ABSTRACT
BACKGROUND@#As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment.@*METHODS@#Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses.@*RESULTS@#In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70-0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80-1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03-1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25-0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67-0.92, P = 0.002).@*CONCLUSIONS@#The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.
Subject(s)
Humans , B7-H1 Antigen/antagonists & inhibitors , Drug Therapy, Combination , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Breast Neoplasms/drug therapyABSTRACT
Objective:To clarify the evidences of hippocampal injury after radiotherapy avoiding hippocampus and explore its relationships with cognition.Methods:A prospective design was adopted in this study.A total of 183 patients with nasopharyngeal carcinoma treated by intensity modulated radiation therapy (IMRT group) and 30 matched healthy control (HC group)were collected in the Affiliated Hospital of Jiangsu University and Southeast University Affiliated Zhongda Hospital from January 2017 to December 2019. All subjects were assessed by Montreal Cognitive Assessment (MoCA-B) at baseline and 6 months after radiotherapy, then the patients with nasopharyngeal carcinoma were divided into cognitive impairment group and non-cognitive impairment group. Subjects were scanned with Siemens 3.0 T MR, and T 1WI was used as analysis sequence.The individual standardized hippocampus ROIs were extracted based on Montreal Neurological Institute(MNI) brain template.All texture features were calculated using the Radiomics developed by C++and Delphi, and the intra group correlation coefficients (ICC), average direction, machine learning (random forest) and autocorrelation matrix were used for reducing the features dimension. One-way ANOVA and generalized linear models were used to compare the differences among different groups. Pearson correlations analyses were used to evaluate the relationships between important texture features and clinical data. Logistic regressions were used to calculate the abilities of texture features to predict cognitive impairment. Results:After 9 patients who lost follow-up were excluded, a total of 164 patients with nasopharyngeal carcinoma were included as IMRT group.Texture features of ROIs were extracted and dimensionally reduced successfully. Five differences features (Variance, Entropy, GlevNonU, RLNonUni and Contrast)were found among HC group, cognitive impairment group and non-cognitive impairment group, and the last three further showed significant differences within IMRT group (GlevNonU, P=0.011;RLNonUni, P<0.001;Contrast, P<0.001). Hippocampal doses were positively correlated with Variance ( r=0.448, P<0.05), and negatively correlated with Entropy ( r=-0.461, P<0.05). There was a positive correlation between MoCA-B scores with GlevNonU, RLNonUniand Contrast ( r=0.503, P<0.05; r=0.587, P<0.05; r=0.531, P<0.05). GlevNonU and Contrast were independent predictors of cognitive impairment in hippocampal avoidance of radiotherapy (OR=0.731, 95%CI 0.610-0.857; OR=0.651, 95%CI 0.496-0.853). Conclusion:Results of texture analysis could be used as micro imaging evidences of hippocampal injury in radiotherapy avoiding hippocampus, and could also effectively predict the occurrences of cognitive impairment.
ABSTRACT
Objective To investigate the practical value of a logistic regression model of serum indexes in distinguishing between geriatric depression and geriatric depressive state. Methods A total of 160 patients were recruited from the outpatient department from January 2013 to January 2016 ,and were divided into a depression group (n= 80)and a depressive state group (n= 80) ,with retrospective diagnoses based on the Chinese Classification of Mental Disorders-Third-Edition(CCMD-3).Serum samples were collected and enzyme linked immunosorbent assays (ELISA)were used to determine the concentrations of brain-derived neurotrophic factor (BDNF ) ,glial cell line-derived neurotrophic factor(GDNF) ,fibroblast growth factor 2(FGF-2) ,vascular endothelial growth factor (VEGF) ,interleukin-1β(IL-1β) ,interleukin-6 (IL-6) ,interleukin-10 (IL-10) ,tumor necrosis factor-α(TNF-α) ,cortisol (CORT ) ,and platelet-derived growth factor (PDGF).Binary logistic regression analysis was used to establish the regression model ,and the ROC curve was drawn to explore its value of differentiating geriatric depression from depressive state. Results The levels of serum BDNF , GDNF and VEGF in the depression group were lower than those in the depressive state group (BDNF :208.7 ± 41.4 vs.262.9 ± 84.6 ng/L ,GDNF :92.3 ± 18.6 vs. 101.4 ± 30.9 ng/L ,VEGF :223.1 ± 98.2 vs. 257.8 ± 77.2ng/L) ,while the levels of IL-1βand CORT in the depression group were higher than in the depressive group(IL-1β:27.0 ± 4.9 vs.19.6 ± 5.7 μg/L ,CORT :96.3 ± 16.7 vs.83.0 ± 17.3 nng/L).In multivariate logistic regression analysis ,BDNF(OR = 0.987 ,P = 0.001) ,IL-1β(OR =1.29 ,P = 0.000)and CORT (OR = 1.065 ,P = 0.000)were selected to build the regression model. The regression equation was P=1/[1+e-(- 8.546 - 0.013(BDNF)+ 0.258(IL -1β)+ 0.063(CORT)) ]and the area under the ROC curve was 0.966.Compared with retrospective diagnoses made two weeks later ,the correct diagnosis rate of the logistic model was 90.47％. Conclusions The Logistic regression model of serum indexes can further differentiate between geriatric depression and depressive state which also offers additional benefits for the diagnosis ,differential diagnosis ,and treatment of depression.
ABSTRACT
BACKGROUND:Bismth-doped iron nanoparticles modified by hyaluronic acid (HA-BiIOPs) not only act as an effective MRI contrast agent, but also as a radiotherapy sensitizer.OBJECTIVE:To fabricate the HA-BiIOPs and to observe its effect to enhance the radiosensitivity of glioblastoma cells U87MG under X-ray radiation.METHODS:HA-BiIOPs were synthesized using hydrothermal polyol method. (1) Cytotoxicity: A cytotoxicity test was carried out on U87MG cells and rat vascular smooth muscle cells (VSMCs). Cell proliferation rate of two kinds of cells cultured with different concentrations of HA-BiIOPs (0, 12.5, 25, 50, 100, 200, 400 mg/L) at 24 hours after culture were determined by cell counting kit-8 assay. (2) Histological analysis: ICR mice were sacrificed after intravenous injection of HA-BiIOPs, and pathological changes of mouse visceral organs were observed under an optical microscope. (3) Cellular uptake: The HA-BiIOPs after entered into the cytoplasm were observed by Prussian blue staining. (4) Radiosensitization test: U87MG cells at Logarithmic growth stage were cultured in culture medium as control group, subjected to X-ray irradiation (0, 3, 6, 9 Gy) as radiotherapy group, cultured in HA-BiIOPs (0, 12.5, 25, 50, 100, 200 and 400 mg/L) as HA-BiIOPs group or subjected to HA-BiIOPs culture plus X-ray irradiation as combined therapy group. Then, the cell proliferation rate and cloning efficiency were measured at 24 hours after treatment.RESULTS AND CONCLUSION:(1) The HA-BiIOPs at different concentrations were non-cytotoxic for VSMC and U87MG cells. (2) After intravenous injection of HA-BiIOPs, there was no obvious toxicity to the mouse susceptible organs. (3) After 6 hours of culture, the HA-BiIOPs could be internalized by U87MG cells. (4) The proliferation rate of U87 cells was negatively correlated with the concentration of HA-BiIOPs (0-200 mg/L) and X-ray dose (0-9 Gy). Especialy, the combination of 6 Gy X-ray irradiation with 200 mg/L HA-BiIOPs dramatically decreased the cell viability that was decreased to (41±7)%. In the combined therapy group with 6 Gy X-ray and 100 mg/L HA-BiIOPs, the cells proliferation rate was significantly lower than that in the control and radiotherapy groups (P < 0.05). These results indicate that HA-BiIOPs have a radiosensitizative effect on glioblastoma cells U87MG.
ABSTRACT
Objective To evaluate cerebral parenchymal atrophy of patients with Alzheimer's disease(AD)through the compara-tive analysis of the volume and morphology of the brain ventricle between patients with AD and normal elderly.Methods 20 patients with AD and 20 normal elderly people were scanned at 3.0T MR,and lateral ventricle section images were achieved,and the lateral ventricle volume and the anterior horn,posterior horn and temporal horn of the lateral ventricle were calculated by analyzing the re-construction of section images with MIMICS software from Belgian.Results As compared with normal elderly group,the patients with AD exhibited significantly increased the volume of left ventricular volume(LV),right ventricular volume (RV)and total vol-ume (TV)(P<0.05).Angle of bilateral anterior horn and temporal horn but not posterior horn of the lateral ventricle in patients with AD were significantly higher than that in normal elderly (P<0.05).The volume of the left,right and total cerebral ventricle, the angle of the anterior horn of the left and right lateral ventricle and the angle of the temporal horn of the left and right lateral ven-tricle were negatively correlated with MMSE (P<0.05).Conclusion Patients with AD exhibites significantly greater volume and an-gle of the lateral ventricular than normal elderly people.These related data measured can predict brain parenchymal atrophy of pa-tients with AD more conveniently and accurately.