Enhancing the Efficiency of a Radiation Oncology Department Using Electronic Medical Records: Protocol for Preparing Radiotherapy.

BACKGROUND: Electronic medical records (EMRs) streamline medical processes, improve quality control, and facilitate data sharing among hospital departments. They also reduce maintenance costs and storage space needed for paper records, while saving time and providing structured data for future research. OBJECTIVE: This study aimed to investigate whether the integration of the radiation oncology information system and the hospital information system enhances the efficiency of the department of radiation oncology. METHODS: We held multidisciplinary discussions among physicians, physicists, medical radiation technologists, nurses, and engineers. We integrated paper records from the radiation oncology department into the existing hospital information system within the hospital. A new electronic interface was designed. A comparison was made between the time taken to retrieve information from either the paper records or the EMRs for radiation preparation. A total of 30 cases were randomly allocated in both the old paper-based system and the new EMR system. The time spent was calculated manually at every step during the process, and we performed an independent 1-tailed t test to evaluate the difference between the 2 systems. RESULTS: Since the system was launched in August 2020, more than 1000 medical records have been entered into the system, and this figure continues to increase. The total time needed for the radiation preparation process was reduced from 286.8 minutes to 154.3 minutes (P<.001)-a reduction of 46.2%. There was no longer any need to arrange for a nurse to organize the radiotherapy paper records, saving a workload of 16 hours per month. CONCLUSIONS: The implementation of the integrated EMR system has resulted in a significant reduction in the number of steps involved in radiotherapy preparation, as well as a decrease in the amount of time required for the process. The new EMR system has provided numerous benefits for the department, including a decrease in workload, a simplified workflow, and conserving more patient data within a confined space.

CircPTK2 inhibits the tumorigenesis and metastasis of gastric cancer by sponging miR-134-5p and activating CELF2/PTEN signaling.

BACKGROUND: CircRNAs are a new subset of noncoding RNAs formed by covalent closed loops and play crucial roles in the regulation of cancer gene expression. However, the roles and underlying mechanisms of circRNAs in gastric cancer (GC) remain indistinct. This study aimed to explore the role and mechanism of hsa_circ_0006421 (circPTK2) in GC. METHODS: The differential expression of circRNAs between GC tissues and adjacent normal tissues were identified by a circRNA expression profiling. Associations of circPTK2 or miR-134-5p expression with clinicopathological characteristics and prognosis of GC patients were analyzed by chi-square of Fisher's exact tests and Kaplan-Meier analysis. CCK8, colony formation, EdU assays and animal models were performed to assess the effects of circPTK2 on proliferation and invasion of GC cells. CircPTK2-specific probes were used to purify the RNA pulled down from the circPTK2, and enrichment of circPTK2 and miR-134-5p was detected by qRT-PCR. The effects of circPTK2 on miR-134-5p expression and CELF2/PTEN signaling were examined by qRT-PCR and Western blotting analysis. RESULTS: Low expression of circPTK2 and high expression of miR-134-5p were related to the poor survival, and high expression of miR-134-5p was related to the tumor recurrence in GC patients. Overexpressing circPTK2 suppressed the proliferation, colony formation, DNA synthesis and cell invasion as well as xenograft tumor growth and lung metastasis in vitro and in vivo, whereas silencing circPTK2 had the opposite effects. Moreover, circPTK2 was negatively correlated and co-localized with miR-134-5p in the cytoplasm of GC tissue cells. circPTK2 bound to and sponged miR-134-5p in GC cells, and miR-134-5p facilitated cell growth and invasion but attenuated circPTK2 induced tumor suppressive effects and CELF2/PTEN signaling activation in GC cells. CONCLUSIONS: circPTK2 functions as a tumor suppressor in GC by sponging miR-134-5p and activating the CELF2/PTEN axis.

CCR7 regulates ANO6 to promote migration of pancreatic ductal adenocarcinoma cells via the ERK signaling pathway.

The increase in migratory ability of pancreatic ductal adenocarcinoma cells is a key event in the development of metastasis to the lymph nodes and distant organs. Although the C-C motif chemokine receptor 7 (CCR7) and its ligand, C-C motif chemokine ligand 21 (CCL21), have been revealed to serve an important role in tumor migration, their precise roles and potential underlying mechanisms remain largely unknown. The present study revealed that overexpression of CCR7 significantly promoted BxPC-3 cell migration, accompanied by the induction of anoctamin 6 (ANO6) expression, indicating that ANO6 is a downstream target of CCR7 signaling. Furthermore, the level of phosphorylated extracellular signal-regulated kinase (ERK) was significantly increased in CCR7-overexpressing BxPC-3 cells, indicating that ERK may be a potential mediator of CCR7-regulated ANO6 expression in BxPC-3 cells. To characterize the receptor-mediated pathway, a specific ERK inhibitor, U0126, was used, which reduced BxPC-3 cell migration and the expression of ANO6. In summary, the results of the present study demonstrate that CCR7 promoted BxPC-3 cell migration by regulating ANO6 expression perhaps via activation of the ERK signaling pathway.

Early prediction of persistent organ failure by serum apolipoprotein A-I and high-density lipoprotein cholesterol in patients with acute pancreatitis.

BACKGROUND: Early identification of acute pancreatitis (AP) patients at high-risk of developing persistent organ failure (persistent OF) is a vital clinical goal. This research intends to assess the ability of apolipoprotein A-I (APO A-I) and high-density lipoprotein cholesterol (HDL-C) to predict persistent OF. METHODS: Between January 2011 and September 2016, a total of 102 adult AP patients with organ failure, local complications or deterioration of former comorbidities disease during hospitalization were included in this study retrospectively. Serum lipids were tested and computed the correlation with clinical outcomes or scoring systems. The AUCs to predict persistent OF were also calculated and compared with each other. RESULTS: Serum APO A-I and HDL-C levels were negatively associated with scoring systems. Meanwhile, serum lipids were negatively correlated with poor clinical outcomes. The AUCs of APO A-I, HDL-C, the combination of APO A-I and BISAP, or the combination of APO A-I and MCTSI to predict persistent OF among Moderately severe acute pancreatitis (MSAP) and Severe acute pancreatitis (SAP) patients were 0.886, 0.811, 0.912, and 0.900 or among those with organ failure were 0.915, 0.859, 0.933, and 0.933, respectively. CONCLUSIONS: The concentrations of APO A-I, HDL-C, and the combinations of APO A-I and scoring systems have high predictive value to predict persistent OF.

[Retracted] Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo.

Following the publication of this article, an interested reader drew to the attention of the Editorial Board that the above article appeared to contain a series of Figures that featured duplicated data. Following an internal investigation, the Editorial Board reached the conclusion that the allegations of the reader were well-founded. Specifically, the GAPDH bands shown in Figs. 2 and 3 are identical with those in Figs. 4C and 5D, with the exception that the images have been reversed. Furthermore, certain data in Fig. 4C of this paper appeared to have been shared with Fig. 3 in the following article (albeit for purportedly different experiments): Zhang J, Zhu J, Zhou Z, Chen W and Chen N: Inhibitory effects of ethyl pyruvate on invasion and metastasis of human gastric cancer SGC-7901 cells via downregulation of Akt pathway. China J Cancer Prev Treat (Chin) 39: 776-779, 2012. Despite numerous attempts at doing so, we were unable to receive any response to our request for further information from the authors of this article. Given the extent of the anomalies with the data between the aforementioned papers, the Editorial Board has therefore decided to retract the article from Oncology Reports. We regret any inconvenience in this regard. [the original article was published in the Oncology Reports 27: 1511-1519, 2012; DOI: 10.3892/or.2012.1623].

Establishing the colitis-associated cancer progression mouse models.

Inflammatory bowel disease (IBD) has been reported as an important inducer of colorectal cancer (CRC). The most malignant IBD-associated CRC type has been highlighted as colitis-associated cancer (CAC). However, lack of CAC cases and difficulties of the long follow-up research have challenged researchers in molecular mechanism probing. Here, we established pre-CAC mouse models (dextran sulfate sodium [DSS] group and azoxymethane [AOM] group) and CAC mouse model (DSS/AOM group) to mimic human CAC development through singly or combinational treatment with DSS and AOM followed by disease activity index analysis. We found that these CAC mice showed much more severe disease phenotype, including serious diarrhea, body weight loss, rectal prolapse and bleeding, bloody stool, tumor burden, and bad survival. By detecting expression patterns of several therapeutic targets-Apc, p53, Kras, and TNF-α-in these mouse models through western blot, histology analysis, qRT-PCR, and ELISA methods, we found that the oncogene Kras expression remained unchanged, while the tumor suppressors-Apc and p53 expression were both significantly downregulated with malignancy progression from pre-CAC to CAC, and TNF-α level was elevated the most in CAC mice blood which is of potential clinical use. These data indicated the successful establishment of CAC development mouse models, which mimics human CAC well both in disease phenotype and molecular level, and highlighted the promoting role of inflammation in CAC progression. This useful tool will facilitate the further study in CAC molecular mechanism.

Potent Anti-Inflammatory Activity of Tetramethylpyrazine Is Mediated through Suppression of NF-k.

The purpose of the current study was to evaluate the anti-inflammatory activity of tetramethlpyrazine on oxazolone-induced colitis mice. Spleen mononuclear cells (SMC), lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were isolated from oxazolone-induced colitis and normal mice. The colitis cells treated by oxazolone were randomly divided into model, low dose, middle dose and high dose groups treated with 0, 0.5, 1.0 and 2.0 g/L tetramethlpyrazine, respectively. The apoptotic rate of SMC and LPMC in the oxazolone-induced group was lower than that in the normal group. Compared with model group, apoptotic rate of SMC was significantly increased in the high dose group, while the apoptotic rate of LPMC in the middle dose group was increased. Compared with SMC, LPMC and PBMC of normal group, the mRNA level of nuclear factor kappa B (NF-kB), transcription factor-activated protein-1 (AP-1) and nuclear factor of activated T cells (NF-AT) were higher in model group. Tetramethylpyrazine inhibited the increase of NF-kB, AP-1 and NF-AT mRNA induced by oxazolone. For SMC, LPMC and PBMC there was significant difference in the mRNA level of AP-1 among the three different doses of tetramethylpyrazine treated groups. However, no significant difference was observed in the mRNA levels of NF-AT and NF-κB between normal and middle groups. Tetramethylpyrazine promoted the apoptotic rate of SMC and LPMC in-vitro, and suppressed the expression of transcription factors in SMC, LPMC and PBMC isolated from oxazolone-induced colitis mice. The study provides a novel insight into the mechanism behind the effect of etramethylpyrazine on colitis.

Eriocalyxin B blocks human SW1116 colon cancer cell proliferation, migration, invasion, cell cycle progression and angiogenesis via the JAK2/STAT3 signaling pathway.

Eriocalyxin B, a natural ent-kaurene diterpene compound, has been shown to prevent carcinogenesis and tumor development. However, little is known regarding the mechanism underlying the antitumor activity of Eriocalyxin B in human colon cancer. The aim of the present study was to examine the role of Eriocalyxin B in SW1116 cells, and to verify the hypothesis that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway may serve as a therapeutic target in human colon cancer treatment. Cell proliferation was measured with a Cell Counting kit­8 assay, and the cell cycle was assessed by flow cytometry. Cell migration and invasion were measured by Transwell analysis. In addition, western blot analysis was performed to detect the protein expression levels in SW1116 cells treated with various concentrations of Eriocalyxin B. The results demonstrated that 1 µmol/l Eriocalyxin B was effective at inhibiting JAK2 and STAT3 phosphorylation, followed by the downregulation of JAK2 and STAT3 downstream target expression, which resulted in the inhibition of cell proliferation, migration, invasion and angiogenesis. Eriocalyxin B also suppressed the expression of proliferation­associated protein (proliferating cell nuclear antigen) and angiogenesis­associated proteins (vascular endothelial growth factor and vascular endothelial growth factor receptor 2), as well as that of migration- and invasion­associated proteins (matrix metalloproteinase 2 and 9). These results suggested that Eriocalyxin B may suppress JAK2/STAT3 signaling, and thus act as a therapeutic or preventive agent in the treatment of human colon cancer.

Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/ß-catenin signalling pathway via suppression of activator protein 2α.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are emerging as key molecules in cancers, yet their potential molecular mechanisms are not well understood. The objective of this study is to examine the expression and functions of lncRNAs in the development of colorectal cancer (CRC). METHODS: LncRNA expression profiling of CRC, adenoma and normal colorectal tissues was performed to identify tumour-related lncRNAs involved in colorectal malignant transformation. Then, we used quantitative reverse transcription PCR assays to measure the tumour-related lncRNA and to assess its association with survival and response to adjuvant chemotherapy in 252 patients with CRC. The mechanisms of CCAL function and regulation in CRC were examined using molecular biological methods. RESULTS: We identified colorectal cancer-associated lncRNA (CCAL) as a key regulator of CRC progression. Patients whose tumours had high CCAL expression had a shorter overall survival and a worse response to adjuvant chemotherapy than patients whose tumours had low CCAL expression. CCAL promoted CRC progression by targeting activator protein 2α (AP-2α), which in turn activated Wnt/ß-catenin pathway. CCAL induced multidrug resistance (MDR) through activating Wnt/ß-catenin signalling by suppressing AP-2α and further upregulating MDR1/P-gp expression. In addition, we found that histone H3 methylation and deacetylases contributed to the upregulation of CCAL in CRC. CONCLUSIONS: Our results suggest that CCAL is a crucial oncogenic regulator involved in CRC tumorigenesis and progression.

Endogenous hydrogen sulfide is associated with angiotensin II type 1 receptor in a rat model of carbon tetrachloride-induced hepatic fibrosis.

The present study aimed to investigate the effects of endogenous hydrogen sulfide (H2S) on the expression levels of angiotensin II type 1 receptor (AGTR1) in a rat model of carbon tetrachloride (CCl4)­induced hepatic fibrosis. A total of 56 Wistar rats were randomly divided into four groups: Normal control group, model group, sodium hydrosulfide (NaHS) group, and DL­propargylglycine (PAG) group. Hepatic fibrosis was induced by CCl4. The rats in the PAG group were intraperitoneally injected with PAG, an inhibitor of cystathionine­Î³­lyase (CSE). The rats in the NaHS group were intraperitoneally injected with NaHS. An equal volume of saline solution was intraperitoneally injected into both the control and model groups. All rats were sacrificed at week three or four following treatment. The serum levels of hyaluronidase (HA), laminin protein (LN), procollagen III (PcIII), and collagen IV (cIV) were detected using ELISA. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin (ALB) were detected using an automatic biochemical analyzer. The liver mRNA expression levels of CSE were detected by reverse transcription­quantitative polymerase chain reaction. The liver expression levels of AGTR1 and the plasma expression levels of H2S were detected using western blot analyses. The results indicated that the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly higher in the PAG group, as compared with the model group (P<0.05). Conversely, the expression levels of ALB were significantly lower in the PAG group, as compared with the model group. In addition, the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly lower in the NaHS group, as compared with the model group (P<0.05). These results suggest that endogenous H2S is associated with CCl4­induced hepatic fibrosis in rats, and may exhibit anti­fibrotic effects. Furthermore, H2S reduced the liver expression levels of AGTR1, which may be associated with the delayed progression of hepatic fibrosis.

Prediction of synchronous colorectal cancers by computed tomography in subjects receiving an incomplete colonoscopy: a single-center study.

AIM: To assess the value of computed tomography (CT) for diagnosis of synchronous colorectal cancers (SCRCs) involving incomplete colonoscopy. METHODS: A total of 2123 cases of colorectal cancer (CRC) were reviewed and divided into two groups according to whether a complete or incomplete colonoscopy was performed. CT results and final histological findings were compared to calculate the sensitivity and specificity associated with CT for detection of SCRCs following complete vs incomplete colonoscopy. Factors affecting the CT detection were also analyzed. RESULTS: Three hundred and seventy-four CRC patients underwent incomplete colonoscopy and 1749 received complete colonoscopy. Fifty-six cases of SCRCs were identified by CT, and 36 were missed. In the incomplete colonoscopy group, the sensitivity and specificity of CT were 44.8% and 93.6%, respectively. The positive and negative predictive values were 23.6% and 95.0%, respectively. In contrast, the sensitivity and specificity of CT for the complete colonoscopy group were 68.3% and 97.0%, while the positive and negative predictive values were 22.2% and 98.7%, respectively. In both groups, the mean maximum dimension of the concurrent cancers identified in the CT-negative cases was shorter than in the CT-positive cases (incomplete group: P = 0.02; complete group: P < 0.01) Topographical proximity to synchronous cancers was identified as a risk factor for missed diagnosis (P = 0.03). CONCLUSION: CT has limited sensitivity in detecting SCRCs in patients receiving incomplete colonoscopy. Patients with risk factors and negative CT results should be closely examined and monitored.

Oleanolic acid induces apoptosis of MKN28 cells via AKT and JNK signaling pathways.

CONTEXT: Oleanolic acid (OA) belongs to the triterpenoid compound group existing widely in food, medicinal herbs and other plants. Its effects on gastric cancer cells and the mechanisms involved have not been investigated. OBJECTIVE: This study aimed to substantiate whether OA induces apoptosis of gastric cancer cell line (MKN28) and to elucidate the molecular mechanism involved. MATERIALS AND METHODS: Cell viability was assessed by MTT assay within the range of 0-160 µg/mL. The effects of OA (5, 10 and 20 µg/mL) on apoptosis of MKN28 cells were evaluated by flow cytometry, DNA fragmentation and mitochondrial membrane potential assays. Western blot and FQRT-PCR assays were used to investigate the mechanism of cell apoptosis induced by OA (5 and 10 µg/mL). RESULTS: OA evidently inhibited cell viability with IC50 of 44.8 and 15.9 µg/mL at 12 and 24 h, respectively. Furthermore, OA increased JNK phosphorylation, decreased AKT phosphorylation, but did not affect p38 and ERK phosphorylation in MKN28 cells. In contrast, OA also significantly enhanced the mRNA expression levels of caspase 3, caspase 9 and Apaf-1 in MKN28 cells. CONCLUSION: OA induces apoptosis of MKN28 cells via the mitochondrial pathway regulated by AKT and JNK signaling pathways.

Inhibition of phosphoinositide 3-kinase/Akt pathway decreases hypoxia inducible factor-1α expression and increases therapeutic efficacy of paclitaxel in human hypoxic gastric cancer cells.

The phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway plays an important role in cell proliferation, transformation, apoptosis, tumor growth and angiogenesis. Paclitaxel is commonly used to treat multiple human malignancies; however, the underlying mechanisms of paclitaxel in gastric cancer (GC) have not been fully investigated. In the present study, specimens from 45 GC and 36 chronic gastritis patients were collected, and the correlations of PI3K, phosphorylated-Akt (p-Akt) and hypoxia-inducible factor-1α (HIF-1α) expression with the clinicopathological characteristics of GC were analyzed by immunohistochemistry. The human SGC-7901 GC cells under hypoxic conditions were pretreated with the PI3K inhibitor, LY294002 (40 µM), and paclitaxel (0.1 µM). The expression levels of PI3K, p-Akt and HIF-1α were detected by quantitative polymerase chain reaction and western blotting. Cell proliferative activity and apoptosis were evaluated by the Cell Counting Kit-8 assay and flow cytometry. As a result, the rates of positive expression of PI3K, p-Akt and HIF-1α were significantly higher in GC compared with chronic gastritis patients (each P<0.01), and were positively associated with the tumor-node-metastasis (TNM) staging, lymph node metastases, lymphatic infiltration and vascular infiltration (each P<0.01), but inversely correlated with tumor differentiation (P<0.01) in patients with GC. Under hypoxic conditions, the combined inhibition of the PI3K/Akt pathway with paclitaxel markedly reduced the proliferative activity and induced cell apoptosis in GC cells compared with the single treatment of PI3K inhibitor or paclitaxel (each P<0.01), and was accompanied by a decreased expression of HIF-1α. Overall, our findings indicate that the increased expression of the PI3K/Akt/HIF-1α pathway was closely correlated with tumor differentiation, TNM staging, lymph node metastases and lymphatic and vascular infiltration. The inhibition of the PI3K/Akt pathway enhanced the therapeutic efficacy of paclitaxel in GC cells under hypoxic conditions, suggesting that the PI3K/Akt/HIF-1α pathway may act as an important therapeutic target for paclitaxel treatment of GC.

Tetramethylpyrazine improves oxazolone-induced colitis by inhibiting the NF-κB pathway.

PURPOSE: Tetramethylpyrazine (TMP) is an effective Chinese plant-derived medicine for colitis in the clinic, but the underlying molecular mechanisms of its use remain poorly understood. The purpose of this study was to investigate the mechanisms involved in its therapeutic action. METHODS: A colitis mouse model was induced by oxazolone enema. TMP was administered at 80 mg/kg/day and sulphasalazine (SASP) was used as positive control and administered at 100 mg/kg/day for the treatment of colitis. On the fourth day after enema, mice were sacrificed. The inflammatory response was assessed by the disease activity index and histology. Colon mucosa was isolated and biochemically analyzed. In addition, in vitro studies were performed to evaluate the activity of TMP in Caco-2 cells. RESULTS: Our results showed that TMP improved the colonic inflammatory status as evidenced by histological findings, as well as SASP. These effects were associated with a decrease in nucleus translocation of NF-κB. Paired with this inhibitive activity, there was a decrease in downstream signaling, such as C-MYC, iNOS and COX-2. In vitro assays revealed that TMP inhibited NF-κB translocation and its downstream production of inflammatory factors, such as TNF-α, IL-6 and IL-8, and that ROS production that was induced by LPS in Caco-2 cells. CONCLUSION: TMP improved the colitis induced by oxazoline, and its activity was associated with inhibition of NF-κB translocation, and subsequent inhibition of pro-inflammatory factor production and oxidative stress.

Temporary placement of a paclitaxel or rapamycin-eluting stent is effective to reduce stenting induced inflammatory reaction and scaring in benign cardia stricture models.

BACKGROUND/AIMS: To investigate whether temporary placement of a paclitaxel or rapamycin eluting stent is more effective to reduce stenting induced inflammatory reaction and scaring than a bared stent in benign cardia stricture models. MATERIALS AND METHODS: Eighty dog models of stricture were randomly divided into a control group (CG, n=20, no stent insertion), a bare stent group (BSG, n=20), a paclitaxel eluting (Pacl-ESG, n=20) and a rapamycin eluting stent group (Rapa-ESG, n=20), with one-week stent retention. Lower-oesophageal-sphincter pressure (LOSP), 5-minute barium height (5-mBH) and cardia diameter were assessed before, immediately after the procedure, and regularly for 6 months. Five dogs in each group were euthanized for histological examination at each follow-up assessment. RESULTS: Stent insertion was well tolerated, with similar migration rates in three groups. At 6 months, LOSP and 5-mBH improved in Pacl-ESG and Rapa-ESG compared to BSG (p<0.05), with no difference between Pacl-ESG and Rapa-ESG (p>0.05). Cardia kept more patency in the Pacl-ESG and Rapa-ESG than in BSG (p<0.05). Reduced peak inflammatory reactions and scarring occurred in the Pacl-ESG and Rapa-ESG compared to BSG (p<0.05), with a similar outcome in the Pacl-ESG and Rapa-ESG (p>0.05). CONCLUSION: Paclitaxel or rapamycin-eluting stents insertion led to better outcomes than bare stents in benign cardia stricture models.

Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB.

Although epithelial barrier dysfunction in the gut has been extensively reported in ulcerative colitis (UC), the pathogenesis of this disease is not completely understood. In the present study, we investigated the role of miR-21 in regulating intestinal epithelial barrier function in UC. Colonic biopsies were obtained from 30 chronic UC patients and 30 healthy controls. Using real-time quantitative polymerase chain reaction (qRT-PCR), we found that both the mucosal and serum levels of miR-21 were upregulated in UC. In situ hybridization (ISH) analysis confirmed the accumulation of miR-21 in UC epithelia cells in vivo. Immunohistochemistry, Western Blot, qRT-PCR, and ultrastructural analyses further demonstrated that the overexpression of miR-21 in UC mucosa and Caco-2 cells impaired the integrity of the tight junctions, resulted in a decrease of the transepithelial electrical resistance (TER) and an increase of the inulin permeability. Furthermore, miR-21 induced the degradation of RhoB mRNA, which led to the depletion of RhoB and the impairment of tight junctions in intestinal epithelial cells.

Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo.

The high mobility group box-B1 (HMGB1)-receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. Ethyl pyruvate (EP), a potent inhibitor of HMGB1 release, can exert antitumor effects on the growth of gastric cancer. Therefore, it is necessary to observe the effects of EP on gastric cancer growth in vitro and in vivo. Human gastric adenocarcinoma tissues of different grades (N=45) were collected. The expression of HMGB1 and RAGE was evaluated immunohistochemically in biopsy samples. After SGC-7901 gastric cancer cells were treated with EP, the expression of HMGB1, RAGE, Akt, phosphorylated Akt (p-Akt) and some transcription factors was identified and the effects of EP on cell proliferation, invasion, cell cycle distribution and apoptosis were assessed. A subcutaneous xenograft tumor model was established, validating the effects of EP on tumor growth in vivo. The expression of HMGB1 and RAGE was respectively observed in 73.3 and 68.9% of the gastric adenocarcinoma tissues. The frequency of positive expression increased with the ascending grade of the tumor malignancy. EP decreased the expression of HMGB1, RAGE, Akt, p-Akt, Ki-67 and matrix metallopeptidase-9 (MMP­9), and increased the expression of p53. Moreover, EP could inhibit tumor cell proliferation and invasion, induce cell cycle arrest and apoptosis and slow the growth of xenograft tumors. In conclusion, HMGB1 and RAGE were strongly expressed in gastric adenocarcinoma, and EP administration inhibited gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways. EP may play a critical role in the treatment of cancer in conjunction with other therapeutic agents.

Tetramethylpyrazine attenuates PPAR-γ antagonist-deteriorated oxazolone-induced colitis in mice.

Tetramethylpyrazine (TMP) is suggested to have anti-inflammatory activity. The aim of this study was to determine the role of peroxisome proliferator activated receptor γ (PPAR-γ) signaling in the pharmacologic effect of TMP on oxazolone (OXZ)-induced colitis. TMP (80 mg/kg/day i.p.) was administered daily 48 h after intrarectal instillation of OXZ, with or without PPAR-γ inhibitor [bisphenol A diglycidyl ether (BADGE) 30 mg/kg] during the 4 days before sacrifice. The inflammatory response was assessed by the disease activity index, macroscopy, histology and myeloperoxidase (MPO) activity. Expression levels of PPAR-γ, NF-κB p65, COX-2, iNOS and TNF-α mRNA in colon mucosa were determined by FQ-PCR, levels of PPAR-γ and NF-κB p65 protein were analyzed by immunohistochemistry, and the total and phosphorylated levels of p38 MAPK were assessed by western blotting. TMP significantly attenuated the damage caused by OXZ and substantially reduced the rise in MPO activity, TNF-α, iNOS, NF-κB p65 and COX-2 expression, as well as the increase in PPAR-γ production; however, no changes in the activation of p38 MAPK were observed. Inhibition of PPAR-γ signaling aggravated inflammation of colon mucosa, and increased p38 phosphrylation. TMP counteracted the effect of inhibition of PPAR-γ. We suggest that the effect of TMP treatment in ulcerative colitis may be related to PPAR-γ signaling, but is independent of PPAR-γ.

Application of the newly developed stents in the treatment of benign cardia stricture: an experimental comparative study.

BACKGROUND: Retrievable temporary stent placement has recently been suggested as a potential treatment for benign esophageal stricture. OBJECTIVE: To assess the efficacy of a newly designed cardia stent for the treatment of benign cardia stricture in a canine model compared with groups that received pneumatic dilation or standard esophageal stent insertion. DESIGN: Basic experimental study. SETTING: GI interventional center. PATIENTS: Forty-eight dog models were randomly divided into a control group (no stent insertion) (n=12), a pneumatic dilation group (PDG) (n=12), a standard esophageal stent group (SESG) (n=12), and a novel cardia stent group (NCSG) (n=12). INTERVENTIONS: Pneumatic dilation, standard esophagus stent, cardia stent. MAIN OUTCOME MEASUREMENTS: Lower esophageal sphincter pressures and the 5-minute barium height were assessed before and immediately after the procedure, after 1 week, and at 1-, 3-, and 6-month follow-up. Three dogs in each group were killed for histological examination. RESULTS: Stent insertion was tolerated by all dogs, with a lower migration rate in the NCSG (0% vs 41.7% in the SESG; P=.0373). At the 6-month follow-up, the lower esophageal sphincter pressure and 5-minute barium height values in the NCSG were still stable compared with those in the PDG and SESG (P<.05). Immunohistochemistry for mouse anti-proliferating cell nuclear antigen and α-smooth muscle actin revealed a stronger inflammatory reaction peak in the PDG than in the SESG and NCSG (P<.05). Collagen proliferation was most severe after 6 months in the PDG (P<.05). LIMITATIONS: Longer follow-up studies are required to assess whether the recurrence rate is lower because of less inflammation and scarring. CONCLUSIONS: The novel cardia stent was more effective than pneumatic dilation or a standard stent in this canine model.