Combining Traditional Chinese Herbs and csDMARDs for the Treatment of Rheumatoid Arthritis Involves Tapering and Discontinuing Glucocorticoids: Protocol for a Two-Stage Non-Randomized Controlled Trial.

Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).

Toxic effects of combined exposure to cadmium and nitrate on intestinal morphology, immune response, and microbiota in juvenile Japanese flounder (Paralichthys olivaceus).

Cadmium (Cd2+) and nitrate (NO3-) are important environmental pollutants in the offshore marine ecological environment. However, limited research has explored their combined effects, particularly regarding their impact on the microbiota and intestinal health of marine fish. In this study, juvenile Japanese flounders (P. olivaceus) were immersed in seawater samples with different combinations of Cd2+ (0, 0.2, and 2 mg/L) and NO3- (0 and 80 mg/L NO3N) for 30 days to explore their toxic impacts on intestinal morphology, tight junction (TJ) barrier, immune response, and microbiota. Our results showed that Cd2+ or NO3- exposure alone led to histopathological damage of the gut, while their co-exposure aggravated intestinal damage. Moreover, co-exposure substantially decreased TJ-related gene expression, including occludin, claudin-10, and ZO-2, suggesting increased TJ permeability in the gut. Regarding the immune response, we observed upregulated expression of immune-related markers such as HSP40, IL-1ß, TNF-α, and MT, suggesting the onset of intestinal inflammation. Furthermore, Cd2+ and NO3- exposure led to changes in intestinal microflora, characterized by decreased the abundance of Sediminibacterium and NS3a_marine_group while increasing the prevalence of pathogens or opportunistic pathogens such as Ralstonia, Proteus, and Staphylococcus. This alteration in microbiota composition increased network complexity and α-diversity, ultimately causing dysbiosis in the fish gut. Additionally, combined exposure resulted in metabolic disorders that affected the predicted functions of the intestinal microbiota. Overall, our study demonstrates that Cd2+-NO3- co-exposure amplifies the deleterious effects compared to single exposure. These findings enhance our understanding of the ecological risks posed by Cd2+-NO3- co-exposure in marine ecosystems.

An integrative analysis to predict the active compounds and explore polypharmacological mechanisms of Orthosiphon stamineus Benth.

BACKGROUND: Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology. METHODS: Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation. RESULTS: A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics. CONCLUSION: This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.

Exposure to nitrate induces alterations in blood parameter responses, liver immunity, and lipid metabolism in juvenile turbot (Scophthalmus maximus).

Nitrate (NO3-) pollution of waterbodies has attracted significant global attention as it poses a serious threat to aquatic organisms and human beings. This study aimed to evaluate the role of NO3-, an end product of biological nitrification processes, in immune status and lipid metabolism to have a comprehensive understanding of its toxic effects on fishes. Therefore, in this work, juvenile turbot (Scophthalmus maximus) were subjected to four nominal concentrations of NO3- (i.e., 0, 50, 200, 400 mg/L of NO3--N) for a 60-day period. The results indicated that increased exposure to NO3- (200 and/or 400 mg/L) enhanced the concentrations of plasma heat shock protein concentrations (HSP70), complement component 3 (C3), complement component 4 (C4), immunoglobulin M (IgM) and lysozyme (LYS), which meant that NO3-caused fluctuations in the plasma immune system. Higher exposure to NO3- (200 and/or 400 mg/L) also caused significant enhancements in plasma glutamic pyruvic transaminase (GPT), as well as glutamic oxaloacetic transaminase (GOT) activity. Furthermore, NO3- exposure resulted in upregulation of liver TNF-α, IL-1ß, HSP70, HSP90, and LYS. Additionally, the results suggested that NO3-exposure caused a certain degree of histological damage and inflammation in the liver and activated the immune defense processes of juvenile turbot. Furthermore, the mRNA expression levels of certain genes associated with lipid metabolism (peroxisome proliferator-activated receptor-alpha [PPAR-α], carnitine palmitoyltransferase 1[CPT1], liver X receptor [LXR] together with sterol regulatory element binding protein-1 [SREBP-1]) increased significantly within fish liver exposed to 200/400 mg/L NO3--N treatments. Finally, the results obtained from the analysis of the integrated biological responses version 2 (IBRv2) also confirmed the toxic effects of NO3- on juvenile turbot. According to these findings, it can be found that NO3- emission in the aquatic environment needs to be strictly controlled, as it may cause immune and lipid metabolism disorders in fish.

Continuous Renal Replacement Therapy in Pediatric Patients With Acute Kidney Injury After Liver Transplantation.

Objective: This study aimed to explore the clinical application of continuous renal replacement therapy (CRRT) in pediatric patients with acute kidney injury (AKI) after liver transplantation. Methods: Pediatric patients who underwent liver transplantation were retrospectively investigated. Those who developed AKI within 1 year after the surgery were included and divided into a CRRT group and a non-CRRT group. The perioperative conditions and postoperative complications of the two groups were compared along with the prognoses of the groups to analyze the high-risk factors of the postoperative CRRT. Results: 189 (36.91%) patients developed AKI within 1 year after the liver transplantation surgery. There were 18 patients in the CRRT group and 171 in the non-CRRT group. The differences in the preoperative conditions were not statistically significant between the two groups. Compared with the non-CRRT group, patients in the CRRT group had significantly longer transplantation times, higher volumes of intraoperative hemorrhage, and increased incidence of postoperative unscheduled surgery, postoperative primary nonfunction of the transplanted liver, secondary liver transplantation, hepatic artery occlusion, and intestinal fistula (P < 0.05). Moreover, the proportion of patients in AKI stage 3 is higher in the CRRT group (83.33%) than that in the non-CRRT group (11.11%), P < 0.001. The median time to initiate CRRT was 10 days postoperatively, the median number of CRRT treatments per patient was 2 times, the average duration of each CRRT treatment was 10.1 h, and the average rate of the decrease in blood creatinine per treatment was 25.6%. Results of multivariate logistic regression analysis showed that AKI stage 3 [OR=40.000, 95%CI (10.598, 150.969), P = 0.016], postoperative unscheduled surgery [OR=6.269, 95%CI (3.051, 26.379), P = 0.007], and hepatic artery occlusion [OR = 17.682, 95%CI (1.707, 40.843), P = 0.001] were recognized as risk factors for postoperative AKI with CRRT therapy. The one- and two-year survival rates were 72.22% and 72.22% in the CRRT group, respectively; and 97.08% and 96.49% in the non-CRRT group, accordingly. There were statistically significant differences in the one- and two-year survival rates between the two groups (P < 0.001). Conclusion: The incidence of AKI after liver transplantation in pediatric patients was high. Patients with AKI stage 3, hepatic artery occlusion, and underwent unscheduled surgery postoperatively were with a high likelihood of receiving CRRT, which was related to a lower one- and two-year survival rates. CRRT effectively improved the one- and two-year survival rates.

[Application of continuous renal replacement therapy in infants with acute kidney injury after liver transplantation].

OBJECTIVE: To investigate the clinical application of continuous renal replacement therapy (CRRT) in infants with acute kidney injury (AKI) after liver transplantation. METHODS: A retrospective study was conducted on infants with AKI after liver transplantation in Tianjin First Center Hospital from January 1, 2019 to June 1, 2021. Infants with AKI within 1 year after liver transplantation were divided into CRRT group and non-CRRT group according to whether CRRT was performed. The preoperative and intraoperative condition, the postoperative complications were compared, the risk factors of CRRT for AKI infants, the clinical characteristics of CRRT were analyzed, and the prognosis between CRRT group and non-CRRT group were compared. RESULTS: (1) A total of 512 cases of pediatric liver transplantation were performed. A total of 189 cases (36.9%) developed AKI within 1 year after surgery, including 18 cases in CRRT group and 171 cases in non-CRRT group. (2) There was no significant difference in preoperative conditions between the two groups. The duration of liver transplantation (hours: 8.8±1.5 vs. 7.5±1.3) and intraoperative blood loss [mL: 370 (220-800) vs. 310 (200-400)] in CRRT group were significantly higher than those in non-CRRT group. CRRT group had significantly higher incidence of postoperative complication [unplanned operation: 8 cases (44.4%) vs. 14 cases (8.2%), primary nonfunction: 1 case (5.6%) vs. 0 case (0%), retransplantation: 3 cases (16.7%) vs. 0 case (0%), hepatic artery thrombosis: 3 cases (16.7%) vs. 4 cases (2.3%), intestinal fistula: 2 cases (11.1%) vs. 2 cases (1.2%)] than non-CRRT group (all P < 0.05). (3) The average start time of CRRT was 10 (1-240) days. The per capita frequency of CRRT treatment was 3.3 (1.0-14.0) times. The average duration of each CRRT treatment was 10.1 (6.0-19.3) hours, the average reduction rate of serum creatinine (SCr) was 25.6% (13.5%-45.0%) after CRRT. (4) In CRRT group, 5 patients died, the 1-year and 2-year survival rates were both 72.22%. In non-CRRT group, 6 patients died, the 1-year and 2-year survival rates were 97.1% and 96.5%, respectively. There were significant differences in 1-year and 2-year survival rates between the two groups (both P < 0.01). CONCLUSIONS: The incidence of AKI after pediatric liver transplantation was high, and most infants treated with CRRT were associated with serious surgical complications. CRRT was a powerful means to remove inflammatory factors and maintain the stability of circulation and internal environment, which could improve the multi-organ dysfunction effectively.

Engineered cytochrome fused extracellular matrix enabled efficient extracellular electron transfer and improved performance of microbial fuel cell.

Microbial fuel cell (MFC) was a promising technology for energy harvesting from wastewater. However, inefficient bacterial extracellular electron transfer (EET) limited the performance as well as the applications of MFC. Here, a new strategy to reinforce the EET by engineering synthetic extracellular matrix (ECM) with cytochrome fused curli was developed. By genetically fusing a minimal cytochrome domain (MCD) with the curli protein CsgA and heterogeneously expressing in model exoelectrogen of Shewanella oneidensis MR-1, the cytochrome fused electroactive curli network was successfully constructed and assembled. Interestingly, the strain with the MCD fused synthetic ECM delivered about 2.4 times and 2.0 times higher voltage and power density output than these of wild type MR-1 in MFC. More impressively, electrochemical analysis suggested that this synthetic ECM not only introduced cytochrome of MCD, but also attracted more self-secreted electrochemically active substances, which might facilitate the EET and improve the MFC performance. This work demonstrated the possibility to manipulation the EET with ECM engineering, which opened up new path for exoelectrogen design and engineering.

Clinical efficacy and safety of robotic distal gastrectomy for gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Robotic distal gastrectomy (RDG) is a new technique that is rapidly gaining popularity and may help overcome the limitations of laparoscopic distal gastrectomy (LDG); however, its safety and therapeutic efficacy remain controversial. Therefore, this meta-analysis was performed to evaluate the safety and efficacy of RDG. METHODS: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for studies that compared RDG and LDG and were published between the time of database inception and May 2021. We assessed the bias risk of the observational studies using ROBIN-I, and a random effect model was always applied. RESULTS: The meta-analysis included 22 studies involving 5386 patients. Compared with LDG, RDG was associated with longer operating time (Mean Difference [MD] = 43.88, 95% CI = 35.17-52.60), less intraoperative blood loss (MD = - 24.84, 95% CI = - 41.26 to - 8.43), a higher number of retrieved lymph nodes (MD = 2.41, 95% CI = 0.77-4.05), shorter time to first flatus (MD = - 0.09, 95% CI = - 0.15 to - 0.03), shorter postoperative hospital stay (MD = - 0.68, 95% CI = - 1.27 to - 0.08), and lower incidence of pancreatic fistula (OR = 0.23, 95% CI = 0.07-0.79). Mean proximal and distal resection margin distances, time to start liquid and soft diets, and other complications were not significantly different between RDG and LDG groups. However, in the propensity-score-matched meta-analysis, the differences in time to first flatus and postoperative hospital stay between the two groups lost significance. CONCLUSIONS: Based on the available evidence, RDG appears feasible and safe, shows better surgical and oncological outcomes than LDG and, comparable postoperative recovery and postoperative complication outcomes.

Research progress on rheumatoid arthritis-associated depression.

Depression is an independent mood disorder and one of the most common comorbidities of rheumatoid arthritis (RA). Growing evidence suggests that there is two-way regulation between RA and depression, resulting in a vicious cycle of RA, depression, poor outcomes, and disease burden. The rising prevalence of RA-associated depression warrants a re-examination of the relationships between them. Here we provide an overview of the etiology and pathological mechanisms of RA-associated depression, and recent advances in treatment with biologics, which will facilitate the development of new and effective prevention and treatment strategies.

Cytochrome C catalyzed oxygen tolerant atom-transfer radical polymerization.

Atom-transfer radical polymerization (ATRP) is a well-known technique for controlled polymer synthesis. However, the ATRP usually employed toxic heavy metal ionas as the catalyst and was susceptible to molecular oxygen, which made it should be conducted under strictly anoxic condition. Conducting ATRP under ambient and biocompatible conditions is the major challenge. In this study, cytochrome C was explored as an efficient biocatalyst for ATRP under biocompatible conditions. The cytochrome C catalyzed ATRP showed a relatively low polymer dispersity index of 1.19. More interestingly, the cytochrome C catalyzed ATRP showed superior oxygen resistance as it could be performed under aerobic conditions with high dissolved oxygen level. Further analysis suggested that the Fe(II) embed in the cytochrome C might serve as the catalytic center and methyl radical was responsible for the ATRP catalysis. This work explored new biocompatible catalyst for aerobic ATRP, which might open new dimension for practical ATRP and application of cytochrome C protein.

Novel insights into the immune regulatory effects of Megalobrama amblycephala intelectin on the phagocytosis and killing activity of macrophages.

Previous studies have found that the expression level of Megalobrama amblycephala intelectin (MaINTL) increased significantly post Aeromonas hydrophila infection, and recombinant MaINTL (rMaINTL) protein could activate macrophages and enhance the phagocytosis and killing activity of macrophages. In order to reveal the immune regulatory mechanisms of MaINTL, primary M. amblycephala macrophages were treated with endotoxin-removed rMaINTL and GST-tag proteins, then total RNA were extracted and used for comparative Digital Gene Expression Profiling (DGE). 1247 differentially expressed genes were identified by comparing rMaINTL and GST-tag treated macrophage groups, including 482 up-regulated unigenes and 765 down-regulated unigenes. In addition, eleven randomly selected differentially expressed genes were verified by qRT-PCR, and most of them shared the similar expression patterns as that of DGE results. GO enrichment revealed that the differentially expressed genes were mainly concentrated in the membrane part and cytoskeleton of cellular component, the binding and signal transducer activity of molecular function, the cellular process, regulation of biological process, signaling and localization of biological process, most of which might related with the phagocytosis and killing activity of macrophages. KEGG analysis revealed the activation and involvement of differentially expressed genes in immune related pathways, such as Tumor necrosis factor (TNF) signaling pathway, Interleukin 17 (IL-17) signaling pathway, Toll-like receptor signaling pathway, and NOD like receptor signaling pathway, etc. In these pathways, TNF-ɑ, Activator protein-1 (AP-1), Myeloid differentiation primary response protein MyD88 (MyD88), NF-kappa-B inhibitor alpha (ikBɑ) and other key signaling factors were significantly up-regulated. These results will be helpful to clarify the immune regulatory mechanisms of fish intelectin on macrophages, thus providing a theoretical basis for the prevention and control of fish bacterial diseases.

[Establishing potential habitats of Mytilopsis sallei with Maxent niche model]. / 应用Maxent建立沙筛贝潜在生境模型.

Mytilopsis sallei, an invasive alien species, has strong reproductive ability and high adaptability. It can severely endanger biodiversity of intertidal ecosystem after invasion. The intertidal zones and oyster breeding areas in some coastal areas of Guangdong Province have been severely invaded by M. sallei. To examine the potential habitat of M. sallei in China, we established a potential habitat prediction model of M. sallei using Maxent and ArcGIS method for China and global scales. The model was verified by the method of receiver operating characteristic curve (ROC) analysis and field investigation. The results showed that M. sallei could distribute with high probabili-ty in the area between North and South America, South India in Asia, Sri Lanka, the south coast of the Yangtze River in China, and in Van Dimen Bay of the southern hemisphere. In China, M. sallei mainly distributed in coastal provinces south of Shanghai. The main environmental factors affecting the suitable distribution areas for M. sallei were water vapor pressure, temperature, and solar radiation. After ROC detection, the AUC values of both the training and testing sets were 0.996, indicating that the prediction reached an excellent level. Our results provide theoretical basis for the risk assessment and management of M. sallei, and complement the potential habitat prediction of invasive species in China.

Roles of EvpP in Edwardsiella piscicida-Macrophage Interactions.

Edwardsiella piscicida is found to be an important facultative intracellular pathogen with a broad host range. These organisms can replicate and survive within host macrophages to escape from the subversion of the immune defense. E. piscicida-macrophage interaction is very important in determining the outcome of edwardsiellasis. As an effector protein of E. piscicida T6SS, EvpP has been determined to be a very important virulence factor for E. piscicida, although its precise role in E. piscicida-macrophage interactions is not yet clear. In this study, the roles of EvpP in E. piscicida-macrophage interactions were characterized. Here, we constructed the deletion mutants of evpP (ΔevpP) and complementation (ΔevpP-C) by the allelic exchange method. Compared to wild type strain (WT), ΔevpP was found to be attenuated for growth within macrophages. In line with this observation, we found its survival capacity was lower than WT under oxidative and acid stress in vitro, which simulate conditions encountered in host macrophages. Attenuation of ΔevpP also correlated with enhanced activation of macrophages, as reflected by augmented NO production in ΔevpP-treated macrophages. Moreover, compared to WT, ΔevpP induced markedly increased apoptosis of macrophages, characterized by increased Annexin V binding and the activation of cleaved caspase-3. These findings provided strong evidence that EvpP is involved in the process of E. piscicida-macrophage interactions and is required for its survival and replication in macrophages. Thus, we propose that EvpP might be an important factor that controlling the fate of E. piscicida inside macrophages. To further exploring the underlying mechanism of EvpP action, the cDNA library was constructed from E. piscicida-infected macrophages and a yeast two-hybrid screen was performed to search for cellular proteins interacting with EvpP. Ribosomal protein S5 (RPS5) was identified as a target of EvpP. Furthermore, the interaction was validated with co-immunoprecipitation assay. This result implies that the observed effect of EvpP on macrophages might be related to RPS5-mediated regulation, contributing to a better understanding of the mechanisms of EvpP involved in E. piscicida-macrophage interactions.

MiR-145 inhibits EGF-induced epithelial-to-mesenchymal transition via targeting Smad2 in human glioblastoma.

Background/Aims: MiR-145 and Smad2 have been widely reported in the development and progression of human malignancies. In the present study, we investigated the correlation between miR-145 and Smad2 in human glioblastoma multiforme (GBM). Methods: The epithelial-mesenchymal transition (EMT) biomarkers and Smad2 were assessed by Western blot. The silencing of Smad2 was conducted by transfection of Smad2 siRNAs. The cell migration and invasion were evaluated using Transwell assays, respectively. The dual luciferase reporter assay was performed to identify whether Smad2 is a direct target of miR-145. Results: The epidermal growth factor (EGF) activated the phosphorylation of Smad2 in U87 and U251 cells in a time- and dose-dependent manner. However, treatment with silencing of Smad2 or overexpression of miR-145 significantly inhibited the expressions of total Smad2, N-cadherin, Vimentin and matrix metallopeptidase 9, but induced the expression of E-cadherin. In addition, silencing of Smad2 or overexpression of miR-145 also inhibited the migration and invasion of U87 and U251 cells. Mechanistically, Smad2 was confirmed to be a target gene of miR-145 by bioinformatics analysis and luciferase reporter assay. Restored Smad2 expression also reversed miR-145-induced inhibition of EMT in U87 and U251 cells. Conclusion: MiR-145 inhibits EGF-induced EMT via targeting Smad2 in human GBM. Therefore, miR-145 may be a promising biomarker and therapeutic target for GBM patients.

A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE.

Methylation variabilities of inflammatory cytokines play important roles in the development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS). With heightened focus on personalized and precise medicine, it is necessary to compare and contrast the difference and similarity of cytokine methylation status between the 3 most classic autoimmune diseases (AIDs). In this study, we integrated 5 Cytokine-Chips from genome-wide DNA methylation datasets of the 3 kind of AIDs, delta-beta value was calculated for intergroup difference, and comprehensive bioinformatics analyses of cytokine genes with aberrant methylations were performed. 125 shared differential methylation variabilities (DMVs) were identified. There were 102 shared DMVs with similar methylation status; 3 hypomethylated differential methylation regions (DMRs) across the AIDs were found, and all 3 DMRs were hypomethylated. DMRs (AZU1, LTBR, and RTEL1) were likely to serve as activator in the inflammatory process. Particularly, AZU1 and LTBR with hypomethylated TSS and first exon located in the promoter regions were able to trigger inflammation signaling cascades and play critical roles in autoimmune tautology. Moreover, functional epigenetic module (FEM) algorithm showed that different inflammatory networks are involved in different AIDs; 5 hotspots were identified as biologically plausible pathways in inducing or perpetuating of inflammation which are epigenetically deregulated in AIDs. We concluded methylation variabilities among the same cytokines can greatly impact the perpetuation of inflammatory process or signal pathway of AIDs. Differentiating the cytokine methylation status will serve as valuable resource for researchers alike to gain better understanding of the epigenetic mechanisms of the three AIDs. Even more importantly, better understanding of cytokine methylation variability existing between the three classic AIDs will aid in identification of potential epigenetic biomarkers and therapeutic targets. This trial is registered with ChiCTR-INR-16010290, a clinical trial for the treatment of rheumatoid arthritis with Warming yang and Smoothening Meridians.

Red Blood Cell Distribution Width in Rheumatoid Arthritis, Ankylosing Spondylitis and Osteoarthritis: True Inflammatory Index or Effect of Anemia?

OBJECTIVE: To date, there have been no studies systematically comparing red blood cell distribution width (RDW) among rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteoarthritis (OA). Therefore, this study aimed to make comparisons and to explore whether erythrocytopenia and hemoglobin (Hb) reduction could influence RDW level and its association with conventional inflammatory or immune markers in RA, AS and OA. METHODS: A total of 222 patients with RA, 150 with AS, 78 with OA and 126 healthy controls (HC) were enrolled. Clinical and laboratory data of all subjects were extracted from electronically stored medical records. RESULTS: Increased RDW level was found only in RA patients and showed significant diagnostic value for RA. It was much higher in those with erythrocytopenia and Hb reduction. However, those without Hb reduction did not show significant difference of RDW from HC. RDW positively correlated with CRP and ESR respectively in RA and OA patients. However, when the patients were divided into Hb reduction and non-Hb reduction groups, the correlations became insignificant. CONCLUSIONS: RDW level is increased only in RA patients, but not in those with AS and OA. However, increased RDW and its association with CRP may be mainly due to Hb reduction. Therefore, whether RDW could be used as useful inflammatory index for RA, AS and OA remains to be evaluated.

MiR-145 inhibits the epithelial-to-mesenchymal transition via targeting ADAM19 in human glioblastoma.

In recent years, increasing studies demonstrated that miR-145 plays a tumor suppressor role in many human cancers. In the present study, we evaluated the expression of miR-145 and A Disintegrin and Metalloproteinase 19 (ADAM19) in glioblastoma multiforme (GBM) tissues and cells. Furthermore, we investigated the mechanisms underlying miR-145/ADAM19-induced GBM biology. Here, we found that miR-145 expression was down-regulated, while ADAM19 expression was up-regulated in GBM tissues and cells. Moreover, miR-145 mimics repressed U87 and U251 cell proliferation, migration and invasion. miR-145 mimics also inhibited the epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Mechanically, the 3' untranslated region (3'-UTR) of ADAM19 mRNA was a direct target for miR-145. In addition, ADAM19 over-expression also partially abrogated miR-145-inhibited EMT. In conclusion, this work suggested that high miR-145 expression inhibited EMT of GBM cells by targeting ADAM19. Thus miR-145/ADAM19 can be suggested as a novel target for GBM patients.

Proteomic analysis of macrophage in response to Edwardsiella tarda-infection.

Edwardsiella tarda is an important facultative intracellular pathogen infecting a wide range of host from fish to humans. This bacterium could survive and replicate in macrophages as an escape mechanism from the host defense. E. tarda -macrophage interaction is vital in determining the outcome of edwardsiellasis. To fully elucidate the pathogenesis of E. tarda, the differential proteomes of RAW264.7 cells in response to E. tarda-infection, were analyzed at different time points with two-dimensional gel electrophoresis (2-DE) followed by liquid-chromatography-tandem mass spectrometry (LC-MS/MS) identification. 26 altered proteins (18 up-regulated and 8 down-regulated proteins) were successfully identified, which are mainly involved in formation of phagosomes, macrophage microbicidal activity and anti-apoptosis of macrophage. Moreover, 6 corresponding genes of the differentially expressed proteins were quantified by quantitative real-time PCR (qPCR) to examine the transcriptional profiles. Western blot analysis further confirmed the differential expression of 5 proteins in the proteomic profiles. Based on these findings, we hypothesize that these differentially expressed proteins likely play a pivotal role in determining the course of E. tarda-infection. The result suggested that E. tarda could develop some strategies to achieve a successful intracellular lifestyle, including modulation of phagosome biogenesis, resistance to macrophage microbicidal agent and anti-apoptosis of macrophages. Thus, this work effectively provides useful and novel protein-related information to further understand the underlying pathogenesis of E. tarda-infection.