The teaching for medical advanced students is a routine and important task in teaching hospital.To increase the teaching quality,we should emphasize professional theory learning,increase clinical skill training,strengthen medical records writing training and enhance emotional exchange.

Epimutations are errors in the normal process of epigenetic regulation which can result in aberrant transcriptional silencing of a normally active gene or reactivation of a normally silent gene.Epimutations are generally considered to be somatic events and to be confined in affected tissues.However, recent studies of patients with hereditary nonpolyposis colorectal cancer(HNPCC) have showed that allele-specific hypermethylation of CpG islands in the promoter region of the MLH1 gene, one of the causes of the tumor,existed in all the tissues examined.In addition,germ-line epimutations of other tumor suppressor genes(TSGs),such as MSH2 and BRCA1,have also been reported,demonstrating that epimutations might arise in the germline(during gametogenesis or early embryonic development).The role of germ-line epimutations might be as important as germ-line mutations in human disease.We reviewed the update on germ-line epimutations of TSGs including the possible mechanisms underlying germ-line epimutations,the possibility of transgenerational inheritance.and their impact on our understanding of human disease.

A novel white-rot fungus AH28-2,which was isolated from 224 fungi samples,ability to produce effectively laccase by induction.Several factors influencing laccase production were investigated.The optimum conditions were as follows:the 300mL Erlenmeyer flask containing 150mL of liquid medium was inoculated with 7.5mL of mycelial fragments and the medium was supplied with lignin at a concentration of 0.1%(initial pH8.5).The cultures was incubated at 28℃ on rotary shaker(150r/min) for 4～5 days.The maximum enzyme activity was 20184IU/L.

OBJECTIVETo study the distribution pattern of TCM Syndrome type and its relationship with renal pathology in patients with IgA nephropathy.

METHODSApopting multicenter coordinated method, patients' TCM Syndrome type was differentiated according to their clinical manifestations, data concerning laboratory examination and renal pathology were collected to establish a database for analyzing the relationship between TCM Syndrome type and renal pathology in 286 patients.

RESULTSPatients of Pi-Fei Qi-deficiency type (type 1) and both Qi-Yin deficiency type (type 2) showed rather milder pathological changes, by Lee classification, most of them belonged to grade I-III (72.3%, 70.2%); patients of Gan-Shen Yin deficiency type (type 3) had severe pathological change and majority of them belonged to grade III-IV (84.6%); and the most severe pathological change was shown in patients of Pi-Shen Yang-deficiency type (type 4), and the Lee's grade IV-V was dominant (88.0%) in them. Syndrome type of patients was significantly correlated with their Lee's grade (r = 0.26, P < 0.01). Percentage of glomerular sclerosis in patients of type 4 was higher than that in patients of the other three types. Semi-quantitative scoring upon pathological changes showed that the total, glomerular, tubulo-interstitial and vascular scores were significantly higher in patients of type 4 than in those of the other three types; those scores were higher in patients of type 3 than in type 1; the total, glomerular and vascular scores were higher in patients of type 3 than in type 2; and scores in patients of type 1 and type 2 showed insignificant difference.

CONCLUSIONMulticentric prospective study proves that the TCM Syndrome typeof patients with IgA nephropathy is significantly correlated with the grade and severity of their renal pathological changes, thus, the TCM Syndrome typing shows definite referential importance to conclude the severity of renal pathological change in patients with IgA nephropathy.

Adolescent ; Adult ; Diagnosis, Differential ; Female ; Glomerulonephritis, IGA ; diagnosis ; pathology ; Humans ; Kidney ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Prospective Studies ; Yang Deficiency ; pathology ; Yin Deficiency ; pathology

OBJECTIVETo explore the pharmacologic mechanism of cinnabar (CA) and realgar (RG) in Angong Niuhuang powder (ANP) by way of studying the characteristics of their effects on organism under physiologic and pathologic states.

METHODSSD rats were randomly divided into six groups, 8-10 rats in each group. Group A: untreated normal rats; Group B: normal rats administered by ANP (drug I) 278 mg/kg; Group C: normal rats administered by ANP subtracted CA and RG (drug II) 222.7 mg/kg; Group D: brain edema model rats established by unilateral common carotid artery injection of Bacillus pertussis 250 million/kg; Group E: model rats administered by ANP 278 mg/kg 1 hr before modeling; Group F: model rats administered by drug II 222.7 mg 1 hr before modeling. Blood sample and brain tissue in Group D were obtained 4 hrs after modeling and those in other groups obtained 5 hrs after drug administration. The total activity of lactate dehydrogenase (LDH) in serum and brain tissue was determined by colorimetry and that of serum LDH isoenzymes (LDH(1-5)) were determined by gel electrophoresis.

RESULTSAs compared with Group A, LDH, LDH1 and LDH2 activities increased in Group D (P < 0.01), and increased also in Group B and C (P < 0.05), while LDH4 and LDH5 decreased obviously in Group B and C. But except that of LDH5, no significant difference of LDH(1-4) in brain tissue and serum was shown in comparison of Group B and C. As compared with Group D, LDH was lower (P < 0.01) and LDH5 was higher (P < 0.01) in Group E and F without significant difference, LDH2, LDH3 were lower in Group E (P < 0.01) but unchanged in Group F, LDH1 and LDH4 were not changed in Group E but significantly lowered in Group F (P < 0.05 and P < 0.01).

CONCLUSIONAdministration of ANP in normal physiologic condition would cause damage on myocardium and kidney to certain extent, administration of ANP and drug II in pathologic (infectious brain edema) would suppress the hyper-activated LDH, with no significant difference between the effects of drug II and ANP. However, CA and RA in ANP are proven to have influence on the serum LDH isoenzymes, indicating that the two ingredients may have some potential pharmacological effects.

Animals ; Arsenicals ; pharmacology ; Brain Edema ; enzymology ; etiology ; Drugs, Chinese Herbal ; chemistry ; Encephalitis ; complications ; Isoenzymes ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Male ; Mercury Compounds ; pharmacology ; Powders ; Rats ; Rats, Sprague-Dawley ; Sulfides ; pharmacology

OBJECTIVE To determine the effects of Danshen injectable powder on myocardial remodeling in pressure overload rats and isoproterenol(ISO)injection mice.METHODS SD Rats were subject to abdominal aortic constriction(AAC)surgery to develop pressure overload.Therapeutic effect of Danshen injectable powder was assessed six weeks after AAC surgery. The lactic dehydrogenase (LDH) and creatine kinase (CK) levels in serum, biometric, echocardiographic parameters, interstitial fibrosis, the expression of DJ-1 and SOD2 were then measured. The myocardial impairment in mice was induced by ISO injection. LDH and CK in serum, biometric, interstitial fibrosis were measured to investigate the cardioprotective effect of Danshen injectable powder. Matrix-assisted laser desorption mass spectrometry imaging(MALDI-MSI)was used to detect the changes of 60-1000 Da molecules in mice heart tissue. RESULTS In AAC rats, we observed compensatory hypertrophy and perivascular fibrosis,however cardiac function had not progressed to deterioration.The levels of LDH and CK were decreased significantly in the Danshen injectable powder groups(P<0.05,P<0.05).Danshen injectable powder could alleviate the perivascular collagen deposits but not cardiac hypertrophy in AAC rats. Furthermore,Danshen injectable powder enhanced the expression levels of SOD2 and DJ-1 in cardio-myocytes (P<0.05, P<0.01). In ISO injection mice, the levels of HWI and LDH were decreased signifi-cantly in drug treatment group compared with model group (P<0.01, P<0.01). In the MALDI-MSI of mice heart section,Danshen injectable powder can improve the reduction of energy metabolism-related substances including adenosine, creatine and ADP induced by ISO impairment. CONCLUSION Danshen injectable powder can attenuate perivascular fibrosis and improve the expression of anti-oxidative stress-related proteins SOD2,DJ-1 in the rats with pressure overload-induced left ventricular remodeling.Danshen injectable powder has cardioprotective effect on ISO impairment in mice which is probably related to improvement of energy metabolism.

AIMTo investigate the aquation of oxaliplatin in aqueous solution at different temperatures and gain the kinetic data.

METHODSElectronic conductometry and high performance liquid chromatography (HPLC) were used to measure the oxaliplatin content in the reaction systems at different time.

RESULTSThe aquation of oxaliplatin followed a pseudo-first-order rate law. In the absence of H+, the observed rate constant kobs was 7.76 x 10(-6).min-1 and the half life t1/2 was 62 days at 25 degrees C. In the presence of H+, the aquation could be accelerated by H+ according to the equation kobs = (2.61 + 21.9 [H+]) x 10(-4).min-1. The mechanism of aquation has also been proposed in this paper. From the mechanism, the rate of aquation following to r = (k1 k2) [l-OHP]/k-1 in the absence of H+ and r = (k1 + K0k3 [H+]) [l-OHP] in the presence of H+ have been deduced, which were in perfect agreement with the experimental results.

CONCLUSIONIn the absence of H+, the aqueous solution of oxaliplatin is stable, which meets to the request of clinical.

Acids ; Antineoplastic Agents ; chemistry ; Chromatography, High Pressure Liquid ; Hydrogen-Ion Concentration ; Kinetics ; Organoplatinum Compounds ; chemistry ; Solutions ; Water ; chemistry

The production conditions of extracellular laccase from Armilliria mellea and the characteristics of the enzyme were studied. The experiment proved that initial pH5.5 of the culture medium and temperature at 25 degrees C were favorable for laccase synthesis. As carbon resources, cellobiose and raffinose were better in terms of productivity than maltose, sorbose and galactose. Organic nitrogen source was more suitable for Armilliria mellea to synthesize laccase than inorganic nitrogen source. Peat extract (PE) enhanced notably the yield of laccase; the maximal yield was 7 times as much as that of the control when PE concentration was 50%. Three isozymes were detected in culture supernatant named A, B and C respectively after their mobility on PAGE. After concentrated by (NH4)2SO4 precipitation, laccase A was further purified to homogeneity by preparative native PAGE and anion exchange column chromatography. The native enzyme was a single polypeptide with a molecular mass of approximately 59 kD estimated by SDS-PAGE, while 58 kD by gel filtration chromatography under non-denaturing conditions. Determined by IEF its isoelectric point was 4.0. The optimal pH value and temperature were 5.6 and 60 degrees C respectively in catalytic reaction of oxidizing guaiacol. At 60 degrees C and 65 degrees C, half-lives of laccase A were 45 min and 36.8 min, respectively. Enzyme activity was inhibited with 100 mmol/L Cl-, but was activated with 1 mmol/L SO4(2-). However, if the concentration of NaN3 was only 1 mmol/L, laccase A lost its activity completely. 10 mmol/L EDTA had no effect on laccase A, while 1 mmol/L Cu2+ could enhance its activity. Laccase A showed a good stability when the pH of the buffer varied from 5.2 to 7.2. Using guaiacol as the substrate, the Km was 1.026 mmol/L and the Vmax was 5 mumol/(min.mg); using ABTS instead, the Km was 0.22 mmol/L and Vmax was 69 mumol/(min.mg).
Agaricales ; drug effects ; enzymology ; growth & development ; Carbohydrates ; pharmacology ; Culture Media, Conditioned ; metabolism ; Electrophoresis, Polyacrylamide Gel ; Enzyme Stability ; Hydrogen-Ion Concentration ; Laccase ; Oxidoreductases ; isolation & purification ; metabolism

Objective To assess the diagnostic value of combined testing of urinary bladder cancer antigen(UBC),hyaluronic acid(HA)and survivin in the detection of bladder cancer.Methods This study included 64 bladder cancer patients and 20 urinary benign disease patients.The examinations of urine UBC by enzyme-linked immunosorbent assay(ELISA),HA by radioimmunology assay,survivin by RT-PCR and urine cytology were performed in them.Results The sensitivity of UBC(85.9%,55/64),HA (89.1%,57/64)and survivin(93.8%,60/64)was significantly higher than that of urine cytology (40.6%,P＜0.01).The specificity of UBC,HA,survivin and urine cytology was 85.0%(17/20),80.0% (16/20),95.0%(19/20)and 95.0%(19/20),respectively;there was no significant difference among these 4 methods(P＞0.05).The sensitivity of UBC,HA and survivin was also significantly higher than that of urine cytology in different histologic stages and grades(P＜0.05).The sensitivity of UBC and survivin was not significantly different among different histologie stages and grades(P＞0.05).With regard to HA test, the sensitivity in G_2 and G_3 groups was significantly higher than G_1 group(P＜0.01),but there was no differ- ence between G_2 and G_3 groups(P＞0.05);and no difference among different histologic stages(P＞0.05). However,the sensitivity of cytology was improved with the higher grade of bladder cancer(P＜0.01);there was no difference among histologic stages(P＞0.05),By combined use of UBC,HA and survivin,both the sensitivity and specificity were 100%.Conclusions The study indicates that UBC,HA and survivin are better diagnostic markers for the early detection of urinary bladder cancer.These tests are simple,feasible and noninvasive with higher sensitivity and specificity.In addition,combined use of them can improve the diag- nostic sensitivity and specificity.

BACKGROUNDShen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels.

METHODSThe Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n = 8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP).

RESULTSSSYX treatment accelerated the HR from (141.8 +/- 36.0) beats per minute to (163.0 +/- 38.0) beats per minute (P = 0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change.

CONCLUSIONSThe present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

Action Potentials ; drug effects ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Guinea Pigs ; Heart ; drug effects ; physiology ; Heart Rate ; drug effects ; Heart Ventricles ; In Vitro Techniques ; Male ; Myocytes, Cardiac ; drug effects ; physiology ; Sinoatrial Node ; drug effects ; physiology ; Swine ; Swine, Miniature