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In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe3O4@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe3O4@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe3O4@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T2 magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.
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Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
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Humanos , Embarazo , Femenino , Lupus Eritematoso Sistémico/patología , Transducción de Señal , Ácido N-Acetilneuramínico/metabolismo , Inmunoglobulina G , Células Dendríticas/patologíaRESUMEN
[This corrects the article DOI: 10.1016/j.apsb.2022.08.024.].
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We report a case of coronavirus disease 2019 (COVID-19) patient who was cured by oral administration of nirmatrelvir/ritonavir (Paxlovid). The patient was treated with Paxlovid after being first infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5 variant. On the 11th day after SARS-CoV-2 nucleic acid test turned negative, SARS-CoV-2 nucleic acid test was positive again, and the threshold of nucleic acid cycle number was equivalent to that of the first infection. The results of two whole gene sequencing showed that it was the same virus strain infection, suggesting that the case was re-positive. Without specific treatment, SARS-CoV-2 nucleic acid detection in nasopharyngeal swab turned negative. It is not uncommon for Paxlovid to recover after treating COVID-19, and most of the patients can recover without specific treatment. However, it is necessary to further study the mechanism that may lead to the recovery of SARS-CoV-2.
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Humanos , COVID-19 , SARS-CoV-2/genética , Administración Oral , Ácidos NucleicosRESUMEN
COVID-19 is a huge threat to global health. Due to the lack of definitive etiological therapeutics currently, effective disease monitoring is of high clinical value for better healthcare and management of the large number of COVID-19 patients. In this study, we recruited 37 COVID-19 patients, collected 176 blood samples upon diagnosis and during treatment, and analyzed cell-free DNA (cfDNA) in these samples. We report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA characteristics reflect patient-specific physiological conditions during treatment. Further analysis on tissue origin tracing of cfDNA reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, we demonstrate the translational merit of cfDNA as valuable analyte for effective disease monitoring, as well as tissue injury assessment in COVID-19 patients.
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Objective:To explore the role of decoy receptor 3(DcR3) and its ligand tumor necrosis factor ligand-related molecule 1A(TL1A) in the treatment of pancreatic cancer implanted tumors in nude mice with CD 4 and CD 8 double negative T cells (DNT cells). Methods:DNT cells derived from peripheral blood of healthy volunteers were cultured in vitro by antibody adsorption method. A nude mouse model of pancreatic cancer implantation was established and randomly divided into DNT cell treatment group (tail vein injection of 1×10 8/ml DNT cell suspension), gemcitabine treatment group (tail vein injection of 50 mg/kg gemcitabine) and control group (no treatment). The tumor volume and weight in each group were measured after 50 days. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of DcR3 and TL1A in nude mice implanted tumor tissues in each group, and TUNEL method was used to detect the apoptosis rate of nude mice implanted tumors in each group. Results:The tumor volume of the DNT cell treatment group, gemcitabine treatment group, and control group was (670.28±124.54), (604.60±179.16), (1738.80±391.39)mm 3, and the tumor weight was (225.60±8.12), (222.69±8.73), (265.07±10.76)mg, and the volume and weight of implanted tumors in the DNT cell treatment group and gemcitabine treatment group were significantly lower than those in the control group, and the differences were statistically significant (all P values <0.001). The expression levels of DcR3 protein and mRNA in the DNT cell treatment group and gemcitabine treatment group (0.56±0.02, 3.74±0.19; 0.57±0.03, 3.40±0.39) were significantly higher than those in the control group (0.39±0.04, 0.92±0.05), while the expression levels of TL1A protein and mRNA (0.41±0.03, 0.83±0.11; 0.40±0.05, 0.79±0.08) were significantly lower than those of the control group (0.81±0.05, 1.70±0.36), and the differences were statistically significant (all P values <0.001). The apoptotic rate of implanted tumors in the DNT cell treatment group was (53.2±11.2)%, and that in the gemcitabine treatment group was (56.2±8.6)%, which were significantly higher than the control group (10.3±3.2)%, and the differences were statistically significant ( all P values <0.001). Conclusions:DNT cells had a significant inhibitory effect on the growth of pancreatic cancer implanted tumors in nude mice. DcR3-TL1A may be involved in the anti-tumor mechanism of DNT cells.
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Objective:To investigate the effectiveness of enhanced recovery after surgery (ERAS) concept in perioperative period of retroperitoneal laparoscopic radical nephrectomy.Methods:The clinical data of 189 patients who underwent retroperitoneal laparoscopic radical nephrectomy from October 2015 to July 2021 were retrospectively analyzed. According to different perioperative management methods, they were divided into two groups: ERAS group ( n=97) and traditional group ( n=92). Patients of ERAS group were managed by the ERAS concept during the perioperative period, patients of traditional group were managed by the traditional method during the perioperative period. First drinking time after surgery, first exhaust time, 24 h postoperative pain score, first activity time out of bed, indwelling time of urinary catheter, indwelling time of drainage tube, postoperative hospital stay, incision length and complications of pneumonia and venous thrombosis were recorded and compared between the two groups. Measurement data were expressed as mean ± standard deviation ( Mean± SD), and independent sample t-test was used for comparison between groups; count data comparison between groups was by Chi-square test or Fisher exact probability method. Results:There were no significant differences in age, gender, body mass index, tumor side, tumor diameter, maximum diameter of samples, T stage, diabetes and hypertension from between two groups ( P >0.05). In ERAS group, the time of first drinking water after surgery was (3.8±1.4) h, the time of first anal exhaust was (10.2±2.5) h, the 24 h pain score was (2.4±1.0), the time of first activity out of bed after surgery was (18.8±3.6) h, the indwelling time of urinary catheter was (19.8±3.7) h, the indwelling time of drainage tube was (3.4±0.5) d, the surgical incision length was (7.2±0.9) cm, and the postoperative hospital stay was (5.5±0.6) d. In the traditional group, the time of first drinking water after surgery was (21.2±4.2) h, the time of first anal exhaust was (20.1±4.3) h, the 24 h pain score was (5.4±1.0), the time of first activity out of bed after surgery was (32.8±7.8) h, the indwelling time of urinary catheter was (55.7±8.0) h, the indwelling time of drainage tube was (4.2±0.5) d, the surgical incision length was (13.6±1.5) cm, and the postoperative hospital stay was (7.2±1.3) d. There were statistically significant differences in these indexes between the two groups ( P<0.05). Conclusion:The clinical application of the concept of ERAS during the perioperative period can promote the rapid postoperative recovery of patients undergoing retroperitoneal laparoscopic radical nephrectomy, and can effectively reflect the minimally invase advantages of retroperitoneal laparoscopic technology.
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Double negative T cell is a kind of special regulatory T cell with a cell phenotype of TCR + CD3 + CD4-CD8-.It plays an important role in many diseases such as autoimmune diseases,tumor immunity,transplant rejection and allergic diseases by expressing unique surface markers and secreting unique effector factors.Pancreatic cancer is a poorly diagnosed malignant tumor of the digestive system,and its early diagnosis rate is not high,the treatment is still based on radical tumor resection.Although the surgical technique is continuously improved,the 5-year survival rate has not improved significantly.At present,there is still a lack of effective treatment.In recent years,double negative T cell has become a new research hotspot in tumor immunity,bringing new hope for the treatment of pancreatic cancer.According to different types of T cell antigen receptor (TCR) expression,double negative T cell can be divided into TCRαβT cell and TCRγδT cell.This review focuses on the source of double negative T cell and possible molecular mechanisms in cancer therapy.
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Objective To investigate the value of post processing technique of MSCT in the diagnosis of bile duct stones.Methods 89 cases with high density bile stones were collected.All of the images were reconstructed by using surface reconstruction(CPR),multiplanar reconstruction(MPR),volume reconstruction(VR), to clearly show the location, size, number and shape of bile duct stones, and provide accurate image information for clinic.Results 396 cases of bile duct stones were detected in all of the 89 patients,after treatment,the reconstructed image of could accurately show the location,size,number and shape of stones.Conclusion Post-processing technique of MSCT can provide accurate image information for the diagnosis of the the biliary stone,and improve the effectiveness and safety of the operation.
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Dendritic cells (DCs) are important immune cells linking innate and adaptive immune responses. DCs encounter various self and non-self antigens present in the environment and induce different types of antigen specific adaptive immune responses. DCs can be classified into lymphoid tissue-resident DCs, migratory DCs, non-lymphoid resident DCs, and monocyte derived DCs (moDCs). Recent work has also established that DCs consist of developmentally and functionally distinct subsets that differentially regulate T lymphocyte function. The development of different DC subsets has been found to be regulated by a network of different cytokines and transcriptional factors. Moreover, the response of DC is tightly regulated to maintain the homeostasis of immune system. MicroRNAs (miRNAs) are an important class of cellular regulators that modulate gene expression and thereby influence cell fate and function. In the immune system, miRNAs act at checkpoints during hematopoietic development and cell subset differentiation, they modulate effector cell function, and are implicated in the maintenance of homeostasis. DCs are also regulated by miRNAs. In the past decade, much progress has been made to understand the role of miRNAs in regulating the development and function of DCs. In this review, we summarize the origin and distribution of different mouse DC subsets in both lymphoid and non-lymphoid tissues. The DC subsets identified in human are also described. Recent progress on the function of miRNAs in the development and activation of DCs and their functional relevance to autoimmune diseases are discussed.
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Animales , Humanos , Enfermedades Autoinmunes , Alergia e Inmunología , Diferenciación Celular , Alergia e Inmunología , Células Dendríticas , Biología Celular , Alergia e Inmunología , MicroARNs , Alergia e Inmunología , Monocitos , Biología Celular , Alergia e Inmunología , Linfocitos T , Biología Celular , Alergia e InmunologíaRESUMEN
Objective To explore the correlation between anxiety and the severity of myocardial brigde of left anterior descending. Methods 118 patients with isolated myocardial bridge of left anterior descending underwent coronary angiography were evaluated with Self-rating Anxiety Scale (SAS). They were divided into anxiety group and non-anxiety group. Results There were 48 cases in the non-anxi-ety group, and 70 cases in the anxiety group. The stricture of myocardial bridge was more serious in the anxiety group than in the non-anxi-ety group (P<0.01), and positively correlated with the SAS score (r=0.765, P<0.01). Conclusion The anxiety is frequent in patients with iso-lated myocardial bridge of left anterior descending, and correlated with the severity of myocardial bridge.
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@#Objective To explore the correlation between anxiety and the severity of myocardial brigde of left anterior descending. Methods 118 patients with isolated myocardial bridge of left anterior descending underwent coronary angiography were evaluated with Self-rating Anxiety Scale (SAS). They were divided into anxiety group and non-anxiety group. Results There were 48 cases in the non-anxiety group, and 70 cases in the anxiety group. The stricture of myocardial bridge was more serious in the anxiety group than in the non-anxiety group (P<0.01), and positively correlated with the SAS score (r=0.765, P<0.01). Conclusion The anxiety is frequent in patients with isolated myocardial bridge of left anterior descending, and correlated with the severity of myocardial bridge.
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Objective To evaluate the effect of early continuous renal replacement therapy(CRRT)on patients with acute kidney injury(AKI)induced by severe sepsis. Methods A prospective study was conducted. 160 patients with AKI induced by severe sepsis admitted to intensive care unit(ICU)of Qingyuan People's Hospital between October 2009 and June 2013 were enrolled. According to the starting time of CRRT,the patients were randomly divided into two groups:an earl y treatment group and a regular treatment group(each,80 cases). All patients were treated in accordance with the principle of the cluster of severe sepsis. In early treatment group,the patents began to receive CRRT when the amount of urine output was0.05). Early treatment group and regular treatment groups of creatinine recovery time were similar(day:5.1±1.3 vs. 5.2±1.2). 28-day survival rate in early treatment group was higher than that in regular treatment group(41.2%vs. 35.0%),but there was no statistically significant difference(P>0.05). Conclusion It is found that there is no evidence to suggest that early CRRT may improve the prognosis of the patients with AKI induced by severe sepsis,but it may be in favor of shortening the time of urine recovery,length of stay in ICU,length of organ support and length of dialysis.
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Objective To evaluate the diagnostic value of ultrasonic elastography (UE) in benign and malignant thyroid nodules by Meta analysis. Methods Computer was used to search China national knowledge infrastructure(CNKI), Wanfang database, and relevant Chinese articles about UE in assessing diagnostic accuracy of benign and malignant thyroid nodules were collected. According to the diagnostic test criteria recommended by Cochrane Screening and Diagnostic Test Group, the literatures were screened and feature information was included in the study. The quality evaluation tool of diagnostic test accuracy(QUADAS-2) was used to assess the quality of the literatures; Meta analysis was performed with Meta-DiSc 1.4 software, and receiver operating characteristic curve(SROC) was drawn. Results According to the key words, two hundred and thirty-one articles were retrieved initially, and finally 16 articles were included after screening; the quality of five articles was grade A; eight was grade B; and three was grade C. Sixteen articles contained 1 325 patients with 1 641 thyroid nodules. The pooled sensitivity and specificity were 0.87 [95%confidence interval (CI): 0.84 - 0.89] and 0.84 (95%CI: 0.82 - 0.86), respectively; the pooled positive and negative likelihood ratios were 5.85 (95%CI:4.47-7.65) and 0.17(95%CI:0.13 - 0.21), respectively; the area under the curve of SROC was 0.93, standard error(SE) =0.01. Conclusion The results of meta-analysis suggest that UE has high value in the diagnosis of benign and malignant thyroid nodules.
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Group cooperative learning is a modem education model.In order to prompt the exploration of the education model in the practice lesson of epidemiology,group cooperative learning method was adopted.There are five key steps for the conduction of group cooperative learning,including task assignment(learning points,research topics,and infomation retrieval) 3-5 days before the task is done,reviewing the key theoretical contents,requiring students to refer to inf'ormation; organizing students to review the theoretical knowledge; students' discussion and making PPT in small groups,team report by representatives,and summing up by teachers at last.Teachers should pay attention to the rationality of interior structure and group members' work.Choosing a proper research subject is very important for arousing the students' interest of study.Based on the active classroom atmosphere and students' feedback,group cooperative learning method plays an important role in promoting the teaching efficiency of practice lesson.However,there are still insufficiencies to be improved.
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Objective To detect the expression of COX-2 and p53 in breast carcinoma tissue and investigate their associations with clinical prognosis.Methods The expression of COX-2 and p53 was carried out in 16 cases of normal epithelial tissue and 152 cases of breast carcinoma tissue using immunohistochemistry SP method.The correlation of their expression with clinical characteristics was analyzed using SPSS software 16.0.Survival analysis was used to investigate their effects on tumor prognosis.Results No positive COX-2and p53 expressions were observed in normal epithelial tissue.Among 152 patients,89 (58.6 %) were positive staining rete for COX-2 and 93 (61.18 %)were shown p53 expression, with a statistically significant associations between expressions of COX-2 and p53 and breast cancer (r =0.426,P < 0.01).The COX-2 and p53 expressions were significantly correlated with pathological grade, clinical stage, lymph node or distant organ metastasis.There was a statistically significant correlation between COX-2 and p53 expression and pathological grade Ⅰ / Ⅱ.The 5-year progress-free survival (PFS) rate in patients with COX-2 over-expression was 61.3 %, which was remarkably lower than that in those with low COX-2 expression.There was no statistically significant difference of 5-year PFS between positive and negative p53 expression.A shorter 5-year PFS was seen in patients with co-expression of COX-2 and p53 than in those with either COX-2 or p53positive expression alone and also than in those with both COX-2 and p53 negative expression.Conclusion Detection of the expressions of COX-2 and p53 can be used to predict the prognosis of breast cancer.
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Objective To investigate the effect of insulin-like growth factor-1 (IGF-1) on intercellular adhesion molecule-1 (ICAM-1) expression in rat model with congestive heart failure (CHF). Methods The model of CHF in male Sprague-Dawley rat was established using subcutaneous injection of isoproterenol. The rats were randomized into model group (n = 10),angiotensin converting enzyme inhibitors (ACEI) group ( n=10) and IGF- 1 group ( n = 10). The rats injected with saline were used as normal controls (n=10). The haemodynamic parameters of rats in each group were detected. The concentration of plasma angiotensin Ⅱ (Ang Ⅱ ) and expression of ICAM-1 in rat myocardium were determined by radioimmunoassay and immunohistochemistry,respectively. Results Compared with model group, ACEI and IGF-1 could rescue the diversities of hemodynamic parameters. In addition, ACEI and IGF-1 could also significantly down-regulated concentration of plasma Ang Ⅱ and inhibited ICAM-1 expression. Compared with ACEI, IGF-1 more significantly inhibited ICAM-I expression (0. 804 ± 0. 024 vs. 1. 254 ± 0. 059) and down-regulated concentration of plasma AngⅡ [(369.2±65.0) μg/L vs. (384.4±56.2) μg/L]. Conclusions IGF-1 can suppress ICAM-1 expression in rat model with CHF induced by isoproterenol. This effect may be related to inhibiting activation of RAS system.
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@#Objective To study the relationship between serum pregnancy-associated plasma protein-A(PAPP-A)and plaque stability of coronary lesion.Methods Levels of serum PAPP-A were measured among 230 patients seemed as coronary heart disease(CHD)including 50 cases with acute myocardial infraction(AMI),110 cases with unstable angina pectoris(UAP),40 cases with stable angina pectoris(SAP)and 30 cases without CHD as control by enzyme-linked immunoassay(ELISA).Anginographic morphology of the coronary lesion was assessed in patients with CHD.Then,the serum PAPP-A levels were compared among different types of CHD and plaque.Results Serum PAPP-A levels were significantly higher in the AMI group(26.13±4.65)mIU/L and UAP group(20.37±5.78)mIU/L than in the SAP group(12.82±3.94)mIU/L and without CHD group(10.70±2.86)mIU/L(P<0.01,UAP group vs AMI group,P<0.05).Serum PAPP-A levels were significantly higher in the type Ⅱ lesions(24.52±4.82)mIU/L than in the other type lesions group(16.82±5.37)mIU/L and in the control group(10.70±2.86)mIU/L(P<0.01).Conclusion Serum PAPP-A level was closely associated with plaque stability of coronary lesion.
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@#Objective To investigate the effect of Puerarin on expression of C-reactive protein(CRP)in iliac artery of atherosclerotic rabbits.Methods Twenty male New Zealand white rabbits were divided into the normal control group(n=6,fed on a normal diet),basic control group(n=8,fed on a cholesterol diet)and Puerarin group(n=8,fed on a cholesterol diet).The balloon injury of iliac arteries was performed in animals of the basic control group and Puerarin group,and the animals of the Puerarin group were injected with Puerarin(25 mg/kg/d per rabbit)after injury.Four weeks after balloon injury,untreated and balloon injury iliac arteries were harvested for immunocytochemical staining.The mRNA and protein expression of CRP were tested by RT-PCR and immunucytochemistry.Results The mRNA and expression of CRP in atheroseclerotic plaque of iliac artery in the Puerarin group was significantly lower than that in the basic control group(P<0.01).Conclusion Puerarin can make atheroseclerotic plaque stable by regulating of the expression of CRP in iliac artery of atherosclerotic rabbit.
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AIM: To investigate the apoptosis of implanted tumor of primary human gastric cancer cells in nude mice induced by genistein and the relation between this apoptosis and expression of bcl - 2 and bax. METHODS: Establishing a transplanted tumor model by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. The different doses of genistein (0.5mg/kg, 1mg/kg and 1.5 mg/kg ) were directly injected beside tumor body respectively,for six times at an interval of two days. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alteration by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis - regulated gene bcl - 2 and bax by immunohistochemical staining and RT- PCR. RESULTS: Genistein could significantly inhibit carcinoma growth when it was injected near the carcinoma. Genistein induced implanted tumors cells to undergo apoptosis with apoptotic characteristics by transmission electron microscope. The apoptosis index of above three groups was increased progressively. Positive rate of Bcl - 2 protein of above three groups was decreased progressively and positive rate of Bax protein of above three groups was increased progressively by immunohistochemical staining. The density of bcl -2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time by RT - PCR. CONCLUSION: Genistein is able to induce the apoptosis of transplanted tumor cells. This apoptosis may be mediated by down - regulating bcl - 2 and up - regulating bax mRNA and its protein.