NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development.

Our study aimed to elucidate the molecular mechanisms underlying NAC1 (nucleus accumbens associated 1) transcriptional regulation of LDHA and its role in HBV immune evasion, thus contributing to the development of cirrhosis and hepatocellular carcinoma (HCC). Utilizing public datasets, we performed differential gene expression and weighted gene co-expression network analysis (WGCNA) on HBV-induced cirrhosis/HCC data. We identified candidate genes by intersecting differentially expressed genes with co-expression modules. We validated these genes using the TCGA database, conducting survival analysis to pinpoint key genes affecting HBV-HCC prognosis. We also employed the TIMER database for immune cell infiltration data and analyzed correlations with identified key genes to uncover potential immune escape pathways. In vitro, we investigated the impact of NAC1 and LDHA on immune cell apoptosis and HBV immune evasion. In vivo, we confirmed these findings using an HBV-induced cirrhosis model. Bioinformatics analysis revealed 676 genes influenced by HBV infection, with 475 genes showing differential expression in HBV-HCC. NAC1 emerged as a key gene, potentially mediating HBV immune escape through LDHA transcriptional regulation. Experimental data demonstrated that NAC1 transcriptionally activates LDHA, promoting immune cell apoptosis and HBV immune evasion. Animal studies confirmed these findings, linking NAC1-mediated LDHA activation to cirrhosis and HCC development. NAC1, highly expressed in HBV-infected liver cells, likely drives HBV immune escape by activating LDHA expression, inhibiting CD8 + T cells, and promoting cirrhosis and HCC development.

Double-balloon enteroscopy for the detection of GIST in a patient with neurofibromatosis type 1.

NF1 is an autosomal dominant hereditary disease, with a prevalence of at least 1 in 4000-5000 population. The diagnosis criteria of NF1 included typical manifestations such as café-au-lait spots, frecking in the axilla or inguinal region, multiple neurofibromas, Lisch nodeules, and distinctive osseous lesions. Genetic testing shows NF1 mutation. It is essential for tumor surveillance in NF1 patients because their life expectancy is about 54 years due to malignancy. A case of NF-1 patient receive laparoscopic small bowel resection and finally diagnosed as adenocarcinoma and ganglioneuroma. About 25% of NF1 patients had GISTs , most of them were asymptomatic and some may manifest with abdominal pain, bowel obstruction, or gastrointestinal bleeding. CT and MRI are commonly used imaging modalities for GIST in NF1, while they may be negative sometimes. As DBE a more practical and non-invasive method now, we consider it is a valuable method for screening and early detecting small intestine disease for NF1 patients.

A case of achalasia associated with early esophageal cancer.

A 65-year-old man was admitted to our hospital complaining of reflux for more than 20 years. After endoscopy and barium-swallow examination, he was diagnosed with achalasia as well as a squamous cell carcinoma. Therefore, peroral endoscopic myotomy (POEM) combined with endoscopic submucosal dissection (ESD) was performed simultaneously. During the procedure, a mucosal erosion with a clear boundary was shown in the middle segment of the esophagus. ESD was first performed and the lesion was removed en-bloc. Subsequent POEM therapy was performed after marking the left esophageal wall 10cm above the cardia. After submucosal injection, the submucosal plane was created through a length 2cm longitudinal incision, then the muscle was cut a length of 10 cm into the esophagus and 2 cm below the cardia, and finally the incision was closed by clips. Pathological examination revealed high-grade intraepithelial neoplasia of squamous epithelium (carcinoma in situ) with a negative margin. The patient was recovered without complication four days after the procedure. The endoscopy showed perfect healing of the esophageal lesions during two-months follow-up , and the reflux symptom was resolved.

The SMAD2/miR-4256/HDAC5/p16INK4a signaling axis contributes to gastric cancer progression.

The dysregulation of exosomal microRNAs (miRNAs) plays a crucial role in the development and progression of cancer. This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer (GC) and the underlying mechanisms. The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics. Next, the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues, and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments. Then, the effect of miR-4256 on its downstream target genes HDAC5/p16INK4a was studied in GC cells, and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation (ChIP). Additionally, the role of the miR-4256/HDAC5/p16INK4a axis in GC was studied using in vitro and in vivo experiments. Finally, the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments. miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues; in vitro and in vivo results showed that miR-4256 promoted GC growth and progression. Mechanistically, miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells, and then restrained the expression of p16INK4a through the epigenetic modulation of HDAC5 at the p16INK4a promoter. Furthermore, miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells. Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16INK4a axis, which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.

Nursing Cooperation Pattern for Patients With Advanced Pancreatic Cancer and Abdominal Pain Undergoing Endoscopic Ultrasound-guided Celiac Plexus Neurolysis.

Context: Patients with pancreatic cancer (PC) at a late stage often suffer from severe abdominal pain due to the invasion of celiac plexus, and the analgesics they receive often have intolerable side effects. Endoscopic, ultrasound-guided, celiac plexus neurolysis (EUS-guided CPN) can have a good therapeutic effect. Objective: The study intended to evaluate the ability of two nursing cooperation patterns to reduce patients' pain, decrease operation times, increase operational efficiency, and increase nurses' satisfaction, for patients with advanced PC and abdominal pain who received EUS-guided CPN. Design: The research team designed a retrospective controlled study. Setting: The study took place at the Shenzhen People's Hospital of the Second Clinical Medical College of Jinan University in Shenzhen, China, and at the Changhai Hospital of the Second Military Medical University in Shanghai, China. Participants: Participants were 40 patients with advanced PC who received EUS-guided CPN at one of the two hospitals between January 2019 and January 2020. Intervention: Twenty participants at Changhai Hospital received the traditional nursing cooperation pattern and became the control group, and 20 participants at the Shenzhen People's Hospital received the new nursing cooperation pattern and became the intervention group. Outcome Measures: The study measured clinical data, nursing measures, diagnostic significance, and key points for the two patterns as well as compared the effects of the new nursing cooperation method to that of traditional nursing. If the measurement data met the requirements for normality, the team used the two independent sample t-test for the intergroup comparisons. If normality wasn't satisfied, the team used medians and interquartile ranges (IQRs) for expression and the rank sum test for the intergroup comparisons. Counting data were expressed using the constituent ratio, and team used the chi-square test for comparisons between groups. P < .05 was considered to be statistically significant. Results: The operations were successful, and no complications occurred. No significant difference existed in the pain scores between the control group and the intervention group (P > .05), while a significant difference occurred in the nurses' operation times and satisfaction. Not only were the scores for operation times for the control group (97) and the intervention group (59) significantly different, but also the nurses' satisfaction was significantly higher for the intervention group postintervention, at 83.35 ± 5.25, than for the control group, at 62.25 ± 8.18 (P < .001). Such a new nursing cooperation method could assist in patient's rehabilitation and increase nurses' satisfaction. Conclusions: The new nursing cooperation method for patients with advanced PC and abdominal pain undergoing EUS-guided CPN can reduce operation time and improve nurses' satisfaction.

Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell-mediated cytotoxicity and PD-1 checkpoint.

BACKGROUND: Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC. METHODS: The tumor and adjacent normal tissues were collected from 73 PC patients. The expression of LINC00460, miR-503-5p, and ANLN was detected using qRT-PCR. We then analyzed the proliferation, migration, invasion, and apoptosis/cell cycle of PC cells by performing the MTT/EdU, transwell, and flow cytometry assays, respectively. The xenograft tumor model were utilized to confirm the effect of LINC00460 knockdown on PC through anti-PD-1 therapy in vivo, and the sensitivity of PANC-1 cells to the cytotoxicity of CD8+ T cells in vitro. Western blotting was used to determine the protein levels. A co-culture model was utilized to explore the effects of exosomes on macrophages. RESULTS: LINC00460 was up-regulated in PC tissues and cells. LINC00460 knockdown suppressed cell proliferation, migration, and invasion, facilitated cell apoptosis and G0/G1 phase arrest, and inhibited the tumor growth through anti-PD-1 therapy. Both miR-503-5p down-regulation and ANLN up-regulation reversed the effects of LINC00460 knockdown on inhibiting the proliferation, migration and invasion, and on promoting the apoptosis, G0/G1 phase arrest, and the sensitivity of PC cells to the cytotoxicity of CD8+ T cells. Exosomes were uptaken by the ambient PC cells. PANC-1 cells-derived exosomal LINC00460-induced M2 macrophage polarization accelerates the cell migration and invasion. CONCLUSIONS: LINC00460 silencing attenuates the development of PC by regulating the miR-503-5p/ANLN axis and exosomal LINC00460-induced M2 macrophage polarization accelerates the migration and invasion of PANC-1 cells, thus LINC00460 may act as a possible therapeutic target for treating PC.

Vitamin D intake as well as circulating 25-hydroxyvitamin D level and risk for the incidence and recurrence of colorectal cancer precursors: A meta-analysis.

Objective: Vitamin D consumption and circulating 25(OH)D level are associated with decreased risk of colorectal cancer (CRC) and colorectal adenoma (CRA), but few studies have assessed their relationship with the incidence and recurrence of CRC precursors. Therefore, we performed this meta-analysis to further evaluate the association. Methods: We searched PubMed, Web of Science, Scopus and Embase databases in English until August 2021. Studies evaluating the association of vitamin D intake and circulating 25(OH)D level with risk of CRC precursors were included. A random-effects model was used to pool the risk estimates. Results: A total of 48 studies were selected for inclusion. The CRC precursors incidence was negatively correlated with total vitamin D intake (RR = 0.84 95%CI: 0.80-0.88) and circulating 25(OH)D level (RR = 0.79 95%CI: 0.67-0.92). However, vitamin D intake and circulating 25(OH)D level did not show significant effects on the risk of CRC precursors recurrence. For dose-response analysis, evidence of a linear association was found between CRC precursors incidence and circulating 25(OH)D level, and the risk decreased by 14% per 10 ng/ml increment of circulating 25(OH)D level (RR = 0.86 95% CI: 0.75-0.99). Conclusion: Vitamin D intake and circulating 25(OH)D level can play an effective role in reducing the risk of incidence of CRC precursors. However, they have not prevented the recurrence of CRC precursors.

Comparison of Two Different Accesses Single Orifice Percutaneous Endoscopic Surgery in Diagnosis of Ascites of Unknown Origin: A Retrospective Study.

Background: Ascites is a common clinical finding caused by many different diseases, so we developed a technique termed single orifice percutaneous endoscopic surgery (SOPES) which can access peritoneal cavity through the contralateral McBurney's point or umbilicus to seek the underlying causes. In this study, we describe the initial clinical experience of SOPES and compare the application of two accesses. Methods: This is a retrospective study performed between 2007 and 2018. Patients with ascites of unknown origin who underwent these two kinds of SOPES were included. Main outcomes were measured by diagnostic accuracy, complication rate, procedure time, time till stitches removal, length of hospital stay, and hospital cost. Results: 148 patients successfully undergone SOPES via the contralateral McBurney's point (IM group, n = 70) or the umbilicus (UM group, n = 78). 63 patients in the IM group and 71 patients in the UM group reached clear diagnosis (90.0% vs. 91.0%, p = 0.831). The overall complication rate was 5.4%, while the UM group was higher than the IM group (10.3% vs. 0%, p = 0.017). All complications were resolved after medical treatment, and no mortality resulted from this procedure. The procedure time and the time until stitches removal in the UM group were longer than that in the IM group. There were no significant differences in length of hospital stay and hospital cost between the two groups. Conclusions: SOPES, which combines the strength of minimally invasive single orifice incision and flexible angles of examination and instrumentation, is a newly developed flexible endoscopic surgical modality that provides new important clinical valuable in evaluation of ascites of unknown origin. Moreover, SOPES via the contralateral McBurney's point was safer than the umbilicus approach.

Long noncoding RNA KIF9-AS1 promotes cell apoptosis by targeting the microRNA-148a-3p/suppressor of cytokine signaling axis in inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) is a chronic intestinal disease. This study was attempted to investigate the effects of long noncoding RNA KIF9-AS1 (KIF9-AS1) on the development of IBD and its underlying mechanism of action. METHODS: Quantitative real time PCR (qRT-PCR) was implemented to examine the expression of KIF9-AS1 and microRNA-148a-3p (miR-148a-3p). The IBD mouse model was induced by dextran sulfate sodium (DSS). The body weight, disease activity index (DAI) score, colon length and histological injury were used to evaluate the colon injury. The levels of proinflammatory cytokines were measured by ELISA. In vitro, IBD was simulated by DSS treatment in colonic cells. Then the apoptosis of colonic cells was detected by flow cytometry assay. Furthermore, a dual-luciferase reporter assay was used to demonstrate the interactions among KIF9-AS1, miR-148a-3p and suppressor of cytokine signaling (SOCS3). RESULTS: KIF9-AS1 expression was upregulated in IBD patients, DSS-induced IBD mice and DSS-induced colonic cells, whereas miR-148a-3p expression was downregulated. KIF9-AS1 silencing attenuated the apoptosis of DSS-induced colonic cells in vitro and alleviated colon injury and inflammation in DSS-induced IBD mice in vivo. Additionally, the mechanical experiment confirmed that KIF9-AS1 and SOCS3 were both targeted by miR-148a-3p with the complementary binding sites at 3'UTR. Moreover, miR-148a-3p inhibition or SOCS3 overexpression reversed the suppressive effect of KIF9-AS1 silencing on the apoptosis of DSS-induced colonic cells. CONCLUSION: KIF9-AS1 silencing hampered the colon injury and inflammation in DSS-induced IBD mice in vivo, and restrained the apoptosis of DSS-induced colonic cells by regulating the miR-148a-3p/SOCS3 axis in vitro, providing a new therapeutic target for IBD.

Long non-coding RNA FTX predicts a poor prognosis of human cancers: a meta-analysis.

BACKGROUND: Several studies have assessed the relationship between long non-coding RNA five prime to Xist (FTX) expression, clinicopathological features, and survival outcomes in patients with cancer with conflicting results. This meta-analysis synthesized existing data to clarify the association between FTX with cancer prognosis. METHODS: PubMed, Embase, Cochrane library, Web of Science, Chinese CNKI, and the Chinese WanFang databases were used to search for relevant studies. The role of FTX in cancers was evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Eleven studies comprising 1210 participants including colorectal cancer (CRC), hepatocellular carcinoma (HCC), gastric cancer (GC), renal cell carcinoma (RCC), osteosarcoma (OSC), and glioma were enrolled in this analysis. The meta-analysis showed that high FTX expression was significantly associated with several clinicopathological characteristics, including lymph node metastasis in patients with CRC, GC, HCC, and RCC, distant metastasis in patients with CRC, GC, HCC, and OSC, larger tumor size in patients with CRC, GC, HCC, RCC, and OSC, and subsequently TNM/clinical stage in patients with CRC, GC, HCC, OSC, and glioma. The pooled results from the survival analysis revealed a significant correlation between high FTX expression and shorter OS in patients with HCC, CRC, GC, OSC, and glioma. Further, FTX overexpression could be an independent predictive marker for shorter OS in patients with CRC, HCC, OSC, and glioma. CONCLUSIONS: FTX may be a potential oncogene, with high FTX expression being associated with a poorer prognosis in patients with CRC, HCC, OSC, and glioma.

miR-802 participates in the inflammatory process of inflammatory bowel disease by suppressing SOCS5.

The present study aims to reveal the detailed molecular mechanism of microRNA (miR)-802 in the progression of inflammatory bowel disease (IBD). IBD tissues were obtained from IBD patients, followed by CD4+ cells isolation. Then, qRT-PCR and ELISA were used to detect the expression of miR-802, suppressor of cytokine signaling 5 (SOCS5), interleukin (IL)-17A and tumor necrosis factor (TNF)-α. Transfection of miR-802 mimics and miR-802 inhibitor in CD4+ cells was detected by Western blot. TargetScan and luciferase reporter assay were used to detect the relationship between SOCS5 and miR-802. Finally, colitis mice model was established to verify whether miR-802 inhibitor was involved in the protective effect of colonic mucosa. The miR-802 was highly expressed in inflamed mucosa and PBMC cells of IBD. The highest expression of miR-802 was observed in CD4+ T cells based on different immune cell subsets analysis. SOCS5 was the target gene of miR-802. The mice model experiments showed that blockade of miR-802 could alleviate mice colitis. Our study suggests that up-regulation of miR-802 plays an important role in inflammatory process of IBD via targeting SOCS5. Moreover, the differentiation of Th17 and secretion of TNF-α in IBD could be stimulated by miR-802.

Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats.

BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM: To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS: IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of C-kit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB. RESULTS: WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-ß), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION: BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.

Magnitude, Risk Factors, and Factors Associated With Adenoma Miss Rate of Tandem Colonoscopy: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: We performed a systematic review and meta-analysis to comprehensively estimate adenoma miss rate (AMR) and advanced AMR (AAMR) and explore associated factors. METHODS: We searched the PubMed, Web of Science, and Ovid EMBASE databases for studies published through April 2018 on tandem colonoscopies, with AMR and AAMR as the primary outcomes. We performed meta-regression analyses to identify risk factors and factors associated with outcome. Primary outcomes were AMR and AAMR and secondary outcomes were AMR and AAMR for different locations, sizes, pathologies, morphologies, and populations. RESULTS: In a meta-analysis of 43 publications and more than 15,000 tandem colonoscopies, we calculated miss rates of 26% for adenomas (95% confidence interval [CI] 23%-30%), 9% for advanced adenomas (95% CI 4%-16%), and 27% for serrated polyps (95% CI 16%-40%). Miss rates were high for proximal advanced adenomas (14%; 95% CI 5%-26%), serrated polyps (27%; 95% CI 16%-40%), flat adenomas (34%; 95% CI 24%-45%), and in patients at high risk for colorectal cancer (33%; 95% CI 26%-41%). Miss rates could be decreased by adequate bowel preparation and auxiliary techniques (P = .06; P = .04, and P = .01, respectively). The adenoma detection rate (ADR), adenomas per index colonoscopy, and adenomas per positive index colonoscopy (APPC) were independently associated with AMR (P = .02, P = .01, and P = .008, respectively), whereas APPC was the only factor independently associated with AAMR (P = .006). An APPC value greater than 1.8 was more effective in monitoring AMR (31% vs 15% for AMR P < .0001) than an ADR value of at least 34% (27% vs 17% for AMR; P = .008). The AAMR of colonoscopies with an APPC value below 1.7 was 35%, vs 2% for colonoscopies with an APPC value of at least 1.7 (P = .0005). CONCLUSIONS: In a systematic review and meta-analysis, we found that adenomas and advanced adenomas are missed (based on AMR and AAMR) more frequently than previously believed. In addition to ADR, APPC deserves consideration as a complementary indicator of colonoscopy quality, if it is validated in additional studies.