OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

Objective:To evaluate the effect of age on mood of patients during induction of general anesthesia with remimazolam.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱpatients of both sexes, undergoing elective surgery with general anesthesia requiring tracheal intubation, aged 5-80 yr, with body mass index 18-30 kg/m 2, were divided into 4 groups ( n=20 each) according to different ages: juvenile group (R 1 group, 5-17 yr), youth group (R 2 group, 18-44 yr), middle-aged group (R 3 group, 45-59 yr) and elderly group (R 4 group, 60-80 yr). Remimazolam was intravenously injected in a loading dose of 0.1 mg/kg for induction of general anesthesia, followed by an infusion of 0.1 mg·kg -1·h -1 for maintenance of general anesthesia, and the other anesthetics for induction and maintenance of anesthesia were all the same in each group.The changes in emotion and brain wave within 3 min after remimazolam injection were recorded.The brain waves and Modified Observer′s Assessment of Alertness and Sedation (MOAA/S) scale score were recorded at 1, 2 and 3 min after administration.Adverse effects during anesthesia induction were also recorded. Results:Compared with group R 1, the incidence of happy mood was significantly decreased, the grade of mood was decreased, and the dream Likert score and MOAA/S score were decreased in R 3 and R 4 groups, and the dream Likert score and MOAA/S score were decreased in group R 2, and the incidence of hypoxemia during induction of general anesthesia was increased in group R 4( P<0.01). Compared with group R 2, the incidence of happy mood was significantly decreased in R 3 and R 4 groups, and MOAA/S score was significantly decreased in group R 4 ( P<0.05). Compared with R 1 and R 2 groups, the proportion of beta bands was significantly decreased, and the proportion of theta and delta bands was increased in R 3 and R 4 groups ( P<0.01). Compared with group R 3, the proportion of beta band was significantly decreased, and the proportion of delta band was increased in group R 4 ( P<0.01). Conclusion:Remimazolam 0.1 mg/kg used for induction of general anesthesia can cause happy mood, accompanied by enhanced brain electrical signal activity of beta band, especially in the patients under 45 yr of age.

OBJECTIVETo investigate the expression of long noncoding RNA linc00261 in hepatocellular carcinoma (HCC) and its correlation with the clinicopathological features and postoperative outcomes of the patients.

METHODSReal-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of linc00261 in surgical specimens of HCC and adjacent tissues from 74 patients. The correlation of the expression level of linc00261 in HCC with the clinicopathological parameters of the patients was analyzed using Chi-square test. The Cox's proportional hazards regression model was used to assess the value of linc00261 in predicting the prognosis of HCC patients after operation. The expression of linc00261 was also examined in 5 HCC cell lines using qRT-PCR. The HCC cell lines MHCC-LM3 and SNU-449 were transfected with small interfering RNAs targeting linc00261 for linc00261 knockdown, and the changes in the cell proliferation, migration and invasion abilities were observed using CCK-8 assay and Transwell assay.

RESULTSThe expression level of linc00261 in HCC was significantly correlated with AFP (=0.032), tumor size (=0.007), microscopic vascular invasion (MVI; =0.01), and TNM stage (=002). The patients with lowered expressions of linc00261 in HCC tissues had a significantly shortened tumor-free survival time ( < 0.05), and a lowered expression of linc00261 was identified as an independent risk factor affecting postoperative recurrence-free survival time of the patients ( < 0.05). In HCC cell lines MHCC-LM3 and SNU-449 cells, linc00261 knockdown obviously promoted the cell migration and invasion ( < 0.01) but did not significantly affect cell proliferation ( > 0.05).

CONCLUSIONSLinc00261 may serve as a new prognostic biomarker for predicting the postoperative outcomes of the patients with HCC.