Flexico: An efficient dual-mode consensus protocol for blockchain networks.

Blockchain is a Byzantine fault tolerant (BFT) system wherein decentralized nodes execute consensus protocols to drive the agreement process on new blocks added to a distributed ledger. Generally, two-round communications among [Formula: see text] nodes are required to tolerate up to [Formula: see text] faults in BFT-based consensus networks. This communication pattern corresponds to the worse-case scenario of consensus achievement, even under asynchronous network conditions. Nevertheless, it is not uncommon for a network to operate under better conditions, where a consensus can be reached with a lower communication cost. Hence, with the addition of a faster optimistic path toward an agreement, the idea of dual-mode consensus has been proposed as a promising approach to enhance the performance of asynchronous BFT protocols. However, this opportunity is not completely exploited by existing dual-mode protocols as the fast path can be followed only in a nonfaulty and synchronous network. This article presents a novel dual-mode protocol consisting of fast and backup subprotocols. To create different consensus committees for fast and backup-mode operations, the network contains both active and passive nodes. A consensus can be expedited through a fast-mode operation when majority of the active nodes can communicate synchronously. Under non-ideal conditions, the backup protocol takes over the agreement process from its fast-mode counterpart without starting over the suspended round. The safety and liveness of the proposed protocol are guaranteed with lower communication costs, which balance the trade-off between protocol efficiency and availability.

Downregulation of miR-375 contributes to ERBB2-mediated VEGFA overexpression in esophageal cancer.

Esophageal cancer (EC) is a lethal cancer with an extremely aggressive nature and poor survival rate. However, the molecular mechanisms driving the occurrence and progression of EC are not well understood. MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of protein-coding genes. miRNA-mediated gene regulation plays an important role in EC. By cross-referencing studies from NCBI, we found that microRNA-375 (miR-375) is one of the most frequently downregulated miRNAs in EC. We assessed expression of miR-375 in EC cell lines and primary EC tissues and their matched normal tissues. We found significant downregulation of miR-375 in both cell lines and EC tissues. Forced expression of miR-375 attenuated EC cell proliferation and invasion. Human epidermal growth factor receptor 2 (HER2, ERBB2), a known proto-oncogene, was identified here as one of the potential target genes of miR-375. Ectopic expression of miR-375 significantly suppressed the expression of ERBB2 and subsequently downregulated one of its target genes, vascular endothelial growth factor A (VEGFA), which is related to cancer invasion and metastasis. These findings suggest that miR-375 acts as a tumor suppressor by blocking the ERBB2/VEGFA pathway with the potential to modulate the occurrence and/ or progression of EC.

Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory skin disorder with unknown pathogenesis. The aberrant expression of microRNAs (miRNAs) is considered to exert a crucial role in LS. We used the next-generation sequencing technology (RNASeq) for miRNA profiling and Ingenuity Pathway Analysis (IPA) for molecular network analysis. We performed qRT-PCR, miRNA transfection and Matrigel assays for functional studies. We identified a total of 170 differentially expressed miRNAs between female LS and matched adjacent normal tissue using RNASeq, with 119 upregulated and 51 downregulated. Bioinformatics analysis revealed molecular networks that may shed light on the pathogenesis of LS. We verified the expression of a set of miRNAs that are related to autoimmunity, such as upregulated miR-326, miR-142-5p, miR-155 and downregulated miR-664a-3p and miR-181a-3p in LS tissue compared to the matched adjacent normal tissue. The differentially expressed miRNAs were also verified in blood samples from LS patients compared to healthy female volunteers. Functional studies demonstrated that a forced expression of miR-142-5p in human dermal fibroblast PCS-201-010 cells resulted in decreased cell proliferation and migration. These findings suggest that differentially expressed miRNAs may play an important role in LS pathogenesis; therefore, they could serve as biomarkers for LS management.

microRNA-196b promotes esophageal squamous cell carcinogenesis and chemoradioresistance by inhibiting EPHA7, thereby restoring EPHA2 activity.

Esophageal cancer (EC) is extremely aggressive and has a very poor survival rate. Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all ECs worldwide, with the majority of the remaining 20% being esophageal adenocarcinoma (EAC). Due to its occult and insidious presentation, ESCC is typically diagnosed and treated in its advanced stages, thereby limiting the success of present therapeutic modalities. microRNAs (miRNAs) can function as tumor suppressors or oncogenes, playing critical roles in cancer initiation and progression by regulating target genes in oncogenic pathways. In the current study, we demonstrated that microRNA-196b (miR-196b) is one of the most upregulated miRNAs in both ESCC and EAC. miR-196b was overexpressed in ESCC and EAC cell lines, cellular exosomal RNAs, and ESCC tissue samples. Functional studies revealed that miR-196b acted as an oncomiR by directly targeting a tumor suppressor, ephrin type-A receptor 7 (EPHA7). EPHA7 abrogates the activity of ephrin type-A receptor 2 (EPHA2), a key molecule involved in the epithelial-to-mesenchymal transition (EMT) and MAPK/ERK pathways, mediating resistance to UV and chemoradiotherapy in both ESCC and EAC. Taken together, these findings suggest that miR-196b is a strong candidate molecular target for EC treatment.

A Point Mutation in DNA Polymerase ß (POLB) Gene Is Associated with Increased Progesterone Receptor (PR) Expression and Intraperitoneal Metastasis in Gastric Cancer.

Increased expression of progesterone receptor (PR) has been reported in gastric cancer (GC). We have previously identified a functional T889C point mutation in DNA polymerase beta (POLB), a DNA repair gene in GC. To provide a detailed analysis of molecular changes associated with the mutation, human cDNA microarrays focusing on 18 signal transduction pathways were used to analyze differential gene expression profiles between GC tissues with T889C mutant in POLB gene and those with wild type. Among the differentially expressed genes, notably, PR was one of the significantly up-regulated genes in T889C mutant POLB tissues, which were subsequently confirmed in POLB gene transfected AGS cell line. Interestingly, patients with T889C mutation and PR positivity were associated with higher incidence of intraperitoneal metastasis (IM). In vitro studies indicate that PR expression was upregulated in AGS cell line when transfected with T889C mutant expression vector. Cotransfection of T889C mutant allele and PR gene induced cell migration in the cell line. These data demonstrated that T889C mutation-associated PR overexpression results in increased IM. Therefore, T889C mutation-associated PR overexpression may serve as a biomarker for an adverse prognosis for human GC.

[Self-control study of dynamic multiple pelvic angiography and pelvic four-contrast defecography in the diagnosis of functional defecation disorder].

OBJECTIVE: To evaluate and compare the value of dynamic multiple pelvic angiography and pelvic four-contrast defecography in the diagnosis of functional defecation disorder. METHODS: From September 2014 to July 2015, a prospective controlled trial was carried out in Chengdu Anorectal Hospital. A total of 32 patients met the inclusion criteria of functional defecation disorder simultaneously underwent pelvic four-contrast defecography and dynamic multiple pelvic angiography. The diagnostic results of these two methods were compared. RESULTS: The absolute values of anorectal angle and level of perineum, peritoneum and bladder from rest to defecation were (29.6±13.6)°, (26.2±14.2) mm, (55.5±25.6) mm and (28.9±16.5) mm in dynamic multiple pelvic angiography, and (24.6±5.8)° (18.7±10.6) mm, (34.5±18.4) mm and (19.2±11.8) mm in pelvic four-contrast defecography respectively, whose differences were statistically significant (P = 0.026, 0.022, 0.000, 0.011 respectively). The diagnostic rate of pelvic peritoneal hernia was 93.8%(30/32) and 68.8%(22/32) in dynamic multiple pelvic angiography and pelvic four-contrast defecography respectively with significant difference(P=0.011). CONCLUSION: Dynamic multiple pelvic angiography has significant advantage in the diagnosis of pelvic peritoneal hernia, and can provide a more objective basis for the diagnosis of functional defecation disorder.

Clinical significance of a point mutation in DNA polymerase beta (POLB) gene in gastric cancer.

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC.

[Laparoscopy-assisted subtotal colectomy with transanal specimen extraction for slow transit constipation].

OBJECTIVE: To investigate the clinical application of laparoscopy-assisted subtotal colectomy with transanal specimen extraction for slow transit constipation(STC). METHODS: Retrospective analysis was performed on the clinical data of 8 cases with STC undergoing the procedure mentioned above from February to November 2013. Pre-and post-operative constipation was assessed using Wexner Constipation and Incontinence Scales, and quality of life was assessed using Gastrointestinal Quality of Life Index. RESULTS: All the operations were completely successful without postoperative complications, such as intestinal fistula, pelvic infection, anastomotic stricture, intestinal obstruction. The Operative time was (287.6 ± 21.5) min, blood loss was (109.7 ± 41.1) ml, time to first flatus was (2.5 ± 0.9) d. The proportion of postoperative constipation symptom index improvement was(77.6 ± 8.3)%. Postoperative quality of life score was 97.3 ± 15.7, significantly higher than that before operation(P<0.05). Postoperative Wexner constipation score was 8.8 ± 3.7, significantly lower than that before operation. CONCLUSION: Laparoscopy-assisted subtotal colectomy with transanal specimen extraction in the treatment of STC has good short-term efficacy with obvious improvement in quality of life.