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Gastric cancer (GC) is the fifth most diagnosed cancer and the third leading cause of cancer-related death worldwide. Although progress has been made in diagnosis, surgical resection, systemic chemotherapy, and immunotherapy, patients with GC still have a poor prognosis. The overall 5-year survival rate in patients with advanced GC is less than 5%. The FOXO subfamily, of the forkhead box family of transcription factors, consists of four members, FOXO1, FOXO3, FOXO4, and FOXO6. This subfamily plays an important role in many cellular processes, such as cell cycle, cell growth, apoptosis, autophagy, stress resistance, protection from aggregate toxicity, DNA repair, tumor suppression, and metabolism, in both normal tissue and malignant tumors. Various studies support a role for FOXOs as tumor suppressors based on their ability to inhibit angiogenesis and metastasis, and promote apoptosis, yet several other studies have shown that FOXOs might also promote tumor progression in certain circumstances. To elucidate the diverse roles of FOXOs in GC, this article systematically reviews the cellular functions of FOXOs in GC to determine potential therapeutic targets and treatment strategies for patients with GC.

BACKGROUND Abnormal expression patterns of mucin 2 (MUC2) have been reported in a variety of malignant tumors and precancerous lesions. Reduced MUC2 expression in the intestinal mucosa, caused by various pathogenic factors, is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability. However, the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer (CRC) is not clear. AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC. METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients, including both cancer tissues and adjacent normal tissues. Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2, diamine oxide (DAO), and D-lactate (D-LAC). The relationship between MUC2 expression and clinical parameters was calculated by the χ2 test or Fisher’s exact test. Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests. RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues (54% vs 79%, P < 0.05), and it was correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in CRC patients (P < 0.05). However, the serum level of MUC2 in CRC patients was higher than that in normal controls, and was positively associated with serum levels of human DAO (χ2 = 3.957, P < 0.05) and D-LAC (χ2 = 7.236, P < 0.05), which are the biomarkers of the functional status of the intestinal mucosal barrier. And the serum level of MUC2 was correlated with TNM stage, tumor type, and distant metastasis in CRC patients (P < 0.05). Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival. CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.

This study aims to explore the mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis(RA) with syndrome of internal obstruction and cold-dampness and the compatibility characteristics based on thequot;disease-syndrome-formulaquot; association network. A gene set associated with the clinical symptoms of RA was collected from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0(TCMIP v2.0). The different expression gene set of RA with syndrome of internal obstruction and cold-dampness was screened out by transcriptomic expression profile detection and bioinformatics data mining of the comparison of RA patients with syndrome of internal obstruction and cold-dampness and healthy volunteers. The chemical composition information of 35 Chinese medicines from Tianhe Zhuifeng Ointment was collected from TCMIP v2.0 and Traditional Chinese Medicine Bank(TCMBank). The candidate targets were predicted based on the similarity principle of compounds structure. The interactive network ofquot;related gene of RA with syndrome of internal obstruction and cold-dampness-candidate target of Tianhe Zhuifeng Ointmentquot; was constructed. The core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome Pathway Database. The compatibility mechanisms of various efficacy groups of Tianhe Zhuifeng Ointment were further explored. The results showed that the candidate targets of Tianhe Zhuifeng Ointment were mainly involved into the modules ofquot;immune-inflammationquot; regulation, nervous system function, cell function, and substance and energy metabolism, etc. The mechanisms of various efficacy groups emphasized on different aspects. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, and the group of pungent analgesia regulatedquot;immune-inflammationquot; system by warming meridians and dissipating cold. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulatedquot;immune-inflammationquot; system by activating blood and dredging channels. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, the group of activating blood and resolving stasis, the group of strengthening sinews and bones, and the group of clearing heat and draining water affected the nervous system by invigorating Qi-blood and benefiting spirit. The group of dispelling wind and removing dampness-dredging channels and activating collaterals and the group of extinguishing wind and stopping convulsions regulated cell function and substance and energy metabolism by dispelling wind and eliminating cold-dampness. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated the cell function and substance and energy metabolism by activating blood and strengthening sinews and bones. The results showed that Tianhe Zhuifeng Ointment exerted the comprehensive efficacy of dispelling wind, removing dampness, activating blood, removing stasis, warming meridians, dredging channels, and strengthening sinews and bones through adjusting the imbalance ofquot;immune-inflammationquot;, regulating nervous system, cell function, and interfering with substance and energy metabolism, thus improving the syndrome of internal obstruction and cold-dampness. The findings of this study laid foundations for clarifying the therapeutic characteristics and clinical orientation of Tianhe Zhuifeng Ointment.

Glutathione peroxidases (GPxs) belong to a family of enzymes that is important in organisms; these enzymes promote hydrogen peroxide metabolism and protect cell membrane structure and function from oxidative damage. Based on the establishment and development of the theory of the pathological roles of free radicals, the role of GPxs has gradually attracted researchers’ attention, and the involvement of GPxs in the occurrence and development of malignant tumors has been shown. On the other hand, the incidence of breast cancer in increasing, and breast cancer has become the leading cause of cancer-related death in females worldwide; breast cancer is thought to be related to the increased production of reactive oxygen species, indicating the involvement of GPxs in these processes. Therefore, this article focused on the molecular mechanism and function of GPxs in the occurrence and development of breast cancer to understand their role in breast cancer and to provide a new theoretical basis for the treatment of breast cancer.

The present study explored the biological connotation of traditional Chinese medicine(TCM) syndromes of rheumatoid arthritis(RA) from thequot;disease-syndrome-symptomquot; association network. RA patients with four TCM syndromes(dampness-heat obstruction, phlegm-stasis obstruction, Qi-blood deficiency, and liver and kidney deficiency), three for each type, were assigned as the RA TCM syndrome group, and three healthy volunteers as the normal control group. The differential gene sets of four syndromes were screened out through transcriptome expression profiling and bioinformatics mining. The relevant gene sets of syndrome-related clinical symptoms were collected from TCMIP v2.0(http://www.tcmip.cn/). Thequot;disease-syndrome-symptomquot; association networks of four RA syndromes were established by using the intersection genes of syndrome-related differential genes and symptom-related genes, and the key network target genes of each syndrome were screened out and the corresponding biological functions were mined through topological feature calculation and enrichment analysis. The genes associated with clinical symptoms such as vasculitis, joint pain, and fever in the damp-heat obstruction syndrome ranked the top, and the key network target genes of this syndrome were most significantly enriched in the pathways related to material and energy metabolism and thermal reaction biological processes. The clinical symptom-related genes of the phlegm-stasis obstruction syndrome were most significantly enriched in the pathways related toquot;immunity-inflammationquot;, nervous system regulation, and sensory response. The clinical symptoms such as hypoglycemia, hypotension, weight loss, palpitation, and arrhythmia in Qi-blood deficiency syndrome were predominant, and its key network target genes were most significantly enriched in the pathways related to the nervous system andquot;immunity-inflammationquot; response. The abnormal symptoms in the liver and kidney in the liver and kidney deficiency syndrome were commonly seen, and its key network target genes were most significantly enriched in thequot;immunity-inflammationquot; regulatory pathways, and liver and kidney development and metabolic response. In conclusion, the differences and connections of the biological basis between different TCM syndromes of RA are in line with the theoretical interpretation of TCM on the etiology and pathogenesis of RA. This study summarized the objective essence of syndromes to a certain extent from thequot;disease-syndrome-symptomquot; association network and is expected to provide a theoretical basis for the discovery of serum biomarkers of RA syndromes.

Background Oral squamous cell carcinoma (OSCC) is a solid tumor of squamous epithelial origin. Currently, surgery is still the main treatment for OSCC, with radiotherapy and chemotherapy as important adjuvant treatments. However, the problem of poor prognosis of OSCC patients still exists in clinical practice. To explore further potential biomarkers or treatment targets in OSCC patients, this study used a high-throughput gene expression database to study the potential molecular mechanisms of OSCC carcinogenesis. Methods The GEO database related to OSCC was searched and analyzed using GEO2R. Oncomine and the Human Protein Atlas were used to evaluate the expression level of differentially-expressed genes (DEGs). The cBioPortal dataset was used to analyze the mutations of the potential DEGs and patient survival. Results Three GEO datasets, GSE146483, GSE138206, and GSE148944, were downloaded and 7 DEGs were found in common in OSCC tissues. Using Oncomine and the Human Protein Atlas, ANXA1, IL1RN, and SPINK5 were decreased in cancer tissues, while protein levels of APOE and IFI35 were increased accordingly. Interestingly, low levels of ANXA1 and SPINKS were associated with the TNM stage of OSCC patients. No mutations in DEGs were found in OSCC patients, based on the cBioPortal dataset. Survival analysis indicated OSCC patients with high MSR1 had poor overall survival (OS), while low expression of CXCR4, ANXA1, IL1RN, and SPINK5 also predicted poor OS in OSCC patients. Conclusions Our findings uncovered 7 potential biomarkers of OSCC patients, with ANXA1 and SPINK5 serving as potential tumor suppressor genes in OSCC.

Tripterygium wilfordii Hook F (TwHF)-based therapy is among the most efficient and crucial therapeutics for the treatment of rheumatoid arthritis (RA), which indicates that TwHF is a potential source of novel anti-RA drugs. However, accumulating studies have observed that TwHF-based therapy induces multi-organ toxicity, which prevents the wide use of this herb in clinical practice, although several recent studies have attempted to reduce the toxicity of TwHF. Notably, our research group developed a "Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis" (No. T/CACM 1337-2020) approved by the China Association of Chinese Medicine to standardize the clinical application of TwHF-based therapy and thus avoid adverse effects. Although great strides have been made toward the characterization of TwHF-based therapy and revealing its underlying pharmacological and toxicological mechanisms, several crucial gaps in knowledge remain as potential barriers to enhance its therapeutic effects on the premise of safety assurance. This review offers a global view of TwHF, ranging from its chemical constituents, quality control, clinical observations, and underlying pharmacological mechanisms to toxic manifestations and mechanisms. We focus on the important and emerging aspects of this field and highlight the major challenges and strategies for using novel techniques and approaches to gain new insights into unresolved questions. We hope that this review will improve the understanding of TwHF application and draw increasing interdisciplinary attention from clinicians that practice both Chinese and Western medicine, basic researchers, and computer scientists.

Background To identify biomarkers for guiding therapy and predicting clinical response of Tripterysium Glycosides Tablets (TGT) treatment is an urgent task due to individual differences in TGT response across rheumatoid arthritis (RA) patients. Competing endogenous RNA (ceRNA) regulatory system may influence drug response with involvement in diverse biological processes. Herein, we aimed to identify a TGT response‐related ceRNA axis. Methods A TGT response‐related ceRNA axis was screened according to clinical cohort‐based RNA expression profiling, lncRNA‐mRNA coexpression, and ceRNA network analyses. Its clinical relevance was evaluated by computational modeling. Regulatory mechanisms of ceRNA axis were also experimentally investigated. Results The ceRNA regulatory axis combined with lncRNA ENST00000494760, miR‐654‐5p, and C1QC was identified as a candidate biomarker for RA patients' response to TGT. Both ENST00000494760 and C1QC mRNA expression were significantly lower, while miR‐654‐5p expression was dramatically higher in TGT responders than nonresponders. Its clinical relevance was verified by computational modeling based on both independent clinical validation cohort and collagen‐induced arthritis (CIA) mice. Mechanistically, miR‐654‐5p directly bound to the 3′‐untranslated region of both ENST00000494760 and C1QC mRNA to inhibit their expression. Moreover, miR‐654‐5p suppressed C1QC mRNA expression, but ENST00000494760 bound to miR‐654‐5p and relieved its repression on C1QC mRNA, leading to RA aggressive progression and weak TGT response. Conclusions LncRNA ENST00000494760 overexpression may sponge miR‐654‐5p to promote C1QC expression in RA patients. This novel ceRNA axis may serve as a biomarker for screening the responsive RA patients to TGT treatment, which will allow improved personalized healthcare., Molecular mechanism underlying individual differences in response to Tripterysium Glycosides Tablets (TGT) is inadequate and the solution is limited. A ceRNA regulatory axis with lncRNA ENST00000494760, miR‐654‐5p and C1QC was identified as a candidate biomarker for rheumatoid arthritis (RA) patients' response to TGT. ENST00000494760 may sponge miR‐654‐5p to promote C1QC expression, leading to RA aggressive progression and weak TGT response.

As important modulators in multiple physiological processes, microRNAs (miRNAs) have been reported in various malignant tumors, including breast cancer. The current study investigated the function of a new tumor suppressor microRNA, miR-488, and its molecular mechanism of metastasis in breast cancers. CCK8 and transwell assays revealed that the upregulated miR-488 level significantly inhibited the proliferation and migration of breast cancer cells. As a potential downstream gene, the mRNA and protein level of FSCN1 was suppressed by increased miR-488 and vice versa. Luciferase assay showed that miR-488 directly bind to the 3′UTR of FSCN1 and suppressed the translation process of FSCN1. The promoter region of miR-488 was directly bound by Notch3 and promoted the expression of miR-488 transcriptionally. Immunohistochemistry results revealed that in patients with breast cancer, the expression of Notch3 and were negatively correlated with the FSCN1 levels significantly. Therefore, the current finding predicted miR-488 as a tumor suppressor molecule in breast cancer, and demonstrated that Notch3/miR-488/FSCN1 axis is established and involved in regulating the metastasis of breast cancers, providing novel therapeutic targets for patients with breast cancers.

The dysfunction of long non-coding RNAs (lncRNAs), without protein-coding potential, has been implicated in drug resistance against treatment in various human diseases, especially in malignant tumors. As the most common-diagnosed female malignancy worldwide, breast cancer is also the second-leading cause of cancer-related mortality in women. Despite the improvement in neo-adjuvant therapy, endocrine therapy, molecular-targeted treatment, and chemotherapy, drug resistance to various treatment regimens is still quite prevalent. This article focused on the lncRNAs and their functions in drug resistance against breast cancer therapeutic agents, in order to develop new precise treatment strategies for patients with breast cancers. The discovery of lncRNA opened new doors to the molecular mechanisms of the biological processes, and has provided new pathways to regulate biochemical events. Thus, lncRNAs may be developed as a biomarker for the detection and/or prevention of breast cancer. Additionally, lncRNA-based approaches may provide an additional treatment modality in personalized medicine alone or in combination with existing tumor-directed interventions to improve patient outcomes. In conclusion, lncRNAs molecules may represent the "next generation" therapy option for breast cancer patients.

The wide application of artemisinins in the treatment of multiple cancers reflects the advantages of traditional Chinese medicine used in this field. The existing basic and clinical studies have revealed that artesunate can effectively suppress the malignant progression of breast cancer,colon cancer,leukemia,melanoma,ovarian cancer,prostate cancer,kidney cancer and various tumors in central nervous system. The pharmacological mechanisms of artesunate against cancers are reflected in many aspects,such as inhibiting tumor cell proliferation,invasion and metastasis,inducing tumor cell apoptosis and autophagy,regulating cell signal transduction and inhibiting tumor angiogenesis. Meanwhile,growing experimental evidences have indicated that artesunate has been used for the sensitization of radiotherapy with X-ray,β-ray,γ-ray and~(60)Co γ-ray,as well as chemotherapy with cisplatin,carboplatin and doxorubicin.This review collected basic and clinical studies on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy published on PubMed and CNKI during April 2000 and February 2019,and summarized the clinical positioning and application of artesunate,with the aim to provide a more comprehensive explanation on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy,and offer the inspiration and ideas for the development of radiotherapy and chemotherapy sensitizers,as well as cancer resistance reversal agents.

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], Plt;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], Plt;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.

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],Plt;0.000 01),IL-1β(Plt;0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], Plt;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-1β(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-1β(SMD=-6.29,95%CI[-9.64,-2.93],Plt;0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],Plt;0.000 01), joint fluid(Plt;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-1β(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-1β(P=0.02), IL-6(Plt;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.

Objective. To investigate the expression patterns and prognostic values of STEAP family members in the occurrence and development of breast cancer. Materials and Methods. The Human Protein Atlas was used to analyze the expression level of STEAPs in human normal tissues and malignant tumors. ONCOMINE datasets were analyzed for the comparison of the STEAPs levels between malignant cancers and corresponding normal tissues. Kaplan-Meier plotter was used to analyze the prognostic value of STEAPs in breast cancer patients. Results. STEAPs were widely distributed in human normal tissues with diverse levels. Normally, it is predicted that STEAP1 and STEAP2 were involved in the mineral absorption process, while STEAP3 participated in the TP53 signaling pathway and iron apoptosis. The results from ONCOMINE showed downregulation of STEAP1, STEAP2, and STEAP4 in breast cancers. Survival analysis revealed that breast cancer patients with high levels of STEAP1, STEAP2, and STEAP4 had a good prognosis, while those with low expression had high overall mortality. Conclusion. STEAP1, STEAP2, and STEAP4 are predicted to be the potential prognostic biomarkers for breast cancer patients, providing novel therapeutic strategies for them.

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],P0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P0.000 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.

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],P0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P0.000 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.

Drug repositioning offers new clinical applications for existing drugs with shorter approval processes and lower costs and risks than de novo experimental drug development. The Fufang-Biejia-Ruangan pill (FBRP) is the first clinically approved anti-fibrosis herbal formula in China. Whether FBRP could be used to treat hepatocellular carcinoma (HCC) remains unclear. Herein, a total of 161 FBRP candidate targets against HCC were identified according to the topological importance in the “hepatic fibrosis-cirrhosis-cancer axis-related gene-FBRP putative target” network, and mostly enriched in phosphatidylinositol 3-kinase (PI3K)/AKT/nuclear factor κB (NF-κB) signaling. Experimentally, FBRP inhibited liver fibrosis and prevented the development of neoplastic lesions at the early stages of hepatocarcinogenesis in a diethylnitrosamine-induced rat HCC model. FBRP inhibited tumor cell proliferation, induced tumor-specific cell death, and suppressed tumor progression in HCC rats while preventing the activation of PI3K, AKT and IKΚB proteins, reducing the nuclear accumulation of NFΚB1 protein, and decreasing the downstream expression of proteins. Consistently, FBRP suppressed HCC cell proliferation and induced cell cycle arrest in vitro. Co-treatment of FBRP with PI3K inhibitor exhibited an additive inhibitory effect on PI3K/AKT/NF-κB activation. Collectively, our data showed the potentials of FBRP in hepatic fibrosis microenvironment regulation and tumor prevention, suggesting that FBRP may be a promising candidate drug for reduction of fibrogenesis and prevention of HCC.

Wutou Decoction (WTD) achieves favorable therapeutic response in treating rheumatoid arthritis (RA), especially for wind-cold-dampness stimulating RA. However, its material basis and molecular mechanisms remain unclear. To address this problem, the main bioactive compounds (BACs) of WTD against RA and the candidate targets were identified in the current study via transcriptional regulatory network analysis, computational structure-based methods, as well as in vivo and in vitro experimental validations. As a result, we successfully established a RA rat model named AIA-S, which simulated the clinical manifestations and pathological changes of wind-cold-dampness stimulating RA, and also displayed the distinctive characteristics and biological basis of inflammatory-immune system imbalance and abnormal energy metabolism changes. In addition, ALOX15B-PPAR-γ-PTGS2-FGF2-IL-1β-c-JUN-MMP13-TGF-β1 signal axis, involved into thermogenesis and energy metabolism, as well as maintaining the balance of inflammation-immune system, was identified as a candidate target of WTD against RA, according to the transcriptional regulatory network analysis on "RA-related gene-WTD-effective gene interaction network". Moreover, Paeoniflorin (PAE) and Talatizidine (TLT) were demonstrated to be the main BACs of WTD against RA for the following reasons: firstly, both PAE and TLT were the BACs of WTD according to ADME analysis in silico and the pharmacokinetics analysis in vivo. Secondly, both PAE and TLT were able to bind with PPAR-γ, c-JUN, MMP13 and TGF-β1, which were the candidate targets of WTD against RA, with the strong binding affinity. Thirdly, the PAE and TLT combination exerted significant therapeutic effects on AIA-S rats through reversing the imbalance of inflammatory-immune system, and the disturbance of thermogenesis and energy metabolism, which were similar to WTD. More importantly, the administration of TLT or PAE alone didn't exert as prominently therapeutic effects as that of the two-BAC-combination did. Fourthly, the PAE and TLT combination promoted adipogenesis and lipogenesis by upregulating the PPAR-γ-induced lipogenic proteins. In conclusion, this study identified PAE and TLT as the main BACs of WTD in alleviating the severity of RA, and also developed a novel combination of PAE and TLT as a promising candidate drug for RA therapy.

Two novel metal-free organic dyes bearing two asymmetric double donor–acceptor segments were synthesized. Their physical, optical, electrochemical properties and photovoltaic performances were investigated. Compared with the mono-anchoring dye containing single donor–acceptor chain, these new dyes exhibited a broader and much stronger absorption in the light wavelength ranging from 400 to 600 nm, showed higher IPCE values and short-circuit current density, which led to more efficient photovoltaic performance. The dye with triphenylamine and phenothiazine as two electron donors and two cyanoacrylic acids as two electron acceptors exhibited an impressive power conversion efficiency of 5.92% under simulated AM 1.5 G illumination condition with an open-circuit photovoltage of 796 mV, a short-circuit photocurrent density of 11.24 mA/cm2, which is 22% higher than that of the mono-anchoring dye based counterpart. The results indicate that the asymmetric di-anchoring organic dyes are promising sensitizers for high efficient dye-sensitized solar cells.

The ANSYS Workbench is used in this paper to analyse a kind of wind tunnel test model support platform with 5 degrees of freedom. The driving rod of the pitch motion is chosen as the main research project. By using static structural analysis, modal analysis and harmonic response analysis, a detailed analysis is made on the stress, deformation and frequency of the driving rod, and provides theoretical support for the future research on the stability of the institution.

In-suit β-Ti (Zr,Nb) dendrite/amorphous matrix composites were prepared by copper injection casting, specimens (1.5:1 aspect ratio) with different diameters were tested under quasi-static compressive loading at different strain rate. The results show that the structure of amorphous composites is amorphous matrix and in-suit β dendritic crystal phase; for 3mm and 4mm specimens, with the change of strain rate, the compressive strength and the fracture strain have no obvious changes. however, positive strain rate sensitivity was observed to 5mm specimens; in the same strain rate, with the decrease of the diameters, compressive strength and fracture strain all have great increases, which indicate the amorphous composites has obvious size effect.

A new wind tunnel test bed based on the parallelogram institution was chosen to be studied in this paper. In the first way the 3D model was built in detail in the SolidWorks, and then the model was imported into ADAMS to build a rigid model and a rigid-flexible model, finally got the curves of the barycenter position’s parameters through carrying out the simulation separately, which would lay the foundation for the simulation of kinematics and dynamics of the wind tunnel test bed.

This paper introduces the characteristics of a 3-RPR parallel mechanism based on the wind tunnel experiment platform, makes use of the constraint condition of the inverse position solution of the structure, and uses MATLAB software to draw images of their work space and analyze the impact of the dimensional parameters of wind tunnel platform on the scope of work space, and it provides a theoretical basis for the design and practical of wind tunnel test platform.

Cloud detection in visible light remote sensing images is a challenge due to only few RGB spectral channels and multiple types of clouds and land covers. In this paper, we propose a new method based on convolutional neural network for cloud detection. Our method automatically learns the intrinsic features of the clouds and the other land covers, and can produce high accuracy for cloud detection. The learned features in our method are then visualized and explained in detail, and compared with other features in a baseline method. Finally, experiments are conducted to demonstrate the effectiveness of our method.

Traditional cam profile curve is not changeable after it is made. So it can’t meet the requirement when the follower needs to change the motion within a short time. Therefore, we designed a new cylindrical cam structure whose profile curve could be reconstructed by adjust inserted depth of the chips. We built its three-dimension object model by SOLIDWORKS and explained its advantages and shortcomings. We illustrated its advantages by provided an example of application. And results show the new cam structure is high versatility and convenient to realize the needs of different follower motion by reconstruct its profile.

The rigid-flexible hybrid modeling of the wind tunnel test platform is established by means of ANSYS and ADAMS for more accurate analysis of the motion performance of the test platform in this paper. We get the kinematical characteristic curve based on the three working conditions of the pitching motion, yawing motion, rolling motion of the test platform. According to the characteristic curve indirectly reflects the rationality of the design configuration. So as to provide fundamental basis for the precision dynamics simulation analysis and make the real physical prototype are offered.

In this article, HNO3 (4 mol/L) was employed to open the ends of carbon nanotubes (CNTs) and a 1:3 mixture of concentrated HNO3 and H2SO4 was employed to obtain acid-treated CNTs. Acetone was used as the solvent to introduce CNTs into epoxy resins. The bending strength of CNTs/epoxy resins composites increased with the increase of the CNTs content at first, and decreased after the CNTs content reached a certain value. The enhancement effect of acid-treated CNTs was better than that of end-opened CNTs, and not end-opened CNTs performed the worst. This was perhaps because the matrix could restrain the CNTs more effectively at each end of the CNTs if the CNTs were end-opened. Besides, the bending strength of the composites with CNTs with smaller diameters was higher than that of the composites with CNTs with bigger diameters.

Though computer technology has brought about virtual manufacturing to expedite design and analysis through simulation and visualization, machines remain essential, as ultimately products need to be made. There is a need for equipment providing more than three degrees of freedom (DOF) arranged in parallel and based on simpler arrangements than 6-DOF arrangements in application. This paper presents a new 4-DOF hybrid parallel platform manipulator with fixed-leg lengths and base mounted prismatic actuators. The movable platform of the manipulator can translate along two directions and rotate around two axes respectively (2T-2R). The kinematics model is formulated, which describes the inverse and forward kinematics transformation. It is very easy to develop a 5-axis NC machine-tool which is of large-workspace based on the 2T-2R, 4-DOF parallel mechanism presented in this paper.

Though computer technology has brought about virtual manufacturing to expedite design and analysis through simulation and visualization, machines remain essential, as ultimately products need to be made. This paper presents a new type of 5-axis parallel machine tool based on a 3 degrees of freedom parallel platform manipulator with base mounted prismatic actuators. This machine tool is different from the Stewart platform type parallel machine tool in that its feed motion in X-direction is realized by the worktable on which work-piece is fixed and the parallel manipulator sliding on the gantry structure of the machine tool is responsible for the translation along Y-direction instead of the movable platform of the manipulator. Due to this special architecture, the workspace in X-direction and Y-direction of the new machine tool is enlarged greatly. And its rigidity is higher because of the adaptation of gantry structure. This machine tool is controlled by a PC based NC system in simultaneous 5 axes control mode.

Carbon nanotubes (CNTs) with different diameters were treated by plasma and acid. The CNTs were dispersed in water and the light transmittance of the CNTs dispersoid (the mixture of CNTs and water) was measured to characterize the dispersibility of CNTs. With the light transmittance of water as the baseline, relative transmittance (RT) of CNTs dispersoid was calculated and the curves of RT varying with time were fitted with a function. The effects of CNTs diameter, acid treatment and plasma treatment on the dispersion of CNTs in water were studied according to the fitting results. It could be concluded that the dispersibility of the CNTs with bigger diameters was better. Plasma treatment could improve the dispersibility of CNTs and if the CNTs were acid-treated, plasma treatment could improve their dispersibility further.

Automatic Dynamic Analysis of Mechanical System (ADAMS) provides a powerful modeling and simulating environment that helps people to build, simulate, refine, and ultimately optimize any mechanical system. In the classroom teaching of mechanism course, to use ADAMS to show the establishment and movement of all kinds of mechanisms and their simulation process of kinematics and kinetics as a demonstration will significantly enrich students' perceptual knowledge, enlighten and guide students cogitation, stimulate their interests in mechanism thereby enhance the effectiveness of course teaching.

Aims To explore the effect and mechanism of exendin-4 on dexamethasone-induced apoptosis in pancreatic β-cells. Methods Murine MIN6 pancreatic β-cells were treated with dexamethasone (100 nmol/l) over 48 h following pretreatment with exendin-4 (100 nmol/l). Cell viability was determined using an MTT assay. The percentage of apoptotic cells was determined through fluorescence microscopy analysis after Hochest/PI staining and a flow cytometric assay after Annexin V-FITC/PI staining. Caspase 3 activity was measured using the caspase 3 activity assay kit. Expression of cyt-c, bcl-2, bax, AKT, and phosphorylated AKT was detected by western blot. Results Exendin-4 reduced the percentage of cells undergoing apoptosis when β-cells were exposed to dexamethasone. Exendin-4 down-regulated caspase 3 activity, reduced cytochrome c levels in cytoplasm, and increased Bcl-2 protein levels and the Bcl-2 to Bax ratio in dexamethasone-treated β-cells. These exendin-4 effects were blocked in the presence of an inhibitor of the phosphoinositide-3 kinase (PI-3K) pathway or of the protein kinase A (PKA) pathway. Exendin-4 reversed dexamethasone-mediated inhibition of Akt phosphorylation, which was abrogated by the PI-3K and PKA inhibitors. Conclusion PI-3K and PKA signaling are involved in the exendin-4-mediated modulation of β-cell apoptosis.