To study the effect of the proliferation and apoptosis of Survivin-T34A mutant on breast cancer MCF-7 cell, we adopted the method of cell culture in vitro to observe the proliferation and apoptosis of the cell. In the experiment, MCF-7 cells were randomly divided into three groups and transfected with normal saline, PORF-9-null and Survivin-T34A, respectively. Breast cancer nude mouse models were established to study anti-tumor effect of Survivin-T34A in vivo. The activity of the cells in the Survivin-T34A-transfected group was lower than that in PORF-9-null group. The increase of cell apoptosis was observed under electron microscopy, meanwhile the apoptotic rate was obviously higher than that in PORF-9-null control by flow cytometry. Tumor inhibition effects of the mouse which received the injection of Survivin-T34A intratumoral injection were apparent, and the inhibition ratio was as high as 47.1%. In conclusion, Survivin-T34A mutant has anti-tumor effect through efficiently inhibiting the growth of breast cancer MCF-7 cell and actively promoting apoptosis of cancer cells.
Animals ; Apoptosis ; Breast Neoplasms ; drug therapy ; pathology ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; pharmacology ; Injections, Intralesional ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Transfection

The present paper is aimedto investigate the effect of basic fibroblast growth factor (bFGF) on proliferation, migration and differentiation of endogenous neural stem cell in rat cerebral cortex with global brain ischemia-reperfusion. A global brain ischemia-reperfusion model was established. Immunohistochemistry was used to observe the pathological changes and the expression of BrdU and Nestin in cerebral cortex. RT-PCR was used to measure the NSE mRNA in brain tissue. The results of measurements indicated that in sham operation group, there was no positive cell in cerebral cortex, and the content of NSE mRNA did not change. In the operation group, the expression of BrdU and Nestin increased significantly at the end of the 3rd day, and peaked on the 7th day. NSE mRNA expression did not significantly increase. In bFGF group, compared with sham operation group and model group, the number of BrdU-positive and Nestin-positive cells increased significantly at each time point (P<0. 05), and peaked at the end of the 11th day, and the content of NSE mRNA increased significantly (P<0. 05). This research demonstrated that the proliferation of endogenous neural stem cells in situ could be induced by global cerebral ischemia and reperfu- sion, and could be promoted and extended by bFGF. In additiion, bFGF might promote endogenous neural stem cells differentiated into neurons.
Animals ; Brain Ischemia ; pathology ; Cell Differentiation ; Cell Movement ; Cell Proliferation ; Cerebral Cortex ; cytology ; metabolism ; pathology ; Fibroblast Growth Factor 2 ; pharmacology ; Nestin ; metabolism ; Neural Stem Cells ; drug effects ; Rats ; Reperfusion Injury

Objective To investigate the clinical effects of sound therapy and psychological counseling on chronic tinnitus .Methods Two hundred and thirty - two cases of chronic tinnitus patients were treated with sound therapy and psychological counseling in this study .The time course of treatment was 12 months .Tinnitus Evalua‐tion Questionnaire(TEQ) was filled out before sound therapy ,3 ,6 and 12 months after the therapy to evaluate the effects .Results After the therapy ,the patients had a significant improvement in tinnitus symptoms .Before the therapy ,178 patients had severe tinnitus ,while after the therapy ,this number decreased obviously .In the end of treatment there were only 36 cases ,with severe tinnitus(15 .52% ) .After the 6 months treatment ,the effective rate was 79 .31% ,after 12 months the effective rate was 86 .21% .Conclusion Sound therapy and psychological counse‐ling are effective treatments for chronic tinnitus ,and the effects are stable and durable .

Objective To evaluate the role of autophagy in hydrogen-induced inhibition of apoptosis in hippocampal neurons in a rat model of orthotopic liver transplantation (OLT).Methods Fifty-six pathogen-free healthy adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 220-250 g,were used in the study.Thirty-two rats were selected and assigned into 4 groups (n =8 each) using a random number table:sham operation group (group S),OLT group,hydrogen-rich saline group (group HS) and chloroquine group (group CQ).The other 24 rats severed as the donors.In group S,laparotomy was performed,and the related blood vessels were isolated.The model of OLT was established in OLT,HS and CQ groups.In group OLT,normal saline 6 ml/kg was slowly injected via the inferior vena cava at 5 min before anhepatic phase.In group HS,hydrogen-rich saline 6 ml/kg was slowly injected via the inferior vena cava at 5 min before anhepatic phase.In group CQ,autophagy inhibitor chloroquine 60 mg/kg was injected intraperitoneally at 1 h before establishment of the model,and the other treatments were similar to those previously described in group HS.At 6 h of reperfusion,the rats were sacrificed and hippocampi were isolated for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity,for pathological examination (with light microscope),and for detection of cell apoptosis (by TUNEL staining) and expression of autophagy-and apoptosis-related proteins caspase-3,cytochrome c (Cyt c),microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ),Beclin-1 and p53 in hippocampal tissues (by Western blot analysis).Apoptosis index (AI) was calculated.Results Compared with group S,the MDA content and AI were significantly increased,the SOD activity was decreased,and the expression of caspase-3,Cyt c,LC3 Ⅱ,Beclin-1 and p53 was up-regulated in OLT,HS and CQ groups (P＜0.05).Compared with group OLT,the MDA content and AI were significantly decreased,the SOD activity was increased,the expression of caspase-3 and Cyt c was down-regulated,and the expression of LC3 Ⅱ,Beclin-1 and p53 was up-regulated in group HS (P＜0.05).Compared with group HS,the MDA content and AI were significantly increased,the SOD activity was decreased,and the expression of caspase-3 and Cyt c was up-regulated,and the expression of LC3 Ⅱ,Beclin-1 and p53 was down-regulated in group CQ (P＜0.05).Conclusion The mechanism by which hydrogen inhibits apoptosis in hippocampal neurons is related to promotion of autophagy in a rat model of OLT.

Objective To explore the influence of icotinib in the apoptosis of the human salivary adenoid cystic carcinoma cells ACC-M, and to clarify the mechanism of icotinib for the treatment of salivary adenoid cystic carcinoma.Methods The ACC-M cells were randomly divided into control group,2,4,8μmo1·L-1 icotinib groups,p38-MAPK inhibitor SB203580 (20μmol· L-1 )group,SB203580 (20 μmol· L-1 )+4μmo1 · L-1 icotinib group;the cells were collected 4 h after treatment.The viability of ACC-M cells was measured by MTT assay.The apoptosis of ACC-M cells was assessed by caspase-3 activity kit. The expression of p-p38-MAPK protein was determined by Western blotting analysis.Results Compared with control group,the inhibitory rates of growth of the ACC-M cells in icotinib groups were significantly decreased (P<0.05 ), and the activities of caspase-3 were increased (P<0.05),and the expression levels of p-p38-MAPK were significantly increased (P<0.05).Compared with 4μmo1·L-1 icotinib group,the expression level of p-p38-MAPK in SB203580+icotinib group were decreased (P < 0.05 ), and the activity of caspase-3 was decreased dramatically (P < 0.05 ). Conclusion Icotinib may induce the apoptosis of ACC-M cells through the activation of p38-MAPK signaling pathway.

[ ABSTRACT] AIM:To investigate the effects of c-Met on the proliferation and the sensitivity to chemotherapeutic drugs of triple negative breast cancer cells.METHODS: Doxorubicin-resistant cells ( MDA-MB-231/ADR) were estab-lished.The expression of c-Met at mRNA and protein levels in the MDA-MB-231/ADR cells and parental MDA-MB-231 cells was detected by real-time PCR and Western blotting.c-Met siRNA and plasmid or AKT siRNA were transfected into the cancer cells.The cell proliferation and the sensitivity to doxorubicin were determined by MTT assay.RESULTS:The expression of c-Met at mRNA and protein levels in MDA-MB-231/ADR cells was significantly higher than that in parental MDA-MB-231 cells.Transfection with pBABE-puro TPR-MET plasmid into the MDA-MB-231 cells induced cell prolifera-tion and resistance to doxorubicin.Meanwhile, inhibition of c-Met in the MDA-MB-231/ADR cells by siRNA reversed the doxorubicin-resistance.In addition, over-expression of c-Met led to higher phosphorylation level of AKT, which was in-volved in the effects of c-Met on the MDA-MB-231 cell proliferation and doxorubicin-resistance.CONCLUSION: c-Met may have the potential as a therapeutic target in the treatment of triple negative breast cancer.

Objective To assess the effect of low-dose cytarabine and aclarubicin in combination with gran-ulocyte colony-stimulating factor (G-CSF) protocol (CAG) in patients with acute myeloid leukemia (AML),and to understand the potential factors affecting the outcome of CAG induction therapy, therefore to find the optimum pa-tients for CAG therapy. Methods Twenty-one AML patients were enrolled in the current study. All patients were treated with CAG regimen including cytarabine (10 mg/m~2, subcutaneously, every 12 h, days 1 - 14), lacinomycin (5～7 mg/m~2,intravenously,every day, days 1 -8) ,and G-CSF (200 μg/m~2,subcutaneously, every day,12 h be-fore Ara-C was given) priming. Results The overall complete remission (CR) rate of the 21 AML patients was 66.7% (14/21). The CR rates was 87.5% (7/8) in patients older than 60 yrs,60.0% (9/15) in the refractory or relapsed patients,83.3% (5/6) in the MDS transformed AML patients. The CR rates for patients with hyperprolif-erative BM and median to poor proliferative BM were 33.3% and 91.7% ,respectively(P =0.009). The median o-verall survival (OS) time of the 21 AML patients was 450 days. Two-year survival rate estimated by Kaplan-Meier Method was 30.6%. The overall median disease free survival (DFS) was 165 days. The median OS time for those refractory or relapsed was 435 days. The median OS time for those with poor cytogenetic state or standard or good cytogenetic state was 140 days and 620 days, respectively (P = 0.001). The median OS time for patients with hyperproliferative BM and median to poor proliferative BM was 321 days and 620 days, respectively (P = 0.05). The median recovery time of granulocytes above 1.0×10~9/L was 8 days. The median duration of fever was 3.5 days. The rate of infections exceeding WHO grade Ⅱ was 42.9%. No early death occurred. Conclusions The CAG induction therapy may have a higher CR rate in patients with refractory or relapsed AML, elderly AML and secondary AML from MDS transformation, and extend the median overall survival time in refractory or relapsed patients. CAG therapy can not improve the outcome of patients whose BM was in high grade proliferation state or whose cytogenetic state was poor. CAG therapy can shorten the duration of agranulocytosis and decrease the inci-dence of serious infection. Therefore, CAG therapy is worth recommending to patients who can not endure the rou-tine intensive chemotherapy.

Objective:To analyze the clinical characteristics, examination results, treatment and prognosis of neonates with influenza virus infection in the neonatal intensive care unit (NICU).Methods:Clinical data of neonates with influenza virus infection who were hospitalized in the NICU of the General Hospital of Southern Theater Command of Chinese People′s Liberation Army from January 2018 to December 2020 were retrospectively analyzed.Results:A total of 11 hospitalized neonates with influenza virus infection in the NICU were recruited, including 2 cases of influenza A and 9 cases of influenza B. Ten cases (90.9%) had respiratory symptoms, and among them, there were 8 cases with increased oxygen demand, 7 cases with complicated pneumonia, 4 cases with dyspnea, and 2 cases with apnea.Seven cases showed abnormal body temperature, including 6 cases of fever, and 1 case of hypothermia.Five cases had circulatory system symptoms.Digestive system symptoms and urinary system symptoms were detected in 5 cases and 3 cases, respectively.Eight cases complicated with systemic symptoms, including 3 cases of poor mental response, 3 cases of worsening jaundice, 3 cases of weight loss, 2 cases of hyperglycemia, 1 case of edema and sclerosis.Ten cases were treated with gamma globulin immunotherapy, 2 cases were treated with plasma immune support, and 1 case was treated with Peramivir antiviral.Eight cases were treated with increased oxygen therapy, among which non-invasive ventilator parameters or modes increased in 4 cases, and nasal cannula oxygen concentration increased in 2 cases.The change of noninvasive-assisted ventilation to invasive-assisted ventilation occurred in 1 case, and 1 case developed the change of nasal cannula to noninvasive-assisted ventilation.Four neonates received anti-shock and (or) myocardial contractility therapy.Conclusions:Neonates with influenza virus infection in the NICU are mainly manifested as respiratory symptoms and fever, and the incidence of complicated pneumonia is high.Multiple systems may be involved at the same time, often leading to severe disease status.Comprehensive supportive treatment is necessary.Neonatologists should pay attention to these symptoms, and early detection of influenza virus and timely isolation are the key methods to prevent influenza outbreaks in NICU.

Objective: To analyze the prognostic factors of adult nonclear cell renal cell carcinoma (nccRCC). Methods: The clinical data of 286 patients with pathologically diagnosed one specific type of nccRCC after radical nephrectomy and nephron sparing surgery(NSS) in the affiliated hospital of Qingdao university followed up from January 2012 to January 2019 were retrospectively analyzed.There were 159 males and 127 females. Their age ranged from 17 to 81 years old, with an average age of 53. Based on the AJCC combination stage, 218 cases were in stage Ⅰ, 56 cases were in stage Ⅱ, 9 cases were in stage Ⅲ, 3 cases were in stage Ⅳ. Assay indicators were collected, including lymphocyte percentage(LY%)(31.5±10.5), neutrophil-lymphocyte ratio(NLR)(2.6±2.8), albumin(40.9±4.7)g/L, prealbumin(255.0±74.3)mg/L, lactate dehydrogenase (LDH)(201.0±174.0)U/L, creatine kinase isoenzyme (CK-MB)(20.0±62.1)U/L, total cholesterol(4.9±1.0)mmol/L, blood urea nitrogen/creatinine (BUN/Cr)(12.9±9.9), blood glucose(5.4±1.3)mmol/L, triglyceride(1.4±1.1)mmol/L, low-density lipoprotein cholesterol (LDL-C)(2.9±0.8)mmol/L. The optimal cut-off value of the above indexes were obtained by the receiver operating characteristic curve(ROC) in the SPSS software, and difference between high cut-off and low cut-off divided basing on the optimal cut-off value were evaluated respectively. The prognostic factors of adult nccRCC were evaluated by univariate and multivariate Cox proportional hazards regression analysis. Kaplan-Meier survival curve was used to study the survival relationship. The log-rank test were used to compare survival rate in two groups. The prognostic factors of nccRCC were analyzed after the results above were presented. Prognostic factors in renal chromophobe cell carcinoma and papillary cell carcinoma were analyzed by the same method. Results: The 286patients were followed up from 1 to 87 months, with an average of 43.9 months. The 3-year and 5-year survival rates were 93.8% and 89.3%, respectively. Results of univariate and multivariate Cox regression model revealed that AJCC combined staging (HR=2.38, 95%CI1.48-3.83), LDH(HR=2.99, 95%CI1.16-7.69), blood glucose (HR=4.13, 95%CI 1.74-9.78), CK-MB (HR=3.85, 95%CI1.63-9.08) were independent prognostic factors of nccRCC. NLR(HR=8.28, 95%CI1.66-41.35) and LDH(HR=9.82, 95%CI2.94-32.82) were the independent prognostic factor in the renal chromophobe cell carcinoma subgroup and the papillary renal cell carcinoma subgroup, separately. Conclusions AJCC combination stage, LDH, blood glucose and CK-MB are independent prognostic factors of adult nccRCC. Patients with low LDH, hypoglycemia, CK-MB and early AJCC stage have better prognosis. NLR is an independent predictor of renal chromophobe cell carcinoma, and the low NLR group has a better prognosis and higher survival rate. LDH is an independent predictor of papillary renal cell carcinoma and low LDH is beneficial to patients' prognosis. NLR and LDH can be used as a prognostic indicator for clinical evaluation in renal chromophobe cell carcinoma and papillary renal cell carcinoma, respectively.

The treatment of acute Stanford type A aortic dissection has always been extremely challenging. Organ malperfusion syndrome is a common severe complication of acute aortic dissection, which can cause organ ischemia and internal environment disorder. Malperfusion increases early mortality, and impacts the long-term prognosis. In recent years, many scholars have done some studies on aortic dissection complicated with malperfusion. They explored the pathogenesis, proposed new classification, and innovated new treatment strategies. However, at present, the treatment strategies of acute Stanford type A aortic dissection complicated with organ malperfusion are different at different centers and consensus on its treatment is still lacking. Therefore, this review summarized the pathogenesis, classification, treatment strategy, and prognosis of acute Stanford type A aortic dissection complicated with malperfusion.