The serum anion gap is associated with the prognosis of coronary artery bypass grafting (CABG): analysis based on the MIMIC-IV database.

OBJECTIVE: The serum anion gap (AG) has been reported to be an important prognostic indicator for patients in intensive care units. To explore the potential relationship between the serum AG and 30-day mortality in patients who underwent CABG. PATIENTS AND METHODS: All data were collected from the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) database. We divided patients into 3 groups according to AG tertiles. The primary outcome of our study was the 30-day mortality of patients who underwent CABG. The relationship between the serum AG and mortality in individuals who underwent CABG was estimated using Cox proportional hazard models. Subgroup analysis for effect modification was conducted with a likelihood ratio test. RESULTS: A total of 5,102 eligible subjects were included in our analysis. After adjusting for confounding factors, every unit increase in the AG was associated with a 22% higher odds of 30-day mortality in patients who underwent CABG [hazard ratio (HR), 95% confidence interval (CI): 1.22, 1.13-1.33] When the AG was converted into a categorical variable, the high AG group had a higher risk of 30-day mortality than the low AG group in the fully adjusted model (HR, 95% CI: 3.99, 1.35-11.76). Tests for trends were statistically significant (p-value < 0.05). Subgroup analysis demonstrated that higher mortality was related to the subgroups of people ≥ 70 years and females. CONCLUSIONS: The serum AG was an independent predictor of short-term prognosis in patients who underwent CABG. A high AG was associated with an increased risk of 30-day mortality after CABG.

Comparison of the efficacy of febuxostat vs. benzbromarone in the treatment of gout: a meta-analysis in Chinese gout patients.

OBJECTIVE: Febuxostat and benzbromarone are two common drugs for the treatment of gout, but the clinical efficacy of these two drugs is controversial. This meta-analysis aimed to compare the efficacy of febuxostat and benzbromarone in the treatment of gout. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for articles related to febuxostat and benzbromarone in the treatment of gout from inception to January 7, 2023. Titles and abstracts were reviewed in accordance with predesigned inclusion and exclusion criteria, and data were extracted independently. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies, and the continuous variables were expressed as the standard mean square error (SMD) by STATA 16 (Stata Corp., College Station, TX, USA). The sensitivity analysis was conducted by randomly removing a study, and the heterogeneity was analyzed by funnel plots and Egger's test. RESULTS: According to the search strategy, a total of 1,043 publications were retrieved from the three aforementioned databases, of which 45 publications were excluded due to duplication. Fourteen studies remained after screening titles and abstracts, and a total of 7 studies met the inclusion criteria after a comprehensive evaluation of the 14 studies. Meta-analysis showed that the uric acid (UA)-reducing effect of febuxostat is better than that of benzbromarone, while febuxostat showed a better ability to improve the estimated glomerular filtration rate (eGFR) and reduce Cr and blood urea nitrogen (BUN). In terms of hepatotoxicity, benzbromarone was not as potent as febuxostat in increasing alanine transaminase (ALT) and aspartate transaminase (AST), suggesting that benzbromarone has less hepatotoxicity. Moreover, there was no significant difference in the effect on blood lipid levels between the two drugs. CONCLUSIONS: The beneficial effect of febuxostat on renal function-related indexes such as the eGFR, Cr and BUN is significant, while benzbromarone is more effective in reducing UA and has relatively less hepatotoxicity. The specific efficacy of the two drugs needs to be confirmed by further research.

Vitamin D3 sensitizes resistant human bladder cancer cells to cisplatin by regulating Sirtuin 1 gene expression.

OBJECTIVE: Cisplatin is a standard chemotherapeutic agent for advanced bladder cancer, but its efficacy is limited due to drug resistance. Vitamin D3 may reverse cancer multidrug resistance, but the potential molecular mechanisms are still only partially known. The purpose of this study was to explore the mechanism by which vitamin D3 reverses cisplatin resistance in bladder cancer to improve therapeutic efficacy and ameliorate the prognosis of cisplatin-resistant bladder cancer. PATIENTS AND METHODS: The levels of vitamin D3 and sirtuin 1 protein were detected in cisplatin-resistant bladder cancer patients and cisplatin-sensitive patients. The cisplatin-resistant bladder cancer cell lines T24/DDP and UMUC3R were used as cell experimental models, and the migration, apoptosis, mitochondrial reactive oxygen species accumulation and autophagy of cells were assessed in the present study. RESULTS: Vitamin D3 levels were decreased, and sirtuin 1 protein levels were increased in cisplatin-resistant bladder cancer patients compared with cisplatin-sensitive bladder cancer patients. Vitamin D3 treatment markedly repressed sirtuin 1 expression, and overexpression of the sirtuin 1 gene led to mitochondrial reactive oxygen species generation, promoted the initiation of autophagosome formation and enhanced autophagic flux. Cisplatin treatment in the presence of vitamin D3 inhibited cell invasion and migration and induced apoptosis and enhancing the sirtuin 1 gene abolished the effect of vitamin D3 by regulating mitochondrial reactive oxygen species accumulation and autophagosome formation. CONCLUSIONS: These data support a mechanism wherein the sirtuin 1 gene plays a crucial role in vitamin D3 reversing cisplatin resistance in bladder cancer and may provide useful preventive and therapeutic applications in the future.

Probiotic Bacillus subtilis 29,784 improved weight gain and enhanced gut health status of broilers under necrotic enteritis condition.

The study investigated the benefit of a Bacillus subtilis probiotic (Bs 29,784) in necrotic enteritis (NE)-challenged broilers. Four treatments were performed with 312 male day-old Ross 308 reared in floor pens from day 0 to day 35: 2 groups fed control diet without or with NE challenge (CtrlNC and CtrlNE); 2 groups fed probiotic and antibiotic supplements in the control diet with NE challenge (ProNE and AntNE). Necrotic enteritis challenge procedures commenced with inoculation of Eimeria spp 1 mL/bird per os at day 9 and Clostridium perfringens EHE-NE18 (approximately 108 cfu/mL) 1 mL/bird per os at day 14 and day 15. Performance parameters were measured on day 16 and day 35. Lesion, cecal microbiota, and jejunal gene expression were analyzed on day 16. Necrotic enteritis challenge significantly suppressed the performance parameters compared with CtrlNC: 27% weight gain reduction, 11 points feed conversion ratio (FCR) increase at day 16, and 12% weight gain reduction, 5-point FCR increase at day 35. By day 35, ProNE and AntNE treatments enabled significantly higher weight gain (4 and 9%, respectively) than CtrlNE. Compared with CtlrNE and contrary to AntNE, ProNE treatment exhibited upregulation of genes coding for tight junctions proteins (CLDN1, JAM2, TJP1), cytokines (IL12, interferon gamma, TGFß), and Toll-like receptors (TLR5, TLR21) suggesting enhanced immunity and intestinal integrity. 16S NGS analysis of cecal microbiota at day 16 showed a decreased alpha diversity in challenged groups. Principal component analysis of operational taxonomic unit (OTU) abundance revealed that ProNE and AntNE grouped closely while both distantly from CtrlNC and CtrlNE, which were separately grouped, indicating the similar effects of ProNE and AntNE on the OTU diversity that were however different from both CtrlNC and CtrlNE. Microbiota analysis revealed an increase of genera Faecalibacterium, Oscillospira, and Butyricicoccus; and a decrease of genera Ruminococcus, Lactobacillus, and Bacteroides; and an increase of the Firmicutes-to-Bacteroidetes ratio in ProNE and AntNE groups compared with the CtlrNE group. It is concluded that Bs 29,784 may enable improved health of broiler chickens under NE conditions thus performance implications.

MicroRNA-448/EPHA7 axis regulates cell proliferation, invasion and migration via regulation of PI3K/AKT signaling pathway and epithelial-to-mesenchymal transition in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is a primary subtype of lung cancers which has a high morbidity and poor prognosis. Emerging evidence has demonstrated that aberrantly expressed microRNAs (miRNAs) were implicated in the regulatory functions of multiple processes during tumorigenesis. In the current study, we explored the functional roles and underlying mechanisms of miR-448 in NSCLC. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction assays were conducted to measure miR-448 expressions in 51 pairs of NSCLC tissues and corresponding normal tissues. Moreover, the relationship between miR-448 expressions and clinicopathological characteristics of NSCLC patients was also determined. We then performed transwell assays to explore the functions of miR-448 in NSCLC cell invasion and migration. As we had identified EPHA7 as a functional target of miR-448 in NSCLC cells, the clinical significance of EPHA7 in NSCLC patients was further investigated. Finally, we detected the influence of miR-448 on tumor growth rate and tumor size of NSCLC using tumor xenografts. RESULTS: Underexpressed miR-448 was identified in NSCLC, and low miR-448 expression was confirmed to be associated with the poor prognosis and adverse clinicopathologic features of NSCLC patients. Moreover, functional assays demonstrated that miR-448 overexpression suppressed NSCLC cell proliferation, invasion and migration. EPHA7 was identified as a direct target of miR-448. Additionally, miR-448 restoration suppressed in vivo NSCLC cell growth. Finally, our studies also indicated that miR-448 exerted anti-NSCLC functions via regulating PI3K/AKT signaling pathway and EMT. CONCLUSIONS: These results showed that miR-448/EPHA7 axis maybe one of the useful diagnostic and prognostic biomarkers for NSCLC patients.

Reduced serum exosomal miR-874 expression predicts poor prognosis in colorectal cancer.

OBJECTIVE: Emerging evidence has indicated that serum exosomal microRNAs (miRNAs) have promising diagnostic and prognostic value for colorectal cancer (CRC). This study aimed to detect serum exosomal miR-874 expression in CRC patients and assess its potential clinical significance. PATIENTS AND METHODS: Blood samples were collected from 125 CRC patients, 45 cases with benign adenomas (AD) and 70 healthy individuals. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to examine serum exosomal miR-874 levels. RESULTS: The results showed that serum exosomal miR-874 levels were significantly downregulated in CRC patients compared to AD cases and healthy controls. Receiver operating characteristic (ROC) curve analysis revealed that serum exosomal miR-874 expression could discriminate CRC patients from healthy controls, as well as patients with AD. In addition, low serum exosomal miR-874 expression was associated with positive distant metastasis, positive lymph node metastasis, poor differentiation, and advanced TNM stage. Moreover, serum exosomal miR-874 expression was identified as a statistically significant independent prognostic factor for overall survival of CRC patients. CONCLUSIONS: Collectively, serum exosomal miR-874 expression might serve as a reliable marker for CRC diagnosis and prognosis prediction.

Microvesicles containing microRNA-216a secreted by tubular epithelial cells participate in renal interstitial fibrosis through activating PTEN/AKT pathway.

OBJECTIVE: The aim of this study was to elucidate the role of microRNA-216a in microvesicles (MVs) during the process of renal interstitial fibrosis and to investigate its underlying mechanism. MATERIALS AND METHODS: Unilateral ureteral occlusion (UUO) model was first established in mice, and kidney tissues and urine in the obscured kidney were collected. NRK-52E cells were induced with 5 ng/mL transforming growth factor-ß1 (TGF-ß1) for constructing the renal interstitial fibrosis model in vitro. Subsequently, the expression levels of E-cadherin, α-smooth muscle actin (α-SMA) and fibronectin (FN) in NRK-52E cells induced with or without TGF-ß1 were determined, respectively. The culture medium was collected from NRK-52E cells of the control group (without TGF-ß1 induction) and the TGF-ß1 group (TGF-ß1 induction), and MVs were observed. Afterward, NRK-52E cells were treated with MVs isolated from the control group or the TGF-ß1 group, followed by detecting the expressions of E-cadherin, α-SMA and FN. Meanwhile, the expression levels of CD63, microRNA-216a, PTEN and p-AKT were determined as well. The microRNA-216 level in kidney tissues and urine of UUO mice were determined. Furthermore, the expressions of PTEN and p-AKT in mouse kidney tissues were accessed by Western blot and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RESULTS: TGF-ß1 induction in NRK-52E cells gradually downregulated E-cadherin, whereas upregulated α-SMA and FN with the prolongation of induction time. MVs isolated from the culture medium of the TGF-ß1 group downregulated E-cadherin, and upregulated FN and α-SMA. The expression levels of CD63 and microRNA-216a were markedly higher in the TGF-ß1 group compared with the control group. Downregulated PTEN and upregulated p-AKT were observed in TGF-ß1-induced cells at both mRNA and protein levels. Besides, microRNA-216a expression in mouse kidney tissues and urine from obscured kidney was remarkably increased with the prolongation of UUO. Consistent with those in NRK-52E cells, the protein level of PTEN was significantly decreased, whereas p-AKT was markedly increased with the prolongation of UUO. CONCLUSIONS: MVs containing microRNA-216a secreted by injured proximal tubular epithelial cells participate in renal interstitial fibrosis by activating the PTEN/AKT pathway.

The influence of different resuscitation solution on lactic acid accumulation after hemorrhagic shock: a network meta-analysis.

OBJECTIVE: To compare the effect of various fluid resuscitation procedures after hemorrhagic shock on the lactic acid accumulation by network meta-analysis. MATERIALS AND METHODS: A number of articles were obtained by searching the databases. Randomized control trials (RCT) were selected by two literature quality assessors; the extracted experimental data were then summarized to compare and analyze the effect of various kinds of infusion procedures at different time points on the concentration of lactic acid in the internal environment of rat models. RESULTS: 9 articles containing 25 independent reports were enrolled. Results revealed that the accumulation of lactic acid generated in the resuscitation using hydroxyethyl starch solution or gelofusine was significantly different from the one using Ringer solution, hypertonic saline or normal salt solution (p<0.05). Compared to the colloidal, the aqueous solution of pyruvate showed a slightly weaker effect in reducing the accumulation of lactic acid. The accumulation of lactic acid is severely affected by hypertonic saline, Ringer lactate solution, and balanced salt solution, i.e., the concentration of lactic acid is increasing with an augment of concentration or prolongation of treatment time. CONCLUSIONS: In terms of the management of lactic acid accumulation after hemorrhagic shock, the effect of colloidal solution was remarkably better than a crystalloid solution, and hypertonic saline and normal salt solution were not recommended as preferable drugs in the treatment of hemorrhagic shock.

Low-dose vitamin A therapy on T lymphocyte function in neonatal pneumonia.

OBJECTIVE: We aimed at studying the effect of adjuvant therapy with low-dose vitamin A on the function of T lymphocytes in neonatal pneumonia. PATIENTS AND METHODS: We recruited 60 cases of neonatal pneumonia which were randomly divided in two equal groups. The control group was treated with conventional anti-inflammatory therapy and aerosol inhalation. The experimental group received oral vitamin A soft capsules for 7 days. RESULTS: Pre-treatment levels vitamin A level and vitamin A deficiency disorders (VADD) percentage revealed no differences between the two groups. The treatment course for the experimental group was shorter than the control group. Serum IgM, IgG, and glutathione peroxidase (GSH-Px) levels were increased, whereas the levels of malondialdehyde were decreased in the experimental group after treatment. The control group showed no changes in these factors. After treatment, both groups showed increased percentages of CD4+ and CD8+ T cells, but the experimental group showed a larger increase. CONCLUSIONS: Neonatal pneumonia is often accompanied by a low level of vitamin A, and adjuvant therapy can shorten its disease course, improve IgM and IgG levels, and improve anti-oxidative and cellar immune function.

Very high external quantum efficiency and wall-plug efficiency 527 nm InGaN green LEDs by MOCVD.

We demonstrate very high luminous efficacy InGaN-based green light-emitting diodes (LEDs) grown on c-plane patterned sapphire substrates (PSS) using metal organic chemical vapor deposition (MOCVD). The 527 nm green LEDs show a peak external quantum efficiency (EQE) of 53.3%, a peak wall-plug efficiency (WPE) of 54.1% and a peak luminous efficacy of 329 lm/W, respectively. A high EQE of 38.4%, a WPE of 32.1% and a very low forward voltage of 2.86 V were obtained at a typical working current density of 20 A/cm2. By operating low cost green LEDs at a low current density, our devices (0.5 mm2) demonstrating an EQE and a WPE higher than 50% and an efficacy of 259 lm/W at 4 A/cm2 with an output power of 24 mW. High crystal quality of the InGaN/GaN MQWs was characterized by X-ray diffraction (XRD) and the advantage of the epitaxy design was investigated by APSYS software simulation. These results provide a simple way to achieve very high efficiency InGaN green LEDs.

Clinical significance of SCCRO (DCUN1D1) in prostate cancer and its proliferation-inhibiting effect on Lncap cells.

OBJECTIVE:   SCCRO/DCUN1D1/DCN1 (squamous cell carcinoma-related oncogene/defective in cullin neddylation 1 domain containing 1/defective in cullin neddylation) is considered as an oncogene, but its role in the prostate cancer (PC) is still not clear. The current study aims to investigate the expression of SCCRO in PC tumor tissues, further its clinical significance, and proliferation inhibiting effect on PC cells in vitro. PATIENTS AND METHODS: RT-PCR was used to detect the expression of SCCRO in PC tissue and corresponding adjacent normal tissues from 160 cases, and its relationship with clinical pathological characteristics was analyzed. Small interfering RNA (siRNA) expression plasmid targeting SCCRO gene was constructed and transferred into PC cell line Lncap. The effect on proliferation was observed by CCK8 assay, and its influence on invasion and migration of Lncap cells was studied by Transwell Matrigel assay after SCCRO gene was silenced. The expression of focal adhesion kinase (FAK) and matrix metalloproteinase-2 (MMP-2) influenced by SCCRO silencing were detected by Western blot. RESULTS: mRNA expression of SCCRO protein increased significantly in cancer tissues compared to adjacent normal tissue, especially for T3+T4, N+, and III+IV patients (p<0.05). SCCRO expression was an independent prognostic factor (p<0.05). After SCCRO gene was knocked down by siRNA, the SCCRO protein level decreased 78.4% in the siRNA-3 group. By CCK8 assay, knocking down SCCRO in Lncap significantly reduced the cell proliferation, as well as its migration and invasion capability compared to siRNA-control group (p<0.01) by transwell invasion and migration assay. The expression of FAK and MMP-2 also reduced in siRNA-3 group compared to siRNA control group (p<0.01). CONCLUSIONS: SCCRO is associated with progression and prognosis of PC. After SCCRO gene was transferred, the growth of Lncap cells was inhibited, and ability of invasion and migration decreased by reducing the expression of FAK and MMP-2. SCCRO has potential to become a new target for the treatment of PC.

Ultralow-frequency Raman system down to 10 cm(-1) with longpass edge filters and its application to the interface coupling in t(2+2)LGs.

Ultralow-frequency (ULF) Raman spectroscopy becomes increasingly important in the area of two-dimensional (2D) layered materials; however, such measurement usually requires expensive and nonstandard equipment. Here, the measurement of ULF Raman signal down to 10 cm(-1) has been realized with high throughput by combining a kind of longpass edge filters with a single monochromator, which are verified by the Raman spectrum of L-cystine using three laser excitations. Fine adjustment of the angle of incident laser beam from normal of the longpass edge filters and selection of polarization geometry are demonstrated how to probe ULF Raman signal with high signal-to-noise. Davydov splitting of the shear mode in twisted (2+2) layer graphenes (t(2+2)LG) has been observed by such system in both exfoliated and transferred samples. We provide a direct evidence of twist-angle dependent softening of the shear coupling in t(2+2)LG, while the layer-breathing coupling at twisted interfaces is found to be almost identical to that in bulk graphite. This suggests that the exfoliation and transferring techniques are enough good to make a good 2D heterostructures to demonstrate potential device application. This Raman system will be potentially applied to the research field of ULF Raman spectroscopy.

IgE and FcεRI are highly expressed on innate cells in psoriasis.

BACKGROUND: Although elevated serum IgE levels have been reported in psoriasis, the role of IgE in psoriasis still needs to be clarified. OBJECTIVES: To analyse serum total IgE levels in addition to the presence and distribution of IgE and FcεRI in psoriatic lesions, and to investigate alteration of IgE and FcεRI after successful systemic treatment. METHODS: Total serum IgE levels were determined using enzyme-linked immunosorbent assay. The expression and localization of IgE and FcεRI was investigated using immunohistochemistry and double immunofluorescence. RESULTS: Elevated total serum IgE levels were found in 39% of patients with psoriasis. The levels of total serum IgE were significantly higher in male patients compared with female patients. Furthermore, total serum IgE levels decreased after successful systemic treatment. A positive correlation between IgE+ and FcεRI+ cells and a significant increase of these cells was found in psoriatic lesions when compared with normal skin. Interestingly, IgE+ and FcεRI+ cells decreased significantly after successful therapy with ustekinumab. IgE and FcεRI were coexpressed on mast cells, epidermal Langerhans cells, dermal dendritic cells, macrophages and a small number of neutrophils. CONCLUSIONS: IgE might participate in the development of psoriasis by activating FcεRI-bearing cells.

Comparison of full-mouth disinfection and quadrant-wise scaling in the treatment of adult chronic periodontitis: a systematic review and meta-analysis.

Scaling and root planing are widely considered as effective methods for treating chronic periodontitis. A meta-analysis published in 2008 showed no statistically significant differences between full-mouth disinfection (FMD) or full-mouth scaling and root planing (FMS) and quadrant scaling and root planing (Q-SRP). The FMD approach only resulted in modest additional improvements in several indices. Whether differences exist between these two approaches requires further validation. Accordingly, a study was conducted to further validate whether FMD with antiseptics or FMS without the use of antiseptics within 24 h provides greater clinical improvement than Q-SRP in patients with chronic periodontitis. Medline (via OVID), EMBASE (via OVID), PubMed and CENTRAL databases were searched up to 27 January 2015. Randomized controlled trials comparing FMD or FMS with Q-SRP after at least 3 mo were included. Meta-analysis was performed to obtain the weighted mean difference (WMD), together with the corresponding 95% confidence intervals. Thirteen articles were included in the meta-analysis. The WMD of probing pocket depth reduction was 0.25 mm (p < 0.05) for FMD vs. Q-SRP in single-rooted teeth with moderate pockets, and clinical attachment level gain in single- and multirooted teeth with moderate pockets was 0.33 mm (p < 0.05) for FMD vs. Q-SRP. Except for those, no statistically significant differences were found in the other subanalyses of FMD vs. Q-SRP, FMS vs. Q-SRP and FMD vs. FMS. Therefore, the meta-analysis results showed that FMD was better than Q-SRP for achieving probing pocket depth reduction and clinical attachment level gain in moderate pockets. Additionally, regardless of the treatment, no serious complications were observed. FMD, FMS and Q-SRP are all effective for the treatment of adult chronic periodontitis, and they do not lead to any obvious discomfort among patients. Moreover, FMD had modest additional clinical benefits over Q-SRP, so we prefer to recommend FMD as the first choice for the treatment of adult chronic periodontitis.

Roles of the AIB1 protein in the proliferation and transformation of human esophageal squamous cell carcinoma.

The aim of this study was to investigate the expression of AIB1 in human esophageal squamous cell carcinoma and its correlation with Ki67 expression. The immunohistochemical method streptavidin-perosidase was used to analyze the expression of AIB1 and Ki67 in specimens from 60 patients with esophageal squamous cell carcinoma and in 20 control individuals with normal esophageal tissue. Expression correlation, clinical significance, and relationships between the two groups were determined. In the 20 individuals with normal esophageal mucosa cells, AIB expression was primarily detected at low levels in the nucleus or not at all, whereas 41.6% of specimens from individuals with esophageal squamous cell carcinoma exhibited high levels of AIB1 expression (P < 0.05). Furthermore, overexpression of AIB1 was observed more frequently in carcinoma specimens with late T stages (T3/ T4) and lymph node metastases (P < 0.05). No significant differences were observed in AIB1 expression by gender, age, or pathological type (P < 0.05). Comparatively, the rate of positive expression of Ki67 In esophageal squamous cell carcinoma specimens was 65.0% (39/60) (P < 0.05). Of these, 29 specimens exhibited simultaneous expression of AIB1, 25 of which demonstrated AIB1 overexpression; expression of AIB1 and Ki67 was positively correlated (P < 0.01). In summary, the results from this study suggested that AIB1 protein expression was associated with the T stage and lymph node metastasis in esophageal squamous cell carcinoma, and that Ki67 might play a role in the AIB1 non-steroid receptor pathway.

LincHOTAIR epigenetically silences miR34a by binding to PRC2 to promote the epithelial-to-mesenchymal transition in human gastric cancer.

lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients.

CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptor CTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.

Aberrant GSTP1 promoter methylation predicts short-term prognosis in acute-on-chronic hepatitis B liver failure.

BACKGROUND: Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF). AIM: To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis. METHODS: One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained. RESULTS: GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-on-chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut-off points showed significantly poorer survival than those below (P < 0.05). CONCLUSIONS: Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure.

Epstein-Barr virus (EBV) DNA in whole blood as a superior prognostic and monitoring factor than EBV-encoded small RNA in situ hybridization in diffuse large B-cell lymphoma.

Epstein-Barr virus (EBV) status was retrospectively analysed by the use of EBV-encoded small RNA (EBER) in situ hybridization (ISH) and EBV DNA analysis in whole blood with diffuse large B-cell lymphoma, to assess the clinical significance for diagnosis, prognostication, and monitoring of tumour burden. Three hundred and twenty-nine patients were retrospectively enrolled, with 232 patients being available for EBER ISH analysis, 189 patients for EBV DNA analysis, and 138 patients for both analyses. EBER was positive in 24 (10.3%) patients, and EBV DNA was positive in 18 (9.5%) patients; the two analyses had 92.8% concordance. Patients with pretreatment EBER positivity had worse overall survival (OS) than those without EBER positivity (p 0.03); the same pattern was observed for EBV DNA (p < 0.01). A significant p-value was also observed for OS when EBER and EBV DNA were combined (p < 0.01). On multivariate analysis, both EBV DNA (hazard ratio 3.71, 95% CI 1.78-7.74, p < 0.01) and EBER (hazard ratio 2.03, 95% CI 1.03-4.00, p 0.04) remained independent predictive factors for OS. Regarding the dynamic changes in copy number of elevated EBV DNA, the transformation from positive to negative after cycle 3 with chemotherapy may have the most capacity to distinguish a superior from an inferior outcome. These findings suggest that EBV DNA in whole blood has good concordance with EBER ISH, and that it may be a better prognostic and monitoring biomarker than EBER.