[Analysis of the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 for intrahepatic parenchymal substantial lesions ≤3.0 cm].

Objective: To investigate the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 in high-risk hepatocellular carcinoma (HCC) patients with intrahepatic parenchymal substantial lesions ≤3.0 cm. Methods: A retrospective analysis was conducted in hospitals between September 2014 to April 2020. 131 pathologically confirmed non-HCC cases with lesions ≤3.0 cm in diameter were randomly matched with 131 cases with lesions ≤3.0 cm in diameter and divided into benign (56 cases), other hepatic malignant tumor (OM, 75 cases), and HCC group (131 cases) in a 1:1 ratio. MRI features of the lesions were analyzed and classified according to LI-RADS v2018 criteria (tie-break rule was applied to lesions with both HCC and LR-M features). Taking the pathological results as the gold standard, the sensitivity and specificity of the LI-RADS v2018 classification criteria and the more stringent LR-5 criteria (with three main signs of HCC at the same time) were calculated for HCC, OM or benign lesions diagnosis. Mann -Whitney U test was used to compare the classification results. Results: The number of cases classified as LR-M, LR-1, LR-2, LR-3, LR-4, and LR-5 in HCC group after applying the tie-break rule were 14, 0, 0, 12, 28, and 77, respectively. There were 40, 0, 0, 4, 17, 14 and 8, 5, 1, 26, 13, 3 cases in benign and OM group, respectively. There were 41 (41/77), 4 (4/14) and 1 (1/3) lesion case in the HCC, OM and benign group, respectively, that met the more stringent LR-5 criteria. The sensitivity of LR-4 combined with LR-5 (LR-4/5) criteria, LR-5 criteria and more stringent LR-5 criteria for HCC diagnosis were 80.2% (105/131), 58.8% (77/131) and 31.3% (41/131), respectively, and the specificity were 64.1% (84/131), 87.0% (114/131) and 96.2% (126/131), respectively. The sensitivity and specificity of LR-M were 53.3% (40/75) and 88.2% (165/187), respectively. The sensitivity and specificity using LR-1 combined with LR-2 (LR-1/2) criteria for the diagnosis of benign liver lesions were 10.7% (6/56) and 100% (206/206), respectively. Conclusions: LR-1/2, LR-5, and LR-M criteria have high diagnostic specificity for intrahepatic lesions with a diameter of ≤3.0 cm. Lesions classified as LR-3 are more likely to be benign. The specificity of LR-4/5 criteria is low, while the more stringent LR-5 criteria has a high specificity for HCC diagnosis.

Long non-coding RNA NEAT1 promotes tumor development and metastasis through targeting miR-224-5p in malignant melanoma.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA NEAT1 promotes tumor development and metastasis through targeting miR-224-5p in malignant melanoma, by J.-X. Zou, T.-W. Ge, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1302-1308-DOI: 10.26355/eurrev_202002_20187-PMID: 32096166" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20187.

Long non-coding RNA NEAT1 promotes tumor development and metastasis through targeting miR-224-5p in malignant melanoma.

OBJECTIVE: Melanoma is one of the most ordinary malignant tumors. Recent studies have revealed that long noncoding RNAs (lncRNAs) play an important role in the progression of tumorigenesis. This work aims to identify how lncRNA NEAT1 functions in the progression of melanoma. PATIENTS AND METHODS: NEAT1 expression of both melanoma patients' tissue samples and cell lines was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the function of NEAT1 was identified by performing the proliferation and transwell assay in vitro. Besides, the underlying mechanism was explored through the Luciferase assay and RNA immunoprecipitation (RIP) assay. In addition, tumor formation and metastasis assays were also conducted in vivo. RESULTS: In this research, NEAT1 expression was significantly higher in melanoma tissues compared with that in skin tissues with the melanocytic nevus. Cell proliferation and invasion of melanoma were inhibited after the knockdown of NEAT1 in vitro. Moreover, the results of further experiments revealed that microRNA-224-5p (miR-224-5p) was upregulated via the knockdown of NEAT1 and was also a direct target of NEAT1 in melanoma. Furthermore, tumor formation and metastasis of melanoma were inhibited via the knockdown of NEAT1 in nude mice. CONCLUSIONS: Our study suggests that NEAT1 enhances melanoma cell proliferation and metastasis via sponging miR-224-5p in vitro and in vivo.

Isolation and characterization of Aeromonas schubertii from diseased snakehead, Channa maculata (Lacepède).

Pure bacterial cultures were isolated from diseased snakeheads, Channa maculata (Lacepède), suffering high mortality in a farm in Zhongshan, southern China. Three isolates, namely ZS20100725, ZS20100725-1 and ZS20100725-2, were identified as Aeromonas schubertii. All the isolates showed high 16S rRNA sequence similarities with A. schubertii. The isolates exhibited strong virulence to snakeheads in experimental challenges with LD(50) ranging between 1.4 × 10(4) and 6.4 × 10(6) CFU g(-1). Two of the isolates were positive for haemolysin, elastase, lipase and lecithinase by phenotypic determination, which was further confirmed by PCR amplification of the haemolysin and elastase genes. In sterile liquid medium, the best growth conditions of strain ZS20100725 were 30 °C, pH 7 and 0.5% salinity (w/v). Antibiotic susceptibility tests showed that strain ZS20100725 was susceptible to cefoxitin, cefoperazone and chloramphenicol. Furthermore, histopathology of diseased snakeheads infected with A. schubertii showed necrosis and congestion in liver, kidney and spleen and also damage to the cardiac muscle, intestine and gills.

Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome.

Response to immunosuppressive therapy (IST) in younger patients with myelodysplastic syndrome (MDS) has been linked to a T-cell-dominant autoimmune process that impairs hematopoiesis. Analysis of the age-adjusted CD4:CD8 ratio in 76 MDS patients compared with 54 healthy controls showed that inadequate CD4+, rather than expansion of CD8+ T cells, was associated with a lower ratio in a group that included both lower and higher risk MDS patients defined by the International Prognostic Scoring System. In younger MDS patients, naive and memory phenotypes defined by CD45RA and CD62L display showed depletion of naive CD4+ and CD8+ T cells, suggesting a possible relationship to IST responsiveness. To determine the correlation between T-cell subset distribution, T-cell turnover and autoimmunity, a cohort of 20 patients were studied before and after IST. The CD4:CD8 ratio correlated inversely with the proliferative T-cell index before treatment in IST-responsive patients, suggesting that proliferation may be linked to accelerated CD4+ T-cell turnover and hematopoietic failure. Our data show seminal findings that both CD4+ and CD8+ T-cell subsets are dysregulated in MDS. Association between these T-cell defects and response to IST suggests that aberrant T-cell homeostasis and chronic activation are critical determinants influencing autoimmune hematopoietic suppression in younger patients.

Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome.

Selected patients with Myelodysplastic Syndromes (MDS) are responsive to immunosuppressive therapy, suggesting that hematopoietic suppressive T cells have a pathogenic role in ineffective hematopoiesis. We assessed T-cell receptor (TCR) clonality through combined flow cytometry and molecular analysis of the complementarity determining region (CDR)-3 of the T-cell receptor-Vbeta gene. We identified clonal T cells in 50% of MDS patients (n=52) compared to 5% of age-matched normal controls (n=20). The presence of T-cell clones was not associated with features linked previously to immunosuppression response, including WHO diagnostic category, karyotype, marrow cellularity, IPSS category, sex or age

Immunological basis for the use of TNFalpha-blocking agents in ankylosing spondylitis and immunological changes during treatment.

TNFalpha is expressed in high amounts at the site of inflammation in ankylosing spondylitis, which provided the basis to initiate treatment studies with TNF-blocking agents. We could show that the immunological effects of infliximab and etanercept differ in patients with AS, although the clinical effect was similarly good. While infliximab induced a downregulation of the production of the T-helper 1-cytokines IFNgamma and TNFalpha, etanercept treatment triggered rather an upregulation of these cytokines secreted by T cells after in vitro stimulation.

R-Ras contains a proline-rich site that binds to SH3 domains and is required for integrin activation by R-Ras.

R-Ras contains a proline-rich motif that resembles SH3 domain-binding sites but that has escaped notice previously. We show here that this site in R-Ras is capable of binding SH3 domains and that the SH3 domain binding may be important for R-Ras function. A fusion protein containing the SH3 domains of the adaptor protein Nck interacted strongly with the R-Ras proline-rich sequence and with the intact protein. The binding was independent of whether R-Ras was in its GDP or GTP form. The Nck binding, which was mediated by the second of the three SH3 domains of Nck, was obliterated by mutations in the proline-rich sequence of R-Ras. The interaction of Nck with R-Ras could also be shown in yeast two-hybrid assays and by co-immunoprecipitation in human cells transfected with Nck and R-Ras. Previous results have shown that the expression of a constitutively active R-Ras mutant, R-Ras(38V), converts mouse 32D monocytic cells into highly adherent cells. Introducing the proline mutations into R-Ras(38V) suppressed the effect of R-Ras on 32D cell adhesion while not affecting GTP binding. These results reveal an unexpected regulatory pathway that controls R-Ras through an SH3 domain interaction. This pathway appears to be important for the ability of R-Ras to control cell adhesion.

An Eph receptor regulates integrin activity through R-Ras.

The ability of integrins to mediate cell attachment to extracellular matrices and to blood proteins is regulated from inside the cell. Increased ligand-binding activity of integrins is critical for platelet aggregation upon blood clotting and for leukocyte extravasation to inflamed tissues. Decreased adhesion is thought to promote tumor cell invasion. R-Ras, a small intracellular GTPase, regulates the binding of integrins to their ligands outside the cell. Here we show that the Eph receptor tyrosine kinase, EphB2, can control integrin activity through R-Ras. Cells in which EphB2 is activated become poorly adherent to substrates coated with integrin ligands, and a tyrosine residue in the R-Ras effector domain is phosphorylated. The R-Ras phosphorylation and loss of cell adhesion are causally related, because forced expression of an R-Ras variant resistant to phosphorylation at the critical site made cells unresponsive to the anti-adhesive effect of EphB2. This is an unusual regulatory pathway among the small GTPases. Reduced adhesiveness induced through the Eph/R-Ras pathway may explain the repulsive effect of the Eph receptors in axonal pathfinding and may facilitate tumor cell invasion and angiogenesis.

Altered expression of tumor suppressors p16 and Rb in gastric carcinogenesis.

AIM: To determine whether expression of the tumor suppressors p16 and Rb is altered in gastric carcinoma. METHODS: Mucosal biopsies were endoscopically obtained from patients with superficial gastritis (n = 12), atrophic gastritis (n = 15), atypical hyperplasia (n = 20) and gastric cancer (n = 40). Upon obtainment, all samples were immediately fixed with 10% buffered formalin, embedded in paraffin, and sectioned serially. Protein expression of p16 and Rb was detected by immunohistochemistry (ABC method). RESULTS: The gastric epithelium samples showed various degrees of nuclear immunostaining for p16 and Rb according to the different stage of lesion. Progressive pathology of the lesions was associated with a decreasing trend in positive immunostaining for p16 protein (83.3% > 73.3% > 30.0% > 27.5%) but an increasing trend for Rb protein (25.0% > 46.7% > 60.0% > 67.5%). A negative correlation was found between these two parameters and gastric cancer. Correlation analysis of the 40 cases of gastric cancer identified a negative correlation for 20 of the cases. When positive (n = 9) and negative tissues (n = 11) were compared, a statistically significant difference was found (50.0%, 22.5%, 27.5%) (P < 0.05). CONCLUSION: Abnormal expression of p16 and Rb may play an important role in gastric carcinogenesis.

The requirement for Vif of SIVmac is cell-type dependent.

The vif gene (viral infectivity factor) of the human and simian immunodeficiency viruses (HIV and SIV) is present in almost all members of the lentivirus group of retroviruses. This gene is highly conserved among different HIV and SIV isolates and is therefore presumed to play an important role in pathogenesis. To analyse the role of Vif in SIV, three SIVmac mutants have been constructed by introducing site-specific mutations or deletions into vif of the pathogenic molecular clone SIVmac239. The effect of Vif on viral replication in T cells was examined by transfecting equal amounts of either vif-positive or vif-negative viral DNA into SupT1, CEM-SS and H9 cells. Reverse transcriptase assay of supernatants from transfected cultures revealed that both SupT1 and CEM-SS cell lines supported replication of all three vif mutants to a level comparable to the parental vif-positive virus, whereas vif mutants did not replicate in H9 cells. Our results demonstrate that the requirement for Vif in SIVmac replication is cell-type dependent and that sequences near both the N and C termini are required for its function. Vif-defective SIVmac239, produced in transfected SupT1 and CEM-SS cells, failed to infect primary T lymphocytes, whereas both vif-positive and vif-defective viruses established productive infection in CEMx174 cells. These findings in primary cells suggest that Vif plays an important role in viral replication in vivo.

The transcriptional transactivator of simian foamy virus 1 binds to a DNA target element in the viral internal promoter.

The transcriptional transactivator (Tas) of simian foamy virus type 1 strongly augments gene expression directed by both the promoter in the viral long terminal repeat and the newly discovered internal promoter located within the env gene. A region of 121 bp, located immediately 5' to the TATA box in the internal promoter, is required for transactivation by Tas. The present study aimed to identify the precise Tas-responsive target(s) in this region and to determine the role of Tas in transcriptional regulation. By analysis of both clustered-site mutations and hybrid promoters in transient expression assays in murine and simian cells, two separate sequence elements within this 121-bp region were shown to be Tas-dependent transcriptional enhancers. These targets, each < 30 bp in length and displaying no apparent sequence homology one to the other, are designated the promoter-proximal and promoter-distal elements. By means of the gel electrophoresis mobility-shift assays, using purified glutathione S-transferase-Tas fusion protein expressed in Escherichia coli, the target proximal to the TATA box exhibited strong binding to glutathione S-transferase-Tas, whereas the distal element appears not to bind. In addition, footprint analysis revealed that 26 bp in the promoter proximal element was protected by glutathione S-transferase-Tas from DNase I. We propose a model for transactivation of the simian foamy virus type 1 internal promoter in which Tas interacts directly with the proximal target element positioned immediately 5' to the TATA box. In this model, Tas attached to this element is presumed to interact with a component(s) of the cellular RNA polymerase II initiation complex and thereby enhance transcription directed by the viral internal promoter.

[Synthesis and antimicrobial activities of tetrahydro-2H-1,3,5-thiadiazine-2-thiones].

Ten 3-benzyl-5-substitued tetrahydro-2H-1,3,5-thiadiazine-2-thiones were synthesized and seven of them are reported for the first time. The structures of the compounds have been elucidated by UV, IR, H-NMR and elemental analysis. The in vitro activity of the compounds against 6 kinds of bacteria and 2 kinds of fungi was tested. The antimicrobial activities of all compounds are more potent than sulfadiazine sodium and less potent than norfloxacini. All compounds were found to be more active against gram-negative and less active against gram-positive bacteria and weak against fungi.