1.Role of PI3K/Akt signaling pathway and autophagy in reduction of adriamycin-induced myocardial injury by sevoflurane in rats
Chinese Journal of Anesthesiology 2016;36(6):728-731
Objective To evaluate the role of phosphatidylinositol 3-kinase/protein-serine-threonine kinases (PI3K/Akt) signaling pathway and autophagy in reduction of adriamycin-induced myocardial injury by sevoflurane in the rats.Methods Thirty-six healthy male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 6 groups (n =6 each) using a random number table:control group (group C),adriamycin-induced myocardial injury group (group Dox),sevoflurane group (group Sev),LY294002 inhibitor group (group LY),solvent control group (group dimethyl sulfoxide [DMSO]),and 3-MA inhibitor group (group 3-MA).Adriamycin 4 mg/kg was injected intraperitoneally once a week for 3 weeks in all the groups except group C.The rats were mechanically ventilated for 2 h in C and Dox groups.The rats inhaled 2.4% sevoflurane for 2 h in group Sev.In group LY,0.3 mg/kg LY294002 was injected via the tail vein at 10 min before anesthesia,and the rats inhaled 2.4% sevoflurane for 2 h.In group DMSO,the equal volume of DMSO was injected,and the rats inhaled 2.4% sevoflurane for 2 h.After the blood samples were collected from the heart,the rats were sacrificed,and myocardial specimens were obtained for determination of cardiac troponin Ⅰ (cTnI) concentrations in serum (by enzyme-linked immunosorbent assay),expression of total Akt (t-Akt),phosphorylated Akt (p-Akt),mammalian target of rapamycin (mTOR),phosphorylated mTOR (p-mTOR) and autophagy marker microtubule-associated protein light chain 3 Ⅱ (LC3 Ⅱ) (by Western blot),and cell apoptosis (by TUNEL).Apoptosis index (AI) was calculated.Results Compared with group C,the expression of p-Akt and p-mTOR was significantly down-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly increased in the other five groups (P< 0.05).Compared with group Dox,the expression of p-Akt and p-mTOR was significantly up-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly decreased in group Sev (P<0.05).Compared with group Sev,the expression of p-Akt and p-mTOR was significantly down-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly increased in group LY,and the expression of LC3 Ⅱ was significantly down-regulated,and serum cTnI concentrations were significantly decreased in group 3-MA (P<0.05).Conclusion Sevoflurane can activate PI3K/Akt signaling pathway and inhibit autophagy,thus reducing adriamycin-induced myocardial injury in rats.
2.Radiosensitization of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts
Guangyin WU ; Qian HAN ; Qingyao ZHU ; Liang LI ; Xin LI
Chinese Journal of Radiological Medicine and Protection 2013;33(4):376-379
Objective To investigate the effect of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts and the underlying mechanisms.Methods The mouse model was established by injecting EC9706 cells subcutaneous in nude mice.When the tumors were 100 mm3 in size,the mice were divided into 4 groups randomly withcontrol group with no treatment; irradiation group with 8 Gy 6 MV Xrays at 1 and 8 d each time; AG1024-treatment group with 30 μg/(kg-d) AG1024 injected intraperitoneally (ip) 5 times a week for two weeks ; combination group:receiving both 30 μg/(kg· d)-1 AG1024 ip and irradiation of 8 Gy X-rays.The diameters of the tumors were measured every 3 days.The mice were sacrificed and the weights of tumors were measured at 15 d after treatment.Tumor inhibition rate was calculated.The cell cycle was examined by flow cytometry.The expression of cell cycle protein D1 (CyclinDl) of the tumors were detected by immunohistochemical staining.Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used to detect the cell apoptosis in the tumor tissue.Results The tumor weight in the irradiation group,AG1024-treatment group and combination group were significantly decreased compared with the control group,and the inhibition rate were 39.16%,18.73%,57.04%,respectively (F =13.566,P < 0.05).After treatment with AG1024 and irradiation,tumor tissue cells were significantly accumulatedin the G0/G1 and G2/M phases and decreased in S phase compared to the irradiation group (t =-6.654,-16.738,12.871,P < 0.05).The CyclinD1 expression of the combination group was significantly decreased compared with the control group.In the combination group,the apoptotic cells were detected by TUNEL assay.Conclusions IGF-1R inhibitor AG1024 could change the cell cycle and induce cell apoptosis,which might result in the enhancement of radiosensitivity on the esophageal cancer xenografts.
3.Application of real-time quantitative PCR for guidance therapy of cytomegalovirus infection after allohematopoietic stem cell transplantation
Xiao-Yan ZHANG ; Jian-Yong LI ; Han-Xin WU ;
Chinese Journal of Infectious Diseases 2001;0(06):-
Objective To discuss the significance of the application of real-time quantitative PCR(RQ PCR)for diagnosis and guidance therapy of cytomegalovirus(CMV)infection after allo- hematopoietic stem cell transplantation(allo-HSCT).Methods Thirty-three patients were undergo- ing allo-HSCT.After hematopoietic reconstitution,patients'peripheral blood samples were detected for CMV DNA by RQ-PCR periodically.Anti-viral therapy was begun,attenuated and stopped ac- cording to the results of CMV DNA detection.The effects of anti-viral therapy and patients' clinical results were observed.Results CMV DNA was detected in blood samples from 13 of 33 patients. There were 21 episodes in these patients.Only 1 episode wasn't controlled hecause the patient gave up the therapy.CMV DNA copies were disappeared soon or decreased and then disappeared during anti-viral therapy in the others'.Patients which had symptoms and/or dysfunction of organs were cured too.Each course of anti-viral therapy was shorter than ordinary course.Conclusions CMV in- fection can he diagnosed as early as possible by RQ PCR.To begin,attenuate and stop anti-viral ther- apy according to the results of RQ-PCR is safe.The course is shortened and the side effects of anti vi- ral drugs were attenuated.
4.Multicentre Investigation of the Traditional Chinese Medicine Named YanTing Medincinal Broth on Retention Enema Treatment of Chronic Pelvic Inflammatory Disease
Yufen HAN ; Lihui HOU ; Xin SUN ; Xiaoke WU
Journal of Medical Research 2006;0(03):-
Objective To evaluate the clinical effectiveness and the safety of the traditional chinese medicine named YanTing Medincinal Broth on retention enema treatment of chronic pelvic inflammatory disease.Methods The research method of random,multicentre and parallel contrast were used.There are 92 cases divided into retention enema group and suppository contrast group at random,there are 47 cases in retention enema group and 45 cases in contrast group.Respectively use retention enema method with YanTing Medincinal Broth and the other method with KangFu inflammation eliminated suppository to treat the chronic pelvic inflammatory disease.The course of the treatment are all 10 days.Traditional chinese medicine syndrome and clinical physical signs are observed before and after the treatment in every group,the contrast curative effect are observed at the same time.Results Traditional chinese medicine syndrome and clinical physical signs are all improved than before treatment(P
5.Systemic therapy of advanced biliary tract cancer
Xin LONG ; Han WU ; Jin PENG ; Fuxiang ZHOU
Journal of International Oncology 2021;48(5):302-307
The incidence rate of biliary tract cancer is increasing year by year. Systemic therapy is the most important treatment for patients with advanced or unresectable biliary tract cancer. Gemcitabine combined with cisplatin is still the standard first-line chemotherapy, while gemcitabine combined with TS-1 and gemcitabine combined with nab-paclitaxel are also the first-line treatment options. Studies have confirmed that immunotherapy as a back-line treatment has a significant advantage in survival, and the disease control rate of nivolumab is 61% and the median overall survival is more than 1 year. In addition, targeted drugs targeting FGFR2, IDH1/2, HER-2 and other major driving genes of biliary tract cancer also show good antitumor activity, and become research hotspots in the treatment of advanced biliary tract cancer. Summarizing the research progress of systematic chemotherapy, immunotherapy and molecular targeted therapy for advanced biliary tract cancer can provide help for clinical practice.
6.THE RESEARCH OF FOUR DRUG RESISYANCE GENE IN MYCOBACTERIUM TUBERCULOSIS
Hong-Min LI ; Xue-Quong WU ; Jian-Qin LIANG ; Li XIAO ; Shu-Xin ZHANG ; Hui-Xin HAN ;
Microbiology 1992;0(02):-
objective To study the reationship beween drug-resistance gene mutation and drug-resistance level in M. tuberculosis. Methods 108 M. tuberculosis clinical isolated strains from sputum specimens were analyzed by PCR-SSCP and traditional drug susceptibility tests. Results the gene mutation rate of SM, RFP, INH and EMBresistance climical isolated strains was 78.5%, 68.2%, 70.5% and 48.6% respectively, and the mutation rate of SM, RFP, INH and EMB high concentration resistance isolated strains was 86.5% , 89% , 84% and 48.6% respectively, but 28.5 % , 16.6% and 7.1% was the mutation rate of low concentration resistance strains. Conclusion The gene mutation was in relation with drug resistance level of M. tube rculosis. The gene mutation rate was hiher in high concentration resistance isolated strains than in low concentration resistane isolated strains.
7.The relationship between early recurrence after radical resection and the expression of Cx43 in AFP positive and HBV related HCC tissues
Zusen WANG ; Liqun WU ; Yujun LI ; Ruyong YAO ; Xin YI ; Chao GENG ; Weiyu HU ; Bing HAN
Chinese Journal of General Surgery 2012;27(10):816-820
Objective To study the expressions of Cx43,CD105 and VEGF in HBV related HCC tissues and the relationships between Cx43 expression and recurrence and prognosis after cancer radical resection in HCC patients stratified by serum AFP levels. Methods The expressions of Cx43,CD105,VEGF in 234 HBV related HCC tissues were examined by tissue microarray and two-step methods of PV-6000 of immunohistochemistry and the expressions of Cx43 in 20 frozen HCC specimens were examined by RT-PCR. Results Cx43 in HCC tissues was positive as examined by both immunohistochemistry and RTPCR methods.Positive Cx43 expression is correlated with lower early recurrence ( Log Rank P =0.001 ),longer disease free survival (Log Rank P =0.026 ) and overall survival( Log Rank P =0.000 ) as showed by the Kaplan-Meier analysis in patients with AFP < 400 μg/L. The expression of Cx43 is an independent prognostic factor.The positive expression of Cx43 related with lower positive expression of CD105 and VEGF (P =0.018,0.023 ),and correlated with histological differentiation (P =0.002),the number of focus (P =0.033 ),blood vessel tumor embolism ( P =0.029 ). Conclusions The expression of Cx43 is correlative with the expression of CD105 and VEGF,and is predictive of HCC early recurrence and poor prognosis after radical hepatectomy in HBV related HCC patients with serum AFP < 400 μg/L.
8.Virological impact of stalk region of neuraminidase in influenza A/Anhui/1/05 (H5N1) and A/Ohio/07/2009 (H1N1) viruses.
Jia WU ; Ting WANG ; Liu ZHANG ; Zhi-Han YE ; Jian-Xin LV
Chinese Journal of Virology 2014;30(3):238-245
This study aims to investigate the virological impact of the stalk region and cysteine (C) in neuraminidase (NA) of influenza A/Anhui/1/05 (H5N1) and A/Ohio/07/2009 (H1N1) viruses. The NA of A/ Anhui/1/05 (H5N1), defined as AH N1, lacked 20 amino acids (including C, defined as s20) as compared with NA of A/Ohio/07/2009 (H1N1) (defined as 09N1). We deleted s20 of 09N1 to construct 09N1-s20, and inserted s20 into AH N1 to construct AH N1+s20. To investigate the impact of C on the biological function of NA, we deleted C in 09N1 to construct 09N1-C and inserted C into AH N1 to construct AH N1-C. The pseudo-type viral particle (pp) system was used to evaluate the impact of these mutants on virology. The combination of 09N1-C and 09H1 (defined as 09H1::09N1-C) showed an infectivity 8 times that of the wild type 09H1::09N1, while the infectivity of the combination of AH N1+C and AH H5 (defined as AH H5::AH N1+C) was much lower than that of the wild type AH H5::AH N1. The infectivity of the combination of 09N1-s20 and 09H1 (defined as 09H1::09N1-s20) was 4 times that of the wild type 09H1::09N1; the infectivity of the combination of AH N1+s20 and AH H5 (defined as AH H5:: AH N1+s20) was 1/7 that of the wild type AH H5::AH N1. The co-existence of 09N1-C and AH H5 displayed 6 times the infectivity of AH H5::09N1, while the infectivity of 09H1::AH N1+C was very low. Multimer analysis showed that in the wild type 09N1, the forms of NA were dimer > tetramer > monomer; the major component of NA in 09N1-C was monomer; in 09N1-s20, the forms of NA were monomer > dimer. AH N1 was mainly composed of monomer; in AH N1+s20, the forms of NA were dimer > monomer > tetramer; in AH N1+C, the forms of NA were dimer > tetramer. Deletion of C or s20 from 09N1 did not change the expression of NA. The study suggested that deletion of C from the stalk region of NA in A/Ohio/07/2009 (H1N1) increases infectivity. Insertion of C into NA's stalk region of A/ Anhui/1/05 (H5N1) significantly decreases infectivity. Cysteine deletion in the stalk region is important for the infectivity of A/Anhui/1/05 (H5N1) and A/Ohio/07/2009 (H1N1). It may interfere with the infectivity via changes in NA polymerization.
Amino Acid Motifs
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Humans
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Influenza A Virus, H1N1 Subtype
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chemistry
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enzymology
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genetics
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pathogenicity
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Influenza A Virus, H5N1 Subtype
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chemistry
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enzymology
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genetics
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pathogenicity
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Influenza, Human
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virology
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Neuraminidase
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chemistry
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genetics
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metabolism
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Viral Proteins
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chemistry
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genetics
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metabolism
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Virulence
9.Clinical features of 241 ileocecal inflammatory mass patients
Ning WANG ; Biaoluo WANG ; Xin WANG ; Shuhui LIANG ; Shuang HAN ; Kaichun WU
Chinese Journal of Digestion 2013;(2):97-100
Objective To investigate the etiology and clinical characters of ileocecal inflammatory mass and to improve the diagnosis and therapy of ileocecal inflammatory mass.Methods From July 2006 to July 2011,the data of ileocecal inflammatory mass cases were collected,including disease history,clinical manifestations,complications,imaging results,colonscopy results,pathological results and diagnosis.The clinical characters were summarized.Results A total of 241 cases with ileocecal inflammatory mass were collected and 83 cases of them were Crohn's disease,79cases were appendicitis with periappendiceal abscess,54 cases were intestinal tuberculosis,eight cases were intestinal malignant lymphoma and 17 cases were undefined.The main manifestations of 85patients were abdominal pain,right inferior abdominal mass and fever,among which 56 patients were Crohn's disease.Among 90 patients with surgical operation,44 patients were Crohn's disease,among which 12 patients received operation because of appendicitis with periappendiceal abscess at first while the pathological examination after operation for the recurrence of ileocecal inflammatory masses proved Crohn's disease.During the course of disease,69 cases had complications of intestinal obstruction,in whom 44 cases were Crohn's disease.Nine cases had intestinal fistula,24 cases had upper gastrointestinal ulcers,one case had impetigo,and all of the above cases were Crohn's disease.Conclusions The common etiologies of ileocecal inflammatory mass were Crohn's disease.Ileocecal inflammatory mass recurrence after surgery,ileocecal inflammatory mass complicated with intestinal obstruction and abenteric manifestations were more common in Crohn's disease.
10.Preparation and in vitro study on diffusion of capsaicin cubosome.
Xin-Sheng PENG ; Yan-Fang ZHOU ; Ke HAN ; Ling-Zhen QIN ; Chuan-Bin WU
China Journal of Chinese Materia Medica 2014;39(4):644-647
This study was to investigate the permeability and absorbability of capsaicin cubosome across abdominal skin of the SD rats in vitro. Diffusion of capsaicin cubosome and cream was performed with the modified Franz diffusion cell technique. The capsaicin cubosome showed no enhancement of skin permeation within 24 hours. However, the deposition amounts of capsaicin in the rat skin in the cubosome group was markedly higher than those in the commercial cream group (P < 0.01). Cubosome showed excellent characetristic of skin-targed which could be a good carrier for the local transdermal drug delivery system.
Administration, Cutaneous
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Animals
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Capsaicin
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administration & dosage
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chemistry
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Kinetics
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Male
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Particle Size
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Permeability
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Rats
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Rats, Sprague-Dawley
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Skin
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drug effects
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metabolism
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Skin Absorption