Effects of GATA6-AS/MMP9 on malignant progression of endometrial carcinoma.

PURPOSE: Previous studies have shown that long non-coding RNA (lncRNA) GATA6-AS is a tumor suppressor gene. However, the role of GATA6-AS in endometrial cancer (EC) has not been reported. We aimed at investigating the expression characteristics of GATA6-AS in EC tissues and cell lines, and explored whether it inhibits the malignant progression of EC through modulating matrix metalloproteinase-9 (MMP9). METHODS: GATA6-AS expression in 17 pairs of EC tissues and adjacent ones was studied by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Meanwhile, GATA6-AS expression levels in EC cell lines were also evaluated by qRT-PCR assay. In addition, GATA6-AS overexpression model was constructed using lentivirus in EC cell lines KLE and HEC-1B. The impacts of GATA6-AS overexpression model was constructed using lentivirus in EC cell lines KLE and HEC-1B on the proliferation capacity and apoptosis of EC cells were assessed by cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU), and flow cytometry experiments. Furthermore, we explored the interaction between GATA6-AS and MMP9 in EC cells via performing luciferase assay and cell reverse experiments. RESULTS: Our data showed that GATA6-AS expression in EC tissue specimens was remarkably lower than that in adjacent ones. In vitro cell experiments revealed that overexpression of GATA6-AS markedly attenuated the proliferation ability of EC cells while elevated their apoptosis. Meanwhile, luciferase assay confirmed the binding relationship between GATA6-AS and MMP9. In addition, cell reverse experiments further demonstrated the mutual regulation between GATA6-AS and MMP9, which was, overexpression of MMP9 reversed the inhibitory influence of upregulation of GATA6-AS on the malignant progression of EC. CONCLUSIONS: lncRNA GATA6-AS, lowly expressed in EC tissue samples. Additionally, lncRNA GATA6-AS may suppress the malignant progression of EC through the modulation of regulating MMP9.

[Significance of peripheral perfusion index in early diagnosis and goal-directed therapy of septic shock patients: a prospective single-blind randomized controlled trial].

OBJECTIVE: To investigate the application of peripheral perfusion index (PPI) in early diagnosis and goal-directed therapy of septic shock, and to provide reference for the early clinical diagnosis and treatment of septic shock. METHODS: A prospective single-blind randomized controlled trial (RCT) was conducted. Adult patients with sepsis admitted to emergency medical department and intensive care unit (ICU) of the First People's Hospital of Lianyungang City in Jiangsu Province from January 2013 to December 2016 were enrolled. The patients were randomly divided into two groups (n = 46). The PPI group was defined using PPI < 1.4 as diagnosis of septic shock standard, and PPI > 2 as treatment guide target. Control group was defined according to the traditional diagnostic criteria of shock which systolic blood pressure was less than 90 mmHg (1 mmHg = 0.133 kPa) or systolic blood pressure value decrease > 40 mmHg baseline and bundle treatment was performed. The volume of fluid resuscitation, organ dysfunction, the sequential organ failure score (SOFA), acute physiology and chronic health evaluation II (APACHE II) score, continuous renal replacement therapy (CRRT) time, mechanical ventilation (MV) time, the length of ICU stay and 28-day mortality were observed. RESULTS: There were 39 and 27 septic shock patients in PPI group and control group respectively. The diagnostic criteria of traditional septic shock with blood pressure as "gold standard", the sensitivity of PPI < 1.4 for septic shock was 94.3%, the specificity was 28.2%, the authenticity was 66.3%, the positive predictive value was 64.1%, the negative predictive value was 78.6%, the positive likelihood ratio was 1.31, the negative likelihood ratio was 0.18. The per capita fluid replacement within 24 hours in the PPI group was significantly higher than that in the control group (mL: 4 601±1 250 vs. 3 458±1 006, P < 0.01), but there was no significant difference in the per capita volume of the patients diagnosed as septic shock (mL: 4 596±1 320 vs. 4 205±1 058, P > 0.05). Compared with the control group, the PPI group treated patients within 48 hours with less vascular active drugs (cases: 6 vs. 15), APACHE II and SOFA score were lower (48 hours: APACHE II was 10.2±2.1 vs. 12.0±3.2; 72 hours: SOFA was 5.1±1.8 vs. 6.0±2.1, APACHE II was 8.9±1.8 vs. 9.8±2.2), the period of CRRT and the length of ICU stay were shorter [the period of CRRT (days): 3.0±0.9 vs. 3.6±1.4, the length of ICU stay (days): 5.2±2.1 vs. 6.3±2.9), the difference was statistically significant (all P < 0.05). There was no significant difference in the liver and kidney function index, arterial blood lactic acid (Lac), MV time (days: 3.3±1.4 vs. 3.5±1.2) and 28-day mortality (15.22% vs. 19.57%) between two groups (all P > 0.05). CONCLUSIONS: The inadequacy of microcirculatory perfusion by oximetry-derived PPI is more sensitive to the diagnosis of septic shock than hypotension of systemic circulation. With PPI guiding the fluid resuscitation of septic shock patients, vasopressors can be withdrawn earlier and the duration of the CRRT and ICU can be decreased.

Comparative study of p38 MAPK signal transduction pathway of peripheral blood mononuclear cells from patients with coal-combustion-type fluorosis with and without high hair selenium levels.

Coal-combustion-type fluorosis has only been reported in China and its pathogenesis has not been fully understood. Fluoride causes chronic toxic effects and selenium modulates cellular activities through signal transduction in human cells. The present study enrolled three groups of subjects with well-defined serum and urine fluoride and hair selenium: high fluoride+high selenium group, high fluoride group and normal control group. The expressions of p38, NF-kB p65, caspase-3 and p53 genes at both protein and mRNA levels in peripheral blood mononuclear cells (PBMCs) were determined by Western blotting and quantitative real-time RT-PCR, respectively. The results showed that the expressions of p38, NF-kB p65, and caspase-3 protein in high fluoride group were higher than those in the other two groups. The mRNA level of NF-kB p65 and caspase-3 was significantly higher in high fluoride+high selenium group than control and lower than high fluoride group. The mRNA and protein level of p53 was significantly higher in high fluoride+high selenium group than that in other two groups. These results suggest that selenium may influence the protein and gene expression associated with p38 signal transduction pathway and up-regulate p53 expression in PBMCs from patients with coal-combustion-type fluorosis.

Selenoprotein P gene r25191g/a polymorphism and quantification of selenoprotein P mRNA level in patients with Kashin-Beck disease.

Kashin-Beck disease (KBD) is an endemic and deformable osteoarthrosis. Epidemiological study has revealed that lower Se level is the principal environmental factor in the pathogenesis of KBD. Selenoprotein P (SEPP1) is a special selenoprotein, which is the primary form of Se in vivo. Our aim was to investigate the putative association of SEPP1 r25191g/a single nucleotide polymorphism (SNP) with KBD risk and the SEPP1 transcriptional levels in whole blood and articular cartilage tissue of KBD cases and controls, respectively. One hundred and sixty-seven cases with KBD and 166 control subjects from Shaanxi province of China were included in the present study. The detection of SNP r25191g/a in the 3' untranslated region was performed using an efficient technique, tetra-primer amplification refractory mutation system PCR. A quantitative analysis of SEPP1 mRNA in KBD and control groups by real-time PCR was also performed. The present results show no significant difference in genotype and allele distribution of SNP r25191g/a between individuals with KBD and controls (P = 0·279 and 0·428, respectively). There was also no association between SNP r25191g/a and risk of KBD (OR 1·153; 95 % CI 0·533, 2·496). However, the frequency of the rare genotype AG of SNP r25191g/a was significantly lower in Chinese population than in the Caucasians. It was shown that the SEPP1 mRNA expression in whole blood was lower in KBD patients than in the control group (0·149-fold, P < 0·001), but that it was much higher in articular cartilage tissue (4·53-fold, P = 0·012). Our aim was to lay a foundation for us to further study the association between the pathogenesis of KBD and SEPP1.

[Expression of PI3K/Akt signal pathway in acute myocardial ischemia].

OBJECTIVE: To explore the influence of the PI3K/Akt-mediated signal pathway in acute myocardial ischemia (AMI) rats, the expression of pAkt, Akt, Caspase3 and p38 in myocardium and somatic muscles of AMI rats were detected. METHODS: The rats model of AMI were established by peritoneal injecting isoprinosine (ISO), and were detected by electrocardiogram and haemodynamics. The expressions of pAkt, Caspase3 and p38 in somatic muscles and cardiac muscles of AMI and normal rats were detected by Dot blot hybridization and Western blot. RESULTS: In contrast with normal rats, electrocardiogram of AMI rats showed a lower displacement of ST segment (> or = 0.1 mv). The expression of pAkt, Caspase3 and p38 were higher than those in normal rats (P < 0.05). No apparent changes were observed in expression of Akt (P = 0.477). CONCLUSION: Expressions of pAkt, Akt and correlated apoptosis molecule Caspase3 and p38 in cardiac and somatic muscles of AMI rats were higher than those in normal rats. No apparent changes were observed in expression of Akt.