1.Amniotic membrane transplantation in the treatment of conjunctival rupture, dehiscence and socket contracture after hydroxyapatite orbital implantation
Xian-Yong, LIU ; Jing-Yi, ZHUANG ; Yi-Jing, XIN
International Eye Science 2014;(12):2271-2273
AlM: To investigate the clinical effect of preserved amniotic membrane transplantation in the treatment to conjunctival rupture, dehiscence and socket contracture after hydroxyapatite ( HA) orbital implantation.
METHODS: ln 16 cases of conjunctival rupture and socket contracture after HA orbital implantation, conjunctival tension was release by operation and preserved amniotic membrane was transplanted on conjunctival scleral exposure area.
RESULTS:ln all cases, conjunctiva healing, completely cover the sclera and conjunctiva socket recover ideal depth after operation in 15 cases, 1 case was fail.
CONCLUSlON: Preserved amniotic membrane transplantation is an effective method to treat conjunctival dehiscence and keeping the ideal conjunctival socket depth after orbital implantation.
2.Universal strategies and methodologies in broad-spectrum antiviral drug discovery
Shu-jing XU ; Dang DING ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(5):1289-1300
Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.
3.Integrated medicinal chemistry: new modalities and methodologies in drug discovery
Shu-jing XU ; Dang DING ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(10):2889-2901
New drug research and development is a technology-intensive industry with high investment, high cycle and high risk. In recent years, with the rapid development of modern disciplines such as omics technology, bioinformatics, high-throughput and high-content screening, and artificial intelligence, the research and development of small-molecule drugs has presented a new paradigm characterized by "integrated medicinal chemistry". This review summarizes new enabling drug discovery technologies, the emergence of new subfields formed through integration innovations and practical chemistry toolbox in the field of medicinal chemistry.
4.Enlightenment of Australian government′s activity based funding payment mode to public hospitals
Xin SHEN ; Heng JIANG ; Jing FENG ; Yong GAN ; Zuxun LU
Chinese Journal of Hospital Administration 2021;37(1):78-81
Based on the needs of healthcare system reform, Australia has implemented activity based funding(ABF) payment mode nationwide, and established the Independent Hospital Pricing Authority as the specific implementation agency in 2011. The main responsibilities and functions of the ABF payment mode covers pricing of medical services, classification of healthcare services, collection of clinical data and cost accounting of healthcare services. ABF payment mode presents outstanding advantages in promoting the capacity of healthcare service, maintaining fairness of healthcare service supplies and carrying out cooperation across different institutions. These efforts provide important references for China in its top-level design of payment method, pilot project of classification system, medical service items and price dynamic adjustment, informationization and information standardization construction among public hospitals.
5.Alternation and modulation of tumor necrosis factor-alpha and protein kinase C in celiac macrophage of mouse after serious scalding
Yong WANG ; Wenhua HUANG ; Daizhi PENG ; Xin ZHOU ; Jing LIU
Chinese Journal of Tissue Engineering Research 2005;9(10):249-251
BACKGROUND: Serious scalding leads to dysfunction of each aspect in immune system, and activated macrophage can secret many bioactive transmitters. The relationship between macrophage dysfunction and signal conduction after scalding is unclear at present.OBJECTIVE: To observe the alternation of tumor necrosis factor- alpha(TNF-α) at different time points after scalding and the activity of nuclear factor κB(NF-κB) and alternation of protein kinase C (PKC) after the application of specific modulator H-7 to explore whether PKC participates in the modulation of TNF-α in macrophage on signal conduction level for the clarification of some mechanisms of macrophage dysfunction.DESIGN: A randomized controlled experimental study by employing experimental animals as subjectsSETTING: An institute of burn research of a military medical university MATERIALS: The study was conducted in the Laboratory (state) of the Institute of Burn Research, Third Military Medical University of Chinese PLA between January and December 1999. Experimental animals were 32 healthy clean inbreeding Kunming white mice.METHODS: 15% Ⅲ scalding was created in mice for the establishment of routine scalding model. Mice were randomly divided into 6 groups according to different time points before or after scalding, I.e. 0(normal control group), 2, 6, 12, 24, or 48 hours group. Celiac macrophages were collected for the detection of TNF-α content by radioimmunoassay, NF-κB activity by electrophoretic mobility shift analysis (EMSA), and membrane or plasma PKC activity by isotope analysis.MAIN OUTCOME MEASURES: ① TNF-α content; ② NF-κB activity; ③Membrane or plasma PKC activity RESULTS: After scalding, macrophage excessively secreted TNF-α and reached its peak of (1 085.65 ± 122.99) ng/L at 12 hours, which was significantly higher than that of control group( t = 14.92, P < 0.01 ).Compared with control group, membrane PKC activity increased after scalding, which significantly heightened to(231.80 ± 31.66) nmol/min · g at 2hours( t = 7. 930, P < 0.01 ), slightly decreased to close to normal level of (174.29±16.80) nmol/min· gat 6hours(t=2.531, P <0.05), and rapidly elevated at 12 hours [512. 10 ±33.42) nmol/min · g] and 24 hours [ (454.70 ± 21.06) nmol/min · g] to reach its peak of(530.49 ± 28.54)nmol/min. G at 48 hours( t = 29.42, 28.03, 30. 19, P < 0. 01 ). Correlation analysis of the alternation between TNF-α and membrane PKC indicated a significant positive correlation( r = 0. 796 4, P < 0. 05) . As indicated by EMSA image, NF-κB activity significantly elevated after scalding. Twelve hours after scalding was set as modulation point, NF-κB activity was significantly inhibited by the application of H-7.CONCLUSION: The secretion of TNF-α and the activities of PKC and NF-κB are significantly activated in celiac macrophage after scalding, and PKC-NF-κB signal pathway participates in the modulation of TNF-α expression, which provide experimental data for the modulation of immune function and rehabilitative intervention during scalding.serious scalding.
6.Changes and immune function mechanism of tumor necrosis factor-alpha in murine peritoneal macrophage after severe scald
Yong WANG ; Daizhi PENG ; Xin ZHOU ; Wenhua HUANG ; Jing LIU
Chinese Journal of Tissue Engineering Research 2005;9(6):233-235
BACKGROUND: Severe scald injury leads to a variety of disorders in the immune system. Activated macrophages are known to secrete many kinds of biologically active transmitter, but the relation between the functional disorder of the macrophages and signal transduction after burn injury has not been fully understood.OBJECTIVE: To observe the changes in nuclear factor(NF) -κκB activity and expressions of IκκB-α and tumor necrosis factor(TNF) -α in peritoneal macrophage of mice at different time points after severe scald injury and after the application of specific NF-κκB inhibitor pyrrolidine dithiocarbamate (PDTC), thereby to explore the mechanism of macrophage dysfunction in light of signal transduction.DESIGN: A randomized controlled experimental research.SETTING: State Key Laboratory of Trauma, Burn and Combined Injury.MATERIALS: The experiment was carried out in the State Key Laboratory of Institute of Burn Research, Third Military Medical University during the period from January to June, 1999, using 30 healthy clean-grade Kunming mice of inbred strain.INTERVENTIONS: Common scald injury models(with third degree burn of 15% total body surface area) were established in the mice, which were randomized into 6 groups according to different time points after the injury for observation, namely 0 hour(normal control group) and postburn 2, 6, 12,24 and 48 hours. Peritoneal macrophages were collected at these time points for examining TNF-α content using radio-immunoassay and NF-κκB activity by means of electrophoretic mobility shift assay(EMSA). The expressions of IκκB-α and TNF-α mRNA were determined by immunoblotting method and reverse transcription-PCR, respectively.MAIN OUTCOME MEASURES:Examinations of ① the content of TNF-α, ② NF-κκB activity,③ expression of IκB-α, and ④ expression of TNF-α mRNA.RESULTS: Macrophage secretion of TNF-α was enhanced postburn, reaching the peak level at 12 hours[(1085.65 ± 122.99) ng/L], which was significantly higher than that in the normal control group( t = 14.92, P < 0.01) .Postburn NF-κκB activity significantly increased after the injury, peaking at 2 hours[ (56. 8 ± 7.3)RDU], which occurred much earlier than the peak of TNF-α secretion( t=13. 31, P < 0.01 ). Compared with that in the normal control group, IκB-α expression decreased significantly 2 hours postburn ( t =4. 23, P < 0. 01) to 0. 632 ±0. 086, followed by gradual increase to the peak level to 1. 161 ± 0. 097 24 hours after the burn injury( t = 7.06, P< 0. 01) and then by slight decrease to 1. 149 ±0. 167 till 48 hours(t = 4. 82, P < 0.01) . Twelve hours after injury was the time point for intervention with PDTC application, when NF-κκB activity and TNF-α mRNA expression both decreased significantly( P < 0.01 ).CONCLUSION: NF-κB activity and TNF-αmRNA expression decrease significantly after severe scald. At high levels, IκB-α and NF-κκB maintain an interaction for their restriction. After burn injury, NF-κκB signal transduction pathway is involved in the modulation of TNF-α expression in mouse peritoneal macrophage.
7.Therapeutic efficacy of pegylated polymyxin E in the treatment of infection induced by gramnegative bacteria and the effect of reducing nephrotoxicity.
Tao ZHANG ; Xin-xin ZHANG ; Yong GAN ; Na WU ; Jing-jing ZHU ; Shu-fang HE ; Hui LTU
Acta Pharmaceutica Sinica 2015;50(5):605-612
Polymyxin E shows effective treatment of the infection induced by resistant gramnegative bacteria, but its nephrotoxicity severely limits the clinical application of this drug. In this work, methoxypolyethylene glycols 2000 (mPEG2K)-polymyxin E (PME) was synthesized via chemical grafting reaction and had been characterized. The antimicrobial activity and cytotoxicity of mPEG2K-PME in vitro were investigated on Escherichia coli and HK-2 cells, separately. Intra-abdominal infection model was further established in order to study the therapeutic effect and the toxic effect on kidney of mice. The results showed that mPEG2K-PME exhibited significant inhibitory effect on Escherichia coli and had a lower toxicity on HK-2 cells in vitro. At the same time, mPEG2K-PME had a good efficacy in the treatment of Escherichia coli infected mice in vivo. Moreover, nephrotoxicity caused by mPEG2K-PME was significantly reduced compared to free PME. mPEG2K-PME is promising in development of new preparations with high efficiency and low toxicity.
Animals
;
Cell Line
;
Colistin
;
pharmacology
;
toxicity
;
Escherichia coli
;
drug effects
;
Escherichia coli Infections
;
drug therapy
;
Humans
;
Kidney
;
cytology
;
drug effects
;
Mice
;
Polyethylene Glycols
;
chemistry
8.Giant ulcerated basal cells carcinoma invading the eyeball, orbit and skull: a case report
Yong, LIU ; Zheng, JING ; Yan-Xin, CHEN ; Hong-Tao, LI ; Lei, ZHANG
International Eye Science 2008;8(8):1528-1529
· Basal ceil carcinoma (BCC) is one of the most common human cancers. The giant ulcerated BCC invading the eyeball and orbit has been rarely reported. We present a case of giant BCC with cutaneous ulcer on the left head,invading the eyeball, orbit and skull.
9.Bioinorganic chemistry strategies in antiviral drug discovery
Shu-jing XU ; Xu-jie ZHANG ; Dang DING ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(3):576-592
Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.
10.Research progress of natural products for the treatment of hyperuricemia and gout
Zhi-jiao ZHANG ; Rui-peng LIANG ; Tong ZHAO ; Shu-jing XU ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(6):1679-1688
Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.