1.Effect of anisodamine on endoplasmic reticulum stress during acute kidney injury in rats
Wei ZHAO ; Guangli WU ; Bin ZHAO ; Zhengjia HE ; Junfang RONG
Chinese Journal of Anesthesiology 2013;(3):366-370
Objective To evaluate the effect of anisodamine on endoplasmic reticulum stress during acute kidney injury (AKI) in rats.Methods Forty-two nale Sprague-Dawley rats,weighing 200-220 g,were randomly divided into 3 groups:control group (group C,n =6),AKI group (n =18) and anisodamine group (group AD,n =18).AKI was induced by intramuscular injection of 50% (v/v) glycerol 10 ml/kg into bilateral hind limbs in groups AKI and AD.In addition,anisodamine 10 mg/kg was injected intraperitoneally 20 min before intramuscular injection of glycerol in group AD.In group C the rats received intramuscular injection of normal saline 10 ml/kg into bilateral hind limbs.Six rats were chosen immediately after injection of normal saline in group C or at 1,6 and 24 h after glycerol injection in groups AKI and AD and then anethetized with intraperitoneal pentobarbital.The animals were sacrificed and kidney specimens were obtained and cut into sections which were stained with hematoxylin and eosin for pathological examination.The pathological changes of the renal tubules were scored.The expression of glucose-regulated protein 78 (GRP78) and oxygen-regulated protein 150 (ORP150) in renal tissues was determined by immuno-histochemistry and Western blot.Results Compared with group C,the pathological scores were significantly increased and the expression of GRP78 and ORP150 was up-regulated at all time points in groups AKI and AD (P < 0.01).Compared with group AKI,the pathological scores were significantly decreased and the expression of GRP78 and ORP150 was down-regulated at all time points in group AD (P < 0.05 or 0.01).Conclusion Anisodamine can ameliorate AKI through inhibiting endoplasmic reticulum stress in renal tubular epithelial cells and decreasing endoplasmic reticulum stress-induced cell apoptosis in rats.
2.Effect of penehyclidine hydrochloride pretreatment on Nrf2∕HO-1 signaling pathway in renal tissues of rats with rhabdomyolysis-induced acute kidney injury
Wei ZHAO ; Guangli WU ; Jingmin ZHANG ; Ting ZHOU ; Junfang RONG
Chinese Journal of Anesthesiology 2016;36(9):1063-1067
Objective To investigate the effect of penehyclidine hydrochloride ( PHC) pretreat?ment on nuclear factor erythroid 2?related factor 2∕heme oxygenase?1 ( Nrf2∕HO?1) signaling pathway in re?nal tissues of rats with rhabdomyolysis?induced acute kidney injury ( AKI) . Methods Thirty?six pathogen?free male Sprague?Dawley rats, weighing 200-220 g, were assigned into 3 groups ( n=12 each) using a random number table: control group (group C), group AKI and PHC pretreatment group (group PHC). Rhabdomyolysis was induced by intramuscular injection of 50% glycerol 10 ml∕kg in bilateral hindlimbs. PHC 0?2 mg∕kg was injected intraperitoneally at 30 min before glycerol was injected intramuscularly in group PHC. At 1 and 6 h after glycerol injection, serum was collected for determination of blood urea nitro?gen ( BUN) and creatinine ( Cr) concentrations, and bilateral kidneys were harvested for pathological ex?amination and for determination of HO?1 activity and expression of Nrf2 mRNA and HO?1 mRNA ( by quan?titative real?time polymerase chain reaction) , Nrf2 in nucleoprotein and total protein and HO?1 in total pro?tein in renal tissues ( by Western blot) . The damage to the renal tubules was scored. Results Compared with group C, the BUN and Cr concentrations in serum and renal tubular damage scores were significantly increased, the expression of Nrf2 in nucleoprotein and total protein and HO?1 in total protein was signifi?cantly up?regulated, and HO?1 activity was significantly increased in AKI and PHC groups, the expression of HO?1 mRNA was significantly up?regulated in group AKI, and the expression of Nrf2 mRNA and HO?1 mRNA was significantly up?regulated in group PHC (P<0?01 or 0?05). Compared with group AKI, the BUN and Cr concentrations in serum and renal tubular damage scores were significantly decreased, the ex?pression of Nrf2 in nucleoprotein and total protein and HO?1 in total protein was significantly up?regulated, and HO?1 activity was significantly increased in group PHC ( P<0?01 or 0?05) . Conclusion The mecha?nism by which PHC pretreatment attenuates rhabdomyolysis?induced AKI may be related to activation of Nrf2∕HO?1 signaling pathway in renal tissues of rats.
3.Comparison of structural characteristics and anticoagulation activity of enoxaparin sodium with different degree of 1,6-anhydro derivatives.
He ZHU ; Youjing LIü ; Xianwei HAN ; Shilong LIU ; Jiejie HAO ; Xiaoliang ZHAO ; Guangli YU
Acta Pharmaceutica Sinica 2014;49(7):1049-53
The fine structure of enoxaparin sodium samples with different degree of 1,6-anhydro derivatives were analyzed with polyacrylamide gel electrophoresis, high performance liquid chromatography, ultraviolet spectroscopy, infrared spectroscopy and nuclear magnetic resonance spectroscopy. A further study of anticoagulation activity of enoxaparins was performed, including those on their inhibition activities of coagulation factor Xa (FXa) and thrombin (FIIa). The results showed that the anti-FXa and -FIIa activities of enoxaparins with different degree of 1,6-anhydro derivatives (20.0%-39.7%) with similar structure characteristics, had decreasing tendency when the degree of 1,6-anhydro derivatives increased. Especially, the anti-FXa activity was sensitive to the change of the degree of 1,6-anhydro derivatives.
4.Vailidation of a LC-MS/MS method for quantification of ibuprofen enantiomers in Beagle dog plasma
Xiuhong ZHAO ; Yuanyuan XIA ; Yurong HUANG ; Aijie ZHANG ; Guangli WEI ; Duanyun SI
Chinese Pharmacological Bulletin 2015;(4):570-575
Aim To develop a simple,rapid and ac-curate analysis method for determination of chiral ibu-profen in Beagle dog plasma.Method The plasma sample was submitted to liquid - liquid extraction u-sing hexane /isopropanol (95 ∶5,V/V),with ketopro-fen as the internal standard (IS).The separation was accomplished in a Lux 5u Cellulose-3 (250 mm·4.6 mm,5 μm)column,and the mobile phase consisted of methanol and a mixture of 1 mmol·L -1 ammonium acetate-methanol-formic acid (90 ∶1 0 ∶0.2,V/V/V) with the volume ratio of 82 ∶1 8 at a flow rate of 0.8 mL· min -1 .The mass spectrometer consisted of an ESI interface operating at negative ionization mode and the detection was performed using multiple reaction monitoring at the transitions of m /z 205.2 /1 61 .2 for ibuprofen and m /z 253.1 /209.2 for ketoprofen (IS). Method validation included the evaluation of the matrix effect, extraction recovery, linearity, lower LOQ, within-run and between-run precision,stability and di-lution effect.Results The calibration curve was line-ar across the concentration range of 0.2 ~50 mg·L -1 for each ibuprofen enantiomer with a lower LOQ of 0.2 mg·L -1 .The within-run and between-run precision (RSD%)was in the range 1 .01 % ~1 3.1 % for each ibuprofen.The pharmacokinetic parameters for orally single dose of (S +)and racemic ibuprofen in Beagle dogs were as follows: Cmax , T1 /2 , AUC(0-t) were (82.98 ±1 4.83 )mg·L -1 ,(3.21 7 ±0.7298)h, (362.0 ±58.67)h·mg·L -1 for (S +)ibuprofen and 70.62 /74.48 mg·L -1 ,1 .520 /5.432 h ,1 77.8 /649.6 h·mg·L -1 for (R -)/(S +)ibuprofen,re-spectively.Conclusions A simple,rapid,accurate, high sensitivity and repeatability method has been suc-cessfully developed,which can analyze the concentra-tions of (R -)/(S +)ibuprofen in Beagle dog plasma simultaneously.The method could be applied for the investigation of pharmacokinetics of ibuprofen enanti-omers in Beagle dogs.
5.The effects of childhood abuse,personality,insecurity on dissociative trait of medical students:a path anal-ysis
Xianghua ZHU ; Haiyan GAO ; Juan QIAO ; Juan ZHAO ; Xiaowei ZUO ; Guangli LIANG ; Jiao LI
Chinese Journal of Behavioral Medicine and Brain Science 2014;(11):1017-1019
Objective To build the relationship model of childhood aubuse, personality, insecurity and dissociative trait in medical students. Methods Through stratified sampling,262 medical students were investiga?ted by the Personal Report of Childhood Abuse( PRCA) ,Dissociative Trait Scale( DTS) ,Self?Rating Feeling of In?security Scale( SRFIS) ,Revised NEO Five?Factor Inventory( NEO?FFI?R) . A path analysis was applied by AMOS (Analysis of Moment Structures) version 7.0. Results ①Childhood abuse was positively related to insecurity, dissociative trait and neuroticism( r=0.248~0.361, P<0.01) ,but was passively related to extraversion,agreeable?ness and conscientiousness( r=-0.168~-0.250, P<0.01). Insecurity was positively related to dissociative trait and neuroticism( r=0.479~0.522, P<0.01) ,but was passively related to extraversion,agreeableness and conscien?tiousness( r=-0.234~-0.324, P<0.01). Dissociative trait was positively related to neuroticism( r=0.597, P<0.01) ,but was passively related to openness, extraversion, agreeableness and conscientiousness ( r=-0. 133~-0.453, P<0.05). ②The path analysis showed that childhood abuse was directly related to insecurity(B=0.339, P<0.01)and personality(B=-0.226, P<0.01)of medical students. Personality was directly related to insecurity and dissociative( B=-0.609~-0.363, P<0.01) . Insecurity was directly related to dissociative trait( B=0.448, P<0.01) . Personality and insecurity mediated entirely the relationship between childhood abuse and dissociative trait of medical students. The model fit indexes were χ2/ df =1.151<3.000, P=O.080>0.05,RMSEA=0.024<0.050, GFI=0.935,AGFI=0.909,NFI=0.923,RFI=0.902,IFI=0.989,TLI=0.986 and CFI=0.989. Conclusion Per?sonality and insecurity as mediated variable mediate the relationship between childhood abuse and dissociative trait of medical students. Childhood abuse has no direct effect on dissociative trait of medical students.
6.The diagnostic value of ultrasound contrast guided transrectal biopsy in prostate cancer
Yunxin ZHAO ; Yi JIANG ; Min YAO ; Jian WANG ; Ying WANG ; Guangli YAO
Clinical Medicine of China 2016;32(1):18-21
Objective To investigate the clinical value of clinical application in diagnosis of prostate cancer (PCa) by prostate biopsy guided by rectal ultrasound contrast guided biopsy.Methods One hundred and ninety-eight patients with prostate in Punan Hospital of Pudong New District of Shanghai were investigated.According to different detection methods, the research objects were divided into two groups, the patients were performed with the ultrasound contrast guided biopsy as the imaging group (n =96), the patients with Doppler ultrasound guided biopsy as the ultrasonic group(n =102).The puncture Results were compared with pathological diagnosis.The positive rate of PCa and number of puncture needle were compared with the two puncture methods.The value of the application of the prostate biopsy guided by rectal ultrasound in diagnosis of prostate cancer was evaluated.Result One hundred and ninety-eight patients were all received pathological diagnosis,78 cases benign lesions, 120 cases were diagnosed as PCa.Thirty-six cases of benign lesions were confirmed by pathological biopsy, 60 case PCa.There were 42 cases of benign lesions in ultrasonic group, 60 case PCa.The positive rate of PCa in the imaging groupwas 62.5% (60/96), the ultrasonic group was 58.82% (60/102).There was no difference in Pca positive rate between the ultrasound group and the contrast group(x2 =0.104, P=0.747).The positive number of Pca in the imaging group was 28.50% (17/60), the difference was statistically significant higher than that of the common group(18.80% (11/60), P =0.001).The average of the patients in the imaging group was 8.19 needle,less than the ultrasonic group per capita 11.31 needle less.When f/tPSA less than or equal to 0.15, Pca positive rate of the contrast group was 46.55% (27/55), higher than the ultrasonic group(9.30% (4/43)), the difference was statistically significant (P =0.001);when f/tPSA more than 0.15, the positive rate of Pca in the contrast group was 92.11% (35/38), less than the ultrasound group (94.92 (56/59)), the difference was not statistically significant (P =0.89).Anal pain, hematuria and hematochezia in contrast group (7.29% (7/96), 2.08% (2/96), 10.42% (10/96)) were significantly less than the ultrasound group(22.55% (23/102), 8.82% (9/102), 23.53% (24/102)), the difference was statistically significant (P =0.003,0.039,0.014).Conclusion Under the guidance of ultrasound contrast, rectal biopsy has important diagnostic value for prostate cancer.Under the premise of reducing the number of puncture needle,can improvethe positive rate of Pca, reduce the pain of patients and the occurrence of complications after puncture.When f/tPSAless than or equal to 0.15,puncture positive rate in contrast group is higher than the ultrasonic group, puncture effect is better.
7.Effect of penehyclidine hydrochloride pretreatment on rhabdomyolysis-induced acute kidney injury in rats
Ting ZHOU ; Guangli WU ; Xudong HUANG ; Wei ZHAO ; Jingmin ZHANG ; Junfang RONG
Chinese Journal of Anesthesiology 2016;36(1):105-108
Objective To evaluate the effect of penehyclidine hydrochloride pretreatment on rhabdomyolysis-induced acute kidney injury (AKI) in rats.Methods Forty-two pathogen-free male SpragueDawley rats,weighing 200-220 g,aged 2 months,were randomly divided into 3 groups using a random number table:control group (group C,n =6),AKI group (n =18),and penehyclidine hydrochloride group (group PH,n =18).The model of rhabdomyolysis-induced AKI was established by injecting 50% glycerol 10 ml/kg into the lateral muscle of bilateral hindlimbs in AKI and PH groups.The equal volume of normal saline was given in group C.Penehyclidine hydrochloride 0.2 mg/kg was injected intraperitoneally at 30 min before administration of glycerol in group PH.Six rats were selected at 1 h after administration of normal saline in group C,or at 1,6 and 24 h after administration of glycerol,blood samples were collected from the inferior vena cava for determination of the serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations by enzymic colorimetric method.The animals were sacrificed,and kidney specimens were obtained for pathologic examination and for determination of the expression of DJ-1 and phosphatase tensin homolog deleted on chromosome 10 (PTEN) encoding protein (by immuno-histochemistry and Western blot).The damage to the renal tubules was scored.Results Compared with group C,the serum BUN and Cr concentrations and renal tubular damage score were significantly increased,the expression of D J-1 was down-regulated,and the expression of PTEN protein was up-regulated in group AKI (P<0.05 or 0.01).Compared with group AKI,the serum BUN and Cr concentrations and renal tubular damage score were significantly decreased,the expression of DJ-1 was up-regulated,and the expression of PTEN protein was down-regulated in group PH (P<0.05 or 0.01).Conclusion Penehyclidine hydrochloride pretreatment can reduce rhabdomyolysis-induced AKI probably by up-regulating the expression of DJ-1 and down-regulating the expression of PTEN protein in rats.
8.The effects of childhood abuse,big five personality on anxiety of college students: a path analysis
Jiao LI ; Xianghua ZHU ; Min TAO ; Houfeng ZHAO ; Chengdong WANG ; Guangli LIANG ; Yongjie YANG ; Deqin GENG
Chinese Journal of Behavioral Medicine and Brain Science 2011;20(8):725-727
Objective To study the mediating effect of big five personality between childhood abuse and anxiety of college students, and to provide basis to intervene their mental disorder.Methods Through stratified sampling,2374 college students in Jiangsu were investigated by the personal report of childhood abuse( PRCA),self-rating anxiety scale(SAS) and the revised NEO five-factor Inventory(NEO-FFI-R).A path analysis was applied by analysis of moment structures(AMOS) version 7.0.Results The path analysis showed that childhood abuse was directly related to anxiety of college students(Sβ=0.123, P<0.01 = ,and was directly related to 4 dimensions of the NEO-FFI-R( exclusion Openness dimension) (Sβ= -0.216 ~ -0.248,0.309; P < 0.01 =.3 dimensions of the NEO-FFI-R( exclusion Openness and Extraversion dimensions) were directly related to anxiety of college students ( Sβ = 0.525,-0.045 ~-0.052, P < 0.05 =.Agreeableness, conscientiousness and neuroticism of NEO-FFI-R mediate the relationship between childhood abuse and anxiety of college students.The model fit indexes were x2/df = 0.546 < 3.000, P = 0.460 > 0.050, RMSEA = 0.001 < 0.050, GFI = 1.000, AGFI = 0.998, NFI = 1.000, RFI = 0.998, IFI = 1.000,TLI = 1.002, CFI = 1.000.Conclusion Big five personality as mediated variable mediates the relationship between childhood abuse and anxiety of college students.
9.Establishment of cyclophosphamide-induced cardiotoxicity mouse model and ultrasound evaluation
Guangli HOU ; Lijun YUAN ; Ruijing SHI ; Lianbi ZHAO ; Zhelong LI
Chinese Journal of Ultrasonography 2017;26(11):1001-1004
Objective To analyze the dose dependent cardiotoxicity of cyclophosphamide and thus establish the mouse models for understanding the underlying mechanisms . Methods Thirty mice ( 7 -8 weeks old) were randomly divided into 6 groups:control of one course group ,control of two courses group , one course of low dose ( 50 mg/kg) group ,two courses of low dose group ,one course of high dose ( 100 mg/kg) group ,two courses of high dose group . The changes of cardiac function and morphology were analyzed at indicated times by ultrasound and histology respectively . Results Compared with the control groups , injection of low dose cyclophosphamide either with one course or two courses ,and injection of high dose with only one course had no in statically significant changes in hair color ,physical activity ,body weight and cardiac function( P > 0 .05) . Treatment of two courses with high dose resulted in significant decrease of physical activity and body weight ( P < 0 .05 ) . Meanwhile ,cardiac systolic function was significantly decreased( P <0 .05) . Histology study revealed robust cardiac hypertrophy and fibrosis . Conclusions Two courses of intraperitoneal injection of cyclophosphamide at high dose result in obvious cardiotoxicity , especially systolic dysfunction .Intraperitoneal injection of two courses of cyclophosphamide serves as a good strategy to induce cardiotoxicity in mice ,which could be applied for future mechanism study .
10.Current status and perspectives of non-invasive brain stimulation therapy applied to insomnia
Guangli ZHAO ; Hao XU ; Han YANG ; Tianmin ZHU ; Siyi YU
Chinese Journal of Neuromedicine 2023;22(1):89-96
Non-invasive brain stimulation (NIBS) is one of the fastest-growing fields of medicine today. Recent studies have highlighted the potential of NIBS as an innovative, safe, and cost-effective treatment method applied to insomnia. Starting from treatment mechanism and clinical effect, we summarize the current research status of repetitive transcranial magnetic stimulation and transcranial electrical stimulation, the two most common NIBSs used in insomnia treatment, and analyze the existing research limitations and its future development direction, in order to provide references for further promoting the clinical application of NIBS in insomnia treatment.