Development of a hydrophilic-lipophilic-balanced copolymer@zirconium-based metal-organic framework-based solid-phase microextraction probe for the trace determination of organophosphorus pesticides in tea infusions.

Organophosphorus pesticides (OPPs) present in tea infusions pose a serious threat to human health. In this study, a sensitive method for the determination of OPPs was developed based on a direct-immersion solid-phase microextraction (DI-SPME) probe. By fine adjustment of the ratio and one-step polymerization of dihydroxy-functionalized zirconium-based metal-organic framework UiO-66-(OH)2 and divinylbenzene-N-vinyl pyrrolidone (DVB-NVP) microspheres, the DVB-NVP@ UiO-66-(OH)2 (D-N@U) composite with an optimal hydrophilic-lipophilic balance (HLB) was achieved. Furthermore, D-N@U was adhesively bonded to stainless-steel wires to fabricate a DI-SPME probe. OPPs, especially those with nonpolar properties characterized by a high octanol-water partition coefficient (log KOW), were selectively and efficiently enriched on the D-N@U-coated DI-SPME probe from tea infusions. Coupled with a gas chromatography-flame photometric detector, the as-fabricated D-N@U-coated DI-SPME probe achieved good performance for OPPs analysis with a wide linear dynamic range of 0.10-500.00 µg/L and low detection limits of 1.96-6.69 ng/L. Moreover, in spiked samples, the recoveries and relative standard deviations were in the ranges of 73.12%-101.20 % and 1.03%-6.56 %, respectively. Owing to its simple operation, high extraction efficiency, and high sensitivity, this approach has great potential for the rapid determination of multiple pesticide trace-level residues in food.

Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

Upconversion fluorescence nanosensor based on enzymatic inhibited and copper-triggered o-phenylenediamine oxidation for the detection of dimethoate pesticides.

Pesticide residues in agricultural products pose a significant threat to human health. Herein, a sensitive fluorescence method employing upconversion nanoparticles was developed for detecting organophosphorus pesticides (OPs) based on the principle of enzyme inhibition and copper-triggered o-phenylenediamine (OPD) oxidation. Copper ions (Cu2+) oxidized the colorless OPD to a yellow 2,3-diaminophenazine (oxOPD). The yellow solution oxOPD quenched the fluorescence of upconversion nanoparticles due to the fluorescence resonance energy transfer. The high affinity of Cu2+ for thiocholine reduced the level of oxOPD, resulting in almost no fluorescence quenching. The addition of dimethoate led to the inhibition of acetylcholinesterase activity and thus prevented the formation of thiocholine. Subsequently, Cu2+ oxidized OPD to form oxOPD, which attenuated the fluorescence signal of the system. The detection system has a good linear range of 0.01 ng/mL to 50 ng/mL with a detection limit of 0.008 ng/mL, providing promising applications for rapid detection of dimethoate.

Pancreatic fistula and biliary fistula after laparoscopic pancreatoduodenectomy: 500 patients at a single institution.

Background: Pancreatic fistula (PF) and biliary fistula (BF) are two major leakage complications after pancreatoduodenectomy (PD). The aim of this study is to investigate the risk factors of PF and BF after laparoscopic PD (LPD). Materials and Methods: We conducted a retrospective analysis of 500 patients who underwent LPD from 1 April 2015 to 31 March 2020. Clinical data from patients were analysed using multivariate logistic regression analysis. Results: PF occurred in 86 (17.2%) patients. Univariate and multivariate analysis indicated that the soft texture of the pancreas (P = 0.001) was the independent risk factor for PF. BF occurred in 32 (6.4%) patients. Univariate and multivariate analysis indicated that history of cardiovascular disease (P < 0.001), surgical time (P = 0.005), pre-operative CA125 (P = 0.036) and pre-operative total bilirubin (P = 0.044) were independent risk factors for BF. Conclusion: The texture of the pancreas was an independent risk factor for PF after LPD, which was consistent with the literatures. In addition, history of cardiovascular disease, surgical time, pre-operative CA125 and pre-operative total bilirubin were new independent risk factors for BF after LPD. Therefore, patients with high-risk factors of BF should be informed that they are at a high risk for this complication.

lncRNA NEAT1 Promotes Colorectal Cancer Progression by Increasing Inflammation.

Background: Colorectal cancer is a digestive tract malignant tumor, ranking the second mortality and the third incidence cancer worldwide. The abnormal expression of NEAT1 is related to the occurrence and development of colorectal cancer. However, the specific mechanism of NEAT1 mediated-inflammatory pathway in the progression of colorectal cancer is still unclear. Methods: In this study, expression of NEAT1 in colorectal cancer patients was analyzed by bioinformatics. Clinical samples including peripheral blood and colorectal cancer tissues were collected for qRT-PCR, Western blot, and immunohistochemistry assay. The role of NEAT1 in the colorectal cancer progression was further confirmed by both in-vivo and in-vitro functional experiments. Results: By bioinformatics prediction, it is found that NEAT1 expression level is significantly higher in the peripheral blood of patients with colorectal cancer and is associated with poor prognosis. In-vitro functional studies indicated that NEAT1 knockdown suppressed the proliferation and migration of colorectal cancer cells by mediating inflammatory response. In-vivo tumorigenesis experiments showed that NEAT1 knockdown suppressed tumor growth. Conclusion: Abnormal high expression level of NEAT1 in colorectal cancer tissues and cells leads to poor prognosis. Mechanistically, NEAT1 triggers off the proliferation and migration of colorectal cancer cells through promoting the inflammatory reaction. Clinically, the expression level of NEAT1 in serum may be a marker for diagnosis and prognosis of colorectal cancer.

Effect of Fentanyl as an Adjuvant to Brachial Plexus Block for Upper Extremity Surgeries: A Systematic Review and Meta-Analysis of RCTs.

Objective: To assess if the addition of fentanyl to brachial plexus block has an impact on anesthetic outcomes and complication rates in patients undergoing upper extremity surgeries. Methods: We explore the PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases for all randomized controlled trials (RCTs) comparing adjuvant fentanyl with placebo/no drug for patients undergoing upper extremity surgery under brachial plexus block. Outcomes assessed were onset, duration of sensory and motor anesthesia, complications, and postoperative analgesia scores. Meta-analysis was conducted utilizing a random-effects model. The risk of bias was assessed using the Cochrane Collaboration's risk of bias assessment tool 2. Certainty of evidence was assessed using GRADE. Subgroup analysis was conducted depending upon the approach of brachial plexus block and type of local anesthetic. Results: Twelve RCTs with 660 patients were included. Addition of fentanyl had no effect on onset of sensory anesthesia (11 studies; MD: 0.48; 95% CI: -1.81, 0.85; I 2 = 96%; p=0.48) but significantly shortened onset of motor anesthesia (8 studies; MD: -2.36; 95% CI: -3.99, -0.74; I 2 = 96%; p=0.48). Duration of sensory anesthesia (9 studies; MD: 82.81; 95% CI: 41.81, 123.81; I 2 = 99%; p < 0.0001) and motor anesthesia (7 studies; MD: 93.41; 95% CI: 42.35, 144.46; I 2 = 99%; p=0.0003) was significantly increased with addition of fentanyl. The certainty of evidence-based on GRADE was deemed to be moderate for both onset and duration of anesthesia. The incidence of overall complications (nausea/vomiting and pruritis) was significantly higher in the fentanyl group (7 studies; OR: 2.14; 95% CI: 1.04, 4.40; I 2 = 8%; p=0.04) but with low certainty of evidence. Conclusions: Adjuvant fentanyl with brachial plexus block improves the onset of motor anesthesia but not sensory anesthesia. The duration of both sensory and motor anesthesia is significantly prolonged with fentanyl by around 83-93 minutes. However, clinicians should be aware that complications such as nausea/vomiting and pruritis are increased twofold with the addition of the drug. Current evidence is limited risk of bias in the RCTs and high heterogeneity in the meta-analyses.

An analysis of the effectiveness of stapler closure combined with a titanium clip in distal pancreatectomy.

PURPOSES: Postoperative pancreatic fistula is the most common and severe postoperative complication of distal pancreatectomy. Treatment of pancreatic stump to reduce the incidence of postoperative pancreatic fistula is crucial. This study evaluated the effectiveness of stapler closure combined with a titanium clip in distal pancreatectomy. METHODS: Prospectively collected data of consecutive patients who underwent distal pancreatectomy from April 2013 to May 2020 with pancreatic transection performed by the bare stapler method (131 patients), stapler + hand-sewn closure method (199 patients), and stapler + titanium clip method (209 patients) were reviewed retrospectively and compared between groups. RESULTS: No statistically significant differences were observed in basic data among the three groups. There were also no significant differences among the three groups in terms of the intraoperative data or tumor pathological types, except for the number of laparoscopic treatment cases (23, 53, and 80 for bare stapler method, stapler + hand-sewn closure method, and stapler + titanium clip method, respectively; P < 0.05) and pancreatic neuroendocrine tumor cases (15, 29, and 12, respectively; P < 0.05). There were no significant differences in postoperative complications or parameters, except for the number of clinical pancreatic fistula cases (31, 27, and 13 for bare stapler method, stapler + hand-sewn closure method, and stapler + titanium clip method, respectively; P < 0.05) and postoperative length of hospital stay (11.6 ± 8.3, 10.6 ± 9.7, and 9.3 ± 6.9 days, respectively; P < 0.05). The stapler + titanium clip group had a significantly lower number of clinical pancreatic fistula cases and shorter postoperative length of hospital stay than the other groups. The univariate analysis showed that pancreatic resection line thickness was an independent risk factor for clinical pancreatic fistula after operation. CONCLUSION: Stapler closure combined with titanium clips to reinforce the pancreatic stump is simple and easy to implement, effectively reduces the incidence of clinical pancreatic fistula, and shortens the postoperative length of hospital stay.

Clinical validation of the risk scoring systems of postoperative pancreatic fistula after laparoscopic pancreatoduodenectomy in Chinese cohorts: A single-center retrospective study.

BACKGROUND: Although several prediction models for the occurrence of clinically relevant postoperative pancreatic fistula after laparoscopic pancreatoduodenectomy exist, most were established using Western cohorts. The utility of these models using a Chinese cohort has not been validated widely. The aim of this study was to validate the original Fistula Risk Score, the alternative Fistula Risk Score, and the updated alternative Fistula Risk Score for patients undergoing laparoscopic pancreatoduodenectomy in a large-scale Chinese cohort externally. METHODS: Three clinically relevant postoperative pancreatic fistula risk models were selected for external validation with our database. Primary outcome was grade B/C postoperative pancreatic fistula (clinically relevant postoperative pancreatic fistula). Performance was measured based on sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio, and area under the curve. The original Fistula Risk Score was also compared with the alternative Fistula Risk Score and the updated alternative Fistula Risk Score. RESULTS: Of the 400 patients who underwent laparoscopic pancreatoduodenectomy, 60 (15.00%) developed clinically relevant postoperative pancreatic fistula. For the original Fistula Risk Score, the alternative Fistula Risk Score, and the updated alternative Fistula Risk Score, the sensitivity was 65.00%, 90.00%, and 90.00%; the specificity was 43.53%, 44.12%, and 37.65%; the positive predictive value was 16.88%, 22.13%, and 20.30%; the negative predictive value was 87.57%, 96.15%, and 95.52%; positive likelihood ratio was 1.151, 1.611, and 1.443; negative likelihood ratio was 0.804, 0.227, and 0.266, respectively. The area under the curve values were 0.608 (95% confidence interval 0.573-0.649), 0.733 (95% confidence interval 0.692-0.797), and 0.720 (95% confidence interval 0.688-0.763) on the original Fistula Risk Score, the alternative Fistula Risk Score, and the updated alternative Fistula Risk Score (P < .05). CONCLUSION: The alternative Fistula Risk Score and the updated alternative Fistula Risk Score had similarly good predictive utility. The original Fistula Risk Score performed less well. We recommended to use the alternative Fistula Risk Score and the updated alternative Fistula Risk Score to predict occurrence of clinically relevant postoperative pancreatic fistula after laparoscopic pancreatoduodenectomy when applied to a Chinese cohort.

Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors.

BACKGROUND: The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. METHODS: We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. RESULTS: Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762). CONCLUSION: These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.

New staging classification for pancreatic neuroendocrine neoplasms combining TNM stage and WHO grade classification [].

AJCC TNM stage and WHO grade (G) are two widely used staging systems to guide clinical management for pancreatic neuroendocrine neoplasms (panNENs), based on clinical staging and pathological grading information, respectively. We proposed to integrate TNM stage and G grade into one staging system (TNMG) and to evaluate its clinical application as a prognostic indicator for panNENs. Accordingly, 5254 patients diagnosed with panNENs were used to evaluate and to validate the applicability of TNMG to panNENs. The predictive accuracy of TNMG system was compared with that of each separate staging/grading system. We found that TNM stage and G grade were independent risk factors for survival in both the Surveillance, Epidemiology, and End Result (SEER) and multicenter series. The interaction effect between TNM stage and G grade was significant. Twelve subgroups combining the TNM stage and G grade were proposed in the TNMG stage, which were classified into five stages TNMG. According to the TNMG staging classification in the SEER series, the estimated median survival for stages I, II, III, IV, and V were 203, 174, 112, 61, and 8 months, respectively. The predictive accuracy of TNMG stage was higher than that of TNM stage and G grade used independently. The TNMG stage classification was more accurate in predicting panNEN patient's prognosis than either the TNM stage or G grade.

Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning.

Therapeutic payload delivery to the central nervous system (CNS) remains a major challenge in gene therapy. Recent studies using function-driven evolution of adeno-associated virus (AAV) vectors have successfully identified engineered capsids with improved blood-brain barrier (BBB) penetration and CNS tropism in mouse. However, these strategies require transgenic animals and thus are limited to rodents. To address this issue, we developed a directed evolution approach based on recovery of capsid library RNA transcribed from CNS-restricted promoters. This RNA-driven screen platform, termed TRACER (Tropism Redirection of AAV by Cell-type-specific Expression of RNA), was tested in the mouse with AAV9 peptide display libraries and showed rapid emergence of dominant sequences. Ten individual variants were characterized and showed up to 400-fold higher brain transduction over AAV9 following systemic administration. Our results demonstrate that the TRACER platform allows rapid selection of AAV capsids with robust BBB penetration and CNS tropism in non-transgenic animals.

Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell line.

AIMS: In tumor cells, shikonin treatment has been reported to inhibit glycolysis by suppressing the activity of pyruvate kinase M2 (PKM2) and to induce apoptosis by increasing reactive oxygen species (ROS) production. However, hepatocellular carcinoma (HCC) shows variable sensitivity to shikonin treatment, and the mechanism for these differences remains unclear. We evaluated the effects of shikonin on metabolic and oxidative pathways in sensitive and refractory HCC cell lines to identify mechanisms of differential sensitivity. MAIN METHODS: Cell viability and apoptosis were evaluated by MTT assay, PI/Annexin V and JC-1 staining. Mitochondrial function was further evaluated by measurements of ROS and mitochondrial mass. Oxygen consumption rates, NAD+/NADH, ATP and lactate were measured as indicators of energy metabolism and glycolysis. Protein expression associated with glycolysis and apoptosis was evaluated by western blotting, RT-qPCR and immunofluorescence staining. KEY FINDINGS: The sensitivity to shikonin treatment was significantly higher for HepG2 cells than for HCCLM3 cells, with less dramatic effects in HCCLM3 cells on apoptosis, ROS, and oxidative phosphorylation. Shikonin up-regulated mitochondrial biogenesis to increase mitochondrial oxidative phosphorylation in HepG2 cells, but displayed the opposite trend in HCCLM3 cells. Mechanistically, shikonin promoted nuclear expression of PKM2 and HIF1α in HCCLM3 cells, with upregulation of glycolysis-related gene transcription and glycolysis. SIGNIFICANCE: These results suggest that PKM2 rewires glucose metabolism, which explains the differential sensitivity to shikonin-induced apoptosis in HCC cells. Our findings elucidate mechanisms for differential responses to shikonin, provide potential biomarkers, and indicate a theoretical basis for targeting glycolytic enzymes in refractory HCC.

The Hsa_circ_0091579/miR-940/TACR1 Axis Regulates the Development of Hepatocellular Carcinoma.

PURPOSE: Circular RNAs (circRNAs) play important roles in hepatocellular carcinoma (HCC) development. The circRNA hsa_circ_0091579 (circ_0091579) is dysregulated in HCC, while the mechanism of circ_0091579 in HCC development is largely unknown. PATIENTS AND METHODS: Thirty paired cancer and adjacent normal tissues were harvested from HCC patients. SNU-387 and Huh7 cells were cultured in this study. circ_0091579, microRNA-940 (miR-940) and tachykinin-1 receptor (TACR1) abundances were measured via quantitative reverse transcription-polymerase chain reaction or Western blot. Cell viability, migration, invasion, colony ability, cell cycle distribution and apoptosis were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell assay, colony formation assay and flow cytometry. The interaction among circ_0091579, miR-940 and TACR1 was tested via dual-luciferase reporter analysis. The anti-HCC role of circ_0091579 knockdown in vivo was investigated using xenograft model. RESULTS: circ_0091579 expression was enhanced in HCC tissue samples and cells. circ_0091579 silence inhibited cell viability, migration, invasion and colony formation, induced cell cycle arrest at G0/G1 phase, and promoted apoptosis in HCC cells. miR-940 was targeted via circ_0091579 and miR-940 knockdown reversed the suppressive effect of circ_0091579 silence on HCC development. miR-940 targeted TACR1 to repress HCC development. circ_0091579 could regulate TACR1 expression by mediating miR-940. Down-regulation of circ_0091579 decreased xenograft tumor growth. CONCLUSION: Knockdown of circ_0091579 repressed HCC development by mediating miR-940/TACR1 axis, indicating a new pathogenesis of HCC.

WITHDRAWN: Novel long-acting BF-30 conjugate corrects pancreatic carcinoma via cytoplasmic membrane permeabilization and DNA-binding in tumor-bearing mice.

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Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro.

Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.

Sirt3 promotes hepatocellular carcinoma cells sensitivity to regorafenib through the acceleration of mitochondrial dysfunction.

Regorafenib, a multiple kinase inhibitor, is recently approved for treatment of patients with advanced hepatocellular carcinoma (HCC). Previous studies demonstrated that regorafenib was a mitochondrial toxicant, which associated with the impairment of mitochondria. Sirt3 is involved in the regulation of mitochondrial function in cancers. This study aimed to investigate the mechanism of Sirt3 involved in the mitochondrial dysfunction which associated with regorafenib treatment in liver cancer cells. We found regorafenib inhibited Sirt3 and p-ERK expression in HCC cells in a dose-dependent manner. Bioinformatics analysis showed that Sirt3 expression was down-regulated in liver cancer tissues and its low expression was correlated with worse overall survival (OS) in liver cancer patients. After transfected with Sirt3 overexpression plasmid, we found that Sirt3 sensitized liver cancer cells to regorafenib and resulted in much more apoptosis with a significant increase of ROS level. However, exogenous antioxidant could not weaken the apoptosis. Mitochondrial membrane potential assay indicated that Sirt3 overexpression accelerated the mitochondrial depolarization process induced by regorafenib and aggravated mitochondrial injury. Cellular oxygen consumption assay showed that mitochondrial dysfunction was caused by the damage of the electron transport chain. The results demonstrated that Sirt3 overexpression promoted the increase of ROS and apoptosis induced by regorafenib through the acceleration of mitochondrial dysfunction by impairing function of the electron transport chain in liver cancer cells. Our studies verified the functional role of Sirt3 in regorafenib treatment and suggested that regorafenib accompanied with Sirt3 activator as a novel treatment strategy for HCC.

A single-center clinical study of hepatic artery variations in laparoscopic pancreaticoduodenectomy: A retrospective analysis of data from 218 cases.

Hepatic artery variations increase the difficulty of laparoscopic pancreaticoduodenectomy (LPD). The safety and efficacy of LPD in the presence of aberrant hepatic arteries (AHA) must be further verified.Patients with normal and variant hepatic arteries who underwent LPD and preoperative arterial angiography were retrospectively analyzed. Variation type, intraoperative management, and clinical treatment outcomes were compared.There were 54 cases (24.8%) of AHA. The most common hepatic artery variation was accessory right hepatic artery (RHA) from the superior mesenteric artery (SMA, n = 12, 5.5%), followed by replaced RHA from the SMA (n = 10, 4.6%), accessory left hepatic artery from the SMA (n = 10, 4.6%), and replaced common hepatic artery from the SMA (n = 6, 2.8%). Each type of arterial variation was successfully preserved in all cases, and there were no significant effects on the evaluated surgical indices, conversion rate, incidence of postoperative complications, or follow-up results.Our findings indicated that preservation of AHAs during total LPD is feasible. There were no significant effects on surgical indices, incidence of postoperative complications, or follow-up outcomes.The influence of AHA on the safety and efficacy of LPD must be further verified. Patients with normal and variant hepatic arteries who underwent LPD and preoperative arterial angiography were retrospectively analyzed. There were 54 cases (24.8%) of AHA. There were no significant effects of AHAs on surgical indices, incidence of postoperative complications, or follow-up outcomes.

RCC2 contributes to tumor invasion and chemoresistance to cisplatin in hepatocellular carcinoma.

Tumor metastasis and chemoresistance are the main causes of treatment failure and high mortality in hepatocellular carcinoma (HCC). Therefore, it is critical to clarify the biological action and potential mechanisms in HCC cells to develop novel therapeutics. The regulator of chromosome condensation 2 (RCC2), a component of the chromosomal passenger complex, was shown to have important roles in tumor development and radio-chemotherapy resistance. However, its role in the aggressive phenotypes and cisplatin (DDP)-resistance of HCC is not known. Therefore, this study aimed to investigate the role of RCC2 in HCC pathogenesis. Interestingly, we found that RCC2 was upregulated in HCC patient specimens and HCC cell lines and was correlated with the pathological grade of HCC. To evaluate the function of RCC2 in HCC cell, lentivirus vector-based shRNAs were transfected into HCC cells. Silencing RCC2 inhibited the HCC cell proliferation, migration, invasion, and increased the apoptosis rate upon DDP treatment. Further analysis showed that RCC2-mediated downregulation of the expression of survival proteins occurred via the AKT and Bcl2 pathways. Our results suggest that RCC2 might act as an oncogenic protein promoting metastatic behaviors and cisplatin resistance in HCC cells, and thereby could be a potential prognostic biomarker and therapeutic target for HCC.

The prognostic value of lncRNA SNHG4 and its potential mechanism in liver cancer.

BACKGROUND AND OBJECT: Emerging evidence shows that non-coding RNA functions as new gene regulators and prognostic markers in several cancers, including liver cancer. Here, we focused on the small nucleolar RNA host gene 4 (SNHG4) in liver cancer prognosis based on The Cancer Genome Atlas (TCGA) data. METHODS: The expression data and clinical information were downloaded from TCGA. Chi-square tests evaluated the correlation between SNHG4 expression and clinical parameters. Differences in survival between high and low expression groups (optic cutoff value determined by ROC) from Cox regression analysis were compared, and P-value was calculated by a log-rank test. Kaplan-Meier curves were compared with the log-rank test. GSEA and ceRNA network were conducted to explore the potential mechanism. RESULTS: Data mining of lncRNA expression data for 371 patients with primary tumor revealed overexpression of SNHG4 in liver cancer. High SNHG4 expression was correlated with histological type (P = 0.01), histologic grade (P = 0.001), stage (P = 0.01), T classification (P = 0.004) and survival status (P = 0.013). Patients with high SNHG4 expression had poor overall survival and relapse-free survival compared with those with low SNHG4 expression. Multivariate analysis identified SNHG4 as an independent prognostic factor of poor survival in liver cancer. GSEA revealed related signaling pathway and ceRNA network explored the further mechanism. CONCLUSION: High SNHG4 expression is an independent predictor of poor prognosis in liver cancer.