Association of thyroid disease and risk of fatty liver disease: an exposure-wide Mendelian randomization study.

OBJECTIVE: Previous studies have often observed a possible association between thyroid and fatty liver diseases. The pathogenesis of both diseases is complex, with many confounding factors and controversies. We used a two-sample Mendelian randomization (MR) analysis to test the causality between thyroid disease and the risk of developing fatty liver disease. MATERIALS AND METHODS: All data were obtained from the genome-wide association studies (GWAS) Catalog database. Thyroid disorders include hypothyroidism, hyperthyroidism, autoimmune thyroiditis, and Hashimoto's thyroiditis. Fatty liver diseases include alcoholic fatty liver disease and non-alcoholic fatty liver disease (NAFLD). The inverse variance weighting (IVW) method was used for MR analysis, and sensitivity analysis was further performed to test its robustness. RESULTS: We discovered no causal relationship between thyroid disease and alcoholic fatty liver disease after excluding weak instrumental variables (IVs). Hyperthyroidism and hypothyroidism had a significant causal relationship with NAFLD. Hypothyroidism increased the risk of NAFLD using the IVW method (OR=7.62, 95% CI: 2.61-22.25, p<0.001). MR-Egger regression did not suggest potential evidence of directional pleiotropy (intercept, p=0.698). Hyperthyroidism also significantly increased the risk of NAFLD (OR=11.83, 95% CI: 2.9-22.54, p=0.026). MR-Egger regression did not suggest any potential directional pleiotropy (intercept, p=0.295). CONCLUSIONS: Hypothyroidism can significantly increase NAFLD incidence, and hyperthyroidism may be a risk factor for NAFLD.

B cells and tertiary lymphoid structures are associated with survival in papillary thyroid cancer.

PURPOSE: The function of B cells in papillary thyroid cancer (PTC) is controversial. The role of B-cell-related tertiary lymphoid structures (TLSs) is still unclear. Whether B cells exert their anti-tumor effect through forming TLS in PTC needs further investigation. METHODS: We detected the percentage of B cells in PTC tissues by multi-parameter flow cytometry. Paraffin-embedded tumor tissues of 125 PTC patients were collected and stained with Haematoxylin-Eosin (H&E) for inflammatory infiltration analysis in combination with clinical features. Multiplexed immunohistochemistry (mIHC) was performed to verify the TLSs in above inflammatory infiltration. Correlation of B cells and TLSs with prognosis was analyzed using the TCGA database. RESULTS: We observed that PTC patients with higher expression of B lineage cell genes had improved survival and the percentage of B cells in the PTC tumor tissues was variable. Moreover, PTC tumor tissues with more B cells were surrounded by immune cell aggregates of varying sizes. We furtherly confirmed the immune cell aggregates as TLSs with different maturation stages. By analyzing PTC data from TCGA database, we found the maturation stages of TLSs were associated with genders and clinical stages among PTC patients. Moreover, patients with high TLSs survived longer and had a better prognosis. CONCLUSION: B cells are associated with the existence of TLSs which have different maturation stages in PTC. Both B cells and TLSs are associated with the survival rate of PTC. These observations indicate that the anti-tumor effects of B cells in PTC are associated with TLSs formation.

Skp2/p27 axis regulates chondrocyte proliferation under high glucose induced endoplasmic reticulum stress.

OBJECTIVE: Diabetes mellitus is closely related to osteoarthritis (OA) and may be an independent risk factor for the development of OA. As one of the main characteristics of diabetes, endoplasmic reticulum (ER) stress resulting from glucose metabolism disorder is one of the main causes of cartilage degeneration. The aim of our study is to illuminate the effect of high glucose to chondrocytes (CHs) and the role of Skp2 in high-glucose induced ER stress in CHs. PATIENTS AND METHODS: We compared the ER stress status between healthy and diabetic OA cartilage using Western blot and quantitative reverse-transcription polymerase chain reaction (RT-PCR) methods. Different concentration of glucose was used to culture CHs for both 24 h and 72 h. Furthermore, Tunicamycin (TM) and 4-Phenylbutyric acid (4-PBA) were used to mediate ER stress of CHs, and human recombinant Skp2 protein was used to promote Skp2 expression. CH viability was determined by CCK8 assay, and cell proliferation was determined by flow cytometry. Western and RT-PCR were performed to measure related gene expression. RESULTS: ER stress makers GADD34, GRP78, and MANF were upregulated in diabetic OA cartilage. The long-term high glucose increased GADD34, GRP78, and MANF expression, but decreased collagen II and proliferation of CHs, and Skp2 expression was negative related to the ER stress level. Additionally, Skp2 overexpression partly reversed ER stress-induced collagen II and proliferation suppression by the suppression of p27 expression. CONCLUSIONS: High glucose raises the ER stress in CHs and overexpression of Skp2 promotes CH proliferation under high glucose treatment.

Long noncoding RNA SNHG14 promotes ovarian cancer cell proliferation and metastasis via sponging miR-219a-5p.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA SNHG14 promotes ovarian cancer cell proliferation and metastasis via sponging miR-219a-5p, by L. Li, R. Zhang, S.-J. Li, published in Eur Rev Med Pharmacol Sci 2019; 23 (10): 4136-4142-DOI: 10.26355/eurrev_201905_17915-PMID: 31173283" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17915.

LncRNA HANR aggravates the progression of non-small cell lung cancer via mediating miRNA-140-5p.

OBJECTIVE: The aim of this study was to elucidate the function of long non-coding ribonucleic acids (lncRNAs) HANR in aggravating non-small cell lung cancer (NSCLC) progression via targeting microRNA-140-5p (miRNA-140-5p). PATIENTS AND METHODS: The relative expression level of HANR in NSCLC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between HANR expression and the prognosis of NSCLC was analyzed. The regulatory effects of HANR on cellular behaviors of NSCLC cells were evaluated by Cell Counting Kit-8 (CCK-8), transwell and wound healing assay. Meanwhile, the relative expression of miRNA-140-5p in NSCLC tissues and cell lines was determined by qRT-PCR. In addition, rescue experiments were carried out to evaluate the potential influence of HANR/miRNA-140-5p on the progression of NSCLC. RESULTS: HANR expression was significantly up-regulated in NSCLC tissues and cell lines. HANR expression was positively correlated with lymphatic metastasis and distant metastasis of NSCLC patients, whereas it was negatively correlated with the overall survival of NSCLC patients. Knockdown of HANR markedly suppressed the proliferative, migratory and invasive abilities of NSCLC cells. In NSCLC tissues, the miRNA-140-5p level was negatively associated with HANR level. Furthermore, inhibited cellular behaviors of NSCLC cells transfected with sh-HANR were partially reversed after miRNA-140-5p knockdown. CONCLUSIONS: LncRNA HANR accelerates the proliferative, migratory and invasive abilities of NSCLC via negatively mediating miRNA-140-5p. Furthermore, HANR is closely correlated with lymphatic metastasis, distant metastasis and poor prognosis of NSCLC.

Long noncoding RNA SNHG14 promotes ovarian cancer cell proliferation and metastasis via sponging miR-219a-5p.

OBJECTIVE: The ovarian cancer is one of the most common fatal cancers. Recently, the role of long noncoding RNAs (lncRNAs) in tumor progression has attracted much attention in researchers. The aim of this study was to investigate the role of lncRNA SNHG14 in the progression of ovarian cancer and to explore the possible mechanism. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect SNHG14 expression in ovarian cancer tissues. To identify the function of SNHG14 in ovarian cancer, functional experiments were conducted in vitro and in vivo. In addition, the luciferase assays and RNA immunoprecipitation assay (RIP) were performed to investigate the underlying mechanism. RESULTS: SNHG14 expression was remarkably higher in ovarian cancer tissues than that of corresponding normal tissues. SNHG14 expression was associated with patients' overall survival time as well. After SNHG14 was silenced in ovarian cancer cells, cell proliferation, migration, and invasion were remarkably inhibited. In addition, the expression of miR-219a-5p was significantly up-regulated after the silence of SNHG14. Further mechanism assays showed that miR-219a-5p was a direct target of SNHG14 in ovarian cancer. CONCLUSIONS: SNHG14 serves as a potential oncogene in ovarian cancer. In addition, it enhances ovarian cell metastasis and proliferation via sponging miR-219a-5p.

Meta-analysis of the effects of helmet-assisted non-invasive ventilation in the treatment of acute respiratory failure.

OBJECTIVE: To study the efficacy of helmet-assisted non-invasive ventilation and conventional ventilation in the treatment of acute respiratory failure (ARF). MATERIALS AND METHODS: Cochrane Library, PubMed, Embase and CNKI databases were searched for randomized controlled trials and case-control trials of helmet-assisted noninvasive ventilation in the treatment of ARF. The outcome measures included respiratory rate, intubation rate, complication rate, mortality rate and arterial blood gas analysis of the commonly used indicators (PaCO2/ PaO2 / pH). The results of the included studies' odds ratio (OR) and its 95% confidential interval (CI) were analyzed using Stata software. RESULTS: The results of the analysis showed that the in-hospital mortality, intubation rate and complication rate were all significantly decreased with the p-value less than 0.05, which was statistically significant. CONCLUSIONS: Helmet-assisted noninvasive ventilation can significantly reduce hospital mortality, intubation rate and complication rate, improving the survival rate and prognosis of patients with ARF.

LncRNA SNHG1 promotes liver cancer development through inhibiting p53 expression via binding to DNMT1.

OBJECTIVE: This study aims to investigate whether long non-coding RNA (lncRNA) SNHG1 could regulate proliferative and invasive abilities of liver cancer (LC) cells via p53 and DNMT1, so as to regulate the occurrence and progression of LC. PATIENTS AND METHODS: SNHG1 expression in LC tissues and paracancerous tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between SNHG1 expression and tumor stage of LC patients was analyzed. The regulatory effects of SNHG1 and p53 on proliferative, invasive capacities and cell cycle were accessed by CCK-8 (cell counting kit-8), transwell assay and flow cytometry, respectively. The binding condition between SNHG1 and DNMT1 was determined by RNA binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP). Western blot was conducted to determine whether SNHG1 could regulate p53 in LC cells. Finally, rescue experiments were carried out to evaluate whether SNHG1 regulates proliferative and invasive abilities of LC cells through p53. RESULTS: SNHG1 expression was higher in LC tissues than that of paracancerous tissues. LC patients with stage III-IV presented higher expression level of SNHG1 than those with stage I-II. Similarly, SNHG1 was highly expressed in LC cells than that of normal liver cells. LC cell lines SMMC-7721 and SK-HEP-1 were selected for this study. SNHG1 knockdown inhibited the proliferative and invasive abilities, and arrested the cell cycle in the G0/G1 phase of SMMC-7721 and SK-HEP-1 cells. RIP and ChIP results demonstrated that SNHG1 could bind to DNMT1 and inhibit p53 expression. Overexpression of p53 partially reversed the inhibitory effects of SNHG1 on proliferative and invasive abilities of LC cells. CONCLUSIONS: High expression of SNHG1 could promote proliferative and invasive abilities of LC cells through targeting inhibition of p53 expression by binding to DNMT1.

Effects of miR-132 on proliferation and apoptosis of pancreatic cancer cells via Hedgehog signaling pathway.

OBJECTIVE: Micro ribonucleic acids (miRNAs) and Hedgehog (Hh) signaling pathway play key roles in the proliferation, migration and invasion of tumor cells. The aim of this study was to investigate the role of miR-132 and Hh signaling pathway in the proliferation and apoptosis of pancreatic cancer cells, and to investigate the possible underlying mechanism. MATERIALS AND METHODS: The expressions of miR-132 and Shh (a ligand of Hh) in clinical pancreatic cancer specimens and pancreatic cancer cell lines were determined by qRT-PCR. Meanwhile, the correlation between the two molecules was analyzed. Pancreatic cancer cell line (MiaPaCe-2a) was transfected with miR-132 mimics and inhibitor. The effects of miR-132 up- and down-regulation on the expressions of miR-132, Shh, Cyclin-D1, cleaved Caspase-3 and cleaved Caspase-9 were detected. In addition, the exact role of miR-132 in the proliferation, apoptosis and distribution of MiaPaCe-2a cells were investigated. RESULTS: The expression level of miR-132 in pancreatic cancer specimens and pancreatic cancer cell lines was significantly elevated when compared with that of control group. Meanwhile, miR-132 expression was negatively correlated with the expression level of Shh. Moreover, transfection with miR-132 mimics evidently up-regulated miR-132 expression. Moreover, miR-132 up-regulation significantly decreased the mRNA and protein expressions of Shh, facilitated the proliferation of MiaPaCe-2a cells, reduced the protein expressions of Cyclin-D1, cleaved Caspase-3 and cleaved Caspase-9, and suppressed cell apoptosis. On the contrary, miR-132 inhibitor transfection significantly inhibited the proliferative activity of MiaPaCe-2a cells, decreased the proportion of cells in G1 phase, and increased the proportion of cells in G2/M phase. CONCLUSIONS: MiR-132 promotes proliferation and inhibits apoptosis of pancreatic cancer cells through Hh signaling pathway.

LncRNA 00152 promotes the development of hepatocellular carcinoma by activating JAK2/STAT3 pathway.

OBJECTIVE: The aim of this study was to explore the regulatory role of lncRNA 00152 and JAK2/STAT3 pathway in the pathogenesis of hepatocellular carcinoma (HCC), and to investigate the possible underlying mechanism. PATIENTS AND METHODS: Expression levels of lncRNA 00152 in HCC tissues, matched para-cancerous tissues and normal liver tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), respectively. The correlation between lncRNA 00152 expression and pathological characteristics of HCC patients was analyzed. Meanwhile, the expression level of lncRNA 00152 in HCC cell lines was detected by qRT-PCR. After knockdown or overexpression of lncRNA 00152 in MHCC97 or HB611 cells, the proliferative ability and cell cycle were detected by EdU assay and flow cytometry, respectively. Also, Western blot was conducted to detect the protein expression levels of JAK2 and STAT3 in MHCC97 and HB611 cells. RESULTS: The expression of lncRNA 00152 in HCC tissues was significantly higher than that of matched para-cancerous tissues and normal liver tissues. LncRNA 00152 expression was positively correlated with tumor stage and tumor size, whereas negatively correlated with the overall survival of HCC patients. High expression of lncRNA 00152 might be a potential hallmark for the diagnosis of HCC, with the AUC of 0.8425. Similarly, lncRNA 00152 was highly expressed in HCC cell lines when compared with that of normal liver cells. Knockdown of lncRNA 00152 in MHCC97 cells remarkably decreased the proliferative ability and arrested cell cycle. Overexpression of lncRNA 00152 in HB611 cells significantly promoted cell proliferation and cell cycle. Furthermore, Western blot results showed that lncRNA 00152 knockdown upregulated the protein expression levels of JAK2 and STAT3 in HCC cells. CONCLUSIONS: High expression of lncRNA 00152 promotes the development of HCC by activating the JAK2/STAT3 pathway.

miR-409 down-regulates Jak-Stat pathway to inhibit progression of liver cancer.

OBJECTIVE: To elucidate the influence of microRNA-409 and the Jak-Stat pathway on the development of liver cancer. PATIENTS AND METHODS: The quantitative Real-time polymerase chain reaction (qRT-PCR) method was used to detect the expression of microRNA-409 in hepatocarcinoma, paracancerous tissues and normal liver tissues, and the correlation between its expression and clinicopathological parameters of patients was analyzed, with the area under the microRNA-409 curve (AUC) being detected. The level of microRNA-409 in different liver cancer cells was detected by qPCR. Then it was overexpressed or knock-downed in the liver cancer cells by cell transfection technique. The cell apoptosis and viability after inhibition or overexpression of microRNA-409 were evaluated by propidium iodide (PI) staining and cell counting kit-8 (CCK-8) assay. Subsequently, Jak2 and Stat3 mRNA levels were detected by qPCR in hepatocarcinoma and paracancerous tissues, with their protein levels analyzed by Western blot after microRNA-409 was inhibited or up-regulated. At last, CCK-8 assay was performed to evaluate the effect of Jak2 on cell viability. RESULTS: Compared with paracancerous and normal liver tissues, the level of microRNA-409 was remarkably reduced in hepatocarcinoma tissues and was negatively correlated with tumor stage, tumor size and overall survival time of patients with liver cancer. Meanwhile, microRNA-409 expression in hepatoma cell lines was also strikingly lower than that in normal liver cells. After overexpression of microRNA-409 in HHCC, cell viability significantly decreased while apoptosis increased, and opposite results were shown in HepG2 cells after miR409 was knock-downed. In liver cancer tissues, the levels of Jak2 and Stat3 were significantly higher than those in adjacent tissues. Additionally, up-regulating microRNA-409 reduced the level of Jak2 and Stat3 protein, while down-regulating it elevated them. In addition, Jak2 could reverse the inhibitory effect of microRNA-409 on the proliferation of hepatoma cells. CONCLUSIONS: Highly-expressed microRNA-409 can down-regulate the Jak-Stat signaling pathway and inhibit cell proliferation to slow down the progression of liver cancer.

MiR-210 knockdown promotes the development of pancreatic cancer via upregulating E2F3 expression.

OBJECTIVE: The aim of this study was to explore the role of microRNA-210 (miR-210) and E2F3 in the development of pancreatic cancer and to investigate the possible underlying mechanism. PATIENTS AND METHODS: The expression level of miR-210 in pancreatic cancer tissues, para-cancerous tissues, and normal pancreatic tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between miR-210 expression and pathological indicators of pancreatic cancer was analyzed. Meanwhile, the expression of miR-210 in pancreatic cancer cells and normal pancreatic ductal epithelial cells was detected by qRT-PCR. After transfection with miR-210 mimics and inhibitor, the viability and cell cycle of pancreatic cancer cells were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The binding condition of miR-210 and E2F3 was verified by Dual-Luciferase reporter gene assay. RESULTS: MiR-210 was lowly expressed in pancreatic cancer tissues than that of para-cancerous tissues. The expression of miR-210 was negatively correlated with TNM stage and tumor size of pancreatic cancer. In vitro experiments showed that the miR-210 was downregulated in pancreatic cancer cells than that of normal pancreatic ductal epithelial cells. Meanwhile, overexpression of miR-210 arrested cell cycle decreased cell viability and downregulated E2F3 expression in pancreatic cancer cells. Dual-Luciferase reporter gene assay indicated that E2F3 bound to mi-210. Further experiments confirmed that E2F3 was negatively regulated by miR-210. CONCLUSIONS: MiR-210 knockdown promotes cell proliferation by upregulating E2F3 expression, thereby promoting the progression of pancreatic cancer.

LncRNA LOC554202 promotes proliferation and migration of gastric cancer cells through regulating p21 and E-cadherin.

OBJECTIVE: To explore whether long noncoding RNA (lncRNA) LOC554202 could regulate proliferative and migratory abilities of gastric cancer (GC) cells. MATERIALS AND METHODS: Expression level of LOC554202 in GC cell lines HGC-27 and MGC-803, as well as normal gastric mucosal cell line GES-1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). LOC554202 knockdown or overexpression in HGC-27 and MGC-803 cells was achieved by transfection of LOC554202-siRNA or pcDNA-LOC554202, respectively. Cell cycle in GC cells was accessed by flow cytometry. Migratory ability of GC cells was determined by wound healing assay and transwell assay. Finally, protein expressions of p21 and E-cadherin in GC cells were detected by Western blot. RESULTS: LOC554202 expression was higher in GC cells than that of gastric mucosal cells (p<0.01). Overexpression of LOC554202 in MGC-803 cells enhanced proliferative and migratory abilities, but decreased protein expressions of p21 and E-cadherin (p<0.01). On the contrary, LOC554202 overexpression in HGC-27 cells decreased proliferative and migratory abilities, but increased protein expressions of p21 and E-cadherin (p<0.01). CONCLUSIONS: LncRNA LOC554202 is highly expressed in GC cells. It could promote proliferative and migratory abilities by downregulating expression levels of p21 and E-cadherin in GC cells.

MiR-508-3p inhibits cell invasion and epithelial-mesenchymal transition by targeting ZEB1 in triple-negative breast cancer.

OBJECTIVE: Recently, studies have identified that microRNAs (miRNAs) are novel regulators for gene expression in tumor progression including breast cancer. The aim of the study is to investigate the clinical significance and underlying functions between miR-508-3p expression and triple-negative breast cancer (TNBC) development. PATIENTS AND METHODS: Quantitative Real-time PCR (QRT-PCR) was performed to determine the expression of miR-508-3p in 54 pairs of TNBC specimens and adjacent non-tumor tissues. The association between miR-508-3p expression and clinicopathological factors was assessed using x2-test. Transwell invasion assays were used to assess cell invasion ability. Luciferase reporter assay, Western blot analyses and qRT-PCR were performed to demonstrate ZEB1 was a direct target of miR-508-3p. RESULTS: We demonstrated that miR-508-3p expression was remarkably decreased in TNBC tissues and cells. Lower miR-508-3p expression significantly associated with lymph node metastasis and distant metastasis in TNBC patients (p < 0.05). Ectopic expression of miR-508-3p significantly suppressed cell invasion ability of TNBC. MiR-508-3p overexpression suppressed cell epithelial-mesenchymal transition (EMT) phenomenon of TNBC by upregulating E-cadherin expression, but downregulating Vimentin expression. In addition, we revealed that ZEB1 was a direct target of miR-508-3p in TNBC cells. MiR-508-3p significantly suppressed cell EMT process by regulating ZEB1 expression. CONCLUSIONS: We found that miR-508-3p may be a potential therapeutic target of TNBC.

MEG3 is involved in the development of glaucoma through promoting the autophagy of retinal ganglion cells.

OBJECTIVE: In this study, we aimed at investigating whether MEG3 may be involved in the pathogenesis of glaucoma by regulating the autophagy of retinal ganglion cells (RGCs). MATERIALS AND METHODS: We used qRT-PCR to detect the expression of MEG3 in RGC-5s cell line under high hydrostatic pressure. RGC-5s were transfected with a lentiviral vector to achieve MEG3 overexpression or knockdown. The influence of overexpression or inhibition of MEG3 on cell proliferation and apoptosis was observed using CCK-8 test and flow cytometry. After overexpression of MEG3 and/or knockdown of MEG3 or Beclin-1, detection of the expressions of autophagy-related and apoptosis-related proteins was performed using Western blot. RESULTS: MEG3 expression level increased in RGC-5 cells under high hydrostatic pressure, while exogenously decreased MEG3 expression can reverse the impact of the high pressure on RGC-5 cells. Additionally, overexpression of MEG3 can improve Atg3 expression, promote cell apoptosis, inhibit cell proliferation, and enhance autophagy levels. Meanwhile, knockdown of Beclin-1 up-regulated Bcl-2 level. CONCLUSIONS: Upregulation of MEG3 is involved in the pathogenesis of glaucoma through promoting apoptosis of retinal ganglion cells, the mechanism of which may be related to the enhanced autophagy levels.

Has-MiR-196a-2 is up-regulated and acts as an independent unfavorable prognostic factor in thyroid carcinoma.

OBJECTIVE: To identify the role of hsa-miR-196a-2 in thyroid cancer by bioinformatics analysis. MATERIALS AND METHODS: The expression profiles of thyroid cancer was download from TCGA. The dysregulated microRNAs were obtained by edger R package. Then, the prognostic data were analyzed by K-M plot. The difference between different groups was analyzed by the t-test. At last, the biological processes of has-miR-196a-2 were obtained with GSEA. RESULTS: In this study, we found that has-miR-196a-2 was upregulated in thyroid carcinoma by analyzing the TCGA database, which was inversely proportional to the prognosis of patients with thyroid carcinoma. Univariate and multivariate COX analysis showed that has-miR-196a-2 was an independent prognostic risk factor for thyroid carcinoma. Higher expressions of has-miR-196a-2 were found in patients with older age, advanced tumor stage, lymph node metastasis, and local infiltration through the t-test. We found that has-miR-196a-2 was enriched in adherent junction, focal adhesion, and actin cytoskeleton, which are closely related to the invasion and migration of the function pathway. Moreover, it is mainly enriched in tumor progression pathways, such as the PPAR pathway and WNT pathway. CONCLUSIONS: Hsa-miR-196a-2 is overexpressed in thyroid tumors and is an independent prognostic risk factor for thyroid carcinoma.

Association of the upregulation of LncRNA00673 with poor prognosis for colorectal cancer.

OBJECTIVE: To investigate the effect and clinical significance of long non-coding RNA 00673 (lncRNA00673) in the occurrence and development of colorectal cancer (CRC) through the research on the expression level, biological effect and clinical significance of lncRNA00673 in CRC. PATIENTS AND METHODS: The relative expression of lncRNA00673 in 71 pairs of CRC tissues and cells was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The correlation of the relative expression of lncRNA00673 with the clinicopathological features of CRC patients was analyzed. The lncRNA00673 interference sequence was designed and synthesized, and its transfection efficiency was detected by qRT-PCR assays. 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and clone formation experiments were performed to investigate the effect of lncRNA00673 on the proliferation ability of CRC cells. RESULTS: In CRC tissues of 71 patients, there were 51 patients whose lncRNA00673 level was up-regulated compared with that of cancer-adjacent tissues. The highly expressed lncRNA00673 was positively correlated with tumor, node and metastasis (TNM) staging, regional lymph node metastasis, distant metastasis and tumor size in CRC patients. Cox proportional-hazards regression model showed that the highly expressed lncRNA00673 was an independent risk factor for the overall survival of CRC patients. Kaplan-Meier curve analysis showed that highly expressed lncRNA00673 was significantly associated with the relatively lower overall survival (OS). MTT and clone formation experiments showed that knockdown of lncRNA0673 could inhibit the proliferation of CRC cells. CONCLUSIONS: The expression level of lncRNA00673 is up-regulated in CRC tissues and cells, which is related to the degree of malignancy and poor prognosis. LncRNA00673 can be used as a potential molecular marker for the prognosis of CRC.

Risk factors for early-onset ventilator-associated pneumonia in aneurysmal subarachnoid hemorrhage patients

This study aimed to investigate the risk factors related to ventilator-acquired pneumonia (VAP) in aneurysmal subarachnoid hemorrhage (SAH) patients. From January 2011 to December 2015, a single-center retrospective study including 200 SAH patients requiring mechanical ventilation (MV) ≥48 h was performed. The clinical data of these patients were collected and analyzed. The age range of the patients were 41-63 and 72 (36%) were male. The Glasgow coma scale score range was 5-15 and the Simplified Acute Physiology Score II range was 31-52. One hundred and forty-eight (74%) patients had a World Federation of Neurosurgeons (WNFS) score ≥III. Aneurysm was secured with an endovascular coiling procedure in 168 (84%) patients and 94 (47%) patients presented VAP. Male gender (OR=2.25, 95%CI=1.15-4.45), use of mannitol (OR=3.02, 95%CI=1.53-5.94) and enteral feeding above 20 kcal·kg−1·day−1 (OR=2.90, 95%CI=1.26-6.67) after day 7 were independent factors for VAP. Patients with early-onset VAP had a longer duration of sedation (P=0.03), MV (P=0.001) and ICU length of stay (P=0.003) and a worse Glasgow Outcome Scale score (P<0.001), but did not have a higher death rate.

ErbB4 signaling in the prelimbic cortex regulates fear expression.

Many psychiatric diseases such as post-traumatic stress disorder (PTSD) are characterized by abnormal processing of emotional stimuli particularly fear. The medial prefrontal cortex (mPFC) is critically involved in fear expression. However, the molecular mechanisms underlying this process are largely unknown. Neuregulin-1 (NRG1) reportedly regulates pyramidal neuronal activity via ErbB4 receptors, which are abundant in parvalbumin (PV)-expressing interneurons in the PFC. In this study, we aimed to determine how NRG1/ErbB4 signaling in the mPFC modulates fear expression and found that tone-cued fear conditioning increased NRG1 expression in the mPFC. Tone-cued fear conditioning was inhibited following neutralization of endogenous NRG1 and specific inhibition or genetic ablation of ErbB4 in the prelimbic (PL) cortex but not in the infralimbic cortex. Furthermore, ErbB4 deletion specifically in PV neurons impaired tone-cued fear conditioning. Notably, overexpression of ErbB4 in the PL cortex is sufficient to reverse impaired fear conditioning in PV-Cre;ErbB4-/- mice. Together, these findings identify a previously unknown signaling pathway in the PL cortex that regulates fear expression. As both NRG1 and ErbB4 are risk genes for schizophrenia, our study may shed new light on the pathophysiology of this disorder and help to improve treatments for psychiatric disorders such as PTSD.

Diabetes mellitus and risk of anastomotic leakage after esophagectomy: a systematic review and meta-analysis.

Diabetes mellitus has the probability to impair the anastomotic healing and cause postesophagectomy anastomotic leakages but previous studies showed controversial results. This review aims to summary the impact of diabetes mellitus on the risk of anastomotic leakage after esophagectomy. We searched the PubMed and EMBASE databases to recognize English articles that met our eligibility criteria. Odds ratio with 95% confidence interval serves as the appropriate summarized statistic. Sensitivity analysis, meta-regression analysis, and publication bias tests were also performed to perceive potential bias risks. Finally, 16 observational studies with 12359 surgical patients were included. An overall analysis identified that diabetes mellitus was significantly associated with the risk of anastomotic leakage after esophagectomy (odds ratio = 1.63; 95% confidence interval = 1.25-2.12; P < 0.001). Further subgroup analysis showed a significant impact of diabetes mellitus in surgical populations from the Europe and America (odds ratio = 1.42; 95% confidence interval = 1.22-1.65; P < 0.001) but not in the Asian populations (odds ratio = 2.27; 95% confidence interval = 0.86-6.05; P = 0.1). The robustness of these estimates was confirmed by meta-regression analysis and sensitivity analysis. No significant publication bias exists between studies. In conclusion, this systematic review demonstrates that diabetes mellitus can be a significant risk factor of anastomotic leakage for patients undergoing esophagectomy. Our findings need to be further confirmed and modified by more well-designed worldwide multivariable analyses in the future.