An immune-related prognostic signature associated with immune landscape and therapeutic responses in gastric cancer.

Immune-related genes (IRGs) have attracted attention in recent years as therapeutic targets in various tumors. However, the role of IRGs in gastric cancer (GC) has not been clearly elucidated. This study presents a comprehensive analysis exploring the clinical, molecular, immune, and drug response features characterizing the IRGs in GC. Data were acquired from the TCGA and GEO databases. The Cox regression analyses were performed to develop a prognostic risk signature. The genetic variants, immune infiltration, and drug responses associated with the risk signature were explored using bioinformatics methods. Lastly, the expression of the IRS was verified by qRT-PCR in cell lines. In this manner, an immune-related signature (IRS) was established based on 8 IRGs. According to the IRS, patients were divided into the low-risk group (LRG) and high-risk group (HRG). Compared with the HRG, the LRG was characterized by a better prognosis, high genomic instability, more CD8+ T cell infiltration, greater sensitivity to chemotherapeutic drugs, and greater likelihood of benefiting from the immunotherapy. Moreover, the expression result showed good consistency between the qRT-PCR and TCGA cohort. Our findings provide insights into the specific clinical and immune features underlying the IRS, which may be important for patient treatment.

Fisetin Ameliorates Alcohol-Induced Liver Injury through Regulating SIRT1 and SphK1 Pathway.

Alcoholic liver disease (ALD) often leads to hepatitis, hepatic cirrhosis, and even hepatocellular carcinoma. Fisetin has been shown to confer protection against liver injury. Herein, we investigated whether fisetin could prevent ethanol-induced hepatotoxicity. Mice were fed on 5% (v/v) Lieber-DeCarli ethanol diet. Human primary hepatic stellate cells (HSCs) co-cultured with ethanol were used to verify the therapeutic effect of fisetin. The results of alanine/aspartate aminotransferase (ALT/AST), Triglyceride (TG), total cholesterol (TC) in serum, Oil O Red and Masson staining revealed that fisetin (80[Formula: see text]mg/kg) ameliorated ethanol-induced mice liver injury and fibrosis. Besides, immunofluorescence results of [Formula: see text]-SMA revealed that fisetin suppressed HSCs activation. The suppression was dose-dependent. Furthermore, fisetin promoted SIRT1-mediated autophagy and inhibited Sphk1-mediated endoplasmic reticulum stress (ER stress) both in vitro and in vivo. Molecular docking results indicated potential interaction of fisetin with SIRT1 and SphK1. The inhibitory effect of fisetin on HSCs activation was reversed on co-culturing with EX-527, a specific inhibitor against STIR1 overexpression. Thus, fisetin has the potential to ameliorate alcohol-induced liver injury through suppression of HSCs activation, SIRT1-mediated autophagy and Sphk1-mediated ER stress.

Qualitative analysis on a proposal for key specific medical treatment for aplastic anemia.

OBJECTIVE: By reviewing the medical treatments for aplastic anemia (AA, Suilao Disease), which is the important research interest of Collaborative Group, Key Department of Blood Disease, State Administration of Chinese medicine, the consensus on the diseases have been reached among the different units of the collaborative group. METHODS: Using qualitative analysis, we determined the characteristics, location and pathogenesis of Suilao disease. We discovered the ways of traditional Chinese medical treatment in curing Suilao disease. RESULTS: Acute AA (acute suilao) and chronic AA (chronic suilao) diseases require different treatment. Acute AA requires 3 phrases of treatments, which are "cold", "warm" and "hot". However, chronic AA requires a dialectic treatment, which involves reinforcement of the Shen (Kidney). Suitable Chinese medical treatments for curing Suilao disease were discussed and reached a consensus. CONCLUSION: It is concluded that a summarized therapy approved by many experts could be widely used.

[Effects of Busui Shengxue Granule on bFGF and bFGFR in bone marrow derived stroma cells of chronic aplastic anemia patients].

OBJECTIVE: To observe the therapeutic effects of Busui Shengxue Granule (BSSXG) on chronic aplastic anemia (CAA) patients and its effects on bone marrow derived stroma cells (BMDSCs) correlated cytokines. METHODS: One hundred and twenty-four patients with CAA were randomly assigned to two groups according to the random digit table. Patients in the test group (61 cases) were treated with BSSXG, while those in the control group (63 cases) were treated with Zaizao Shengxue Tablet (ZST). The therapeutic course was 6 months for all. Besides, 10 healthy subjects were recruited as the normal control group. Changes of the symptom integral, therapeutic efficacy judgment, and changes of peripheral hemogram of patients were observed. The mRNA expression of b-fibroblast growth factors (bFGF) and b-fibroblast growth factors receptor (bFGFR) were detected by reverse transcription PCR. RESULTS: The total effective rate of the test group was 75.0% (45/61), higher than that of the control group (58.7%, 37/63). Its symptom integral and peripheral hemogram were obviously improved, better than those of the control group (P < 0.05, P < 0.01). The mRNA expressions of bFGF and bFGFR of the test group were obviously lower than those of the normal control group (P < 0.05, P < 0.01). They were somewhat improved after treatment in the two groups, with better results obtained in the test group. CONCLUSIONS: BSSXG showed better clinical effects. It could improve the symptom integral and peripheral hemogram of CAA patients, improve the clinical efficacy, and regulate the expression levels of bFGF and bFGFR. It improved the hematopoietic microenvironment and promoted the hematopoiesis of the bone marrow through regulating the proliferation and oriental differentiation of stroma cells, and promoting the bone marrow angiogenesis.

Effect of busui shengxue granule (see text) on chronic aplastic anemia patients' hematopoietic adhesion molecule VLA-6/CD49f and its ligand laminin.

OBJECTIVE: To observe the effect of Busui Shengxue Granule ((see text) Herbal granule for replenishing marrow to produce blood) on chronic aplastic anemia (CAA) patients' integrin alpha 6 (VLA-6/CD49f) and laminin (Ln). METHODS: Sixty-five patients were divided into experimental group and control group through random number table. There were 34 patients, 17 were male and 17 female, aged 2-67, with a medianage of 30.2 +/- 8.6, in the experimental group, including 17 patients of kidney-yin deficiency and 17 of kidney-yang deficiency, treated by Busui Shengxue Granule. There were 31 patients in the control group, 16 were male and 15 female, aged 4-65, with a medianage of 31.2 +/- 8.0; administered Zaizhang Shengxue Tablet (see text) Herbal tablet for chronic aplastic anemia). Both groups were treated for six months and compared with 10 normal persons after the treatment. Flow cytometry was adopted to detect the change in the expression of VLA-6/CD49f, receptor in mononuclear cells of CAA patients and normal persons. Enzyme-linked immunosorbent assay was applied to detect the expression of peripheral serum Ln. RESULTS: CAA patients' VLA-6/CD49f was in the state of low expression and Ln in the state of high expression. After the treatment, both VLA-6/CD49f and Ln were regulated to some extent and the change in the experimental group was better than that of the control group. Compared with the kidney-yin deficiency patients, those indices of kidney-yang deficiency patients were easier to correct. CONCLUSION: The VLA-6/CD49f and Ln expressions of CAA patients are abnormal. The treatment with Busui Shengxue Granule makes both of them improved.