Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p?<?0.001). The psoriasis group also had a significantly high mean melting temperature (78.62?±?0.20) when compared with the inactive SLE group (78.49?±?0.29, p?<?0.05) and control group (78.44?±?0.25, p?<?0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28?±?0.21 vs 78.44?±?0.25, p?<?0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.     

Comparison of the practicability of ultrasound and spiral computed tomography in the diagnosis of colon cancer: A protocol for systematic review and meta-analysis

Background:Colon cancer is a common malignant tumor of the gastrointestinal tract. Therefore, a clear diagnosis is particularly important for the treatment of colon cancer. Ultrasound and spiral computed tomography (CT) can both be used in the diagnosis, but each has its own advantages and disadvantages, which could cause confusion in clinical choice. The purpose of this study was to systematically evaluate the practicability of spiral CT and ultrasound in the diagnosis of colon cancer.Methods:A systematic search was performed by retrieving on English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (CNKI, Wanfang, Weipu [VIP], CBM). Besides, manually search for Google and Baidu academic of diagnostic experimental study of ultrasound and spiral CT in the diagnosis of Colon Cancer. The retrieval time limit was from the establishment of the database to October 2020. Two researchers independently extracted and evaluated the quality of the data in the included study. A meta-analysis was performed using Meta Disc1.4 and RevMan5.3 software.Results:Sensitivity, specificity, positive Likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were used to determine the diagnostic efficacy of ultrasonography and helical CT in colorectal cancer.Conclusions:This study will compare the practicability of CT and ultrasound in the diagnosis of colon cancer and provide reliable evidence-based basis for clinicians to choose the appropriate or best evidence-based basis.Ethics and dissemination:The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF Registration number:DOI 10.17605/OSF.IO/WAJHQ     

Learning to Discretize: Solving 1D Scalar Conservation Laws via Deep Reinforcement Learning

Conservation laws are considered to be fundamental laws of nature. It has broad applications in many fields, including physics, chemistry, biology, geology, and engineering. Solving the differential equations associated with conservation laws is a major branch in computational mathematics. The recent success of machine learning, especially deep learning in areas such as computer vision and natural language processing, has attracted a lot of attention from the community of computational mathematics and inspired many intriguing works in combining machine learning with traditional methods. In this paper, we are the first to view numerical PDE solvers as an MDP and to use (deep) RL to learn new solvers. As proof of concept, we focus on 1-dimensional scalar conservation laws. We deploy the machinery of deep reinforcement learning to train a policy network that can decide on how the numerical solutions should be approximated in a sequential and spatial-temporal adaptive manner. We will show that the problem of solving conservation laws can be naturally viewed as a sequential decision-making process, and the numerical schemes learned in such a way can easily enforce long-term accuracy. Furthermore, the learned policy network is carefully designed to determine a good local discrete approximation based on the current state of the solution, which essentially makes the proposed method a meta-learning approach. In other words, the proposed method is capable of learning how to discretize for a given situation mimicking human experts. Finally, we will provide details on how the policy network is trained, how well it performs compared with some state-of-the-art numerical solvers such as WENO schemes, and supervised learning based approach L3D and PINN, and how well it generalizes.     

补骨脂素抗增生性瘢痕作用机制研究

目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。     

动脉栓塞对骨盆肿瘤手术疗效的影响

[目的]探讨供血动脉栓塞对骨盆肿瘤手术疗效的影响。[方法]本组16例，脊索瘤7例，骨巨细胞瘤3例，骨转移瘤3例，骨肉瘤2例，神经纤维瘤1例。术前1d行肿瘤血管造影并用明胶海绵进行供血动脉栓塞。与对照组（结扎双侧髂内动脉骨盆肿瘤切除术）比较，观察其对术中出血量、手术时间、住院时间、术后下床时间、伤口愈合时间及术后各种功能恢复的影响。[结果]骨盆肿瘤切除术前肿瘤供血动脉栓塞与结扎双侧髂内动脉比较，除术中出血量外（P〉0．05），手术、住院、术后下床及伤口愈合时间在统计学上均有非常显著性差异（P〈0．001），而且结扎双侧髂内动脉可能对患者的性功能、排便功能等存在着不良的影响。[结论]肿瘤供血动脉栓塞骨盆肿瘤切除术可大大缩短手术、住院、术后下床、伤口愈合时间，且能更好地保护盆腔内外各组织器官的血运，从而避免其功能的损害。     

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK(-/-) mice.

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.     

早产儿呼吸机相关性肺炎抗生素应用策略

随着新生儿高级生命支持技术的发展。新生儿、早产儿抢救效率大为提高，患儿存活率、存活时间等指标也不断提高。在系列生命支持技术中，新生儿、早产儿的呼吸支持占了极其重要的地位。在呼吸机使用频率增加的同时，由于呼吸机使用所导致的呼吸机相关性肺炎（ventilator associated pneumonia，VAP）的发病率也随之提高，成了NICU中十分重要的问题，能否处理得当，直接关系到新生儿抢救的转归。可以肯定的是VAP增加了病人的死亡率、延长机械通气时间、增加住院天数，同时大大提高了治疗费用。