Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Identification of New Psychoactive Tryptamines 4-OH-MET and 4-AcO-DMT Using High Resolution Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy / 法医学杂志

Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry （GC-QTOF-MS）, ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry （UPLC-LTQ-Orbitrap MS） and 1H-nuclear magnetic resonance spectroscopy （1H-NMR）. Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 （molecular ion peak）, 72.080 6 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation （CID） mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 （molecular ion peak）, 58.065 1 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and 1H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and 1H-NMR can be used together to identify unknown new psychoactive substances.

Effect of axial length and corneal curvature radius and their ratio on refractive errors in children and adolescents / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the association between refractive status and refractive factors, and to explore the effectiveness of mean ocular axial length(AL), mean corneal radius of curvature(CR)and their ratio in the assessment of amitropia in children and adolescents.<p>METHODS: Cross sectional study, 816 cases(1632 eyes)aged 3-16 years old suspected ametropia were selected in the Affiliated Eye Hospital of Nanjing Medical University from December 2017 to December 2018. Uncorrected visual acuity(UCVA), mean AL and mean CR were tested. Autorefraction was performed after cycloplegia, which was measured as the spherical equivalent(SE).<p>RESULTS: Among 816 cases of children and adolescents aged 3-16, 773 were ametropia, accounting for 94.7%, with the highest proportion aged 7-14. The difference(one eye)in the mean AL, and AL/CR ratio of different refractive groups were statistically significant(<i>P</i><0.05). In different refractive states, the mean AL and AL/CR ratio showed a low correlation with SE in emmetropes and low hyperopes but higher correlation in moderately hyperopic and myopic children. The mean AL, AL/CR ratio were higher correlation with SE increased with age. Sensitivity was 0.880, specificity was 0.916, and accuracy was 89.2%. The area under ROC curve was 0.954.<p>CONCLUSION: The proportion of myopia among children and adolescents gradually increases and shows a large increase after 7 years old. The AL and AL/CR ratio showed higher correlation in moderate hyperopes, myopes and older ages. The AL/CR ratio is highly accurate in the diagnosis of myopia in adolescents and children.

Drug resistance analysis on smear-positive pulmonary tuberculosis in Taizhou City from 2015 to 2017 / 上海预防医学

[Objective]To ascertain the drug resistance for pulmonary tuberculosis in Taizhou City, and to provide basis for tuberculosis prevention and control strategy. [Methods] The sputum samples were collected form 267 smear positive pulmonary tuberculosis patients who registered in a drug susceptibility testing (DST) monitoring site in Taizhou City form 2015 to 2017. Then with culture, identification of Mycobacterium and DST for 9 anti-tuberculosis drugs [isoniazid (INH) , rifampicin (RFP) , ethambutanol (EMB) , streptomycin (SM) , kanamycin (KAM) , ofloxacin (OFX) , crinkledmycin (CPM) , promethylamine (PTO) and para amino salicylate (PAS) ] by using proportion method performed on all sputum specimens. [Results]Of the 267 smear positive cases, 220 were cultured with 190 culture positive (17 were identified as nontuberculous mycobacterial infections) , 28 culture negative, and 2contaminated. Among 160 cases with the result of DST to 9 drugs, the overall drug resistance rate was22.5％. The overall drug resistance rates were 21.4％ and 33.3％ in the newly diagnosed patients and retreated patients respectively. There was no significant difference between the two groups (P>0.05). The multidrug resistance rate was 3.1％, and had a significant difference between the new and retreated patients (0.7％ vs. 26.7％, P<0.01). Drug resistances rates of the 9 drugs ranged from high to low as:INH (8.1％) , PTO (8.1％) , SM (6.9％) , RFP (6.3％) , OFX (2.5％) , PAS (2.5％) , EMB (2.5％) , CPM (2.5％) and KAM (2.5％). There was no gender difference found in drug resistance rates (P> 0.05). Neither was there age difference (P> 0.05). [Conclusion] The epidemic of drugresistant of tuberculosis in Taizhou City are still high, especially that of acquired multi-drug resistance of tuberculosis. We must continue to improve the "three-in-one"management model, improve the quality of clinical diagnosis and treatment, and strengthen community medication management.

Changes in C-reactive protein and procalcitonin levels in neonates with necrotizing enterocolitis and their clinical significance / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes in C-reactive protein (CRP) and procalcitonin (PCT) levels in neonates with necrotizing enterocolitis (NEC) and their clinical significance.</p><p><b>METHODS</b>According to the modified Bell's staging criteria, 142 neonates with NEC were divided into stage I group (n=40), stage II group (n=72), and stage III group (n=30). All the 18 neonates who underwent surgical treatment had stage III NEC, and among the 124 neonates who underwent conservative treatment, 12 had stage III NEC and the others had stage I or II NEC. CRP and PCT were measured before treatment, on the next day after treatment, and during the recovery stage.</p><p><b>RESULTS</b>Before treatment, on the next day after treatment, and during the recovery stage, the stage III group had a higher level of CRP than the stage I and stage II groups (P<0.05). On the next day after treatment, the stage II and stage III groups had an increase in CRP (P<0.05), and the stage III group had an increase in PCT (P<0.05). The stage II and stage III groups had lower CRP and PCT in the recovery stage than before treatment and on the next day after treatment (P<0.05). The stage III group had higher incidence rate of respiratory failure and rate of mechanical ventilation than the stage I and stage II groups (P<0.05), and the stage III group had a higher incidence rate of sepsis than the stage II group (P=0.010). Gastrointestinal perforation and intestinal stenosis were observed in 10 and 8 neonates respectively in the stage III group. CRP on the next day after treatment had a value in predicting stage III NEC (P<0.05), and CRP before treatment and on the next day after treatment had a value in predicting the need for surgery (P<0.05).</p><p><b>CONCLUSIONS</b>Levels of CRP and PCT and their changes can help with the early diagnosis of Bell stage II/III NEC, and CRP can be used to predict the development of stage III NEC and the need for surgery.</p>

Effects of phytosterol ester on aortic aging and expression of related genes in rats / 中国病理生理杂志

AIM: To explore the protective effect of phytosterol ester (PSE) on aortic aging in rats.ME-THODS: The female SD rats (12 months old, n=42) were randomly divided into control group, model group and PSE group.During the experiment, the rats in control group, model group and PSE group were treated with basic feed, high-fat diet (HFD) and HFD with 2% PSE (W/W) for 6 months, respectively.The morphological changes of the aorta were observed by HE staining and Masson staining, and the absolute area of smooth muscle cells and collagen fiber in the vascular wall were measured by image analysis.The levels of advanced glycosylation end products (AGEs), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in the plasma were detected.The expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor γ (PPARγ) at mRNA and protein levels in the vascular tissue was determined by real time PCR and Western blot, respectively.RESULTS: PSE significantly lowered plasma TC and LDL-C, and increased plasma HDL-C level (P<0.05), but had no effect on plasma TG level.PSE significantly attenuated the thickening of intima and media of aging aortic, and decreased the migration of vascular smooth muscle cells (VSMC) and the amount of VSMC and collagen fiber in the aorta (P<0.05).PSE significantly reduced the contents of AGEs and MDA (P<0.05), but had no effect on the activity of SOD and CAT in the plasma.PSE also down-regulated the expression of PPARγ and up-regulated the expression of SIRT1 (P<0.05).CONCLUSION: PSE is able to attenuate the senescence process in the aorta by reducing the production of reactive oxygen species in plasma, and activating SIRT1, or inhibiting the expression of PPARγ in vascular tissues.

Effect of high temperature preconditioning on hydrogen peroxide-induced expression of mitochondrial metallothionein in rat cardiomyocytes / 中华麻醉学杂志

Objective To investigate the effects of high temperature preconditioning on hydrogen peroxide (H2 O2)-induced expression of mitochondrial metallothionein (MT) in rat cardiomyocytes.Methods The rat cardiomyocytes H9C2 cultured in vitro were randomly divided into 3 groups (n =6 each):control group (group C) ;H2O2 group (group H2O2); high temperature preconditioning group (group HTP).The cells were continuously cultured for 3 h in group C.The cells were cultured for 3 h in serum-free DMEM liquid culture medium containing H2O2 0.5 mmol/L in an incubator filled with 5％ CO2 at 37 ℃ in group H2O2.In group HTP,the cells were cultured in serum-containing DMEM liquid culture medium,then placed in a warm bath of 42 ℃ for 1 h,cultured for 12 h in an incubator filled with 5％ CO2 at 37 ℃,DMEM liquid culture medium was then removed,and the other procedures were similar to those previously described in group H2 O2.Myocardial cell apoptosis was observed by flow cytometry.The apoptotic rate was calculated.The ultrastructure of myocardial mitochondria was examined with electron microscope.The expression of mitochondrial MT in cardiomyocytes was determined using Western blot.Results Compared with group C,the apoptotic rate was significantly increased,and the expression of mitochondrial MT was up-regulated in groups H2O2 and HTP (P ＜ 0.01).The apoptotic rate was significantly lower,and the expression of mitochondrial MT was higher in group HTP than in group H2O2 (P ＜ 0.01).The mitochondrial injury was attenuated in group HTP as compared with group H2 O2.Conclusion The mechanism by which high temperature preconditioning reduces H2 O2-induced myocardial damage may be related to up-regulation of expression of mitochondrial MT in cardiomyocytes and endogenous myocardium-protective mechanism in rats.

Study on microwave digestion of vacant gelatin capsules / 中国药学杂志

OBJECTIVE: To assure the safety and improve the efficiency of microwave digestion of vacant gelatin capsules. METHODS: Different digestion conditions were investigated by using microwave digestion system with temperature and pressure sensors to determine the optimal experimental method. RESULTS: Using high proportion of hydrogen peroxide in pre-digestion could moderate the increase of pressure in microwave digestion process and at the same time shorten time and improve the digestion efficiency. CONCLUSION: This method, which improves the experimental safety and applicability, is an effective way to solute the long pre-digestion time of the method of Ch. P(2010) and the burst with ordinary digestion tanks.

Effect of Gingkgo biloba leaf extract induced delayed preconditioning on cytochrome c oxidase expression during myocardial ischemia-reperfusion in rats / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of Gingkgo biloba leaf extract (EGb761) induced delayed preconditioning on cytochrome c oxidase (CcO) expression during myocardial ischemia-reperfusion in rats.@*METHODS@#Four groups (10 in each) of Sprague-Dawley male rats were studied. In the sham group, the rats received no treatment. Rats in the ischemia-reperfusion (IR) group were treated with NS (1.0 mL/kg intravenously) 24 h before ischemia. Rats in the M group were treated with EGb761 (100 mg/kg intravenously) 24 h before the ischemia. In the D group , EGb761-treated rats that received the 5-hydroxydecanoate (5-HD), an inhibitor of mitochondrial KATP channels 15 min before the ischemia. The IR, M, and D groups were subjected to ischemia by 30 min of coronary artery occlusion before 2 h of reperfusion. At the end of the reperfusion, myocardial infarct size was measured. CcO was measured by Western blot. The myocardial ultrastructure was observed under the electron microscope.@*RESULTS@#The infarct size was significantly smaller in the M group [(23.78 ± 4.82)%] than in the I/R group [(37.87 ± 5.92)%] (P0.05).@*CONCLUSION@#EGb761 induced delayed preconditioning attenuates myocardial ischemia-reperfusion injury possibly through up-regulating CcO expression in rats.

Effects of hydrogen sulfide preconditioning on myocardial ischemia reperfusion injury in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of hydrogen sulfide preconditioning on myocardial ischemia reperfusion injury in rats.</p><p><b>METHODS</b>Sprague-Dawley male rats were divided into 4 groups with 10 in each group: in S group rats received sham operation; in IR group rats were given with NS (1.0 ml/kg iv) 24 h before ischemia; in H group rats were treated with NaHS (0.05 mg/kg iv) 24 h before ischemia; and in D group, NaHS-treated rats received 5-hydroxydecanoate (5-HD) 15 min before ischemia. Rats in IR group,H group and D group were subjected to ischemia by occlusion of coronary artery for 30 min followed by 2 h of reperfusion. At the end of the reperfusion,myocardial infarct size was measured. SAM-s was measured by Western blotting. Plasma SOD activity and MDA were determined at the end of reperfusion.</p><p><b>RESULTS</b>The infarct size was significantly lesser in H group (25.40 % ± 3.54%) than that in IR group (38.27% ±5.64%,P<0.05). The SAM-s protein expression in myocardium was significantly lower in H group than that in IR group. The plasma MDA content was significantly lower and SOD activity was higher in H group than those in IR group,but there was no difference between IR group and D group.</p><p><b>CONCLUSION</b>The hydrogen sulfide preconditioning attenuates myocardial IR injury possibly through down-regulating SAM-s expression,reducing the production of oxygen free radicals and enhancing anti-oxidize effect in rats.</p>

Proteomics analysis of adenosine A1 receptor agonist-induced delayed myocardial protection in rabbits / 中南大学学报(医学版)

OBJECTIVE@#To investigate the changes of myocardial protein expression profiles in 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine A1 receptor agonist-induced delayed myocardial protection in New Zealand rabbits .@*METHODS@#A total of 8 rabbits were randomly divided into a CCPA group (CCPA group) and a normal saline group (NS group). CCPA and NS were infused into rabbits in the CCPA group and the NS group respectively. Twenty-four hours later, the rabbits were subjected to 30 min left anterior descending coronary artery occlusion and were reperfused for 2 hours, then the ischemic zone tissues of left ventricle were sampled for proteomic analysis.A total of 12 other New Zeland rabbits were divided into a sham group (Sham group), a normal saline group (NS group) and a CCPA group (CCPA group). The expression of αB-crystalline, one of the differential proteins, was confirmed by Western blot.@*RESULTS@#Analysis of two dimensional gel electrophoresis showed that the expression of 55 protein spots were different between the two groups, 17 protein spots were preliminarily identified with the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and Mascot and Expasy bioinformatics software. These proteins included stress proteins, metabolism-associated proteins, signal transduction pathway-related proteins, ionophorous proteins, immunity-associated proteins, and so on. Western blot showed that the expression of αB-crystalline was significantly up-regulated in the CCPA group.@*CONCLUSION@#The myocardial protein expression profiles are changed markedly in the preconditioning late phase of CCPA .The differential proteins might be involved in the delayed cardioprotection induced by CCPA.

Effect of hydrogen sulfide-induced delayed preconditioning on glutathione S-transferase expression during myocardial ischemia-reperfusion in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of hydrogen sulfide-induced delayed preconditioning on glutathione S-transferase (GST) expression during myocardial ischemia-reperfusion in rats.</p><p><b>METHODS</b>Sprague-Dawley male rats were randomly divided into 4 groups (n= 10 in each): Group S (sham operation group), Group IR (ischemia/reperfusion group), Group H (IR+ NaHS 0.05 mg/kg iv, 24 h before ischemia) and Groups D receiving IR+NaHS 24 h before ischemia and 5-hydroxydecanoate (5-HD)15 min before ischemia. Animals in groups IR, H and D were subjected to ischemia by 30 min of coronary artery occlusion followed by 2 h of reperfusion. At the end of the reperfusion, myocardial infarct size (IS) was examined. Glutathione S-transferase (GST) was measured by Western blotting. The myocardial ultrastructures were observed under the electron microscopy.</p><p><b>RESULTS</b>The IS was significantly smaller in Group H than that in Group IR [(25.40 ± 3.54)% compared with (38.27 ± 5.64)%, P<0.05]. The GST expression in myocardium was significantly higher in Group H than that in Group IR. Microscopic examination showed less myocardial damage in Group H than in Group IR. The protective effects of delayed preconditioning by hydrogen sulfide was prevented by 5-HD pre-treatment.</p><p><b>CONCLUSION</b>The hydrogen sulfide-induced delayed preconditioning attenuates myocardial IR injury possibly through up-regulating glutathione S-transferase expression in rats.</p>

Effect of sevoflurane postconditioning on myocardial oxidative stress injury in patients undergoing heart valve replacement with cardiopulmonary bypass / 中华麻醉学杂志

Objective To investigate the effect of sevoflurane postconditioning on the myocardial oxidative stress injury in patients undergoing heart valve replacement with cardiopulmonary bypass (CPB) . Methods Thirty ASA Ⅱ or Ⅲ and NYHA class Ⅱ or ID patients, aged 30-59 yr, weighing 42-62 kg, scheduled for cardiac valve replacement with CPB, were randomly divided into 2 groups ( n = 15 each) : control group (group C) and sevoflurane postconditioning group (group S) . Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg, fentanyl 3-6 μg/kg, vecuronium 0.10-0.15 mg/kg and etomidate 0.1-0.2 mg/kg. The patients were tracheal intu- bated and mechanically ventilated. Anesthesia was maintained with intermittent iv boluses of fentanyl and midazolam and continuous infusion of atracurium and propofol. In group S, 2% sevoflurane was given over 15 min via the cardiopulmonary bypass machine immediately after aortic unclamping. Blood samples from the internal jugular vein were collected immediately before skin incision (T1 ) and at 30 min, 3 h and 24 h after aortic unclamping (T2-4 ) for measurement of the plasma malondialdehyde level. Myocardial tissues were taken from the left auricle before operation and after termination of CPB for determination of α-glutathione-S-transferase expression by Western blot. Results The plasma malondialdehyde concentration was significantly lower at T2, 3, while a-glutathione-S-transferase expression in myocardial tissues higher after termination of CPB in group S than in group C ( P ＜ 0.05) . Conclusion Sevoflurane postconditioning can enhance the antioxidant capacity and attenuate the myocardial oxidative stress injury in patients undergoing cardiac valve replacement with CPB, which may be helpful to reduce myocardial ischemia-reperfusion injury.

Effect of isoflurane delayed preconditioning on the expression of Bcl-2 and caspase-3 in myocardium during ischemia reperfusion in rabbits / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of isoflurane delayed preconditioning on the activation of caspase-3 and the expression of Bcl-2 in rabbit myocardium during ischemia reperfusion and the possible mechanism.@*METHODS@#Forty New Zealand male white rabbits were randomly divided into 4 groups: a sham group (Group C), an I/R group, an isoflurane group (Group S), and an isoflurane + opioid recepters inhibitor group (Group N). Group S was exposed to 2.0% isoflurane for 2 h. Group N was given naloxone (6.0 mg/kg) before exposing to 2.0% isoflurane. Group C and Group I/R were exposed for 2 h to 100% oxygen, serving as untreated controls. Twenty-four hours later, Group S and Group N underwent 40 min of coronary occlusion followed by 2 h of reperfusion. At the end of the reperfusion, infarct size(IS) and area at risk(AAR) were defined by Evans and TTC staining. The myocardial ultrastructure was observed by electron microscopy. The levels of the myocardial Bcl-2 and caspase-3 expression were determined by Western blot.@*RESULTS@#The caspase-3 activity of Group S was significantly lower than that of Group I/R(P<0.05). The IS was significantly reduced in Group S(19.7%+/-2.8%) as compared with Group I/R(37.8%+/-1.7%) (P<0.05). Microscopic examination showed less myocardial damage in Group S than in Group I/R.@*CONCLUSION@#Isoflurane delayed preconditioning can inhibit the apoptosis of myocardium by up-regulating the expression of Bcl-2 and down-regulating the activation of caspase-3, which may be part of the molecular mechanism of isoflurane delayed preconditioning on myocardial preservation.

Glycyrrhiznatis ameliorates rabbit myocardial ischemia-reperfusion injury through P38MAPK pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of p38MAPK pathway in the protective effect of glycyrrhiznatis against myocardial ischemia-reperfusion in rabbits.</p><p><b>METHODS</b>Thirty rabbits were randomly divided into control group, I/R group, and glycyrrhiznatis group. In the latter two groups, the left anterior descending branch of the coronary artery was ligated for 40 min followed by 120 min of reperfusion, and in glycyrrhiznatis group, glycyrrhiznatis was given intravenously at 2.5 mg/kg before the occlusion. Blood samples were taken to measure the plasma levels of TNF-alpha, IL-6, and IL-8 at 20 min before (T(0)) and 20 min (T(1)) and 40 min (T(2)) after the occlusion, and at 1 h (T(3)) and 2 h (T(4)) after the reperfusion. At the end of the reperfusion, the infarct size and the area at risk were defined by Evams and TTC staining. The heart was harvested and the levels of the p38 MAPK measured by Western blotting. The ultrastructures of the cardiac myocytes were observed under electron microscope.</p><p><b>RESULTS</b>The p38MAPK activity and the plasma levels of the inflammatory factors were significantly lower in gtycyrrhiznatis group than in I/R group (P<0.05). Glycgrrhiznatis significantly reduced the infarct size as compared with that in I/R group.</p><p><b>CONCLUSIONS</b>lycyrrhiznatis can reduce myocardial ischemia-reperfusion injury by inhibiting p38MAPK activity and modulating the cytokine expression.</p>

Association between the epidermal growth factor gene and intelligence in major depression patients / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the association between the epidermal growth factor (EGF) gene and intelligence in patients with major depression.</p><p><b>METHODS</b>Intelligence measurement using Wechsler Adult Intelligence Scale (WAIS) was performed on 120 unrelated patients with major depression and 46 control subjects. Blood was collected from all subjects for extraction of genomic DNA. Four single nucleotide polymorphisms (SNPs) in the EGF gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI- TOF-MS).</p><p><b>RESULTS</b>Mean scores of both score lang and score task, two subtests in WAIS, differed significantly between major depression patients and controls (P<0.0001). Quantitative trait analysis showed that the genotype of rs2250724 was closely associated with score lang and score task in major depression patients. The associations were still significant after 10 000 permutations.</p><p><b>CONCLUSIONS</b>Although preliminary, our results provide evidence for association between the EGF gene and intelligence in patients with major depression. Genetic variation in the EGF gene may increase the susceptibility of major depression.</p>

Role of mitochondrial permeability transition pore in attenuation of myocardial ischemia-reperfusion injury by delayed preconditioning with sevoflurane in rats / 中华麻醉学杂志

Objective To investigate the role of mitochondrial permeability transition pore (mPTP) in attenuation of myocardial ischemia-reperfusion (I/R) injury by delayed preconditioning with sevoflurane in rats.Methods Eighty male SD rats, weighing 250-300 g, were randomly assigned into 5 groups ( n = 16 each): Ⅰsham operation group (group S), Ⅱ group I/R, Ⅲ sevoflurane delayed preconditioning group (group SP), Ⅳ the mPTP opener atractyloside + sevoflurane delayed preconditioning group (group A + SP), and Ⅴ atractyloside group (group A). Myocardial I/R was induced by ligation of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion in group I/R, SP, A + SP and A. In group SP and A + SP, 2.5%sevoflurane was inhaled for 1 h, while pure oxygen was inhaled for 1 h in the other groups, and then myocardial ischemia was performed 24 h later. In group A + SP and A, atractyloside 5 mg/kg was injected intravenously via caudal vein 15 min before ischemia. Blood samples were taken from carotid arteries for detection of serum cardiac troponin-Ⅰ (cTnI) concentrations at the end of reperfusion. Then the rats were sacrificed and hearts removed. The myocardial infarct size (IS) and expression of Bcl-2 and Bax in the myocardium were determined. Myocardial ultrastructure was examined with the electron microscope. Results Serum cTnI concentrations and Bax expression were significantly higher, the myocardial IS was significantly larger and Bcl-2 expression was significantly lower in the other groups than in group S ( P ＜ 0.05). Serum cTnI concentrations and Bax expression were significantly lower, the myocardial IS was significantly smaller and Bcl-2 expression was significantly higher in group SP than in group I/R ( P ＜ 0.05). Microscopic examination showed less damage in group SP than in group I/R. The protection provided by sevoflurane preconditioning was abolished by atractyloside. Conclusion Inhibition of mPTP opening can result in an up-regulation of Bcl-2 expression and down-regulation of Bax expression, which plays a role in attenuation of myocardial I/R injury by delayed preconditioning with sevoflurane in rats.

Isoflurane preconditioning decreases the plasma concentration of matrix metalloproteinase-9 and protects myocardium against cardiopulmonary bypass in cardiac valve replacement / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of isoflurane preconditioning on the plasma concentration of matrix metalloproteinase (MMP)-9 and myocardial ultramicrostructure in patients undergoing cardiac valve replacement.@*METHODS@#Thirty patients undergoing elective cardiac valve replacement with cardiopulmonary bypass (CPB) were randomly assigned to a control group (ný15) and an isoflurane group (ný15). In the isoflurane group, isoflurane of 1.0 minimum alveolar concentration end-tidal( 1.1% approximately 1.2%) was administered for 30 min followed by a 15 min washout period before the CPB. The control group did not inhale isofurane, and there was no difference in the other drugs in the 2 groups. Blood samples for MMP-9 were obtained before incision(T(0)) and at 30 min (T(1)),6 h (T(2)),12 h (T(3)), and 24 h (T(4)) after the reperfusion. Right atrial biopsies were collected before and after the CPB to observe the myocardial ultramicrostructure.@*RESULTS@#Compared with T(0), the mean MMP-9 level significantly increased at T(1), T(2) and T(3) in the control group(P<0.01), while the MMP-9 level only at T(1) significantly increased in the isoflurane group (P<0.01). The mean MMP-9 level was significantly reduced in the isoflurane group at T(2) compared with each time point in the control group. The difference in MMP-9 levels between T(1), T(2), T(3) and T(0) was significantly lower in the isoflurane group than that in the control group (P<0.01). The ultramicrostructure injury of myocardium under electron microscope in the control group was worse than that in the isoflurane group.@*CONCLUSION@#The plasma concentration of MMP-9 is inhibited by isoflurane preconditioning in patients undergoing cardiac valve replacement after CPB, which might be part of its protective mechanism against myocardium injury after CPB.

Metallothionein mediates cardioprotection induced by delayed preconditioning with adenosine A1 receptor agonist in rabbits / 中南大学学报(医学版)

Objective To investigate the protective effect of adenosine A1 receptor agonist (2-chloro-N6-cyclopentyladenosine, CCPA) delayed preconditioning on myocardial ischemia reperfu-sion injury and the potential mechanism in rabbits. Methods Thirty New Zealand male white rabbits were randomly assigned to 3 groups:a control group, an I/R group, and a CCPA group. CCPA group was given CCPA 0.1 mg/kg before the myocardial ischemia. Twenty-four hours later I/R group and CCPA group underwent 40 min of coronary occlusion followed reperfusion for 2 h. At the end of the reperfusion, blood samples were taken from the arterial line for determining the plasma level of malondialdhyde and superoxide dismutase activity. The infarct size and area at risk were de-fined by Evans and TIC staining. The heart was harvested and levels of metallothionein (MT) were determined by Western blot, and ultrastructures were observed under the electron microscope. Results The MT level of CCPA group was significantly higher than that of the I/R group (P<0.05). CCPA significantly reduced the infarct size (22.1%±3.8% in the CCPA group) of the left yen-tricular area at risk as compared with the control (41.8%±4.3% in the I/R group,P<0.05). The injury of I/R group was worse than that of the CCPA group under the light microscope. CCPA group had higher superoxide dismutase and lower malondialdhyde than those of the I/R group. Con-clusion CCPA can increase the level of metallothionein during ischemia-reperfusion, which may be part of the molecular mechanism of CCPA delayed preconditioning on cardioprotection.

Preconditioning of morphine protects rabbit myocardium from ischemia-reperfusion injury / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the protective effects of preconditioning morphine on rabbit myocardium during ischemia-reperfusion.</p><p><b>METHODS</b>Thirty New Zealand male white rabbits were randomly assigned to three groups: control, I/R and morphine groups. In morphine group 1.0 mg/kg morphine was given preoperationaly, in control and I/R groups 1.0 ml/kg NS was given. Twenty-four hours later rabbits in morphine and I/R groups underwent 40 min of coronary occlusion followed by 2 hours of reperfusion; for control group only sham operation was performed. At the end of the reperfusion, infarct size (IS) and area at risk (AAR) were defined by Evans blue and TTC staining. At the end of the reperfusion blood samples were taken for determination of plasma SOD activity and MDA levels. The heart was harvested and levels of the HSP27 were determined by Western blot, and the heart ultrastructures were observed under the electron microscopy.</p><p><b>RESULTS</b>Compared with I/R group,morphine significantly reduced infarct size (21.5%+/-2.4% Compared with 37.8%+/-1.7%, P<0.05). The morphine had a lower level of MDA and higher levels of SOD and HSP27 than those in I/R.</p><p><b>CONCLUSION</b>Preconditioning of morphine demonstrates cardioprotective effect on ischemia/reperfusion injury, which may be associated with increased HSP27 levels in the heart.</p>