A Secure Secret Key Agreement Scheme among Multiple Twinning Superlattice PUF Holders.

Modern cryptography attributes the security of a cryptographic system to the security of the key. How to securely distribute the key has always been a bottleneck in key management. This paper proposes a secure group key agreement scheme for multiple parties using a multiple twinning superlattice physical unclonable function (PUF) that can be synchronized. By sharing the challenge and helper data among multiple twinning superlattice PUF holders, the scheme employs a reusable fuzzy extractor to obtain the key locally. Moreover, adopting public-key encryption encrypts public data for establishing the subgroup key, which provides independent communication for the subgroup. At the same time, when the subgroup membership changes, the public key encrypts new public data to update the subgroup key, forming scalable group communication. This paper also presents a cost and formal security analysis, which shows that the proposed scheme can achieve computational security by applying the key obtained by the computationally secure reusable fuzzy extractor to the EAV-secure symmetric-key encryption, which has indistinguishable encryption in the presence of an eavesdropper. Additionally, the scheme is secure against physical attacks, man-in-the-middle attacks, and machine learning modeling attacks.

An SSL-PUF Based Access Authentication and Key Distribution Scheme for the Space-Air-Ground Integrated Network.

The Space-Air-Ground Integrated Network (SAGIN) expands cyberspace greatly. Dynamic network architecture, complex communication links, limited resources, and diverse environments make SAGIN's authentication and key distribution much more difficult. Public key cryptography is a better choice for terminals to access SAGIN dynamically, but it is time-consuming. The semiconductor superlattice (SSL) is a strong Physical Unclonable Function (PUF) to be the hardware root of security, and the matched SSL pairs can achieve full entropy key distribution through an insecure public channel. Thus, an access authentication and key distribution scheme is proposed. The inherent security of SSL makes the authentication and key distribution spontaneously achieved without a key management burden and solves the assumption that excellent performance is based on pre-shared symmetric keys. The proposed scheme achieves the intended authentication, confidentiality, integrity, and forward security, which can defend against masquerade attacks, replay attacks, and man-in-the-middle attacks. The formal security analysis substantiates the security goal. The performance evaluation results confirm that the proposed protocols have an obvious advantage over the elliptic curve or bilinear pairings-based protocols. Compared with the protocols based on the pre-distributed symmetric key, our scheme shows unconditional security and dynamic key management with the same level performance.

The inflammatory cytokine profiles and ocular biometric characteristics of primary angle-closure glaucoma.

OBJECTIVE: To investigate the pathogenesis of primary angle-closure disease (PACG) by measuring the anatomical structures of the anterior and posterior segments of the eye and inflammatory markers in the peripheral blood. METHODS: This case-control study enrolled patients diagnosed with acute PACG (APACG) and chronic PACG (CPACG). It also enrolled control subjects without PACG. The anterior and posterior anatomical features were measured in all study participants. The levels of interleukin (IL)-6, tumour necrosis factor-α and the neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood were measured. RESULTS: This study analysed a total of 99 eyes: 34 eyes from 34 patients with APACG, 28 eyes from 28 patients with CPACG and 37 eyes from 37 control patients with senile cataract. The axis length, corneal diameter, anterior chamber depth and anterior chamber volume were significantly smaller in the APACG and CPACG groups compared with the controls. The level of IL-6 in the peripheral blood of patients with PACG was significantly lower than that of the controls. The NLR in the peripheral blood of patients with PACG was significantly greater than that of the controls. CONCLUSIONS: Changes in the ocular anatomy and some inflammatory markers might be involved in the pathogenesis of PACG.

Construction of Chromosome Segment Substitution Lines and Inheritance of Seed-Pod Characteristics in Wild Soybean.

Genetic populations provide the basis for genetic and genomic research, and chromosome segment substitution lines (CSSLs) are a powerful tool for the fine mapping of quantitative traits, new gene mining, and marker-assisted breeding. In this study, 213 CSSLs were obtained by self-crossing, backcrossing, and marker-assisted selection between cultivated soybean (Glycine max [L.] Merr.) variety Suinong14 (SN14) and wild soybean (Glycine soja Sieb. et Zucc.) ZYD00006. The genomes of these 213 CSSLs were resequenced and 580,524 single-nucleotide polymorphism markers were obtained, which were divided into 3,780 bin markers. The seed-pod-related traits were analyzed by quantitative trait locus (QTL) mapping using CSSLs. A total of 170 QTLs were detected, and 32 QTLs were detected stably for more than 2 years. Through epistasis analysis, 955 pairs of epistasis QTLs related to seed-pod traits were obtained. Furthermore, the hundred-seed weight QTL was finely mapped to the region of 64.4 Kb on chromosome 12, and Glyma.12G088900 was identified as a candidate gene. Taken together, a set of wild soybean CSSLs was constructed and upgraded by a resequencing technique. The seed-pod-related traits were studied by bin markers, and a candidate gene for the hundred-seed weight was finely mapped. Our results have revealed the CSSLs can be an effective tool for QTL mapping, epistatic effect analysis, and gene cloning.

Min-entropy estimation for semiconductor superlattice true random number generators.

Semiconductor superlattice true random number generator (SSL-TRNG) has an outstanding practical property on high-throughput and high-security cryptographic applications. Security in random number generators is closely related to the min-entropy of the raw output because feeding cryptographic applications with insufficient entropy leads to poor security and vulnerability to malicious attacks. However, no research has focused on the min-entropy estimation based on the stochastic model for SSL-TRNG, which is a highly recommended method for evaluating the security of a specific TRNG structure. A min-entropy estimation method is proposed in this paper for the SSL-TRNG by extending the Markov stochastic model derived from the memory effects. By calculating the boundary of the transition matrix, the min-entropy result is the average value of each sample (1 bit) is 0.2487. Moreover, the experimental results show that the estimator is accurate enough to adjust compression rate dynamically in post-processing to reach the required security level, estimating entropy on the fly rather than off-line.

Fine mapping and candidate gene analysis of proportion of four-seed pods by soybean CSSLs.

Soybean yield, as one of the most important and consistent breeding goals, can be greatly affected by the proportion of four-seed pods (PoFSP). In this study, QTL mapping was performed by PoFSP data and BLUE (Best Linear Unbiased Estimator) value of the chromosome segment substitution line population (CSSLs) constructed previously by the laboratory from 2016 to 2018, and phenotype-based bulked segregant analysis (BSA) was performed using the plant lines with PoFSP extreme phenotype. Totally, 5 ICIM QTLs were repeatedly detected, and 6 BSA QTLs were identified in CSSLs. For QTL (qPoFSP13-1) repeated in ICIM and BSA results, the secondary segregation populations were constructed for fine mapping and the interval was reduced to 100Kb. The mapping results showed that the QTL had an additive effect of gain from wild parents. A total of 14 genes were annotated in the delimited interval by fine mapping. Sequence analysis showed that all 14 genes had genetic variation in promoter region or CDS region. The qRT-PCR results showed that a total of 5 candidate genes were differentially expressed between the plant lines having antagonistic extreme phenotype (High PoFSP > 35.92%, low PoFSP< 17.56%). The results of haplotype analysis showed that all five genes had two or more major haplotypes in the resource population. Significant analysis of phenotypic differences between major haplotypes showed all five candidate genes had haplotype differences. And the genotypes of the major haplotypes with relatively high PoFSP of each gene were similar to those of wild soybean. The results of this study were of great significance to the study of candidate genes affecting soybean PoFSP, and provided a basis for the study of molecular marker-assisted selection (MAS) breeding and four-seed pods domestication.

High throughput error correction in information reconciliation for semiconductor superlattice secure key distribution.

Semiconductor superlattice secure key distribution (SSL-SKD) has been experimentally demonstrated to be a novel scheme to generate and agree on the identical key in unconditional security just by public channel. The error correction in the information reconciliation procedure is introduced to eliminate the inevitable differences of analog systems in SSL-SKD. Nevertheless, the error correction has been proved to be the performance bottleneck of information reconciliation for high computational complexity. Hence, it determines the final secure key throughput of SSL-SKD. In this paper, different frequently-used error correction codes, including BCH codes, LDPC codes, and Polar codes, are optimized separately to raise the performance, making them usable in practice. Firstly, we perform multi-threading to support multi-codeword decoding for BCH codes and Polar codes and updated value calculation for LDPC codes. Additionally, we construct lookup tables to reduce redundant calculations, such as logarithmic table and antilogarithmic table for finite field computation. Our experimental results reveal that our proposed optimization methods can significantly promote the efficiency of SSL-SKD, and three error correction codes can reach the throughput of Mbps and provide a minimum secure key rate of 99%.

Prognostic Value of the post-operative Red Blood Cell Distribution Width in rectal cancer patients with neoadjuvant chemoradiation followed surgery.

Purposes Several studies have reported that elevated red  cell distribution width (RDW) is related to poor prognosis in several cancers; however, the prognostic significance of perioperative RDW in rectal cancer patients which received neoadjuvant chemoradiation therapy (NACRT) is unclear. Methods A total of 120 rectal cancer patients who received NACRT followed surgery were retrospectively reviewed from Affiliated Cancer Hospital of Zhengzhou University between 2013 to 2015. Data for peripheral blood tests prior to the initiation of NACRT，before surgery and first chemotherapy after surgery were collected，respectively. The optimal cutoff values of RDW was determined by ROC analysis, respectively. The relationship between RDW and the prognosis of patients was evaluated by, respectively. Results The post-operative RDWHigh (≥15.55) patients had significantly worse five-year overall survival (OS, P=0.001) and disease-free survival (DFS, P=0.001) than the post-operative RDWLow (<15.55) patients, respectively. Whereas high pre-operative RDW  (≥16.45) was the only marker correlated with worse DFS (P=0.005) than the pre-operative RDWLow (<16.45)patients, no relationship was found between pre-RDW and prognosis(OS, P=0.069; DFS, P=0.133). Multivariate analysis showed post-operative RDW had better predictive value than pre-RDW and pre-operative RDW. Conclusion Post-operative RDW might be a useful prognostic indicator in rectal cancer patients received neoadjuvant chemoradiation.

Comparison of outcomes of pedicled jejunal and colonic conduit for esophageal reconstruction.

BACKGROUND: At present, the gastric tube is the first choice for esophageal reconstruction after esophagectomy for various benign and malignant diseases. However, when the stomach is not available, a pedicled jejunum or colon is used to reconstruct the esophagus. The present study aimed to compare the postoperative outcomes and quality of life of patients receiving jejunal and colonic conduits. METHODS: In the present retrospective study, the clinical data of 71 patients with esophageal carcinoma, who received jejunal reconstruction (jejunum group, n = 34) and colonic reconstruction (colon group, n = 37) from 2005 to 2015, were compared. RESULTS: Compared with the colon group, the jejunum group had a lower incidence of postoperative anastomotic leakage, lesser duration of postoperative drainage, and faster recovery. Furthermore, the scores were better in the jejunum group than in the colon group, in terms of short-term overall quality of life, physical function and social relationships. Moreover, the jejunal group had a significantly lower frequency of pH < 4 simultaneous reflux time > 5 min (N45) and the longest reflux time (LT) at 24 weeks after surgery. CONCLUSION: In esophageal cancer, when gastric tube construction is not feasible, a pedicled jejunum may be preferred over a colonic conduit due to lower incidence of acid reflux, anastomotic leakage and higher postoperative short-term quality of life, and rapid postoperative recovery.

microRNA-29b inhibits cell growth and promotes sensitivity to oxaliplatin in colon cancer by targeting FOLR1.

The present study was aimed to explore the functional role of microRNA (miR)-29b in colon cancer, as well as underlying mechanisms. Expressions of miR-29b and folate receptor 1 (FOLR1) were measured in both human colon tumor samples and cell lines. Colon cancer cell lines SW480 and SW620 were transfected with miR-29b mimic, antisense oligonucleotides (ASO)-miR-29b, small interfering (siRNA) against FOLR1 (si-FOLR1), or corresponding negative controls (NCs), and then were incubated with or without oxaliplatin (L-OHP). Thereafter, cell viability, cytotoxicity, cell apoptosis, and expression of FOLR1, ATP Binding Cassette Subfamily G Member 2 (ABCG2) and p-glycoprotein (p-gp) were analyzed. We found that miR-29b was significantly decreased, while FOLR1 was statistically elevated in colon cancer samples and cell lines compared to the nontumor samples and nontumourigenic immortalized human colon epithelial cell line FHC. Overexpression of miR-29b markedly inhibited cell viability, promoted sensitivity to L-OHP, stimulated cell apoptosis (all p < .05), and decreased the levels of ABCG2 and p-gp in cancer cells, whereas suppression of miR-29b showed contrary results. Moreover, we observed that FOLR1 was a direct target of miR-29b and was negatively regulated by miR-29b. In addition, the findings revealed that the effects of FOLR1 inhibition on cell viability, sensitivity to L-OHP, cell apoptosis, and the levels of ABCG2 and p-gp were similar to overexpression of miR-29b. Taken together, our study suggests that miR-29b inhibits cell growth and promotes sensitivity to L-OHP in colon cancer by targeting FOLR1.

Combined Linkage Mapping and BSA to Identify QTL and Candidate Genes for Plant Height and the Number of Nodes on the Main Stem in Soybean.

Soybean is one of the most important food and oil crops in the world. Plant height (PH) and the number of nodes on the main stem (NNMS) are quantitative traits closely related to soybean yield. In this study, we used 208 chromosome segment substitution lines (CSSL) populations constructed using "SN14" and "ZYD00006" for quantitative trait locus (QTL) mapping of PH and NNMS. Combined with bulked segregant analysis (BSA) by extreme materials, 8 consistent QTLs were identified. According to the gene annotation of the QTL interval, a total of 335 genes were obtained. Five of which were associated with PH and NNMS, potentially representing candidate genes. RT-qPCR of these 5 candidate genes revealed two genes with differential relative expression levels in the stems of different materials. Haplotype analysis showed that different single nucleotide polymorphisms (SNPs) between the excellent haplotypes in Glyma.04G251900 and Glyma.16G156700 may be the cause of changes in these traits. These results provide the basis for research on candidate genes and marker-assisted selection (MAS) in soybean breeding.

[Detection and clinical significance of myeloid-derived suppressor cells in peripheral blood of patients with rectal carcinoma].

OBJECTIVE: To study the expression of myeloid-derived suppressor cells (MDSC) in peripheral blood of patients with rectal carcinoma and to preliminarily explore its clinical significance. METHODS: Blood samples from 76 rectal carcinoma patients who underwent surgery in Department of General Surgery, The Affiliated Cancer Hospital, Zhengzhou University between June and October 2013 were collected before operation, postoperative day 10 and 2 years after operation respectively. Flow cytometry was used to detect MDSC percentage in peripheral blood of 76 rectal carcinoma patients and 40 healthy people. The change of MDSC percentage in peripheral blood of rectal carcinoma patients after treatment was investigated. Furthermore, the relationship of peripheral blood MDSC percentage with clinicopathological characteristics was examined. RESULTS: Preoperative MDSC percentage in peripheral blood of 76 rectal carcinoma patients [(3.52±0.68)%] was higher than that of 40 healthy people[(0.92±0.21)%], with significant difference (t=3.026, P=0.005). Preoperative MDSC percentage in peripheral blood of rectal carcinoma patients was significantly related with histological classification (t=2.453, P=0.018), depth of tumor invasion (t=2.051, P=0.035), lymph node metastasis (t=2.328, P=0.022), TNM stage (t=2.529, P=0.016). Univariate analysis showed that TNM stage, histological classification, lymph node metastasis, preoperative MDSC percentage in peripheral blood were the prognostic factors in rectal carcinoma. Multivariate analysis showed that TNM stage (HR=2.535, 95%CI: 0.851 to 4.160, P=0.038) and preoperative MDSC percentage in peripheral blood (HR=3.651, 95%CI: 0.877 to 14.263, P=0.031) were independent prognostic factors of rectal carcinoma. MDSC percentage in peripheral blood of rectal carcinoma patients decreased significantly on the postoperative 10-day [(2.41±0.46)%] compared to that before operation [(3.52±0.68)%], whose difference was statistically significant (t=1.778, P=0.043). During follow-up, tumor recurrence or metastasis was found in 23 patients. MDSC percentage in peripheral blood of rectal carcinoma patients with recurrence or metastasis [(4.37±1.23)%] was higher than that of rectal carcinoma patients without recurrence or metastasis [(2.36±0.35)%] two years after operation, with statistically significant difference (t=1.982, P=0.039). CONCLUSIONS: MDSC percentage in peripheral blood of rectal carcinoma patients is significantly elevated compared to that of healthy people. Increased MDSC percentage indicates poor prognosis and tumor progression in rectal carcinoma patients. Measurement of peripheral blood MDSC percentage may have a potential clinical value in prognosis prediction of rectal carcinoma.

[MiR-145 inhibits drug resistance to Oxaliplatin in colorectal cancer cells through regulating G protein coupled receptor 98].

OBJECTIVE: To predict and identify the target gene of miR-145, and to explore the underlying mechanism of the inhibition of miR-145 on drug resistance to Oxaliplatin (L-OHP) in human colorectal cancer cells. METHODS: L-OHP-resistant human colorectal cancer cell line (HCT116/L-OHP) was established in vitro by exposing to increased concentrations of L-OHP in cell culture medium. MiR-145-mimics and its negative control (NC-miRNA) were transfected into HCT116/L-OHP cells using liposome to establish HCT116/L-OHPmimics over-expressing miR-145 and HCT116/L-OHPNC. The target genes of miR-145 were predicted by bioinformatic analysis, and validated by dual luciferase activity assay. After determination of G protein coupled receptor 98(GPR98) as target gene, corresponding plasmids were constructed and transfected to establish HCT116/L-OHPGPR98 over-expressing GPR98 and HCT116/L-OHPcontrol. HCT116/L-OHP cells over-expressing both GPR98 and miR-145 (HCT116/L-OHPmimics+GPR98) were acquired through modification of the binding sites of GPR98 cDNA with miR-145. CCK-8 assay was used to assess the proliferation (A value) and sensitivity to L-OHP (the lower the IC50, the stronger the sensitivity) in HCT116/L-OHP cells. Real-time quantitative PCR was used to measure the mRNA expression of miR-145 and GPR98. Western blot was used to examine the protein expression of GPR98 and drug-resistant associated protein, such as P-glycoprotein (gp), multiple drug-resistance protein 1(MRP1), cancer-inhibition gene PTEN. RESULTS: HCT116/L-OHP cell line was successfully established with IC50 of (42.34±1.05) mg/L and miR-145 mRNA expression of 0.27±0.04, which was higher than (9.81±0.95) mg/L (t=39.784, P=0.000) and lower than 1.00±0.09 (t=13.021, P=0.000) in HCT116 cells. Based on HCT116/L-OHP cells, HCT116/L-OHPmimics cells were established successfully, with relative miR-145 expression of 10.01±1.05, which was higher than 1.06±0.14 in HCT116/L-OHPNC and 1.00±0.16 in HCT116/L-OHP (F=161.797, P=0.000). GPR98 was identified to be the target gene of miR-145. The relative mRNA and protein expressions of GPR98 in HCT116/L-OHPGPR98 cells were 8.48±0.46 and 1.71±0.09, respectively, which were higher than those in HCT116/L-OHPcontrol (mRNA: 3.65±0.40, protein: 1.21±0.10) and HCT116/L-OHP (mRNA: 3.49±0.35, protein: 1.22±0.08; all P<0.05). The A value was 1.31±0.10, and the relative protein expressions of P-gp and MRP1 were 1.53±0.18 and 1.49±0.20 in HCT116/L-OHPGPR98 cells, which were higher than those in HCT116/L-OHP (A value: 0.82±0.08, relative protein expression: 1.00±0.06 and 1.21±0.13, all P<0.05). The A value was 0.89±0.08, and the relative protein expressions of P-gp and MRP were 1.02±0.24 and 1.38±0.25 in HCT116/L-OHPmimics+GPR98 cells, which were higher than those in HCT116/L-OHPmimics(A value: 0.20±0.05, relative protein expression: 0.20±0.07, 0.55±0.10, all P<0.05). The relative protein expression of PTEN in HCT116/L-OHPGPR98 cells was 0.12±0.03, which was lower than 1.25±0.14 in HCT116/L-OHP cells(P<0.05). In addition, relative protein expressions of P-gp and MRP1 were 1.02±0.24 and 1.38±0.25 in HCT116/L-OHPmimics+GPR98 cells, which were higher than those in HCT116/L-OHPmimics cells (0.20±0.07 and 0.55±0.10), while PTEN expression in HCT116/L-OHPmimics+GPR98 cells was lower as compared to HCT116/L-OHPmimics cells (1.41±0.16 vs. 1.98±0.13, P<0.05). CONCLUSION: MiR-145 inhibits drug resistance to L-OHP of HCT116 cells through suppressing the expression of target gene GPR98.

miR-20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway in colon cancer.

Chemoresistance is a major obstacle to cancer therapy including that of colon cancer (CC). Although the dysregulation of many miRNAs has been implicated in 5-fluorouracil (5-FU) resistance in CC cells, the specific role of miR-20b in chemoresistance has not been documented. In the present study, we first determined the expression of miR-20b by RT-PCR and the levels of a disintegrin and metalloprotease 9 (ADAM9) and epidermal growth factor receptor (EGFR) by western blotting in CC and adjacent non-cancerous tissues from 5-FU-sensitive or -resistant CC patients. Subsequently, 5-FU-sensitive (HCT116) and -resistant (HCT116-R) cells were obtained, and the levels of miR-20b, ADAM9 and EGFR were detected. Meanwhile, the 5-FU resistance of the cells was examined by assessing cell viability (by MTT assay) and apoptosis (by flow cytometry). After transfection of miR-20b into HCT116-R cells, drug resistance was reexamined. We then confirmed the relationship between miR-20b and ADAM9 by luciferase reporter assay. Finally, 5-FU resistance in HCT116 and HCT116-R cells was compared after transfection with miR-20b. Our results showed that miR-20b was expressed at lower levels in the 5-FU-resistant tissues and cells than in the 5-FU-sensitive tissues and cells. The opposite was the case for expression of ADAM9 and EGFR. In addition, we demonstrated that ADAM9 is a direct target of miR-20b and that miR-20b decreased the 5-FU resistance of HCT116-R cells. Our findings suggest that miR-20b reduces 5-FU resistance to induce apoptosis in vitro by suppressing ADAM9/EGFR in CC cells.

Downregulation of YEATS4 by miR-218 sensitizes colorectal cancer cells to L-OHP-induced cell apoptosis by inhibiting cytoprotective autophagy.

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Deregulation of microRNAs (miRNAs) has been reported to participate in CRC progression. In the present study, we observed downregulation of miR-218 and upregulation of YEATS domain containing 4 (YEATS4) in CRC tissues and in multidrug-resistant HCT-116/L-OHP cells compared with these levels in normal tissues and parental HCT-116 cells, respectively. The results indicated that miR-218 overexpression significantly decreased the IC50 value of oxaliplatin (L-OHP) in the HCT-116/L-OHP cells, and suppression of miR-218 significantly enhanced the IC50 of L-OHP in the HCT-116 cells. Flow cytometric analysis showed that miR-218 overexpression alone promoted cell apoptosis in the HCT-116/L-OHP cells, which was further enhanced in response to L-OHP, and miR-218 inhibition decreased cell apoptosis in the HCT-116 cells following treatment with L-OHP. Western blot analysis indicated that, compared with the small increase observed in HCT-116 cells, the relative LC3 II level in HCT-116/L-OHP cells after lysosome inhibition via chloroquine (CQ) was markedly upregulated following L-OHP treatment, suggesting induction of autophagy. Exposure of HCT-116/L-OHP cells to L-OHP after control mimic transfection increased autophagic flux, as reflected by increased LC3 II levels, while miR-218 overexpression partly reversed L-OHP-mediated LC3 II accumulation. Additionally, both miR-218 overexpression and CQ treatment promoted L-OHP-induced HCT-116/L-OHP cell apoptosis. Molecularly, our results confirmed that miR-218 directly targets the YEATS4 gene and inhibits YEATS4 expression. Furthermore, YEATS4 overexpression without the 3'-untranslated region (3'-UTR) restored miR-218-inhibited YEATS4 and LC3 II expression, and abolished miR-218-stimulated cell viability loss and cell apoptosis increase in response to L-OHP. In conclusion, miR-218 sensitized HCT-116/L-OHP cells to L-OHP-induced cell apoptosis via inhibition of cytoprotective autophagy by targeting YEATS4 expression.

Clinicopathological and Prognostic Analysis of Neuroendocrine Carcinoma of the Colorectum.

BACKGROUND: Neuroendocrine carcinoma of the colorectum is a kind of malignant tumor composed of neuroendocrine cells, with a unique hormone synthesis and secretory function. In recent years, more and more attention is being paid to this kind of tumor, with its high malignant potential, poor differentiation, high invasiveness and early metastasis. OBJECTIVES: The aim of this study was to evaluate the clinicopathological characteristics and prognosis of neuroendocrine carcinoma of the colorectum. MATERIAL AND METHODS: The clinical data on 49 patients treated for neuroendocrine carcinoma of the colorectum from January 1995 to January 2013 were retrospectively analyzed and relevant scientific literature was investigated. RESULTS: The study subjects included 34 males and 15 females, out of whom 27 patients underwent curative operations, while 18 underwent palliative resections and four others underwent biopsy. All 49 patients underwent adjuvant chemotherapy after operation. Of the 45 resection samples, vascular invasion was found in 33 patients (73.3%) and regional lymph node metastasis was found in 35 patients (77.8%). All the patients were followed up for a period of 3 to 68 months. The 1-year, 3-year and 5-year survival rates were 49.1%, 17.2% and 6.9%, respectively. The patients' survival time was related to the tumor stage, vascular invasion and surgery type (radical or not), but not related to age, gender, tumor size or tumor location. CONCLUSIONS: Neuroendocrine carcinoma of the colon lacked specific clinical manifestations, but showed a high degree of malignancy and a poor prognosis. Tumour stage, vascular invasion and surgery type (radical or not) were important factors influencing the prognosis.

Protease-activated receptor 4: a critical participator in inflammatory response.

Protease-activated receptors (PARs) are G protein-coupled receptors of which four members PAR1, PAR2, PAR3, and PAR4 have been identified, characterized by a typical mechanism of activation involving various related proteases. The amino-terminal sequence of PARs is cleaved by a broad array of proteases, leading to specific proteolytic cleavage which forms endogenous tethered ligands to induce agonist-biased PAR activation. The biological effect of PARs activated by coagulation proteases to regulate hemostasis and thrombosis plays an enormous role in the cardiovascular system, while PAR4 can also be activated by trypsin, cathepsin G, the activated factor X of the coagulation cascade, and trypsin IV. Irrespective of its role in thrombin-induced platelet aggregation, PAR4 activation is believed to be involved in inflammatory lesions, as show by investigations that have unmasked the effects of PAR4 on neutrophil recruitment, the regulation of edema, and plasma extravasation. This review summarizes the roles of PAR4 in coagulation and other extracellular protease pathways, which activate PAR4 to participate in normal regulation and disease.

[Function of death associated protein kinase(DAPK) in colorectal cancer chemoresistance].

OBJECTIVE: To investigate the role of death associated protein kinase(DAPK) in colon cancer drug-resistance. METHODS: Immunohistochemistry was used to detect DAPK expression in colon carcinoma tissues of 61 cases and adjacent tissues of 32 cases. 5-fluorouracil (5-FU)-induced drug-resistant colon cancer cell lines HCT116/5-FU model was established. DAPK-siRNA was transfected into cells to down-regulate the DAPK gene expression (DAPK-siRNA grouyp), FAM-siRNA was transfected as control group, and DAPK over-expression plasmid vectors were constructed to up-regulate the DAPK gene expression(DAPK over-expression group). Real-time quantitative PCR and Western blotting were used to examine the mRNA and protein expression levels of DAPK, multidrug resistance protein (MRP) and P- glycoprotein (P-gp). MTT and flow cytometry were used to detect cell proliferation and apoptosis for cells treated with 5-FU (8 mg/L) and cells without treatment of 5-FU in 3 groups respectively. RESULTS: Positive expression rate of DAPK in colon cancer tissues was significantly lower than that in adjacent normal tissues [18.0% (11/61) vs. 90.6% (29/32), P < 0.05]. Compared with FAM-siRNA group, DAPK mRNA and protein expression levels were significantly lower in DAPK-siRNA group, but significantly higher in DAPK over-expression group (P<0.05). After treatment of 5-FU, cell proliferation was significantly inhibited, but cell apoptosis was significantly increased in DAPK over-expression group compared to FAM-siRNA group (P < 0.05). Cell proliferation and apoptosis were not significantly different between DAPK siRNA and FAM-siRNA groups (all P < 0.05). Compared with FAM-siRNA group, DAPK over-expression could significantly reduce the mRNA and protein levels of MRP and P-gp, whereas DAPK siRNA had no obvious such effects. CONCLUSION: DAPK can inhibit the proliferation and promote the apoptosis in drug-resistant colon cancer cells, and it probably enhances the sensitivity of cancer cells to drugs by down-regulating the mRNA and protein levels of MRP and P-gp.

[Expression of angiopoietin-2 and vascular endothelial growth factor in human colon cancer].

OBJECTIVE: To investigate the association of the expressions of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF) in colorectal cancer tissues with Dukes' clinicopathological features. METHODS: Ang-2 and Tie-2 mRNA expressions were detected in colorectal cancer tissues, adjacent tissues, and normal tissues by real time-PCR. Quantikine immunoassays were used to measure the protein expressions of Ang-2 and VEGF in the tissues and serum samples. RESULTS: Ang-2 and Tie-2 levels were significantly higher in the serum of the patients than in the normal tissues (P<0.05), and their expressions were strongly correlated (r=0.879, P=0.000). Tumor tissue Ang-2 and VEGF levels were significantly higher than their levels in the adjacent and normal tissues (P<0.05). In colorectal cancer patients, the peripheral blood level of Ang-2 was significantly higher than that in healthy control subjects, and comparable with that in mesenteric blood (P>0.05). In Dukes' stage C and D patients, serum Ang-2 and VEGF levels were significantly higher than those in patients in Dukes' stage A and B (P<0.05). CONCLUSION: Ang-2 and VEGF over expressions may play an important role in the occurrence and progression of colorectal cancer.