Rheumatoid arthritis and the risk of chronic kidney diseases: a Mendelian randomization study

BackgroundThe extra-articular lesions of rheumatoid arthritis (RA) are reported to involve multiple organs and systems throughout the body, including the heart, kidneys, liver, and lungs. This study assessed the potential causal relationship between RA and the risk of chronic kidney diseases (CKDs) using the Mendelian randomization (MR) analysis.MethodIndependent genetic instruments related to RA and CKD or CKD subtypes at the genome-wide significant level were chosen from the publicly shared summary-level data of genome-wide association studies (GWAS). Then, we obtained some single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs), which are associated with RA in individuals of European origin, and had genome-wide statistical significance (p5 × 10−8). The inverse-variance weighted (IVW) method was the main analysis method in MR analysis. The other methods, such as weighted median, MR–Egger, simple mode, and weighted mode were used as supplementary sensitivity analyses. Furthermore, the levels of pleiotropy and heterogeneity were assessed using Cochran’s Q test and leave-one-out analysis. Furthermore, the relevant datasets were obtained from the Open GWAS database.ResultsUsing the IVW method, the main method in MR analysis, the results showed that genetically determined RA was associated with higher risks of CKD [odds ratio (OR): 1.22, 95% confidence interval (CI) 1.13–1.31; p < 0.001], glomerulonephritis (OR: 1.23, 95% CI 1.15–1.31; p < 0.000), amyloidosis (OR = 1.43, 95% CI 1.10–1.88, p < 0.001), and renal failure (OR = 1.18, 95% CI 1.00–1.38, p < 0.001). Then, using multiple MR methods, it was confirmed that the associations persisted in sensitivity analyses, and no pleiotropy was detected.ConclusionThe findings revealed a causal relationship between RA and CKD, including glomerulonephritis, amyloidosis, and renal failure. Therefore, RA patients should pay more attention to monitoring their kidney function, thus providing the opportunity for earlier intervention and lower the risk of progression to CKDs

Electroacupuncture activates corticotrophin-releasing hormone-containing neurons in the paraventricular nucleus of the hypothalammus to alleviate edema in a rat model of inflammation

<p>Abstract</p> <p>Background</p> <p>Studies show that electroacupuncture (EA) has beneficial effects in patients with inflammatory diseases. This study investigated the mechanisms of EA anti-inflammation, using a rat model of complete Freund's adjuvant (CFA)-induced hind paw inflammation and hyperalgesia.</p> <p>Design</p> <p>Four experiments were conducted on male Sprague-Dawley rats (n = 6–7/per group). Inflammation was induced by injecting CFA into the plantar surface of one hind paw. Experiment 1 examined whether EA increases plasma adrenocorticotropic hormone (ACTH) levels. Experiments 2 and 3 studied the effects of the ACTH and corticotropin-releasing hormone (CRH) receptor antagonists, ACTH_(11–24)and astressin, on the EA anti-edema. Experiment 4 determined whether EA activates CRH neurons in the paraventricular nucleus of the hypothalammus. EA treatment, 10 Hz at 3 mA and 0.1 ms pulse width, was given twice for 20 min each, once immediately post and again 2 hr post-CFA. Plasma ACTH levels, paw thickness, and paw withdrawal latency to a noxious thermal stimulus were measured 2 h and 5 h after the CFA.</p> <p>Results</p> <p>EA significantly increased ACTH levels 5 h (2 folds) after CFA compared to sham EA control, but EA alone in naive rats and CFA alone did not induce significant increases in ACTH. ACTH_(11–24)and astressin blocked EA anti-edema but not EA anti-hyperalgesia. EA induced phosphorylation of NR1, an essential subunit of the N-methyl-D-aspartic acid (NMDA) receptor, in CRH-containing neurons of the paraventricular nucleus.</p> <p>Conclusion</p> <p>The data demonstrate that EA activates CRH neurons to significantly increase plasma ACTH levels and suppress edema through CRH and ACTH receptors in a rat model of inflammation.</p

Transient mTOR Inhibition Facilitates Continuous Growth of Liver Tumors by Modulating the Maintenance of CD133+ Cell Populations

The mammalian target of the rapamycin (mTOR) pathway, which drives cell proliferation, is frequently hyperactivated in a variety of malignancies. Therefore, the inhibition of the mTOR pathway has been considered as an appropriate approach for cancer therapy. In this study, we examined the roles of mTOR in the maintenance and differentiation of cancer stem-like cells (CSCs), the conversion of conventional cancer cells to CSCs and continuous tumor growth in vivo. In H-Ras-transformed mouse liver tumor cells, we found that pharmacological inhibition of mTOR with rapamycin greatly increased not only the CD133+ populations both in vitro and in vivo but also the expression of stem cell-like genes. Enhancing mTOR activity by over-expressing Rheb significantly decreased CD133 expression, whereas knockdown of the mTOR yielded an opposite effect. In addition, mTOR inhibition severely blocked the differentiation of CD133+ to CD133- liver tumor cells. Strikingly, single-cell culture experiments revealed that CD133- liver tumor cells were capable of converting to CD133+ cells and the inhibition of mTOR signaling substantially promoted this conversion. In serial implantation of tumor xenografts in nude BALB/c mice, the residual tumor cells that were exposed to rapamycin in vivo displayed higher CD133 expression and had increased secondary tumorigenicity compared with the control group. Moreover, rapamycin treatment also enhanced the level of stem cell-associated genes and CD133 expression in certain human liver tumor cell lines, such as Huh7, PLC/PRC/7 and Hep3B. The mTOR pathway is significantly involved in the generation and the differentiation of tumorigenic liver CSCs. These results may be valuable for the design of more rational strategies to control clinical malignant HCC using mTOR inhibitors

The Study of Semantic Prosody of Chinese Logical Resultative Formulae: A Corpus-assisted Discourse Analysis Approach

Logical resultative formulae refer to theformularized expressions denoting causal/resultative relationsbetween two situations or events. In Chinese such expressions asyinwei… suoyi (因为/because…所以/so), yuanyinshi (原因是/Thereason is…)， jinran…jiu(既然/ since…就/then), etc. are widelyused cases. These expressions frequently serve as the bridgelinking two clauses; yet in communication they do not just fulfillconjunction functions, instead they convey the addresser’sattitudinal meaning, namely semantic prosody. However, up tonow, no research has been done concerning semantic prosodies ofChinese logical resultative formulae. Thus, with the help ofcorpus-assisted discourse analysis approach, the present articleattempts to do a research on semantic prosodies of Chinese logicalresultative formulae so that we can avoid misusing theseexpressions while expressing cause and effect relations in Chinese

Influences of 1,2-dichlorobenzene on bacterial community structure in wetland soil

In order to explore the response of the soil microbial community to 1,2-dichlorobenzene exposure in Wetland soil, a short-term (7 weeks) mesocosm study was conducted at four 1,2-dichlorobenzene concentrations of (100, 400 and 800) μg g -1. Dry soil, sterile and unsterile controls were also compared. The results obtained showed a significant effect of 1,2-dichlorobenzene on the development of bacterial populations in soils contaminated with different concentrations of 1,2-dichlorobenzene at the early time after application. In general, however, the number of populations of the same soil sample treated with the same concentration of 1,2-dichlorobenzene differed significantly with the increasing incubation time within the early 5 weeks. The scale of differences in banding patterns-showed that the microbial community structures of 1,2-dichlorobenzene-treated and non-1,2-dichlorobenzene-treated soils were not significantly different after 7 weeks of incubation. DNA in application-responsive bands from the 1,2-dichlorobenzene treatments was recovered and amplified using the universal primers. PCR products were recovered and cloned into pGEM-T Easy (Promega) and two clones were obtained. The two clones were sequenced using the automated Model 3730 DNA sequencing system. The two cloned sequences had very high similarities to an uncultured bacterium reported previously in the database of NCBI

Numerical simulation of interfacial reaction between titanium and zirconia

Based on the conservation laws of energy and mass, and taking into account the effect of chemical reaction between liquid titanium and zirconia ceramic mold on the concentration field and the temperature field, a comprehensive mathematical model for numerical simulation of heat and mass transfer has been established to study the interfacial reaction between liquid Ti and ZrO2 ceramic mold. With the proposed model, numerical simulations were preformed to investigate the effects of pouring temperature and holding time on the oxygen concentrations and reactive layer thickness in metal. The results showed that both the oxygen concentration and the thickness of reactive layer in metal increase with the increase of the holding time and the pouring temperature. The development of reactive layer thickness with time consists of three stages: inoculation (0-1 s), linear increase (1-5 s) and parabolic increase (after 5 s)