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.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.
5.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.
6.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.
7.Study of Bone Mineral Density Measuring System with Quantitative CT
Jing-Xin LIU ; Guang ZHANG ; Jing SUN ; Yong HAN ; Xue-Feng HAN
Chinese Journal of Medical Instrumentation 2001;25(3):130-131,148
This paper introduces a kind of bone mineral density(BMD) measuring system with quantitative CT(QCT). This system includs a self-made solid calibration phantom for BMD and the measuring software. The results of the tests have showed that this system is reliable,cheap and ease of use for BMD measurement.
8.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
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Colistin
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pharmacology
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toxicity
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Escherichia coli
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drug effects
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Escherichia coli Infections
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drug therapy
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Humans
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Kidney
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cytology
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drug effects
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Mice
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Polyethylene Glycols
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chemistry
9.Coronary renal shunt via splenic vein for portal hypertension after splenectomy
Mingguo TIAN ; Yong YANG ; Peng DU ; Yang DING ; Guojun XIN ; Jing ZHAN
Chinese Journal of Digestive Surgery 2016;15(7):735-741
Objective To investigate the clinical efficacy of coronary renal shunt via splenic vein for portal hypertension (PHT) after splenectomy.Methods The retrospective descriptive study was adopted.The clinical data of 5 patients with PHT who were admitted to the People's Hospital of Ningxia Autonomous Region from August 2012 to April 2015 were collected.Operative procedures:two procedures of coronary renal shunt via splenic vein (SV) were carried out after primary splenectomy.Procedure 1:the SV was freed from the residual end to the right for 5-6 cm in length and end-to-side spleno-renal shunt was carried out.The anterior wall of superior mesenteric vein (SMV) was exposed beneath the pancreatic neck and dissected behind the neck upward until the upper edge of the SV and its confluence with the left gastric vein (LGV) were exposed.The SV was ligated with clip between portal vein (PV) and LGV to let blood flow from LGV drain through the whole course of SV to left renal vein (LRV).Procedure 2:the peritoneum at the inferior border of the pancreas was incised,and the junctions of the SV and SMV and junctions of the SV and LGV were exposed.The inferior mesenteric vein (IMV) was divided between ligations.Dissection of the SV was carried out to the left for 3-4 cm in length and was divided.Its distal end was tied and proximal stump anastomosed to LRV by the end-to-side anastomosis.The SV was ligated with clip between PV and LGV.The right gastric and gastroepiploic vessels were ligated at the junction of the antrum and the body,and from this point,the hepatogastric ligment and the omentum were divided upward and downward respectively to completely separate the venous flow between the hepatointestinal area and the stomach in the two procedures.Patients took oral enteric-coated aspirin and warfarin after operation.(1) Intraoperative observation indicators included surgical procedures,operation time,volume of blood loos and free portal pressure (FPP).(2) Postoperative observation indicators included recovery of patients,time to anal exsufflation,time for diet intake,time of abdominal drainage,duration of hospital stay and occurrence of complications.(3)The follow-up using telephone interview and outpatient examination was performed to detect the changes of platelet (PLT),portal vein thrombosis (PVT),patency of spleno-renal vein anastomosis,oral anticoagulants and gastroesophageal varices up to October 2015.Measurement data with skewed distribution were analyzed by M (range).Results (1)Intraoperative observation indicators:5 patients underwent successful coronary renal shunt via splenic vein.Two patients received procedure 1 and 3 patients received procedure 2.Operation time and volume of blood loss were 226 minutes (range,195-298 minutes) and 425ml (range,235-820 mL).FPP was 3.46 kPa (range,2.69-4.61 kPa) before spleen resection,2.69 kPa (range,2.11-3.07 kPa) after spleen resection,2.98 kPa (range,2.30-3.36 kPa) after spleno-renal anastomosis,respectively.(2) Postoperative observation indicators:5 patients had good recovery,and time to anal exsufflation,time for fluid diet intake,time of abdominal drainage removal and duration of hospital stay were respectively 3 days (range,2-4 days),3 days (range,2-4 days),5 days (range,4-9 days) and 14 days (range,10-17 days).Of 5 patients,1 was complicated with pleural effusion and atelectasis and 1 with serum tumescence of incision.(3) Follow-up situations:5 patients were followed up for a median time of 18 months (range,6-36 months).The level of postoperative PLT was continuously growing,and the dose of oral warfarin was increased according to the level of growing PLT.The follow-up results of procedure 1 in 2 patients:1 patient was followed up for 36 months and complicated with splenic vein thrombosis at postoperative month 6,and underwent transcatheter hepatic arterial chemoembolization (TACE) due to primary liver cancer at postoperative month 12,and then no special treatment was conducted due to splenic vein occlusion and sever esophageal varices without red-color sign or bleeding at postoperative month 36.The other patient was followed up for 24 months,and didn't undergo special treatment due to mild hepatic encephalopathy with a level of blood ammonia of 76 μmol/L at postoperative month 3,and then was found to have mild esophageal varices at postoperative month 18 by computed tomography (CT) and gastroscopy.Three patients using procedure 2 were followed up at month 6,12,18,with increased body mass index (BMI) and without occurrence of peritoneal effusion and hepatic encephalopathy,and they were complicated with mild gastroesophageal varices by reexamination of CT angiography and gastroscopy at postoperative month 6.Conclusion Coronary renal shunt via splenic vein for PHT after splenectomy could relieve hypersplenism and reduce selectively vein decompression of gastroesophageal varices.
10.The renoprotective role of all-trans retinoic acid in retarding rat glomerulosclerosis with 5/6 nephrectomy
Man LI ; Jing XIN ; Yong GU ; Ai PENG ; Shaojun LIU ; Qiuyu ZHU ; Shanyan LIN
Chinese Journal of Pathophysiology 2000;0(07):-
AIM: To explore if all trans retinoic acid (atRA) retards glomerulosclerosis of rats with 5/6 nephrectomy. METHODS: Wistar male rats were operated by subtotal nephrectomy and were randomly divided into A1 (5 mg?kg~(-1)?d~(-1) atRA), A2 (10 mg?kg~(-1)?d~(-1) atRA), A3 (20 mg?kg~(-1)?d~(-1) atRA) and NX (vehicle) groups. Each group included 8 rats. 8 health rats were assigned as sham-operation group (sham group). Animals were sacrificed 10 weeks after treatment. The concentrations of plasma atRA were measured by reversed phase high performance liquid chromatography (RP-HPLC). Glomerulosclerosis was evaluated by glomerulosclerosis index system. The expression of transforming growth factor-beta 1 (TGF?1) was measured by renal immunohistochemical staining and Western blotting. RESULTS: The concentrations of atRA in atRA groups were much higher than that in NX and sham groups. Compared to NX, the remnant kidney sclerosis was ameliorated significantly in A1, A2 and A3 groups. The expressions of TGF?1 decreased parallelized to the levels of glomerulosclerosis. CONCLUSION: atRA has a beneficial effect on retarding the progression of renal fibrosis in the 5/6 nephrectomic rats, possibly through downregulating the glomerular TGF?1 expression.