A meta-analysis of phosphate binders lanthanum carbonate versus sevelamer hydrochloride in patients with end-stage renal disease undergoing hemodialysis

Background and Objectives: The purpose of this study was to compare the effects of phosphate binders lanthanum carbonate (LC) versus sevelamer hydrochloride (SH) in end-stage renal disease (ESRD) patients undergoing hemodialysis.Methods: Studies including randomized controlled trials (RCTs) comparing phosphate binders lanthanum carbonate versus sevelamer hydrochloride, in ESRD patients undergoing hemodialysis, were identified using a pre-defined search strategy. Phosphate, calcium, calcium-phosphorus product, intact parathyroid hormone, alkaline phosphatase, total cholesterol, and triglyceride were extracted and compared by RevMan 5.1 (The Cochrane Collaboration, Oxford, UK).Results: Six studies were identified. Meta-analysis showed that SH treatment reduced levels of phosphate, intact parathyroid hormone, and total serum alkaline phosphatase (ALP) when compared with LC treatment. Furthermore, patients on SH treatment tended to have reduced calcium levels, calcium-phosphorus product, total cholesterol, and triglyceride when compared to patients treated with LC, but there was no statistical difference.Conclusion: SH treatment of patients with ESRD is more effective compared to LC treatment. However, more well-designed random control trails are required for confirmation.Keywords: End-stage renal disease, hemodialysis, phosphate binders, lanthanum carbonate (LC), sevelamer hydrochloride (SH), meta-analysis

A meta-analysis of phosphate binders lanthanum carbonate versus sevelamer hydrochloride in patients with end-stage renal disease undergoing hemodialysis

Background and Objectives: The purpose of this study was to compare the effects of phosphate binders lanthanum carbonate (LC) versus sevelamer hydrochloride (SH) in end-stage renal disease (ESRD) patients undergoing hemodialysis. Methods: Studies including randomized controlled trials (RCTs) comparing phosphate binders lanthanum carbonate versus sevelamer hydrochloride, in ESRD patients undergoing hemodialysis, were identified using a pre-defined search strategy. Phosphate, calcium, calcium-phosphorus product, intact parathyroid hormone, alkaline phosphatase, total cholesterol, and triglyceride were extracted and compared by RevMan 5.1 (The Cochrane Collaboration, Oxford, UK). Results: Six studies were identified. Meta-analysis showed that SH treatment reduced levels of phosphate, intact parathyroid hormone, and total serum alkaline phosphatase (ALP) when compared with LC treatment. Furthermore, patients on SH treatment tended to have reduced calcium levels, calcium-phosphorus product, total cholesterol, and triglyceride when compared to patients treated with LC, but there was no statistical difference. Conclusion: SH treatment of patients with ESRD is more effective compared to LC treatment. However, more well-designed random control trails are required for confirmation

Potential Implications of Quercetin in Autoimmune Diseases

Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although their etiology and pathogenesis remain unclear, the application of dietary supplements is gradually increasing in patients with autoimmune diseases, mainly due to their positive effects, relatively safety, and low cost. Quercetin is a natural flavonoid that is widely present in fruits, herbs, and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammation, anti-oxidation, and neuroprotection. In several recent studies quercetin has reportedly attenuated rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus in humans or animal models. This review summarizes the evidence for the pharmacological application of quercetin for autoimmune diseases, which supports the view that quercetin may be useful for their prevention and treatment

Synergistic and Hepatoprotective Effect of Total Glucosides of Paeony on Ankylosing Spondylitis: A Systematic Review and Meta-Analysis

The objective of this systematic review was to conduct a meta-analysis of the efficacy and safety of total glucosides of paeony (TGP) for the treatment of ankylosing spondylitis (AS). TGP is commonly applied as a complementary medicine, especially in combination with disease-modifying antirheumatic drugs (DMARDs) and/or non-steroidal anti-inflammatory drugs (NSAIDs) to treat AS in China. Nevertheless, the efficacy and safety of TGP combination treatment still needs more validation. A systematic literature search was conducted using PubMed, EMBASE, Web of Science, the Cochrane library, ClinicalTrials, the Chinese Biomedical Literature database (CBM), the China National Knowledge Internet (CNKI), the Wan Fang Medical Database and the VIP Database for available randomized controlled trials (RCTs) investigating the efficacy and safety of TGP on AS up to November 2018. Review Manager 5.3 software and Stata 12.0 software were used to analyze all included studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. The pooled results of 23 RCTs exhibited better symptoms improvement (SI) (95% CI 1.16 to 1.36), lower erythrocyte sedimentation rate (ESR) (95% CI −5.89 to −1.32), lower levels of C-reactive protein (CRP) (95% CI −5.01 to −1.49), morning stiffness (MS) time (95% CI −3.46 to −1.86), finger to floor distance (FFD) (95% CI −4.80 to −0.86), peripheral joint pain index (PJPI) (95% CI −3.48 to −0.69), and higher level of thoracic expansion (TE) (95% CI 0.18–0.40) in TGP group. While Schober's test (Schober) showed no significant difference between the two groups. Adverse events (AEs) were significantly decreased (95% CI 0.48–0.79) with the usage of TGP. It is worthwhile to apply TGP as an auxiliary medicine on AS for better efficacy and less side effects, especially when considering the impact of traditional treatment on the liver. Still, further clinical trials with larger sample and better methodological quality are warranted to ascertain the potential benefits of TGP on AS

Multifaceted oncostatin M: novel roles and therapeutic potential of the oncostatin M signaling in rheumatoid arthritis

Rheumatoid arthritis (RA) is a self-immune inflammatory disease characterized by joint damage. A series of cytokines are involved in the development of RA. Oncostatin M (OSM) is a pleiotropic cytokine that primarily activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and other physiological processes such as cell proliferation, inflammatory response, immune response, and hematopoiesis through its receptor complex. In this review, we first describe the characteristics of OSM and its receptor, and the biological functions of OSM signaling. Subsequently, we discuss the possible roles of OSM in the development of RA from clinical and basic research perspectives. Finally, we summarize the progress of clinical studies targeting OSM for the treatment of RA. This review provides researchers with a systematic understanding of the role of OSM signaling in RA, which can guide the development of drugs targeting OSM for the treatment of RA

Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2

大多数真核生物的体细胞是二倍体，即仅含有两组染色体，分别遗传自父本和母本。而一些特定组织如心脏、肝脏等就含有多倍体细胞，特别是肝脏组织含有较高比例的四、八倍体等多倍体细胞。肝脏是人体的重要解毒器官，同时酒精、肝炎病毒等毒性物质或毒性代谢物容易诱发肝细胞的基因突变，多倍体被认为有利于提供代偿性的正常基因来维持肝脏稳态。然而肝脏受损后，多倍体细胞将会受胁迫进行增殖，再生修复受损的肝组织。因此研究机体调控多倍体细胞产生及多倍体细胞进行细胞分裂的调控机理对于理解肝癌的发病机理和肝癌的治疗至关重要。Hippo信号通路在调节组织成体干细胞的分化和增殖，调控器官再生与尺寸大小中具有重要作用。深入研究发现, Hippo信号通路下游效应分子YAP通过AKT-SKP2信号促进二倍体细胞向多倍体转化及多倍体细胞的生长增殖。本项研究阐明了Hippo缺失及YAP激活促进多倍体细胞产生及增殖作为肝癌发生发展中的一个重要机制，为肝癌诊疗提供了新的策略。 周大旺，博士，厦门大学生命科学学院教授、副院长、国家杰出青年基金获得者。【Abstract】Polyploidy can lead to aneuploidy and tumorigenesis. Here, we report that the Hippo pathway effector Yap promotes the diploid-polyploid conversion and polyploid cell growth through the Akt-Skp2 axis. Yap strongly induces the acetyltransferase p300-mediated acetylation of the E3 ligase Skp2 via Akt signaling. Acetylated Skp2 is exclusively localized to the cytosol, which causes hyper-accumulation of the cyclin-dependent kinase inhibitor p27, leading to mitotic arrest and subsequently cell polyploidy. In addition, the pro-apoptotic factors FoxO1/3 are overly degraded by acetylated Skp2, resulting in polyploid cell division, genomic instability, and oncogenesis. importantly, the depletion or inactivation of Akt or Skp2 abrogated Hippo signal deficiency-induced liver tumorigenesis, indicating their epistatic interaction. Thus, we conclude that Hippo-Yap signaling suppresses cell polyploidy and oncogenesis through Skp2.该研究工作获得了国家自然科学基金委、国家重点基础研究发展计划(973)项目、青年千人计划和中央高校基本科研基金的资助。 The Yap (S127A) transgenic mice were kindly provided by Dr. Fernando Camargo from Harvard Medical School, Boston, MA. D.Z. and L.C. were supported by the National Natural Science Foundation of China (31625010,U1505224, and J1310027 to D.Z.; 81422018, U1405225, and 81372617 to L.C.; 81472229 to L.H.), the National Basic Research Program (973) of China (2015CB910502 to L.C.), the Fundamental Research Funds for the Central Universities of China-Xiamen University (20720140551 to L.C. and 2013121034 and 20720140537 to D.Z.)

Hippo信号通路通过调控Skp2活性从而抑制细胞多倍体产生及肝癌发生

文章简介在这项研究中,课题组揭示了Hippo信号通路在限制肝脏细胞的染色体由两倍体向多倍/非整倍体转变过程中起关键作用,该机制异常将导致基因组不稳定继而诱发肝癌的发生发展。课题组通过对Hippo信号通路重要成员(WW45,Mst1/2,Lats1/2)肝脏特异性敲除和过表达国家自然科学基金委;;国家重点基础研究发展计划(973)项目;;青年千人计划;;中央高校基本科研基金的资

Current Status, Challenges and Resilient Response to Air Pollution in Urban Subway

Subway air pollution mainly refers to inhalable particulate matter (PM) pollution, organic pollution, and microbial pollution. Based on the investigation and calculation of the existing researches, this paper summarizes the sources of air pollutants, chemical compositions, and driving factors of PM variations in subway. It evaluates the toxicity and health risks of pollutants. In this paper, the problems and challenges during the deployment of air pollution governance are discussed. Results show that the global PM compliance rate of subway is about 30%. Subway air pollution is endogenous, which means that pollutants mainly come from mechanical wear and building materials erosions. Particles are mainly metal particles, black carbon, and floating dust. The health risks of some chemical elements in the subway have reached critical levels. The variations of PM concentrations show spatial-temporal characteristics, which are mainly controlled by train age, brakes types, and environmental control systems. The authors then analyze the dynamics of interactions among government, companies and public during the air pollution governance by adding the following questions: (a) who pays the bill; (b) how to evaluate the cost-effectiveness of policies; (c) how the public moves from risk perception to actions; (d) how to develop clean air technology better so as to ultimately incentivize stakeholders and to facilitate the implementation of subway clean air programme in a resilient mode

A systematic review and meta-analyses of the relationship between glutathione S-transferase gene polymorphisms and renal cell carcinoma susceptibility

Abstract Background Association of GSTM1- and GSTT1-null genotypes, GSTP1 A/G gene polymorphism with renal cell carcinoma (RCC) susceptibility was detected, and the relationship between the GSTM1/GSTT1-null genotype and clinical TNM stages of RCC was assessed, using meta-analysis method. Methods Association investigations according to eligibility criteria were searched and identified from the databases of Cochrane Library, PubMed, and Embase from establishment time of databases to July 1, 2017, and eligible reports were analyzed by meta-analysis. 95% confidence intervals (CI) were also detected, and odds ratios (OR) was used to express the results for dichotomous data. Results This meta-analysis indicated that there was no an association between GSTM1-null genotype, GSTT1-null genotype, GSTP1 A/G gene polymorphism and RCC risk in the overall population of Caucasians or Asians. The dual GSTM1–GSTT1-null genotype was also not associated with RCC in the overall population of Caucasians. Interestingly, there was an association between the dual GSTM1-GSTT1-null genotype and the susceptibility of RCC in Asians. Relationship of the GSTM1-null genotype with clinical TNM stage of RCC was not observed in the overall population of Asians or Caucasians. In this meta-analysis, no association between the GSTT1-null genotype and clinical TNM stage of RCC was observed in Caucasians or Asians. Interestingly, GSTT1-null genotype was detected to be associated with the clinical TNM stages in patients with RCC in the overall population. Conclusion The dual GSTM1-GSTT1-null genotype is detected to be associated with the onset of RCC in Asians, and there is an association between the GSTT1-null genotype and the clinical TNM stages in patients with RCC in the overall population