Mechanism of Reactive Oxygen/Nitrogen Species in Liver Ischemia-Reperfusion Injury and Preventive Effect of Chinese Medicine.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.

Survival outcomes and treatment experience of 124 patients with primary central nervous system lymphoma.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a rare malignancy of the central nervous system with high invasiveness. There is little consensus on the treatment of PCNSL. This study retrospectively studied data from PCNSL patients in a single center to summarize treatment experience and explore prognostic factors. METHODS: Survival curves were drawn using the Kaplan-Meier method and prognostic factors were analyzed using Cox's hazards model. RESULTS: In multivariate analysis, cerebrospinal fluid lactic acid dehydrogenase (CSF LDH; p = 0.005 and p = 0.002), neutrophil to lymphocyte ratio (NLR; p = 0.014 and p = 0.038), and completion of four cycles of induction therapy (p < 0.001and p < 0.001) were significant and independent predictors of overall survival (OS) and progression-free survival (PFS), respectively. CONCLUSION: On the basis of this study, we propose that PCNSL patients should receive early induction therapy with sufficient cycles. Subsequent consolidation therapy can prevent relapses and improve survival. In patients with PCNSL, the independent prognostic factors for OS and PFS were CSF LDH level, NLR, and full cycles of induction therapy.

Clinical Outcomes and Prognostic Analysis of 101 Patients of Central Neurocytoma: A 10-Year Treatment Experience at a Single Institution.

Objective: Central neurocytoma (CN) is a rare type of tumor that currently lacks an optimal treatment protocol. This study aimed to explore the clinical outcomes of CN in a cohort of 101 patients and identify prognostic factors associated with multiple treatment modalities. Methods: This monocentric study retrospectively analyzed the clinical data of 101 CN patients who underwent surgical resection. The patients were followed up, and their overall survival (OS) and progression-free survival (PFS) were calculated. Results: For the entire cohort, the 5- and 10-year OS rates were 88.7% and 82.8%, respectively, and the 5- and 10-year PFS rates were 86.5% and 64.9%, respectively. Of the 82 (81.19%) patients with CN who underwent gross total resection (GTR), 28 (28/82, 34.1%) also received radiotherapy (RT). Of the 19 (18.81%) patients with CN who underwent subtotal resection (STR), 11 (11/19, 57.9%) also received RT or stereotactic radiosurgery (SRS). Compared to STR, GTR significantly improved the 5-year OS (92.4% vs. 72.4%, P=0.011) and PFS (92.4% vs. 60.4%, P=0.009) rates. Radiotherapy did not affect OS in the GTR group (p=0.602), but it had a statistically significant effect on OS in the STR group (P<0.001). However, the OS (P=0.842) and PFS (P=0.915) in the STR plus radiotherapy group were comparable to those in the GTR alone group. Compared to STR alone, STR plus radiotherapy improved the 5-year PFS rate from 25% to 75% in patients with atypical CN (P=0.004). Cox regression models and a competing risk model showed that the removal degree and radiotherapy were independent prognostic factors for survival. With improvements in modern radiotherapy techniques, severe radiotherapy toxicity was not observed. Conclusion: Our findings support the use of GTR whenever possible. Radiotherapy can improve the prognosis of patients who undergo STR, especially in atypical CNs having a higher tendency to relapse. Close imaging follow-up is necessary. Our findings will help clinicians to select optimal, individualized treatment strategies to improve OS and PFS for patients with CN.

Ethyl Acetate Fraction of Dicliptera chinensis (L.) Juss. Ameliorates Liver Fibrosis by Inducing Autophagy via PI3K/AKT/mTOR/p70S6K Signaling Pathway.

OBJECTIVE: To investigate the molecular mechanism underlying the anti-hepatic fibrosis activity of ethyl acetate fraction Dicliptera chinensis (L.) Juss. (EDC) in human hepatic stellate cells (HSCs) in vitro and in a carbon tetrachloride (CCl4)-induced hepatic fibrosis mouse model in vivo. METHODS: For in vitro study, HSCs were pre-treated with platelet-derived growth factor (10 ng/mL) for 2 h to ensure activation and treated with EDC for 24 h and 48 h, respectively. The effect of EDC on HSCs was assessed using cell counting kit-8 assay, EdU staining, transmission electron microscopy, immunofluorescence staining, and Western blot, respectively. For in vivo experiments, mice were intraperitoneally injected with CCl4 (2 ° L/g, adjusted to a 25% concentration in olive oil), 3 times per week for 6 weeks, to develop a hepatic fibrosis model. Forty 8-week-old male C57BL/6 mice were divided into 4 groups using a random number table (n=10), including control, model, positive control and EDC treatment groups. Mice in the EDC and colchicine groups were intragastrically administered EDC (0.5 g/kg) or colchicine (0.2 mg/kg) once per day for 6 weeks. Mice in the control and model groups received an equal volume of saline. Biochemical assays and histological examinations were used to assess liver damage. Protein expression levels of α -smooth muscle actin (α -SMA) and microtubule-associated protein light chain 3B (LC3B) were measured by Western blot. RESULTS: EDC reduced pathological damage associated with liver fibrosis, downregulated the expression of α -SMA and upregulated the expression of LC3B (P<0.05), both in HSCs and the CCl4-induced liver fibrosis mouse model. The intervention of bafilomycin A1 and rapamycin in HSCs strongly supported the notion that inhibition of autophagy enhanced α -SMA protein expression levels (P<0.01). The results also found that the levels of phosphoinositide (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and p-p70S6K all decreased after EDC treatment (P<0.05). CONCLUSIONS: EDC has anti-hepatic fibrosis activity by inducing autophagy and might be a potential drug to be further developed for human liver fibrosis therapy.

Intensity-modulated radiotherapy for gliomas:dosimetric effects of changes in gross tumor volume on organs at risk and healthy brain tissue.

AIM: The aim of this study was to explore the effects of changes in the gross tumor volume (GTV) on dose distribution in organs at risk (OARs) and healthy brain tissue in patients with gliomas. METHODS: Eleven patients suffering from gliomas with intensity-modulated radiotherapy (IMRT) plans treated with a simultaneous integrated boost technique planned before therapy (initial plans) were prospectively enrolled. At the end of radiotherapy, patients underwent repeat computed tomography and magnetic resonance imaging, and IMRT was replanned. The GTV and dosimetric parameters between the initial and replanned IMRT were compared using the Wilcoxon two-related-sample test, and correlations between the initial GTV and the replanned target volumes were assessed using the bivariate correlation test. RESULTS: The volume of the residual tumor did not change significantly (P>0.05), the volume of the surgical cavity decreased significantly (P<0.05), and the GTV and target volumes decreased significantly at the end of IMRT (all P<0.05). The near-maximum dose to OARs and volumes of healthy brain tissue receiving total doses of 10-50 Gy were lower in the replanned IMRT than in the initial IMRT (all P<0.05). The GTV in the initial plan was significantly positively correlated with the changes in the GTV and planning target volume 1 that occurred during IMRT (all P<0.05). CONCLUSION: The reduction in the GTV in patients with gliomas resulted from shrinkage of the surgical cavity during IMRT, leading to decreased doses to the OARs and healthy brain tissue. Such changes appeared to be most meaningful in patients with large initial GTV values.