TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma.

Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.

Practice Trends among US Gastroenterologists following the 2020 American Gastroenterological Association Guidelines on Gastric Intestinal Metaplasia: Data from a Tertiary Care Center.

BACKGROUND AND AIMS: Studies show variability in gastroenterologists' management of gastric intestinal metaplasia (GIM) in the United States. In 2020, the American Gastroenterological Association published GIM guidelines, recommending physician-patient shared decision-making on GIM surveillance based on risk factors. We compared gastroenterologists' communication trends of a GIM finding and surveillance recommendations before and after 2020 and evaluated patient and provider factors associated with a surveillance recommendation. METHODS: A sample of patients diagnosed with GIM on biopsies from upper endoscopies performed in 2018 (cohort A) and 2021 (cohort B) were included. Logistic regression analysis assessed the association between patient/provider characteristics and surveillance recommendations in the overall cohort and over time. MATERIALS: In all, 347 patients were included: 175 in cohort A and 172 in B. Median age was 65.7 (56.0, 73.4), and 54.5% were females. Communication to patients about GIM findings and surveillance recommendations increased from 24.6% <2020 to 50% >2020 (P<0.001) and 20% <2020 to 41.3% >2020 (P<0.001), respectively. Overall, endoscopy >2020, family history of gastric cancer, autoimmune gastritis, female providers, and gastroenterologists with 10 to 20 years of experience were associated with a surveillance recommendation. The effect of family history of gastric cancer and the effect of the patient's female sex on surveillance was significantly different between both cohorts [Odds ratio (OR): 0.13, 95% (Confidence interval) CI: 0.02, 0.97 and OR 3.39, 95% CI: 1.12, 10.2, respectively). CONCLUSIONS: Despite a 2-fold increase in surveillance recommendations after 2020, there was no meaningful effect of any of the patients' factors on a recommendation for surveillance over time, which raises the question as to whether surveillance is being offered to both average and high-risk patients without thorough risk stratification.

Endoscopic submucosal dissection with versus without traction for pathologically staged T1B esophageal cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: Positive vertical margins (VMs) are common after endoscopic submucosal dissection (ESD) of T1b esophageal cancer (EC) and are associated with an increased risk of recurrence. Traction during ESD provides better exposure of the submucosa and may allow deeper dissection, potentially reducing the risk of positive VMs. We conducted a retrospective multicenter study to compare the proportion of resections with positive VMs in ESD performed with versus without traction in pathologically staged T1b EC. METHODS: Patients who underwent ESD revealing T1b EC (squamous or adenocarcinoma) at 10 academic tertiary referral centers in the United States (n = 9) and Brazil (n = 1) were included. Demographic and clinical data were abstracted. ESD using either traction techniques (tunneling, pocket) or traction devices (clip line, traction wire) were classified as ESD with traction (Tr-ESD) and those without were classified as conventional ESD without traction. The primary outcome was a negative VM. Multivariable logistic regression was used to assess associations with negative VMs. RESULTS: A total of 166 patients with pathologically staged T1b EC underwent Tr-ESD (n = 63; 38%) or conventional ESD without traction (n = 103; 62%). Baseline factors were comparable between both groups. On multivariable analysis, Tr-ESD was found to be independently associated with negative VMs (odds ratio, 2.25; 95% confidence interval, 1.06-4.91; P = .037) and R0 resection (odds ratio, 2.83; 95% confidence interval, 1.33-6.23; P = .008). CONCLUSION: Tr-ESD seems to be associated with higher odds of negative VMs than ESD without traction for pathologically staged T1b EC, and future well-conducted prospective studies are warranted to establish the findings of the current study.

Identification of signature of tumor-infiltrating CD8 T lymphocytes in prognosis and immunotherapy of colon cancer by machine learning.

BACKGROUND: To explore the specific marker of CD8+ T cell subsets which are closely related to the prognosis and immunotherapy of patients with colon cancer. METHODS: 18 kinds of immune cell expression profile data sets were obtained from GEO database. Compared with other immune cell types, the specific markers of CD8 (+) T cells (TI-CD8) in colorectal cancer were screened. Regression analyses were used to further screen prognostic related genes and construct a prognostic evaluation model. The patients were stratified and analyzed according to the risk scores, KRAS mutation status, stage, lymphatic infiltration and other indicators. The landscape of infiltration level, mutation and copy number variation of immune subsets in high and low TI-CD8Sig score groups were compared and analyzed. The difference of drug response between high and low TI-CD8Sig score groups was analyzed. Differential expression of the model genes was verified by the HPA database. RESULTS: Six prognostic-related CD8T cell-specific gene targets were further screened, and the prognostic evaluation model was constructed. The AUC value of the model is >0.75. FAT3 and UNC13C showed a high mutation state in the low-risk group, while USH2A, MUC5B et al. specifically showed a high mutation state in the high-risk group. Compared with the low-risk group, the high-risk group had lower effective rate of drug response. The expression of PD-1 gene was positively correlated with the level of TI-CD8Sig score. CONCLUSION: The risk assessment model based on CD8T cell-specific marker genes can effectively predict the prognosis and the drug response of patients with CRC.

The role of platelets in the regulation of tumor growth and metastasis: the mechanisms and targeted therapy.

Platelets are a class of pluripotent cells that, in addition to hemostasis and maintaining vascular endothelial integrity, are also involved in tumor growth and distant metastasis. The tumor microenvironment is a complex and comprehensive system composed of tumor cells and their surrounding immune and inflammatory cells, tumor-related fibroblasts, nearby interstitial tissues, microvessels, and various cytokines and chemokines. As an important member of the tumor microenvironment, platelets can promote tumor invasion and metastasis through various mechanisms. Understanding the role of platelets in tumor metastasis is important for diagnosing the risk of metastasis and prolonging survival. In this study, we more fully elucidate the underlying mechanisms by which platelets promote tumor growth and metastasis by modulating processes, such as immune escape, angiogenesis, tumor cell homing, and tumor cell exudation, and further summarize the effects of platelet-tumor cell interactions in the tumor microenvironment and possible tumor treatment strategies based on platelet studies. Our summary will more comprehensively and clearly demonstrate the role of platelets in tumor metastasis, so as to help clinical judgment of the potential risk of metastasis in cancer patients, with a view to improving the prognosis of patients.

Identification of inflammatory factor-related genes associated with the prognosis and immune cell infiltration in colorectal cancer patients.

This study aims to identify the inflammatory factor-related genes which help to predict the prognosis of patients with colorectal cancer. GSEA (Gene Set Enrichment Analysis) was used to acquire inflammation-related genes and the corresponding expression information was collected from TCGA database to determine the DEGs (differentially-expressed genes) in CRC patients. We conducted enrichment analysis and PPI (protein-protein interaction) of these DEGs. Besides, key genes that are both differentially-expressed and prognosis-related were screened out, which were used to establish the prognostic model. We obtained 79 DEGs and 19 prognostic genes, 10 prognostic-related differential genes were eventually screened. These genes were used to construct the prognostic model. We also identified that the immune infiltration score of macrophages between different risk groups was significantly different and similar distinction was witnessed in immune function score of APC (antigen-presenting cell) co-stimulation and type I IFN (interferon) response.

The value of serum TRAP1 in diagnosing small cell lung cancer and tumor immunity.

This study set out to investigate the clinical significance of serum tumor necrosis factor receptor-associated protein 1 (TRAP1) in diagnosing small cell lung cancer (SCLC) with different clinical stages, and to compare the diagnostic efficiency with neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Besides, to analyze the role of serum TRAP1 in tumor immunity. A total of 91 patients with SCLC, 99 patients with non-small cell lung cancer (NSCLC), 102 patients with pulmonary nodules (PN), and 75 healthy people were included. The concentrations of serum TRAP1 was detected by enzyme-linked immunosorbent assay (ELISA). NSE, CEA, and CA19-9 were detected by chemiluminescence. The results showed that level of TRAP1 in Group SCLC was lower than other three groups (P < 0.01), whereas NSE in SCLC was significantly higher than the others (P < 0.01), and the levels of CEA and CA19-9 were higher than healthy people and PN patients (P < 0.01). There was a significant difference in TRAP1 levels between patients with limited-stage disease SCLC (LD-SCLC) and extensive-stage disease SCLC (ED-SCLC) (P < 0.0001). The sensitivity and specificity of TRAP1 in diagnosing LD-SCLC were 0.964 and 0.560, respectively, and the area under the curve (AUC) was 0.819. The sensitivity and specificity in diagnosing ED-SCLC were 0.810 and 0.868, respectively, and the AUC was 0.933, which showed high diagnostic value. The AUC of these two groups can be increased to 0.946 and 0.947 in combination of four biomarkers, effectively improving the diagnosis rate of SCLC. Our findings have revealed that serum TRAP1 has high diagnostic value for SCLC and high diagnostic sensitivity for LD-SCLC. It is a potential biomarker for SCLC. Combined detection can effectively improve the diagnosis rate of SCLC. TRAP1 may be secreted into the circulation by mature immune cells and participates in tumor immunity as a carrier of tumor antigens.

Synthesis of 3-Thiocyanobenzothiophene via Difunctionalization of Active Alkyne Promoted by Electrochemical-Oxidation.

A novel and green method for the synthesis of 3-thiocyanatobenzothiophenes via electrochemical-oxidation promoted difunctionalization of active alkyne has been developed. In this protocol, inexpensive and easily available potassium thiocyanate was chosen as the thiocyanation reagent, 2-alkynylthioanisoles as the substrates, a variety of 3-thiocyanatobenzothiophenes were obtained in moderate to good yields under oxidant- and catalyst-free conditions. Moreover, the continuous flow system has good applicability for this transformation, the use of continuous flow system has overcome the disadvantage of low efficiency in traditional electrochemical amplification, and realized the stable and excellent yields of target products in the scale-up reactions.

Spatio-Temporal Variation and Its Driving Forces of Soil Organic Carbon along an Urban-Rural Gradient: A Case Study of Beijing.

Rapid urbanization has reshaped land cover and the ecological environment, potentially improving or deteriorating soil organic carbon (SOC). However, the response of SOC to urbanization has not yet been fully exploited. Herein, by using the land-use transfer matrix, the Sen & Mann-Kendall tests, the Hurst index, and a geographical and temporal weighted regression (GTWR) model, as well as an urban-rural gradient perspective, we assessed the dynamic response of SOC to Beijing's urbanization from 2001 to2015 and identified the main drivers. The results found that SOC stock decreased by 7651.50 t C during the study period. SOC density varied significantly along an urban-rural gradient, with high value areas mainly being located in remote mountainous rural areas and low value areas mainly being located in urban areas on the plains. There was an uneven variation in SOC density across the urban-rural gradient, with suburban areas (25-40 km away from urban cores) losing the most SOC density while urban areas and rural areas remained relatively unchanged. GTWR model revealed the spatio-temporal non-flat stability of various driving forces. Precipitation, the proportion of forest, the proportion of grassland, the population, distance to the urban center, the slope, and the silt content are the main factors related to SOC stock change. As a result, we suggest policy makers reconceptualize the uneven variation in the SOC between urban and rural areas, emphasize suburban areas as a target for controlling SOC loss, and take into consideration the spatial and temporal heterogeneity of the factors influencing SOC stock when evaluating policies.

Robustly Stable Ferroelectric Polarization States Enable Long-Term Nonvolatile Storage against Radiation in HfO2-Based Ferroelectric Field-Effect Transistors.

The ferroelectric field-effect transistors (FeFETs) with HfO2-based ferroelectric layers in the gate stacks are emerging as one of the most promising candidates for the next-generation nonvolatile memory devices due to their scalability and compatibility with conventional Si technology. Moreover, owing to the high radiation hardness of the HfO2-based ferroelectric thin films, HfO2-based FeFETs have attracted great interest in the fields of radiation-hard (rad-hard) memory. However, the reliability of their memory states under irradiation, which represents the validity of the stored information, has not been investigated. Here, we focus on the impact of the total ionizing dose (TID) on erased and programmed states of HfO2-based FeFETs. The TID radiation (X-ray) characteristics of erased and programmed HfO2-based FeFETs are characterized using an on-site read operation. Both the erased and programmed states show robust stability under irradiation at a dose rate of 90 rad(Si)/s, and even at 230 rad(Si)/s, only the erased state shows a slight variation. The possible factors contributing to memory state degradation are discussed. Through the analysis of the threshold voltage shift and subthreshold swing evolution, as well as studies of ferroelectric polarization stability under radiation, it is revealed that the erased state degradation is caused by oxide-trapped charges rather than interface degradation or polarization switching. The physical mechanism of the difference in radiation-induced oxide-trapped charges buildup in programmed and erased FeFETs is analyzed to explain different TID radiation characteristics between them. Our work suggests that the HfO2-based FeFETs have great potential in radiation environment applications.

CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies and solid tumors. Here, we combined bioinformatics and experimental approaches to assess the potential of CEP192 as a prognostic and therapeutic target in HCC. CEP192 expression increased with tumor stage and was associated with poor clinicopathologic features, frequent recurrence, and higher mortality. Upon single-cell RNA sequencing, CEP192 was found to be involved in the proliferation and self-renewal of hepatic progenitor-like cells. This observation was further evidenced using CEP192 silencing, which prevented tumor cell proliferation and self-renewal by arresting cells in the G0/G1 phase of the cell cycle. Notably, CEP192 was highly correlated with multiple tumor-associated cytokine ligand-receptor axes, including IL11-IL11RA, IL6-IL6R, and IL13-IL13RA1, which could promote interactions between hepatic progenitor-like cells, PLVAP+ endothelial cells, tumor-associated macrophages, and CD4+ T cells. Consequently, CEP192 expression was closely associated with an immunosuppressive tumor microenvironment and low immunophenoscores, making it a potential predictor of response to immune checkpoint inhibitors. Taken together, our results unravel a novel onco-immunological role of CEP192 in establishing the immunosuppressive tumor microenvironment and provide a novel biomarker, as well as a potential target for therapeutic intervention of HCC.

m6A Regulator-Based Methylation Modification Patterns Characterized by Distinct Tumor Microenvironment Immune Profiles in Rectal Cancer.

Background: Previous studies reported the related role of RNA n6-methyladenosine (m6A) modification in tumorigenesis and development. However, it is not clear whether m6A modification also plays a potential role in the immune regulation of rectal cancer (RC) and the formation of tumor microenvironment. Methods: In this study, we screened 23 m6A regulatory factors from 369 rectal cancer specimens, further determined the modification patterns of m6A in RC, and systematically linked these modification patterns with the characteristics of TME cell infiltration. The principal component analysis (PCA) algorithm was used to evaluate the m6A modification pattern of a single tumor related to immune response. Results: Three different m6A modification patterns were found in the measurement results, which are related to different clinical results and biological pathways. TME identification results show that the identified m6A pattern is closely related to immune characteristics. According to the m6Ascore extracted from m6A-related signature genes, RC patients were divided into high and low score subgroups combined with tumor mutation burden. Patients with high tumor mutation burden and higher m6Ascore have a significant survival advantage and enhanced immune infiltration. Further analysis showed that patients with higher m6Ascore had higher PD-L1 expression levels and showed better immune response and lasting clinical benefits. Conclusions: M6A modification plays a crucial role in the formation of TME diversity and complexity. The evaluation of the m6A modification mode will help us to enhance our understanding of the characteristics of TME infiltration and provide new insights for more effective immunotherapy strategies.

Surgery Treatment of Primary Tumors of the Inferior Vena Cava.

Background: Primary tumor of the inferior vena cava is a rare tumor, which arises from the smooth muscle of vascular walls. Surgery appears the only curative treatment. However, the optimal surgical methods and surgical management are not well-studied. In this article, we reviewed the successful treatment experience of patients in our center who had resection of primary tumor of the inferior vena cava and reviewed the relevant literature. Methods: Four cases of patients who undergoing initial resection of primary tumors of the inferior vena cava from September 2017 to August 2021 in the Second Affiliated Hospital of Nanchang University were screened and followed up. They were discussed and cases reported in this field were reviewed. Results: Among the four patients, three of them were female. The median age of the disease is 53.75 years (range 45-60 years). After surgical treatment, tumors were removed in all patients, and some patients had reconstruction of inferior vena cava. There were no disease-specific deaths, no serious complications, and no recurrence during follow-up in these cases. Conclusions: Careful preoperative examination, correct surgical treatment methods, and multidisciplinary collaboration can lead to safe and successful operations, which improve the survival rate of patients.

Construction of a prognostic assessment model for colon cancer patients based on immune-related genes and exploration of related immune characteristics.

Objectives: To establish a novel risk score model that could predict the survival and immune response of patients with colon cancer. Methods: We used The Cancer Genome Atlas (TCGA) database to get mRNA expression profile data, corresponding clinical information and somatic mutation data of patients with colon cancer. Limma R software package and univariate Cox regression were performed to screen out immune-related prognostic genes. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used for gene function enrichment analysis. The risk scoring model was established by Lasso regression and multivariate Cox regression. CIBERSORT was conducted to estimate 22 types of tumor-infiltrating immune cells and immune cell functions in tumors. Correlation analysis was used to demonstrate the relationship between the risk score and immune escape potential. Results: 679 immune-related genes were selected from 7846 differentially expressed genes (DEGs). GO and KEGG analysis found that immune-related DEGs were mainly enriched in immune response, complement activation, cytokine-cytokine receptor interaction and so on. Finally, we established a 3 immune-related genes risk scoring model, which was the accurate independent predictor of overall survival (OS) in colon cancer. Correlation analysis indicated that there were significant differences in T cell exclusion potential in low-risk and high-risk groups. Conclusion: The immune-related gene risk scoring model could contribute to predicting the clinical outcome of patients with colon cancer.

Exploring the Potential Molecular Mechanism of Scutellaria baicalensis Georgi in the Treatment of Gastric Cancer Based on Network Pharmacological Analysis and Molecular Docking Technology.

Objective: To explore the molecular mechanism of Scutellaria baicalensis Georgi in treating gastric cancer by network pharmacological analysis and molecular docking. Methods: Taking Scutellaria baicalensis Georgi as the object, the active components and corresponding potential drug targets in Scutellaria baicalensis Georgi were obtained from the database of TCM Pharmacological System Analysis Platform (TCMSP). GeneCards/OMIM/DrugBank and other databases were used to collect gastric cancer-related genes, and the obtained genes were intersected with drug targets to obtain the target genes of Scutellaria baicalensis Georgi on gastric cancer. Furthermore, the interaction network of Scutellaria baicalensis Georgi-active ingredients-target-gastric cancer-related genes was constructed. Protein-protein interaction analysis and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on target genes. The PubChem website was used to screen the compounds corresponding to the target genes, and the target protein and 3D structure pdb format files were obtained from the PDB database. Finally, the molecular docking calculation was performed by the AutoDock Vina program. The in vivo cell experiments on the effect of Scutellaria baicalensis on proliferation and migration of gastric cancer cells were used to determine the therapeutic effect of Scutellaria baicalensis on gastric cancer, and the two genes ESR1 and FOS are the key targets of Scutellaria baicalensis on gastric cancer. Results: A total of 10 gastric cancer-related target genes were screened out, and Scutellaria baicalensis Georgi contained 10 active compounds targeting 10 gene sites. There are 30 effective compounds in Scutellaria baicalensis Georgi targeted to treat gastric cancer, and there are 91 corresponding targeting gene sites, involving a total of 10 pathways. The results of molecular docking show that ESR1, FOS, and Scutellaria baicalensis Georgi have good binding free energy and docking fraction. The docking fraction of FOS is -4.200 and the binding free energy is -27.893 kcal/mol. The docking fraction of ESR1 is -5.833 and the binding free energy is -30.001 kcal/mol. The effect of Scutellaria baicalensis Georgi on gastric cancer was verified by in vitro cell experiments and Western blotting. Conclusion: Scutellaria baicalensis Georgi can target and regulate multiple signal pathways by acting on ESR1 and FOS gene loci, thus having a potential therapeutic effect on gastric cancer.

Distribution, diagnosis, and analysis of related risk factors of multidrug-resistant organism in patients with malignant neoplasms.

OBJECTIVE: In this study, we sought to investigate the distribution characteristics, early diagnosis, and related risk factors of multidrug-resistant organism (MDRO) in patients with malignant tumors. METHODS: A total of 278 patients with malignant tumors and infections were selected in the Department of Oncology for retrospective study, including 128 MDRO patients and 150 non-MDRO patients. The markers of bacterial culture were detected, and the serum procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) levels were measured in patients' blood samples. The diagnostic value of PCT, CRP, and SAA for MDRO was evaluated, the distribution of MDRO in different years and different infection sites was analyzed, and the related risk factors of MDRO infection were studied. RESULTS: The PCT, CRP, and SAA in the MDRO group were significantly higher than those of the non-MDRO group (all P<0.001). The area under the curve of receiver operating characteristics for the diagnosis of MDRO by PCT, CRP, and SAA. The combination of the three was 0.792, 0.811, 0.755, and 0.842, respectively. The distribution of MDRO strains in different years was statistically different (P<0.05), as well as the distribution of MDRO in different infection sites (P<0.05). Multivariate regression analysis demonstrated that invasive operation, excessive bed rest, hypoproteinemia, PCT, and SAA were independent risk factors for MDRO infection in patients with malignant tumors (all P<0.05). CONCLUSION: The combination of CRP, PCT, and SAA displays a value for early diagnosis of MDRO infection. MDRO infections in malignant tumors mainly include carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Escherichia coli. There are differences in terms of MDRO strains in different years and different infection sites, and there are many risk factors regarding MDRO infection in patients with malignant tumors. Intervention should be taken in order to reduce the rate of MDRO infection.

Downregulation of PRAME Suppresses Proliferation and Promotes Apoptosis in Hepatocellular Carcinoma Through the Activation of P53 Mediated Pathway.

BACKGROUND/AIMS: The expression of PRAME and its role in hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to examine the functional role of PRAME in HCC development and exploring the molecular mechanism. METHODS: We first detected PRAME expression in 96 human HCC tissue samples and correlated with clinicopathological characteristics and prognosis of the patients. We then established stable HCC cell lines with PRAME overexpression and knockdown followed by functional analysis in vitro. Further, we examined the relationship between PRAME and p53 pathway in vitro by using Western blotting. Finally, PRAME expression was detected to evaluate its correlation with p-p53 and p53 pathway related apoptotic proteins in xenograft tumor mouse model using immunohistochemistry. RESULTS: PRAME expression was significantly higher in HCC tissues than in adjacent non-tumor tissues and their expression was positively correlated with alpha fetoprotein levels and tumor size. In addition, PRAME expression was associated with AJCC stage and is a potential biomarker of poor prognosis regarding 5-year overall survival in HCC. In vitro studies, we found that PRAME expression was higher in HCC cell lines than in normal hepatic cell line. Inhibited cell proliferation and increased cell apoptosis was observed in PRAME knockdown HCC cells. Futher, increased cell apoptosis was correlated with the proportion of cells in G0/G1 stage, activated p53 mediated apoptosis, and increased cyclin p21 expression. Xenograft analysis in nude mice also found that PRAME knockdown inhibited tumorigenesis while PRAME overexpression had opposite effect. CONCLUSIONS: In HCC, PRAME serves as a potential biomarker for poor prognosis and novel therapeutic target in treating this cancer. PRAME is a potential biomarker of poor prognosis in HCC. PRAME surpresses HCC cell death in vitro and in vivo by regulating p53 apoptotic signaling and may serve as a potential therapeutic target in HCC.

Diagnostic and prognostic roles of serum vitronectin in hepatitis B-related hepatocellular carcinoma.

BACKGROUND: Vitronectin (VN) might be involved in the progression of hepatocellular carcinoma (HCC). OBJECTIVE: This study was designed to evaluate the diagnostic and prognostic value of serum vitronectin among HCC patients. METHODS: A total of 105 patients with HCC, 91 with liver cirrhosis, 102 with chronic hepatitis, and 100 healthy subjects were recruited. Serum VN and alpha-fetoprotein (AFP) levels were measured. RESULTS: Serum VN levels were significantly higher in HCC patients than in the other groups. Based on area under receiver operating characteristic curve, serum VN had similar diagnostic value, compared with serum AFP, in distinguishing HCC from the groups, and also improved the diagnostic value of AFP alone. Serum VN levels were associated with the degree of histological differentiation, multiple foci, vascular tumor thrombosis and tumor node metastasis stage. Serum VN was an independent predictor for early recurrence and disease-free survival. Moreover, serum VN possessed similar prognostic predictive performance as compared to serum AFP and also significantly enhanced the prognostic value of AFP alone. CONCLUSIONS: Elevated serum VN levels represented high diagnostic value and had close relation to clinicopathological factors and early recurrence, suggesting that serum VN might be a useful diagnostic and prognostic marker for HCC.

Study on protecting effects of baicalin and octreotide on hepatic injury in rats with severe acute pancreatitis.

AIM: To investigate the protective effects and mechanisms of baicalin and octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, baicalin treated group, and octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and caspase-3, and changes of apoptotic indexes. RESULTS: Rat survival at 12 h, expression levels of Bax, caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both baicalin and octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, caspase-3 protein, and inducing apoptosis.