Targeting GATA1 and p2x7r Locus Binding in Spinal Astrocytes Suppresses Chronic Visceral Pain by Promoting DNA Demethylation / 神经科学通报·英文版

Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal diseases. In this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1 (GATA1) in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation (NCI). The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay, chromatin immunoprecipitation, patch clamp, and interference in vitro and in vivo. In addition, a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG island. We showed that NCI caused the induction of GATA1, Ten-eleven translocation 3 (TET3), and purinergic receptors (P2X7Rs) in astrocytes of the spinal dorsal horn, and demonstrated that inhibiting these molecules markedly increased the pain threshold, inhibited the activation of astrocytes, and decreased the spinal sEPSC frequency. NCI also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1-TET3 physical interaction and GATA1 binding at the p2x7r promoter. Importantly, we showed that demethylation of the p2x7r locus (and the attendant increase in P2X7R expression) was reversed upon knockdown of GATA1 or TET3 expression, and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r promoter. These results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r transcription in spinal dorsal horn astrocytes, and provide a potential therapeutic strategy by targeting GATA1 and p2x7r locus binding.

Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues Memory Impairment in Rats with Type 2 Diabetes / 神经科学通报·英文版

Purinergic receptors have been reported to be involved in brain disorders. In this study, we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus (T2DM). T2DM rats exhibited a worse performance in the T-maze and Morris water maze (MWM) than controls. Microglia positive for P2X purinoceptor 4 (P2X4R) in the hippocampus were reduced and activated microglia were increased in T2DM rats. Long Amplicon PCR (LA-PCR) showed that DNA amplification of the p2x4r gene in the hippocampus was lower in T2DM rats. Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2DM rats in the MWM. Most importantly, P2X4R overexpression suppressed the activated microglia and rescued the memory impairment of T2DM rats. Overall, T2DM led to excessive activation of microglia in the hippocampus, partly through the DNA damage-mediated downregulation of P2X4Rs, thus contributing to memory impairment.

Design mentality of establishing performance distribution system based on homogeneous subsidy base / 医学研究生学报

Performance management is a key direction of the reform of the national medical and health system, and it is also an important starting point for promoting the development of hospital connotation. In view of the contradiction among the current hospital performance distribution system, this paper proposes a design mentality of performance distribution system based on homogenization subsidy base, and expounds the basic connotation and cognitive basis of homogenization subsidy base. The key elements of the design of the performance distribution system are discussed from four aspects: pre-adjusted total control, coefficientized personnel attendance, same performance appraisal, and homogenization subsidy base. At the same time, this paper also analyzes the characteristics of the performance distribution system based on the homogenization subsidy base. The application prospects of the performance distribution system are prospected from three aspects: the national medical reform requirements, the discipline development discipline and the system's own characteristics.

The cultivation and realization of preponderant disciplines in hospital / 医学研究生学报

This paper analyses the Methods of selecting the cultivation direction of hospital′s dominant disciplines and points out that hospitals should analyse the development environment Objective ly, design the discipline distribution scientifically, and harbor the construction thoughts multi-dimensionally. Based on the practical experience of Nanjing General Hospital, this paper expounds vital Methods to develop preponderant disciplines, proposes that "fusion" and "differentiation" are the developing trend and regards the three major factors-leading talents, strong team, and major projects, as the critical points to prompt the cultivation of preponderant discipline. Lastly, the paper further discusses the implementation of cultivation through strengthening the platform construction, enhancing exchange and cooperation, focusing on achievement transformation and highlighting technical features.

Practice and experience of the scientific research management / 中华男科学杂志

The practice and experience of the scientific research management in Nanjing General Hospital from 1997 to 2002 is summarized in this review. By presenting the achievement gained in the past 6 years, the author prove to the scientific research managers that the effective manage thought is the key of scientific research management, and also expatriate the experience of the key points management in the management of scientific research subjects.