Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer.

BACKGROUND: Zinc finger and BTB domain-containing protein 4 (ZBTB4) belongs to the zinc finger protein family, which has a role in regulating epigenetic inheritance and is associated with cell differentiation and proliferation. Previous studies have identified aberrant ZBTB4 expression in cancer and its ability to modulate disease progression, but studies on the immune microenvironment, immunotherapy and its role in cancer are still lacking. METHODS: Human pan-cancer and normal tissue transcriptome data were obtained from The Cancer Genome Atlas. The pan-cancer genomic alteration landscape of ZBTB4 was investigated with the online tool. The Kaplan-Meier method was used to evaluate the prognostic significance of ZBTB4 in pancreatic cancer. In parallel, ZBTB4 interacting molecules and potential functions were analyzed by co-expression and the correlation between ZBTB4 and immune cell infiltration, immune modulatory cells and efficacy of immune checkpoint therapy was explored. Next, we retrieved the Gene Expression Omnibus database expression datasets of ZBTB4 and investigated ZBTB4 expression and clinical significance in pancreatic cancer by immunohistochemical staining experiments. Finally, cell experiments were performed to investigate changes in pancreatic cancer cell proliferation, migration and invasion following overexpression and knockdown of ZBTB4. FINDINGS: ZBTB4 showed loss of expression in the majority of tumors and possessed the ability to predict cancer prognosis. ZBTB4 was closely related to the tumor immune microenvironment, immune cell infiltration and immunotherapy efficacy. ZBTB4 had good diagnostic performance for pancreatic cancer in the clinic, and ZBTB4 protein expression was lost in pancreatic cancer tumor tissues. Cell experiments revealed that overexpression of ZBTB4 inhibited the proliferation, migration and invasion of pancreatic cancer cells, while silencing ZBTB4 showed the opposite effect. CONCLUSIONS: According to our results, ZBTB4 is present in pancreatic cancer with aberrant expression and is associated with an altered immune microenvironment. We show that ZBTB4 is a promising marker for cancer immunotherapy and cancer prognosis and has the potential to influence pancreatic cancer progression.

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization.

Macrophages are a type of immune cells with high levels of plasticity and heterogeneity. They can polarize into M1 or M2 functional phenotypes. These two phenotypes exhibit a dynamic balance during polarization-related diseases and play opposing roles. Long noncoding RNAs (lncRNAs) play an important role in biological processes such as cell proliferation, death, and differentiation; however, how long noncoding RNAs affect the cellular functionality of macrophages remains to be studied. Long noncoding RNA Gm9866 was found to be closely related to macrophage polarization through bioinformatics analysis. In this study, by conducting real-time polymerase chain reaction analysis, it was observed that long noncoding RNA Gm9866 expression significantly increased after treatment with interleukin-4 but significantly decreased after treatment with lipopolysaccharide. Fluorescence in situ hybridization revealed that long noncoding RNA Gm9866 was expressed mainly in the nucleus. Real-time polymerase chain reaction analysis showed that overexpression of long noncoding RNA Gm9866 in RAW264.7 cells further promoted the expression of M2 markers MRC1 (macrophage mannose receptor 1) and MRC2 (macrophage mannose receptor 2). Western blotting analysis demonstrated inhibition of nuclear factor-κB (NF-κB) expression. EdU (5-ethynyl-2'-deoxyuridine) and TUNEL (TdT-mediated dUTP nick-end labeling) staining assays revealed that overexpression of long noncoding RNA Gm9866 promoted cell proliferation and inhibited apoptosis. These findings thus indicated that long noncoding RNA Gm9866 promoted macrophage polarization and inhibited the nuclear factor-κB signaling pathway. Thus, long noncoding RNA Gm9866 may serve as a potential diagnostic and therapeutic target for polarization-related diseases such as infectious diseases, inflammatory diseases, liver fibrosis, and tumors.

5-Iodotubercidin Inhibits the Growth of Insulinoma Cells by Inducing Apoptosis.

INTRODUCTION: 5-Iodotubercidin, a type of purine derivative, has attracted increasing attention in tumor chemotherapy because of its potential as an antitumor agent in recent years. In this study, we confirmed the effects on apoptosis in insulinoma cell lines induced by 5-iodotubercidin and tried to illuminate the underlying mechanisms. METHODS: We used 5-iodotubercidin in the treatment of insulinoma cells and the cell proliferation was examined using CCK-8 assay, colony-forming assays, and insulinoma animal models. Cell apoptosis was examined using TUNEL assays and Western blotting. Cellular DNA damage was shown by comet assay and immunofluorescence. The expression of apoptosis-regulating proteins and DNA damage biomarker was investigated by Western blotting. Subcutaneous inoculation of the insulinoma cells into nude mice was to measure blood glucose, insulin levels, and tumor growth. ATM siRNA and p53 siRNA were used as loss-of-function targets to evaluate 5-iodotubercidin treatment. RESULTS: 5-Iodotubercidin inhibited the proliferation of insulinoma cells and induced DNA damage and cell apoptosis. Moreover, 5-iodotubercidin induced ATM and p53 activated. In vivo, 5-iodotubercidin inhibited the growth of Ins-1 and Min-6 cells xenografts in nude mice. CONCLUSION: 5-Iodotubercidin induces DNA damage leading to insulinoma cells apoptosis by activating ATM/p53 pathway. Therefore, this is a potential strategy for treating insulinoma.

Differential Plasma Proteins Identified via iTRAQ-Based Analysis Serve as Diagnostic Markers of Pancreatic Ductal Adenocarcinoma.

Objective: We aimed to identify differentially expressed proteins in the plasma of patients with pancreatic cancer and control subjects, which could serve as potential tumor biomarkers. Methods: Differentially expressed proteins were determined via isostatic labeling and absolute quantification (iTRAQ). Potential protein biomarkers were identified via enzyme-linked immunosorbent assay (ELISA) in 40 patients and 40 control subjects, and those eventually selected were further validated in 40 pancreatic cancer and normal pancreatic tissues. Results: In total, 30 proteins displayed significant differences in expression among which 21 were downregulated and 9 were upregulated compared with the control group. ELISA revealed downregulation of peroxiredoxin-2 (PRDX2) and upregulation of alpha-1-antitrypsin (AAT), Ras-related protein Rab-2B (RAB2B), insulin-like growth factor-binding protein 2 (IGFBP2), Rho-related GTP-binding protein RhoC (RHOC), and prelamin-A/C (LMNA) proteins in 40 other samples of pancreatic cancer. Notably, only AAT, RAB2B, and IGFBP2 levels were consistent with expression patterns obtained with iTRAQ. Moreover, all three proteins displayed a marked increase in pancreatic cancer tissues. Data from ROC curve analysis indicated that the diagnostic ability of AAT, RAB2B, and IGFBP2 combined with carbohydrate antigen 19-9 (CA19-9) for pancreatic cancer was significantly greater than that of the single indexes (area under the curve (AUC): 90% vs. 75% (CA19-9), 76% (AAT), 71% (RAB2B), and 71% (IGFBP2), all P < 0.01). Conclusion: AAT, RAB2B, and IGFBP2 could serve as effective biomarkers to facilitate the early diagnosis of pancreatic cancer.

Prediction of acute pancreatitis complications using routine blood parameters during early admission.

BACKGROUND: There have been many reports on biomarkers for predicting the severity of acute pancreatitis (AP), but few studies on biomarkers for predicting complications; some simple and inexpensive indicators, in particular, are worth exploring. METHODS: We retrospectively collected clinical data of 809 AP patients, including medical history and results of routine blood tests, and grouped them according to the occurrence of complications. Differences in clinical characteristics between groups with and without complications were compared using t-test or χ2 test. Receiver operating curve (ROC) and area under the curve were calculated to evaluate the ability of predicting the occurrence of complications for the routine blood parameters with statistical differences. Then, through univariate and multivariate analyses, independent risk factors closely associated with complications were identified. Finally, we built a three-parameter prediction system and evaluated its ability to predict AP complications. RESULTS: Compared with the group without complications, the patients in the complication group had higher white blood cells, neutrophils, C-reactive protein, and erythrocyte sedimentation rate (ESR), and lower red blood cells and hemoglobin (Hb) (all p < .05), and most of them had severe pancreatitis. In addition, pseudocysts were more common in patients with alcoholic etiology, recurrence, low BMI, and high platelet (PLT) and plateletocrit. Acute respiratory failure was more common in patients with first onset and high mean PLT volume (MPV). Sepsis was more common in patients with lipogenic etiology, high MPV, and low lymphocytes. Infectious pancreatic necrosis was more common in patients with alcoholic etiology. Acute renal failure was more common in patients with monocytes and high MPV and low PLT. Multivariate analysis showed that PLT and ESR were risk factors for pseudocyst development. The ROC showed that the combination of Hb, PLT and ESR had a significantly higher predictive ability for pseudocyst than the single parameter. CONCLUSION: Routine blood parameters can be used to predict the complications of AP. A predictive model combining ESR, PLT, and Hb may be an effective tool for identifying pseudocysts in AP patients.

A novel diagnostic model for insulinoma.

The aim is to describe a simple and feasible model for the diagnosis of insulinoma. This retrospective study enrolled 37 patients with insulinoma and 44 patients with hypoglycemia not due to insulinoma at the First Affiliated Hospital of Guangxi Medical University. General demographic and clinical characteristics; hemoglobin A1c (HbA1c), insulin and C-peptide concentrations; and the results of 2-h oral glucose tolerance tests (OGTT) were recorded, and a logistic regression model predictive of insulinoma was determined. Body mass index (BMI), HbA1c concentration, 0-h C-peptide concentration, and 0-h and 1-h plasma glucose concentrations (P < 0.05 each) were independently associated with insulinoma. A regression prediction model was established through multivariate logistics regression analysis: Logit p = 7.399+(0.310 × BMI) - (1.851 × HbA1c) - (1.467 × 0-h plasma glucose) + (1.963 × 0-h C-peptide) - (0.612 × 1-h plasma glucose). Using this index to draw a receiver operating characteristic (ROC) curve, the area under the curve (AUC) was found to be 0.957. The optimal cut-off value was - 0.17, which had a sensitivity of 89.2% and a specificity of 86.4%. Logit P ≥ - 0.17 can be used as a diagnostic marker for predicting insulinoma in patients with hypoglycemia.

A stomach like a utility room: Case report.

BACKGROUND: Foreign body (FB) ingestion is an emergency that is more common in children and adults with mental disorders. A wide array of FBs can be ingested, and most of them do not need to be treated. However, if the FB blocks the digestive tract or causes damage, it needs to be removed by endoscopy or even surgery.We describe here a stomach full of FBs, but these FBs did not cause serious damage. CASE PRESENTATION: A 9-year-old male child with mental retardation suffered abdominal pain after swallowing FBs. X-ray and computed tomography (CT) found a large number of FBs of different shapes. We tried to remove them under endoscopy but failed; we then changed to laparotomy and removed a large number of FBs. The patient started normal feeding on the 4th day and was discharged home. CONCLUSIONS: FB ingestion is very common. Symptoms are used to determine whether further treatment, which is usually feasible, is required. However, for patients who cannot accurately describe the ingestion of FBs, such as children, patients with mental disorders, and patients who are inebriated, FBs should still be treated with caution, especially when the clinical symptoms and related examinations are not typical, and adequate plans should be made, as shown in this case. There may be unexpected discoveries.

The relationship between cardiac muscularis propria and clinical outcomes of peroral endoscopic myotomy in achalasia.

BACKGROUND AND AIM: Achalasia patients usually present lower esophageal sphincter thickening, which can impact the expansibility of cardia. We aimed to investigate the effect of cardiac muscularis propria (MP) on perioperative adverse events (AEs) and treatment outcomes of patients treated with peroral endoscopic myotomy (POEM). METHODS: We retrospectively reviewed 114 patients with achalasia undergoing pre-POEM endoscopic ultrasonography (EUS) between May 2013 and November 2019. Cardiac MP thickness was measured using EUS. POEM failure was defined as Eckardt score >3. Risk factors for perioperative AEs and POEM failure were identified. RESULTS: Patients were divided into the thin (n = 52) and the thick group (n = 62) based on the median of cardiac MP thickness (3.0 mm). Perioperative AEs rate of the thin group seemed to be slightly higher than that of the thick group (11.5% vs. 4.8%, P = 0.30). During a median follow-up of 30 months (range 1-77), 100 patients completed follow-up, 16 (16%) of which occurred clinical failure. The clinical outcomes of patients in the thin group were significantly poorer than those patients in the thick group (P = 0.006). Cardiac MP thickness was an independent risk factor for POEM failure (hazard ratio 3.9, P = 0.02; Cox regression), but not the risk factor for perioperative AEs (odds ratio 2.6, P = 0.2; logistic regression). CONCLUSION: Cardiac MP thickness could be a novel predictive factor for POEM failure in patients with achalasia.

The efficacy and safety of pioglitazone in psoriasis vulgaris: A meta-analysis of randomized controlled trials.

Pioglitazone may have potential benefits in the treatment of cutaneous and metabolic derangements of psoriasis, but its role in the treatment of psoriasis remains in debate. We therefore conducted a meta-analysis to evaluate the clinical efficacy and safety of pioglitazone in psoriasis vulgaris (PsV).We performed a comprehensive search in database of PubMed, Web of Science, Cochrane library, Embase and China National Knowledge Infrastructure (CNKI), and Wan fang database through March 2019 to identify eligible studies. Randomized controlled trials that have evaluated the effect and safety of pioglitazone in PsV were included. Treatment success was defined as ≥75% reduction in psoriasis area and severity index (PASI) score after treatment. Weighted mean differences (WMD), relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled to compare the clinical efficacy and safety between different groups.Six randomized controlled trials (n = 270) were included. Meta-analysis showed that pioglitazone was associated with a remarkable reduction in PASI score in patients with PsV (weight mean difference: 2.68, 95% CI 1.41-3.94, P < .001). The treatment success rate in the pioglitazone group was higher than in the control group (RR 3.60, 95 CI 1.61-8.01, P < .001). Compared with control group, pioglitazone was not related to a pronounced increase in total adverse events (RR 1.180, 95 CI 0.85-1.63, P = .33). Moreover, the risk of common adverse events in the 2 groups were similar, such as elevated liver enzyme, fatigue, nausea, weight gain.This meta-analysis suggested pioglitazone is an effective and safe drug in the treatment of patients with PsV.

Manganese levels and hepatocellular carcinoma: A systematic review and meta-analysis based on Asian cohort.

Several studies have investigated the relationship between Manganese (Mn) levels and hepatocellular carcinoma (HCC), but the results were inconsistent. Thus, we conducted a systematic review and meta-analysis to evaluate the association between Mn levels and HCC. Nine studies focusing on hair Mn levels, 6 studies on serum Mn levels and 6 studies on tissue Mn levels were identified in a systematic search of PubMed, CNKI, Wanfang and SinoMed databases. Standard mean differences (SMD) with the corresponding 95% confidence intervals (CI) were pooled to compare the Mn levels between HCC and controls. In serum, the Mn levels in HCC were significantly lower than in healthy controls (SMD (95% CI): -0.941 (-1.559, -0.323)). In hair, the Mn levels in HCC were slightly lower than in healthy controls, but not significant (SMD (95% CI): -0.168 (-0.766, 0.430)). In tissue, the Mn levels in tumors were significantly lower than in adjacent normal tissues (SMD (95% CI): -4.867 (-7.143, -2.592)). Subgroup analysis showed consistent results. In conclusion, this meta-analysis suggested an inverse association between Mn levels and HCC.

Combined spinal-epidural anesthesia with hypobaric ropivacaine in sitting position significantly increases the incidence of hypotension in parturients undergoing cesarean section.

AIM: Maternal position during induction of combined spinal-epidural anesthesia (CSEA) may affect hemodynamics and block characteristics. This study aimed to assess whether the sitting position is more likely to induce hypotension and higher block level than the lateral position in CSEA with hypobaric ropivacaine. METHODS: Ninety American Society of Anesthesiologists physical status I and II parturients undergoing elective cesarean section were randomized into three groups: the sitting, left-lateral, and right-lateral position groups. The L3-4 interspace was selected as the puncture site, and subarachnoid injection of 2.5 mL 0.5% hypobaric ropivacaine was administered. After the epidural catheter was inserted and fixed, the patient's position was changed to the left-leaning supine position. The blood pressure was measured once every 1 min followed by once every 3 min after the delivery. The sensory block level was regularly measured. RESULTS: A total of 88 parturients were included in this study. The incidences of hypotension in the sitting, left-lateral, and right-lateral position groups were 72%, 38%, and 40%, respectively, P = 0.012. Incidence and total dose of the phenylephrine supplement in the sitting position group were significantly higher than in the other two groups. The sitting position group showed a significantly higher block level (T4 [T3, T4]) as compared to the left-lateral (T6 [T5, T6]) and right-lateral position groups (T6 [T4, T6]), P < 0.01. The Apgar scores of neonates at 1 min and 5 min, and the pH values of the umbilical arterial and venous blood were similar among the three groups. CONCLUSION: As compared to the lateral positions, CSEA with hypobaric ropivacaine in the sitting position is more likely to cause hypotension and excessively high block level.