Association of ankylosing spondylitis with cardiovascular disease: a bidirectional two-sample mendelian randomization study

BackgroundsCurrent observational investigations hint at a potential linkage between ankylosing spondylitis and cardiovascular wellness. However, the nature of this causality remains to be elucidated. Consequently, this study is designed to evaluate the causal interconnection between ankylosing spondylitis and cardiovascular-related conditions utilizing a bidirectional two-sample Mendelian Randomization (MR) methodology.MethodsIn this study, we conducted Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. The fixed-effects inverse variance weighted (IVW) model was used as the primary analysis method, and MR-Egger regression and the weighted median method were employed as supplementary approaches. Horizontal pleiotropy and heterogeneity were evaluated using various statistical tests, including MR-PRESSO global test, MR-Egger intercept, and Cochran’s Q test.ResultsThe MR result demonstrated an increased risk of heart failure in individuals with ankylosing spondylitis (OR: 1.0132, 95% CI = 1.0043-1.0221, p = 0.003). The MR analysis results did not demonstrate a causal relationship between ankylosing spondylitis and other cardiovascular diseases, such as atrial fibrillation, coronary artery disease, ischemic stroke, myocardial infarction, and valvular heart disease (all p > 0.05). No evidence of reverse causality was found between ankylosing spondylitis and mentioned cardiovascular diseases in reverse MR analyses. Sensitivity analysis verified the reliability of the results.ConclusionOur MR study indicates a relationship between ankylosing spondylitis and an increased risk of heart failure. Further research is needed to confirm these findings and elucidate the underlying mechanisms involved

Effects of different tooth movement patterns and aligner thicknesses on maxillary arch expansion with clear aligners: a three-dimensional finite element study

ObjectivesThe objective of this study was to investigate the biomechanical effects of different tooth movement patterns and aligner thicknesses on teeth and periodontal tissues during maxillary arch expansion with clear aligners, to facilitate more precise and efficient clinical orthodontic treatments.MethodsThree-dimensional models including teeth, maxilla, periodontal ligament, and aligner were constructed and subjected to finite element analysis. Tooth displacement trends and periodontal ligament stresses were measured for seven tooth displacement patterns (divided into three categories including overall movement of premolars and molars with gradually increasing molar expansion in each step; distributed movement of premolars and molars; and alternating movement between premolars and molars at intervals) and two aligner thicknesses (0.5 mm and 0.75 mm) during maxillary arch expansion with clear aligners.ResultsWhen expanding the maxillary arch with clear aligners, the effective expansion of the target teeth mainly showed a tilting movement trend. Increasing the amount of molar expansion increased the buccal displacement of the first molar but decreased the buccal displacement of the premolars. The mean buccal displacement of the target teeth was greater in the posterior teeth interval alternating movement group (0.026 mm) than in the premolar/molar distributed movement group (0.016 mm) and the overall movement group (0.015 mm). Increasing aligner thickness resulted in greater buccal displacement of the crowns and increased stress on the periodontal ligaments.ConclusionIncreasing the amount of molar expansion reduces the efficiency of premolar expansion. Alternating movement of premolars and molars at intervals achieves a higher arch expansion efficiency, but attention should be paid to the anchorage of adjacent teeth. Increasing the thickness of the aligner increases the expansion efficiency but may also increase the burden on the periodontal tissues

Danhong Injection Alleviates Cardiac Fibrosis via Preventing the Hypermethylation of Rasal1 and Rassf1 in TAC Mice

Background/Aim. Danhong injection (DHI) is a Chinese patent drug used for relieving cardiovascular diseases. Recent studies have suggested that DNA methylation plays a pivotal role in the maintenance of cardiac fibrosis (CF) in cardiovascular diseases. This study was aimed at identifying the effect and the underlying mechanism of DHI on CF, especially the DNA methylation. Methods. A CF murine model was established by thoracic aortic constriction (TAC). A 28-day daily treatment with or without DHI via intraperitoneal injection was carried out immediately following TAC surgery. The changes in cardiac function, pathology, and fibrosis following TAC were measured by echocardiography and immunostaining. We used methyl-seq analysis to assess the DNA methylation changes in whole genes and identified the methylation changes of two Ras signaling-related genes in TAC mice, including Ras protein activator like-1 (Rasal1) and Ras-association domain family 1 (Rassf1). Next, the methylation status and expression levels of Rasal1 and Rassf1 genes were consolidated by bisulfite sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blotting, respectively. To determine the underlying molecular mechanism, the expressions of DNA methyltransferases (DNMTs), Tet methylcytosine dioxygenase 3 (TET3), fibrosis-related genes, and the activity of Ras/ERK were measured by RT-qPCR and Western blotting. Results. DHI treatment alleviated CF and significantly improved cardiac function on day 28 of TAC. The methyl-seq analysis identified 42,606 differential methylated sites (DMSs), including 19,618 hypermethylated DMSs and 22,988 hypomethylated DMSs between TAC and sham-operated mice. The enrichment analysis of these DMSs suggested that the methylated regulation of Ras signal transduction and focal adhesion-related genes would be involved in the TAC-induced CF development. The results of bisulfite sequencing revealed that the TAC-induced methylation affected the CpG site in both of Rasal1 and Rassf1 genes, and DHI treatment remarkably downregulated the promoter methylation of Rasal1 and Rassf1 in CF hearts. Furthermore, DHI treatment upregulated the expressions of Rasal1 and Rassf1, inhibited the hyperactivity of Ras/ERK, and decreased the expressions of fibrosis-related genes. Notably, we found that DHI treatment markedly downregulated the expression of DNMT3B in CF hearts, while it did not affect the expressions of DNMT1, DNMT3A, and TET3. Conclusion. Aberrant DNA methylation of Rasal1 and Rassf1 genes was involved in the CF development. DHI treatment alleviated CF, prevented the hypermethylation of Rasal1 and Rassf1, and downregulated DNMT3B expression in CF hearts

Restructuring the production of medicines: An investigation on the pharmaceutical sector in China and the role of mergers and acquisitions

In places like China, an ageing population coupled with changes in living standards and increases in disposable income, imply a shift of the demand for health-related goods and services which is likely to affect the whole organization of the industries that supply such goods and services at the global level. One of the industries most likely to be affected is the pharmaceutical sector. In the early 2000s China was already the second largest global producer of pharmaceutical ingredients. The pharmaceutical sector has become one of the most important industries promoted by the Chinese government and Five-Year Plan of China’s Strategic Emerging Sectors, mergers and acquisition (M&A) activity has been the key strategy to restructure the sector and increase its competitiveness. This paper firstly provides an updated picture of the evolution of M&As in the pharmaceutical sector, compared to other sectors, in China in the period 2005–2013. Secondly, we develop a composite indicator to measure the industrial performance of all Chinese industrial sectors over time, which allows us to assess the performance of the pharmaceutical industry compared to that of other sectors of the Chinese economy. Finally, we develop and estimate an empirical model that tests the relationship between the number of M&A in a sector and its performance, with a particular focus on the pharmaceutical case. The results offer some initial evidence of positive effects from the process of restructuring of the pharmaceutical sector in China