Associations between the 1438A/G, 102T/C, and rs7997012G/A polymorphisms of HTR2A and the safety and efficacy of antidepressants in depression: a meta-analysis.

The correlations between hydroxytryptamine receptor 2A (HTR2A) gene polymorphisms (1438A/G, 102T/C, and rs7997012G/A) and the safety and efficacy of antidepressants in depression patients were constantly reported, but conclusions are debatable. This meta-analysis ascertained forty-two studies on the efficacy (including response and remission) and side-effect issued before February 2020. Pooled analyses indicated significant associations of 1438A/G polymorphism (16 studies, 1931 subjects) and higher response within dominant model (OR: 1.40, 95% CI: 1.12-1.76); rs7997012G/A polymorphism (nine studies, 1434 subjects) and higher remission in overall models (dominant model: OR: 1.30, 95% CI: 1.01-1.66; recessive model: OR: 2.20, 95% CI: 1.53-3.16; homozygote model: OR: 2.73, 95% CI: 1.78-4.17); 102T/C polymorphism (eight studies, 804 subjects) and reduced risk of side-effect within recessive (OR: 0.57, 95% CI: 0.4-0.83) and homozygote models (OR: 0.54, 95% CI: 0.29-0.99). For depression patients, genotyping of HTR2A polymorphisms is a promising tool for estimating the outcome and side-effect of antidepressants.

Astrocyte elevated gene-1 promotes progression of cervical squamous cell carcinoma by inducing epithelial-mesenchymal transition via Wnt signaling.

OBJECTIVE: The aim of this study was to investigate the association of astrocyte elevated gene-1 (AEG-1) with epithelial-mesenchymal transition of cervical squamous cell carcinoma (CSCC) and the underlying mechanisms. METHODS: The expression of proteins was determined by immunohistochemistry in tissues. Overexpression and knockdown of AEG-1 in SiHa cells were achieved by stable AEG-1 gene transfection (SiHa-AEG-1+) and AEG-1-siRNA (SiHa-AEG-1-), respectively. The cellular levels of messenger RNA and proteins were assessed with reverse transcription polymerase chain reaction and Western blotting, respectively. The cell invasion capacity was assessed by the chamber invasion assay. RESULTS: AEG-1 was overexpressed in clinical CSCC and associated with lymph node metastasis, parametrial involvement, stromal invasion, and vascular invasion. A high level of vimentin and a low level of E-cadherin were also detected in the cancer tissues. AEG-1 expression was positively correlated with vimentin expression and negatively with E-cadherin expression in CSCC tissues. In addition, high level of AEG-1 was related to unfavorable prognosis of CSCC. On a cellular level, overexpression of AEG-1 was found to lead to an up-regulation of vimentin and a down-regulation of E-cadherin on messenger RNA and protein level in SiHa cells, whereas AEG-1 knockdown led to a contrary result. Meanwhile, the nuclear levels of NF-κB p65 and ß-catenin were also increased in SiHa-AEG-1+, whereas their nuclear levels were decreased in SiHa-AEG-1-. Inhibition of Wnt signaling significantly reduced vimentin level and enhanced E-cadherin level in SiHa-AEG+, but inhibition of NF-κB signaling did not. SiHa-AEG-1+ and SiHa-AEG- showed an enhanced and a decreased invasive capacity, respectively. The enhanced invasiveness of SiHa-AEG-1+ was weakened by inhibition of Wnt signaling. CONCLUSIONS: AEG-1 was associated with the progression of CSCC by promoting epithelial-mesenchymal transition via Wnt signaling pathway.

[Protective effect of forsythiaside A on acute lung injure induced by lipopolysaccharide in mice].

OBJECTIVE: To study the potential protective effect of monomer forsythiaside A (FA), a key component of traditional Chinese medicine, on acute lung injury induced by lipopolysaccharide (LPS) in mice and its possible mechanism. METHODS: The mouse model of acute lung injury was induced by LPS of 10 mg/kg, ip. The experiment was carried out in six groups: control group: without any treatment (n=8); acute lung injury model group: mice were given LPS at a dose of 10 mg/kg (n=8); antibody group: mice were given anti-TLR4/MD antibody (50 µg/20 g body weight) 12 h before modeling (n=8); high-, medium- and low-dose FA groups: mice were respectively given FA at 80 mg/kg (n=8), 20 mg/kg (n=8) and 5 mg/kg (n=8). Mice in all FA treatment groups were given FA once a day till 7 days before modeling. Blood and lung tissue specimens were taken 4 h after modeling. Amount of endotoxin in plasma was measured by kinetic turbidimetric assay. Degree of lung damage was graded by HE staining. Expression of TLR4 at both mRNA and protein levels were measured by RT-PCR and Western blotting, respectively. Expressions of MyD88 and NF-κB were detected by immunohistochemistry. Content of TNF-α in serum was detected by ELISA. RESULTS: Compared with the control group, endotoxin and TNF-α in the model group significantly increased (P<0.01), with obvious pathological damages in lung tissue, such as thickened alveolar septum, hyperemia, edema and infiltration of a lot of neutrophils. Compared with the model group, FA groups presented significantly decreased endotoxin level (P<0.01), attenuated lung damages, down-regulated expressions of TLR4 mRNA and protein, MyD88 and NF-κB proteins in the lung (P<0.01), and significantly dropped TNF-α content in plasma (P<0.01). In addition, the protective effect of FA was dose dependent. CONCLUSION: FA has a protective effect on acute lung injury induced by LPS in mice. The mechanism may be related to the interference in LPS-TLR4-MyD88-NF-κB signaling pathway.

[Gastroscopic and pathological characteristics of patients with or without schistosomiasis in Poyang Lake area].

OBJECTIVES: To understand the gastroscopic and pathological characteristics of patients with miasis in Poyang Lake area, and to explore the relationship between schistosomiasis and pathological changes of gastric mucosa. METHODS: Volunteers with or without schistosomiasis were recruited and divided into a case group and a control group. All the objects were examined by electronic gastroscopy and pathological examinations. RESULTS: Two hundred and fifty-three volunteers diagnosed with chronic or advanced schistosomiasis in the case group showed different degrees of gastric mucosal changes, including 7 cases with schistosomal eggs deposited beneath the gastric mucosa (with an incidence of 2.77%) , 33 cases with dysplastic hyperplasia and intestinal metaplasia (with an incidence of precancerous lesion of 13.04%), and 1 case with gastric cancer. While in the 200 volunteers without schistosomiasis in the control group, the results showed milder gastric mucosal changes, 33 cases were detected with dysplastic hyperplasia and intestinal metaplasia (with an incidence of 7.50%), and 1 case was diagnosed gastric cancer. The difference between the incidences of precancerous lesion in the two groups had no statistic significance (P > 0.05). CONCLUSIONS: The incidence and extent of gastric mucosal changes in schistosomiasis patients are higher and more serious than those in non-schistosomiasis patients, and gastrointestinal schistosomiasis is not related to gastric cancer.

Expression of MMP9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication.

Matrix metalloproteinase 9 (MMP9) and CD147 play a role in invasion and metastasis of many types of human malignancies. The correlation of the expression of MMP9 and CD147 with invasion and metastasis of invasive squamous cell carcinoma (SCC) of the uterine cervix has not been examined. In the present study, RT-PCR assay was used to detect the expression level of MMP9 mRNA semiquantitatively, and immunohistochemical stain was adapted to evaluate the score of CD147 on the cell membrane or in the cytoplasm of tumor cells of 65 cases of invasive squamous cell carcinoma of the uterine cervix and 21 cases of chronic cervitis tissues. MMP9 and CD147 expression in correlation with invasion, metastasis, and differentiation of invasive SCC of the uterine cervix was analyzed statistically. We found that MMP9 and CD147 expression was elevated significantly in tumor tissue compared to the control (cervical epithelium of chronic cervitis) (P<0.01). In the comparison of MMP9 and CD147 expression in 47 cases with lymph node metastasis and 18 cases without lymph node metastasis, there was a significantly higher expression of MMP9 and CD147 in the group with lymph node metastasis (P<0.05 for MMP9, P<0.01 for CD147). MMP9 expression was significantly higher in 24 cases of poor differentiation than in 41 cases of moderate differentiation (P<0.05). No difference was found in CD147 expression between poor and moderate differentiation (P>0.05). No significant difference in MMP9 and CD147 expression levels was obtained between 26 cases of FIGO stage I tumors and 39 cases of stage II tumors (P>0.05 for MMP9, P>0.05 CD147). There was no correlation between MMP9 or CD147 expression levels and the resected tumor size (P>0.05). The positive correlation (r=0.568, P<0.001) of MMP9 expression and CD147 score was seen in the tumor tissues of 65 cases. The data in this study show that MMP9 and CD147 expression are correlated with invasion, metastasis of squamous cell carcinoma of the uterine cervix, and that MMP9 expression is correlated with poor differentiation of invasive squamous cell carcinoma of the uterine cervix.