[Effect and mechanism of 1, 25(OH)2D3 on myocardial inflammation induced by Coxsackie virus B3 in mice].

Objective: To explore the effect and mechanism of 1, 25(OH)2D3 on myocardial inflammation induced by Coxsackie virus B3 (CVB3) in mice. Methods: Wild type (WT) and 1α-hydroxylase knockout [1(OH)ase-/-] male mice were divided into four groups: WT group, WT+CVB3 group, 1(OH)ase-/-+CVB3 group and 1(OH)ase-/-+CVB3+VD3 group, with 8 mice in each group. The indicators for evaluating myocardial cell injury were examined by different methods. The mRNA levels of pro-inflammatory cytokines [interlenkin (IL)-1ß, IL-6, interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α)] were determined by quantitative real-time PCR. Hematoxylin-eosin (HE) staining was used to observe the myocardial histopathological changes. The apoptosis of myocardial cells was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. Fluo-4/AM fluorescence probe was used to detect intracellular calcium ion content. Meanwhile, the expression levels of Ca2+/Calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) protein as well as endoplasmic reticulum stress-related proteins like glucose-related protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the myocardial tissues were detected by Western blot. Results: Compared with WT group, the mRNA levels of pro-inflammatory factors increased in the cardiomyocytes of mice in WT+CVB3 group, including IL-1ß (14.88±3.32 vs 1.03±0.02, P=0.009), IL-6 (7.00±1.09 vs 1.81±0.18, P=0.005), IFN-γ (4.70±1.11 vs 1.34±0.34, P=0.006) and TNF-α (17.20±3.22 vs 1.02±0.12, P<0.001). Similarly, the infiltration of inflammatory cells, and the apoptosis rate of cardiomyocytes elevated (16.66%±1.09% vs 7.85%±1.12%, P=0.012). The level of calcium ions in myocardial cytoplasm was significantly higher in WT+CVB3 group than that in the WT group (2.98±1.05 vs 0.96±0.10, P=0.006). Likewise, the expression levels of pCaMKⅡ(1.97±0.34 vs 1.00±0, P<0.001), GRP78 (1.78±0.19 vs 1.00±0, P=0.005) and CHOP (1.62±0.09 vs 1.00±0, P=0.002) in WT+CVB3 group up-regulated. The above myocardial cell injury markers were more significant in the 1(OH)ase-/-+CVB3 group. In the 1(OH)ase-/-+CVB3+VD3 group, 1, 25(OH)2D3 supplementation significantly improved myocardial cell injury indicators. Meanwhile, the specific inhibitors of CaMKⅡ can also reduce the myocardial injury and apoptosis rate of CVB3-infected mice. Conclusion: 1, 25(OH)2D3 deficiency can aggravate myocardial inflammation through over activation of CaMKⅡ.

Utility of the DECAF score for predicting survival of patients with COPD: a meta-analysis of diagnostic accuracy studies.

OBJECTIVE: The DECAF (Dyspnea, Eosinopenia, Consolidation, Acidemia, Atrial Fibrillation) score is a widely used system for predicting the survival of patients with acute aggravation of chronic obstructive pulmonary disease (COPD). Evaluations of the predictive accuracy of DECAF have shown differing results. We performed this meta-analysis to evaluate the DECAF score as a survival predictor in patients with COPD. MATERIALS AND METHODS: We have included the studies examining the accuracy of DECAF scoring system as index test with occurrence of events (mortality and need for invasive/non-invasive ventilation) as reference standards irrespective of the study design employed, type of participants and severity of the condition. We conducted a systematic search for all studies reporting the predictive accuracy of DECAF scores in the databases of PubMed Central, Scopus, Medline, Embase, and Cochrane from inception until September 2020. We have used the quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool to evaluate the risk of bias. We used the STATA software "midas" package to perform the meta-analysis. RESULTS: We included 21 studies with 6429 patients. Most studies included were prospective. Most studies were conducted in the United Kingdom. Most studies used a cut-off value of the DECAF score ≥3 to predict the in-hospital or 30-day mortality and need for mechanical ventilation. All the studies used the occurrence of in-hospital/30-day mortality or patient undergoing mechanical ventilation as the reference standards. The pooled sensitivity and specificity of the DECAF score for predicting in-hospital mortality among patients with acute exacerbation of COPD were 74% (95% CI, 67%-79%) and 76% (95% CI, 68%-82%), respectively; and those for the 30-day mortality were 72% (95% CI, 59%-82%) and 83% (95% CI, 67%-93%), respectively. The overall quality of the studies in our meta-analysis was high. We found no significant publication biases as per Deek's test and funnel plot. CONCLUSIONS: This review has certain strengths. It is the first meta-analysis assessing the predictive utility of the DECAF score for in-hospital mortality among patients with AECOPD. Most studies included were of high quality according to the QUADAS-2 tool. Despite these strengths, our review had some limitations. We found a significant between-study variability in our analysis that can limit its value for inferring or interpreting the pooled findings. The predictive accuracy of the scoring system depends on many factors such as the ethnicity of the participants or patients, the timing of the scoring system assessment, and the AECOPD severity. We could not assess the influence of these variables in our study. Despite these shortcomings, our findings provide valuable information and important implications for the clinical practice involving patients with AECOPD. We found that the DECAF score can predict in-hospital and 30-day mortalities with satisfactory sensitivity and specificity.

LINC00240 sponges miR-4465 to promote proliferation, migration, and invasion of hepatocellular carcinoma cells via HGF/c-MET signaling pathway.

OBJECTIVE: LINC00240, as a novel long non-coding RNAs (lncRNAs), has never been studied in hepatocellular carcinoma (HCC). This research reported the expression and function of LINC00240 in HCC. PATIENTS AND METHODS: LINC00240 expression in 180 HCC patients was downloaded from the Cancer Genome Atlas (TCGA) database. HCC patients' survival was analyzed via Kaplan­Meier analysis. The expression of LINC00240, miR-4465 and HGF in Hep3B and Huh7 cells were regulated by transfection. Cell viability was determined by MTT assay. Transwell experiment was used for the detection of cells migration and invasion abilities. The interaction between LINC00240, miR-4465 and HGF was reflected by Luciferase reporter assay. LINC00240, miR-4465, HGF and p-c-MET expression in HCC cells were researched by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. RESULTS: TCGA data showed that high LINC00240 expression was markedly associated with lower survival of HCC patients (p = 0.036). LINC00240 expression was aberrantly upregulated in HCC cells. Silencing of LINC00240 significantly reduced HCC cells viability, migration and invasion. miR-4465 was a target gene of LINC00240. Silencing of LINC00240 reduced HCC cells viability, migration and invasion via directly promoting miR-4465 expression. HGF was target gene of miR-4465. miR-4465 up-regulation obviously suppressed HGF and p-c-MET expression. According to rescue experiment, LINC00240 silencing inhibited HCC cells viability, migration and invasion by suppressing HGF/c-MET signaling pathway via targeting miR-4465. CONCLUSIONS: LINC00240 sponges miR-4465 to promote HCC cells proliferation, migration and invasion via HGF/c-MET signaling pathway.

[Clinical significance and mechanism of TBX5 gene in colorectal cancer].

Objective: To examine the expression of T-box5 (TBX5) in colorectal cancer tissues and its clinical significance, and explore the effects of TBX5 on the invasion and metastasis of colorectal cancer cells and its mechanism. Methods: The expressions of TBX5 in cancer and adjacent normal tissues were tested by immunohistochemistry (IHC), and the relationship between TBX5 and clinicopathological features and prognosis of colorectal cancer was analyzed. Real-time quantitative PCR (RT-qPCR) and western blot were used to detect the expressions of TBX5 in different colorectal cancer cell lines. TBX5 overexpression plasmid was constructed and transfected into human colorectal cancer cell line HT-29, and cell counting kit-8 (CCK-8) was used to detect the activities of transfection HT-29 cells. Cell scratch test and Transwell assay were used to detect the migration and invasion abilities of cells, while RT-qPCR and western blot were used to detect the mRNA and protein expressions of PCNA, p21, p16, p27, MMP-2, MMP-7 and TIMP-1. Results: The positive rate of TBX5 protein in colorectal cancer tissues was 24.44% (22/90), significantly lower than 65.56% of adjacent normal tissues (P<0.001). The expression of TBX5 was significantly related to lymph node metastasis, depth of invasion and nerve invasion (P<0.05). The survival period of 22 patients with positive TBX5 expression was (60.2±2.4) months, better than (44.3±2.8) months of 68 patients with negative TBX5 expression (P<0.05). Among human colon cancer cell lines of HT29, SW620, SW480, LOVO and HCT116, the expression of TBX5 in HT29 cells was the weakest. After transfection, the expression of TBX5 in transfection group was significantly higher than those in control group and blank group (P=0.043 and P<0.001). Cell viability in transfection group was significantly lower than those in control group and blank group (both P<0.001). The ratio of cells in G(0)/G(1) phase was increased (P=0.009), while in G(2)/M phase was decreased (P<0.001). Cells' abilities of migration and invasion in transfection group were also significantly decreased (both P<0.001). Overexpression of TBX5 downregulated the expressions of PCNA, MMP-2 and MMP-7, while upregulated the expressions of p21, p16, p27 (P<0.05 for all). TBX5 had marginal effect on the expression of TIMP-1 (P>0.05). Conclusions: Downregulation of TBX5 is a marker of poor prognosis in patients with colorectal cancer. TBX5 may inhibit the progression of colorectal cancer by inhibiting proliferation, invasion and metastasis related genes.

Recurrent synovial chondromatosis of the temporomandibular joint: report of two cases.

Synovial chondromatosis is the most common tumour-like lesion that is found in the temporomandibular joint (TMJ). Although it is benign and self-limiting, it can recur. We retrospectively reviewed 274 cases that were treated in our department from 2001-16 and found two recurrences, the radiological, surgical, histopathological, and follow-up results of which we report here. The reasons for their recurrence were analysed and elucidated.

Correlation between the disc status in MRI and the different types of traumatic temporomandibular joint ankylosis.

OBJECTIVES: We aimed to investigate the correlation between the disc status in MRI and the different types of traumatic temporomandibular joint (TMJ) ankylosis. METHODS: 51 consecutive patients (69 joints), diagnosed with traumatic TMJ ankylosis with a residual condyle (Types A2 and A3), were included in this study. All patients had pre-operative MRI, which was reviewed to determine the disc shape, length and position. The results were compared using the Mann-Whitney test. RESULTS: There were 37 joints of Type A2 ankylosis and 32 joints of Type A3. All joints of Type A2 and 27 joints of Type A3 (84.4%) definitely had a discernible disc, while 5 joints of Type A3 had no discernible discs. Among the discernible discs, the lateral disc of Type A2 and the whole disc of Type A3 had severe deformity, while the medial disc of Type A2 had mild deformity. The mean (standard deviation) disc length was 10.88 (1.19) mm in Type A2, but 7.50 (0.82) mm in Type A3. There was a significant difference between Types A2 and A3 (p < 0.05). As for the disc position, the intermediate position was found in all joints. CONCLUSIONS: There is a correlation between the disc status and the different types of traumatic TMJ ankylosis. Therefore, MRI examination is needed to help treatment planning and predict post-operative TMJ function.

Estrogen receptor beta variants mRNA expressions in gastric cancer tissues and association with clinicopathologic parameters.

BACKGROUNDS/AIMS: The aim of this study is to examine the expression of estrogen receptor beta-1, 2 ,5 in gastric cancer tissues and evaluate their correlation with clinicopathological features. METHODOLOGY: Real-time quantitative PCR assay was applied to detect the expression of estrogen receptor beta-1, 2, 5 mRNAs in 44 gastric cancer tissues and their paired normal tissues and correlate their mRNA levels with the clinicopathological properties of the tumors. 2(deltaCT) method was used to obtain the relative quantity of target mRNA expression. RESULTS: In almost all patients, estrogen receptor beta-1, 2, 5 mRNAs were expressed in gastric cancers and their matched normal tissues; however estrogen receptor beta-5 mRNA was not found in 8 normal gastric tissues. Estrogen receptor beta-5 had a much higher expression than estrogen receptor beta-1, 2 in gastric cancer tissues. Higher estrogen receptor beta-5 mRNAlevel was observed in gastric cancers than matched normal tissues (p = 0.001) and its increased expression was correlated with pTNM stage of the tumor (p = 0.032) and the lymph node metastasis (p = 0.026). Decreased mRNA level of estrogen receptor beta-1 was observed in gastric cancers compared to their matched normal tissues (p = 0.008). Estrogen receptor beta-1, 2 were not correlated with lymph node metastasis, gender, age, tumor size, tumor grade and pTNM stage (p > 0.05). CONCLUSIONS: This is the first study investigating the clinicopathologic role of estrogen receptor beta variants in gastric cancer. Our study shows that estrogen receptor beta-5 is the most important factor for gastric cancer development and progression among the three estrogen receptor beta variants.