Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause : A Randomized Controlled Trial.

BACKGROUND: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. OBJECTIVE: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. DESIGN: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395). SETTING: University teaching hospitals in Hong Kong, China, and Australia. PATIENTS: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: Standard hemostatic treatment (n = 97) or OTSC (n = 93). MEASUREMENTS: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. RESULTS: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). LIMITATION: Clinicians were not blinded to treatment and the option of crossover treatment. CONCLUSION: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. PRIMARY FUNDING SOURCE: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

The role of circular RNA hsa_circ_0001789 as a diagnostic biomarker in gastric carcinoma.

BACKGROUND: Circular RNA (circRNA) is a kind of endogenous non-coding RNAs and has shown diagnostic values in various cancers. This study aimed to explore whether hsa_circ_0001789 could be a novel biomarker for gastric cancer (GC). METHODS: Quantitative reverse transcriptase PCR was used to detect the expression of hsa_circ_0001789 in 108 paired GC and paracancerous tissues as well as in 24 paired plasma specimens. Possible associations between hsa_circ_0001789 expression and clinicopathologic factors of GC patients were examined using one-way ANOVA. A receiver operating characteristic (ROC) curve was established to investigate the diagnostic value of hsa_circ_0001789 in GC. RESULTS: GC tissues and plasma samples showed down-regulated hsa_circ_0001789 levels than their counterparts, which were closely correlated with the malignant characteristics of GC. The area under the ROC curve (AUC) of hsa_circ_0001789 in GC tissues was 0.82, while the cut-off value was 9.5, indicating a favorable diagnostic value. Compared with the traditional tumor biomarkers, hsa_circ_0001789 had preferred AUCs that reached 0.786 for predicting the stage of invasion, 0.603 for predicting the stage of lymphatic metastasis, 0.722 for predicting the stage of distant metastasis, and 0.786 for predicting TNM stage. CONCLUSIONS: Hsa_circ_0001789 may be a novel biomarker for the diagnosis of gastric carcinoma.

Reduced expression of circRNA hsa_circ_001888 in gastric cancer and its clinical significance.

BACKGROUND: Circular RNAs (circRNAs) are a novel family of endogenous RNAs. Recent studies have demonstrated that circRNAs are potential novel biomarkers for diagnosing cancers. However, little is known about the role of circRNAs in gastric cancer (GC). This study aimed to identify the relationship between GC and a new circRNA named hsa_circ_001888. METHODS: Hsa_circ_001888 expression levels were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in GC cell lines, tissues, and plasma samples. Then, the associations between the expression level of hsa_circ_001888 and the clinicopathological features of patients with GC were further investigated. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic value of hsa_circ_001888. RESULTS: In this study, hsa_circ_001888 was first found to be significantly downregulated in GC cell lines (AGS and MKN-45), tissues, and plasma samples compared to control samples. Clinicopathological features showed that the expression of hsa_circ_001888 in GC tissues was associated with differentiation and in GC plasma linked with serum CEA and CA19-9 levels. The areas under the ROC curves of hsa_circ_001888 in tissues and plasma were 0.654 and 0.66, respectively. CONCLUSIONS: Hsa_circ_001888 may serve as a potential biomarker in the diagnosis of GC and may be involved in GC development.

The clinical significance of vitamin D levels and vitamin D receptor mRNA expression in colorectal neoplasms.

BACKGROUND/AIM: This study aimed to investigate the clinical significance of changes in vitamin D [25(OH)D] levels and vitamin D receptor (VDR) mRNA expression in colorectal adenoma development. METHODS: Plasma concentrations of 25(OH)D and mRNA expression of VDR in tissues were determined by enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, the concentration of plasma 25(OH)D and levels of VDR mRNA in tissues were compared among healthy individuals and adenoma and adenocarcinoma patients. RESULTS: Vitamin D receptor expression in colorectal adenocarcinoma tissues was significantly lower than that in para-cancerous tissues that were >5 cm away from malignant tumor sites (p < 0.01). The level of VDR expression in normal colorectal tissues from healthy individuals was significantly higher than that in colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the VDR expression was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.106). The concentration of 25(OH)D in healthy individuals was significantly higher than that in patients with colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the concentration of 25(OH)D was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.489). A low concentration of 25(OH)D was considered a risk factor for colorectal adenoma and colorectal adenocarcinoma, with odds ratios of 4.875 and 2.925, respectively. CONCLUSIONS: The 25(OH)D levels and VDR mRNA expression might be associated with the development of colorectal adenoma and its progression to adenocarcinoma.

Early-life exposure to three size-fractionated ultrafine and fine atmospheric particulates in Beijing exacerbates asthma development in mature mice.

BACKGROUND: Epidemiological studies have suggested that elevated levels of air pollution contribute to an increased incidence or severity of asthma. Although late-onset adult asthma seems to be more attributable to environmental risk factors, limited data is available on the impact of early-life exposure to size-fractionated ambient particulate matter (PM) on asthma in adults. We aimed to determine the effect on the development and exacerbation of asthma in the adult after the mice were exposed as juveniles to three size-fractionated ambient particulates collected from Beijing. METHODS: The three size-fractionated ambient particulates were collected from urban Beijing in winter, heavily affected by traffic and coal-fired emissions. The typical morphological and major chemical components of the PM were characterized first. Oxidative stress and expression of DNA methyltransferases (DNMTs) were then examined in vitro and in the lungs of mouse pups 48 h after exposure to PM by oropharyngeal aspiration. When the exposed and control juvenile mice matured to adulthood, an antigen-induced asthma model was established and relevant bio-indices were assessed. RESULTS: PM with different granularities can induce oxidative stress; in particular, F1, with the smallest size (< 0.49 µm), decreased the mRNA expression of DNMTs in vitro and in vivo the most significantly. In an asthma model of adult mice, previous exposure as juveniles to size-fractionated PM caused increased peribronchiolar inflammation, increased airway mucus secretion, and increased production of Th2 cytokines and chemokines. In general, F1 and F2 (aerodynamic diameter < 0.95 µm) particulates affected murine adult asthma development more seriously than F3 (0.95-1.5 µm). Moreover, F1 led to airway inflammation in the form of both increased neutrophils and eosinophils in BALF. The activation of the TGF-ß1/Smad2 and Smad3/Stat3 signaling pathways leading to airway fibrosis was more profoundly induced by F1. CONCLUSION: This study demonstrated that exposure to ambient PM in juvenile mice enhanced adult asthma development, as shown by increased Th2 responses, which might be associated with the persistent effects resulting from the oxidative stress and decreased gene expression of DNMTs induced by PM exposure. The observed differences between the effects of three size-fractionated particulates were attributed to particle sizes and chemical constituents, including heavy metals and also PAHs, since the amounts of PAH associated with more severe toxicity were enriched equivalently in the F1 and F2 fractions. Relative to the often mentioned PM2.5, PM with an aerodynamic diameter smaller than 0.95 µm had a more aggravating effect on asthma development.

The functional sites of miRNAs and lncRNAs in gastric carcinogenesis.

Gastric cancer is one of the most common malignant diseases and has one of the highest mortality rates worldwide. Its molecular mechanisms are poorly understood. Recently, the functions of non-coding RNAs (ncRNAs) in gastric cancer have attracted wide attention. Although the expression levels of various ncRNAs are different, they may work together in a network and contribute to gastric carcinogenesis by altering the expression of oncogenes or tumor suppressor genes. They affect the cell cycle, apoptosis, motility, invasion, and metastasis. Dysregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), including miR-21, miR-106, H19, and ANRIL, directly or indirectly regulate carcinogenic factors or signaling pathways such as PTEN, CDK, caspase, E-cadherin, Akt, and P53. Greater recognition of the roles of miRNAs and lncRNAs in gastric carcinogenesis can provide new insight into the mechanisms of tumor development and identify targets for anticancer drug development.

Significance of estrogen receptor subtypes in breast tumorigenesis and progression.

The aim of the study was to investigate the effects of estrogen receptor (ER) subtypes (ERα and ERß) on breast cancer development and progression. The expression level of ERα and ERß in breast cancer tissues and paired normal breast tissues were detected by Western blot analysis and immunohistochemistry (IHC) staining. The features of ERα and ERß status in cancer tissues or normal breast tissues and the correlations between clinicopathological characteristics and prognosis were analyzed. The expression levels of ERα and ERß in breast cancer tissues are significantly lower than those in the paired normal tissues. The expression of ERß is decreased more than that of ERα. ERα expression levels in cancer tissues are associated with tumor diameter, tumor-node-metastasis (TNM) stage, and progesterone receptor (PR) status. However, ERß expression levels in cancer tissues are not correlated with clinicopathological factors of patients with breast cancer. In conclusion, ER subtypes might play different roles in the development of breast cancer.

Increased expression of long intergenic non-coding RNA LINC00152 in gastric cancer and its clinical significance.

It has been known that differential expression of long non-coding RNA (lncRNA) plays critical roles in carcinogenesis. However, the significance of lncRNA, especially long intergenic ncRNA (lincRNA, the main type of lncRNA family), in the diagnosis of gastric cancer is largely unknown. The aim of this study was to determine the expression level of LINC00152, a newfound lincRNA, in gastric carcinoma and its clinical association. The expression of LINC00152 in 71 pairs of tumorous and adjacent normal tissues from patients with gastric cancer was detected by quantitative real-time reverse transcription-polymerase chain reaction. And then, the potential associations between its level in gastric cancer tissue and the clinicopathological features were analyzed. Finally, a receiver operating characteristic (ROC) curve was constructed for differentiating patients with gastric cancer from patients with benign gastric diseases. The results showed that the expression level of LINC00152 in gastric carcinoma was significantly increased, compared with matched normal tissue (P=0.045) and normal mucosa from health control (P=0.004), respectively. Levels of LINC00152 in gastric cancer cell lines, BGC-823, MGC-803, and SGC-7901, were significantly higher than those in human normal gastric epithelial cell line GES-1. In addition, high expression of LINC00152 was correlated with invasion (P=0.042). LINC00152 levels in gastric juice from patients with gastric cancer were further found significantly higher than those from normal controls (P=0.002). Moreover, the area under the ROC curve (AUC) was up to 0.645 (95 % CI=0.559-0.740, P=0.003). This study highlights that lincRNA LINC00152 might be a novel biomarker for predicting gastric cancer.

lncRNA-AC130710 targeting by miR-129-5p is upregulated in gastric cancer and associates with poor prognosis.

Long noncoding RNAs (lncRNAs) play an important role in cancer occurrence and development. However, there is largely unknown about lncRNAs significance in the diagnosis and treatment of gastric cancer. In our study, we focused on AC130710, one of lncRNAs. Gastric cancer tissues and adjacent tissues were gathered from 78 patients with gastric cancer. The AC130710 levels were detected by reverse transcription polymerase chain reaction (RT-PCR). Then, we further analyzed the association between AC130710 level and the clinicopathological factors of patients with gastric cancer. Finally, the molecular mechanism underling AC130710 highly expressed in gastric cancer cells was explored. The results showed that AC130710 in cancer tissues from patients with gastric cancer was significantly higher than those in adjacent noncancerous tissues (P < 0.05). Its expression level was significantly associated with tumor size (P = 0.013), tumor-node-metastasis (TNM) stages (P = 0.030), and distal metastasis (P = 0.018). AC130710 expression in MGC-803 was significantly higher than that in normal gastric mucosa cell line GES-1 (P < 0.001). Moreover, miR-129-5p may play an important role in the downregulation of AC130710 in gastric cancer cells. These results indicated that lncRNA-AC130710 may be a potential tumor marker for gastric cancer prognosis.

Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer.

BACKGROUND: MicroRNAs (miRNAs) play a crucial role in carcinogenesis; however, it largely remains unclear whether miRNAs in gastric juice, which is specific for gastric tissues, can be used as biomarkers for gastric cancer. The objective of the current study was to investigate the feasibility of using gastric juice miRNAs as potential biomarkers to assist in screening for gastric cancer. METHODS: Gastric juice samples were collected from 141 patients who underwent upper gastrointestinal endoscopy examination between September 2010 and December 2011. Gastric cancer and adjacent normal biopsy specimens also were collected. The existence and stability of miRNAs in gastric juices were determined by real-time reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and sequencing. miRNA levels in tissues and gastric juices were detected by RT-qPCR. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases. RESULTS: Levels of miRNA-21 (miR-21) and miR-106a in gastric cancer tissues were significantly higher compared with the levels in adjacent tissues (P = .006 and P = .001, respectively). Patients who had gastric cancer had significantly different levels of gastric juice miR-21 and miR-106a compared with patients who had benign gastric diseases (both P < .001). There were significant correlations between miR-21/miR-106a levels and Borrmann types. miR-21 levels in intestinal type gastric cancer specimens were higher than that in diffuse (P = .003) or mixed (P < .001) gastric cancer types. The area under the ROC curve was up to 0.969 for miR-21 and 0.871 for miR-106a. CONCLUSIONS: The current results indicated that certain miRNAs in gastric juice are potential biomarkers that can assist in screening for gastric cancer.

Long non-coding RNA expression profile in human gastric cancer and its clinical significances.

BACKGROUND: Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome yet their potential roles in human cancers are not well understood. The aim of the present study was to determine the lncRNA expression profile in gastric cancer and its potential clinical value. METHODS: The global lncRNA expression profile in gastric cancer was measured by lncRNA microarray. Levels of two representative lncRNAs, H19 and uc001lsz, were confirmed by real-time reverse transcriptase-polymerase chain reaction. The relationship between their levels and clinicopathological factors of patients with gastric cancer was explored. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases. RESULTS: Total of 135 lncRNAs, which differential expression levels between tumor and non-tumorous tissues were more than twofold, were found (GEO No. GSE47850). The most down-regulated lncRNAs in gastric cancer tissues were FER1L4, uc001lsz, BG491697, AF131784, uc009ycs, BG981369, AF147447, HMlincRNA1600, and AK054588; while the most up-regulated ones were H19, HMlincRNA717, BM709340, BQ213083, AK054978, and DB077273. H19 was found highly expressed in stomach and liver cancer cell lines, while lowly expressed in lung cancer and prostate cancer cell lines. Uc001lsz was lowly expressed in gastric, lung and liver cancer cell lines, while highly expressed in prostate cancer. The areas under ROC curves were up to 0.613, 0.751, and 0.761 for H19, uc001lsz, and the combination, respectively. CONCLUSIONS: The lncRNA expression profile in gastric cancer suggests the potential roles of lncRNAs in gastric cancer occurrence and development. The overexpression of H19 in gastric cancer suggests that H19 may be participated in gastric cancer. The reduced expression of uc001lsz in gastric cancer cell lines and tissues, its associations with TNM stage, and its dysregulation in early cancer and precancerous lesions suggest that uc001lsz may be a potential marker for the diagnosis of early gastric cancer.

Decreased expression of long noncoding RNA AC096655.1-002 in gastric cancer and its clinical significance.

Long noncoding RNAs (lncRNAs) are newfound noncoding RNAs that are greater than 200 nucleotides in length. They have emerged recently as major players in governing fundamental biological processes. However, the expression level of lncRNAs and their clinical significances are not well understood. To investigate the lncRNA expression in gastric cancer, real-time reverse transcriptase-polymerase chain reaction was conducted. Then, the association between the level of AC096655.1-002, one of lncRNA, in gastric cancer tissues and the clinicopathological features of patients with gastric cancer was further analyzed. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values. The results showed that AC096655.1-002 was significantly downregulated in gastric cancer tissues compared with paired adjacent non-tumorous tissues (P < 0.001). Its expression level was significantly correlated with lymph node metastasis (P < 0.001), distant metastasis (P < 0.001), tumor-node-metastasis stages (P < 0.001), and differentiation (P = 0.030). The area under the ROC curve of AC096655.1-002 was up to 0.731. For the detection of gastric cancer, the use of AC096655.1-002 showed a remarkable improvement compared with the use of serum carcinoembryonic antigen. These results indicated that lncRNA AC096655.1-002 may be a potential biomarker in the diagnosis of gastric carcinoma.

Transfer RNA-derived small RNAs (tsRNAs) in gastric cancer.

Transfer RNA-derived small RNAs (tsRNAs) are newly discovered noncoding RNAs (ncRNAs). According to the specific cleavage of nucleases at different sites of tRNAs, the produced tsRNAs are divided into tRNA-derived stress-inducible RNAs (tiRNAs) and tRNA-derived fragments (tRFs). tRFs and tiRNAs have essential biological functions, such as mRNA stability regulation, translation regulation and epigenetic regulation, and play significant roles in the occurrence and development of various tumors. Although the roles of tsRNAs in some tumors have been intensively studied, their roles in gastric cancer are still rarely reported. In this review, we focus on recent advances in the generation and classification of tsRNAs, their biological functions, and their roles in gastric cancer. Sixteen articles investigating dysregulated tsRNAs in gastric cancer are summarized. The roles of 17 tsRNAs are summarized, of which 9 were upregulated and 8 were downregulated compared with controls. Aberrant regulation of tsRNAs was closely related to the main clinicopathological factors of gastric cancer, such as lymph node metastasis, Tumor-Node-Metastasis (TNM) stage, tumor size, and vascular invasion. tsRNAs participate in the progression of gastric cancer by regulating the PTEN/PI3K/AKT, MAPK, Wnt, and p53 signaling pathways. The available literature suggests the potential of using tsRNAs as clinical biomarkers for gastric cancer diagnosis and prognosis and as therapeutic targets for gastric cancer treatment.

Tumor budding as an indicator for lymph node metastasis and prognosis of early gastric cancer.

BACKGROUND: Tumor budding, considered as an independent risk factor reflecting prognosis of some malignant tumors, has been recognized as an important clinicopathological indicator of colorectal carcinoma. However, the evaluation of tumor budding and its clinicopathological significance in gastric cancer remain controversial. AIM: To investigate the relationship between tumor budding and clinical biological behavior of early gastric cancer (EGC) and assess the predictive value of tumor budding for lymph node metastasis as well as its impact on prognosis of EGC patients. METHODS: Tissue specimens of 164 EGC patients who underwent radical gastrectomy between June 2011 and January 2017 from a single center were selected to carry out HE and CK staining respectively, so as to evaluate tumor budding under light microscopy. Clinicopathological data and follow-up results of all EGC patients were collected for statistical analysis among tumor budding, EGC clinicopathological factors and prognosis. RESULTS: Of all 164 EGC patients, there were 84 (51.2%) cases with mucosal invasion and 80 (48.8%) cases with submucosal invasion. Meanwhile, 32 cases (19.5%) had lymph node metastasis, 19 (11.6%) had lympho-vascular invasion and 4 (2.4%) had early recurrence. Tumor budding were observed in 90 (54.9%) patients, with low-grade budding 68 (41.5%) cases and high-grade budding 22 (13.4%) cases. Tumor budding was closely correlated with tumor size (c2 = 6.609, P = 0.037), tumor histologic differentiation (c2 = 10.522, P = 0.032), depth of invasion (c2 = 8.787, P = 0.012), lymph node metastasis (c2 = 24.226, P < 0.01), TNM stage (c2 = 24.226, P < 0.01), lympho-vascular invasion (c2 = 8.225, P = 0.016) and early recurrence (c2 = 6.462, P = 0.040). Additionally, tumor budding was correlated with postoperative survival rate as well. Multiple regression analysis revealed that tumor budding was an independent influencing factor of postoperative 3-year survival rate, 5-year survival rate, OS, DFS and DSS (P < 0.05). Furthermore, tumor budding was an independent risk factor of lymph node metastasis of EGC patients, and high-grade budding was a high-risk indicator of lymph node metastasis. CONCLUSION: Tumor budding is related to tumor size, tumor histologic differentiation, depth of invasion, lymph node metastasis, lympho-vascular invasion and early recurrence of EGC. Tumor budding, especially high-grade budding can serve as an indicator for predicting lymph node metastasis of EGC, and high-grade budding could be an important parameter for evaluating prognosis of EGC patients.

Gastric juice microRNA-421 is a new biomarker for screening gastric cancer.

MicroRNA-421 (miR-421) plays crucial roles during carcinogenesis and is a potential tumor marker in the diagnosis of several types of cancers. However, whether miR-421 in gastric juice, which is specific for gastric tissue, can be used as a biomarker for gastric cancer screening is unclear. In the present study, real-time quantitative reverse transcription-polymerase chain reaction was used to analyze miR-421 levels in gastric juice from patients with gastric cancer or benign gastric disease, or normal. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values. The results showed that gastric juice levels of miR-421 in patients with gastric cancer were significantly different from those in benign gastric diseases (P < 0.001). The area under the ROC curve of miR-421 was up to 0.767 (95 % CI = 0.684-0.850). The levels of miR-421 in gastric juice from gastric patients were not significantly associated with the main clinicopathological factors such as tumor size, Lauren's classification, and Borrmann's classification. For the detection of early gastric cancer, the use of gastric juice miR-421 showed a remarkable improvement compared with the use of serum carcinoembryonic antigen alone. These results indicated that gastric juice miRNAs such as miR-421 are useful biomarkers for screening gastric cancer.

Hsa_circ_0001696 modulates cell proliferation and migration in colorectal cancer.

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA molecules that are extensively expressed in a variety of species. Recently, increasing evidence suggests that circRNAs have vital functions indifferent types of human cancer, such as gastric cancer, papillary thyroid cancer and lung cancer. However, the roles of circRNAs in the development of colorectal cancer (CRC) remain unclear. The present study aimed to determine the molecular mechanism underlying hsa_circ_0001696 on the proliferation and migration of CRC cells. Reverse transcription-quantitative PCR analysis was performed to detect hsa_circ_0001696 expression in 18 paired CRC tissues and matched adjacent normal tissues. RNA interference was also performed to decrease hsa_circ_0001696 expression, and its biological effects were further assessed via flow cytometry, wound healing, colony formation and western blot assays. The results demonstrated that hsa_circ_0001696 expression was significantly lower in CRC tissues compared with adjacent normal tissues. Furthermore, hsa_circ_0001696 knockdown promoted cell proliferation and migration, and the number of cell colonies significantly increased. In addition, western blot analysis demonstrated that the protein expression levels of cyclin-dependent kinase 4 (CDK4), cyclin D, cyclin E and matrix metalloproteinase 9 (MMP9) increased. Taken together, the results of the present study demonstrated that hsa_circ_0001696 expression was downregulated in CRC tissues, and inhibition of hsa_circ_0001696 promoted cell proliferation and migration by regulating the levels of CDK4, cyclin D, cyclin E and MMP9.

Effects of aspirin on the gastrointestinal tract: Pros vs. cons.

Acetylsalicylic acid, also known as aspirin, is often used in clinical antipyretic, analgesic and antiplatelet therapy. Aspirin can cause numerous side effects in the gastrointestinal (GI) tract, ranging from unpleasant GI symptoms without gastric mucosal lesions to ulcer bleeding and even death. However, recent studies have found that aspirin can significantly prevent GI tumors. Despite impressive advances in cancer research, screening and treatment options, GI tumors remain a leading cause of death worldwide. Prevention is a far better option than treatment for tumors. Therefore, the present review assesses the pros and cons of aspirin on the GI tract and, on this the basis, the appropriate dose of aspirin to protect it.

Zenker's diverticulum treated with submucosal tunneling endoscopic septum division surgery: Two case reports.

INTRODUCTION: Zenker's diverticulum (ZD) refers to a pouch-like structure similar to the esophageal lumen formed from the herniation of the esophageal mucosa; this structure makes it difficult for food to pass through the esophagus to the stomach. The development of endoscopic technology has made minimally invasive surgical treatments for ZD possible. PATIENT CONCERNS: A female 72-year-old patient was admitted to our hospital due to recurrent dysphagia for more than 5 years. A 62-year-old female patient underwent a gastroscopic examination due to recurrent dysphagia for 10 years and aggravated dysphagia accompanied by bad breath for 1 year. DIAGNOSIS: A significant diverticulum with food residue at the entrance of the esophagus was found on gastroscopy in both cases. INTERVENTIONS: After completing a relevant examination and excluding surgical contraindications, both patients underwent submucosal tunneling endoscopic septum division. OUTCOMES: Both patients were discharged after symptoms alleviated on postoperative day 4. A 3-month follow-up gastroscopy showed the disappearance of the diverticulum and recovery of the esophageal anatomical structure. No symptom relapse was found at the 6-month follow-up assessment. CONCLUSION: Submucosal tunneling endoscopic septum division has become the most common minimally invasive treatment option. It is efficient and safe for relieving symptomatic ZD in the short term.

Carbonic anhydrase IV inhibits cell proliferation in gastric cancer by regulating the cell cycle.

Carbonic anhydrase IV (CA4) is silenced in colorectal cancer. However, the effect of CA4 on the development of gastric cancer (GC) is poorly understood. The present study aimed to determine the role of CA4 in GC tumorigenesis and its underlying molecular mechanism. The levels of CA4 in GC cells and tissues were evaluated by reverse transcription-quantitative PCR and immunohistochemistry. CA4 expression was suppressed in GC cells and tissues compared with adjacent healthy tissues and normal human gastric epithelial cells, respectively. This reduced expression was significantly associated with tumor size, invasion and differentiation. Analyses with a real-time cell analyzer and clonogenic assays were conducted to validate the impact of CA4 on GC cell lines (AGS and HGC-27) and normal human gastric epithelial cell line (GES-1) proliferation. The effects of CA4 on the cell cycle in GC cells were determined by flow cytometry. The levels of CA4 and cell cycle-associated proteins were confirmed by western blotting. CA4 overexpression inhibited GC cell proliferation and reduced colony-forming ability, arrested the cell cycle in the G2/M phase, inhibited cyclin B1 and cyclin-dependent kinase 2 expression and induced p21 expression. These results indicate that CA4 may serve an important role in GC tumorigenesis by inhibiting cellular proliferation via regulating the expression of cell cycle-associated proteins. CA4 may serve as a diagnostic biomarker and a potential therapeutic target in GC.