Synthesis of Unsymmetrical Trisulfides from S-Substituted Sulphenylthiosulphates.

Trisulfide unit is widely found in natural products and has garnered attention due to the unique pharmacological and physiochemical properties. However, despite limited progress, widely applicable approaches for constructing unsymmetrical trisulfides have so far remain scarce. In this work, an easy-to-prepare, solid-state and scalable reagent, S-substituted sulphenylthiosulphate, has been developed for the divergent synthesis of unsymmetrical trisulfides. Alkyl electrophile substrates, including bromides, chlorides, iodides and tosylates, with diverse substituents are smoothly converted to the corresponding trisulfides with S-substituted sulphenylthiosulphates and thiourea as another sulfur source. Furthermore, the late-stage modification of drug molecules was successfully achieved through this method.

Glucocorticoids promote the development of azoxymethane and dextran sulfate sodium-induced colorectal carcinoma in mice.

BACKGROUND: Stress has been suggested as a promoter of tumor growth and development. Glucocorticoids (GCs) are the main stress hormones and widely prescribed as drugs. However, the effect of GCs on the development and progression of colorectal carcinoma (CRC) is unclear. METHODS: We evaluated the effect of corticosterone (CORT) on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in the colorectum of C57BL/6 strain mice. Plasma level of CORT was detected by radioimmunoassay. The expression of proliferation markers (Ki-67 and PCNA), nuclear factor (NF)-κB p65 and phosphoto-p65 (P-p65), as well as cyclooxygenase (COX)-2 were determined by immunohistochemistry. Inflammation in colorectum was evaluated by histopathology. RESULTS: CORT feeding in drinking water of mice not only significantly elevated plasma CORT concentration, but also significantly increased the incidence and neoplasms burden (number and size of neoplasms) in colorectum. CORT also significant enhanced the expression of cell proliferation marker (Ki-67 and PCNA), NF-κB p65 and P-p65 as well as COX-2 in colorectal neoplasm of AOM/DSS-treated mice. CONCLUSION: In this study, we have found for the first time that CORT at stress level potentially promotes the growth and development of AOM/DSS-induced colorectal adenoma and carcinoma in mice. Up-regulation of NF-κB and COX-2 may be involved in the promoting effect of CORT.

Performance Analysis of Positioning Solution Using Low-Cost Single-Frequency U-Blox Receiver Based on Baseline Length Constraint.

With the rapid development of the satellite navigation industry, low-cost and high-precision Global Navigation Satellite System (GNSS) positioning has recently become a research hotspot. The traditional application of GNSS may be further extended thanks to the low cost of measuring instruments, but effective methods are also desperately needed due to the low quality of the data obtained using these instruments. Thus, in this paper, we propose the analysis and evaluation of the ambiguity fixed-rate and positioning accuracy of single-frequency Global Positioning System (GPS) and BeiDou Navigation Satellite System (BDS) data, collected from a low-cost u-blox receiver, based on the Constrained LAMBDA (CLAMBDA) method with a baseline length constraint, instead of the classical LAMBDA method. Three sets of experiments in different observation environments, including two sets of static short-baseline experiments and a set of dynamic vehicle experiments, are adopted in this paper. The experiment results show that, compared to classical LAMBDA method, the CLAMBDA method can significantly improve the success rate of the GNSS ambiguity resolution. When the ambiguity is fixed correctly, the baseline solution accuracy reaches 0.5 and 1 cm in a static scenario, and 1 and 2 cm on a dynamic platform.

A Triple Checked Partial Ambiguity Resolution for GPS/BDS RTK Positioning.

Reliable and accurate carrier phase ambiguity resolution is the key to high-precision Global Navigation Satellite System (GNSS) positioning and application. With the fast development of modern GNSS, the increased number of satellites and ambiguities makes it hard to fix all ambiguities completely and correctly. The partial ambiguity fixing technique, which selects a suitable subset of high-dimensional ambiguities to fix, is beneficial for improving the fixed success rate and reliability of ambiguity resolution. In this contribution, the bootstrapping success rate, bounded fixed-failure ratio test, and the new defined baseline precision defect are used for the selection of the ambiguity subset. Then a model and data dual-driven partial ambiguity resolution method is proposed with the above three checks imposed on it, which is named the Triple Checked Partial Ambiguity Resolution (TC-PAR). The comprehensive performance of TC-PAR compared to the full-fixed LAMBDA method is also analyzed based on several criteria including the fixed rate, the fixed success rate and correct fixed rate of ambiguity as well as the precision defect and RMS of the baseline solution. The results show that TC-PAR could significantly improve the fixed success rate of ambiguity, and it has a comparable baseline precision to the LAMBDA method, both of which are at centimeter level after ambiguities are fixed.

Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy.

Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1)-excision repair cross-complimentary group 4 (ERCC4) genes have been implicated in the prognosis of various cancers. We conducted a cohort study to investigate the role of ERCC1-ERCC4 gene polymorphisms on the response to chemotherapy and the role of these two gene polymorphisms on the clinical outcomes of gastric cancer. Four hundred forty-seven patients with newly diagnosed and histopathologically confirmed primary gastric cancer were collected in our study and were followed up until March 2012. ERCC1 (rs11615, rs3212986C>A, and rs2298881) and ERCC4 (rs226466C>G, rs2276465, and rs6498486) were selected and genotyped. The overall chemotherapy response rate for treatment was 68 %. Carriers of the rs11615 TT and T allele and ERCC1 rs2298881 CC and C allele had a marginally significantly higher response rate to the chemotherapy. In the Cox proportional hazard model, the hazard ratios (HRs) for overall survival (OS) in patients carrying ERCC1 rs11615 TT genotype and T allele were 0.53 (0.29-0.95) and 0.63 (0.42-0.94), respectively. Similarly, we found a significant decreased risk of death from gastric cancer among patients carrying ERCC1 rs2298881 CC genotype and C allele when compared with CC genotype, and HRs (95% confidence interval (CI)) of OS were 0.50 (0.24-0.98) and 0.62 (0.40-0.96), respectively. Moreover, individuals carrying ERCC1 rs11615 T allele and rs2298881 C allele could decrease a 0.62-fold risk of death from gastric cancer. This study reported a carriage of ERCC1 rs11615, and rs2298881 polymorphism can be used as a predictor of response to folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX)-based chemotherapy in gastric cancer patients.

Expression of orphan nuclear receptor NR4A2 in gastric cancer cells confers chemoresistance and predicts an unfavorable postoperative survival of gastric cancer patients with chemotherapy.

BACKGROUND: NR4A2, an orphan nuclear receptor essential in the generation of dopaminergic neurons, has been recently linked to inflammation and cancer. This study sought to identify the role of NR4A2 on chemoresistance and postoperative prognosis of gastric cancer (GC). METHODS: NR4A2 was transfected into GC cells to investigate its effects on chemoresistance to 5-fluorouracil and the tumorigenicity in nude mice. This study also investigated prostaglandin E2 (PGE2 )-induced NR4A2 expression and its effect on chemoresistance. Surgical specimens from patients with stage I through III GC were examined immunohistochemically for NR4A2 expression. Median follow-up time was 76 months for 245 patients. RESULTS: Ectopic expression of NR4A2 significantly increased the chemoresistance and attenuated 5-fluorouracil-induced apoptosis. Transient treatment of GC cells with PGE2 significantly upregulated NR4A2 expression via the protein kinase A pathway and increased the chemoresistance. Ectopic expression of NR4A2 significantly increased the tumorigenicity. In clinical samples, NR4A2 was preferentially expressed in lymphocytes and epithelial cytoplasm in adjacent mucosa. High expression of NR4A2 (immunoreactive score ≥ 3) in cancer cells significantly predicted an unfavorable postoperative disease-specific survival of patients with stage I to III GC (P = .011), especially for those who received 5-fluorouracil-based chemotherapy (P = .016). This effect was not found in those without the chemotherapy. In multivariate Cox analyses, age, TNM (tumor/node/metastasis) stage, and high NR4A2 expression significantly predicted an unfavorable postoperative survival. CONCLUSIONS: High NR4A2 expression in GC cells confers chemoresistance, attenuates 5-fluorouracil-induced apoptosis, and predicts an unfavorable survival, especially for those who received chemotherapy. NR4A2 might serve as a prognostic and predictive factor and therapeutic target for patients with GC. Cancer 2013;119:3436-3445.. © 2013 American Cancer Society.

Genetic polymorphisms of XRCC1 gene and susceptibility to gastric cancer in Chinese Han population.

This study aims to evaluate whether the c.1471G > A and c.1686C > G genetic polymorphisms of XRCC1 gene influencing gastric cancer susceptibility. A total of 813 subjects with Chinese Han ethnicity were enrolled. Our data suggest that the allele and genotype frequencies are significantly different from gastric cancer patients with cancer-free controls. We find that c.1471G > A and c.1686C > G genetic polymorphisms statistically increase the risk of gastric cancer. Our findings indicate these two genetic polymorphisms are related with the susceptibility to gastric cancer, and could be used as molecular markers for detecting gastric cancer in Chinese Han ethnicity.

D9S168 microsatellite alteration predicts a poor prognosis in patients with clear cell renal cell carcinoma and correlates with the down-regulation of protein tyrosine phosphatase receptor delta.

BACKGROUND: The role of microsatellite alterations in surgically excised tumors in predicting the prognosis of patients with clear cell renal cell carcinoma (ccRCC) remains largely unknown. METHODS: Specimens from 93 patients with sporadic ccRCC were used to screen microsatellite alterations using 12 markers on chromosomes 3p, 9p, and 14q according to disease stage. Survival was evaluated by using the Kaplan-Meier method and Cox regression analysis. The expression of targeted genes was examined using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Of the markers that were screened, D9S168 (9p23-22) had the highest frequency (36.9%) of microsatellite alteration in the specimens. D9S168 alterations were frequent in high-stage tumors. Seventy-eight patients who had ccRCC without distant metastasis at the time of surgery were followed for a median of 31.7 months. Overall survival and disease-free survival were poorer for patients with D9S168 alteration than for those without alteration (P < .001 for each; log-rank test). Cox regression analysis indicated that D9S168 alteration was associated independently with cancer-related death (P = .010). The D9S168 alteration, which was located at the 5'-untranslated region of a gene that encodes protein tyrosine phosphatase (PTP) receptor delta (PTPRD), was associated significantly with low expression of PTPRD at the messenger RNA level (P = .001). Immunohistochemistry revealed that the expression of PTPRD was strong in normal kidney proximal tubular epithelial cells, from which ccRCC originated, and was greatly down-regulated in ccRCC (P < .001; Wilcoxon rank-sum test). CONCLUSIONS: D9S168 microsatellite alteration in tumors predicted a poor prognosis for patients with ccRCC after curative nephrectomy. The authors concluded that PTPRD is a putative tumor suppressor in ccRCC and has therapeutic potential.

Diagnostic and Prognostic Values of MANF Expression in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and its prognosis is still poor. Mesencephalic astrocyte-derived neurotrophic factor (MANF) plays a key role in endoplasmic reticulum stress. ER stress plays a key role in HCC carcinogenesis. To confirm the clinical and prognostic value of MANF in HCC, we investigated the expression level of MANF in HCC as recorded in databases, and the results were verified by experiment. Survival analysis was probed by the Kaplan-Meier method. Cox regression models were used to ascertain the prognostic value of MANF in HCC tissue microarray. The diagnostic value of MANF in HCC was evaluated by receiver operating characteristic curve analysis. Potential correlation between MANF and selected genes was also analyzed. Results showed that MANF was overexpressed in HCC. Patients with high MANF expression levels had a worse prognosis and higher risk of tumor recurrence. Furthermore, the expression level of MANF had good diagnostic power. Correlation analysis revealed potential regulatory networks of MANF in HCC, laying a foundation for further study of the role of MANF in tumorigenesis. In conclusion, MANF was overexpressed in HCC and related to the occurrence and development of HCC. It is a potential diagnostic and prognostic indicator of HCC.

Mesencephalic Astrocyte-Derived Neurotrophic Factor, a Prognostic Factor of Cholangiocarcinoma, Affects Sorafenib Sensitivity of Cholangiocarcinoma Cells by Deteriorating ER Stress.

PURPOSE: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignant tumor characterized by high malignancy and poor prognosis. Although the efficacy of sorafenib against cholangiocarcinoma cell lines has been demonstrated in vivo and in vitro, limited clinical data are available on the efficacy of sorafenib in patients with cholangiocarcinoma. Sorafenib can enhance endoplasmic reticulum (ER) stress-mediated apoptosis, and ER stress and unfolded protein response are also the mechanisms by which cancer cells resist drug therapy. Mesencephalic astrocyte-derived neurotrophic factor (MANF), initially identified as a neurotrophic factor, can be regulated by ER stress activation. There are no available studies on the diagnostic value and therapeutic significance of MANF in ICC. Hence, the purpose of this study was to evaluate the role of MANF in cholangiocarcinoma, investigating the possibility of whether sorafenib could become a reliable strategy for cholangiocarcinoma therapy. METHODS: In this study, the expression level of MANF in ICC patients was investigated by bioinformatic analysis and the results were verified by tissue microarray assay. Cholangiocarcinoma cell lines were also used to determine how MANF regulates the therapeutic effect of sorafenib and to identify the underlying mechanisms. RESULTS: The results showed that MANF was correlated with poor prognosis and MANF knockdown could facilitate sorafenib-mediated apoptosis and increase the sensitivity of sorafenib treatment by activating excessive ER stress. CONCLUSION: MANF is a prognostic marker of cholangiocarcinoma. MANF knockdown increases sorafenib-mediated ER stress and apoptosis in the cholangiocarcinoma cell lines. This mechanism may lead to a new therapeutic strategy in cholangiocarcinoma.

Screening and Identification of Key Biomarkers for Bladder Cancer: A Study Based on TCGA and GEO Data.

Bladder cancer (BLCA) is a common malignant cancer, and it is the most common genitourinary cancer in the world. The recurrence rate is the highest of all cancers, and the treatment of BLCA has only slightly improved over the past 30 years. Genetic and environmental factors play an important role in the development and progression of BLCA. However, the mechanism of cancer development remains to be proven. Therefore, the identification of potential oncogenes is urgent for developing new therapeutic directions and designing novel biomarkers for the diagnosis and prognosis of BLCA. Based on this need, we screened overlapping differentially expressed genes (DEG) from the GSE7476, GSE13507, and TCGA BLCA datasets. To identify the central genes from these DEGs, we performed a protein-protein interaction network analysis. To investigate the role of DEGs and the underlying mechanisms in BLCA, we performed Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) analysis; we identified the hub genes via different evaluation methods in cytoHubba and then selected the target genes by performing survival analysis. Finally, the relationship between these target genes and tumour immunity was analysed to explore the roles of these genes. In summary, our current studies indicate that both cell division cycle 20 (CDC20) and abnormal spindle microtubule assembly (ASPM) genes are potential prognostic biomarkers for BLCA. It may also be a potential immunotherapeutic target with future clinical significance.

Identification of novel hub genes associated with liver metastasis of gastric cancer.

Understanding hub genes involved in gastric cancer (GC) metastasis could lead to effective approaches to diagnose and treat cancer metastasis. In this study, 272 differentially expressed genes between synchronous liver metastasis and the paired GC were selected from microarray assays. KEGG pathway analysis indicated that of 13 enriched pathways, 8 were involved in cancer metastasis. Literature-based annotations showed that the differentially expressed genes significantly enriched known metastasis-related genes. With the use of protein-protein interaction network, we found a subnetwork significantly enriching the metastasis-related genes and hubs. Unannotated hubs in this subnetwork were predicted to be novel metastasis-associated genes. Nine hubs in this subnetwork were validated by using quantitative RT-PCR, and 4 hubs were further validated by immunohistochemistry. NR4A2 was significantly down-regulated in synchronous liver metastasis compared with the paired GC at both transcriptional and translational levels. NR4A2 immunostaining was apparent in the mesenchymal cells of pathologically normal gastric mucosa and in the epithelial cells of primary GC. HSP90AA1 was not only up-regulated in the metastatic GC compared with primary GC at both transcriptional and translational levels, but also up-regulated in primary GC compared with the normal mucosa at the translational level. NR4A2, NR3C1, ARF3, XAB2, and alternatively spliced variants of NR4A2, SP8 and SP-novel, were significantly down-regulated, whereas CCNE1 significantly up-regulated, in primary GC compared with the normal gastric mucosa. Conclusively, NR4A2 and HSP90AA1 stand out as promising diagnostic markers and therapeutic targets for liver metastasis of GC. CCNE1 and NR3C1 indicate primary GC, rather than distant metastasis.

[Influences of the phosphorylation of p38 mitogen activated protein kinase on gene expression of tumor necrosis factor-alpha in multiple organ dysfunction syndrome in pigs].

OBJECTIVE: To investigate that the phosphorylation of the p38 mitogen activated protein kinase (p38MAPK) influences gene expression of tumor necrosis factor-alpha (TNF-alpha) in multiple organ dysfunction syndrome (MODS) in pigs. METHODS: Thirty pigs were divided into MODS group and control group, and an animal model of MODS of "two-hit" injury, including hemorrhagic shock and endotoxemia, was reproduced. The content of p38MAPK's phosphorylation was assessed with Western blotting. TNF-alpha mRNA in peripheral blood monocytes was assayed with real time-polymerase chain reaction (RT-PCR). TNF-alpha was monitored in the peripheral blood plasma with enzyme linked immunosorbent assay (ELISA). RESULTS: Phosphorylation of p38MAPK was obviously increased in extent, which enhanced gene expression of TNF-alpha and then secretion of TNF-alpha by the peripheral blood mononuclear cell in MODS, and the differences were statistically significant compared with that of control group (P<0.05 or P<0.01). CONCLUSION: p38MAPK's phosphorylation is important in pathogenesis of MODS, and phosphorylation of p38MAPK can enhance TNF-alpha mRNA transcription and secretion of TNF-alpha from peripheral blood mononuclear cells, which is the mechanism of increased TNF-alpha in MODS.

The circular RNA PVT1/miR-203/HOXD3 pathway promotes the progression of human hepatocellular carcinoma.

Accumulating evidence suggests that circular RNAs (circRNAs) play important roles in various physiological and pathological processes. In the present study, we explored the role of circRNA PVT1 in hepatocellular carcinoma (HCC). qRT-PCR was performed to detect the relative expression of circPVT1 in HCC tissues and cell lines. The oncogenic roles of circPVT1 in HCC were evaluated by cell counting kit-8 (CCK-8) assay, ethynyl deoxyuridine (EdU) incorporation assays, transwell assays, flow cytometry and in vivo xenograft growth. Furthermore, bioinformatics, luciferase reporter assays and rescue experiments were conducted to determine the underlying mechanism of circPVT1 in HCC. Enhanced circPVT1 expression was detected in HCC tissues, which was closely associated with poor prognosis of patients with HCC. Knockdown of circPVT1 decreased the proliferation and migration ability of HCC cell lines in vitro Conversely, upregulation of circPVT1 improved the growth and migration in HCC cells. Mechanistically, we found that circPVT1 could bind directly to miR-203 and contributed to the initiation and progression of HCC by regulating miR-203/homebox D3 (HOXD3) pathway. In conclusion, our study reveals that circPVT1 participates in the progression of HCC through the miR-203/homeobox D3 (HOXD3) pathway and might represent a potential therapeutic target for HCC treatment.

Genome-wide screening identifies oncofetal lncRNA Ptn-dt promoting the proliferation of hepatocellular carcinoma cells by regulating the Ptn receptor.

Oncofetal genes are genes that express abundantly in both fetal and tumor tissues yet downregulated or undetected in adult tissues, and can be used as tumor markers for cancer diagnosis and treatment. Meanwhile, long noncoding RNAs (lncRNAs) are known to play crucial roles in the pathogenesis of hepatocellular carcinoma (HCC), including tumor growth, proliferation, metastasis, invasion, and recurrence. We performed a genome-wide screening using microarrays to detect the lncRNA expression profiles in fetal livers, adult livers, and liver cancer tissues from mice to identify oncofetal lncRNAs in HCC. From the microarray data analysis, we identified lncRNA Ptn-dt as a possible oncofetal gene. Both in vitro and in vivo experiments results confirmed that overexpression of Ptn-dt significantly promoted the proliferation of mouse HCC cells. RNA pulldown assay showed that Ptn-dt could interact with the HuR protein. Interestingly, miR-96 binds with HuR to maintain its stability as well. Overexpression of lncRNA Ptn-dt led to the downregulation of miR-96, which might be due to the interaction between Ptn-dt and HuR. Meanwhile, previous studies have reported that Ptn can promote tumor growth and vascular abnormalization via anaplastic lymphoma kinase (Alk) signaling. In our study, we found that overexpression of Ptn-dt could promote the expression of Alk through repressing miR-96 via interacting with HuR, thus enhancing the biologic function of Ptn. In summary, a new oncofetal lncRNA Ptn-dt is identified, and it can promote the proliferation of HCC cells by regulating the HuR/miR-96/Alk pathway and Ptn-Alk axis.

Global analysis of metastasis-associated gene expression in primary cultures from clinical specimens of clear-cell renal-cell carcinoma.

Metastatic clear-cell renal-cell carcinoma (ccRCC) has a poor prognosis and unpredictable course, and there are no molecular markers that reliably predict ccRCC metastasis. In this study, ccRCC specimens from 84 patients were directly cultured in vitro. Primary cultures from 38 of 94 specimens contained more than 90% tumor cells at the fourth passage. After identification by immunostaining, the primary cultures of metastatic and nonmetastatic ccRCC specimens from the age- and gender-matched patients were subjected to cDNA microarray assays. A total of 842 differentially expressed genes with a FDR (false discovery rate) of 4.79% were identified. Pathway analysis and co-occurrence with "cancer", "metastasis" and "invasion" in the literature annotations functionally enriched the 842 genes and provided an indication of the reliability of our microarray assays. Novel genes associated with metastasis were selected based on protein-protein interactions between 205 differentially expressed genes that co-occurred with "metastasis" and those that did not co-occur with "metastasis" on Medline, and the results of co-expression analysis between the co-occurred genes and unpublished genes. FSTL1, AV722783, SLC15A1, DDX17, ORC2L and PKMYT1 were found to be potential ccRCC metastasis-associated novel genes, according to expression patterns in cultures and tumor tissues. Interestingly, the upregulated genes (CAV1, PKMYT1 and ORC2L) were also upregulated and the downregulated genes (FSTL1, GSTM3, CYR61, SLC15A1 and AV722783) were also downregulated in the primary ccRCC specimens compared with expression in adjacent renal tissues in 37 patients. This study has identified new candidate biomarkers and targets for the early diagnosis and treatment of ccRCC metastasis.

The prevalence of Th17 cells in patients with gastric cancer.

Th17 cells have emerged as an important mediator in inflammatory and autoimmune diseases. However, recent studies suggest a potential impact of Th17 cells on tumor. The current study was designed to investigate the possible involvement of Th17 cells in gastric cancer. Compared with healthy volunteers, patients with gastric cancer had a higher proportion of Th17 cells in peripheral blood. Notably, the increased prevalence of Th17 cells was associated with clinical stage. In addition, increased populations of Th17 cells were present in tumor-draining lymph nodes with advanced disease. Furthermore, the mRNA expression levels of Th17-related factors (IL-17, IL-23p19, and RORC) in tumor tissues and the serum concentrations of IL-17 and IL-23 cytokines were significantly increased in patients with advanced gastric cancer. The results indicate that Th17 cells may contribute to gastric cancer pathogenesis.

Clinical management of abdominal trauma.

OBJECTIVE: To improve the prognosis of patients with abdominal trauma. METHODS: Between January 1993 and December 2005, 415 patients were enrolled in this research. The patients consisted of 347 males and 68 females with mean age of 36 years (ranging from 3-82 years). All abdominal traumas consisted of closed traumas (360 cases, 86.7%) and open traumas (55 cases, 13.3%). RESULTS: A total of 407 cases (98.1%) were fully recovered from trauma and the other 8 cases (1.9%) died of multiple injuries. The mean injury severity score (ISS) of all patients was 22 while the mean ISS of the patients who died in hospital was 42. Postoperative complications were seen in 9 patients such as infection of incisional wounds (6 cases), pancreatic fistula (2 cases) and intestinal fistula (1 case). All these postoperative complications were cured by the conservative treatment. CONCLUSION: Careful case history inquisition and physical examination are the basic methods to diagnose abdominal trauma. Focused abdominal ultrasonography is always the initial imaging examination because it is non-invasive and can be performed repeatedly with high accuracy. The doctors should consider the severity of local injuries and the general status of patients during the assessment of abdominal trauma. The principle of treatment is to save lives at first, then to cure the injuries. Unnecessary laparotomy should be avoided to reduce additional surgical trauma.

Integrated miRNA-risk gene-pathway pair network analysis provides prognostic biomarkers for gastric cancer.

PURPOSE: This study aimed to identify molecular prognostic biomarkers for gastric cancer. METHODS: mRNA and miRNA expression profiles of eligible gastric cancer and control samples were downloaded from Gene Expression Omnibus to screen the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs), using MetaDE and limma packages, respectively. Target genes of the DEmiRs were also collected from both predictive and experimentally validated target databases of miRNAs. The overlapping genes between selected targets and DEGs were identified as risk genes, followed by functional enrichment analysis. Human pathways and their corresponding genes were downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for the expression analysis of each pathway in gastric cancer samples. Next, co-pathway pairs were selected according to the Pearson correlation coefficients. Finally, the co-pathway pairs, miRNA-target pairs, and risk gene-pathway pairs were merged into a complex interaction network, the most important nodes (miRNAs/target genes/co-pathway pairs) of which were selected by calculating their degrees. RESULTS: Totally, 1,260 DEGs and 144 DEmiRs were identified. There were 336 risk genes found in the 9,572 miRNA-target pairs. Judging from the pathway expression files, 45 co-pathway pairs were screened out. There were 1,389 interactive pairs and 480 nodes in the integrated network. Among all nodes in the network, focal adhesion/extracellular matrix-receptor interaction pathways, CALM2, miR-19b, and miR-181b were the hub nodes with higher degrees. CONCLUSION: CALM2, hsa-miR-19b, and hsa-miR-181b might be used as potential prognostic targets for gastric cancer.

Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche.

Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high-stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/ß-catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC.