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Triple negative breast cancer is a subtype of breast cancer with poor prognosis and lack of effective treatment. Cyclin dependent kinase (CDK) 4/6 inhibitors promote antitumor immunity by influencing the triple negative breast cancer immune microenvironment, such as increasing the tumor cell surface pragrammed death-ligand 1 protein expression, enhancing T cell activation and antigen presentation, changing the proportion of T cell subgroup and inducing lymphocyte infiltration. The change of immune microenvironment is related to tumor progression, but its mechanism is extremely complex. Exploring the mechanism of CDK4/6 inhibitor affecting immune microenvironment and its biomarkers can provide a new direction for the diagnosis and treatment of triple negative breast cancer.
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Objective@#To investigate the clinicopathological characteristic and risk factors for recurrence in different subtypes of mucinous breast cancer(MBC).@*Methods@#Clinical data of 97 MBC patients at Zhejiang Cancer Hospital from August 2005 to November 2012 were retrospectively analyzed. All of patients were divided into 3 subtypes according to the mucinous components in the tumors, named as partial mixed MBC with less than 50% of mucinous components, main mixed MBC where the mucinous component accounted for 50% to 90%, and pure MBC with more than 90% of mucinous components. In this study, 43, 16 and 38 patients were included in partial mixed MBC, main mixed MBC, and pure MBC, respectively. Follow-up was collected by out-patient, in-patient system and phone call. The relationship between different subtypes and clinicopathological significance were analyzed by χ2 test. Kaplan-Meier curve combined with Log-rank test was used to evaluate the risk factors of relapse free survival(RFS) at 3- and 5-year. Cox proportional hazard regression model was used for multivariate analysis.@*Results@#The median follow-up time was 65 months (range 24-125). Of the 97 patients, 14 patients were relapse or metastasis at the end point. The 3- and 5-year RFS were 90.7% and 85.7%, respectively. Tumor size, number of involved lymph nodes (LN), axillary LN metastasis, TNM stages and p53 mutant status were all related with subtypes of MBC(all of P<0.05). There was no correlation between subtypes of MBC and the other parameters, including age at surgery, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor-2 (HER-2) overexpression, menstruation status, and the relapse of disease(all of P>0.05). Univariate analysis showed menstruation status and TNM stages were associated with the relapse of breast cancer(P<0.05). The patients with menopause and stage Ⅲ-Ⅳ showed significantly shorter RFS time(both of P<0.05). Multivariate Cox proportional hazard regression analysis revealed that tumor size, PR status and postoperative radiotherapy were the independent prognostic factors for the relapse of MBC.@*Conclusions@#Tumor size, status of axillary LN metastasis, TNM stages, and p53 mutation status are differ among different subtypes of MBC. The tumor size (>30 mm), PR status and postoperative radiotherapy are the independent risk factors for recurrence, whereas the proportion of the mucinous component is not associated with relapse in MBC patients.
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Objective To introduce extrapedicular infiltration anesthesia as an improved method of local anesthesia which applied to unipedicular percutaneous vertebroplasty or percutaneous kyphoplasty.Methods From March 2015 to March 2016,20 patients in our hospital received percutaneous vertebroplasty or percutaneous kyphoplasty with 1％ lidocaine local infiltration anesthesia and extrapedicular infiltration anesthesia.The visual analogue score of patients during the operation and whether they needed additional sedative anesthesia were evaluated.The anaesthetic effect of nerve root block was observed.Results The visual analogue score of all the patients ranged from 1 point to 3 point,averagely (2.5 ± 0.7) point.Among the 20 patients,there were 2 cases of 1 point,7 cases of 2 point and 11 cases of 3 point.No patients required additional sedative anesthesia,and no nerve root block effects were observed.Conclusion Extrapedicular infiltration anesthesia provides good local anesthetic effects without significant complications,which deserved further use in unipedicular percutaneous vertebroplasty and percutaneous kyphoplasty.
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The development of primary or acquired taxane resistance inevitably becomes to be the main problem.Ixabepilone is effective in metastatic breast cancer (MBC) patients including those heavily pretreated or resistant to taxanes.Eribulin has been used for the treatment of MBC patients who have received at least two prior chemotherapy regimens.New microtubule-targeting agents are promising to be effective options for patients progressing after standard taxane-containing chemotherapy.
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It has been shown that the PIK3CA mutation in HER2 positive breast cancer is up to 25%, and thus activates PI3K-Akt signaling pathway,promotes HER2 mediated tumor cell epithelial transformation, alters the intrinsic phenotype of HER2 overexpression breast cancer,and finally leads to resistance to anti HER2 targeted therapy.Some studies have shown that the PIK3CA gene mutation is associated with the efficacy of anti-HER2 targeted therapy.Therefore,real-time monitoring of PIK3CA gene mutation will promote indivi-dualized anti-HER2 targeted therapy.
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Thalidomide has anti-tumor effects such as anti-tumor angiogenesis,improvement of immune function and cachexia of patients with advanced tumors,which has been effectively used in elderly patients with castration-resistant prostate cancer,chemotherapy resistant advanced colorectal cancer,advanced hepatocellular carcinoma and metastatic breast cancer.As the in-depth study of the anti-tumor mechanism of thalidomide, more and more clinical researches have focused on the function of thalidomide on non-hematological malignan-cies,especially it has obtained some achivements in the postoperative adjuvant therapy for high-risk colorectal cancer and primary hepatocellular carcinoma and the salvage therapy for metastatic triple-negative breast cancer and refractory gynecological tumor.
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Objective To investigate the risk factors that cause arterial blood lactate (Lac) elevation in patients after gastrointestinal operation.Methods The data of 216 patients who had undergone gastrointestinal operation, and transferred to intensive care unit (ICU) of Ningxia Medical University General Hospital from November 2013 to November 2014 were retrospectively analyzed.According to the initial level of blood Lac after operation,the patients were divided into two groups: high Lac group (Lac ＞ 2 mmol/L, n =100) and normal Lac group (Lac ≤ 2 mmol/L, n =116).The baseline data of two groups were recorded as follows: ① baseline data: gender, age, preoperative acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, previous diseases, initial Lac level after operation;② preoperative risk factors: 24-hour total amount of fluid, and the amount of colloid for resuscitation;③ intraoperative risk factors: the proportion of emergency operation, operation time, site of operation, usage of antibacterial drug, the highest and lowest mean arterial pressure and its difference (MAPmax, MAPmin, A MAP),total amount of fluid and colloid for resuscitation.The risk factors of increasing Lac post gastrointestinal operation was evaluated using multiple linear regression analysis.Results ① There were no significant differences in baseline data such as gender, age, preoperative APACHE Ⅱ score and previous diseases between the two groups (all P ＞ 0.05).Initial Lac level in high Lac group was significantly higher than that of normal Lac group (mmol/L: 5.1 ± 3.6 vs.1.3 ±0.4,t =10.584,/P =0.000).② There were no significant differences in 24-hour amount of fluid and colloid for resuscitation before operation, and intraoperative MAPmax between two groups.Compared with normal Lac group, intraoperative A MAP [mmHg (1 mmHg =0.133 kPa): 35.8 ± 14.4 vs.28.7 ± 13.7, t =3.727, P =0.000], the proportion of emergency operations (19.0％ vs.9.5％, x 2 =9.869, P =0.007), intraoperative transfusion volume [mL: 4 500 (3 500, 5 800) vs.3 700 (2 812, 5 075), Z =-3.244, P =0.001], intraoperative colloid volume [mL: 1 000 (1 000, 1 900) vs.1 000 (1 000, 1 787), Z =-2.347, P =0.019], and operation time (minutes: 222.0±91.5 vs.187.0±75.9, t =3.026,P =0.003) in high Lac group were significantly increased, and the levels of intraoperative MAPmin (mmHg: 68.7 ± 11.6 vs.75.9± 10.6, t =-4.716, P =0.000) and intraoperative antibiotics usage (62.0％ vs.86.2％, x 2 =18.318, P =0.000)were significantly decreased.③The patients undergoing operation of esophagus, stomach, duodenal and intestine,and colon accounted for 6.9％, 22.7％, 16.7％, and 53.7％, respectively, their Lac was 2.8 (1.6, 5.4), 2.3 (1.2, 5.8),2.5 (1.5, 5.2), 1.7 (1.1, 2.9) mmol/L, respectively, indicating that surgical site had an influence on the occurrence of postoperative hyperlactacidemia (x 2 =11.032, P =0.012).④ It was showed by multiple linear regression analysis that the operation site (t =-2.725, P =0.007), MAPmin (t =-4.533, P =0.000), non-antibiotics usage during operation (t =2.441, P =0.016) were the risk factors of Lac increase in patients after gastrointestinal operation.⑤ The incidence of postoperative incipient procalcitonin (PCT) increase (PCT ＞ 0.5 μg/L) in patients and usage of antibiotics was significantly lower than that in patients who did not receive antibiotics during operation [17.89％ (17/95) vs.67.74％ (21/31), x 2 =27.572, P =0.000].Conclusions The surgical site showed an influence on the occurrence of hyperlactacidemia in patients after gastrointestinal operation, and the lowest occurrence rate was found in the colonic operation.In patients suffering from gastrointestinal operation, antibiotics should be routinely used to improve MAP.Excessive preoperative and intraoperative fluid infusion cannot reduce the occurrence of hyperlactacidemia.
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Pterostilbene,a dimethyl ester derivative of resveratrol with antioxidant and antiproliferative properties,has been shown to inhibit a variety of primary tumors and act as a potential chemopreventive agent in carcinogenesis.The anticancer mechanisms of pterostilbene include inducing tumor cell apoptosis,causing cell cycle arrest,blocking tumor cell growth and proliferation signal transduction.Pterostilbene is expected to develop to a new generation of anticancer drug,and will be paid more attention in the future.
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Triple-negative breast cancer(TNBC) has distinct biological and clinical characteristics. Therapeutic strategies for TNBC remain a challenge. Studies about epidemiology,molecular characteristics,chemotherapy and targeted-therapy are ongoing,In particular,preliminary results of stage II or III clinical trials indicate new chemotherapy or combination targeted therapy may have a good efficacy.
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The etiopathogenisis of breast cancer is very complex, its pathogenesis and development can not be completely elucidated by one-factor or multiple-factor model Epidemiologic studies indicate that deterio-ration of environment,changing of life style and dietary pattern and so on are common factors. It is of great sig-nificance to comprehend some known factors and high-risk factors which is helpful to prevention and early diag-nosis of breast cancer. The incidence and the mortality of breast cancer have fallen down due to screening and prophylactic therapy for high-risk population.
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Objective: To observe the safety and clinical efficacy of tumor antigen-pulsed dendritic cell(DC) vaccine in treatment of advanced malignant tumor.Methods: Ninety-one patients with non-small cell lung cancer,colon and rectal cancer,melanoma,renal carcinoma,breast cancer and other malignant tumors were enrolled in this study.All patients met the selecting standard and signed informed consent.Human dendritic cells were obtained from peripheral blood monocytes by culturing them with granulocyte macrophage-colony stimulating factor and interleukin-4.DC vaccine was prepared from tumor antigen pulsed immature dendritic cells in vitro.Patients received the vaccine therapy once every week and one cycle was defined as once every week for 3 weeks.Results: All the patients received 96 cycles of DC vaccine treatment.Symptoms of toxicity included fever,shivering,aching pain of muscle,asthenia,itching,stifle and transient fatigue;most of the symptoms automatically recovered.Clinical efficacy of the treatment was evaluated in 76 patients.Thirty-one of the 76 patients were stable after treatment and 45 were in progressive situation,with the clinical benefiting rate being 40.8%.Eighty-five patients were followed up.The median time for progression was 2.6 months;the overall survival time was 0.9-30.6 months;and the median survival period was 4.5 months,with the one year survival rate being 9.2%.Conclusion: The results suggest that the DC vaccine therapy is well tolerated in treating patients with advanced malignant tumors and has satisfactory clinical benefit;the clinical value of DC vaccine therapy needs to be further observed.
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Entry of enveloped viruses into host cells requires fusion of the viral envelope with a cellular membrane. This step is mediated by viral glycoproteins that undergo a dramatic conformational change. Recent advances in structure and function of the fusion proteins of the class Ⅱ viruses, Rhabdoviruses and Herpesviruses were described. Proteomics computational analyses to locate the functional domain of fusion protein were introduced. The fusion proteins of class Ⅱ and class Ⅰ viruses differ radically in their initial structures but refold toward similar final conformation (trimer of hairpin). The Rhabdoviruses and Herpesviruses have a novel fold combining features of fusion proteins from class Ⅰ and class Ⅱ. The fusion proteins of these viruses have a different conformation change and mediate a different fusion process, therefore, the proteins belong to a novel class of fusion proteins. The potent inhibitor of virus entry should be new strategies for developing antiviral drugs.
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Hybrid linear analysis (HLA) was applied to resolution of overlapping spectra of Fe3+ -salicylfluorone and Al3+ -salicylfluorone complexes and simultaneous spectrophotometric determination of Fe3 + and Al3 + . The absorbance matrix of 7 standard mixtures at 41 measuring points ranged from the wavelength of 550 nm to 630 nm was used for calibration. To avoid the effect of interaction between the two components on the determination, the column vector of K matrix obtained from the standard mixtures with least squares was used as the pure spectrum of component. The recoveries of the two elements for the analysis of the synthetic samples were 93.3% ～ 107.5% in the range of the concentration ratio of Fe3+:Al3+ = 10:1 to 1:8. Comparing with the partial least squares (PLS) model,the HLA method was simple,accuracy and precise.
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A new method for simultaneous spectrophotometric determination of Zn, Cd and Hg using 2-(5-Br-2-pyridylazo)-5-diethylaminophenol as the color developing reagent was proposed. The absorption spectra of these three complexes have similar features with severe overlap in visible spectral range. For resolving these spectra, hybrid linear analysis was used, and the pure spectrum of each component was obtained from the calibration mixtures by least squares method. The effects of reaction condition, selection of wavelengths, determination of pure spectrum and additivity of absorbances etc. on the determination were discussed. The proposed method offers the advantages of simple, rapid, and accuracy. It has been successfully applied to the simultaneous determination of Zn, Cd and Hg in synthetic sample. A comparison was also made with the partial least squares method.
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0.05,X 2 =0.45),and the focus stability ratio were42.5%and32.4%respectively.Compared with the FOLFOX4group,the hospitalization course in capecitabine group is significantly shorter(8.5days vs25.3days,P=0.000)and the total medical cost was significantly lower(5941.7RMB vs13304.6RMB,P=0.001).The cost structure analysis showed that the direct and indirect medical costs of the FOLFOX4group increased more significantly(P=0.001)and the incidence for adverse effects of this group was lower than that of the capecitabine group.CONCLUSION:From the perspective of pharmacoeconomic evaluation,capecitabine is better than FOLFOX4in treating the digestive malignant tumor.