Combination of S-Detect and strain elastography in the conventional ultrasonic diagnosis of breast tumors / 中国综合临床

Objective:To explore the value of s-detect combined with elastography in the differential diagnosis of benign and malignant breast tumors.Methods:The ultrasound diagnosis data of 136 patients with breast mass examined by ultrasound in the First Affiliated Hospital of Shantou University Medical College from April 2018 to January 2020 were retrospectively analyzed. The breast lesions diagnosed as BI-RADS 3 or above were analyzed by conventional ultrasound, strain elastic imaging strain ratio (SR) and S-Detect Computer-aided Diagnosis (CAD) technology successively and were used for cross-sectional study. The corresponding benign and malignant judgment results were obtained, and the efficacy of individual diagnosis and combined diagnosis were compared and analyzed.Results:Conventional ultrasound, SR, S-Detect alone and conventional ultrasound+SR, conventional ultrasound+S-detect, conventional ultrasound + S-detect +SR combined diagnosis of breast tumors, the area under the receiver operating curve (AREA under the receiver operating curve) Characteristic curve, AUC) were 0.776, 0.839, 0.802, 0.861, 0.832 and 0.870, respectively. SR, S-Detect, conventional ultrasound +SR, conventional ultrasound + S-detect and conventional ultrasound +SR+ S-detect were compared with conventional ultrasound group, Z values were 1.49, 0.70, 2.76, 2.52, 2.96, respectively, and P values were 0.137, 0.484, 0.006, 0.012 and 0.003, respectively. The difference was statistically significant. The accuracy of conventional ultrasound +S-Detect+SR was the highest (84.1%), compared with pathological results, its Kappa value was 0.687, showing the strongest consistency. Conclusion:S-detect combined with strain elastography assisted by conventional ultrasound can significantly improve the diagnostic efficiency of benign and malignant breast tumors.

Bibliometric Analysis of Astragalus membranaceus in the Treatment of Diabetes Based on VOSviewer Software / 中国药房

OBJECTIVE：To provide referenc e for intuitively and c onveniently cognizing the research focus of Astragalus membranaceus in the treatment of diabetes. METHODS ：Using the method of bibliometrics ，the literatures about the treatment of diabetes by A. membranaceus were retrieved from CNKI full-text database during Jan. 1st，2000-Jun. 30th，2020. Bibliometric method was used to statistically analyze the number of articles ，authors and their research directions ，keywords，distribution of research institutions ，source journals ，frequency of citations ，fund funding ，etc. VOSviewer software was used for visual display. RESULTS：A total of 2 960 literatures were included ，and the number of literatures showed an increasing trend ；the author with the most literatures was Fan Ying from Liaoning University of TCM ，whose research direction was the effect of different effective parts of A. membranaceus on serum insulin and adiponectin in diabetic animal models ；in the keyword frequency analysis ，diabetic nephropathy（845 times），A. membranaceus （615 times），diabetes（587 times），A. membranaceus injection（350 times），diabetic peripheral neuropathy （303 times），qi tonifying drug （202 times）were hot topics. There were 10 institutions with more than 20 literatures，of which Nanjing University of TCM has published the most literatures （58 pieces）. Shaanxi Journal of Traditional Chinese Medicine ，Chinese Journal of Integrated Traditional and Western Nephropathy and Inner Mongolia Journal of Traditional Chinese Medicine were the journals with a large number of； literatures；Research Progress on Chemical Constituents and Pharmacological Effects of Astragalus membranaceus published from Chen guohui and others was cited most frequently，for 690 times；there are many projects funded by national scientific research funds （including National Natural Science Foundation of China and the National Key Basic m Research Special Foundation of China ）. CONCLUSIONS ：In the past 20 years， the level of researches about A. membranaceus in the treatment of diabetes have been steadilyimproved. However ，the distribution of literature is uneven and there are few high-quality core journals. Mainly ，there are relatively few clinical trials. It is suggested that researchers should explore the methods and ideas of A. membranaceus in the treatment of diabetes from the perspectives of macro clinical efficacy ，micro pharmacology ，A. membranaceus genetic resource bank and traditional Chinese medicine formulations.

Outpatient loyalty and its influential factors with high-end medical services in a comprehensive grade-A tertiary hospital / 中南大学学报(医学版)

To evaluate the loyalty and its influential factors for outpatients with high-end medical services in a comprehensive grade-A tertiary hospital.
 Methods: A total of 3 196 outpatients from July 2017 to June 2018, who visited the International Medical Department of a comprehensive grade A tertiary hospital, were investigated by a self-designed loyalty questionnaire. The Cronbach's alpha coefficient was 0.893. A third-party organization conducted the survey and 1 883 valid questionnaires were collected. Chi-square test and logistic stepwise regression model was used to analyze the influential factors for patients' loyalty.
 Results: The loyalty of outpatients with high-end medical services was 95.8%, and the satisfaction of all aspects of outpatient service was more than 94%. After adjusting for sex, age, the protective factors were diagnostic and therapeutic effect (OR=5.45, P<0.001), service level of nurses (OR=3.91, P=0.044), doctors' skills of communication and explanation (OR=2.95, P=0.046), degree of convenience (OR=3.04, P=0.038) and visits in recent three months (OR=2.11, P=0.008).
 Conclusion: The loyalty of outpatients with high-end medical services in a comprehensive grade A tertiary hospital is relatively high. Significant diagnostic and therapeutic effect, good service of nurses, good skills of communication and explanation, convenience and multiple visits are related to high loyalty.

Application values of double contrast enhanced ultrasonography in the diagnosis of micro vessel formation on gastric cancer / 中国医师杂志

Objective To discuss the application of double contrast enhanced ultrasonography in the diagnosis of micro vessel formation on gastric cancer.Methods 52 cases of patients with gastric cancer who scheduled for elective tumor resection on our hospital from August 2015 to October 2017 were enrolled in the study.Oral ultrasonic contrast agent,and intravenous contrast agent were used to assess the preoperative condition.The image feature of gastric ultrasound imaging was observed,and the time-intensity curve (TIC) parameters of gastric lesions and normal gastric were recorded,the relationship of gastric carcinoma TIC parameters and the expression of micro vessel density (MVD),vascular endothelial growth factor (VEGF) expression were analyzed.Results Comparison of gastric lesions and normal gastric tissue,there were statistically significant difference on the basic strength (BI),enhanced intensity (EI),peak intensity (PI),perfusion time (WIT) (P ＜ 0.05);Correlation analysis showed that EI,PI were positively correlated with MVD,BI,WIT was negatively correlated with MVD (P ＜ 0.05);EI,PI were positively correlated with VEGF,BI was negatively correlated with VEGF (P ＜ 0.05).Conclusions Gastric ultrasound imaging technology can accurately assess the blood perfusion characteristics of gastric carcinoma,with a certain value on the gastric cancer angiogenesis evaluation.

Molecular and phylogenetic analysis of Anaplasma spp. in sheep and goats from six provinces of China

Members of the genus Anaplasma are important emerging tick-borne pathogens in both humans and animals in tropical and subtropical areas. Here, we investigated the presence of Anaplasma spp. in 621 sheep and 710 goats from six provinces of China. Polymerase chain reaction (PCR) and DNA sequencing were conducted to determine the prevalence of Anaplasma (A.) phagocytophilum, A. ovis and A. bovis targeting the 16S ribosomal RNA or the major surface protein 4 gene. PCR revealed Anaplasma in 39.0% (240/621) of sheep and 45.5% (323/710) of goats. The most frequently detected species was A. ovis (88/621, 14.2% for sheep; 129/710, 18.2% for goats), followed by A. bovis (60/621, 9.7% for sheep; 74/710, 10.4% for goats) and A. phagocytophilum (33/621, 5.3% for sheep; 15/710, 2.1% for goats). Additionally, eight sheep and 20 goats were found to be infected with three pathogens simultaneously. DNA sequencing confirmed the presence of these three Anaplasma species in the investigated areas, and phylogenetic analysis indicated that there was geographic segregation to a certain extent, as well as a relationship between the host and cluster of A. ovis. The results of the present study provide valuable data that helps understand the epidemiology of anaplasmosis in ruminants from China.

In vitro evolutional selection of a combinatorial phage library displaying randomly-rearranged various binding domains of SpA and SpG with four human IgG subclasses / 生物工程学报

Protein A and protein G are two well-defined immunoglobulin (Ig)-binding proteins (IBPs), which show affinity for specific sites on Ig of mammalian hosts. Protein A and protein G contained several highly homologous IgG-binding domains which had been demonstrated to have function to bind to IgG. Whether combinations of Ig-binding domains of various IBPs could produce useful novel binding properties remains interesting. We constructed a combinatorial phage library which displayed randomly-rearranged A, B, C, D and E domains of protein A, B2 and B3 domains of protein G. Four rounds molecular evolution of this library directed by all four human IgG subclasses respectively generated a common arrangement of D-C respectively which didn't exist in SpA. The dynamic loss of control phages and increase of the phages displaying two or more binding domains, especially the selective enrichment of D-C and strict selection of its linking peptides demonstrated the efficient molecular evolutions and the significance of the selected D-C arrangement. The phage binding assays confirmed that D-C possessed a binding advantage with four human IgG subclasses compared to SpA. In this work, a novel combination of Ig-binding domains, D-C, was obtained and presented the novel Ig binding properties which provided a novel candidate molecule for the purification, production and detection of IgG antibodies and a new approach for the further study of structures and functions of IBPs.

Von Willebrand factor research on related factor of coagulation abnormalities in type 2 diabetic nephropathy / 中国综合临床

Objective To study the early changes of the coagulation system in type 2 diabetic nephropathy.Methods Sixty-two cases of patients with type 2 diabetic nephropathy were divided into two groups:normal albuminuria group ( N-UAlb group,UACR ＜ 30 mg/g,32 cases ),microalbuminuria group ( MUAlb group,UACR:30～300 mg/g,30 cases).Thirty healthy persons constituted a control group (NC group).Fibrinogen( FIB ),antithrombin Ⅲ ( AT-Ⅲ ),protein C ( PC ),protein S ( PS ) were measured by coagulation analyzer,while yon willebrand factor (vWF) and platelet granule membrane protein 140 (GMP-140) were detected by ELISA assay,platelet count (PLT),mean platelet volume(MPV),platelet hematocrit (PCT),platelet distribution width(PDW) by hematology analyzer.Results The level of fibrinogen,GMP-140 and vWF in the M-UAlb group were (4.20 ± 1.53 ) g/L,( 30.03 ± 7.77 ) μg/L,and ( 315.53 ± 47.24 ) ％ respectively,vwhich were significantly higher than those in the N-UAlb group [ ( 3.21 ± 0.89 ) g/L,( 18.22 ± 5.08 ) μg,/L and ( 191.88 ± 57.25 ) ％ respectively ] and the NC group [ ( 2.75 ± 0.53 ) g/L,( 14.26 ± 2.29 ) μg/L and ( 138.12 ± 61.27 ) ％ respectively ] ( F =5.42,10.42,30.44,P ＜ 0.05 or 0.01 ).The fibrinogen,vWF,GMP-140 were positively correlated with UACR ( r =0.313,P ＜ 0.05 ; r =0.620,P ＜ 0.01 ; r =0.680,P ＜ 0.01 ) and PC was negatively correlated with UACR ( r =-0.255,P ＜ 0.05 ).Conclusion Hypercoagulable state in diabetic nephropathy is associated with the high fibrinogen,endothelial dysfunction and platelet activation,and these changes have already emerged in patients without albuminuria.This might mind us that we should strengthen anticoagulant therapy on patients when they are not progressing to albuminuria.

Risk Factors for Leukoaraiosis: A Logistic Regression Analysis / 中国康复理论与实践

@#Objective To investigate the risk factors for leukoaraiosis. Methods 204 cases of inpatients were registered. The severity of leukoaraiosis was as the dependent variable, the possible risk factors were as independent variables, unconditional logistic regression was analyzed with SAS 9.2 software, significant level α=0.10. Results 5 factors, that were carotid stenosis, age, low density lipoprotein cholesterol,apolipoprotein B and apolipoprotein A, were included, in which the former 4 were risk factors (OR>1, P<0.05), the latter was protection factor (OR=0.715, P=0.0993). Conclusion The vascular risk factors contribute to formation of leukoaraiosis, and carotid stenosis relate to leukoaraiosis.

Constructing a phage-displayed random mutation library of HIV-1 Tat38-61 at the sites of 51 and 55 amino acids in basic region / 生物工程学报

We constructed a phage-displayed random mutation library of Tat38-61(51N/55N), for studying the molecular evolution screening of HIV-1 Tat38-61 epitope. We used primers containing the random nucleotide sequences, and introduced the random mutations at the sites of 51 and 55 amino acids coding sequences into full-length Tat sequences by overlapping PCR. With the randomly mutated full-length Tat as template, the Tat38-61(51N/55N) mutants which contained recognition sequences for the Xba I in both ends were amplified by PCR using the designed primers. The mutants were cloned into Xba I site in the phagemid vector pCANTAB5S, then the recombinants were transformed into E. coli TG1, a phage-displayed the random mutation library of Tat38-61(51N/55N) was constructed by the rescue of help virus M13KO7. The results showed that the library consisted of about 5.0 x 10(6) colonies and the phage library titer was 2.65 x 10(12) TU/mL. More than 56.50% colonies in the library were positive for insertion. Sequence analysis showed that the nucleotides encoding amino acids at the sites of 51 and 55 distributed randomly. The constructed mutation library could meet the requirements for the following molecular evolution screening, and might prepare the Tat mutants for the further study of new Tat vaccine candidates.

Preparation of a toxicity fusion protein targeting to CD123 on leukemia stem cell / 白血病·淋巴瘤

Objective To construct a fusion protein that used for treatment of resistance and palindromia in leukemia and studied its biological activity. Methods IL-3 and LP gene fragments were amplified by PCR. After enzymatic digestion and T4 ligation, the fusion gene was cloned into expression vector pAYZ. The product was purified by exchange chromatography and anti-Etag affinity chromatography. IL3-G4SLP fusion protein was analyzed by SDS-PAGE and Western blot. Protein biological activity was detected by FACS. Results The fusion protein was expressed as soluble protein by E.Coli 16C9. The protein expression level was about 1 mg/L, its purity was over 95 %, and the expression level was about 1 mg/L. The fusion protein can combined specificely with CD123 on leukemia stem cells. Conclusion Fusion protein IL-3-G4S-LP can target on leukemia stem cells and maybe as a potential drug used for treatment of resistance and palindromia in leukemia.

Clinical analysis of hysterectomy in obstetric emergency / 中国基层医药

Objective The indication of hysterectomy in obstetrics emergency was studied in order to defend and decrease the incidence of hysterectomy.Method 27 cases with hysterectomy in obstetric emergency were retrospectively analyzed.Results The all indication of 27 cases of hysterectomy was endometrorrhagia in obstetric emergency.The first cause of endometrorrhagia was placental complication,the second cause was puerperal disseminated intravascular coagulation,the third cause was puerperal uterine anonym.Conclusion In order to decrease the incidence of hysterectomy in obstetric emergency,the family planning and health work of perinatal period should be done goodly,the antenatal examination should be strengthened and disseminated intravascular coagulation should be made a diagnosis and treatment timely.

Construction and expression of disulphide stabilized anti-CD3/anti-Pgp diabody / 生物工程学报

We constructed and expressed an anti-CD3/anti-Pgp (P-glycoprotein) diabody previously. However, the two chains of diabody are associated non-covalently, resulting in being capable of dissociating. The aim of this study is to enhance the stability of the diabody. We introduced cysteine residues into the CD3 or Pgp V-domain to covalently lock the two chains together. The disulphide crosslinked diabody were expressed by Escherichia coli (E. coli) 16C9 and purified by a cation exchange column and an anti-Etag affinity chromatography. The purified proteins were verified through SDS-PAGE. Flow cytometry (FCM) was used to analyse the binding properties, competitive binding capacity and stability in vitro. The dsPpg-diabody failed to form disulphide bond properly. The designed disulphide bridge between the different chains of dsCD3-diabody was formed correctly. FCM demonstrated the dsCD3-diabody has specific antigen binding activity, the same binding activity and competitive binding activity as its parent diabody. The dsCD3-diabody retained the full activity even after 72 h incubation at 37 degrees C in human serum, in contrast, the parent diabody began to lose activity after only 1 h and lose all its activity 24 hours later. The induced disulphide bond in the CD3 V-domain effectively enhanced the stability of anti-CD3/anti-Pgp diabody. The method of stabilizing a diabody by introducing a disulphide bond into is practical.

Construction,expression and in vitro specific killing activity of a recombinant fusion protein:anti-CD20Fab-LDM / 中国药理学通报

Aim To construct and express anti-CD20Fab-LDP,generate anti-CD20Fab-LDM and identify its biological activity.Methods PCR and overlapping PCR were used to construct anti-CD20Fab-LDP.DNA sequence was analyzed by the Terminus of Dideoxy Nucleotide.The product was purified by affinity chromatography and analyzed by Western blot and its antigen-binding activity was examined by FACS.Specific killing activity in vitro of anti-CD20Fab-LDM was analyzed by MTT.Results The data of DNA sequence showed that anti-CD20Fab-LDP was correct.The fusion protein was recovered in high yield(up to 4 mg·L~(-1))after proteinG purification.The fusion protein could bind to Raji cells(CD20+),and similar affinity data were obtained with anti-CD20Fab.Anti-CD20Fab-LDP showed potent cytotoxicity to Raji cells with IC_(50) values of 0.9×10~(-10) mol·L~(-1).Conclusions Anti-CD20Fab-LDP with high level expression was successfully obtained and could bind to Raji cells cells.Anti-CD20Fab-LDM showed specific killing activity to Raji cells in vitro.

Soluble-expression, purification and activity analysis of extracellular domain III of flt1 / 生物工程学报

To prepare a soluble human extracellular III domain of Flt1 and analyze its biological activity. The gene encoding extracellular domain III of Flt-1 was cloned into the expression vector pAZY by RT-PCR from human umbilical vein endothelial cell (HUVEC), and induced to express in Escherichia coli by low phosphoric medium, the product was purified by E-tag affinity chromatography. SDS-PAGE and Western blotting analysis showed that Flt-1 gene domain III gene was expressed in E. coli and the yield of the soluble fusion protein was about 1.10 mg/L. Enzyme-Linked ImmunoSorbent Assay (ELISA) revealed that the Flt-1 domain III was able to bind to VEGF165 dose-dependently. Monolayer denudation assay and Transwell assay showed that the fusion protein could inhibit HUVECs migration induced by conditional medium with 50 ng/mL VEGF165 and 100 ng/mL bFGF. In conclusion, Flt-1 gene domain III gene has been successfully cloned and expressed in E. coli, which will be useful in both the research on the function of Flt-1 gene domain III and preparation of anti-Flt-1 monoclonal antibody in the future.

Investigation in the requirement for health education during and after hospitalization of patients with cerebral apoplexy / 中国实用护理杂志

Objective To investigate and analyze the requirement for health education during and after hospitalizadon of patients with cerebral apoplexy.Methods 150 sober patients with cerebral apoplexy from department of neurology were investigated by questionnaires and the results were analyzed. Results The education content that most patients wanted to understand during hospitalization was treatment method and limbs activity(83.6%and 82.2%);The health education style that they prefered was to communicate directly with doctors and nurses(74.0%);The education content after hospitalization that most patients required was self-nursing knowledge.clinical manifestation and first aid when relapse(90.4%,87.7%and 87.7%).The health education style that they most needed after hospitalization Was that Some reference books would he recommended to them (56.2%).The time choice for health education was consultation whenever they had problems.Conclusion Medical workers should supply selective education and instruction according to the health education requirement and style at different stages of patients with cerebral apoplexy.

The application value of ultrasonography in the victims of Wenchuan earthquake ZHANG Hai-feng, / 中华超声影像学杂志

Objective To investigate the application value of uItrasonography in the classifying patients,preventing and treating the major earthquake-induced complications.Methods Seven hundred and forty-three patients were divided into four sorts by region of injuries:thoracic cavity,abdominal cavity,blood vessels of limbs and crush.According to the admission time,there were two phases and the data was analyzed respectively.Results Abnormal ultrasonic image was found in 218 of all patients,with positive ratio 29.3%.In the first phase,the morbidity of crush-induced hematoma was the highest,followed by pleural effusion,spleen rupture,liver fracture,injury of blood vessels,renal damage,intestinal rupture and crush syndrome with renal failure.Compared with that of the first phase,the morbidity of the injury of blood vessels and crush syndrome with renal failure increased in the second phase.Conclusions It was important to analyze the earthquake-induced injury because the major earthquake often cause the damage of multiple organs.

Inhibitory effect of arsenic trioxide on angiogenesis of chick embryo chrioallantoic membrane / 中国癌症杂志

Background and purpose:Arsenic trioxide(As_(2)O_(3)) injection actually has an effect on solid tumors such as hepatoma in the clinic.In order to find out its mechanism of action,we studied the action of arsenic trioxide injection on angiogenesis of chick embryo chrioallantoic membrane(CAM).Methods:The effect of arsenic trioxide injection on angiogenesis was investigated by CAM model and computer image analysis.Results:Administered at three different concentrations of arsenic trioxide injection at 10,20 and 40,3 days later,the vessel area were 25.66%?4.17%,24.74%?2.54% and 21.51%?6.70%,respectively.Compared to the NS control group(vessel area was 30.68%?(4.64%)),there was an obvious difference(P0.05 among the three different concentration groups).Conclusions:arsenic trioxide injection has a strong inhibitory effect on angiogenesis,which may be used in suppressing cancer angiogenesis.

The impact of 5-Aza-CdR on demathylation of transcription regulation of E-cadherin gene in tumor cell line / 中国癌症杂志

Background and purpose:To explore the possibility of genetic re-expression silenced by DNA aberrant hypermethylation which is a common epigenetic modification in carcinogenesis. 5-Aza-CdR, an inhibitor of DNA methylation, was used to determine the effects of expression of tumor suppressor gene E-cadherin in tumor cell lines. Methods:Methylation specific PCR(MSP) was utilized to examine methylation status of E-cad gene on breast carcinoma cell line MDA-MB-435 before and after the treatment with 5-Aza-CdR. Immunohistochemistry(IHC) was used to test the expression of E-cad protein. Semi-quantitative RT-PCR method was used to detect the changes of E-cad mRNA.Results:1).E-cad methylation was positive(116bp) and unmethylation was negative on MDA-MB-435 cell before the treatment with 5-Aza-CdR. After being treated with 5.0umol/L 5-Aza-CdR for 3 days, methylation turned negative and unmethylation positive bands(97bp) were detected. 2).The E-cad protein expression was not detected by immunohistochemistry on MDA-MB-435 cell before the treatment, while E-cad staining was positive on the cell membrane after the treatment. 3). The E-cad mRNA failed to be amplified in cells before the treatment. After incubation at variable concentrations of 0.5 ?mol/L, 1.0 ?mol/L, 2.0 ?mol/L and 5.0 ?mol/L 5-Aza-CdR for 3 days, respectively, E-cad mRNA expression was detected on the fourth day in a dose-dependent manner. Correlation between the mRNA expression level and the agent concentration was observed.Conclusions:The demethylation agent 5-Aza-CdR can reverse the aberrant E-cad methylation status in MDA-MB-435 and re-expressed E-cad mRNA and protein.

Effect and mechanism of astragalus polysaccharides on apoptosis of the islet beta cell in diabetes mellitus rats / 中国药理学通报

Aim To probe the mechanism of the therapeutic effect of APS against DM rats by measuring the level of TNF-?,as well as observing the change of caspase-3 protein in pancreatic beta cells.Methods Thirty DM rats induced by STZ were randomly divided into three groups:DM group,APS low dosage group,APS high dosage group,and another 10 normal rats were taken as the control group.The drug was given for 6 weeks.The research included measuring the level of TNF-? in serum and the expression of caspase-3 protein in pancreatic beta cells.Results ① The level of TNF-? was higher in model group than that of the normal group(P

Regulatory effect of catalpol from Radix Rehmanniae on M_2 receptor density in M_2 receptor transfected CHO cells / 中国药理学通报

Aim To investigate the effect of catalpol from Radix Rehmanniae on M_2 receptor density in CHO cells transfected with gene of M_2 receptors(CHO m2).Methods Cultured CHOm2 cells were randomly divided into 4 groups:three concentrations of catalpol :10-6、10-5、10-4 mol?L-1,and saline control.After addition of catalpol and saline for 72 h,M_2 Receptor density was measured by single point 3H-NMS binding assay,the content of protein was measured with Lowry's method.Competitive binding assay using the binding system of 3H-NMS was performed to address the question about whether catalpol could occupy the M receptor binding site.Addition of catapol to brain homogenate and measuring the enzyme activity with the Ellman's colorimetric method were performed to address the question about whether catalpol could in-hibit acetylcholinesterase activity.Results Catalpol can elevate the M_2 receptor density in CHO m2 cells significantly at the doses of 10-5、10-4 mol?L-1(P