Endoscopic Features and Clinical Characteristics of Ulcerations With Isolated Involvement of the Small Bowel.

BACKGROUND: Double-balloon enteroscopy (DBE) enables the detection of ulcerations in the small bowel. However, determining an etiological diagnosis remains challenging. This study was conducted to investigate the clinical and endoscopic features of ulcerations with isolated involvement of the small bowel (UIISB) to improve diagnostic ability. METHODS: Patients (n = 565) who underwent DBE and presented with ulcerations in the small bowel at Nanfang Hospital from January 2005 to January 2018 were eligible. Medical records were retrospectively examined. Predictors to determine ulceration etiology were identified by logistic regression analysis. RESULTS: After excluding patients with extra-ulcerations in other sites (n = 306) and those without follow-up records (n = 50), 209 patients with UIISB were enrolled. Among them, 59.3% of the ulcers were in the ileum, 26.8% in the jejunum, and 13.4% in the jejunoileum. Initial symptoms included abdominal pain (54.1%) and obscure gastrointestinal bleeding (30.0%). The multiplicity of ulceration was categorized as a single (22.0%) or multiple (78.0%). Cases were diagnosed with Crohn's disease (50.7%), chronic nonspecific inflammation (21.5%), diverticulum (9.1%), lymphoma (6.2%), gastrointestinal stromal tumor (4.3%), intestinal tuberculosis (1.9%), adenocarcinoma (1.4%), infective enteritis (1.4%), hemangioma (1.0%), cryptogenic multifocal ulcerous stenosing enteritis (1.0%), anastomotic ulcer (0.5%), intestinal duplication (0.5%), or neuroendocrine tumor (0.5%). Etiology identification indicated the if patients were aged 40 years or more, or had overt bleeding, single ulceration, and ulcer at jejunum, it as more prone to be neoplastic (P < .05). CONCLUSION: When we manage patients with UIISB, Crohn's disease should be first under consideration. Age≥40, overt bleeding, single ulceration, and ulcer at jejunum were reasonable indications for etiology of neoplasm or non-neoplasm.

miR­92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in gastric carcinoma cells.

MicroRNAs (miRNAs) are a class of short noncoding RNAs that negatively regulate gene expression and act as oncogenes or tumor suppressors. Numerous miRNAs have been reported be associated with the occurrence and development of gastric carcinoma (GC). For instance, miR­92a has been observed to be overexpressed in GC; however, the precise mechanisms underlying the role of miR­92a in GC and its role in clinical therapy require further investigation. In the present study, it was reported that miR­92a expression was significantly upregulated in GC tissues compared with in adjacent tissues. Additionally, suppression of miR­92a significantly reduced SGC7901 cell viability as demonstrated by a Cell Counting Kit­8 and colony formation assays. Suppression of miR­92a inhibited SGC7901 cell proliferation as determined by Ki­67 immunofluorescence staining, and the expression levels of proliferating cell nuclear antigen, cyclin dependent kinase (CDK)4 and CDK6, and increased that of p53. In addition, we reported that suppression of miR­92a induced apoptosis in SGC7901 cells. Furthermore, bioinformatics analysis identified that ING2 as a potential target of miR­92a. Downregulation of miR­92a significantly increased ING2 expression at the mRNA and protein levels. A dual­luciferase reporter assay validated a direct binding site of miR­92a on ING2. In addition, SGC7901 cells with suppression of miR­92a were more sensitive to doxorubicin treatment. Knockdown of miR­92a reduced the half­maximal inhibitory concentration of doxorubicin from 147.6 nM to 82.1 nM in SGC7901 cells. Knockdown of miR­92a also reduced SGC7901 cell survival under doxorubicin stimulation. Furthermore, SGC7901 cells with suppression of miR­92a harbored a greater number of DNA damage foci upon doxorubicin treatment compared with in control cells. The findings of the present study revealed that miR­92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in GC cells, which suggests a potential therapeutic strategy for the treatment of GC.

Pseudoginsenoside-F11 attenuates cerebral ischemic injury by alleviating autophagic/lysosomal defects.

AIMS: Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been reported to exert wide-ranging neuroprotective properties. The aim of this study was to investigate the effect and potential mechanisms of PF11 on the autophagic/lysosomal pathway following ischemic stroke. METHODS: Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). Cerebral ischemia outcome, TUNEL staining, Fluoro-Jade B staining were carried out 24 hours poststroke. The autophagic/lysosomal-related proteins were measured. RESULTS: A single administration of PF11 significantly decreased the infarct area, reduced the brain water content, and improved neurological functions, even 4 hours after the onset of pMCAO. Meanwhile, PF11 lessened the ischemic insult-mediated loss of neurons and activation of astrocytes and microglia. Furthermore, PF11 attenuated pMCAO-induced accumulations of autophagosomes and apoptosis. We further observed a remarkable effect of PF11 in reversing the ischemic insult-induced accumulation of autophagosomes (LC3-II) and abnormal aggregation of autophagic proteins (SQSTM1 and ubiquitin). Furthermore, PF11 was capable of improving lysosomal function and lysosome/autophagosome fusion following pMCAO, and this change was reversed by the lysosomal inhibitor chloroquine. Also, the improvement of ischemic outcome and the antiapoptotic effect induced by PF11 was reversed by CQ. CONCLUSION: These findings indicate that the autophagic flux is impaired in a rat model of pMCAO, and that PF11 exerts an excellent protective effect against ischemic stroke by alleviating autophagic/lysosomal defects.

Knockdown of Histone Methyltransferase hSETD1A Inhibits Progression, Migration, and Invasion in Human Hepatocellular Carcinoma.

Our aim was to study the expression of human SET domain containing protein 1A (hSETD1A) in hepatocellular carcinoma patients and its relationship with human hepatocellular carcinoma cell function. A total of 30 patients with hepatocellular carcinoma were enrolled in this study. The expression of hSETD1A was detected by real-time polymerase chain reaction (PCR) and Western blotting. The immortalized normal human liver cell line including SMMC-7721 was subjected to real-time PCR for hSETD1A mRNA. Furthermore, hSETD1A-small hairpin RNA (shRNA) was used to knock down hSETD1A expression in SMMC-7721 cells. Cell proliferation, cell apoptosis, and cell migration were determined by CCK8, flow cytometry, and Transwell assays. The positive expression rate level of hSETD1A mRNA and protein in liver carcinoma tissues was 73.33%. hSETD1A knockdown using a specific hSETD1A-shRNA inhibited cell proliferation and promoted cell apoptosis in SMMC-7721 cells. It was also found that downregulation of hSETD1A inhibited cell migration ability but did not affect cell invasion. In conclusion, the expression of hSETD1A occurs at a high rate in hepatocellular carcinoma patients. The expression state of hSETD1A may be a prognostic factor in hepatocellular carcinoma.

Treatment outcomes of spontaneous rupture of hepatocellular carcinoma with hemorrhagic shock: a multicenter study.

BACKGROUND: Spontaneous rupture is one of the most fatal complications of HCC. The incidence of HCC still remains a significant health problem in Eastern Asia. Many studies have shown that the in-hospital or 30-day mortality rates are as high as 25-100 %. It is often difficult to stratify these patients based on clinical manifestations and biochemical data, for deciding on an appropriate treatment strategy, especially when the patient's hemodynamic status is unstable. This study aimed to explore the clinical outcomes of treatment of spontaneously ruptured hepatocellular carcinoma with hemorrhagic shock. METHODS: One hundred and sixty two patients with hemorrhagic shock secondary to spontaneous rupture of hepatocellular carcinoma were included in this retrospective study. The therapeutic methods included conservative treatment, transcatheter arterial embolization (TAE) and hepatectomy. The outcomes in terms of 30 day and 1 year survival were analyzed. RESULTS: Thirty five (21.6 %) received only conservative management, TAE was performed in 48 (29.6 %) and partial hepatectomy (emergency and staged) in 106 (65.4 %) patients. The 30-day survival rate was lower in patients receiving conservative treatment (8.6 %) than in those receiving either hepatectomy or TAE (88.2 %; P < 0.001). Conservative treatment was associated with poorer long-term survival (0 % at 1 year) when compared to those receiving either hepatectomy or TAE (54.3 % at 1 year; P < 0.001). The survival rates at 30 days and 1 year were 92.5 % and 59.4 % for the patients who underwent hepatectomy, which were significantly higher (66.7 and 28.6 % respectively) than those receiving TAE alone (P = 0.003 and P = 0.009, respectively). Multivariate Cox-regression analysis showed that hepatectomy and TAE were significant protective factors for survival as compared with conservative treatment (all P < 0.01). CONCLUSIONS: Partial hepatectomy, tended to provide better survival than transcatheter arterial embolization alone or conservative treatment in the management of patients with hemorrhagic shock secondary to spontaneous rupture of hepatocellular carcinoma.

Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells.

Arsenic trioxide has been proven to trigger apoptosis in human hepatocellular carcinoma cells. Endoplasmic reticulum stress has been known to be involved in apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein. However, it is unknown whether endoplasmic reticulum stress mediates arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Our data showed that arsenic trioxide significantly induced apoptosis in human hepatocellular carcinoma cells. Furthermore, arsenic trioxide triggered endoplasmic reticulum stress, as indicated by endoplasmic reticulum dilation, upregulation of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein. We further found that 4-phenylbutyric acid, an inhibitor of endoplasmic reticulum stress, alleviated arsenic trioxide-induced expression of CCAAT/enhancer-binding protein homologous protein. More important, knockdown of CCAAT/enhancer-binding protein homologous protein by siRNA or inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid alleviated apoptosis induced by arsenic trioxide. Consequently, our results suggested that arsenic trioxide could induce endoplasmic reticulum stress-mediated apoptosis in hepatocellular carcinoma cells, and that CCAAT/enhancer-binding protein homologous protein might play an important role in this process.