Gender disparities in all-cause mortality among individuals with early-onset cardiovascular diseases.

BACKGROUND AND OBJECTIVE: Gender disparities in mortality among individuals with early-onset cardiovascular disease (CVD) remain uncertain. This study aimed to investigate gender differences in all-cause mortality and identify influencing factors. METHODS: Data extracted from the Kailuan Study, a prospective cohort study initiated in 2006, were analyzed. A total of 2,829 participants with early-onset CVD were included. Cox proportional hazard models were used to assess hazard ratios (HR) and 95% confidence intervals (CI) for gender disparities in all-cause mortality, adjusting for various factors. RESULTS: Males experienced a median follow-up duration of 7.54 years with 276 recorded deaths, and females had a median follow-up of 6.45 years with 105 recorded deaths. Gender disparities in all-cause mortality were observed, with men experiencing a higher all-cause mortality risk compared to women (HR: 1.42, 95% CI: 1.04, 1.92) in the fully adjusted model. Both in men and women with early-onset CVD, elevated hs-CRP levels and an eGFR < 60 mL/min/1.73m2 notably escalated the risk of all-cause mortality. Furthermore, the utilization of antiplatelet agents and successful blood glucose control might mitigate the risk of all-cause mortality. Smoking and eGFR decline modified the association between gender and all-cause death, women were more vulnerable to tobacco consumption and kidney misfunctioning than men (P-interaction = 0.019). CONCLUSION: The study highlights gender disparities in all-cause mortality among individuals with early-onset CVD, with men experiencing a higher risk of mortality compared to women. Addressing these disparities is important for improving outcomes in this population. Further research is needed to develop sex-specific interventions and strategies to reduce gender-related mortality disparities in early-onset CVD.

scGraph: a graph neural network-based approach to automatically identify cell types.

MOTIVATION: Single-cell technologies play a crucial role in revolutionizing biological research over the past decade, which strengthens our understanding in cell differentiation, development and regulation from a single-cell level perspective. Single-cell RNA sequencing (scRNA-seq) is one of the most common single cell technologies, which enables probing transcriptional states in thousands of cells in one experiment. Identification of cell types from scRNA-seq measurements is a fundamental and crucial question to answer. Most previous studies directly take gene expression as input while ignoring the comprehensive gene-gene interactions. RESULTS: We propose scGraph, an automatic cell identification algorithm leveraging gene interaction relationships to enhance the performance of the cell-type identification. scGraph is based on a graph neural network to aggregate the information of interacting genes. In a series of experiments, we demonstrate that scGraph is accurate and outperforms eight comparison methods in the task of cell-type identification. Moreover, scGraph automatically learns the gene interaction relationships from biological data and the pathway enrichment analysis shows consistent findings with previous analysis, providing insights on the analysis of regulatory mechanism. AVAILABILITY AND IMPLEMENTATION: scGraph is freely available at https://github.com/QijinYin/scGraph and https://figshare.com/articles/software/scGraph/17157743. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Atrial fibrillation increases the risk of new-onset myocardial infarction amongst working-age population: a propensity-matched study.

OBJECTIVE: The aim of this study was to investigate the association between atrial fibrillation (AF) and new-onset myocardial infarction (MI) among a working-age population in an industrial city of North China. METHODS: In total 77,670 participants aged under 60 years were selected for this cohort study. Participants were divided into an AF group (n = 121) and a non-AF group (n = 74,565) based on their medical histories. Thereafter, 121 participants from the AF group were propensity-matched with 363 participants from the non-AF group. All participants were followed up from June 2006 to December 2020; new-onset MI was regarded as the endpoint of this study. Multivariate Cox proportional hazards regression analysis models were designed to analyze the correlation between AF and new-onset MI. RESULTS: During the 14-year follow-up, eight cases of new-onset MI were documented in the AF group, while five cases were documented in the non-AF group. The cumulative incidence of new-onset MI in the AF group (7.40%) was markedly higher than in the non-AF group (1.41%; p < 0.001). Atrial fibrillation was associated with an increased risk of new-onset MI in both univariate analysis (hazard ratio: 5.202, 95% confidence interval [CI]: 1.700-15.913) and multivariable-adjusted analysis (hazard ratio: 5.335, 95% CI: 1.683-16.910). CONCLUSION: Atrial fibrillation increased the risk of new-onset MI amongst working-age individuals in an industrial city of North China.

Integration of network pharmacology and intestinal flora to investigate the mechanism of action of Chinese herbal Cichorium intybus formula in attenuating adenine and ethambutol hydrochloride-induced hyperuricemic nephropathy in rats.

CONTEXT: Cichorium intybus L. (Asteraceae) formula (CF) has been applied as a folk medicine to treat hyperuricemic nephropathy (HN). However, the exact mechanism remains unclear. OBJECTIVE: To explore the therapeutic effect and mechanism of CF on HN. MATERIALS AND METHODS: Through network pharmacological methods, the targets of the active component of CF against HN were obtained. Subsequently, Male Wistar rats were divided into control, HN, allopurinol (50 mg/kg), CF high-dose (8.64 g/kg) and CF low-dose (2.16 g/kg) groups. The HN model was induced via intragastric administration of adenine (100 mg/kg) and ethambutol hydrochloride (250 mg/kg) for 3 weeks. After CF treatment, biochemical indicators including UA, UREA and CREA were measured. Then, HE staining, qRT-PCR and gut microbiota analysis were conducted to further explore the mechanism. RESULTS: The network pharmacology identified 83 key targets, 6 core genes and 200 signalling pathways involved in the treatment of HN. Compared to the HN group, CF (8.64 g/kg) significantly reduced the levels of UA, UREA and CREA (from 2.4 to 1.57 µMol/L, from 15.87 to 11.05 mMol/L and from 64.83 to 54.83 µMol/L, respectively), and mitigated renal damage. Furthermore, CF inhibited the expression of IL-6, TP53, TNF and JUN. It also altered the composition of gut microbiota, and ameliorated HN by increasing the relative abundance of some probiotics. CONCLUSIONS: This work elucidated the therapeutic effect and underlying mechanism by which CF protects against HN from the view of the biodiversity of the intestinal flora, thus providing a scientific basis for the usage of CF.

Hepatic Arterial Infusion Chemotherapy with Oxaliplatin Plus Raltitrexed as an Alternative Option in Advanced Hepatocellular Carcinoma Patients with Failure of, or Unsuitability for, Transarterial Chemoembolization.

Background and Objectives: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed (HAICROX) as an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients who are ineligible for, or failed, the transarterial chemoembolization (TACE) treatment. Materials and Methods: From July 2020 to November 2021, a total of 35 HCC patients were enrolled and received HAIC with oxaliplatin plus raltitrexed. The overall survival (OS) and time to progression (TTP) were primary and secondary endpoints, respectively. The tumor response was assessed by the modified response evaluation criteria in solid tumors (mRECIST), and the adverse events were investigated using the common terminology criteria for adverse events version 5.0 (CTCAE 5.0). Results: The median OS and TTP were 10 months (95% confidence interval (CI): 5.5-14.6) and 3.5 months (95% CI: 2.3-4.7), respectively. By means of multivariate analysis, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy was found to be an independent prognostic factor for better survival. No patients experienced toxicity-related death. Thrombocytopenia, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) elevation were the most common toxicities. No grade 3 or higher adverse events related to HAICROX were observed. Conclusion: HAICROX showed valuable efficacy and tolerable toxicity in advanced HCC patients who progressed on TACE or were ineligible for TACE. HAICROX is a promising treatment for advanced-stage HCC patients with TACE failure or ineligibility.

Recurrence Outcome in Hepatocellular Carcinoma within Milan Criteria Undergoing Microwave Ablation with or without Transarterial Chemoembolization.

Background and Objectives: The recurrence outcome in patients who underwent microwave ablation (MWA) with or without transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) within Milan criteria remains unclear. The aim of this retrospective study was to identify the predictive factors of recurrence in these patients. Materials and Methods: From May 2018 to April 2021, 66 patients with HCC within Milan criteria were enrolled. Local tumor progression (LTP) and recurrence-free survival (RFS) were evaluated. Univariate and multivariate analyses were used to evaluate the risk factors of recurrence. The propensity score analysis was conducted to reduce potential confounding bias. Results: During the median follow-up of 25.07 months (95% confidence interval [CI], 21.85, 28.28), the median time to LTP and RFS were 20.10 (95%CI, 14.67, 25.53) and 13.03 (95%CI, 6.36, 19.70) months. No group difference (MWA vs. MWA + TACE) was found in 1-year cumulative LTP (p = 0.575) and RFS (p = 0.515), but meaningful significant differences were found in two-year recurrence (LTP, p = 0.007 and RFS, p = 0.037). Univariate and multivariate analyses revealed that treatment received before ablation was an independent risk factor of LTP (hazard ratio [HR] 4.37, 95%CI, 1.44, 13.32) and RFS (HR 3.41, 95%CI, 1.49, 7.81). Conclusions: The LTP and RFS in the MWA group were similar to that in the MWA combined with TACE. For HCC within Milan criteria, both groups preferentially selected MWA. More endeavor and rigorous surveillance should be taken to relapse prevention, in patients who have received previous treatment.

Multi-labelled proteins recognition for high-throughput microscopy images using deep convolutional neural networks.

BACKGROUND: Proteins are of extremely vital importance in the human body, and no movement or activity can be performed without proteins. Currently, microscopy imaging technologies developed rapidly are employed to observe proteins in various cells and tissues. In addition, due to the complex and crowded cellular environments as well as various types and sizes of proteins, a considerable number of protein images are generated every day and cannot be classified manually. Therefore, an automatic and accurate method should be designed to properly solve and analyse protein images with mixed patterns. RESULTS: In this paper, we first propose a novel customized architecture with adaptive concatenate pooling and "buffering" layers in the classifier part, which could make the networks more adaptive to training and testing datasets, and develop a novel hard sampler at the end of our network to effectively mine the samples from small classes. Furthermore, a new loss is presented to handle the label imbalance based on the effectiveness of samples. In addition, in our method, several novel and effective optimization strategies are adopted to solve the difficult training-time optimization problem and further increase the accuracy by post-processing. CONCLUSION: Our methods outperformed the SOTA method of multi-labelled protein classification on the HPA dataset, GapNet-PL, by above 2% in the F1 score. Therefore, experimental results based on the test set split from the Human Protein Atlas dataset show that our methods have good performance in automatically classifying multi-class and multi-labelled high-throughput microscopy protein images.

S100A11 promotes cell proliferation via P38/MAPK signaling pathway in intrahepatic cholangiocarcinoma.

S100A11 is reported to associate with progression and poor prognosis in several tumors. We previously reported that S100A11 was highly expressed in intrahepatic cholangiocarcinoma (ICC) cells and promoted TGF-ß1-induced EMT through SMAD2/3 signaling pathway. Here, we explored the prognostic role of S100A11 on ICC patients and preliminary molecular mechanisms how S100A11 regulated ICC cell proliferation. Our results showed that S100A11 was obviously increased in ICC tumor tissues. High expression of S100A11 was closely correlated with lymph node metastasis (LNM) and TNM stage and was an independent risk factor for patients' overall survival (OS) and recurrence-free survival (RFS). The nomograms comprising LNM and S100A11 achieved better predictive accuracy compared with TNM staging system for OS and RFS prediction. Silencing S100A11 significantly suppressed RBE cells and HCCC9810 cells proliferation, colony formation, and activation of P38/mitogen-activated protein kinase (MAPK) signaling pathway in vitro and inhibited tumor growth in vivo. In contrast, the overexpression of S100A11 in RBE cells and HCCC9810 cells achieved the opposite results. S100A11-induced proliferation was abolished after treatment with P38 inhibitor. Our findings suggest S100A11/P38/MAPK signaling pathway may be a potential therapeutic target for ICC patients.

Overexpression of interleukin-35 in intrahepatic cholangiocarcinoma is a prognostic indicator after curative resection.

Interleukin-35 (IL-35) is implicated in tumorigenesis, but its exact impact on intrahepatic cholangiocarcinoma (ICC) is not clear. The aim of the present study was to explore the specific effect of IL-35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Immunohistochemistry was applied to explore IL-35 expression as well as IL-35 receptor (IL-35R) in 102 ICC patients. Results showed that IL-35 was highly expressed in ICC tumor tissues and was positively associated with lymph node metastasis (LNM), TNM stage and vascular invasion and was an independent prognostic factor for patients' overall survival (OS) and recurrence-free survival (RFS). High expression of IL-35R (gp130 and IL-12Rß2) was also observed in ICC cancer tissues, but only gp130 was an independent prognostic factor for OS and RFS and was indispensable in IL-35-mediated ICC clinical prognosis. The nomogram comprising carcinoembryonic antigen, LNM, IL-35 and gp130 expression achieved better predictive accuracy compared with TNM stage for OS. Our data support that high IL-35 expression correlates with ICC aggressiveness and emerges as a valuable biomarker for evaluating ICC progression and prognosis in clinical work.

Prognostic Nomogram Based on Histological Characteristics of Fibrotic Tumor Stroma in Patients Who Underwent Curative Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients. MATERIALS AND METHODS: The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed. Tumor-stroma ratio and morphological maturity of FTS were evaluated on hematoxylin and eosin-stained tumor sections. CD3, CD8, and α-smooth muscle actin (α-SMA) staining were performed on corresponding tissue microarrays. The nomogram was established on variables selected by multivariate analyses and was validated in 10-fold cross-validation. RESULTS: Rich tumor stroma and strong α-SMA expression were associated with poor overall survival (OS). However, in multivariate analyses, these two biomarkers failed to stratify both OS and recurrence-free survival (RFS). Immature FTS was correlated with tumor multiplicity, advanced clinical stage, and sparser CD3 and CD8 positive tumor-infiltrating lymphocytes (TILs) and was identified as an independent prognostic indicator for both OS and RFS. The nomogram comprising FTS maturity, tumor number, microvascular invasion, and lymph node metastasis possessed higher predictive power relative to conventional staging systems. CONCLUSION: Immature FTS was an independent risk factor for survival and was associated with sparser CD3 and CD8 positive TILs in ICC. The prognostic nomogram integrating the maturity of FTS offers a more accurate risk stratification for postoperative ICC patients. IMPLICATIONS FOR PRACTICE: Accumulating evidence has suggested that fibrotic components in tumor microenvironment (TME) play a complicated and vital role in TME reprogramming and cancer progression. However, in clinical practice, the evaluation of fibrotic tumor stroma (FTS) is still neglected to some extent. This study's findings indicated that, in intrahepatic cholangiocarcinoma (ICC), the histological maturity of FTS is a robust prognostic indicator for patients who underwent curative resection. Moreover, prognostic nomogram constructed on the maturity of FTS possessed higher predictive power relative to the conventional tumor-node-metastasis staging systems. Taken together, the evaluation of FTS should be emphasized in clinical routine for more accurate prognostic prediction in postoperative ICC patients.

Differential responses of MET activations to MET kinase inhibitor and neutralizing antibody.

BACKGROUND: Aberrant MET tyrosine kinase signaling is known to cause cancer initiation and progression. While MET inhibitors are in clinical trials against several cancer types, the clinical efficacies are controversial and the molecular mechanisms toward sensitivity remain elusive. METHODS: With the goal to investigate the molecular basis of MET amplification (METamp) and hepatocyte growth factor (HGF) autocrine-driven tumors in response to MET tyrosine kinase inhibitors (TKI) and neutralizing antibodies, we compared cancer cells harboring METamp (MKN45 and MHCCH97H) or HGF-autocrine (JHH5 and U87) for their sensitivity and downstream biological responses to a MET-TKI (INC280) and an anti-MET monoclonal antibody (MetMab) in vitro, and for tumor inhibition in vivo. RESULTS: We find that cancer cells driven by METamp are more sensitive to INC280 than are those driven by HGF-autocrine activation. In METamp cells, INC280 induced a DNA damage response with activation of repair through the p53BP1/ATM signaling pathway. Although MetMab failed to inhibit METamp cell proliferation and tumor growth, both INC280 and MetMab reduced HGF-autocrine tumor growth. In addition, we also show that HGF stimulation promoted human HUVEC cell tube formation via the Src pathway, which was inhibited by either INC280 or MetMab. These observations suggest that in HGF-autocrine tumors, the endothelial cells are the secondary targets MET inhibitors. CONCLUSIONS: Our results demonstrate that METamp and HGF-autocrine activation favor different molecular mechanisms. While combining MET TKIs and ATM inhibitors may enhance the efficacy for treating tumors harboring METamp, a combined inhibition of MET and angiogenesis pathways may improve the therapeutic efficacy against HGF-autocrine tumors.

S100A11 promotes TGF-ß1-induced epithelial-mesenchymal transition through SMAD2/3 signaling pathway in intrahepatic cholangiocarcinoma.

AIM: Our previous study found S100A11 was significantly raised in intrahepatic cholangiocarcinoma cells, but the relationship between S100A11 and intrahepatic cholangiocarcinoma remains unclear. METHODS: We investigated the effect of silencing S100A11 on TGF-ß1-induced epithelial-mesenchymal transition (EMT), cell migration and invasion. RESULTS: Our results demonstrated silencing S100A11 inhibited TGF-ß1-induced cell migration, invasion and EMT, expression of EMT markers E-cadherin, N-cadherin, ß-catenin, vimentin, Slug and Snail was reversed. Furthermore, TGF-ß1-induced p-SMAD2 and 3 were also inhibited due to low S100A11 expression. CONCLUSION: Our present study indicated that S100A11 promotes EMT through accumulation of TGF-ß1 expression, and TGF-ß1-induced upregulation of p-SMAD2 and 3.

S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway.

AIM: We explored the expression of S100A6 and its role in intrahepatic cholangiocarcinoma (ICC). METHODS: The expression of S100A6 in ICC samples was detected by immunohistochemistry. In vitro experiments, we silenced and overexpressed S100A6 to investigate its role in cell functions. RESULTS: The expression of S100A6 was markedly increased in ICC tissues and cell lines. S100A6 overexpression was an independent risk factor for patients' survival. Silencing S100A6 resulted in a suppression of proliferation and p38/MAPK activity, while overexpressing S100A6 caused a promotion of proliferation and p38/MAPK. DISCUSSION:  S100A6 participated in the proliferation of ICC cells and correlated with a more aggressive behavior of ICC. Conclusion: S100A6 may serve as a novel prognostic marker and a potential therapeutic target for ICC patients.

Transarterial Chemoembolization versus Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma after Resection within Barcelona Clinic Liver Cancer Stage 0/A: A Retrospective Comparative Study.

PURPOSE: To compare outcomes of transarterial chemoembolization with radiofrequency (RF) ablation in treatment of recurrent hepatocellular carcinoma (HCC) after resection within Barcelona Clinic Liver Cancer (BCLC) stage 0/A. MATERIALS AND METHODS: From January 2007 to December 2011, 110 consecutive patients with recurrent HCC meeting BCLC stage 0/A criteria underwent transarterial chemoembolization (n = 78; mean tumor size, 1.9 cm ± 1.0) or RF ablation (n = 32; mean tumor size, 1.9 cm ± 0.6) as initial treatment. The primary outcome was overall survival (OS). Kaplan-Meier method was used to construct survival curves, which were compared by log-rank test. Prognostic factors for OS were analyzed using univariate and multivariate Cox proportional hazard models. RESULTS: No significant differences between baseline clinical characteristics of the 2 treatment groups were identified. The 1-, 3-, and 5-year OS rates were 89.7%, 61.0%, and 36.6% for the transarterial chemoembolization group and 90.1%, 72.8%, and 60.0% for the RF ablation group. There was no significant difference in OS rates between the groups (P = .159). Subgroup analysis indicated that RF ablation achieved better survival than transarterial chemoembolization among patients ≤ 55 years old and patients with BCLC stage 0 (P = .036 and P = .045). Multivariate analysis revealed that serum albumin (≤ 35 g/L) (hazard ratio = 2.797; 95% confidence interval, 1.366-2.726; P = .005) and α-fetoprotein (> 400 ng/mL) (HR = 2.336; 95% CI, 1.210-4.508; P = .011) levels before treatment were 2 significant risk factors for poor prognosis. CONCLUSIONS: Transarterial chemoembolization might provide a similar OS as RF ablation in patients with recurrent BCLC stage A HCC. However, RF ablation could provide better OS in patients with recurrent BCLC stage 0 HCC.

High platelet counts increase metastatic risk in huge hepatocellular carcinoma undergoing transarterial chemoembolization.

AIM: Accumulating evidence suggests platelets play critical roles in tumor metastasis. Moreover, the role of platelets in metastasis is partially correlated with inflammation. However, evidence regarding the contribution of platelets to hepatocellular carcinoma (HCC) metastasis is lacking. This study investigated the association between platelets and metastatic risk in HCC. METHODS: We used huge HCC (diameter over 10 cm), a tumor subgroup with a strong inflammatory background, as a model to evaluate the potential predictive role of platelets and platelet-related biomarkers for metastasis in HCC patients undergoing transarterial chemoembolization. A logistic regression model was used to analyze risk factors for metastasis. RESULTS: Patients with huge HCC (n = 178) were enrolled, and 24.7% (44/178) of patients had remote metastases after treatment. Univariate analyses showed high platelet counts (P = 0.012), pretreatment platelet-to-lymphocyte ratios (pre-PLR) of 100 or more (P = 0.018) and post-PLR of 100 or more (P = 0.013) were potential risk factors for metastasis. Furthermore, multivariate analyses showed high platelet counts (odds ratio, 2.18; 95% confidence interval, 1.074-4.443; P = 0.031) and platelet-related biomarkers were independent risk factors for HCC metastasis. Particularly, the risk of metastasis in patients with high post-PLR values was significantly greater than patients with low post-PLR values. For tumor response and survival, patients with high platelet counts had faster disease progression (P = 0.002) and worse survival (P < 0.0001). CONCLUSION: High platelet counts increase the extrahepatic metastasis risk of huge HCC undergoing chemoembolization, which supply clinical verification of the association between high platelet counts and HCC metastasis.

Comparison of transarterial chemoembolization with radiofrequency ablation for unresectable Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma: a propensity score matching.

BACKGROUND AND AIM: Radiofrequency ablation (RFA) is recommended as one of the standard treatments for early hepatocellular carcinoma (HCC). Because of high-risk tumor locations unfit for RFA, transarterial chemoembolization (TACE) is served as an alternative option in these settings. To define the role of TACE on early HCC, we retrospectively compared the efficacies of TACE with RFA in patients with unresectable Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC. MATERIALS AND METHODS: Treatment-naïve patients with unresectable BCLC stage 0/A HCC who underwent TACE or RFA were recruited from 2007 to 2011. In all, 208 patients who underwent TACE and 235 patients who underwent RFA were included in the final analysis. Using the propensity model to correct selection bias, 103 patients were selected from each treatment arm. Cumulative overall survival (OS) as the primary end point was compared after adjustment with propensity score matching. RESULTS: In all patients, the OS rate was significantly higher in patients treated with RFA than that in those who received TACE (1-, 3-, and 5-year OS rates, 93.7%, 72.6%, and 58.1% vs 88.1%, 50.3%, and 30.4%, respectively; P < 0.001). However, adjustment with propensity score matching yielded comparable OS between the two groups (P = 0.207). Subgroup analysis showed that RFA provided better OS than TACE in patients with serum γ-glutamyltranspeptidase < 75 IU/L (P = 0.035). Univariate and subsequent multivariate analyses revealed that Child-Pugh class B (hazard ratio = 1.805; 95% confidence interval, 1.805-3.003; P = 0.023) and hepatitis C virus positivity (hazard ratio = 2.478; 95% confidence interval, 1.136-5.404; P = 0.023) were independent predictors of poor prognosis. CONCLUSION: Transarterial chemoembolization is an effective alternative treatment for unresectable BCLC stage 0/A HCC when RFA is not feasible.

Differentially expressed gene profiles of intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and combined hepatocellular-cholangiocarcinoma by integrated microarray analysis.

Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are common primary liver cancers worldwide. However, the survival and prognosis of ICC are much poorer than those of HCC, indicating the different molecular characteristics and mechanisms between ICC and HCC. To identify differentially expressed (DE) genes between ICC and HCC or combined hepatocellular-cholangiocarcinoma (CHC), we performed integrated analysis of publicly available microarray Gene Expression Omnibus (GEO) datasets by MetaOmics. Three GEO datasets comprising 32 ICC biochips, 77 HCC biochips, and 34 CHC biochips were available for the data integration. We identified 7313 DE genes between ICC and HCC, including 3650 upregulated genes and 3663 downregulated genes. The S100 family members on chromosome 1q21 were extensively upregulated in ICC, and S100A11 had the greatest degree of upregulation in ICC. Based on the DE genes, combined gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed the enhanced pathways of local adhesion, ECM-receptor interaction, and regulation of action cytoskeleton, suggesting the enhanced communication between ICC and the microenvironment. Additionally, development-related genes and development-related pathways, including the Notch, Wnt, and TGF-ß signaling pathways, were shown to be active prominently in ICC. Taken together, we identified the characteristically upregulated or downregulated DE genes and pathways in ICC compared with HCC or CHC. These DE genes and pathways supply new transcriptomics evidence for ICC and could help identify new therapeutic targets.

Imbalance in systemic inflammation and immune response following transarterial chemoembolization potentially increases metastatic risk in huge hepatocellular carcinoma.

Inflammation plays a critical role in tumor metastasis. However, few inflammation-related biomarkers are currently available to predict the risk of metastasis for advanced hepatocellular carcinoma (HCC). Using huge tumors (diameter >10 cm) as a model, we evaluated the potential risk of pre- and post-treatment inflammatory responses in the development of metastasis of HCC patients undergoing transarterial chemoembolization (TACE). A logistic regression model was used to analyze the risk factors. One hundred and sixty-five patients with huge HCC were enrolled in the study. Metastases were identified in 25.5% (42/165) patients by imaging evaluation post-TACE. Neutrophils increased, whereas lymphocytes decreased significantly post-TACE. Univariate analysis showed that high post-treatment neutrophil-to-lymphocyte ratio (NLR; p = 0.003), low post-treatment lymphocyte count (p = 0.047), and high baseline NLR (p = 0.100) were potential risk factors for metastasis. Further, multivariate analysis showed that high post-treatment NLR, but not pre-treatment NLR, was an independent risk factor for metastasis; this was confirmed by receiver operating characteristic curve analysis. Post-treatment NLR, however, had no correlation to tumor response and overall survival of patients. In conclusion, post-treatment NLR but not pre-treatment NLR independently increases the risk of metastasis in huge HCC. Our findings suggest the potential contribution of treatment-related inflammation to metastasis in advanced HCC.

The platelet-to-lymphocyte ratio predicts poor survival in patients with huge hepatocellular carcinoma that received transarterial chemoembolization.

Inflammation is particularly strong in huge hepatocellular carcinoma (HCC). However, it is unclear whether the platelet-to-lymphocyte ratio (PLR), as an inflammatory-related marker, can predict survival of patients with huge HCC. In this study, we enrolled 291 patients with huge HCC (diameter over 10 cm) who were undergoing repeated transarterial chemoembolization (TACE) at our institute. The baseline PLR was calculated from complete serum blood counts before the first chemoembolization. We found that a baseline PLR cutoff value over 150 best predicted huge HCC survival. The 12, 24, and 36 months survival rates in the high PLR group (22.6, 8.1, and 4.1 %, respectively) were significantly lower than in the low PLR group (35.6, 22.4, and 14 %, respectively). Thus, a significant difference was found in overall survival (log-rank test, p < 0.0001). Univariate analyses indicated a high PLR (p < 0.0001) was predictor of poor survival, and multivariate Cox analyses further showed that a high PLR (p = 0.002) was an independent factor that predicted worse survival. In conclusion, for patients with huge HCC, a high baseline PLR is a useful predictor of poor survival in patients undergoing chemoembolization. Additional anti-inflammatory or anti-platelet treatments, in combination with TACE, may improve survival in HCC patients with high PLR.

Comparison of Plastic Surgery Residency Training in United States and China.

BACKGROUND: Residency training is internationally recognized as the only way for the physicians to be qualified to practice independently. China has instituted a new residency training program for the specialty of plastic surgery. Meanwhile, plastic surgery residency training programs in the United States are presently in a transition because of restricted work hours. The purpose of this study is to compare the current characteristics of plastic surgery residency training in 2 countries. METHODS: Flow path, structure, curriculum, operative experience, research, and evaluation of training in 2 countries were measured. The number of required cases was compared quantitatively whereas other aspects were compared qualitatively. RESULTS: Plastic surgery residency training programs in 2 countries differ regarding specific characteristics. Requirements to become a plastic surgery resident in the United States are more rigorous. Ownership structure of the regulatory agency for residency training in 2 countries is diverse. Training duration in the United States is more flexible. Clinical and research training is more practical and the method of evaluation of residency training is more reasonable in the United States. The job opportunities after residency differ substantially between 2 countries. Not every resident has a chance to be an independent surgeon and would require much more training time in China than it does in the United States. CONCLUSIONS: Plastic surgery residency training programs in the United States and China have their unique characteristics. The training programs in the United States are more standardized. Both the United States and China may complement each other to create training programs that will ultimately provide high-quality care for all people.