Low T3 syndrome as a predictor of poor prognosis in peripheral T-cell lymphomas.

PURPOSE: The purpose of the study was to evaluate the prognostic value of low T3 syndrome in peripheral T-cell lymphomas (PTCLs). METHODS: One hundred and seventy-four patients of newly diagnosed PTCLs were enrolled in the study. We performed statistical analysis based on the clinical data collected. RESULTS: Thirty-Six (20.69%) patients had low T3 syndrome at first admission. Results suggested that the patients with higher score of ECOG PS, International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PIT), bone marrow involvement and lower level of albumin tended to develop low T3 syndrome. The median progression-free survival (PFS) and overall survival (OS) were 10 months and 36 months, respectively, for all patients. Pre-existing low T3 syndrome was in correlation with worse PFS and OS. Patients with low T3 syndrome showed worse PFS (4 months vs 13 months, P = 0.0001) and OS (7 months vs 83 months, P < 0.0001) than patients without low T3 syndrome. IPI and PIT, respectively, combined with low T3 syndrome improved the ability to predict OS and PFS of PTCLs. CONCLUSIONS: The study indicated that low T3 syndrome may be a good candidate for predicting prognosis of peripheral T-cell lymphomas.

Prognostic value of POD18 combined with improved IELSG in primary central nervous system lymphoma.

PURPOSE: The International Extranodal Lymphoma Study Group (IELSG) score is widely used in clinical practice to stratify the risk of primary central nervous system lymphoma (PCNSL) patients. Our study aims to confirm and improve the IELSG score in PCNSL patients based on Chinese populations. MATERIALS AND METHODS: A total of 79 PCNSL patients were retrospectively analyzed. All patients treated with high-dose methotrexate (HD-MTX)-based therapy collected clinical data. The receiver-operating characteristic (ROC) curve was used to determine the optimal cut-off values for the factors in IELSG score. Progression of disease (POD) at the most landmark time point was determine by Epanechnikov kernel and the area under the ROC curve (AUROC). Kaplan-Meier and multivariable regression methods were used to analyze survival data. Nomogram was generated for calculating the weight of each selected factor. RESULTS: The traditional IELSG score had no significant difference on OS and PFS except ECOG ≥ 2 and could not stratify the risk groups in PCNSL. The improved IELSG scoring system was established, which incorporated age ≥ 54 years, ECOG ≥ 2, deep brain structure, elevated CSF protein, and LDH/ULN > 0.75. On the other hand, POD18 was identified as a new powerful prognostic factor for PCNSL. In multivariate analysis, POD18 and the improved IELSG scoring system were independent prognostic factors for OS. Nomogram including the two significant variables showed the best performance (C-index = 0.828). CONCLUSIONS: In this study, the IELSG score was improved and a new prognostic indicator POD18 was incorporated to construct a nomogram prognostic model, thereby further improving the predictive ability of the model.

miR-139-5p protects septic mice with acute lung injury by inhibiting Toll-like receptor 4/Myeloid differentiation factor 88/Nuclear factor-&mac_kgr;B signaling pathway.

OBJECTIVES: To investigate the role of miR-139-5p and the TLR4/MyD88/NF-κB signaling pathway in acute lung injury in septic mice. METHOD: A total of 140 healthy male SPF C57BL/6 mice were divided into seven groups, i.e., Normal, Control, NC, miR-139-5p mimic, miR-139-5p inhibitor, TAK-242, and miR-139-5p inhibitor+TAK-242 groups. The levels of miR-139-5p, proteins related to the TLR4/MyD88/NF-κB signaling pathway (TLR4, MyD88, and p-NF-κB p50), and MPO, SOD, GSH, and MDA in lung tissue were measured. The lung tissue wet-to-dry mass ratio (W/D), arterial oxygen partial pressure (PaO2), and carbon dioxide partial pressure (PaCO2) were measured. RESULTS: A web-based bioinformatic tool predicted that MyD88 was a target of miR-139-5p, which was verified by a dual luciferase reporter assay. Compared with those in the Normal group, the levels of miR-139-5p, PaO2, SOD, and GSH were significantly lower, while those of TLR4, MyD88, p-NF-κB p50, W/D, PaCO2, IL-1ß, TNF-α, IL-6, MPO, and MDA were higher in all other groups. Moreover, compared with their levels in the Control group, these indicators exhibited contrasting results in the miR-139-5p mimic and TAK-242 groups, but were similar in the miR-139-5p inhibitor group. In the miR-139-5p inhibitor+TAK-242 group, acute lung injury, aggravated by miR-139-5p inhibitor, was partially rescued by TAK-242. CONCLUSION: miR-139-5p inhibits the TLR4/MyD88/NF-κB signaling pathway to alleviate acute lung injury in septic mice.

Real-World Effectiveness of Direct-Acting Antiviral Regimens against Hepatitis C Virus (HCV) Genotype 3 Infection: A Systematic Review and Meta-Analysis.

Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.

miR-139-5p protects septic mice with acute lung injury by inhibiting Toll-like receptor 4/Myeloid differentiation factor 88/Nuclear factor-&mac_kgr; B signaling pathway

OBJECTIVES: To investigate the role of miR-139-5p and the TLR4/MyD88/NF-κB signaling pathway in acute lung injury in septic mice. METHOD: A total of 140 healthy male SPF C57BL/6 mice were divided into seven groups, i.e., Normal, Control, NC, miR-139-5p mimic, miR-139-5p inhibitor, TAK-242, and miR-139-5p inhibitor+TAK-242 groups. The levels of miR-139-5p, proteins related to the TLR4/MyD88/NF-κB signaling pathway (TLR4, MyD88, and p-NF-κB p50), and MPO, SOD, GSH, and MDA in lung tissue were measured. The lung tissue wet-to-dry mass ratio (W/D), arterial oxygen partial pressure (PaO2), and carbon dioxide partial pressure (PaCO2) were measured. RESULTS: A web-based bioinformatic tool predicted that MyD88 was a target of miR-139-5p, which was verified by a dual luciferase reporter assay. Compared with those in the Normal group, the levels of miR-139-5p, PaO2, SOD, and GSH were significantly lower, while those of TLR4, MyD88, p-NF-κB p50, W/D, PaCO2, IL-1β, TNF-α, IL-6, MPO, and MDA were higher in all other groups. Moreover, compared with their levels in the Control group, these indicators exhibited contrasting results in the miR-139-5p mimic and TAK-242 groups, but were similar in the miR-139-5p inhibitor group. In the miR-139-5p inhibitor+TAK-242 group, acute lung injury, aggravated by miR-139-5p inhibitor, was partially rescued by TAK-242. CONCLUSION: miR-139-5p inhibits the TLR4/MyD88/NF-κB signaling pathway to alleviate acute lung injury in septic mice.

The complete plastid genome and phylogenetic analysis of Gracilaria chilensis.

Gracilaria chilensis is an economically important species of macroalgae. The plastid genome sequence of G. chilensis is 185,640 bp with a GC content of 29.34%. A total of 236 genes were determined, containing 203 protein-encoding genes, three rRNA genes, 30 tRNA genes, and one intron (with intronic ORF) inserted into the trnM gene. The gene content and structure of Gracilariaceae species were relatively well conserved. The phylogenetic analysis, based on the red algal plastid genomes, suggested that G. chilensis had a closer relationship with Gracilaria tenuistipitata var. liui in Gracilaria.

Periplaneta americana extract promotes intestinal mucosa repair of ulcerative colitis in rat.

PURPOSE: To investigate the mechanism of Periplaneta americana extract promoting intestinal mucosal repair of OXZ-induced colitis in rat. METHODS: All experiments used an equal number of male and female SD rats (n=48). We injected OXZ into the colon to induce UC rat model. To determine the optimal concentration of P. Americana's extract (PA-40), it was classified into low (L), medium (M), and high (H) doses. After OXZ treatment, each drug was administered by enema for 7 consecutive days. Rats were divided into the following 6 groups: (1) Saline treatment group (NC), (2) OXZ treatment UC model group (MC), (3) OXZ + budesonide group (BUN), (4) OXZ + PA-40 L group, (5) OXZ + PA-40 M group, (6) OXZ + PA-40 H group. Disease activity index (DAI) scores, colon length, histopathological score, serum cytokine level (IL-4, IL-10, iNOS, tNOS), and amount of MPO, EGF, IL-13 in colonic mucosa were measured. RESULTS: PA treatment had a significant healing effect on the OXZ-colitis model and significantly reduced the lesioned area, especially in the PA-40H groups. PA treatment did not alter the expression of IL-10 and MPO level, but increased EGF (epidermal growth factor) and decrease IL-13 in the colonic tissue. PA inhibited the rise of NOSs (nitric oxide synthase) and decreased the serum IL-4 level. CONCLUSIONS: The data suggest that Periplaneta americana extract may be a potential compound for the treatment of colonic lesions. The mechanism may be related to inhibiting the secretion of IL-13 and promoting the formation of EGF.

Characterization of Pneumocystis jirovecii pneumonia at three tertiary comprehensive hospitals in southern China.

Due to the increasing use of immunosuppressant therapy, Pneumocystis jirovecii pneumonia (PJP) has become an emerging concern in human immunodeficiency virus (HIV)-negative patients. In this study, we conducted a retrospective study of 96 hospitalized patients with PJP from January 2015 to June 2019 at three tertiary comprehensive hospitals in Southern China. Information was collected regarding patient demographics, clinical manifestations, risk factors, laboratory analyses, radiological images, and treatment outcomes. PJP infection was most commonly found in middle-aged men. Kidney diseases (35.5%) and connective tissue diseases (38.7%) were the predominant risk factors for PJP. About half of the patients (48.4%) received glucocorticoid, immunosuppressant, and/or chemotherapy in a low dose or in a short-term (< 3 months). None of the patients had previously received trimethoprim-sulfamethoxazole (TMP-SMX) for PJP prophylaxis. All patients had two or more clinical manifestations (cough, dyspnea, fever, and chest pain). Biochemical investigations of CRP, ESR, PaO2, LDH, and KL-6 showed that over 90% of the patients exceeded the reference range of indicators. Our analyses revealed the dominant risk factors (HIV, kidney diseases, and connective tissue diseases) and the most consistent biochemical indicators (LDH, BG, and KL-6) for PJP. Moreover, early prophylaxis, diagnosis, and treatment should contribute to improve the survival of these PJP patients.

Periplaneta americana extract promotes intestinal mucosa repair of ulcerative colitis in rat

Purpose: To investigate the mechanism of Periplaneta americana extract promoting intestinal mucosal repair of OXZ-induced colitis in rat. Methods: All experiments used an equal number of male and female SD rats (n=48). We injected OXZ into the colon to induce UC rat model. To determine the optimal concentration of P. Americana's extract (PA-40), it was classified into low (L), medium (M), and high (H) doses. After OXZ treatment, each drug was administered by enema for 7 consecutive days. Rats were divided into the following 6 groups: (1) Saline treatment group (NC), (2) OXZ treatment UC model group (MC), (3) OXZ + budesonide group (BUN), (4) OXZ + PA-40 L group, (5) OXZ + PA-40 M group, (6) OXZ + PA-40 H group. Disease activity index (DAI) scores, colon length, histopathological score, serum cytokine level (IL-4, IL-10, iNOS, tNOS), and amount of MPO, EGF, IL-13 in colonic mucosa were measured. Results: PA treatment had a significant healing effect on the OXZ-colitis model and significantly reduced the lesioned area, especially in the PA-40H groups. PA treatment did not alter the expression of IL-10 and MPO level, but increased EGF (epidermal growth factor) and decrease IL-13 in the colonic tissue. PA inhibited the rise of NOSs (nitric oxide synthase) and decreased the serum IL-4 level. Conclusions: The data suggest that Periplaneta americana extract may be a potential compound for the treatment of colonic lesions. The mechanism may be related to inhibiting the secretion of IL-13 and promoting the formation of EGF.(AU)

Periplaneta americana extract promotes intestinal mucosa repair of ulcerative colitis in rat

Abstract Purpose: To investigate the mechanism of Periplaneta americana extract promoting intestinal mucosal repair of OXZ-induced colitis in rat. Methods: All experiments used an equal number of male and female SD rats (n=48). We injected OXZ into the colon to induce UC rat model. To determine the optimal concentration of P. Americana's extract (PA-40), it was classified into low (L), medium (M), and high (H) doses. After OXZ treatment, each drug was administered by enema for 7 consecutive days. Rats were divided into the following 6 groups: (1) Saline treatment group (NC), (2) OXZ treatment UC model group (MC), (3) OXZ + budesonide group (BUN), (4) OXZ + PA-40 L group, (5) OXZ + PA-40 M group, (6) OXZ + PA-40 H group. Disease activity index (DAI) scores, colon length, histopathological score, serum cytokine level (IL-4, IL-10, iNOS, tNOS), and amount of MPO, EGF, IL-13 in colonic mucosa were measured. Results: PA treatment had a significant healing effect on the OXZ-colitis model and significantly reduced the lesioned area, especially in the PA-40H groups. PA treatment did not alter the expression of IL-10 and MPO level, but increased EGF (epidermal growth factor) and decrease IL-13 in the colonic tissue. PA inhibited the rise of NOSs (nitric oxide synthase) and decreased the serum IL-4 level. Conclusions: The data suggest that Periplaneta americana extract may be a potential compound for the treatment of colonic lesions. The mechanism may be related to inhibiting the secretion of IL-13 and promoting the formation of EGF.

Test-retest reproducibility of a multi-atlas automated segmentation tool on multimodality brain MRI.

INTRODUCTION: The increasing use of large sample sizes for population and personalized medicine requires high-throughput tools for imaging processing that can handle large amounts of data with diverse image modalities, perform a biologically meaningful information reduction, and result in comprehensive quantification. Exploring the reproducibility of these tools reveals the specific strengths and weaknesses that heavily influence the interpretation of results, contributing to transparence in science. METHODS: We tested-retested the reproducibility of MRICloud, a free automated method for whole-brain, multimodal MRI segmentation and quantification, on two public, independent datasets of healthy adults. RESULTS: The reproducibility was extremely high for T1-volumetric analysis, high for diffusion tensor images (DTI) (however, regionally variable), and low for resting-state fMRI. CONCLUSION: In general, the reproducibility of the different modalities was slightly superior to that of widely used software. This analysis serves as a normative reference for planning samples and for the interpretation of structure-based MRI studies.

Therapeutic Effect of HGF on NASH Mice Through HGF/c-Met and JAK2-STAT3 Signalling Pathway.

INTRODUCTION AND AIM: Hepatocyte growth factor (HGF) has been shown to ameliorate liver inflammation and fibrosis; however, the mechanism underlying its effects in non-alcoholic steatohepatitis (NASH) is unclear. This study aimed to analyse the relationship between the JAK2-STAT3 signalling pathway and the ameliorating effect of HGF on NASH. MATERIAL AND METHODS: Mice were fed a high-fat diet (HFD) for 16 weeks, and then plasma and hepatic tissues were collected. Histological and clinical chemistry assays were performed to assess liver disease. The mRNA and protein levels of JAK2, STAT3, and c-Met were assessed by real-time PCR and western blotting, respectively. RESULTS: Serum ALT, AST, and TG levels were increased in NASH mice. Histological analysis showed different degrees of steatosis, inflammatory infiltrates, and fibrosis in HFD animals. Exogenous administration of recombinant human (rh) HGF via the tail vein for 14 days markedly decreased ALT and AST to levels lower than those in the control group. Compared with the levels in HFD mice, c-Met, p-c-Met, JAK2, p-JAK2, and p-STAT3 levels were increased in mice that were administered HGF (P < 0.05). Furthermore, silencing of HGF or blocking of its receptor c-Met affected JAK2 and STAT3 protein phosphorylation. CONCLUSIONS: Excess HGF highly probable improved NASH liver function. Combined with its ligand, c-Met, HGF may promote the phosphorylation of JAK2-STAT3 and inhibit inflammation in NASH. Therefore, it may be potentially useful treatment for NASH.

NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome.

Although B cell development requires expression of the B cell antigen receptor (BCR), it remains unclear whether engagement of self-antigen provides a positive impact for most B cells. Here, we show that BCR engagement by self-ligand during development in vivo results in up-regulation of the Nod-like receptor member Nod1, which recognizes the products of intestinal commensal bacteria. In anti-thymocyte/Thy-1 autoreactive BCR knock-in mice lacking self-Thy-1 ligand, immunoglobulin light chain editing occurred, generating B cells with up-regulated Nod1, including follicular and marginal zone B cells with natural autoreactivity. This BCR editing with increased Nod1 resulted in preferential survival. In normal adult mice, most mature B cells are enriched for Nod1 up-regulated cells, and signaling through Nod1 promotes competitive survival of mature B cells. These findings demonstrate a role for microbial products in promoting survival of mature B cells through up-regulated Nod1, providing a positive effect of BCR engagement on development of most B cells.

The complete mitochondrial genome of the economic red alga, Gracilaria chilensis.

Gracilaria chilensis is an economically important marine alga. In this study, we obtained complete mitogenome of G. chilensis by high-throughput sequencing, which was mapped as a circular molecule of 26,897 bp with 27.56% GC content and was identified 53 genes, including 25 protein-coding genes, 2 rRNA genes, 26 tRNA genes, and 1 group II intron inserted into the trnI gene. In addition, a 162-bp stable stem loop was found in intergenic regions, which was most likely associated with DNA transcription and replication. The Bayesian phylogenetic tree of Gracilariaceae revealed that G. chilensis and G. salicornia and G. changii shared a closer relationship than G. vermiculophylla in the genus Gracilaria.

Design, synthesis, and structure-activity relationship of novel and effective apixaban derivatives as FXa inhibitors containing 1,2,4-triazole/pyrrole derivatives as P2 binding element.

Four series of novel and potent FXa inhibitors possessing the 1,2,4-triazole moiety and pyrrole moiety as P2 binding element and dihydroimidazole/tetrahydropyrimidine groups as P4 binding element were designed, synthesized, and evaluated for their anticoagulant activity in human and rabbit plasma in vitro. Most compounds showed moderate to excellent activity. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human FXa in vitro and rat venous thrombosis in vivo. The most promising compound 14a, with an IC50 (FXa) value of 0.15µM and 99% inhibition rate, was identified for further evaluation as an FXa inhibitor.

Long-term effect of biochar application on yield-scaled greenhouse gas emissions in a rice paddy cropping system: A four-year case study in south China.

To evaluate long-term effect of biochar application on yield-scaled greenhouse gas emissions (YSGE) in a paddy rice cropping system, a 4-year field experiment by static chamber - gas chromatograph method was conducted in South China. Principal component analysis and terminal restriction fragment length polymorphism (T-RFLP) and real-time qPCR was used to unravel the microbial mechanisms of biochar addition. Six treatments were included: control (CK), application of 5tha(-1) biochar (BC1), application of 10tha(-1) biochar (BC2), application of 10tha(-1) biochar (BC3), rice straw return at 2400kgha(-1)(RS) and inoculated rice straw return at 2400kgha(-1)(RI). The results indicated that biochar amendment significantly decreased methane (CH4) and gross greenhouse gas (GHG) emissions. This may primarily be ascribed to the stimulated biodiversity and abundance of methanotrophic microbes, increased soil pH and improved aeration by reducing bulk density after biochar incorporation. Compared with CK, RS and RI, 26.18%, 70.02%, 66.47% of CH4 flux and 26.14%, 70.16%, 66.46% of gross GHG emissions were reduced by biochar (mean of three biochar treatments), respectively. Furthermore, biochar significantly increased harvest index of double rice production (p<0.05). In comparison with CK, RS and RI, 29.14%, 68.04%, 62.28% of YSGE was reduced by biochar, respectively, and the highest biochar addition rate (20tha(-1)) contributed most to the mitigation of GHG emissions (36.24% decrease compared to CK) and improvement of rice yield (7.65% increase compared to CK). Results of our study suggested that long-term application of biochar should be the potential way to mitigate GHGs emissions and simultaneously improve rice productivity in the paddy rice system.

Antihyperlipidemic effect of Cyclocarya paliurus (Batal.) Iljinskaja extract and inhibition of apolipoprotein B48 overproduction in hyperlipidemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (CP) Batal., the sole species in its genus, is a native plant to China. As a traditional Chinese folk medicine, the tree leaves have been widely used for the treatment of metabolic disorders, including hyperlipidemia, obesity, diabetes and hypertension. AIM OF THE STUDY: The study aimed to evaluate the antihyperlipidemic effect of CP ethanol extract, as well as its inhibitory activity on apolipoproteinB48 (apoB48), in normal and hyperlipidemic mice. MATERIALS AND METHODS: The antihyperlipidemic effect of CP was evaluated in hyperlipidemic mice induced by high-fat diet for 4 weeks. CP ethanol extract (0.37, 0.75 and 1.5g/kg/day) was orally administrated once daily. Lipids and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), together with the indices of hepatic and renal functions were examined. RT-qPCR and western blotting were used to analysis the expression levels of tumor necrosis factor (TNF-α), total- and triglyceride-rich apoB48 (TRL-apoB48), as well as the phosphorylation of the mitogen-activatein kinase (MAPK). RESULTS: CP as well as simvastatin remarkably lowered the levels of TC, TG, LDL-C and MDA, and at the same time, elevated the HDL-C, SOD and GSH-Px in high-fat diet mice. It also decreased the serum concentration of total- and TRL-apoB48 in the fasting state. CP inhibited TNF-α expression and phosphorylation level of MAPK. Furthermore, the HE staining of liver and kidney, together with hepatic and renal function analysis showed hepato- and renoprotective activities of CP. CONCLUSIONS: These results suggested that CP possesses beneficial potentials for use in treating hyperlipidemia and the underlying lipid-lowering mechanism might associate with a down-regulation of the intestinal-associated lipoprotein apoB48, which may provide evidence about its practical application for treating hyperlipidemia and its complications.