High incidence of gallstones after Roux-en-Y reconstruction gastrectomy in gastric cancer: a multicenter, long-term cohort study.

BACKGROUND: Roux-en-Y reconstruction is a common anastomosis technique during gastrectomy in gastric cancer. There is a lack of studies on gallstones after Roux-en-Y reconstruction gastrectomy. This study investigated the incidence and potential risk factors associated with gallstones after Roux-en-Y reconstructive gastrectomy in gastric cancer. METHODS: The study analyzed data from gastric cancer who underwent radical gastrectomy and Roux-en-Y reconstruction at two hospitals between January 2014 and December 2020. The patients fall into distal and total gastrectomy groups based on the extent of gastrectomy. The cumulative event probability curve was plotted using the Kaplan-Meier, and differences in gallstone between groups were evaluated using the Log-Rank. Propensity score matching was applied to construct a balanced total versus distal gastrectomies cohort. A Cox regression was employed to analyze the risk factors for gallstones after Roux-en-Y reconstructive gastrectomy in gastric cancer. Further subgroup analysis was performed. RESULTS: Five hundred thirty-one patients were included in this study, 201 in the distal gastrectomy group and 330 in the total gastrectomy. During the follow-up, gallstones occurred in 170 cases after gastrectomy, of which 145 cases accounted for 85.29% of all stones in the first two years after surgery. Then, to reduce the impact of bias, a 1:1 propensity score matching analysis was performed on the two groups of patients. A total of 344 patients were evaluated, with each subgroup comprising 172 patients. In the matched population, the Cox regression analysis revealed that females, BMI ≥23 kg/m 2 , total gastrectomy, No.12 lymph node dissection, and adjuvant chemotherapy were risk factors for gallstones after Roux-en-Y reconstructive gastrectomy. Subgroup analysis showed that open surgery further increased the risk of gallstones after total gastrectomy. CONCLUSION: The incidence of gallstones increased significantly within 2years after Roux-en-Y reconstructive gastrectomy for gastric cancer. Patients with these risk factors should be followed closely after gastrectomy to avoid symptomatic gallstones.

A novel machine learning model and a public online prediction platform for prediction of post-ERCP-cholecystitis (PEC).

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an established treatment for common bile duct (CBD) stones. Post- ERCP cholecystitis (PEC) is a known complication of such procedure and there are no effective models and clinical applicable tools for PEC prediction. Methods: A random forest (RF) machine learning model was developed to predict PEC. Eligible patients at The First Hospital of Lanzhou University in China with common bile duct (CBD) stones and gallbladders in-situ were enrolled from 2010 to 2019. Logistic regression analysis was used to compare the predictive discrimination and accuracy values based on receiver operation characteristics (ROC) curve and decision and clinical impact curve. The RF model was further validated by another 117 patients. This study was registered with ClinicalTrials.gov, NCT04234126. Findings: A total of 1117 patients were enrolled (90 PEC, 8.06%) to build the predictive model for PEC. The RF method identified white blood cell (WBC) count, endoscopic papillary balloon dilatation (EPBD), increase in WBC, residual CBD stones after ERCP, serum amylase levels, and mechanical lithotripsy as the top six predictive factors and has a sensitivity of 0.822, specificity of 0.853 and accuracy of 0.855, with the area under curve (AUC) value of 0.890. A separate logistic regression prediction model was built with sensitivity, specificity, and AUC of 0.811, 0.791, and 0.864, respectively. An additional 117 patients (11 PEC, 9.40%) were used to validate the RF model, with an AUC of 0.889 compared to an AUC of 0.884 with the logistic regression model. Interpretation: The results suggest that the proposed RF model based on the top six PEC risk factors could be a promising tool to predict the occurrence of PEC.

HIF-1α mediates renal fibrosis by regulating metabolic remodeling of renal tubule epithelial cells.

Hypoxia-inducible factor 1-α (HIF-1α) mediates the occurrence and development of renal diseases and fibrosis. In the process, dysregulated cellular metabolism was suggested to be involved in several pathological processes. Here, we found that HIF-1α expression was increased in the early stage of renal fibrosis, and significant metabolic remodeling was triggered. Epigenetic events that drive diseases were characterized previously. Our study showed that ten-eleven translocation-2 (TET2) was upregulated in both renal fibrosis models and metabolite-treated samples. Furthermore, we found that the promoter of α-SMA was hypomethylated at CpG sites, which promoted the expression of α-SMA and the occurrence of renal fibrosis. HIF-1α inhibition alleviated renal fibrosis development by improving metabolic remodeling and TET2 activation. Our studies provide novel insight into HIF-1α-mediated metabolic remodeling in the pathogenesis of renal fibrosis and propose a concept that targets this pathway to treat fibrotic disorders.

High serum uric acid may associate with the increased risk of colorectal cancer in females: A prospective cohort study.

Elevated serum uric acid (SUA) levels have been previously reported to play a role in multiple types of cancers. However, epidemiological studies evaluating SUA levels and colorectal cancer risk remain sparse. This cohort study included 444 462 participants between the ages of 40 and 69 years from the UK Biobank, followed up from 2006 to 2010. Multivariable adjusted Cox regression models were used to estimate hazard ratios (HRs). During a mean follow-up of 6.6 years, 2033 and 855 cases of colon and rectal cancers, respectively, were diagnosed. The multivariable-adjusted HRs for risks of colon cancer in the lowest uric acid categories (≤3.5 mg/dL) compared with the reference groups were 1.31 (95% confidence interval [CI] = 0.75-2.29) in males and 1.26 (95% CI = 1.03-1.55) in females. The HRs in the highest uric acid groups (>8.4 mg/dL) were 1.16 (95% CI = 0.83-1.63) in males and 2.00 (95% CI = 1.02-3.92) in females. The corresponding HRs of rectal cancer in the lowest uric acid groups compared with the reference group were 2.21 (95% CI = 1.15-4.23) in males and 0.98 (95% CI = 0.66-1.45) in females. The HRs in the highest uric acid groups were 1.35 (95% CI = 0.82-2.23) in males and 3.81 (95% CI = 1.38-10.56) in females. In conclusion, SUA showed a U-shaped association with colon cancer risk in both male and female populations. The same pattern was observed in male patients with rectal cancer. However, SUA levels were positively associated with occurrence of rectal cancer in female subjects.

Preoperative prognostic nutritional index predicts short-term complications after radical resection of distal cholangiocarcinoma.

Background: The occurrence of postoperative complications of distal cholangiocarcinoma (dCCA) is an indicator of poor patient prognosis. This study aimed to determine the immune-nutritional indexes (INIs) that can predict short-term postoperative complications. Methods: A retrospective analysis of 148 patients with dCCA who were operated radical pancreaticoduodenectomy at the First Hospital of Lanzhou University from December 2015 to March 2022 was conducted to assess the predictive value of preoperative INIs and preoperative laboratory tests for short-term postoperative complications, and a decision tree model was developed using classification and regression tree (CART) analysis to identify subgroups at risk for overall complications. Results: In this study, 83 patients (56.08%) experienced overall complications. Clavien-Dindo grade III-V complications occurred in 20 patients (13.51%), and 2 patients died. The areas under curves (AUCs) of the preoperative prognostic nutritional index (PNI), controlling nutritional status (CONUT) score, and neutrophil-to-lymphocyte ratio (NLR) were compared; the PNI provided the maximum discrimination for complications (AUC = 0.685, 95% CI = 0.600-0.770), with an optimal cutoff value of 46.9, and the PNI ≤ 46.9 group had higher incidences of overall complications (70.67% vs. 40.00%, P < 0.001) and infectious complications (28.77% vs. 13.33%, P = 0.035). Multivariate logistic regression analysis identified PNI (OR = 0.87, 95% CI: 0.80-0.94) and total bilirubin (OR = 1.01, 95% CI: 1.00-1.01) were independent risk factors for overall complications (P < 0.05). According to CART analysis, PNI was the most important parameter, followed by the total bilirubin (TBIL) level. Patients with a PNI lower than the critical value and TBIL higher than the critical value had the highest overall complication rate (90.24%); the risk prediction model had an AUC of 0.714 (95% CI, 0.640-0.789) and could be used to stratify the risk of overall complications and predict grade I-II complications (P < 0.05). Conclusion: The preoperative PNI is a good predictor for short-term complications after the radical resection of dCCA. The decision tree model makes PNI and TBIL easier to use in clinical practice.

A meta-analysis of based radiomics for predicting lymph node metastasis in patients with biliary tract cancers.

Background: To assess the predictive value of radiomics for preoperative lymph node metastasis (LMN) in patients with biliary tract cancers (BTCs). Methods: PubMed, Embase, Web of Science, Cochrane Library databases, and four Chinese databases [VIP, CNKI, Wanfang, and China Biomedical Literature Database (CBM)] were searched to identify relevant studies published up to February 10, 2022. Two authors independently screened all publications for eligibility. We included studies that used histopathology as a gold standard and radiomics to evaluate the diagnostic efficacy of LNM in BTCs patients. The quality of the literature was evaluated using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the receiver operating characteristic curve (AUC) were calculated to assess the predictive validity of radiomics for lymph node status in patients with BTCs. Spearman correlation coefficients were calculated, and Meta-regression and subgroup analyses were performed to assess the causes of heterogeneity. Results: Seven studies were included, with 977 patients. The pooled sensitivity, specificity and AUC were 83% [95% confidence interval (CI): 77%, 88%], 78% (95% CI: 71, 84) and 0.88 (95% CI: 0.85, 0.90), respectively. The substantive heterogeneity was observed among the included studies (I 2 = 80%, 95%CI: 58,100). There was no threshold effect seen. Meta-regression showed that tumor site contributed to the heterogeneity of specificity analysis (P < 0.05). Imaging methods, number of patients, combined clinical factors, tumor site, model, population, and published year all played a role in the heterogeneity of the sensitivity analysis (P < 0.05). Subgroup analysis revealed that magnetic resonance imaging (MRI) based radiomics had a higher pooled sensitivity than contrast-computed tomography (CT), whereas the result for pooled specificity was the opposite. Conclusion: Our meta-analysis showed that radiomics provided a high level of prognostic value for preoperative LMN in BTCs patients.

Could saline irrigation clear all residual common bile duct stones after lithotripsy? A self-controlled prospective cohort study.

BACKGROUND: A previous study showed that irrigation with 100 mL saline reduced residual common bile duct (CBD) stones, which potentially cause recurrent stones after endoscopic retrograde cholangiopancreatography. AIM: To determine whether saline irrigation can improve CBD clearance after lithotripsy. METHODS: This prospective self-controlled study enrolled patients receiving mechanical lithotripsy for large (> 1.2 cm) CBD stones. After occlusion cholangiography confirmed CBD stone clearance, peroral cholangioscopy (POC) was performed to determine clearance scores based on the number of residual stones. The amounts of residual stones spotted via POC were graded on a 5-point scale (score 1, worst; score 5, best). Scores were documented after only stone removal (control) and after irrigation with 50 mL and 100 mL saline, respectively. The stone composition was analyzed using infrared spectroscopy. RESULTS: Between October 2018 and January 2020, 47 patients had CBD clearance scores of 2.4 ± 1.1 without saline irrigation, 3.5 ± 0.7 with 50 mL irrigation, and 4.6 ± 0.6 with 100 mL irrigation (P < 0.001). Multivariate analysis showed that CBD diameter > 15 mm [odds ratio (OR) = 0.08, 95% confidence interval (CI): 0.01-0.49; P = 0.007] and periampullary diverticula (PAD) (OR = 6.51, 95%CI: 1.08-39.21; P = 0.041) were independent risk factors for residual stones. Bilirubin pigment stones constituted the main residual stones found in patients with PAD (P = 0.004). CONCLUSION: Irrigation with 100 mL of saline may not clear all residual CBD stones after lithotripsy, especially in patients with PAD and/or a dilated (> 15 mm) CBD. Pigment residual stones are soft and commonly found in patients with PAD. Additional saline irrigation may be required to remove retained stones.

Associations between serum uric acid and hepatobiliary-pancreatic cancer: A cohort study.

BACKGROUND: Uric acid is the end product of purine metabolism. Previous studies have found that serum uric acid (SUA) levels are associated with the total cancer risk. However, due to the dual effect of uric acid on cancer, the relationship between the SUA levels and most specific-site cancer remains unclear. AIM: To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer. METHODS: In this prospective cohort study, 444462 participants free of cancer from the UK Biobank were included. The SUA levels were measured at baseline, and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry. The hazard ratios (HRs) and 95% confidence intervals (CIs) between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders. RESULTS: In total, 920 participants developed liver, gallbladder, biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up. We found that the HR of pancreatic cancer in the highest SUA group was 1.77 (95%CI: 1.29-2.42) compared with that in the lowest group. After stratifying by gender, we further found that SUA was associated with an increased risk of pancreatic cancer only among the females (highest quartile vs lowest quartile HR 2.04, 95%CI: 1.35-3.08). Among the males, the SUA levels were positively associated with the gallbladder cancer risk (highest quartile vs lowest quartile HR 3.09, 95%CI: 1.28-7.46), but a U-shaped association with the liver cancer risk was observed (P-nonlinear = 0.03). CONCLUSION: SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer. High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males. A U-shaped association with the liver cancer risk was identified.

Identification of hub genes involved in the occurrence and development of hepatocellular carcinoma via bioinformatics analysis.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy, which is a major cause of cancer morbidity and mortality worldwide. Thus, the aim of the present study was to identify the hub genes and underlying pathways of HCC via bioinformatics analyses. The present study screened three datasets, including GSE112790, GSE84402 and GSE74656 from the Gene Expression Omnibus (GEO) database, and downloaded the RNA-sequencing of HCC from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) in both the GEO and TCGA datasets were filtered, and the screened DEGs were subsequently analyzed for functional enrichment pathways. A protein-protein interaction (PPI) network was constructed, and hub genes were further screened to create the Kaplan-Meier curve using cBioPortal. The expression levels of hub genes were then validated in different datasets using the Oncomine database. In addition, associations between expression and tumor grade, hepatitis virus infection status, satellites and vascular invasion were assessed. A total of 126 DEGs were identified, containing 70 upregulated genes and 56 downregulated genes from the GEO and TCGA databases. By constructing the PPI network, the present study identified hub genes, including cyclin B1 (CCNB1), cell-division cycle protein 20 (CDC20), cyclin-dependent kinase 1, BUB1 mitotic checkpoint serine/threonine kinase ß (BUB1B), cyclin A2, nucleolar and spindle associated protein 1, ubiquitin-conjugating enzyme E2 C (UBE2C) and ZW10 interactor. Furthermore, upregulated CCNB1, CDC20, BUB1B and UBE2C expression levels indicated worse disease-free and overall survival. Moreover, a meta-analysis of tumor and healthy tissues in the Oncomine database demonstrated that BUB1B and UBE2C were highly expressed in HCC. The present study also analyzed the data of HCC in TCGA database using univariate and multivariate Cox analyses, and demonstrated that BUB1B and UBE2C may be used as independent prognostic factors. In conclusion, the present study identified several genes and the signaling pathways that were associated with tumorigenesis using bioinformatics analyses, which could be potential targets for the diagnosis and treatment of HCC.

Cytokines predict virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy.

BACKGROUND: Chronic hepatitis B virus infection remains a major global public health problem. Peginterferon-alpha-2a (PEG-IFN) has direct antiviral and immunoregulatory effects, and it has become one of the first choice drugs for the treatment of chronic hepatitis B (CHB). Cytokines play an important role in immunity, and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response. AIM: To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB. METHODS: Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients. RESULTS: The monokine induced by INF-γ (CXCL9) and serum interferon-inducible protein 10 ( IP-10) levels at baseline were higher in virological responders than in non-virological responders (NRs) and decreased during treatment, whereas the NRs did not exhibit significant changes. The macrophage inflammatory protein 1d (MIP-1d) levels at baseline and during treatment were significantly higher in the virological responders than in the NRs, while thymus and activation-regulated chemokine (TARC) levels at baseline and during treatment were significantly lower in the virological responders than in the NRs. The CXCL9, IP-10, MIP-1d, and TARC baseline levels exhibited the expected effects for interferon treatment. The area under the receiver operating characteristic curve values of CXCL9, IP-10, MIP-1d, and TARC for predicting virological responses were 0.787, 0.799, 0.787, and 0.77 (P = 0.01, 0.013, 0.01, and 0.021), respectively. CONCLUSION: We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN. Therefore, cytokines can be used as an indicator of antiviral drug selection before CHB treatment.

Bioinformatics combined with quantitative proteomics analyses and identification of potential biomarkers in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is an invasive malignancy arising from biliary epithelial cells; it is the most common primary tumour of the bile tract and has a poor prognosis. The aim of this study was to screen prognostic biomarkers for CCA by integrated multiomics analysis. METHODS: The GSE32225 dataset was derived from the Gene Expression Omnibus (GEO) database and comprehensively analysed by using R software and The Cancer Genome Atlas (TCGA) database to obtain the differentially expressed RNAs (DERNAs) associated with CCA prognosis. Quantitative isobaric tags for relative and absolute quantification (iTRAQ) proteomics was used to screen differentially expressed proteins (DEPs) between CCA and nontumour tissues. Through integrated analysis of DERNA and DEP data, we obtained candidate proteins APOF, ITGAV and CASK, and immunohistochemistry was used to detect the expression of these proteins in CCA. The relationship between CASK expression and CCA prognosis was further analysed. RESULTS: Through bioinformatics analysis, 875 DERNAs were identified, of which 10 were associated with the prognosis of the CCA patients. A total of 487 DEPs were obtained by using the iTRAQ technique. Comprehensive analysis of multiomics data showed that CASK, ITGAV and APOF expression at both the mRNA and protein levels were different in CCA compared with nontumour tissues. CASK was found to be expressed in the cytoplasm and nucleus of CCA cells in 38 (45%) of 84 patients with CCA. Our results suggested that patients with positive CASK expression had significantly better overall survival (OS) and recurrence-free survival (RFS) than those with negative CASK expression. Univariate and multivariate analyses demonstrated that negative expression of CASK was a significantly independent risk factor for OS and RFS in CCA patients. CONCLUSIONS: CASK may be a tumour suppressor; its low expression is an independent risk factor for a poor prognosis in CCA patients, and so it could be used as a clinically valuable prognostic marker.

Comparison of endoscopic naso-gallbladder drainage and percutaneous transhepatic gallbladder drainage in acute suppurative cholecystitis: Study Protocol Clinical Trial (SPIRIT Compliant).

INTRODUCTION: Transitional drainage, which is followed by cholecystectomy plays a key role in the management of acute cholecystitis, especially in high-risk surgical patients. Endoscopic naso-gallbladder drainage (ENGBD) is an alternative to percutaneous transhepatic gallbladder drainage (PTGBD) for patients who need temporary drainage. There is a lack of prospective comparison on the relevant outcomes of the two drainage methods during the period of drainage, especially the subsequent cholecystectomy. METHODS: This is a randomized controlled two-arm non-blind single center trial. Patients with acute cholecystitis undergo emergent or early cholecystectomy and need drainage will be randomly assigned to group PTGBD or ENGBD. Pain score is defined as the primary endpoint, whereas several secondary endpoints, such as the rates of technical success, clinical remission, open conversion of cholecystectomy will be determined to elucidate more detailed differences between two groups. The general feasibility, safety, and quality checks required for high-quality evidence will be adhered to. DISCUSSION: This study would provide the first type A evidence concerning the comparison of ENGBD versus PTGBD in surgically high-risk patients with acute cholecystitis, it will be the first trial designed to determine the impact of two drainage methods on not only peri-drainage but also peri-LC. TRIAL REGISTRATION: NCT03701464. Registered on October 10, 2018.

Quantitative Proteomic Analysis and Evaluation of the Potential Prognostic Biomarkers in Cholangiocarcinoma.

Background & Aims: Cholangiocarcinoma (CCA) patients have poor outcomes since the late diagnosis limits the benefits of surgery therapy and curative treatment options. The present study was designed to screen the biomarkers for CCA patients. Methods: Quantitative iTRAQ proteomic analysis was used to identify differentially expressed proteins between CCA and pericarcineous tissue. We examined the expression profile of PRDX2, BGN, LUM, and PPP3CA in CCA tissue using immunohistochemistry. We further investigated the correlation between PPP3CA expression and the survival of CCA patients (n=91). Results: 2,886 confidential proteins were identified by using the iTRAQ technique, 233 of which were differentially expressed. PRDX2, BGN, PPP3CA, and LUM were expressed in CCA tissue, whereas they were not expressed in choledocal cyst tissue except for LUM. PPP3CA was expressed in the cytoplasm of carcinoma cells in 22 cases (24.2%) of 91 CCA patients. Patients with PPP3CA-positive expression showed a significantly shorter survival period than did non-expressing patients (P = 0.030). The univariate analysis showed that tumor size (P = 0.002), vascular invasion (P = 0.001), histological grading (P = 0.011), and PPP3CA expression (P = 0.033) were statistically significant risk factors affecting the prognosis of CCA patients. The multivariate analysis demonstrated PPP3CA expression (P = 0.009) and vascular invasion (P = 0.012) were statistically significant independent risk factors of CCA patients. Conclusions: The results suggested that the expression of PPP3CA in CCA patients is a new independent factor for poor prognosis and a useful prognostic predictor for patients with CCA.

Targeting cyclin-dependent kinases in gastrointestinal cancer therapy.

Cyclin-dependent kinases (CDKs) play an important role in cell-cycle progression. CDKs are positively modulated by regulatory mitotic cyclins and negatively controlled by endogenous CDK inhibitors (CDKIs) cyclically as cells progress through different cell cycles of transitions. When activated by cyclins, cyclin-CDK complexes were able to facilitate the transition of cell cycle from one phase to the next, e.g., from G1 to S or from G2 to M. DNA damages may cause inhibition of CDKs leading to cell-cycle arrest, while unrepairable DNA damage causes cells to undergo apoptosis. Disruption of cell cycle progression is an important cancer hallmark to mediate uncontrolled cell proliferation, tumorigenesis, and metastasis. Aberrantly expressed CDKs are causally linked to the development of gastrointestinal cancers, and as such, CDKs may not only form a class of potential biomarkers for the diagnosis and therapy of gastrointestinal cancers. In this review article, we summarized the data from translational studies using CDKs as a target for gastrointestinal cancer treatment.

Peroxiredoxin2 downregulation enhances hepatocellular carcinoma proliferation and migration, and is associated with unfavorable prognosis in patients.

It has been revealed by our previous proteomic study that the expression profile is different between well­differentiated and poorly differentiated hepatocellular carcinoma (HCC). Among those differently expressed proteins, peroxiredoxin2 (PRDX2) was our protein of interest. The present study aimed to further investigate the value of PRDX2 as a prognostic factor in HCC. Tissue microarrays were used to investigate the expression difference between HCC tissues and their adjacent normal liver tissues. The expression of PRDX2 at both mRNA and protein levels was examined by q­RT­PCR, western blotting and immunohistochemical assessment in HCC tissues and cell line HCCLM3. Silencing of PRDX2 in HCCLM3 was achieved usingpGMLV­SC1 lentiviral vectors. Cell Counting Kit­8 (CCK­8) and Transwell migration assays were used to assess cell proliferation and migration, respectively. Categorical variables were assessed using the Chi­square test, and ordinal variables were examined using the Mann­Whitney U test. The difference of continuous variables between groups were compared with t­tests. The Kaplan­Meier method was used to calculate the overall survival (OS) and disease­free survival (DFS) of patients, and the log­rank test was used to analyze the differences between groups. The results revealed that the expression of PRDX2 was decreased at both the mRNA and protein levels in an HCC cell line compared to that of a normal human liver cell line. PRDX2 protein expression levels were significantly downregulated in HCC tissues and were positively linked to overall survival (OS) and disease­free survival (DFS) of HCC patients. Patients with high PRDX2 expression levels had longer OS and DFS times than those with lower PRDX2 expression. Silencing of PRDX2 in the HCC cell line HCCLM3 promoted cancer cell proliferation and migration. Our findings indicated that PRDX2 may play an important role in HCC development; PRDX2 may serve as a useful prognostic factor and a therapeutic target.

Curcumol Exerts Anticancer Effect in Cholangiocarcinoma Cells via Down-Regulating CDKL3.

Curcumol is the major component extracted from root of Rhizoma Curcumae. Recent studies have shown that curcumol exerts therapeutic effects against multiple conditions, particularly cancers. However, the therapeutic role and mechanism of curcumol against cholangiocarcinoma cells are still unclear. In our current research, we tested the effect of curcumol in cholangiocarcinoma cells, and using two-dimensional electrophoresis, proteomics and bioinformatics, we identified cyclin-dependent kinase like 3 (CDKL3) as a potential target for curcumol. We have demonstrated that curcumol can evidently suppress growth and migration of cholangiocarcinoma cells. Furthermore, curcumol could significantly block the cell cycle progression of the cholangiocarcinoma cells. These effects could be largely attributed to the inhibition of CDKL3 by curcumol. Further studies have recapitulated the oncogenic role of CDKL3 in that knockdown of CDKL3 by lentiviral mediated transfection of shRNA against CDKL3 also led to a significant inhibition on cell proliferation, migration, invasion, and cell cycle progression. Given the high level of CDKL3 expression in human cholangiocarcinoma tissues and cell lines, we speculated that CDKL3 may constitute a potential biological target for curcumol in cholangiocarcinoma.

Identification and Comparison of Differentiation-Related Proteins in Hepatocellular Carcinoma Tissues by Proteomics.

Histological differentiation is a major pathological criterion indicating the risk of tumor invasion and metastasis in patients with hepatocellular carcinoma. The degree of tumor differentiation is controlled by a complex interacting network of associated proteins. The principal aim of the present study is to identify the possible differentiation-related proteins which may be used for early diagnosis and more effective therapies. We compared poorly differentiated and well-differentiated hepatocellular carcinoma tissues by using 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Among the 11 identified protein spots, 6 were found to be upregulated in poorly differentiated hepatocellular carcinoma tissues and 5 were correspondingly downregulated. Immunohistochemistry was performed on 106 hepatocellular carcinoma tissues to confirm the results of the proteomic analysis. By using bioinformatic tools GO and STRING, these proteins were found to be related to catalytic activity, binding, and antioxidant activity. In particular, our data suggest that overexpression of peroxiredoxin-2, annexin A2, and heat shock protein ß-1 was correlated with tumor invasion, metastasis, and poor prognosis, and therefore, these proteins may serve as potential diagnostic and therapeutic biomarkers.

Simulating adsorption of organic pollutants on finite (8,0) single-walled carbon nanotubes in water.

Understanding the mechanism and thermodynamics of the adsorption of chemicals on carbon nanotubes (CNTs) is important to risk assessment and pollution control of both CNTs and chemicals. We computed the adsorption of cyclohexane, benzene derivatives, and polycyclic aromatic hydrocarbons (PAHs) on (8,0) single-walled carbon nanotubes by the M05-2X of density functional theory. The computed adsorption energies (E(a)) in the aqueous phase are lower than those in the gaseous phase, indicating that the adsorption in the aqueous phase is more favorable. The contribution of π-π interactions and the enhancing effect of a -NO(2) substituent on the adsorption were quantified. For a hypothetical aromatic with the same hydrophobicity (logK(OW)) to cyclohexane, π-π interactions contribute ca. 24% of the total interactions as indicated by E(a). -NO(2) enhances the π-π interactions due to its electron withdrawing effects, and contributes 24% to the value of E(a). Simple linear regression showed the computed Gibbs free energy changes for the adsorption correlate significantly with the experimental values (r = 0.97, p < 0.01). The correlation together with the computed thermodynamic parameters may be employed to predict the adsorption affinity of other chemicals. The study may pave a new way for evaluating/predicting the adsorption affinity of organic compounds on SWNTs and probing the adsorption mechanisms.

Study of 1-3-2 type piezoelectric composite transducer array.

Based on a new structure of precise location and decoupling between the transducer elements, high frequency underwater transmission transducer arrays with 4 elements and 8 elements serried uniform linear array were studied, using novel 1-3-2 type piezoelectric composite as the sensing material. There are ceramic framework supports in the transverse and longitudinal directions in 1-3-2 type piezoelectric composite structure; the transducer is free from the influence of outside mechanical impact and the environment temperature change. Transducer and array samples have been designed, fabricated and measured. The resonant frequency is 150 kHz, resonant transmission response greater than 160 dB, and bandwidth is from 140 kHz to 160 kHz. The results indicate that, the transducer array has wide bandwidth, high sensitivity, stabile performance, and good coherence.