Factors associated with spatial distribution of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) was firstly identified in mainland China in 2009 and the geographic distribution has expanded in recent years. In this study, we constructed ecological niche models (ENM) of SFTS with meteorological factors, environmental factor, and density of domestic animals using MaxEnt. We found four significant associated factors including altitude, yearly average temperature, yearly accumulated precipitation, and yearly average relative humidity which accounted for 94.1% percent contribution. SFTS occurrence probability was high when altitude was between -100 m and 100 m, and the probability was nearly 0 when altitude was beyond 3000 m. Response curves of SFTS to the yearly average temperature, yearly accumulated precipitation, and yearly average relative humidity were all reversed V-shape. SFTS occurrence probability was high where the yearly average temperature, yearly accumulated precipitation, and yearly relative humidity were 12.5-17.5 °C, 700-2250 mm and 63-82%, respectively. ENMs predicted that the potential high-risk areas were mainly distributed in eastern areas and central areas of China. But there were some predicted potential high-risk areas where no SFTS case was reported up to date. More researches should be done to make clear whether SFTS case had occurred in these areas.

Distinctive evolutionary pattern of organelle genomes linked to the nuclear genome in Selaginellaceae.

Plastids and mitochondria are endosymbiotic organelles that store genetic information. The genomes of these organelles generally exhibit contrasting patterns regarding genome architecture and genetic content. However, they have similar genetic features in Selaginellaceae, and little is known about what causes parallel evolution. Here, we document the multipartite plastid genomes (plastomes) and the highly divergent mitochondrial genomes (mitogenomes) from spikemoss obtained by combining short- and long-reads. The 188-kb multipartite plastome has three ribosomal operon copies in the master genomic conformation, creating the alternative subgenomic conformation composed of 110- and 78-kb subgenomes. The long-read data indicated that the two different genomic conformations were present in almost equal proportions in the plastomes of Selaginella nipponica. The mitogenome of S. nipponica was assembled into 27 contigs with a total size of 110 kb. All contigs contained directly arranged repeats at both ends, which introduced multiple conformations. Our results showed that plastomes and mitogenomes share high tRNA losses, GC-biased nucleotides, elevated substitution rates and complicated organization. The exploration of nuclear-encoded organelle DNA replication, recombination and repair proteins indicated that, several single-targeted proteins, particularly plastid-targeted recombinase A1, have been lost in Selaginellaceae; conversely, the dual-targeted proteins remain intact. According to the reported function of recombinase A1, we propose that the plastomes of spikemoss often fail to pair homologous sequences during recombination, and the dual-targeted proteins play a key role in the convergent genetic features of plastomes and mitogenomes. Our results provide a distinctive evolutionary pattern of the organelle genomes in Selaginellaceae and evidence of their convergent evolution.

Quantitative proteomics reveals the regulatory networks of circular RNA BTBD7_hsa_circ_0000563 in human coronary artery.

BACKGROUND: BTBD7_hsa_circ_0000563, which is located on chromosome 14, contains conserved binding sites with miR-155/130a and RNA-binding proteins according to bioinformatic prediction. We investigated the association of BTBD7_hsa_circ_0000563 expression in coronary artery segments with atherosclerotic stenosis and identified the proteome-wide BTBD7_hsa_circ_0000563-regulated proteins in human coronary artery. METHODS: The atherosclerotic grade and extent in coronary artery segments were determined by hematoxylin and eosin staining. BTBD7_hsa_circ_0000563 expression in eight coronary artery segments from one patient was quantified by RT-qPCR assay. A proteomic approach was adopted to reveal significant differences in protein expression between among four groups differing in their BTBD7_hsa_circ_0000563 expression levels. RESULTS: The RT-qPCR assay revealed that coronary artery segments with severe atherosclerotic stenosis had significantly low BTBD7_hsa_circ_0000563 levels. The proteomic analysis identified 49 differentially expressed proteins among the segment groups with different BTBD7_hsa_circ_0000563 expression levels, of which 10 were downregulated and 39 were upregulated with increases in the BTBD7_hsa_circ_0000563 level. The 10 downregulated proteins were P61626 (LYSC_HUMAN), P02760 (AMBP_HUMAN), Q02985 (FHR3_HUMAN), P01701 (LV151_HUMAN), P06312(KV401_HUMAN), P01624 (KV315_HUMAN), P13671 (CO6_HUMAN), P01700(LV147_HUMAN), Q9Y287(ITM2B_HUMAN), and A0A075B6I0 (LV861_HUMAN). The top 10 upregulated proteins were Q92552 (RT27_HUMAN), Q9UJY1(HSPB8_HUMAN), Q9Y235(ABEC2_HUMAN), P19022 (CADH2_HUMAN), O43837(IDH3B_HUMAN), Q9H479(FN3K_HUMAN), Q9UM22(EPDR1_HUMAN), P48681(NEST_HUMAN), Q9NRP0(OSTC_HUMAN), and Q15628(TRADD_HUMAN). CONCLUSION: BTBD7_hsa_circ_0000563 is involved in the atherosclerotic changes in human coronary artery segments. Verification, mechanistic, and function studies are needed to confirm whether patients with coronary artery disease would benefit from such personalized medicine in the future.

Circular RNA profile in coronary artery disease.

Circular RNAs (circRNAs) are potential biomarkers and therapeutic targets of coronary artery disease due to their high stability, covalently closed structure. And implied roles in gene regulation. The aim of this study was to identify and characterize circRNAs from human coronary arteries. Epicardial coronary arteries were removed during the autopsy of an 81-year-old man who died from heart attack. The natural history and histological classification of atherosclerotic lesions in coronary artery segments were analyzed by hematoxylin and eosin staining, and their circRNA expression profiles were characterized by RNA sequencing. RNA sequencing identified 1259 annotated and 381 novel circRNAs. Combined with the results of histologic examination, intersection analysis identified 54 upregulated and 12 downregulated circRNAs, representing 4.0% of the total number. Coronary artery segments with or without severe atherosclerosis showed distinctly different circRNA profiles on the basis of hierarchical clustering. Our results suggest that these 66 circRNAs contribute to the pathology underlying coronary artery atherosclerosis and may serve as diagnostic or therapeutic targets in coronary artery disease.

Meta-analysis of microarray datasets identify several chromosome segregation-related cancer/testis genes potentially contributing to anaplastic thyroid carcinoma.

AIM: Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid malignancy. Identification of novel drug targets is urgently needed. MATERIALS & METHODS: We re-analyzed several GEO datasets by systematic retrieval and data merging. Differentially expressed genes (DEGs) were filtered out. We also performed pathway enrichment analysis to interpret the data. We predicted key genes based on protein-protein interaction networks, weighted gene co-expression network analysis and genes' cancer/testis expression pattern. We also further characterized these genes using data from the Cancer Genome Atlas (TCGA) project and gene ontology annotation. RESULTS: Cell cycle-related pathways were significantly enriched in upregulated genes in ATC. We identified TRIP13, DLGAP5, HJURP, CDKN3, NEK2, KIF15, TTK, KIF2C, AURKA and TPX2 as cell cycle-related key genes with cancer/testis expression pattern. We further uncovered that most of these putative key genes were critical components during chromosome segregation. CONCLUSION: We predicted several key genes harboring potential therapeutic value in ATC. Cell cycle-related processes, especially chromosome segregation, may be the key to tumorigenesis and treatment of ATC.

Prognostic Value of C-met Expression in Cholangiocarcinoma.

AIM: To explore the relationship of clinicopathological features and the proteins of C-met expression in the prognosis of cholangiocarcinoma. METHODS: Clinical data and the completed follow-up information of patients with cholangiocarcinoma who underwent cholangiocarcinoma operation from January 2004 to December 2010 were analyzed retrospectively. The relationship of clinicopathological features and C-met in the prognosis of the patients was analyzed. RESULTS: Patients with high expression of C-met had significantly shorter overall survival than those with low expression of C-met, the difference being statistically significant (P = .003). Patients with high C-met expression had significantly shorter disease-free survival time than those with low expression of C-met, the difference being statistically significant (P = .009). By COX multivariate analysis, high C-met expression in tumor tissues was an independent risk factor in predicting overall survival and disease-free survival for patients with cholangiocarcinoma (P = .038, .048, relative risk = 1.390, 1.427). CONCLUSION: Patients with high C-met expression in cancer tissues had shorter disease-free survival and overall survival. High expression of C-met is an independent risk factor for overall survival and disease-free survival.

Prognostic Factors of Cholangiocarcinoma After Surgical Resection: A Retrospective Study of 293 Patients.

BACKGROUND: Cholangiocarcinoma is one of the most common malignancies in China. Surgical resection is the only treatment option; however, diagnosis at advanced stage precludes surgery. Comprehensive knowledge of prognostic markers is missing. Hence, the aim of this study was to determine clinicopathological indexes that would be indicative of prognosis in post-operative cases of cholangiocarcinoma. MATERIAL AND METHODS: A retrospective analysis of 293 cases of cholangiocarcinoma patients attending the 301 Military Hospital in Beijing, China between January 2004 and December 2010 were included in the study. The patients had follow-up history until August 2012. Cox proportional hazards model analysis was performed to identify indexes of prognosis. All indicators were analyzed by univariate and multivariate analysis. RESULTS: The median follow-up time was 55.90 months, with recurrence and metastasis in 162 cases (55.3%) and death in 223 cases (76.1%). The 1-year, 3-year, and 5-year survival rates were 71.7%, 38.2%, and 10.6%, respectively. The independent risk factors of overall survival were degree of tumor differentiation, TNM stage, surgical margin, intraoperative blood transfusion, tumor location, alkaline phosphatase levels in blood, and relapse. CONCLUSIONS: Good prognosis in cholangiocarcinoma patients is indicated by highly differentiated tumor, early stages of TNM staging, no resection margin invaded, no intraoperative blood transfusion, intrahepatic tumor, normal alkaline phosphatase levels, and no relapse.

Prognostic value of neutrophil distribution in cholangiocarcinoma.

AIM: To explore the relationship of clinicopathological features and the distribution of neutrophils in the tumor microenvironment with the prognosis of cholangiocarcinoma. METHODS: Two hundred and fifty-four formalin-fixed and paraffin embedded tissue blocks were analyzed, including tissues from cholangiocarcinoma (n = 254), and tumor adjacent tissues (n = 238). Tissue sections were stained for CD15 using immunohistochemical staining. CD15 expression was detected to identify the distribution of neutrophils in the local tumor microenvironment. The neutrophil density of the tumor tissues and the adjacent tumor tissues was detected to reflect their inflammatory status. Clinical data and follow-up information of cholangiocarcinoma patients who underwent surgery from January 2004 to December 2010 were analyzed retrospectively. The relationship between clinicopathological features and the distribution of neutrophils with prognosis of the patients were analyzed. RESULTS: The positive expression level of CD15 was only significantly related to the TNM stage. CD15 expression was higher in tumor tissues than in adjacent tissues (73.6% vs 54.6%), with significant differences. Patients with high expression of CD15 had significantly shorter overall survival (OS) than those with low expression of CD15 (median overall survival time 39.77 mo vs 16.87 mo, P = 0.008). Patients with high CD15 expression had significantly shorter disease free survival time (DFS) than those with low expression of CD15 (median DFS 38.27 mo vs 16.83 mo, P = 0.029). COX multivariate analysis indicated that high CD15 expression in tumor tissues was an independent risk factor for predicting OS for patients with cholangiocarcinoma [P = 0.012, relative risk (RR) = 1.601], but it was not an independent risk factor for predicting DFS (P = 0.073, RR = 1.462). CONCLUSION: Patients with high CD15 expression in cancer tissues had shorter DFS and OS. High expression of CD15 is an independent risk factor for OS.

Retrospective evaluation of the efficacy of first-line treatment of advanced gastric cancer with docetaxel and oxaliplatin.

The incidence rate of gastric cancer is highest in China, where 5 in 10 new cases of stomach cancer across the world are diagnosed. Even though surgical management is the treatment of choice, it is not significantly effective due to advanced stage of the disease at diagnosis and the increased chances of primary tumor recurrence and metastasis to secondary organs. First-line chemotherapy of advanced gastric cancer patients recommend oxaliplatin and docetaxel; however, not much is known about their usage in Chinese patients. Therefore we retrospectively analyzed 199 cases of advanced gastric cancer (intestinal, diffuse, and mixed types) receiving either docetaxel or oxaliplatin-based first-line chemotherapy. The end-points determined were objective response rate (ORR, sum of complete and partial responses), disease control rate (DCR, sum of complete response, partial response, and stable disease), median progression-free survival (mPFS), and median overall survival (OS) time. Both docetaxel and oxaliplatin-based chemotherapy exhibited improved ORR and DCR; however, the comparison of short-term objective efficacy (ORR and DCR) was not statistically significant (p > .05) between the two groups. Our results indicated that PFS and OS of intestinal-type gastric cancer were extended compared with diffuse-type and mixed-type gastric cancer. Adverse reactions were within the control range and after symptomatic treatment were significantly ameliorated. Both docetaxel and oxaliplatin-based chemotherapy thus had a robust treatment outcome and can prospectively be used as one of the effective chemotherapy regimens for advanced gastric cancer patients in China.

Retrospective analysis of 119 small bowel adenocarcinoma in Chinese patients.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare occurrence and few studies have addressed it adequately, especially in China. METHODS: Clinicopathological features, survival and prognostic analysis were retrospectively done in SBA patients admitted between 2001 and 2011 in the People's Liberation Army General Hospital. RESULTS: The study included 68 men and 51 women with a median age of 56.5 year. Tumors mainly occurred in duodenum (93.3%). Abdominal pain was the most frequent symptom (36.8%). Patients (30.3%) who received postoperative adjuvant chemotherapy had an increased, but not significant, median overall survival (MOS) rate compared to those who did not receive chemotherapy (37 vs 35 months, p = .324). One year disease free survival rate was higher in patients receiving postoperative chemotherapy (83.3% vs 71.1%). Patients survived longer in the curative surgery group (median survival time of 49.0 months) than those in the palliative group (7.0 months) (p < .001). Node-negative patients survived longer than node-positive patients (median OS: 49.0 vs 21.0 months, p = .004). Depth (95% CI: 1.013-1.517, p = .037), node involvement (95% CI: 1.234-3.890, p = .007), palliative surgery (95% CI, 2.998-10.555, p = .0005), and the site of tumor (95% CI: 0.052-0.970, p = .045) were independent predictors of OS in a multivariate analysis. CONCLUSIONS: SBA is rare and there is lack of obvious clinical manifestations. Depth, node involvement, palliative surgery, and the site of tumor are associated with a poor prognosis. Our analysis highlights the need for further studies to find out the exact role of postoperative adjuvant chemotherapy in these patients.

Retrospective analysis of 102 cases of solid pseudopapillary neoplasm of the pancreas in China.

OBJECTIVE: Clinicopathological features and surgical outcomes in patients with solid pseudopapillary neoplasm (SPN) of the pancreas were analysed. METHODS: Data regarding clinicopathological features, surgery and outcome for patients with SPN were retrospectively collected and analysed. Patients were followed-up by telephone interview. RESULTS: The study included 102 patients (89 females/13 males), 99 of whom underwent surgical resection. A total of 89 patients (87.3%) were followed-up (mean duration 26.98 months, range 2-95 months); 86 (96.6%) had no relapse or metastasis. CONCLUSIONS: Surgical resection is the primary therapy for SPN, and results in a good prognosis.

Proinflammatory conditions promote hepatocellular carcinoma onset and progression via activation of Wnt and EGFR signaling pathways.

The aim of the current study was to investigate how proinflammatory conditions affect growth and progression of hepatocellular carcinoma. Human hepatoma cell lines were treated with lipopolysaccharide (LPS) or cyclooxygenase-2 inhibitor, Celecoxib, and in vitro proliferation, apoptosis, and cell cycle progression were assessed. This was followed up with in vivo xenograft assays to monitor tumor growth and metastatic progression under different treatment conditions. While LPS induced cell proliferation, Celecoxib induced apoptosis. Flow cytometry analysis demonstrated that S-phase cell count in LPS group was higher than control group (41.9 ± 3.2 vs 30.6 ± 0.1%, respectively), whereas G0/G1-phase cells were significantly higher in the Celecoxib group in comparison with the control group (69.6 ± 5.0 vs 50.4 ± 1.6%, respectively) (p < 0.05). Immunoblot analyses showed induction of epidermal growth factor receptor expression and induction and nuclear accumulation of Wnt/ß-catenin and p65 in LPS group. Xenograft assays showed that LPS treatment induced comparatively large, rapidly growing tumors (2,702 ± 572 mm(3)) that metastasized to lungs, whereas Celecoxib treatment alone (1,008 ± 296 mm(3)) or in combination with LPS (1,303 ± 283 mm(3)) suppressed tumor growth in comparison to control groups (2,072 ± 456 mm(3)) (n = 5; p < 0.05). Inflammation can thus promote hepatoma cell proliferation and growth, and enhance the invasion and metastatic ability of hepatocarcinoma cells through inducing tumor angiogenesis, which in turn may be related to the activation of Wnt/ß-catenin and EGFR signaling pathways.