A prominent gene activation role for C-terminal binding protein in mediating PcG/trxG proteins through Hox gene regulation.

The evolutionarily conserved C-terminal binding protein (CtBP) has been well characterized as a transcriptional co-repressor. Herein, we report a previously unreported function for CtBP, showing that lowering CtBP dosage genetically suppresses Polycomb group (PcG) loss-of-function phenotypes while enhancing that of trithorax group (trxG) in Drosophila, suggesting that the role of CtBP in gene activation is more pronounced in fly development than previously thought. In fly cells, we show that CtBP is required for the derepression of the most direct PcG target genes, which are highly enriched by homeobox transcription factors, including Hox genes. Using ChIP and co-IP assays, we demonstrate that CtBP is directly required for the molecular switch between H3K27me3 and H3K27ac in the derepressed Hox loci. In addition, CtBP physically interacts with many proteins, such as UTX, CBP, Fs(1)h and RNA Pol II, that have activation roles, potentially assisting in their recruitment to promoters and Polycomb response elements that control Hox gene expression. Therefore, we reveal a prominent activation function for CtBP that confers a major role for the epigenetic program of fly segmentation and development.

Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2.

OBJECTIVE: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. METHODS: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. RESULTS: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. CONCLUSION: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.

[Latest Findings on the Interaction Mechanism Between Depressive Disorder and Intestinal Permeability].

The intestinal barrier, a complex structure consisting of multiple layers of defense barriers, blocks the transfer of intestinal and foreign bacteria and their metabolites into the internal environment of the human body. Intestinal permeability can be used to evaluate the integrity of the intestinal barrier. Increased intestinal permeability has been observed in patients with depressive disorder. Some studies have reported an interaction between depressive disorder and intestinal barrier. Herein, we reviewed reported findings on the mechanisms of how systematic low-grade inflammation, vagal nerve dysfunction, and hypothalamic-pituitary-adrenal axis dysfunction cause changes in intestinal permeability in patients with depressive disorder and the pathogenic mechanism of how bacterial translocation caused by damaged intestinal barrier leads to depressive disorder. In addition, the potential mechanisms of how antidepressants improve intestinal permeability and how probiotics improve depressive disorder have been discussed.

Naked cuticle inhibits wingless signaling in Drosophila wing development.

Wnt signaling is one of the major signaling pathways that regulate cell differentiation, tissue patterning and stem cell homeostasis and its dysfunction causes many human diseases, such as cancer. It is of tremendous interests to understand how Wnt signaling is regulated in a precise manner both temporally and spatially. Naked cuticle (Nkd) acts as a negative-feedback inhibitor for Wingless (Wg, a fly Wnt) signaling in Drosophila embryonic development. However, the role of Nkd remains controversial in later fly development, particularly on the canonical Wg pathway. In the present study, we show that nkd is essential for wing pattern formation, such that both gain and loss of nkd result in the disruption of Wg target expression in larvae stage and abnormal adult wing morphologies. Furthermore, we demonstrate that a thirty amino acid fragment in Nkd, identified previously in Wharton lab, is critical for the canonical Wg signaling, but is dispensable for Wg/planar cell polarity pathway. Putting aside the pleiotropic nature of nkd function, i.e. its role in the Decapentaplegic signaling, we conclude that Nkd universally inhibits the canonical Wg pathway across a life span of Drosophila development.

Effect of cinnamon essential oil on gut microbiota in the mouse model of dextran sodium sulfate-induced colitis.

Increasing evidence has confirmed that the antimicrobial and anti-inflammatory effects of cinnamon essential oil (CEO) contribute to protection against inflammatory bowel disease (IBD). The dextran sodium sulfate (DSS)-induced colitis mouse model was established to investigate the correlation between the protective effects of CEO and the regulation of intestinal microflora. The symptoms of IBD were assessed by measuring the hemoglobin content, myeloperoxidase activity, histopathological observation, cytokines, and toll-like receptor (TLR4) expression. The alteration of the fecal microbiome composition was analyzed by 16S rRNA gene sequencing. The results indicated that the oral administration of CEO enriched with cinnamaldehyde effectively alleviated the development of DSS-induced colitis. In contrast to the inability of antibiotics to regulate flora imbalance, the mice fed with CEO had an improved diversity and richness of intestinal microbiota, and a modified community composition with a decrease in Helicobacter and Bacteroides and an increase in Bacteroidales_S24-7 family and short-chain fatty acids (SCFA)-producing bacteria (Alloprevotella and Lachnospiraceae_NK4A136_group). Moreover, the correlation analysis showed that TLR4 and tumor necrosis factor-α was positively correlated with Helicobacter, but inversely correlated with SCFA-producing bacteria. These findings indicated from a new perspective that the inhibitory effect of CEO on IBD was closely related to improving the intestinal flora imbalance.

Transcriptomic Analysis, Motility and Biofilm Formation Characteristics of Salmonella typhimurium Exposed to Benzyl Isothiocyanate Treatment.

Salmonella typhimurium (S. typhimurium) is a common foodborne pathogen that not only causes diseases and contaminates food, but also causes considerable economic losses. Therefore, it is necessary to find effective and feasible methods to control S. typhimurium. In this study, changes in S. typhimurium after treatment with benzyl isothiocyanate (BITC) were detected by transcriptomics to explore the antibacterial effect of BITC at subinhibitory concentration. The results showed that, in contrast to the control group (SC), the BITC-treated group (SQ_BITC) had 197 differentially expressed genes (DEGs), of which 115 were downregulated and 82 were upregulated. We screened out eight significantly downregulated virulence-related genes and verified gene expression by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). We also selected motility and biofilm formation to observe the effects of BITC on the other virulence related factors of S. typhimurium. The results showed that both swimming and swarming were significantly inhibited. BITC also had a significant inhibitory effect on biofilm formation, and showed an effect on bacterial morphology. These results will be helpful for understanding the mechanism of the antibacterial action of BITC against S. typhimurium and other foodborne pathogens.

[Systematic reviews of effects of Tripterygium Glycosides Tablets on pro-inflammatory factors in rheumatoid arthritis].

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1ß(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1ß(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1ß(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1ß(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1ß(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

[Meta-analysis of RCT studies on clinical efficacy of single administration of Tripterygium Glycosides Tablets or combined administration with methotrexate against rheumatoid arthritis].

To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.

Effects of dipeptidyl peptidase-4 inhibitors on transforming growth factor-ß1 signal transduction pathways in the ovarian fibrosis of polycystic ovary syndrome rats.

AIM: Examine the effects of dipeptidyl peptidase-4 (DPP4) inhibitor Sitagliptin on the transforming growth factor-ß1 (TGF-ß1) signal transduction pathway in polycystic ovary syndrome (PCOS) rats with ovarian fibrosis. METHODS: Thirty rats were divided randomly into the PCOS model group, Sitagliptin treatment group and blank control group. Dehydroepiandrosterone was administered to the model group and treatment group to establish the models. Then, the phenotype of rats was recorded, and the serum sex hormone levels were measured. The pathological structures of the rat ovaries were observed. The protein and mRNA expression levels of DPP4, connective tissue growth factor (CTGF), TGF-ß1 and Smad2/3 in the ovaries were analyzed. RESULTS: There was no statistically difference in fasting body weight and blood glucose among the three groups before Sitagliptin treatment (P > 0.05). The fasting blood glucose level was significantly decreased after the administration of Sitagliptin (P < 0.05). The level of testosterone in the model group was reduced remarkably after Sitagliptin treatment (P < 0.001). The protein expression levels of DPP4, CTGF and TGF-ß1 in the ovarian stroma were lower in the treatment group than in the model group (P < 0.01, P < 0.001, P < 0.05). The mRNA levels of DPP4, CTGF and TGF-ß1 in the model group also greatly declined after Sitagliptin treatment (P < 0.05, P < 0.001, P < 0.01). CONCLUSION: The DPP4 inhibitor Sitagliptin lowers fasting blood glucose, relieves the high androgen state of PCOS rats and delays the process of ovarian fibrosis, which may be related to reducing the levels of factors related to the TGF-ß1/Smad2/3 signaling pathway.

Transcriptomic Analysis of Vibrio parahaemolyticus Reveals Different Virulence Gene Expression in Response to Benzyl Isothiocyanate.

Vibrio parahaemolyticus isolated from seafood is a pathogenic microorganism that leads to several acute diseases that are harmful to our health and is frequently transmitted by food. Therefore, there is an urgent need for the control and suppression of this pathogen. In this paper, transcriptional analysis was used to determine the effect of treatment with benzyl isothiocyanate (BITC) extracted from cruciferous vegetables on V. parahaemolyticus and to elucidate the molecular mechanisms underlying the response to BITC. Treatment with BITC resulted in 332 differentially expressed genes, among which 137 genes were downregulated, while 195 genes were upregulated. Moreover, six differentially expressed genes (DEGs) in RNA sequencing studies were further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Genes found to regulate virulence encoded an l-threonine 3-dehydrogenase, a GGDEF family protein, the outer membrane protein OmpV, a flagellum-specific adenosine triphosphate synthase, TolQ protein and VirK protein. Hence, the results allow us to speculate that BITC may be an effective control strategy for inhibiting microorganisms growing in foods.

Influence of Oxygen-Containing Sulfur Flavor Molecules on the Stability of ß-Carotene under UVA Irradiation.

The influence of 11 kinds of oxygen-containing sulfur flavor molecules was examined on ß-carotene stability under UVA irradiation in ethanol system. Both the effects of sulfides on dynamic degradation of ß-carotene and the relation between structure and effect were investigated. The oxidation products of ß-carotene accelerated by sulfides under UVA irradiation were also identified. The results indicated that the disulfides had more obvious accelerative effects on the photodegradation of ß-carotene than mono sulfides. The degradation of ß-carotene after methyl (2-methyl-3-furyl) disulfide (MMFDS), methyl furfuryl disulfide (MFDS) and bis(2-methyl-3-furyl) disulfide (BMFDS) exposure followed first-order kinetics. Furan-containing sulfides such as MMFDS and BMFDS showed more pronounced accelerative effects than their corresponding isomers. The oxidation products were identified as 13-cis-ß-carotene, 9,13-di-cis-ß-carotene and all-trans-5,6-epoxy-ß-carotene. These results suggest that both the sulfur atom numbers and the furan group in oxygen-containing sulfides play a critical role in the photooxidation of ß-carotene.

[Meta-analysis of laboratory index of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis].

The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.

[Clinical symptoms effect of Tripterygium Glycosides Tablets alone or combined with methotrexate in treatment of rheumatoid arthritis: a Meta-analysis].

To systematically review the improvement effects of Tripterygium Glycosides Tables( TGT) alone or in combination with methotrexate( MTX) on the clinical signs and symptoms of rheumatoid arthritis( RA),and provide a basis for the rational use of TGT in clinic,in the current study,six literature databases including CNKI,Wan Fang,VIP,PubMed,EMbase,and Cochrane Library,were systematically searched,according to the inclusion and exclusion criteria. Review Manager 5.3 software was used to input the literatures,and we assessed the risk bias on the level of outcome indicators for each included literature. A total of 18 literatures were included,and the classification results showed that: compared with MTX,TGT alone can reduce the number of joint swelling( MD =0. 18,95%CI[-1.06,1.42],P = 0.78) and joint tenderness( MD =-0.06,95% CI[-1.69,1.56],P = 0.94) in RA patients with the same effect as MTX. In terms of drug combination,TGT combined with MTX had an advantage over MTX alone in lessening the morning stiffness time( MD = 18. 24,95% CI[12. 64,23. 84],P < 0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P<0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P< 0.000 01). In conclusion,this Meta-analysis suggest that TGT alone was superior to MTX in improving joint swelling and tenderness in RA patients,TGT combined with MTX may improve the clinical manifestation of RA patients better than MTX alone.

Association between X-Ray Repair Cross-Complementing Group 1 Arg399Gln Polymorphism and Cervical Cancer Risk: A Meta-Analysis in the Chinese Population.

BACKGROUND: Many studies have examined the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with cervical cancer susceptibility. However, the results of these studies are inconsistent. To further assess the effects of XRCC1 Arg399Gln polymorphism on the risk of cervical cancer in the Chinese population, a meta-analysis was performed. METHODS: Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine through December 2015. Pooled ORs and 95% CIs were used to assess the strength of the associations. RESULTS: This meta-analysis identified 7 studies, including 1,589 cases and 2,235 controls. In the total analyses, a significantly elevated risk of cervical cancer was associated with variants of XRCC1 Arg399Gln (GA vs. GG: OR 1.30, 95% CI 1.13-1.49; AA + GA vs. GG: OR 1.27, 95% CI 1.02-1.58). In the subgroup analyses stratified by geographic areas and histopathology type, it revealed the significant result in South China. CONCLUSIONS: This meta-analysis showed that the XRCC1 Arg399Gln GA variant might be risk alleles for cervical cancer susceptibility in the Chinese population, and further studies in other ethnic groups are required to arrive at definite conclusions.

[Effect of Heixiaoyao Powder on Hippocampal Gene Expression Profile of Alzheimer's Disease Rats].

Objective To observe the effect of Heixiaoyao Powder (HP) on gene microarray profile of hippocampus in Aß23₋35 fragments induced Alzheimer's disease rat model. Methods Female SD rats were chosen to establish AD model by injecting Aß25₋35 amyloid into hippocampus ,and then they were divid- ed into 6 groups, i.e., the sham-operation group, the model group,the Western medicine (WM) group, high, middle, and low dose HP groups, 14 in each group. After 7 days of modeling, all rats were administered with respective solution at the daily dose of 3 mL/kg by gastrogavage for 28 successive days. Normal saline was administered to rats in the sham-operation group and the model group. Huperzine A Tablets wa- ter solution was administered to rats in the WM group at the daily dose of 0. 02 mL/kg. HP at the daily dose of 4. 25, 8. 50, 17. 00 g/kg was administered to rats in the low, middle, high HP groups. All rats were sacri- ficed after ending gastrogavage, and their hippocampal tissues were collected to extract tissue RNA. Rat gene microarray was used to screen differentially expressed genes, and then differentially expressed genes with partial dose-dependently changing obtained by microarry were verified by qRT-PCR. Results Compared with the sham-operation group, 538 genes were up-regulated, and 579 genes were down-regulated in the model group. mRNA expressions of wisp1 , crebbp, igfbp-1 , znf483, zfp37, and zic4 increased, while mRNA expressions of casq2 and bcl-2 decreased in the model group (P <0. 05). Compared with the model group, 276 genes were up-regulated, and 170 genes were down-regulated in the 3 HP groups. Of them, 71 up-regulated genes dose-dependently and 70 down-regulated genes dose-dependently. mRNA expressions of igfbp-1 , znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 in- creased in the WM group (P <0. 01). mRNA expressions of wisp1 , crebbp, igfbp-1 , znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 increased in the high dose HP group (P <0. 01). mRNA expressions of crebbp, igfbp-1, znf483, zfp37, and zic4 decreased (P <0. 01, P <0. 05), while mR- NA expressions of casq2 and bcl-2 increased in the middle dose HP group (P <0. 01, P <0. 05). mRNA ex- pressions of igfbp-1 , znf483, zfp37, and zic4 decreased in the low dose HP group (P <0. 01). Compared with the middle dose HP group, mRNA expressions of crebbp, zfp37, and zic4 increased (P <0.01) , mR- NA expressions of igfbp-1 and bcl-2 decreased in the middle dose HP group (P <0. 01, P <0. 05); mRNA expressions of crebbp, znf483, and zfp37 increased (P <0. 01, P <0. 05), mRNA expressions of igfbp-1, zic4, and bcl-2 decreased in the low dose HP group (P <0. 01). Compared with the middle HP group, mRNA expressions of casq2, zic4, and bcl-2 decreased in the low dose HP group (P <0. 01, P <0. 05). Conclusion HP could affect the occurrence of AD by regulating mRNA expressions of zfp37, znf483, and zic4, and af- fect the metabolism of Aß and abnormal phosphorylation of Tau protein by inhibiting wnt signal pathway re- lated genes such as wisp-1 , crebbp, igfbp-1 , and casq2.

[Effect of Guiqicongzhi Decoction on Expression of HSP27 and HSP70 in Brain Tissue of VD Model Rats].

OBJECTIVE: To study the effect of Guiqicongzhi Decoction on expression of HSP27 and HSP70 in brain tissue of VD model rats. METHODS: The method of "repeatedly clip carotid artery join with injection of sodium nitroprusside and with permanent unilateral carotid artery ligation" was used to prepare the vascular dementia model. And then the effect of Guiqicongzhi Decoction on the model rats from rats praxiology, histopathological and the molecules expression of heat shock protein (HSP) were observed. RESULTS: Compared with control group, the navigation incubation period extended and space search ability became worse in model group; cell number was less, contour fuzzy shrivel, cytoplasm deep stain and nuclear was not clear in hippocampus pathological section; as well as an increase in the expression of HSP27 and HSP70. The above indexes changed significantly in middle dose group and high dose group. The curative effect of middle dose group was better than piracetam. CONCLUSION: Guiqicongzhi Decoction can protect brain tissue and improve the pathological damage and memory functions of VD rats, the mechanism maybe related to the regulation of HSP27 and HSP70 expression.

MYC protein expression is associated with poor prognosis in diffuse large B cell lymphoma patients treated with RCHOP chemotherapy.

This study aims to investigate the prognostic significance of the MYC protein expression in diffuse large B cell lymphoma (DLBCL) patients treated with RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). A total of 60 patients with DLBCL from 2008 to 2013 were included. Formalin-fixed, paraffin-embedded DLBCL samples were analyzed for MYC protein expression and divided into high or low MYC group. The MYC protein expression and the international prognostic variables were evaluated. The high MYC protein expression predicted a shorter 3-year estimated overall survival (OS) and progression-free survival (PFS) versus the low MYC protein expression (57 % vs. 96 %, P < 0.001 and 50 % vs. 96 %, P = 0.001, respectively). Multivariate analysis confirmed the prognostic significance of the MYC protein expression for both OS (HR, 11.862; 95 % CI, 1.462-96.218; P = 0.021) and PFS (HR, 6.073; 95 % CI, 1.082-34.085; P = 0.040). MYC protein expression with International Prognostic Index (IPI) score distinguished patients into three risk groups with different 3-year OS rates (χ (2) 23.079; P < 0.001) and distinct 3-year PFS rates (χ (2) 15.862; P < 0.001). This study suggests that the MYC protein expression is an important inferior prognostic factor for survival in patients with DLBCL treated with RCHOP. The combinative model with IPI score and MYC protein expression could stratify DLBCL patients into prognostically relevant subgroups more effectively than either the IPI or the MYC alone.

Sodium tanshinone IIA sulfonate attenuates radiation-induced fibrosis damage in cardiac fibroblasts.

The main pathological change in radiation-induced heart disease is fibrosis. Emerging evidence has indicated that sodium tanshinone IIA sulfonate (STS) was used for treating fibrosis diseases. The present study was undertaken to characterize the effect of STS on radiation-induced cardiac fibrosis (RICF) on cultured cardiac fibroblasts (CFs). CFs were irradiated with 1 or 2 Gy X-rays, and the expression of TGF-ß1 and collagen I (Col-1) increased, indicating that low-dose X-rays promoted fibrosis damage effect. The fibrosis damage was accompanied by morphologic changes in the endoplasmic reticulum (ER), as well as an increase in the expression of the ER stress-related molecules, GRP78 and CHOP. Administration of STS reduced ROS production and decreased the expression of Col-1, TGF-ß1, p-Smad2/3, GRP78, and CHOP in irradiated CFs, thus weakening the radiation-induced fibrosis damage and ER stress. Radiation-induced fibrosis damage was observed on a cellular level. The involvement of ER stress in radiation-induced fibrosis damage was demonstrated for the first time. STS attenuated the fibrosis damage effect in CFs and this effect may be related to its antioxidant action, and also related to its inhibition of ER stress and TGF-ß1-Smad pathway. These results suggest that STS shows a good prospect in clinical prevention and treatment of RICF.

[Effect of Xiaoyao Powder on the ethology, morphology, and activities of neurotransmitters of Alzheimer's disease model mice].

OBJECTIVE: To investigate the effect of Xiaoyao Powder (XP) and its compatible prescriptions on the ethology, morphology, and activities of neurotransmitters, thus exploring their effects and mechanism in preventing and treating D-galactose induced Alzheimer's disease (AD) model mice, and clarifying the compatibility mechanism for soothing Gan, nourishing blood, and invigorating Pi. METHODS: Sixty SPF mice were randomly divided into the blank control group, the model group, and the XP group, Shugan Jianpi group (SJ), Shugan Yangxue group (SY), and Jianpi Yangxue group (JY), 10 in each group.The AD mouse model was prepared by peritoneal injecting D-galactose. Meanwhile, mice in the blank control group and the model group were administered with physiological saline (at the daily dose of 24 mL/kg) by gastrogavage. Mice in the XP group (2.485 g/kg), the SY group (1.136 g/kg), the SJ group (1.775 g/kg), and the JY group (2.059 g/kg) were administered with corresponding medicated decoction by gastrogavage, with the gastric volume of 24 mL/kg. On the 41st day the training of capability for learning and memory was started. On the 42nd day capability for learning and memory was tested. The brain tissue was cut. One half was used to determine the contents of homogenate acetyl cholinesterase (AchE), choline acetyltransferase (ChAT), and monoamine oxidase (MAO).Another half was used to carry out morphological observations. RESULTS: The capability for learning and memory could be improved and the latency time could be lowered in all the treatment groups. Besides, the homogenate AchE and MAO could also be elevated, ChAT could be lowered; the morphology, number, and distribution of neurons could be improved. But the improvement of ethology, morphology, and activities of neurotransmitters were most obviously seen in the XP group. CONCLUSIONS: XP could improve the ethology, morphology, and activities of neurotransmitters, and showed better effects on prevention and treatment of AD. The rationality of compatibility methods and combination thinking ways of soothing Gan, nourishing blood, and invigorating Pi were clarified.

Obesity-related indices as predictors of lower extremity arterial disease in type 2 diabetes mellitus.

PURPOSE: The aim of this study was to investigate the relationship between obesity and lower extremity arterial disease (LEAD) in patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective study included 1821 patients with type 2 diabetes: 364 patients with LEAD and 1457 patients without LEAD. The patients were divided into training and internal test cohorts in a 7:3 ratio. LASSO regression analysis was used in the training cohort to filter relevant variables. Univariate and multivariate regression analyses were conducted to assess independent risk factors. A diagnostic nomogram was constructed and its discrimination was evaluated using the area under the ROC curve (AUC). The consistency was assessed using a calibration plot. The clinical application of the nomogram was evaluated by performing a decision curve analysis (DCA) and validated by an internal test cohort of the training cohorts. RESULTS: The LEAD group exhibited significantly higher values in obesity-related indices compared to the non-LEAD group, including waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), conicity index (CI), body adiposity index (BAI), and abdominal volume index (AVI). Multivariate analysis identified BMI, CI, BAI, and other parameters as independent risk factors for LEAD. A nomogram was constructed, and the AUC value of the nomogram was 0.746 in the training cohort and 0.663 in the internal test cohort. CONCLUSION: Obesity-related indices are associated with LEAD in patients with T2DM. Therefore, it is important to manage waist circumference and weight to reduce the risk of LEAD in patients with T2DM.