PRKCDBP Methylation is a Potential and Promising Candidate Biomarker for Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#The occurrence and development of lung cancer are closely linked to epigenetic modification. Abnormal DNA methylation in the CpG island region of genes has been found in many cancers. Protein kinase C delta binding protein (PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies. This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer (NSCLC).@*METHODS@#We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues. Promoter activity was measured by the dual luciferase assay, with 5'-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP.@*RESULTS@#The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant (>10 cm) non-tumor tissues. Receiver operating characteristic (ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line (AUC) was 0.717. Dual luciferase experiment confirmed that the promoter region was able to promote gene expression. Meanwhile, in vitro methylation of the fragment (PRKCDBP_Me) could significantly reduce the promoter activity of the fragment. Demethylation of 5'-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels.@*CONCLUSIONS@#PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.

Progress in brewer's yeast cell wall stress response / 生物工程学报

Yeast cell wall plays an important role in the establishment and maintenance of cell morphology upon the cell wall stress. The cell wall of yeast consists of β-glucans, mannoproteins and chitin. The composition and structure remodel due to cell wall stress. Brewer's yeast cell wall exhibits stress response during long-term acclimation in order to adapt to environmental changes. This paper reviews the composition and structure of yeast cell wall and the molecular mechanisms of cell wall remodeling and signal pathway regulation.

Clinicopathological features analysis of common complications in pediatric liver transplantation / 中华器官移植杂志

Objective The purpose of this study was to explore common complications and their clinicopathological features in pediatric liver transplantation.Methods Clinical and pathological data of 240 liver biopsies from 168 children that conducted liver puncture from January 2015 to May 2018 in Tianjin First Central Hospital was retrospectively analyzed.We comprehensively analyzed incidence rate and pathological features of various complications,and correlations between acute rejection and C4d staining result or Banff score.Results A total of 86.67％ (208/240) liver biopsies could be definitely diagnosed with incidence rate of main complications in descending order as follows:T cell mediated rejection (TCMR) 60.57％ (126/208),drug-induced liver injury (DILI) 17.31％ (36/208),biliary complication 8.17％ (17/208),vascular complication 3.37％ (7/208),ischemia/reperfusion injury (IRI) 2.88％ (6/208),antibody mediated acute rejection (AMR) 1.92％ (4/208),HBV infection 1.92％ (4/208),non-alcoholic fatty liver disease (NAFLD) 1.44％ (3/208),chronic rejection (CR) 0.96 ％ (2/208) and HCV infection 0.48 ％ (1/208).TCMR and AMR in acute rejection (AR) accounted for 96.92％ (126/130) and 3.08％ (4/160),and into(portal-based,PB)type TCMR accounted for 96.03％(121/126) with the detectable rate of BP type subtype TCMR of 26.45％(32/121)within 30 d.There were 65.87％ (83/126)、25.40％ (32/126) 和4.76％ (6/126) of BP TCMR samples with "Banff ACR RAI" score within 3-5,6-7 and 8-9,and RAI score was negatively correlated with postoperative time (r =0.127,P =0.084).The incidence rate of central perivenulitis (CP) and portal eosinophils infiltration (PEI) in BP TCMR was 63.63％ (77/121) 和43.80％ (53/ 121),respectively,additionally,the PEI level was positively correlate with RAI score (P＜0.05).CP TCMR and AMR occurred within 30d-365 d and 8 d-180 d,respectively postoperative,while,the two CR occurred at 1095 d and 1335 d postoperative,and significant correlation was strikingly observed between rejection subtype and postoperative time (Z =9.231,P =0.026).C4d positive rate was 10％ (24/240),which was associated with Banff score and postoperative time,besides,C4d score was also correlated with rejection subtype and RAI score.The occurrence of DILI was mainly at time of ＜90 d or ＞180 d postoperative,and the detectable rate of biliary complication within 180 d postoperative was 82.35％ (14/17),IRI Appear in ＜30d.Hepatic artery complication account for nearly 57.14％ (4/7),occurrence time is ≤90 d.Occurrence of HBV infection,CMV infection and NAFLD were mainly at ＞365 d,＜90 d and ＜365 d,respectively.Conclusion There were lots of differences in clinical and pathological features among multi pediatric liver transplantation complications.Liver puncture plays an important role in rejection subtype classification and grading,as well as in non-rejection complications identification.

STIM1 promotes arterial smooth muscle cells proliferation by regulating Akt/mTOR pathway / 中国药理学通报

Aim To investigate the expression of stro-mal interaction molecule 1 (STIM1) in rat pulmonary arterial hypertension ( PAH ) tissues and effects of STIM1 on arterial muscle cells proliferation. Methods PAH was induced by a single intraperitoneal injec-tion of MCT at a dose of 60 mg·kg - 1 . The mRNA or protein expressions of STIM1 in monocrotaline-induced pulmonary hypertensive rats were measured by real-time PCR or Western blot, respectively. The arterial smooth muscle cells A7R5 were transiently transfected with STIM1 plasmids to prepare STIM1 overexpressed cells. Cell proliferations were detected by using CCK-8 kits. The expressions of Akt/ mTOR pathway molecules of A7R5 were measured by Western blot. Results The right ventricular systolic blood pressure ( RVSP) and right ventricular mass index ( RVMI ) were markedly elevated in MCT-treated rats (P < 0. 01) in comparison to control rats. The mRNA and protein ex-pression levels of STIM1 in monocrotaline-induced pul-monary hypertensive rats were 2. 19 and 1. 66 folds of control rats, respectively. STIM1 were transiently over-expressed in cultured A7R5. Cells transfected with STIM1 grew more quickly than non-transfected control. Overexpression of STIM1 significantly increased the phosphorylation of Akt, mTOR, p70-S6K, and 4E-BP1, but did not change their protein expression lev-els. Conclusion STIM1 are over-expressed in rat PAH tissues. Overexpression of STIM1 can promote ar-terial smooth muscle cells proliferation by regulating Akt/ mTOR pathway.

Regulation of autophagy by store-operated calcium channel in arterial smooth muscle cells / 中国药理学通报

Aim To investigate the effect of store-oper-ated calcium channel( SOCC) on autophagy in rat arte-rial smooth muscle cells A7 R5 . Methods Lentiviruses containing STIM1 or Orai1 gene were packaged in 293 T cells and then were used to infect rat arterial smooth muscle cells A7 R5 . The expression levels of STIM1 , Orai1 and Beclin 1 , a critical autophagy-regu-lating protein, of lentivirus-infected A7R5 cells, were detected by Western-blot. Autophagy in lentivirus-in-fected A7 R5 cells was induced by starvation or rapamy-cin, an inhibitor of mammalian target of rapamycin ( mTOR ) . Autophagy marker LC3 of these cells was detected by Western-blot. Results The constructions of vector pLV-STIM1 and pLV-Orai1 were confirmed by restriction enzymes digestion analysis. Compared with the control group, expressions of STIM1 or Orai1 protein was significantly increased after lentivirusLV-STIM1 and LV-Orai1infection, whereas the expressions of autophagy related protein Beclin-1 were down-regu-lated. Starvation or rapamycin stimulated A7R5 auto-phagy but overexpression of STIM1 or Orai1 significant-ly inhibited starvation or rapamycin induced autoph-agy. Conclusion Overexpression of store-operated calcium channel components STIM1 and/or Orai1 in rat arterial smooth muscle cells A7 R5 inhibit autoph-agy. This mechanism might contribute to the develop-ment of pulmonary arterial hypertension.

Immunohistochemical evaluation of midkine and nuclear factor-kB as markers for diagnosis and prediction of synchronous metastasis in papillary thyroid cancer / 中华内分泌代谢杂志

Objective Midkine ( MK ) and nuclear factor-kappa B ( NF-kB ) play pivotal roles in tumorigenesis, which are considered as promising cancer biomarkers. The efficacy of MK and NF-kB as markers for diagnosis and prediction of synchronous metastasis in papillary thyroid cancer ( PTC ) was the aim of present investigation. Methods Seventy six cases of PTC and seventy cases of multi-nodular goiter ( MNG ) were retrieved. The PTC group was further divided into subgroup 1 (16 cases with synchronous metastasis) and subgroup 2 (60 cases without metastases). A retrospective review of clinical information, radiological examinations,131 I treatments and post-131 I-therapy scans were done. Immunohistochemistry of MK, NF-kB p65, and Ki-67 was performed on paraffin-embedded specimens and results were quantified. Diagnostic values of the parameters were conducted by receiver operating characteristic (ROC) curves. Diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were determined. Protein levels of MK and NF-kB p65 were then confirmed by Western blot. Results Immunoreactivities of MK and NF-kB p65, and positive percentage of Ki-67 were significantly higher in PTC group than in MNG group (all P<0. 01). ROC showed good differential diagnostic capabilities of all three parameters with diagnostic accuracies of 82. 192% , 80. 137% , and 84. 091%respectively. Moreover, all three parameters were significantly higher in subgroup 1 than those in subgroup 2 (all P<0. 01). ROC showed good predicting efficacies in synchronous metastasis of all three parameters with diagnostic accuracies of 82. 895% , 80. 263% , and 76. 316% respectively. By one-way analysis of variance, Western blot showed that MK and NF-kB p65 protein levels in lesions from subgroup 1 were significantly higher than those from subgroup 2, both were significantly higher than those in MNG lesions ( P<0. 01). Conclusion MK and NF-kB immunohistochemistry can potentially be used for differential diagnosis between PTC and MNG, and for prediction of synchronous metastases.

Correlation between urinary fluoride level and prevalence of dental caries-the effects of defluoridation for 10 years / 中华地方病学杂志

Objective To study the relationship between the level of fluoride in urine and the prevalence of dental caries in children before and after the defluoridation, and to provide a basis for assessment of the effects of defluoridation projects and for control of dental caries.Methods Wamiao Village, in Jiangsu Province, a formerly severe endemic fluorosis area, was selected to carry out the study.All children aged 8-13 years old before the defuoridation were investigated from September to November in 2002, and children 8-10 years old who were born after the defluoridation were investigated from September to November in 2013.Urinary fluoride level of the children and the prevalence of dental caries were determined, and their relationships were analyzed.The urina sanguinis samples of children were collected in the morning, and the urine fluoride level was tested using the fluoride ion selective electrode.Dental caries diagnoses was referenced to Dental Caries.Results Totally children's urine samples were 236 and 68 respectively before and after defluoridation.Urinary fluoride level of the children was significantly decreased from (3.53 ± 1.81)mg/L (before defluoridation) to (1.39 ± 0.66)mg/L (after defluoridation, t =9.506, P ＜ 0.01);the prevalence of dental caries was increased from 52.73％ (29/55, before defluoridation) to 63.24％ (43/68, after defluoridation), however, the difference was not significant (x2 =1.383, P ＞ 0.05).The DMFT increased from 1.18 (before defluoridation) to 1.68 (after defluoridation), and the epidemic levels of dental caries were all at lower levels.The relationship between urine fluoride level and the prevalence of dental caries as well as the DMFT before defluoridation was a U-shape dose-response curve;which was gone after defluoridation.Conclusions The urinary fluoride level is significantly decreased after defluoridation for 10 years, the prevalence of dental caries is increased but not significantly.The results of this study indicate that the measure of fluoridation to prevent dental caries needs to be further validated.

Small Interfering RNA of Cystathionineβ-Synthase/Cystathionineγ-Lyase-Derived Hydrogen Sulfide Synthesis Induces Apoptosis of Rat Hepatic BRL Cell Line / 天津医药

Objective To explore the inhibitory effects of endogenous hydrogen sulfide, a novel and important gas-eous transmitter generated in mammalian tissues mainly by cystathionine β-synthase (CBS) or cystathionineγ-lyase (CSE) on the apoptosis of the rat hepatic BRL cell line in physiological condition. Methods BRL cells were cultured, and divid-ed randomly into several groups in different phases of the experiment, including negative-siRNA (control) group, CBS siRNA (CBS 1~3) group and CSE siRNA (CSE 1~3) group, which were used to select the most efficient sequences of siRNAs at 48 or 24-hour transfection. Solution group and (CBS+CSE) siRNA group were added to detect the variation of apoptosis. The BRL cell line was observed and evaluated at 0, 4, 8, 12, and 24 hrs after siRNA transfection. When the mechanisms of the apoptosis were detected, CBS/CSE siRNAs were transfected individually or jointly into BRL cells, and compared with nega-tive-siRNA group to examine the variation. The genic and protein expression of CBS/CSE were detected by RT-PCR and Western blot assay. After transfection of CBS/CSE siRNA, the apoptosis of BRL cells was detected by Hoechst stain and flow cytometry (FCM). The mitochondrial membrane potential (MMP) changes were observed by fluorescent staining. Western blot assay was used to examine the protein expression of intracytoplasm cytochrome C (Cyt C) and cleaved-caspase 3. Re-sults CBS and CSE were observed in BRL cells. After transfection of CBS/CSE siRNA, endogenous H2S generation de-creased and the apoptosis of BRL cells increased. Accordingly, the expression of intracytoplasm-Cyt C and cleaved-caspase 3 increased. Conclusion The inhibition of endogenous H2S synthesis induced the apoptosis of BRL cells under physiologi-cal condition, which may be involved in mitochondrial pathway of apoptosis.

Clinical characteristics of gastric mucosa-associated lymphoid tissue lymphoma and the effects of Helicobacter pylori eradication therapy / 中华消化内镜杂志

ObjectiveTo review the clinical characteristics of patients with gastric mucosa-associated lymphoid tissue(MALT) lymphoma and to investigate the effects of Helicobacter pylori (Hp) eradication therapy in these patients.MethodsClinical data of ninety-five patients with gastic MALT lymphoma were reviewed with respect to their clinical manifestations,endoscopic features,histopathological features and Hp infection.The follow-up data of patients treated by Hp eradication therapy were analyzed.The survival curve was calculated with Kaplan-Meier,while the predictive factors for resistance to Hp eradiation were then analyzed by using Cox proportional hazards model.ResultsThe clinical manifestations and endoscopic features of 85 patients with gastric MALT lymphoma were non-specific.Hp positive was found in 97.9％ (93/95) patients at presentation,and 36 patients were treated by Hp eradication with a median follow-up duration of ( 58.1 ± 29.9) months.Total remission was achieved in 94.4％ ( 34/36),including 24 complete remission 10 partial remission.Therapy failure occurred in 2 patients.3-year survival rate of patients treated by Hp eradication were 86.2％ (25/29). Cox multivariate analysis showed that age ( ≥60 years),multiple lesions and non-superficial lesions were independent predictors of resistance to Hp eradication therapy.ConclusionGastric MALT lymphoma is associated with Hp infection.Eradication of Hp can effectively induce remission in these patients.

Endoscopic and pathological characteristics of Barrett's esophagus / 中华消化内镜杂志

Objective To investigate the endoscopic and pathological characteristics of Barrett's esophagus (BE).Methods Data of 152 patients who were diagnosed as having BE with endoscopy and pathology were retrospectively analyzed.Results BE was most commonly seen in patients of 40-60 years old.The clinical manifestations overlapped in different patients,including regurgitation and heartburn in 78 (51.32%),dysphagia in 9 (5.92%),retrosternal pain in 12 (7.89%),upper abdominal pain or discomfort in 67 (44.08%),and asymptomatic in 8 (5.26%).Long segment BE (LSBE) was determined in 7 patients (4.61%),and short segment BE (SSBE) in 145 (95.39%).The metaplasia pattern under endoscopy included island like in 98 (64.47%),tongue like in 39 (25.66%) and circumferential in 15 (9.87%).Stratified squamous epithelia in the lower part of the esophagus were replaced by columnar epithelia in all cases,and intestinal metaplasia occurred in 68 cases (44.74 %).Conclusion BE is most frequently seen in the middle-aged and can be diagnosed by endoscopy and pathology without special clinical manifestations.Island pattern occurs in most cases and is with lowest rate of intestinal metaplasia,which is associated with age.Patients with specialized intestinal metaplasia and dysplasia should be followed up for surveillance of cancer.

Expression and significance of caveolin-1 in femoral nerve of diabetic foot amputation patients / 中华内分泌代谢杂志

Objective To investigate the expression and significance of caveolin-1 in femoral nerve of diabetic patients with foot amputation. Methods Forty patients with foot amputation were assigned to 3 groups according to their duration of type 2 diabetes: group A ( ＜6 years＝, group B (6-10 years), and group C ( ＞10 years). Hematoxylin and eosin (HE) stain and Weil's stain were used to examine the femoral nerve. Silver staining was used to observe the axons and to count the nerve fiber density. The expression of caveolin-1 in Schwann cells of femoral nerve was tested by immunohistochemisty. Results There were evident progressive pathological changes in femoral nerve in the 3 groups. The variance of nerve fiber density in the 3 groups reached statistical significance ( P＜0. 05 ＝, the nerve fiber density showed negative correlation with HbA1C( r =-0. 792, P＜0. 01 ＝ and duration ( r=-0.592, P＜0. 01 ＝. The expression of caveolin-1 in Schwann cells of femoral nerve was positive in all the 3 groups and the variance with statistical significance (P＜0. 01 ), it was negatively correlated with HbA1C (r=-0. 762, P＜0. 01 )and duration (r=-0. 532, P＜0. 01 ), and it was positively correlated with nerve fiber density (r=0. 721, P＜0.01 ), the partial correlation coefficient of caveolin-1 and HbA1Cwas-0. 505 ( P＜0. 01 ).Conclusion In patients with diabetic foot amputation, caveolin-1 may play a role in the development of diabetic peripheral neuropathy and diabetic foot.

The expression and clinical significance of apoptosis stimulating protein of p53 in nonsmall-cell lung cancer / 中华检验医学杂志

Objective To investigate the expression and regulation of ASPP family mRNA in NSCLC cell lines.and study the diagnostic and therapeutic significances of apoptosis stimulating of ps3 expression in NSCLC Patients.Methods Real-time fluorescence quantitative PCR wag established and used to measure the expression Ievels of ASPP mRNA in NSCLC cell lines A549(wild-type p53)and NCI-H157 (mutant-type p53)with p53 different genetic background,and ASPP mRNA was also detected in NSCLC tissue,peripheral blood of 37 NSCLC patients.Western Bloting was used to examine the levels of ASPP1 and ASPP2 proteins of NSCLC cell Iines.Chemosensitivity of the cell lines to CDDP was analyzed by MTT assay,and detect the change of ASPP1 and ASPP2.Compared with the ASPPs mRNA expression between NSCLC patients and healthy controls.and monitoring ASPPs mRNA expression in patients with NSCLC chemotherapy.Results The slope rotes of standard curves were-3.249,-3.358 respectively.and correlation coefficients were more than 0.98.Amplification efficiency of standard curves were 1.156.1.028 respectively.The IC_(50) values of NCI-H157 and A549 cells were 3.70.10.48 μg/ml respectively.Mean ASPP1 ASPP2 mRNA levels were a statistically significant 2.66 folds and 6.98 folds higher in NCI-H157 cell compared to A549 cell The levels of ASPP1 mRNA in tumor tissues and peripheral blood were (4.27±0.57)×10~3,(2.49±0.32)×10~3 in patients with NSCLC respectively,and the levels of ASPP2 mRNA in tumor tissues and peripheral blood were(2.34±0.75)×10~3,(7.00±1.17)×10~3 in Patients with NSCLC respectively.The levels of ASPP1 and ASPP2 mRNA in tissues and peripheral blood were(1.32±0.21)×10~4,(1.46±0.31)×10~4 and(1.38±0.19)×10~4,(1.28±0.18)×10~4 in control groups respectively.The ASPP1,ASPP2 mRNA levels in patients with NSCLC were significantly lower than those of control groups(t=2.58,3.94,3.62,3.76,P＜0.05).Before chemotherapy the levels of ASPP1 and ASPP2 mRNA in patients with NSCLc were(2.34±0.56)×10~3 and(6.64±0.72)×10~3,and after 2 periods of postoperative chemotherapy the levels were(3.66±0.64)×10~3 and(9.42±0.44)×10~3,the expression was higher than those of ehemotherapy before(t=3.02,4.50,P＜0.05).Conclusions The expression of ASPP1.ASPP2 mRNA in p53 mutant-type cell lines is higher than that in p53 wild-type cell lines.The expression of ASPP maybe has close relationship with chemotherapeutic sensitivity of NSCLC.In NSCLC patient chemotherapy process,the change of ASPP1 and ASPP2 mRNA expression may be related with chemotherapy medicine function.Enhance the expression of ASPP1 and ASPP2 will be beneficial to the tumot treatment.

On the teachers'leading role in physiology teaching / 中华医学教育探索杂志

The combination of teachers'leading role and the students'main role is a basic principle of teaching. This paper discusses how to play the leading role of teachers from pre-teaching preparation and classroom teaching to coaching students and answering the questions after school..

Obervations on the clinical efficiency of autologous bone marrow stem cell transplantation on chronic ischemic disease of lower limb / 中国普通外科杂志

Objective To explore the application of autologous bone marrow stem celI transplantation in the treatment of chronic ischemic disease of lower extremity and evaluate the effect.Methods Forty patients with chronic ischemic limbs were treated from January 2008 to April 2009.The bone marrow of each patient was stimulated by an injection of the recombinant human granulocyte macrophage colony-stimulatory factor(GCSF),300?g /d,for 2-3 days.Then,200 mL of bone marrow was withdrawn from the iliac spine and the stem cells were obtained.After the bone marrow separation and purification,they were transplanted into the more severely ischemic limb.After the transplantation,they were foIlowed up by phone once a month for six months.The skin temperature,transcutaneous oxygen pressure(TcPO2),digital subtraction angiography(DSA)and ankle/brachial index(ABI)were rechecked at 6 months later,and the symptoms of pain,cold,numbness,intermittent claudication and physical signs of ulcer and gangrene were also evaluated.Results All of the 40 patients were followed-up.At 6 months post-transplantation,the various indices were compared with before transplantation.(1)The skin temperature and TcPO2 had significante improvement (P0.05).(3)DSA and all of the clinical symptoms showed general improvement in more than 60% of cases.(4)There were no serious complications.Conclusions Transplantation of stimulated autologous bone marrow stem cells is effective in the treatment of ischemic disease of lower limb,which is a simple,safe and effective treatment for ischemic disease of lower limb.

TheEffectofIntermitentCyclicEtidronateDisodiumofDifferentDosesonExperimentalOsteoporosisinOvariectomizedRats / 中华骨科杂志

Thetherapeuticeffectsofintermitentcyclicetidronatedisodium(HEBP)ofdifferentdosesonovariectomy-inducedosteoporosiswerestudied.53femaleWistarrats,weighingwithanaver-ageof266gmwererandomlydividedinto5groups.Gourp1hadbilateralovariectomy(OVX)andwasgivenlowdoseHEBPof25mg/kgBW/day;group2hadOVXandgivenmediumdoseHEBPof36mg/kgBW/day;group3hadOVXandgivenhighdoseHEBPof51mg/kgBW/day;group4hadOVXandgroup5hadshamOVX.HEBPwasadministratedoralyduringfastingfor5daysfolowedbyarestperiodof25daysandtheregimewasrepeatedfor3times.Alanimalsweresacrificedat90thdayafterOVX.RadioimmunoassayofserumestradiolconfirmedthesuccessofOVX.TheserumCaandPcon-tent,AKPaseactivity,femoralrelativedryweight,CaandPcontentwereanalysedrespectively.Therighttibiaewereprocessedundecalcifiedforquantitativebonehistomorphometry.TheresultsshowedthatthebonecalciumcontentandtrabecularbonevolumeofOVX-ratstreatedwithHEBP,especialywiththelowdosegroupwerehigherthanthatofthesimplyOVX-ratandtheboneturnoverparameterssuchasAKPaseactivity,boneformationsurface,boneresorptionsurface,activeformationsurface,bonemineralappositionrateandboneformationratewerelowerthanthoseofthesimplyOVX-rat.TheresultsindicatetheHEBPcouldretardthedegreeofosteopososisthroughreducingtheelevatedboneresorptionandboneturnoverinducedbyOVX.Meanwhile,theresultssuggestthattheefectoflowdoseHEBP(25mg/kgBW/day)wasmoreefectivethanthatofthehighdose.