1.Analysis of the research status and intervention strategies for the treatment of hepatic encephalopathy based on gut microbiota regulation
Jia-ting YIN ; Yin PENG ; Wen-hao XU ; Meng-fei MAO ; Jin-ao DUAN ; Jian-ming GUO
Acta Pharmaceutica Sinica 2021;56(4):895-905
Hepatic encephalopathy is a common metabolic neuropsychiatric syndrome in the development of end-stage liver disease. Since the concept of intestinal-liver-brain axis was proposed, the relationship between the pathogenesis of hepatic encephalopathy and the gut microbiota has been a hot research topic. In recent years, studies have confirmed that gut microbiota is involved in and affects various pathological processes of hepatic encephalopathy. This article combines the latest research progress at home and abroad to elaborate on the research status of regulating gut microbiota and thus interfering with the pathological process of hepatic encephalopathy, hoping to provide new ideas and methods for the intervention of hepatic encephalopathy based on the regulation of gut microbiota.
2.Design, synthesis and biological evaluation of novel 3-(2-oxo-2-substituted acetamido)benzamides as PARP-1 inhibitors.
Yu-wen YIN ; Ming JI ; Ran CAO ; Xiao-guang CHEN ; Bai-ling XU
Acta Pharmaceutica Sinica 2015;50(6):738-745
Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents
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Benzamides
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chemistry
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DNA Repair
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Drug Design
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Humans
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Molecular Docking Simulation
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Poly(ADP-ribose) Polymerase Inhibitors
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chemical synthesis
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chemistry
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Poly(ADP-ribose) Polymerases
3.Surgical treatment of familial adenomatous polyposis:a report of 45 cases
Yin WEN ; Jingbo LU ; Ming ZHU ; Chengtang WU ; Lie LI ; Wei ZHU
Chinese Journal of General Surgery 2001;0(09):-
Objective To summarize the clinical data of 45 cases of familial adenomatous polyposis(FAP) and the experiences of treatment and diagnosis of FAP. Methods Retrospectively analyzed of the clinical data was made on 45 FAP patients.The choice of operative procedure included total colectomy+ileostomy in 25 cases,subtotal colectomy+rectal polyposis electrocautery in 15,and total colectomy with ileo-anal anastomosis in 5. Results Average age of patients at first diagnosis was 33.5 years. A family history was found in 35 patients. Bleeding, diarrhea, pain are common clinical presentations, and the numbers of polyposis were all more than 100. All patients without malignant change survived for 3-21years;and metastasis of liver was the main cause of death in patients with malignant change. There were age differences between malignant and non malignant group. Conclusions FAP lacks typical clinical presentation, and misdiagnosis is not uncommon. Surgical therapy should be done on an individual basis and according to the actual condition of patients.
4.Changes of respiratory and hemodynamic functions in children with laparoscopic Nissen's fundoplication
ying, SUN ; wen-yin, XU ; jia-ping, ZHANG ; yan-ting, WANG ; jie, BAI ; yi-ming, WU
Journal of Shanghai Jiaotong University(Medical Science) 2006;0(05):-
Objective To observe the changes of respiratory and hemodynamic functions in children with different age undergoing laparoscopic Nissen's fundoplication(LNF). Methods Thirty-three children with LNF were divided into three groups according to the age: group Ⅰ,1 to 12 months,n=13;group Ⅱ,1 to 3 years old,n=10;and group Ⅲ,4 to 7 years,n=10.Heart rate(HR),mean arterial pressure,Ppeak,compliance of the respiratory system(CRS) and end-tidal carbon dioxide pressure(PETCO2) were recorded 5 min before pneumoperitoneum(T0),10 min(T1),60 min(T2) after pneumoperitoneum and 10 min after deflation(T3),and parameters of blood gas analysis such as PaCO2 were measured at the same time. Results Compared with those at T0,HR,Ppeak,PETCO2 and the difference between PaCO2 and PETCO2(Pa-ETCO2)were significantly increased at T1 and T2,while CRS was significantly decreased.The most significant changes were found in group Ⅰ. Conclusion The changes of respiratory and hemodynamic functions are observed in children undergoing LNF,and anesthesia management should be enhanced for those within 1 to 12 months old who experience the most significant changes.
5.Increased ostial pulmonary vein diameter in congestive heart failure: a multi-slice computed tomography angiography evaluation
Lei GAO ; Xihai ZHAO ; Xin LIU ; Caiyi LU ; Ming YIN ; Yuxiao ZHANG ; Yi WEN ; Shiwen WANG
Journal of Geriatric Cardiology 2006;3(1):45-50
Background and Objectives The relationship between left atrial (LA) size and congestive heart failure (CHF) is well recognized;however, there is little information on the association of pulmonary vein (PV) diameter and CHF.The purpose of this study was to investigate the changes of PV and LA sizes in CHF patients by multislice computed tomography (MSCT) angiography using a new 64-slice scanner. Methods and Results We assessed diameters of PVs ostium and LA by 64-slice MSCT with three-dimensional reconstruction in 25 CHF patients and in 26 age- and sex-matched non-CHF controls. Compared with controls, CHF patients showed significant greater diameters of left superior pulmonary vein (LSPV) and right inferior pulmonary vein (RIPV) in both anteriorposterior(AP) and superior-inferior (SI) directions (P<0.01), significant dilation of right superior pulmonary vein (RSPV) in AP direction (P<0.05), as well as significant increase of LA transverse, AP, and SI diameters (P<0.01). Conclusion Significant dilation of PVs with simultaneous LA enlargement was demonstrated in CHF patients. This anatomic and geometric changes may participate in the perpetuation of AF.
6.Relative factors in home safety evaluated by multilevel statistical models
Shu-Mei WANG ; Jin-Liang ZOU ; Wen-Yan XU ; Ming-Min YIN
Chinese Journal of Epidemiology 2010;31(9):975-978
Objective To understand the situations of home establishments and the related domestic behaviors that causing injuries. Methods A total of 9760 families with regular residents in a community in Shanghai were investigated. Questionnaire was designed bascd on the Guidelines for Conducting Community Surveys on Injuries and Violence and International Classification of External Causes of Injuries. Results Inside the home settings, relative factors were found on issues as fire protection and using of electricity. In terms of household settings, 14.85% of the families had smoke alarm systems in the kitchen; 40.75% had no windows set for emergence. 50% to 70% of the residents had the idea of safe behaviors, including 35.93% of the families stored cleaning products,other chemicals or medical substances in alternative containers, such as used drinking bottle. Only 1.81% of the people being investigated thought that home was also a high risk place where injury might occur and it was placed number 9 in a multiple choice questionnaire. Data from the multiple level model analysis showed that factors as number of family members, space, education, profession etc. were closely related to the situation of home settings and their resident's behaviors. Conclusion Many injury related factors were found related to home establishments and people' s daily behaviors at home which called for interventions to be taken.
7.The role of T-type calcium channel in the pathogenesis of neuropathic pain in rats
Zhi-Xin CHEN ; Yin-Ming ZENG ; Jun-Ke WANG ; Xianjie WEN ;
Chinese Journal of Anesthesiology 1994;0(01):-
Objective To investigate the effect of intrathecal(IT)mibefradil on the mechanical and thermal hyperalgesia following chronic compression of dorsal mot ganglion(CCD)in rats,trying to elucidate the role of T-type calcium channels in the nociceptive signal transmission at spinal level.Methods Forty-eight male SD rats weighing 230-250 g were randomly divided into 6 groups(n=8 each):group Ⅰ sham operation;group Ⅱ CCD;group Ⅲ CCD+normal saline(N.S.)and group Ⅳ,Ⅴ,Ⅵ CCD+mibefradil 50 ?g(Ⅳ),100 ?g (Ⅴ),200 ?g(Ⅵ).The animals were anesthetized with intraperitoneal(IP)1% pentobarbital 40 mg?kg~(-1). Intrathecal catheter was placed according to the technique described by Yaksh et al.Five days after IT catheter placement L_4 and I_5 dorsal root ganglion(DRG)compression(CCD)was performed in group Ⅱ-Ⅵ.In sham operation group(Ⅰ)only L_(4-5) transverse processes and intervertebral foramina were exposed but DRGs were not compressed.In group Ⅳ,Ⅴ,and Ⅵ 5 days after CCD model was established a bolus of mibefradil 50,100 and 200 ?g in 10 ?l NS was given IT.In group Ⅲ NS 10 ?l was given IT instead of mibefradil.Mechanical withdrawal threshold(MWT)using Von Frey filament and thermal withdrawal latency(TWL)using radiant heat applied to the plantar surface were measured before CCD(baseline)and 1,3,5,7,14 and 21 days after CCD in group Ⅰ and Ⅱ and before and 30,60,120,240 and 480 min after IT mibefradil in group Ⅲ-Ⅵ.Results The animals in group Ⅱ(CCD group)developed mechanical and thermal hyperalgesia from the 1st day after operation to the end of the experiment.IT mibefradil 50,100 and 200 ?g can all attenuate both mechanical and thermal hyperalgesia induced by CCD.Conclusion Spinal T-type calcium channel may play an important role in the pathogenesis of neuropathic pain.
8.Inhibition of Combination of Icaritin and Doxorubicin on Human Osteosarcoma MG-63 Cells in vitro.
Si-wen LIN ; Xue-qin LI ; Su-yun LIU ; Jian-ming SHI ; Jun-huai XU ; Long-huo MAO ; Ming YIN
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(6):729-734
OBJECTIVETo explore the inhibition and molecular mechanism of icaritin (ICT) combined doxorubicin (DOX) on human osteosarcoma MG-63 cells in vitro.
METHODSThe control group, ICT groups (10, 20, 40, 80, and 160 µmol/L), DOX groups (1, 2, 4, 8, and 16 µg/mL), and combination groups (20 µmol/ L ICT +1 µg/mL DOX, 20 µmol/L ICT +2 µg/mL DOX, 20 µmol/L ICT +4 µg/mL DOX, 40 µmol/L ICT +1 µg/mL DOX, 40 µmol/L ICT +2 µg/mL DOX, 40 µmol/L ICT +4 µg/mL DOX, 80 µmol/L ICT +1 µg/mL DOX, 80 µmol/L ICT +2 µg/mL DOX, 80 µmol/L ICT +4 µg/mL DOX) were set up. Human osteosarcoma MG-63 cells were respectively cultured and their effects on morphological changes were observed using inverted phase contrast microscope after 24-and 48-h intervention. The cell proliferation inhibition rate of each group was de- termined using CCK-8, and IC50 calculated. The MG-63 apoptosis rate was detected using Annexin V-FITC/ PI double dye flow cytometry. Expression levels of bcl-2, caspase-3, and p21 were detected using RT-PCR.
RESULTSICT and DOX could obviously inhibit the proliferation of MG-63 cell. Along with ICT concentration increasing from 10 µmol/L to 160 µmol/L, the cell proliferation inhibition rate also increased gradually from 9.67% ± 3.62% to 89.18% ± 9.66%. The IC50 was 46.93 µmol/L and 3.87 µg/mL respectively. ICT and DOX could cause either early or late stage apoptosis, down-regulate Bcl-2 gene expression, and up-regulate gene expressions of Caspase-3 and p21 respectively (P < 0.05). Aforesaid changes were more obviously seen in combination groups than in lCT groups and DOX groups (P < 0.05).
CONCLUSIONCT combined DOX had additive or synergistic inhibition effect for the proliferation of osteosarcoma MG-63 cells, which might be related with regulating gene expressions of bcl-2, caspase-3, and p21.
Apoptosis ; Bone Neoplasms ; metabolism ; pathology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Down-Regulation ; Doxorubicin ; pharmacology ; Drug Synergism ; Flavonoids ; pharmacology ; Humans ; Osteosarcoma ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism
9.Proton MR spectroscopy study in neonates with hypoxic ischemic encephalopathy
Wen-Zhen ZHU ; Jian-Pin QI ; Cheng-Yuan WANG ; Li-Ming XIA ; Li-Wen CHANG ; Jun-Wu HU ; Ding-Yi FENG ; Ming-Li ZOU ; Yin-Hua ZENG ;
Chinese Journal of Radiology 1999;0(10):-
Objective To investigate the metabolic alterations in the brain of neonates with HIE and correlate those alterations with clinical grading and prognosis of HIE.Methods Fourty-six eases of full-term neonates diagnosed as HIE clinically were performed MRI and 1~H-MRS,9 healthy neonates without the evidence of asphyxia were studied as controls,1~H-MRS techniques included single voxel proton MRS and two dimensional muhi-voxel chemical shift spectroscopy imaging,point resolved spectroscopy sequence was used for 1~H-MRS.Metabolic changes in the spectroscopy were analyzed in neonates with HIE,and study the relationgship between MRS findings and prognosis.Results(1)The typical 1~H-MRS manifestations of full- term neonates suffering from HIE were as follows:the peaks of Lac were elevated,GLx-? were elevated and NAA were decreased.(2)GLx-?/Cr ratio in control,mild,moderate and severe HIE group was 0.16, 0.21,0.64,and 1.31,respectively.Lac/Cr ratio in control,mild,moderate and severe HIE group was 0.12,0.14,0.19,and 0.26,respectively.There was a significant difference in the ratio of GLx-? and Lac/Cr between HIE group and control group(t=5.01,P
10.Effects of different acupuncture and moxibustion methods on ultrastructure of gastrocnemius in rats.
Ming GAO ; Hua-Yuan YANG ; Tang-Yi LIU ; Xun-Jie GU ; Yin-E HU ; Gang XU ; Wen-Chao TANG
Chinese Acupuncture & Moxibustion 2014;34(3):261-265
OBJECTIVETo explore the efficacy differences in early intervention of different acupuncture and moxibustion methods on gastrocnemius fatigue in rats induced by electrical stimulation.
METHODSFifty male SD rats were randomly divided into a control group, a model group, a hand acupuncture group, an electroacupuncture group and a moxibustion group, 10 rats in each group. Electrical stimulation of the sciatic nerve was given in the control group and gastrocnemius fatigue test was induced by electrical stimulation of the sciatic nerve in the model group after anesthesia without other treatment, but just take 6 times interval stimulation in the control group. The hand acupuncture group, the electroacupuncture group and the moxibustion group were treated with the corresponding acupoints stimulation method respectively for 20 min before gastrocnemius fatigue test, and Dazhui (GV 14) and Zusanli (ST 36) were selected. Immediately after gastrocnemius fatigue test, three or four gastrocnemius tissues at the same site on the right side were quickly taken for making specimen for transmission electron microscope (TEM). The changes of skeletal muscle ultrastructure of myofibrils, mitochondria, sarcoplasmic reticulum, glycogen particles were observed under TEM.
RESULTS(1) Muscle fibers disorder, partial mitochondrial vacuolization and glycogen particles smaller were shown in the model group. (2) No abnormalities were shown in the hand acupuncture group and the moxibustion group with mitochondrial morphology and number, which better than that in the model group, and glycogen particles increased. (3) Abnormal changes in morphology were shown in the electroacupuncture group with part of the muscle fibers derangement, Z line malalignment and a few mitochondria vacuolization.
CONCLUSIONHand acupuncture, electroacupuncture and moxibustion have the different effects on ultrastructure of gastrocoemius in rats. Acupuncture and moxibustion have shown good effects on the prevention and treatment of exercise-induced skeletal muscle cell and organelle damage and delaying exercise-induced fatigue.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Glycogen ; metabolism ; Male ; Mitochondria ; metabolism ; ultrastructure ; Moxibustion ; Muscle, Skeletal ; metabolism ; ultrastructure ; Rats ; Rats, Sprague-Dawley