Objectives:Neoadjuvant chemotherapy with dual HER2 blockade is the standard of care for early-stage HER2-positive breast cancer. However, the role of anthracyclines remains controversial. This meta-analysis aimed to evaluate the efficacy and safety of neoadjuvant dual HER2 blockade combined with anthracycline-containing vs. anthracycline-free chemotherapy. Methods:A literature search was conducted across PubMed, EMBASE, and the Cochrane Library. Eligible studies included patients with resectable stage I-III HER2-positive breast cancer receiving neoadjuvant dual HER2 blockade with either an anthracycline-containing (A-based) or anthracycline-free (non-A) chemotherapy regimen. Standard meta-analytic methods using a random-effects or fixed-effect model were applied according to heterogeneity (I2). Results:Seven articles met the inclusion criteria. The addition of anthracyclines to dual HER2 blockade therapy (DHBT) did not significantly improve the pCR rate (OR, 1.07; 95 % CI, 0.81-1.43; p=0.62), composite DFS/EFS/PFS (HR, 0.50; 95 % CI, 0.18-1.38; p=0.18), or overall survival (OS) (HR, 0.77; 95 % CI, 0.39-1.51; p=0.45). The incidence of cardiac adverse events did not differ significantly between the A-based and non-A groups (OR, 0.96; 95 % CI, 0.31-2.91; p=0.94). No significant difference was observed in the incidence of LVEF decline ≥10 % from baseline to <50 % between the A-based and non-A groups (OR, 1.47; 95 % CI, 0.79-2.77; p=0.23). Notably, the non-A group had a significantly higher incidence of grade ≥3 diarrhea (OR, 0.60, favoring the A-based group; 95 % CI, 0.38-0.95; p=0.03). Conclusions:In resectable HER2-positive breast cancer, neoadjuvant DHBT without anthracyclines achieves pCR rates non-inferior to A-based regimens, with no early survival detriment observed. While short-term cardiotoxicity is unremarkable, grade ≥3 diarrhea occurs more frequently with non-A approaches.
Objectives:Renal allograft rejection diagnosis requires invasive biopsy. We assessed whether peripheral blood mRNA of 14 Hippo, interferon (IFN) and NF-κB pathway genes and 11 serum biomarkers could distinguish acute rejection from stable graft function. Methods:Three groups: biopsy-confirmed acute rejection (n=20), stable graft (n=25), healthy controls (n=30). PBMC mRNA was quantified by qRT-PCR; serum biomarkers by ELISA and spectrophotometry. Statistical analyses used Mann-Whitney U with Benjamini-Hochberg correction; ROC analyses used bootstrap 95 % CIs and 5-fold cross-validation. GEO datasets GSE51675 and GSE145408 provided directional cross-validation. Results:Thirteen of 14 genes were upregulated in rejection vs. controls (pFDR<0.01); TEAD1 (log2FC=+2.44) and TRAF6 (+2.40) led. ISG15 was downregulated in both transplant groups, consistent with calcineurin inhibitor-mediated suppression, while serum free ISG15 protein was unchanged in stable graft but markedly lower in rejection than in both controls and stable graft (pFDR<0.001 and 0.002), discriminating rejection from stable graft in a way the mRNA signal did not. Only TEAD1 (Cohen's d=1.40) and YAP1 (d=1.17) discriminated rejection from stable graft with adequate power. TEAD1 mRNA (AUC=0.849) and serum leptin (AUC=0.922) were the strongest single markers; their combination yielded cross-validated AUC=0.990. Conclusions:PBMC YAP1/TEAD1 with serum leptin are promising non-invasive biomarkers for acute renal rejection. ISG15 downregulation is more consistent with calcineurin inhibitor-mediated suppression than with generalized immune impairment, although this interpretation requires direct mechanistic confirmation; notably, serum free ISG15 protein discriminated rejection from stable graft even though PBMC ISG15 mRNA did not, suggesting the protein-level measurement warrants further evaluation as a candidate marker. Prospective multicentre validation is required.
Objectives:Fumaria agraria is still poorly characterized, although the interest in plant-derived bioactive compounds is growing. This study aimed to investigate its phytochemical composition and its antioxidant potential. Methods:Sequential solvent extraction yielded n-hexane, ethyl acetate and methanol fractions. Fatty acids were determined by gas chromatography with flame ionization detection (GC-FID) and phenolic compounds in the polar fractions by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Antioxidant activity was assessed via DPPH, ABTS, and FRAP assays, alongside total phenolic (TPC) and flavonoid (TFC) content. Results:GC-FID analysis identified five fatty acids dominated by unsaturated forms (76.51 %), with linoleic acid as the principal individual component (40.29 %). LC-MS/MS analysis revealed 11 phenolic compounds, with luteolin being the most abundant phenolic compound, accounting for 67 % of the total identified polyphenols. The polar extracts exhibited the highest TPC, TFC, and antioxidant activity in all assays. Conclusions:F. agraria is a valuable source of unsaturated fatty acids and flavonoids, particularly luteolin, which likely contribute to the antioxidant activity of its polar extracts. These findings support its traditional medicinal use and highlight its potential as a source of natural antioxidant compounds, although further in vivo studies are required to confirm these results.
Objectives:Glioblastoma (GBM) is a highly aggressive brain cancer. Golgi dysfunction plays a role in tumorigenesis. Methods:This study analyzed the role of Golgi apparatus-related genes (GARGs) in GBM using bioinformatics. Prognostic genes were identified using differential expression, Cox, and Lasso analyses. A prognostic model and nomogram were constructed based on gene expression and clinical characteristics. Immune infiltration and drug sensitivity analyses were performed in different risk groups. Reverse transcription quantitative PCR (RT-qPCR) was employed to explore the expression of prognostic genes. Results:A total of 5 prognostic genes (CD14, FMOD, LGR6, SLC16A13, and KDELR2) of GBM were identified, and on the basis of the prognostic genes, a prognostic model was built. There was a significant survival difference between patients in the high and low risk groups for GBM. Receiver operating characteristic (ROC) curve indicated that the predictive effect of the prognostic model in the training set was moderate, with an AUC value of around 0.7. The nomogram showed that risk score had a better predictive effect than age. Drug sensitivity analysis demonstrated that sorafenib was more sensitive in the low-risk group of GBM. RT-qPCR results revealed that compared with the control group, the expression levels of CD14 and SLC16A13 were significantly downregulated in GBM cell lines, while FMOD and LGR6 were markedly upregulated. The expression of KDELR2 exhibited obvious cell line-dependent variation. Conclusions:In summary, this study establishes a Golgi apparatus-related gene signature that not only offers prognostic insights but may also informs tailored therapeutic strategies for GBM patients.
Objectives:This study aimed to evaluate the association between admission blood gas, platelet, and inflammatory parameters and the presence of IVH. Methods:This retrospective case-control study included 356 preterm infants admitted to a tertiary neonatal intensive care unit between 2016 and 2025, including 165 infants with IVH and 191 without IVH. Initial blood gas and complete blood count parameters were analyzed. Multivariable logistic regression was used to identify independent factors associated with IVH. Results:Lower gestational age was significantly associated with IVH presence and severity (p<0.001). Lactate levels were higher in the IVH group (3.10 vs. 2.60 mmol/L; p=0.013). In the exploratory integrated model including gestational age, lactate, platelet count, MPV, and the N/L ratio, lactate showed a borderline association with IVH (OR=1.099, 95 % CI: 0.995-1.214; p=0.063), whereas lower platelet count, lower MPV, and higher N/L ratio remained independently associated with IVH. Conclusions:Lower platelet counts, lower MPV values, and higher N/L ratios were independently associated with IVH in the exploratory integrated model, while admission lactate showed a borderline association after adjustment for gestational age and hematological parameters. These findings should be interpreted as early associations rather than validated predictive biomarkers, and prospective studies with standardized cranial ultrasonography and external validation are needed.
