed research, high-quality clinical studies with rigorous designs are required to confirm the findings. Systematic Review: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024561845, Identifier CRD42024561845.

Background The optimal management of gastrointestinal stromal tumor (GIST) ≤ 2 cm in diameter remains debated. This study aimed to compare long-term survival outcomes between patients with small GIST undergoing endoscopic treatment (ET) and those treated with surgical resection (SR). Methods Between 2000 and 2021, patients with small GIST were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was employed to minimize selection bias in the comparison process. Kaplan–Meier analysis and multivariate Cox proportional hazards models were applied to evaluate the effects of demographic and clinical characteristics on overall survival (OS) and cancer-specific survival (CSS). Results A total of 1400 patients with small GIST were included, comprising 470 (33.57%) undergoing ET and 930 (66.43%) receiving SR. The 5-year OS and CSS rates were compared between the ET and SR groups both before and after PSM. Before PSM, the 5-year OS rates were 75.28% vs. 83.96% (P = 0.878), and CSS rates were 94.38% vs. 95.09% (P = 0.284). After PSM, the corresponding rates were 85.81% vs. 86.45% (P = 0.393) for OS and 96.77% vs. 95.48% (P = 0.075) for CSS. Multivariable analysis adjusting for covariates demonstrated comparable risks of OS (HR = 0.96, 95% CI 0.74–1.24, P = 0.737) and CSS (HR = 1.26, 95% CI 0.72–2.20, P = 0.426) between the two treatment groups. No significant differences were observed between the groups after PSM. Conclusions Our findings demonstrate comparable long-term OS and CSS outcomes between endoscopic and surgical treatment groups in patients with GIST ≤ 2 cm in diameter.