Esophageal Stent for Refractory Variceal Bleeding: A Systemic Review and Meta-Analysis

Background. Preliminary studies suggest that covered self-expandable metal stents may be helpful in controlling esophageal variceal bleeding. Aims. To evaluate the effectiveness and safety of esophageal stent in refractory variceal bleeding in a systematic review and meta-analysis. Methods. A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane Library covering the period from January 1970 to December 2015. Data were selected and abstracted from eligible studies and were pooled using a random-effects model. Heterogeneity was assessed using 2 test. Results. Five studies involving 80 patients were included in the analysis. The age of patients ranged from 18 to 91 years. The mean duration of follow-up was 46.8 d (range, 30-60 d). The success rate of stent deployment was 96.7% (95% CI: 91.6%-99.5%) and complete response to esophageal stenting was in 93.9% (95% CI: 82.2%-99.6%). The incidence of rebleeding was 13.2% (95% CI: 1.8%-32.8%) and the overall mortality was 34.5% (95% CI: 24.8%-44.8%). Most of patients (87.4%) died from hepatic or multiple organ failure, and only 12.6% of patients died from uncontrolled bleeding. There was no stent-related complication reported and the incidence of stent migration was 21.6% (95% CI: 4.7%-46.1%). Conclusion. Esophageal stent may be considered in patients with variceal bleeding refractory to conventional therapy

The bladder microbiome of NMIBC and MIBC patients revealed by 2bRAD-M

BackgroundBladder cancer (BCa) is the most common malignancy of the urinary tract which can be divided into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), and their microbial differences are not fully understood. This study was conducted by performing 2bRAD sequencing for Microbiome (2bRAD-M) on NMIBC and MIBC tissue samples to investigate the microbiota differences between NMIBC and MIBC individuals.MethodsA total of 22 patients with BCa, including 7 NMIBC and 15 MIBC, were recruited. Tumor tissues were surgically removed as samples and DNA was extracted. Type IIB restriction endonucleases were used to enzymatically cleave the microbial genome for each microbe’s tag and map it to species-specific 2bRAD markers to enable qualitative and quantitative studies of microbes between MIBC and NMIBC tissues.ResultsA total of 527 species were detected. The microbial diversity of NMIBC tissues was significantly higher than that of MIBC tissues. Microbial composition of the two tumor tissues was similar, where Ralstonia_sp000620465 was the most dominant species. 4 species (Acinetobacter_guillouiae, Anoxybacillus_A_rupiensis, Brevibacillus_agri and Staphylococcus_lugdunensis) were enriched in NMIBC, while Ralstonia_mannitolilytica, Ralstonia_pickettii, and Ralstonia_sp000620465 were overrepresented in MIBC. 252 discriminatory character taxa were also revealed by linear discriminant analysis effect sizea (LEfSe). Species importance point plots identified Ralstonia_sp000620465, Cutibacterium_acnes and Ralstonia_pickettii as the three most important species between the two groups. Meanwhile, functional annotation analysis showed 3011 different COGs and 344 related signaling pathways between MIBC and NMIBC microbiome.ConclusionThis first 2bRAD-M microbiome study on MIBC and NMIBC tissues revealed significant differences in the microbial environment between the two groups, which implies a potential association between tumor microbial dysbiosis and BCa, and provides a possible target and basis for subsequent studies on the mechanisms of BCa development and progression

Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis

There are numerous types of pathological changes in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), including apoptosis of neurons. HIV-1 transactivator of transcription (Tat) protein, which is encoded by HIV-1, may promote apoptosis in HAND. Forkhead box O3 (FOXO3) is a multispecific transcription factor that has roles in many biological processes, including cellular apoptosis. The aim of this study was to determine whether FOXO3 is activated by HIV-1 Tat and to investigate its role in neuronal apoptosis in HAND. We employed tissue staining and related molecular biological experimental methods to confirm our hypothesis. The in vivo experimental results demonstrated that the expression of nuclear FOXO3 increased in the apoptotic neurons of the cerebral cortexes of rhesus macaques infected with simian human immunodeficiency virus (SHIV). The in vitro investigation showed that HIV-1 Tat activated FOXO3, causing it to move from the cytoplasm to the nucleus via the c-Jun N-terminal kinase (JNK) signaling pathway in SH-SY5Y cells. Moreover, FOXO3 down-regulated expression of the anti-apoptosis gene B-cell lymphoma 2 (Bcl-2) and up-regulated the expression of the pro-apoptosis gene Bcl-2-like 11 (Bim) after entering the nucleus, eventually causing cellular apoptosis. Finally, reduction of nuclear FOXO3 reversed cellular apoptosis. Our results suggest that HIV-1 Tat induces FOXO3 to translocate from the cytoplasm to the nucleus via the JNK signaling pathway, leading to neuronal apoptosis. Agents targeting FOXO3 may provide approaches for restoring neuronal function in HAND

Biomimetic Nanosilica-Collagen Scaffolds for In Situ Bone Regeneration: Toward a Cell-Free, One-Step Surgery.

Current approaches to fabrication of nSC composites for bone tissue engineering (BTE) have limited capacity to achieve uniform surface functionalization while replicating the complex architecture and bioactivity of native bone, compromising application of these nanocomposites for in situ bone regeneration. A robust biosilicification strategy is reported to impart a uniform and stable osteoinductive surface to porous collagen scaffolds. The resultant nSC composites possess a native-bone-like porous structure and a nanosilica coating. The osteoinductivity of the nSC scaffolds is strongly dependent on the surface roughness and silicon content in the silica coating. Notably, without the use of exogenous cells and growth factors (GFs), the nSC scaffolds induce successful repair of a critical-sized calvarium defect in a rabbit model. It is revealed that topographic and chemical cues presented by nSC scaffolds could synergistically activate multiple signaling pathways related to mesenchymal stem cell recruitment and bone regeneration. Thus, this facile surface biosilicification approach could be valuable by enabling production of BTE scaffolds with large sizes, complex porous structures, and varied osteoinductivity. The nanosilica-functionalized scaffolds can be implanted via a cell/GF-free, one-step surgery for in situ bone regeneration, thus demonstrating high potential for clinical translation in treatment of massive bone defects

MicroRNA-29a-3p Downregulation Causes Gab1 Upregulation to Promote Glioma Cell Proliferation

Background/Aims: Glioma causes significant human mortalities annually. Molecularly-targeted therapy is a focus of glioma research. Methods: Grb2-associated binding 1 (Gab1) expression and microRNA-29a-3p (“miR-29a-3p”) expression in human glioma cells and tissues were tested by Western blotting assay and qRT-PCR assay. shRNA/siRNA strategy was applied to silence Gab1 in human glioma cells. miR-29a or anti-sense miR-29a construct was transfected to human glioma cells. Cell proliferation was tested by BrdU ELISA assay and cell counting assay. Results: We show that expression of Gab1 was significantly elevated in human glioma tissues and cells, which correlated with downregulation of its putative microRNA: miR-29a-3p. In A172 glioma cells and primary human glioma cells, Gab1 shRNA/siRNA inhibited Akt-Erk activation and cell proliferation. Forced-expression of miR-29a-3p downregulated Gab1, inhibiting glioma cell proliferation, whereas miR-29a-3p was in-effective on cell proliferation in Gab1-silenced A172 cells. Furthermore, introduction of a 3’-untranslated region (3’-UTR) mutant Gab1 (UTR-G160A) blocked miR-29a-3p-induced inhibition on Akt signaling and A172 cell proliferation. Conclusions: miR-29a-3p downregulation leads to Gab1 upregulation to promote glioma cell proliferation

Horizontal visibility graphs transformed from fractional Brownian motions: Topological properties versus Hurst index

Nonlinear time series analysis aims at understanding the dynamics of stochastic or chaotic processes. In recent years, quite a few methods have been proposed to transform a single time series to a complex network so that the dynamics of the process can be understood by investigating the topological properties of the network. We study the topological properties of horizontal visibility graphs constructed from fractional Brownian motions with different Hurst index $H\in(0,1)$. Special attention has been paid to the impact of Hurst index on the topological properties. It is found that the clustering coefficient $C$ decreases when $H$ increases. We also found that the mean length $L$ of the shortest paths increases exponentially with $H$ for fixed length $N$ of the original time series. In addition, $L$ increases linearly with respect to $N$ when $H$ is close to 1 and in a logarithmic form when $H$ is close to 0. Although the occurrence of different motifs changes with $H$, the motif rank pattern remains unchanged for different $H$. Adopting the node-covering box-counting method, the horizontal visibility graphs are found to be fractals and the fractal dimension $d_B$ decreases with $H$. Furthermore, the Pearson coefficients of the networks are positive and the degree-degree correlations increase with the degree, which indicate that the horizontal visibility graphs are assortative. With the increase of $H$, the Pearson coefficient decreases first and then increases, in which the turning point is around $H=0.6$. The presence of both fractality and assortativity in the horizontal visibility graphs converted from fractional Brownian motions is different from many cases where fractal networks are usually disassortative.Comment: 12 pages, 8 figure

The tomato Prf complex is a molecular trap for bacterial effectors based on Pto transphosphorylation

The bacteria Pseudomonas syringae is a pathogen of many crop species and one of the model pathogens for studying plant and bacterial arms race coevolution. In the current model, plants perceive bacteria pathogens via plasma membrane receptors, and recognition leads to the activation of general defenses. In turn, bacteria inject proteins called effectors into the plant cell to prevent the activation of immune responses. AvrPto and AvrPtoB are two such proteins that inhibit multiple plant kinases. The tomato plant has reacted to these effectors by the evolution of a cytoplasmic resistance complex. This complex is compromised of two proteins, Prf and Pto kinase, and is capable of recognizing the effector proteins. How the Pto kinase is able to avoid inhibition by the effector proteins is currently unknown. Our data shows how the tomato plant utilizes dimerization of resistance proteins to gain advantage over the faster evolving bacterial pathogen. Here we illustrate that oligomerisation of Prf brings into proximity two Pto kinases allowing them to avoid inhibition by the effectors by transphosphorylation and to activate immune responses

Epidemiology and mechanism of drug resistance of Mycoplasma pneumoniae in Beijing, China: A multi-center study

Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community-acquired respiratory tract infections (RTIs). We aimed to investigate the prevalence of M. pneumoniae infection, antibiotic resistance and genetic diversity of M. pneumoniae isolates across multiple centers in Beijing, China. P1 protein was detected by Nested PCR to analyze the occurrence of M. pneumoniae in pediatric patients with RTI. M. pneumoniae isolates were cultured and analyzed by Nested-PCR to determine their genotypes. Broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of antibiotics. Out of 822 children with RTI admitted to 11 hospitals in Beijing, 341 (41.48%) were positive for M. pneumoniae by Nested PCR and 236 (69.21%) samples had mutations in 23S rRNA domain V. The highest proportion of M. pneumoniae positive samples was observed in school-age children (118/190; 62.11%) and in pediatric patients with pneumonia (220/389; 56.56%). Out of 341 M. pneumoniae positive samples, 99 (12.04%) isolates were successfully cultured and the MIC values were determined for 65 M. pneumoniae strains. Out of these, 57 (87.69%) strains were resistant to macrolides, and all 65 strains were sensitive to tetracyclines or quinolones. M. pneumoniae P1 type I and P1 type II strains were found in 57/65 (87.69%) and 8/65 (12.31%) of cultured isolates, respectively. Overall, we demonstrated a high prevalence of M. pneumoniae infection and high macrolide resistance of M. pneumoniae strains in Beijing. School-age children were more susceptible to M. pneumoniae, particularly the children with pneumonia. Thus, establishment of a systematic surveillance program to fully understand the epidemiology of M. pneumoniae is critical for the standardized use of antibiotics in China