[Protective effects of Lycium ruthenicum Murr. juice on alcoholic liver injury in rats].

Objective: To study the protective effects of Lycium ruthenicum Murr. juice on alcoholic liver injury in rats and explore the regulatory mechanism of toll-like receptors 4 (TLR4)/p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in this process. Methods: Sixty male SD rats were randomly divided into control group (C), model group (M), low-dose Lycium ruthenicum Murr. juice group (LLM), medium-dose Lycium ruthenicum Murr. juice group (MLM) and high-dose Lycium ruthenicum Murr. juice group (HLM), 12 rats in each group. The group M, LLM, MLM and HLM were treated with 20 ml/kg (8 g/(kg·d)) ethanol (400 g/L) intragastrically and the gavage was divided into two sessions, group C was treated with an equal volume of distilled water at the same time point. Four hours before the first alcohol gavage session, rats in each dose group of Lycium ruthenicum Murr. juice were administered with 2.4, 4.8, 9.6 ml/(kg·d) Lycium ruthenicum Murr. juice respectively, and the other groups were given equal volume of distilled water at the corresponding time points. Four weeks later, the rats were sacrificed 24 hours after the end of the last experiment, blood and liver were collected. The liver index was calculated. The morphology of the liver was observed by HE staining. The expressions of hepatic TLR4, p38 MAPK and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were detected by immunohistochemistry. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by colorimetry. The levels of hepatic tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-10 (IL-10) and interleukin-18 (IL-18) were detected by enzyme linked immunosorbent assay. Results: Compared with group C, the alcoholic liver injury model was established successfully in Group M. Compared with group M, related indicators in each dose group of Lycium ruthenicum Murr. juice were improved, the improvement of hepatic morphology in group HLM was the most significant, the liver index, the levels of serum ALT, AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-1ß, IL-18 were decreased (P＜ 0.05 or P＜0.01), while the level of hepatic IL-10 was increased (P＜0.01). Comparison among the dose groups of Lycium ruthenicum Murr. juice, the levels of liver index, serum AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-18 in HLM were lower than those in LLM (P＜0.05 or P＜0.01); the level of hepatic IL-10 in HLM was higher than that in LLM and MLM (P＜0.05 or P＜0.01); the other indicators in each dose group had no statistical difference (P＞0.05). Conclusion: Lycium ruthenicum Murr. juice can improve the inflammatory stress by regulating TLR4/p38 MAPK signaling pathway, relieve alcoholic liver injury in rats, and the effect of high-dose group is better than the others.

HS3ST3A1 and CAPN8 Serve as Immune-Related Biomarkers for Predicting the Prognosis in Thyroid Cancer.

Background: Thyroid cancer (TC) tends to be a common malignancy worldwide and results in various outcomes due to its different subtypes. The tumor microenvironment (TME) was demonstrated to play crucial roles in various malignancies, including thyroid cancer. This study combined the ESTIMATE and CIBERSORT algorithms, identified four TME-related genes, and evaluated their correlation with clinical characteristics. These findings revealed the malignant performance of TME in TC, and the TME-related DEGs might serve as prognostic biomarkers, which can be utilized for the prediction of immunotherapy effects in patients with TC. Methods: The clinical and gene expression profiles of TC patients were collected from the TCGA dataset. The ESTIMATE algorithm was utilized to estimate stromal and immune scores and predict the level of stromal and immune cell infiltration. The differential expressed genes related to TME were filtered by the "limma" package in R, and the PPI network was constructed by a string website. KEGG pathway and GO analyses were performed to investigate the biological progression and molecular functions of TME-related DEGs. Then, univariate Cox regression analysis was employed to screen four genes correlated with clinical characteristics. GSEA was conducted to assess their roles in the TME of TC. To further investigate the association between TME-related genes and tumor-infiltrating immune cells (TIICs), the CIBERSORT algorithm was performed. Finally, the malignancy behaviors of the two genes were verified by RT-qPCR, IHC, MTT, colony formation, and transwell assays. Results: Four TME-related DEGs, LRRN4CL, HS3ST3A1, PCOLCE2, and CAPN8, were identified and were significantly predictive of poor overall survival. KEGG and GO pathway analysis established that the TME-related DEGs were involved in immune responses and pathways in cancer. Furthermore, the malignancy behaviors of HS3ST3A1 and CAPN8 were verified by cellular functional experiments. These results revealed that the TME-related genes HS3ST3A1 and CAPN8 were able to serve as predictors of prognosis in patients with TC. Conclusion: HS3ST3A1 and CAPN8 may serve as valuable prognostic biomarkers and TME indicators, which can be utilized for the prediction of immunotherapy effects and provide novel treatment strategies for patients with TC.

[The Expression of WTAP Gene in Acute Myeloid Leukemia and Its Clinical Significance].

OBJECTIVE: To investigate the expression of WTAP gene in acute myeloid leukemia (AML) and its clinical significance. METHODS: 74 acute myeloid leukemia patients with non-M3 type and 19 normal donors were selected, and real-time quantitative polymerase chain reaction was used to detect the mRNA expression level of WTAP gene in their bone marrow cells. The relationship between the mRNA expression level of WTAP gene and the clinical characteristics was analyzed. RESULTS: The relative mRNA expression of WTAP gene in the non-M3 AML group was significantly higher than that in the healthy control group, and the difference showed statistically significant (P<0.01). There showed no statistically significant difference in WTAP gene expression among each subtypes (all P>0.05) according to the classification of FAB. The mRNA expression level of WTAP gene in FLT3-ITD mutated AML patients was higher than that in FLT3-ITD unmutated group (P=0.016), and the mRNA expression level of WTAP gene in AML patients with CEBPα mutation was lower than that in CEBPα unmutated group (P=0.016). The expression level of WTAP mRNA was positively correlated with WT1 expression (r=0.6866, P<0.01). There was no relationship between WTAP mRNA expression level and other clinical parameters, such as age, gender, white blood cell count, hemoglobin level, platelet count, bone marrow original proportion of immature cells, chromosome karyotype, and NPM1, DNMT3A, ASXL1, NRAS, TET2 genes mutation status (P>0.05). The expression level of WTAP mRNA showed no obvious effect on the complete remission of patients after first treatment. The different expression level of WTAP gene at initial diagnosis showed also no effect on the overall survival time of patients. CONCLUSION: The expression level of WTAP gene is increasing in new diagnosed non-M3 acute myeloid leukemia. There is a positive correlation between the expression level of WTAP gene and the expression level of WT1 fusion gene. WTAP mRNA always shows higher expression in patients with FLT3-ITD mutation than that in patients without FLT3-ITD mutation, and shows lower expression in patients with CEBPα mutation than that in unmutated group.

Goiter and hearing impairment: A case of a male patient with Pendred syndrome.

Pendred syndrome is a rare genetic disease that causes a disturbance in thyroid hormone synthesis, which results in thyroid dysfunction and the development of goiter and sensorineural deafness. The present report describes the case of a young euthyroid male, who developed a large goiter and hearing impairment, despite no family history of these conditions. A left lobectomy and a subtotal right lobectomy were performed, and the patient was administered permanent hormone replacement therapy with thyroxine. Patients with Pendred syndrome exhibit distinct clinical features and the mechanisms associated with the molecular genetics of this disease have been clarified. Thus, gene detection is considered to be a reliable diagnostic method. Certain patients require surgical intervention in order to relieve the symptoms. Misdiagnosis can be significantly reduced by increasing the understanding of Pendred syndrome.