Wogonoside (WG) is a flavonoid chemical component extracted from Scutellaria baicalensis, which exerts therapeutic effects on liver diseases. Ferroptosis, a novel form of programmed cell death, regulates diverse physiological/pathological processes. In this study, we attempted to investigate a novel mechanism by which WG mitigates liver fibrosis by inducing ferroptosis in hepatic stellate cells (HSCs). A CCl4‐induced mouse liver fibrosis model and a rat HSC line were employed for in vivo and in vitro experiments, both treated with WG. Firstly, the levels of the fibrotic markers α‐smooth muscle actin (α‐SMA) and α1(I)collagen (COL1α1) were effectively decreased by WG in CCl4‐induced mice and HSC‐T6 cells. Additionally, mitochondrial condensation and mitochondrial ridge breakage were observed in WG‐treated HSC‐T6 cells. Furthermore, ferroptotic events including depletion of SLC7A11, GPX4 and GSH, and accumulation of iron, ROS and MDA were discovered in WG‐treated HSC‐T6 cells. Intriguingly, these ferroptotic events did not appear in hepatocytes or macrophages. WG‐elicited HSC ferroptosis and ECM reduction were dramatically abrogated by ferrostatin‐1 (Fer‐1), a ferroptosis inhibitor. Importantly, our results confirm that SOCS1/P53/SLC7A11 is a signaling pathway which promotes WG attenuation of liver fibrosis. On the contrary, WG mitigated liver fibrosis and inducted HSC‐T6 cell ferroptosis were hindered by SOCS1 siRNA and pifithrin‐α (PFT‐α). These findings demonstrate that SOCS1/P53/SLC7A11‐mediated HSC ferroptosis is associated with WG alleviating liver fibrosis, which provides a new clue for the treatment of liver fibrosis.

Two new furanoid norditerpenes (1, 2) were isolated from the root tubers of Dioscorea bulbifera L. Their structures were established on the basis of extensive spectroscopic analysis.

OBJECTIVEThe authors retrospectively analyzed the follow-up data in 130 patients with intracranial benign meningiomas after Gamma Knife radiosurgery (GKRS), evaluated the tumor progression-free survival (PFS) rate and neurological function preservation rate, and determined the predictors by univariate and multivariate survival analysis.METHODSThis cohort of 130 patients with intracranial benign meningiomas underwent GKRS between May 2012 and May 2015 at the Second Hospital of Tianjin Medical University. The median age was 54.5 years (range 25–81 years), and women outnumbered men at a ratio of 4.65:1. All clinical and radiological data were obtained for analysis. No patient had undergone prior traditional radiotherapy or chemotherapy. The median tumor volume was 3.68 cm3 (range 0.23–45.78 cm3). A median margin dose of 12.0 Gy (range 10.0–16.0 Gy) was delivered to the tumor with a median isodose line of 50% (range 50%–60%).RESULTSDuring a median follow-up of 36.5 months (range 12–80 months), tumor volume regressed in 37 patients (28.5%), was unchanged in 86 patients (66.2%), and increased in 7 patients (5.4%). The actuarial tumor progression-free survival (PFS) rate was 98%, 94%, and 87% at 1, 3, and 5 years, respectively, after GKRS. Tumor recurred in 7 patients at a median follow-up of 32 months (range 12–56 months). Tumor volume ≥ 10 cm3 (p = 0.012, hazard ratio [HR] 8.25, 95% CI 1.60–42.65) and pre-GKRS Karnofsky Performance Scale score < 90 (p = 0.006, HR 9.31, 95% CI 1.88–46.22) were independent unfavorable predictors of PFS rate after GKRS. Of the 130 patients, 101 (77.7%) presented with one or more neurological symptoms or signs before GKRS. Neurological symptoms or signs improved in 40 (30.8%) patients, remained stable in 83 (63.8%), and deteriorated in 7 (5.4%) after GKRS. Two (1.5%) patients developed new cranial nerve (CN) deficit. Tumor volume ≥ 10 cm3 (p = 0.042, HR = 4.73, 95% CI 1.06–21.17) and pre-GKRS CN deficit (p = 0.045, HR = 4.35, 95% CI 0.84–22.48) were independent unfavorable predictors for improvement in neurological symptoms or signs. Six (4.6%) patients developed new or worsening peritumoral edema with a median follow-up of 4.5 months (range 2–7 months).CONCLUSIONSGKRS provided good local tumor control and high neurological function preservation in patients with intracranial benign meningiomas. Patients with tumor volume < 10 cm3, pre-GKRS Karnofsky Performance Scale score ≥ 90, and no pre-GKRS CN deficit (I–VIII) can benefit from stereotactic radiosurgery. It can be considered as the primary or adjuvant management of intracranial benign meningiomas.

Object The goal of this study was to assess neuroimaging and clinical outcomes in patients harboring brainstem metastases that were treated with the Leksell Gamma Knife. Methods Twenty-eight patients with brainstem metastases (32 lesions: 8 midbrain, 21 pontine, and 3 medullary) were consecutively treated with GKS. The primary cancer diagnoses in this group included 22 cases of lung cancer, 5 cases of breast cancer, and 1 case of rectal cancer. The median age of the patients was 61 years (range 45–83 years). The median treated lesion volume was 0.78 cm3 (range 0.03–5.6 cm3), and the median GKS margin dose was 16 Gy (range 12–20 Gy). Overall survival in these patients was calculated using the Kaplan-Meier method. Results The median survival time was 9 months after GKS (range 2–32 months). Survival was 39.3% at 1 year and 10.7% at 2 years. The tumor control rate in the series was 90.6% (29 of 32 lesions). Development of peritumoral edema occurred in 1 patient after GKS; 4 months after GKS, the edema disappeared. Conclusions Gamma Knife surgery using a median margin dose of 16 Gy is a safe and effective local therapy for patients with brainstem metastases.

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