Expression Changes of Long Noncoding RNA in the Process of Endothelial Cell Activation.

BACKGROUND: Endothelial cells have been shown to be in response to a variety of local and systemic stimuli, and are able to transition between quiescent and activated states. Endothelial cell activation is critical for the pathogenesis of various cardiovascular diseases. However, the expression changes of long non-coding RNAs (lncRNAs) are still unknown in the process of endothelial cell activation. Thus, this study was aimed to investigate expression changes of lncRNA before and after endothelial cell activation. MATERIALS AND METHODS: In an experimental model of peripheral venous congestion, endothelial cells were activated and analyzed with Affymetrix HG-U133 plus2.0 microarray. We analyzed these microarray data and reannotated the microarray probes for lncRNA. RESULTS: According to the definition of absolute fold change>2 and p value <0.05, 27 differentially expressed lncRNAs were identified and only 1 lncRNA transcript, ENST00000509256 was down-regualted. Co-expression network of lncRNA and mRNA were constructed to predict function of the dysregulated lncRNA. Gene set enrichment analyses suggested that these ENST00000509256 was associated with many important functions, such as cell-cell signaling and regulation of cell differentiation. CONCLUSION: Many lncRNAs are dysregulated upon endothelial cell activation and further experiments are needed to identify the potential biological functions of these lncRNAs.

TM4SF1 Regulates Pancreatic Cancer Migration and Invasion In Vitro and In Vivo.

BACKGROUND/AIMS: The cell surface protein transmembrane 4 L6 family member 1 (TM4SF1) has been detected in various tumors and plays a major role in the development of cancer. We aimed to investigate the effects of TM4SF1 on the migration and invasion of pancreatic cancer in vitro and in vivo and explore its related molecular mechanisms. METHODS: qRT-PCR and immunohistochemical analyses were used to measure the expression of TM4SF1 in pancreatic cancer tissues and adjacent tissues. TM4SF1 was silenced using siRNA and shRNA to investigate the role of this protein in the proliferation and metastasis of pancreatic cancer cells. MTS and Transwell assays were used to examine the effect of TM4SF1 on pancreatic cancer cell lines. The expression and activity of MMP-2 and MMP-9 were determined by qRT-PCR, western blots and gelatin zymography. In vivo, orthotopic pancreatic tumor models were used to examine the formation of metastasis. RESULTS: qRT-PCR and immunohistochemical analyses showed that TM4SF1 was highly expressed in pancreatic cancer tissues compared with the adjacent tissues. In in vitro experiments the silencing of TM4SF1 reduced cell migration and invasion and down-regulated the expression and activity of MMP-2 and MMP-9. However, no significant difference in cell proliferation was detected after silencing TM4SF1. Additionally, knocking down TM4SF1 decreased the formation of lung and liver metastases in orthotopic pancreatic tumor models. CONCLUSION: Our results demonstrate that the expression of TM4SF1 is higher in pancreatic cancer tissues and pancreatic cancer cell lines than controls. Knockdown of TM4SF1 inhibited the migration and invasion of pancreatic cancer cells by regulating the expression and activity of MMP-2 and MMP-9, which suggests that TM4SF1 may play a significant role in metastasis in pancreatic cancer.

Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease.

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM). METHODS: Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. RESULTS: SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. CONCLUSION: CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients.

Diagnostic value of autofluorescence imaging combined with narrow band imaging in intraepithelial neoplasia of Barrett's esophagus.

PURPOSE: To evaluate the diagnostic values of Auto Fluorescence Imaging (AFI) combined with Narrow Band Imaging (NBI) in the diagnosis of the intraepithelial neoplasia of Barrett's esophagus (BE). METHODS: Seventy four suspicious BE intraepithelial lesions were assessed in 50 patients by AFI, who were further subjected to NBI mode to observe the changes of gastric mucosal capillaries and gastric pits. The corresponding lesions were biopsied for pathological examination. RESULTS: Among the 74 AFI-diagnosed cases of suspicious lesions, 44 (59.5%) were high-grade intraepithelial neoplasias (BEHGIN), while the remaining 30 cases (40.5%) were false-positive. The NBI-diagnostic results of these 44 BEHGIN lesions were as follows: 39 cases were confirmed and 5 were suspicious; among the 30 false-positive BEHGIN cases, NBI gave 7 false-positive cases. The false-positive rates decreased from 40.5% of AFI to 9.5% (7/74) of NBI-AFI (p<0.05). The positive predictive value of AFI in BEHGIN was 59.5% (44/74), while that of AFI-NBI combination was 84.8% (39/46; p<0.05). CONCLUSIONS: The AFI-NBI combination technology could significantly improve (p<0.05) the detection rate of BEHGIN.

Endoscopic variceal ligation combined with sclerotherapy for management of gastroesophageal variceal bleeding in pediatric patients: a single-center retrospective study.

Objectives: Portal hypertension (PH) frequently gives rise to severe and life-threatening complications, including hemorrhage accompanied by the rupture of esophageal and gastric varices. In contrast to the guidelines for the management of PH in adults, the optimal endoscopic management of variceal bleeding for secondary prophylaxis in children remains unclear. The present study evaluated the efficacy and safety of endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST) to control gastroesophageal variceal bleeding in children. Methods: This retrospective study included children with gastroesophageal variceal bleeding who underwent EST or EVL at Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between February 2013 and March 2020. Short-term hemostasis rate and long-term rebleeding rate were evaluated. Adverse events related to the procedures, such as esophageal ulcer, esophageal stricture, abnormal embolization, pneumonia and perforation, were also recorded. Results: EVL (n = 8) and EST (n = 13) were performed successfully in all pediatric patients diagnosed with moderate to severe esophageal varices concurrent with gastric varices. Hemostasis was achieved during episodes of upper gastrointestinal bleeding. The mean volume of each single aliquot of cyanoacrylate injected was 0.3 ± 0.1 ml (range: 0.1-0.5 ml). Varices were eradicated in six (75%) of the eight patients who underwent EVL after a median 2 (range: 1-4) procedures and a median time of 3.40 months (range: 1.10-13.33 months). Eleven (52.4%) of the 21 patients developed rebleeding events, with the mean duration of hemostasis being 11.1 ± 11.6 months (range 1.0-39.2 months). No treatment-related complications, for example, distal embolism, occurred except for abdominal pain in one patient (4.8%). Conclusions: EST, alone or in combination with EVL, is an effective and safe method of managing gastroesophageal variceal hemorrhage in children undergoing secondary prophylaxis.

Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma.

BACKGROUND: Lactate, previously considered a metabolic byproduct, is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment. Further investigations confirmed that lactate is a primary regulator, introducing recently described post-translational modifications of histone and non-histone proteins, termed lysine lactylation. Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation. However, our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited. AIM: To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer. METHODS: RNA-seq and clinical data of pancreatic adenocarcinoma (PDAC) were obtained from the GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) databases via Xena Explorer, and GSE62452 datasets from GEO. Data on lactylation-related genes were obtained from publicly available sources. Differential expressed genes (DEGs) were acquired by using R package "DESeq2" in R. Univariate COX regression analysis, LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model. Further analyses, including functional enrichment, ESTIMATE, and CIBERSORT, were performed to analyze immune status and treatment responses in patients with pancreatic cancer. PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention; two PDAC cell lines with the most pronounced lactylation were selected. Subsequently, RT-PCR was employed to assess the expression of LRGs genes; SLC16A1, which showed the highest expression, was selected for further investigation. SLC16A1-mediated lactylation was analyzed by immunofluorescence, lactate production analysis, colony formation, transwell, and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells. In vivo validation was performed using an established tumor model. RESULTS: In this study, we successfully identified 10 differentially expressed lactylation-related genes (LRGs) with prognostic value. Subsequently, a lactylation-related signature was developed based on five OS-related lactylation-related genes (SLC16A1, HLA-DRB1, KCNN4, KIF23, and HPDL) using Lasso Cox hazard regression analysis. Subsequently, we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma. A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups. Furthermore, we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport. Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression, indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma. CONCLUSION: We constructed a novel lactylation-related prognostic signature to predict OS, immune status, and treatment response of patients with pancreatic adenocarcinoma, providing new strategic directions and antitumor immunotherapies.

Endoscopic polidocanol foam sclerobanding for the treatment of grade II-III internal hemorrhoids: A prospective, multi-center, randomized study.

BACKGROUND: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain. AIM: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL. METHODS: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range. RESULTS: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]. CONCLUSION: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure.

Ductular reaction in non-alcoholic fatty liver disease: When Macbeth is perverted.

Non-alcoholic fatty liver disease (NAFLD) or metabolic (dysfunction)-associated fatty liver disease is the leading cause of chronic liver diseases defined as a disease spectrum comprising hepatic steatosis, non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and hepatic carcinoma. NASH, characterized by hepatocyte injury, steatosis, inflammation, and fibrosis, is associated with NAFLD prognosis. Ductular reaction (DR) is a common compensatory reaction associated with liver injury, which involves the hepatic progenitor cells (HPCs), hepatic stellate cells, myofibroblasts, inflammatory cells (such as macrophages), and their secreted substances. Recently, several studies have shown that the extent of DR parallels the stage of NASH and fibrosis. This review summarizes previous research on the correlation between DR and NASH, the potential interplay mechanism driving HPC differentiation, and NASH progression.

Feasibility and efficacy of endoscopic purse-string suture-assisted closure for mucosal defects induced by endoscopic manipulations.

BACKGROUND: Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close, although complete closure is recommended for better recovery. Endoscopic purse-string assisted suturing (EPSS) has been used in clinical practice and has proven to be an effective and safe technique for the closure of large mucosal defects. However, details regarding the efficacy of endoscopic pre-purse-string suture (P-EPSS) are unknown, especially that it offers several advantages over conventional EPSS (C-EPSS). AIM: To elucidate the outcomes of EPSS-assisted closure in different clinical situations, and evaluate the efficacy of P-EPSS. METHODS: This retrospective observational study included a total of 180 patients who underwent closure assisted by P-EPSS (n = 63) or C-EPSS (n = 117) between July 2014 and June 2020. The P-EPSS and C-EPSS groups were compared and the intergroup differences in aspects such as the lesion size, location, and mor-phology, incidence of complete closure, intraoperative perforation, and delayed adverse events were evaluated. Data on the features and clinical course of cases with adverse events were collected for further analysis. RESULTS: Patients with lesion size larger than 3 cm, lesions located at the fundus of stomach, or submucosal tumors originating from the deep mucosa were more likely to undergo P-EPSS-assisted closure. The P-EPSS group showed a sign-ificantly higher proportion of intraoperative perforation (56% vs 17%) and a much shorter procedure time (9.06 ± 6.14 min vs 14.84 ± 7.25 min). Among adverse events, the incidence of delayed perforation (5% vs 4%; P = 0.82) and delayed bleeding (3% vs 4%; P = 0.96) did not differ significantly between the groups. Multivariate analysis revealed that lesions with incomplete closure [odds ratio (OR) = 21.33; 95% confidence interval (CI): 5.45-83.45; P < 0.01] or size greater than 3 cm (OR = 3.14; 95%CI: 1.08-9.18; P = 0.039) showed a statistical tendency to result in an increase in delayed adverse events. CONCLUSION: The present study revealed that EPSS could achieve secure complete closure of mucosal defect. P-EPSS could shorten the procedure and yield complete closure of mucosal defects. Rather than closure-type selection, incomplete closure or lesion size larger than 3 cm were associated with worse outcomes.

Potential factors affecting success rate and long term outcome in single balloon enteroscopy-assisted therapeutic endoscopic retrograde cholangiopancreatography in patients with pancreaticojejunal anastomotic stenosis: a retrospective study.

Background: Pancreaticojejunal anastomotic stenosis (PJS) after pancreaticoduodenectomy (PD) is difficult to treat. Single-balloon enteroscope-assisted endoscopic retrograde pancreatography (SBE-assisted ERP) is a safe way to treat PJS with the strength of minimally invasion and repeatability, but since its technical difficulty and few patient number, data on long-term outcomes remain limited. The optimal treatment is still unknown. We aim to study the safety, effectiveness, and long-term outcome of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERP in patients with PJS in this study. Methods: The clinical information of patients undergoing SBE-assisted therapeutic ERP from March 2016 to March 2021 were retrospectively analyzed. All patients were diagnosed as PJS and without any contraindication for therapeutic endoscopy. Treatment details, postoperative complications, factors influencing technical success rate were evaluated. Long-term outcomes results were obtained by clinical or telephone follow-up. Results: Sixteen patients with median age of 51 years were included in this study, surgical reconstruction methods including PD with Whipple reconstruction, PD with Child reconstruction, pylorus-preserving pancreaticoduodenectomy (PpPD) with Whipple reconstruction. Eight patients were successfully treated. No serious complications happened. Risk factors for the failure of pancreaticojejunal anastomotic site identification include the digestive tract reconstruction sequence, pancreaticojejunostomy method, pancreatic duct tube implantation, pancreatic duct width before surgery, and pancreatic fistula during perioperative period. The median follow-up time was 77.2 months, the mean indwelling time of the stent was 62.3 months [interquartile range (IQR), 6.8-153.7 months]. Two of eight patients developed recurrent PJS. The variation in body mass index (BMI) was +2.46 in the non-recurrence group compared to -1.09 in the recurrence group and -2.12 in the endoscopic retrograde cholangiopancreatography (ERCP) treatment failure group. Conclusions: ERP intervention should be carried out early once PJS occurs in order to increase success rate. BMI is a crucial indicator which can reflex PJS rehabilitation degree during follow-up. In order to reduce PJS recurrence rate, a wider pancreatic stent and a longer stent indwelling time are recommended.

Preservation of basal AcSDKP attenuates carbon tetrachloride-induced fibrosis in the rat liver.

BACKGROUND & AIMS: N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous tetrapeptide which has antifibrogenic effects at physiological concentrations in various tissues. AcSDKP is produced locally in the liver, however, little is known about its biological effect in this organ. We hypothesize that basal levels of endogenous AcSDKP decrease during the development of liver fibrosis and preservation of basal AcSDKP attenuates liver fibrosis. METHODS: Endogenous levels of AcSDKP in the liver were measured by enzyme immunoassay after 2, 6, and 10 weeks of carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. Subcutaneous osmotic pump infusion of vehicle or AcSDKP (800 microg/kg/day) was administered to CCl(4)-treated rats for 8 weeks to study the effect of exogenous AcSDKP on liver fibrosis. The effect of AcSDKP on profibrogenic properties of hepatic stellate cells was studied in vitro. RESULTS: Endogenous AcSDKP was significantly decreased in the liver of CCl(4)-treated rats. Chronic AcSDKP infusion preserved basal levels of AcSDKP and reduced liver injury, inflammation, fibrosis, and profibrogenic transforming growth factor-beta signaling. This was demonstrated by decreased aminotransferase serum levels, CD45 positive cells, collagen accumulation, alpha-smooth muscle actin positivity, transforming growth factor-beta1, phosphorylated Smad2/3 protein, increased bone morphogenetic protein-7, and phosphorylated Smad1/5/8. Further, AcSDKP exerts antifibrogenic effects on hepatic stellate cells (HSCs) by downregulation of HSC activation in vitro. CONCLUSIONS: Maintaining physiological levels of AcSDKP is critical in negatively regulating the development of fibrosis in chronic liver injury. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.

[Preliminary study on the validity of whole body diffusion-weighted imaging for the detection of malignant lesions].

OBJECTIVE: To evaluate the validity of whole body diffusion-weighted imaging (WBDWI) for the detection of malignant lesions. METHODS: Nine healthy volunteers, 4 postoperative cases of malignant tumor and 16 malignant tumor cases were included in this study. 29 cases underwent whole body diffusion-weighted imaging on GE Signa Excite HD MR scanner within one week after or before PET examination. The images were double-blindly evaluated by two radiologists without the knowledge of the original PET results. Clinical diagnoses of malignant lesions were mainly based on PET results taken as gold standard. The malignant lesions were evaluated according to nine locations: lymph node; central nervous system; lung; liver, gallbladder, pancreas and spleen; digestive tract; kidney and adrenal gland; pelvic; skeleton, and soft tissue of each subject. The sensitivity, specificity, positive predicative value, negative predicative value, Youden's index and likelihood ratio of WBDWI were analyzed. RESULTS: The images of all the 9 healthy volunteers were normal. 57 malignant lesions were found in the 20 malignant cases by PET, among whom 48 lesions were detected by WBDWI including 2 false positive lesions. Among the 261 locations of 29 cases, the WBDWI examination showed 21 true positive locations, 2 false positive locations and 3 false negative locations. The sensitivity, specificity, positive predicative value, negative predicative value, Youden's index and likelihood ratio of WBDWI were 87.5%, 99.2%, 91.3%, 98.7%, 86.7%, and 103.7, respectively. CONCLUSION: The validity of WBDWI is high, and it could be a new whole body imaging technique for staging of malignant tumors.

Combining protein arginine methyltransferase inhibitor and anti-programmed death-ligand-1 inhibits pancreatic cancer progression.

BACKGROUND: Immunotherapy targeting programmed death-1 (PD-1) or programmed death-ligand-1 (PD-L1) has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma (PDAC). Studies have shown that PD-L1 expression in tumors is an important indicator of the efficacy of immunotherapy. Tumor cells usually evade chemotherapy and host immune surveillance by epigenetic changes. Protein arginine methylation is a common posttranslational modification. Protein arginine methyltransferase (PRMT) 1 is deregulated in a wide variety of cancer types, whose biological role in tumor immunity is undefined. AIM: To investigate the combined effects and underlying mechanisms of anti-PD-L1 and type I PRMT inhibitor in pancreatic cancer in vivo. METHODS: PT1001B is a novel type I PRMT inhibitor with strong activity and good selectivity. A mouse model of subcutaneous Panc02-derived tumors was used to evaluate drug efficacy, toxic and side effects, and tumor growth in vivo. By flow cytometry, we determined the expression of key immune checkpoint proteins, detected the apoptosis in tumor tissues, and analyzed the immune cells. Immunohistochemistry staining for cellular proliferation-associated nuclear protein Ki67, TUNEL assay, and PRMT1/PD-L1 immunofluorescence were used to elucidate the underlying molecular mechanism of the antitumor effect. RESULTS: Cultured Panc02 cells did not express PD-L1 in vitro, but tumor cells derived from Panc02 transplanted tumors expressed PD-L1. The therapeutic efficacy of anti-PD-L1 mAb was significantly enhanced by the addition of PT1001B as measured by tumor volume (1054.00 ± 61.37 mm3 vs 555.80 ± 74.42 mm3, P < 0.01) and tumor weight (0.83 ± 0.06 g vs 0.38 ± 0.02 g, P < 0.05). PT1001B improved antitumor immunity by inhibiting PD-L1 expression on tumor cells (32.74% ± 5.89% vs 17.95% ± 1.92%, P < 0.05). The combination therapy upregulated tumor-infiltrating CD8+ T lymphocytes (23.75% ± 3.20% vs 73.34% ± 4.35%, P < 0.01) and decreased PD-1+ leukocytes (35.77% ± 3.30% vs 6.48% ± 1.08%, P < 0.001) in tumor tissue compared to the control. In addition, PT1001B amplified the inhibitory effect of anti-PD-L1 on tumor cell proliferation and enhanced the induction of tumor cell apoptosis. PRMT1 downregulation was correlated with PD-L1 downregulation. CONCLUSION: PT1001B enhances antitumor immunity and combining it with anti-PD-L1 checkpoint inhibitors provides a potential strategy to overcome anti-PD-L1 resistance in PDAC.

Preliminary study on the inhibitory effect of tumor suppressor gene KPC1 on the proliferation in gastric carcinoma cell.

BACKGROUND: To investigate Kip1 ubiquitination-promoting complex 1 (KPC1) expression and its relationship with NF-κB p50 in gastric cancer cell lines. METHODS: The expression of KPC1 and NF-κB p50 in tissue samples from 159 gastric cancer patients after tumor resection and normal gastric mucosa samples from 56 patients as negative controls was retrospectively studied. The relationship between KPC1, NF-κB p50, and clinicopathological factors was analyzed, and the correlation between KPC1 and cytoplasmic NF-κB p50 was determined. The expression level of KPC1 and NF-κB p50 was researched using reverse transcription (RT) polymerase chain reaction (RT-PCR) and Western blotting in 3 differentiated human gastric cancer cell lines (AGS, SGC-7901 and MGC-803). RESULTS: Immunohistochemistry indicated that KPC1 and NF-κB p50 expression was significantly decreased in gastric cancer cases, and the level of expression varied across the differentiated gastric cancer tissues. KPC1 and NF-κB p50 expression was significantly connected with tumor differentiation, tumor-node-metastasis (TNM) staging, and metastasis of 159 patients suffering from gastric cancer (P<0.05), but not correlated with age and lesion size (P>0.05). KPC1 was positively connected with the expression of NF-κB p50 by the Spearman correlation analysis (r=0.427, P<0.05). The expression of KPC1 and NF-κB p50 mRNA was reduced, and there were differences in the 3 differentiated human gastric cancer cell lines, as confirmed by western blotting. CONCLUSIONS: The co-expression of KPC1 and cytoplasmic NF-κB p50 in gastric cancer promotes tumor suppressor gene expression. Therefore, limiting the growth of tumor cells may inhibit the development of gastric cancer.

A Delta-radiomics model for preoperative evaluation of Neoadjuvant chemotherapy response in high-grade osteosarcoma.

BACKGROUND: The difficulty of assessment of neoadjuvant chemotherapeutic response preoperatively may hinder personalized-medicine strategies that depend on the results from pathological examination. METHODS: A total of 191 patients with high-grade osteosarcoma (HOS) were enrolled retrospectively from November 2013 to November 2017 and received neoadjuvant chemotherapy (NCT). A cutoff time of November 2016 was used to divide the training set and validation set. All patients underwent diagnostic CTs before and after chemotherapy. By quantifying the tumor regions on the CT images before and after NCT, 540 delta-radiomic features were calculated. The interclass correlation coefficients for segmentations of inter/intra-observers and feature pair-wise correlation coefficients (Pearson) were used for robust feature selection. A delta-radiomics signature was constructed using the lasso algorithm based on the training set. Radiomics signatures built from single-phase CT were constructed for comparison purpose. A radiomics nomogram was then developed from the multivariate logistic regression model by combining independent clinical factors and the delta-radiomics signature. The prediction performance was assessed using area under the ROC curve (AUC), calibration curves and decision curve analysis (DCA). RESULTS: The delta-radiomics signature showed higher AUC than single-CT based radiomics signatures in both training and validation cohorts. The delta-radiomics signature, consisting of 8 selected features, showed significant differences between the pathologic good response (pGR) (necrosis fraction ≥90%) group and the non-pGR (necrosis fraction < 90%) group (P < 0.0001, in both training and validation sets). The delta-radiomics nomogram, which consisted of the delta-radiomics signature and new pulmonary metastasis during chemotherapy showed good calibration and great discrimination capacity with AUC 0.871 (95% CI, 0.804 to 0.923) in the training cohort, and 0.843 (95% CI, 0.718 to 0.927) in the validation cohort. The DCA confirmed the clinical utility of the radiomics model. CONCLUSION: The delta-radiomics nomogram incorporating the radiomics signature and clinical factors in this study could be used for individualized pathologic response evaluation after chemotherapy preoperatively and help tailor appropriate chemotherapy and further treatment plans.

Effects of exogenous annexin-1 on lipopolysaccharide-induced proliferation and reactive oxygen species production partially through modulation of CRAC channels but independent of NF-kappaB pathway.

OBJECTIVE: To investigate the effects of exogenous annexin-1 (ANXA1) on lipopolysaccharide(LPS)-induced proliferation, reactive oxygen species (ROS) production, and calcium signal transduction in RAW264.7 macrophages. METHODS: RAW264.7 macrophages were treated with or without LPS in the absence or presence of ANXA1. The proliferation effects were detected by Cell Counting Kit-8 assay. ROS were quantified by flow cytometry and fluorescence microscopy. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was analyzed by laser confocal scanning microscopy. IkappaBalpha degradation and NF-kappaB translocation were tested by Western blot. RESULTS: Exogenous ANXA1 inhibited LPS-induced proliferation and ROS production in a dose-dependent manner. LPS evoked [Ca(2+)](i) increase through CRAC channels, and ANXA1 suppressed LPS-induced [Ca(2+)](i) increase in a dose-dependent manner. The CRAC channels were associated with LPS-induced proliferation and ROS production. Exogenous ANXA1 had no effect on LPS-induced IkappaB degradation and NF-kappaB translocation. CONCLUSIONS: ANXA1 inhibited LPS-induced proliferation and ROS production in RAW264.7 macrophages partially through modulation of CRAC channels but independent of the NF-kappaB pathway.

Moderate to severe hepatic steatosis leads to overestimation of liver stiffness measurement in chronic hepatitis B patients without significant fibrosis.

BACKGROUND: Liver stiffness measurement (LSM) by transient elastography is a noninvasive method for the diagnosis of hepatic fibrosis. The impact of hepatic steatosis on LSM remains to be explored. AIM: To determine whether LSM is affected by hepatic steatosis in patients with chronic hepatitis B (CHB). METHODS: Consecutive patients with biopsy-proven CHB were prospectively enrolled. Hepatic steatosis was classified by pathology as none (S0, <5%), mild (S1, 5%-33%), and moderate-severe (S2-3, >33%), and quantitatively by controlled attenuation parameter (CAP) as CAP S0 (≤247 dB/m), CAP S1 (248-267 dB/m) and CAP S2-3 (≥268 dB/m). Liver fibrosis was assessed by METAVIR classification and noninvasively by LSM. RESULTS: The prevalence of non-alcoholic fatty liver disease (n = 223) in CHB patients (n = 593) was 37.6%. Forty-eight belonged to S2-3 and 127 belonged to CAP S2-3. In patients without significant fibrosis (F0-1), the median LSM (kPa) was 7.4 in S2-3 and 7.1 in CAP S2-3, which was significantly higher than that in S0/S1 (P = 0.005) and CAP S0/S1 (P = 0.003). No significant difference was found in significant fibrosis (F2-4). For LSM identifying significant fibrosis (F2-4), the negative predictive value was higher in CHB patients with CAP ≥ 268 compared to those with CAP < 268 (0.81 vs 0.73); the positive predictive value was lower in CAP ≥ 268 than its counterpart (0.65 vs 0.76). CONCLUSIONS: Moderate-severe steatosis increased the LSM value in CHB patients without significant fibrosis. A CAP ≥ 268 did not affect LSM for ruling out, but it slightly affected LSM for ruling in significant fibrosis. TRIAL REGISTRATION: ChiCTR-DDT-13003983.

Application of single balloon enteroscopy-assisted therapeutic endoscopic retrograde cholangiopancreatography in patients after bilioenteric Roux-en-Y anastomosis: Experience of multi-disciplinary collaboration.

BACKGROUND: Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM: To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS: This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS: Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION: Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.

Formyl-peptide receptor like 1: a potent mediator of the Ca2+ release-activated Ca2+ current ICRAC.

In electrically non-excitable cells, one major source of Ca(2+) influx is through the store-operated (or Ca(2+) release-activated Ca(2+)) channel by which the process of emptying the intracellular Ca(2+) stores results in the activation of Ca(2+) channels in the plasma membrane. Using both whole-cell patch-clamp and Ca(2+) imaging technique, we describe the electrophysiology mechanism underlying formyl-peptide receptor like 1 (FPRL1) linked to intracellular Ca(2+) mobilization. The FPRL1 agonists induced Ca(2+) release from the endoplasmic reticulum and subsequently evoked I(CRAC)-like currents displaying fast inactivation in K562 erythroleukemia cells which expresses FPRL1, but had almost no effect in K562 cells treated with FPRL1 RNA-interference and HEK293 cells which showed no FPRL1 expression. The currents were impaired after either complete store depletion by the sarco/endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin, or after inhibition of PLC by U73122. Our results present the first evidence that FPRL1 is a potent mediator in the activation of CRAC channels.

Biodistribution and toxicity assessment of intratumorally injected arginine-glycine-aspartic acid peptide conjugated to CdSe/ZnS quantum dots in mice bearing pancreatic neoplasm.

Quantum dots (QDs) conjugated with arginine-glycine-aspartic acid (RGD) peptides (which are integrin antagonists) are novel nanomaterials with the unique optical property of high molar extinction coefficient, and they have potential utility as photosensitizers in photodynamic therapy (PDT). Our group previously demonstrated significant benefits of using PDT with QD-RGD on pancreatic tumor cells. This study aimed to evaluate the biodistribution and toxicity of QD-RGD in mice prior to in vivo application. Mice with pancreatic neoplasms were intratumorally injected with varying doses of QD-RGD, and the biodistribution 0-24 h post injection was compared to that in control mice (intravenously injected with unconjugated QD). Various tissue samples were collected for toxicity analyses, which included inductively coupled plasma mass spectrometry (ICP-MS) to assess Cd2+ concentrations and hematoxylin-eosin staining for histopathological examination. Fluorescent imaging revealed relatively sufficient radiant efficiency in mice under specific conditions. The ICP-MS and HE data showed no significant signs of necrosis due to Cd2+ release by QDs. The mice survived well and had no apparent weakness or weight loss during the 4 weeks post injection. These findings provide novel insights into the biodistribution of QD-RGD and encourage profound in vivo studies regardless of safety concerns. These findings alleviate safety concerns and provide novel insights into the biodistribution of QD-RGD, offering a solid foundation for comprehensive in vivo studies.