PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients.

BACKGROUND/AIM: Gliomas are the most prevalent brain tumors with metabolic alterations playing a pivotal role in disease progression. However, the precise coordination of metabolic alterations with tumor-promoting cellular mechanisms, leading to tumor initiation, progression, and aggressiveness, resulting in poor outcomes, remains poorly understood in gliomas. MATERIALS AND METHODS: We conducted a metabolism-targeted differential gene expression analysis using glioma patients' expression profiling data from The Cancer Genome Atlas (TCGA) database. In addition, pathway enrichment analysis, gene set enrichment analysis (GSEA), transcription factor prediction, network construction, and correlation analyses were performed. Survival analyses were performed in R. All results were validated using independent GEO expression datasets. RESULTS: Metabolism-targeted analysis identified 5 hits involved in diverse metabolic processes linking them to disease aggressiveness in gliomas. Subsequently, we established that cell cycle progression and hyper-proliferation are key drivers of tumor progression and aggressiveness in gliomas. One of the identified metabolic hits, DNA primase 2 (PRIM2), a gene involved in DNA replication was found directly associated with cell cycle progression in gliomas. Furthermore, our analysis indicated that PRIM2, along with other cell cycle-related genes, is under the control of and regulated by the oncogenic MYC transcription factor in gliomas. In addition, PRIM2 expression alone is enough to predict MYC-driven cell cycle progression and is associated with tumor progression, aggressive disease state, and poor survival in glioma patients. CONCLUSION: Our findings highlight PRIM2 as a marker of MYC-driven cell cycle progression and hyper-proliferation, disease onset and progression, tumor aggressiveness, and poor survival in glioma patients.

Paper test strip for fluorescence detection of iron ion based on nitrogen, zinc and copper codoped carbon dots.

In this study, a test strip for fluorometric analysis of iron ion (Fe3+) was constructed based on nitrogen, zinc and copper codoped carbon dots (NZC-CDs) as fluorescence probes. NZC-CDs were synthesized by hydrothermal method. The morphology, size, components, crystal state and optical properties of NZC-CDs were characterized by transmission electron microscope (TEM), Fourier-transform infrared (FT-IR), x-ray photoelectron spectroscopy (XPS), x-ray diffraction (XRD), UV-vis absorption and fluorescence spectroscopy techniques, respectively. NZC-CDs exhibited bright blue fluorescence under UV lamp with a quantum yield at 17.76%. The fluorescence of NZC-CDs was quenched by Fe3+possibly due to the static quenching. The possible fluorescence quenching mechanism was also discussed. The quenching fluorescence was linear with the concentration of Fe3+in the range of 2.5-400µM with a low detection limit of 0.5µM. For the convenient detection, the test strips based on filter paper were employed for Fe3+assay. Moreover, the present approach was successfully applied in the determination of Fe3+in real samples including black fungus, duck blood and pork liver. The sensing method had the potential application in more food analysis.

Local Delivery of Nimustine Hydrochloride against Brain Tumors: Basic Characterization Study.

Convection-enhanced delivery (CED) delivers agents directly into tumors and the surrounding parenchyma. Although a promising concept, clinical applications are often hampered by insufficient treatment efficacy. Toward developing an effective CED-based strategy for delivering drugs with proven clinical efficacy, we performed a basic characterization study to explore the locally delivered characteristics of the water soluble nitrosourea nimustine hydrochloride (ACNU). First, ACNU distribution after CED in rodent brain was studied using mass spectrometry imaging. Clearance of 14C-labeled ACNU after CED in striatum was also studied. ACNU was robustly distributed in rodent brain similar to the distribution of the hydrophilic dye Evans blue after CED, and locally delivered ACNU was observed for over 24 h at the delivery site. Subsequently, to investigate the potential of ACNU to induce an immunostimulative microenvironment, Fas and transforming growth factor-ß1 (TGF-ß1) was assessed in vitro. We found that ACNU significantly inhibited TGF-ß1 secretion and reduced Fas expression. Further, after CED of ACNU in 9L-derived intracranial tumors, the infiltration of CD4/CD8 lymphocytes in tumors was evaluated by immunofluorescence.CED of ACNU in xenografted intracranial tumors induced tumor infiltration of CD4/CD8 lymphocytes. ACNU has a robust distribution in rodent brain by CED, and delayed clearance of the drug was observed at the local infusion site. Further, local delivery of ACNU affects the tumor microenvironment and induces immune cell migration in tumor. These characteristics make ACNU a promising agent for CED.

Timing of endoscopy in patients with cirrhosis and acute variceal bleeding: a single-center retrospective study.

BACKGROUND: The optimal timing of endoscopy in liver cirrhosis with acute variceal bleeding (AVB) remains controversial in current guidelines and studies. METHODS: Consecutive patients with liver cirrhosis and AVB were screened. The timing of endoscopy was calculated from the last presentation of AVB or the admission to endoscopy. Early endoscopy was defined as the interval < 12 h, < 24 h, or < 48 h. A 1:1 propensity score matching (PSM) analysis was performed. Five-day failure to control bleeding and in-hospital mortality were evaluated. RESULTS: Overall, 534 patients were included. When the timing of endoscopy was calculated from the last presentation of AVB, PSM analysis demonstrated that the rate of 5-day failure to control bleeding was significantly higher in early endoscopy group defined as < 48 h (9.7% versus 2.4%, P = 0.009), but not < 12 h (8.7% versus 6.5%, P = 1.000) or < 24 h (13.4% versus 6.2%, P = 0.091), and that the in-hospital mortality was not significantly different between early and delayed endoscopy groups (< 12 h: 6.5% versus 4.3%, P = 1.000; <24 h: 4.1% versus 3.1%, P = 1.000; <48 h: 3.0% versus 2.4%, P = 1.000). When the timing of endoscopy was calculated from the admission, PSM analyses did not demonstrate any significant difference in the rate of 5-day failure to control bleeding (< 12 h: 4.8% versus 12.7%, P = 0.205; <24 h: 5.2% versus 7.7%, P = 0.355; <48 h: 4.5% versus 6.0%, P = 0.501) or in-hospital mortality (< 12 h: 4.8% versus 4.8%, P = 1.000; <24 h: 3.9% versus 2.6%, P = 0.750; <48 h: 2.0% versus 2.5%, P = 1.000) between early and delayed endoscopy groups. CONCLUSION: Our study could not support any significant association of timing of endoscopy with cirrhotic patients with AVB.

Microbial fertilizer regulates C:N:P stoichiometry and alleviates phosphorus limitation in flue-cured tobacco planting soil.

Fertilization can be optimized and managed during the flue-cured tobacco growing period by studying the response of soil and microbial biomass stoichiometric characteristics to fertilization. In this study, we investigated the effect of compound fertilizers combined with microbial fertilizer treatments on the stoichiometric characteristics of the rhizosphere soil and the limitations of microbial resources during the flue-cured tobacco growing period. The results indicated that soil and microbial C:N:P varied greatly with the growing period. The effect of sampling time was usually greater than that of fertilization treatment, and microbial C:N:P did not vary with the soil resource stoichiometric ratio. The microbial metabolism of the tobacco-growing soil was limited by phosphorus after extending the growing period, and phosphorus limitation gradually increased from the root extension to the maturation periods but decreased at harvest. The rhizosphere soil microbial nitrogen and phosphorus limitations were mainly affected by soil water content, soil pH, microbial biomass carbon, and the ratio of microbial biomass carbon to microbial biomass phosphorus. Applying microbial fertilizer reduced phosphorus limitation. Therefore, applying microbial fertilizer regulated the limitation of microbial resources by affecting the soil and microbial biomass C:N:P in flue-cured tobacco rhizosphere soils.

Factors of easy and difficult cecal intubation during unsedated colonoscopy.

BACKGROUND AND AIMS: difficulty of cecal intubation should be a main indicator for the need of sedated colonoscopy and skilled endoscopists. The present study aimed to explore the factors associated with easy and difficult cecal intubation in unsedated colonoscopy. METHODS: all consecutive patients who underwent unsedated colonoscopy at our department by the same endoscopist from December 3, 2020 to August 30, 2022 were retrospectively collected. Age, gender, body mass index (BMI), reasons for colonoscopy, position change, Boston Bowel Preparation Scale score, cecal intubation time (CIT) and major colonoscopic findings were analyzed. CIT < 5 min, CIT 5-10 min and CIT > 10 min or failed cecal intubation were defined as easy, moderate and difficult cecal intubation, respectively. Logistic regression analyses were performed to identify independent factors associated with easy and difficult cecal intubation. RESULTS: overall, 1,281 patients were included. The proportions of easy and difficult cecal intubation were 29.2 % (374/1,281) and 27.2 % (349/1,281), respectively. Multivariate logistic regression analysis found that age ≤ 50 years, male, BMI > 23.0 kg/m2 and the absence of position change were independently associated with easy cecal intubation, and that age > 50 years, female, BMI ≤ 23.0 kg/m2, position change, and insufficient bowel preparation were independently associated with difficult cecal intubation. CONCLUSIONS: some convenient factors independently associated with easy and difficult cecal intubation have been identified, which will be potentially helpful to determine whether a colonoscopy should be sedated and a skilled endoscopist should be selected. The current findings should be further validated in large-scale prospective studies.

Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization.

BACKGROUND: Endoscopic variceal treatment (EVT) is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis. Proton pump inhibitors (PPIs) are widely used for various gastric acid-related diseases. However, the effects of PPIs on the development of post-EVT complications, especially gastrointestinal bleeding (GIB), remain controversial. AIM: To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization. METHODS: Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command, treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included. Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 143 patients were included. The incidence of post-EVT GIB and other post-EVT complications was 4.90% and 46.85%, respectively. In the overall analyses, postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB (OR = 0.525, 95%CI = 0.113-2.438, P = 0.411) or other post-EVT complications (OR = 0.804, 95%CI = 0.413-1.565, P = 0.522). In the subgroup analyses according to the enrollment period, type and route of PPIs after the index EVT, use of PPIs before the index EVT, use of vasoactive drugs after the index EVT, indication of EVT (prophylactic and therapeutic), and presence of portal venous system thrombosis, ascites, and hepatocellular carcinoma, the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant. CONCLUSION: Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.

The Incidence of Acute Pancreatitis After Device Assisted Enteroscopy: a Systematic Review and Meta-analysis.

Background: The diagnosis of small bowel diseases is challenging and device assisted enteroscopy (DAE) is a technique for visualizing the entire small bowel. DAE is considered as a safe procedure and the reported rate of adverse events associated with DAE in the literature is low. Objective: The present study tried to investigate the actual incidence of AP after DAE with a systematic review and meta-analysis of available relevant studies. Methods: Studies were searched through the PubMed, EMBASE, and Cochrane library databases. The following data were extracted from all eligible studies: author, country, publication year, publication type, study design, type of DAE used, route of DAE, number of patients with AP after DAE, and number of patients with hyperamylasemia after DAE.A random-effects model with RStudio version 4.2.0 was performed in all analyses. Heterogeneity was assessed using the I2 test. The risk of bias was assessed by the Newcastle-Ottawa Scale criteria and the publication bias was assessed by the Egger test. Results: Twenty three studies involving a total of 11145 patients were included in the analysis. The overall, pooled AP rate after DAE was 1% (95% CI:0-1%). There was significant heterogeneity among the studies (I2 = 65%; P < 0.01).The pooled AP rate was 1% (95% CI:0-2 %)in peroral route group. The pooled proportion of patients having hyperamylasemia after DAE was 29% (95% CI: 16-46%).Among the patients who had hyperamylasemia AP were identified in 2% (95% CI: 0-6%) of patients. Conclusion: The incidence of AP after DAE is about 1%. Hyperamylasemia is a common change in the patients undergoing DAE and only 2% of the patients with hyperamylasemia present with AP.

Successful treatment of acute symptomatic extensive portal venous system thrombosis by 7-day systemic thrombolysis.

Acute portal venous system thrombosis (PVST) can cause acute mesenteric ischemia and even intestinal infarction, which are potentially fatal, and requires recanalization in a timely fashion. Herein, we report a 56-year-old man with acute non-cirrhotic symptomatic extensive PVST who achieved portal vein recanalization after systemic thrombolysis combined with anticoagulation. Initially, anticoagulation with enoxaparin sodium for 4 d was ineffective, and then systemic thrombolysis for 7 d was added. After that, his abdominal pain completely disappeared, and portal vein system vessels became gradually patent. Long-term anticoagulation therapy was maintained. In conclusion, 7-d systemic thrombolysis may be an effective and safe choice of treatment for acute symptomatic extensive PVST which does not respond to anticoagulation therapy.

Prevalence and Clinical and Endoscopic Characteristics of Cervical Inlet Patch (Heterotopic Gastric Mucosa): A Systematic Review and Meta-Analysis.

BACKGROUND: Cervical inlet patch (CIP), also called gastric inlet patch, is a heterotopic columnar mucosal island located in the cervical esophagus, which has been under-recognized by clinicians. AIM: We conducted a systemic review and meta-analysis to explore the prevalence and clinical and endoscopic characteristics of CIP. MATERIALS AND METHODS: Studies were searched through the PubMed, EMBASE, and Cochrane Library databases. The prevalence of CIP with 95% confidence interval (CI) was pooled by using a random-effect model. The association of CIP with demographics, clinical presentations, and endoscopic features was evaluated by odds ratios (ORs). RESULTS: Fifty-three studies including 932,777 patients were eligible. The pooled prevalence of CIP was 3.32% (95% CI=2.86%-3.82%). According to the endoscopic mode, the pooled prevalence of CIP was higher in studies using narrow-band imaging than in those using white light and esophageal capsule endoscopy (9.34% vs. 2.88% and 0.65%). The pooled prevalence of CIP was higher in studies where the endoscopists paid specific attention to the detection of this lesion (5.30% vs. 0.75%). CIP was significantly associated with male (OR=1.24, 95% CI=1.09-1.42, P=0.001), gastroesophageal reflux disease (OR=1.32, 95% CI=1.04-1.68, P=0.03), reflux symptoms (OR=1.44, 95% CI=1.14-1.83, P=0.002), dysphagia (OR=1.88, 95% CI=1.28-2.77, P=0.001), throat discomfort (OR=4.58, 95% CI=1.00-21.02, P=0.05), globus (OR=2.95, 95% CI=1.52-5.73, P=0.001), hoarseness (OR=4.32, 95% CI=1.91-9.78, P=0.0004), cough (OR=3.48, 95% CI=1.13-10.72, P=0.03), Barrett's esophagus (OR=2.01, 95% CI=1.37-2.94, P=0.0003), and esophagitis (OR=1.62, 95% CI=1.27-2.07, P=0.0001). CONCLUSION: CIP appears to be common by using narrow-band imaging, especially if the endoscopists would like to pay attention to the detection of this lesion. CIP is clearly associated with acid-related symptoms and Barrett's esophagus.

Endoscopic treatment for gastric antral vascular ectasia.

Gastric antral vascular ectasia (GAVE) is one of the uncommon causes of upper gastrointestinal bleeding. Major treatment of GAVE includes pharmacotherapy, endoscopy, and surgery. The efficacy and safety of pharmacotherapy have not been sufficiently confirmed; and surgery is just considered when conservative treatment is ineffective. By comparison, endoscopy is a common treatment option for GAVE. This paper reviews the currently used endoscopic approaches for GAVE, mainly including argon plasma coagulation (APC), radiofrequency ablation (RFA), and endoscopic band ligation (EBL). It also summarizes their efficacy and procedure-related adverse events. The endoscopic success rate of APC is 40-100%; however, APC needs several treatment sessions, with a high recurrence rate of 10-78.9%. The endoscopic success rates of RFA and EBL are 90-100% and 77.8-100%, respectively; and their recurrence rates are 21.4-33.3% and 8.3-48.1%, respectively. Hyperplastic gastric polyps and sepsis are major adverse events of APC and RFA; and Mallory-Weiss syndrome is occasionally observed after APC. Adverse events of EBL are rare and mild, such as nausea, vomiting, esophageal or abdominal pain, and hyperplastic polyps. APC is often considered as the first-line choice of endoscopic treatment for GAVE. RFA and EBL have been increasingly used as alternatives in patients with refractory GAVE. A high recurrence of GAVE after endoscopic treatment should be fully recognized and cautiously managed by follow-up endoscopy. In future, a head-to-head comparison of different endoscopic approaches for GAVE is warranted.

Brunner's Gland Hamartoma of the Duodenum: A Literature Review.

Brunner's gland hamartoma is a benign tumor of the duodenum, but has malignant potential with a very low risk of progression into adenocarcinoma. It is uncommon with a frequency of less than 1.0% among the primary tumors of the small intestine. In addition, its clinical manifestations are nonspecific, etiology remains unclear, and treatment strategy needs to be further refined. This literature review mainly discusses the epidemiology, clinical features, possible etiology and pathogenesis, diagnostic methods, malignant potential, treatment, and prognosis of Brunner's gland hamartoma.

Construction of a ratio fluorescence assay of 5-aminosalicylic acid based on its aggregation induced emission with blue emitting N/P-codoped carbon dots.

Herein, a novel ratio fluorescence method based on N/P-doped carbon dots (NPCDs) for detecting 5-aminosalicylic acid (5-ASA) in mesalazine enteric coated tablets and blood were reported for the first time. NPCDs were successfully prepared through a simple one-step hydrothermal strategy by employing adenosine triphosphate (ATP) and p-toluidine as raw materials. NPCDs exhibit bright blue emissions with excitation/emission peaks at 340/423 nm with moderate quantum yield (20.75%). In addition, 5-ASA has a certain weak fluorescence emission peak at 487 nm. Adding 5-ASA into NPCDs significantly enhanced the fluorescence intensity, which may result from aggregation induced emission (AIE) of 5-ASA on the surface of NPCDs. Therefore, NPCDs only provide self-calibration signals, and their fluorescence remains almost unchanged when co-existing with 5-ASA. Therefore, the ratio of fluorescence at F 487/F 423 was used for detection of 5-ASA. For the fluorometric determination assay, there was a good linear relationship between F 487/F 423 and 5-ASA concentration between 0.50 and 130 µM (R 2 = 0.9979). The detection limit was about 0.13 µM. Therefore, this method is simple, sensitive and low cost, and will be successfully applied to the detection of 5-ASA in drugs.

Gastrointestinal Bleeding due to Pancreatic Disease-Related Portal Hypertension.

BACKGROUND AND AIMS: Left-sided portal hypertension (LSPH) is a rare type of portal hypertension, which occurs due to obstruction, stenosis, or thrombosis within the splenic vein. Pancreatic diseases are the most common etiology of LSPH. This study is aimed at reporting our experiences and discussing the presentation, management, and prognosis of LSPH secondary to pancreatic diseases. Patients and Methods. We retrospectively reviewed five patients who were diagnosed with LSPH secondary to pancreatic diseases at our department. We collected the demographic information, history, comorbidities, clinical presentations, laboratory tests, esophagogastroduodenoscopy (EGD), images, and outcome data. RESULTS: Three elderly patients (>60 years old) were diagnosed with pancreatic cancer, of whom one underwent laparoscopic radical distal pancreatectomy and splenectomy, one received chemotherapy, and another one chose conservative management due to multiple systemic metastases. Two younger patients (<40 years old) were diagnosed with acute recurrent pancreatitis and chronic pancreatitis. Four of these five included patients presented with hematemesis and/or melena at our admission. All patients had gastric varices, and one of them also had esophageal varices. One elderly patient with metastatic pancreatic cancer underwent endoscopic variceal treatment as a rescue therapy but finally died of refractory gastrointestinal (GI) bleeding; another younger patient with chronic pancreatitis died of massive GI bleeding; and the remaining three patients survived at their last follow-up. CONCLUSIONS: LSPH should be seriously taken into consideration in patients with pancreatic diseases who develop upper GI bleeding. Clinicians should individualize the treatment strategy of LSPH according to the patients' clinical conditions and nature of pancreatic diseases.

A Small Jejunal Angioleiomyoma Detected by Double-Balloon Enteroscopy: A Case Report.

BACKGROUND Angioleiomyoma in the small intestine is a rare cause of gastrointestinal bleeding. Only 7 cases of angioleiomyoma in the small intestine were reported in the English literature, with 4 of them causing gastrointestinal bleeding. The diagnosis of angioleiomyomas in the small intestine before surgery is difficult. CASE REPORT We report the case of a 42-year-old man with recurrent melena who underwent repeated esophagogastroduodenoscopy and colonoscopy, without positive finding. During a double-balloon enteroscopy, an elevated lesion with a diameter of 6 mm was found in the jejunum. The lesion was resected laparoscopically assisted with double-balloon enteroscpy. A microscopic examination showed fibric membrane of the mass and numerous vascular channels surrounded by proliferated smooth muscle. There were exudative fibrin and many thrombi formed by red blood cells. Immunohistochemistry was positive for SMA and CD34. A pathological diagnosis of jejunal angioleiomyoma with thrombus was established. During a 5-year follow-up, there was no further gastrointestinal bleeding. CONCLUSIONS The gastroenterologists should consider angioleiomyoma in the small intestine when assessing obscure gastrointestinal bleeding.

A Large Intracolonic Mass in a Patient with Peutz-Jeghers Syndrome.

Peutz-Jeghers syndrome (PJS) is characterized by scattered black pigmentations on fingers and lips and multiple polyps in the gastrointestinal tract. Patients with PJS often have severe complications secondary to multiple large polyps. Herein, we present a young woman complicated with a large polyp in her colon without any clinical symptoms. We also emphasized the necessity of early diagnosis and treatment of multiple polyps in such patients.

Controllable Photodynamic Therapy Implemented by Regulating Singlet Oxygen Efficiency.

With singlet oxygen (1O2) as the active agent, photodynamic therapy (PDT) is a promising technique for the treatment of various tumors and cancers. But it is hampered by the poor selectivity of most traditional photosensitizers (PS). In this review, we present a summary of controllable PDT implemented by regulating singlet oxygen efficiency. Herein, various controllable PDT strategies based on different initiating conditions (such as pH, light, H2O2 and so on) have been summarized and introduced. More importantly, the action mechanisms of controllable PDT strategies, such as photoinduced electron transfer (PET), fluorescence resonance energy transfer (FRET), intramolecular charge transfer (ICT) and some physical/chemical means (e.g. captivity and release), are described as a key point in the article. This review provide a general overview of designing novel PS or strategies for effective and controllable PDT.