[A nomogram to predict non-sentinel lymph node metastasis for breast cancer patients with positive axillary sentinel lymph node].

Objective: To identify the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1~2 positive axillary sentinel lymph node (SLN) and construct an accurate prediction model. Methods: Retrospective chart review was performed in 917 breast cancer patients who underwent surgery treatment between 2002 and 2017 and pathologically confirmed 1-2 positive SLNs. According to the date of surgery, patients were divided into training group (497 cases) and validation group (420 cases). A nomogram was built to predict nSLN metastasis and the accuracy of the model was validated. Results: Among the 917 patients, 251 (27.4%) had nSLN metastasis. Univariate analysis showed tumor grade, lymphovascular invasion (LVI), extra-capsular extension (ECE), the number of positive and negative SLN and macro-metastasis of SLN were associated with nSLN metastasis (all P<0.05). Multivariate Logistic regression analysis showed the numbers of positive SLN, negative SLN and macro-metastasis of SLN were independent predictors of nSLN metastasis (all P<0.05). A nomogram was constructed based on the 6 factors. The area under the receiver operating characteristic curve was 0.718 for the training group and 0.742 for the validation group. Conclusion: We have developed a nomogram that uses 6 risk factors commonly available to accurately estimate the likelihood of nSLN metastasis for individual patient, which might be helpful for radiation oncologists to make a decision on regional nodal irradiation.

Knockdown of lncRNA HCP5 protects against cerebral ischemia/reperfusion injury by regulating miR-652-3p.

Previous studies have shown that lncRNAs play crucial roles in cerebral ischemia/reperfusion injury. In this study, the function and possible mechanism of lncRNA HCP5 in cerebral ischemia/reperfusion injury was investigated. An oxygen glucose deprivation (OGD) model in N2a cells was used to simulate cerebral ischemia/reperfusion injury in vitro. The functional mechanism of lncRNA HCP5 was detected using Trypan blue staining, JC-1, MTT and dual luciferase reporter assays. The expression of apoptosis-related proteins (Bcl-2 and Bax) was measured by Western blot analysis. We found that lncRNA HCP5 was upregulated in N2a cells treated with OGD/R, and knockdown of lncRNA HCP5 enhanced cell viability and reduced cell death. In addition, miR-652-3p was found to act as a sponge for lncRNA HCP5. The overexpression of miR- 652-3p can prevent cerebral ischemic reperfusion injury, however, lncRNA HCP5 attenuated the protective effect of miR-652-3p in cerebral ischemic reperfusion injury. In conclusion, upregulation of lncRNA HCP5 may exacerbate cerebral ischemic reperfusion injury by sponging miR-652-3p.

Diffusion-limited PBPK model for predicting pulmonary pharmacokinetics of florfenicol in pig.

For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been thought to be responsible for antimicrobial efficacy. In this study, a diffusion-limited physiologically based pharmacokinetic (PBPK) model was developed to predict the pulmonary pharmacokinetics of florfenicol (FF) in pigs. The model included separate compartments corresponding to blood, diffusion-limited lung, flow-limited muscle, liver, and kidney and an extra compartment representing the remaining carcass. The absorption rate constant and renal and hepatic clearance of FF were determined in vivo. Other parameters were taken from the literature or optimized based on existing pharmacokinetic data. All mathematical operations during the development of the model were performed using acslXtreme version 3.0.2.1 (Aegis Technologies Group, Inc., Huntsville, AL, USA). The model accurately predicted the concentration-time courses of FF in lung interstitial fluid, serum, and plasma following different dosing schedules, except at the dose of 15 mg/kg. When compared with the tissue residue data, the model generally underestimated the FF concentration at the injection site, whereas it gave good predictions of FF concentrations in lung, liver, and kidney at early time points. The model predictions provide a scientific basis for the dosage regimen design of FF.

[Analysis of the clinicopathological characteristics and prognosis in 674 cases of breast intraductal papillary tumor].

Objective: Breast intraductal papillary tumors are clinically common diseases derived from the ducts. The aim of this study is to investigate the clinicopathological characteristics of intraductal papillary tumors and risk factors for carcinogenesis. Methods: The clinicopathological data of 674 patients with breast intraductal papillary tumors, who underwent surgery in the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from January 2010 to July 2015, were retrospectively analyzed. Results: The median follow-up time was 46 months. The 674 cases were classified into 547 intraductal papilloma, 88 cases of intraductal papillary carcinoma, 32 cases of intracystic papillary carcinoma, and 7 cases of solid papillary carcinoma of breast. After a median follow-up time of 46 months, 13 out of 547 (2.4%) intraductal papillomas had local recurrence in the original dissected quadrat, another 10 cases developed breast cancer in the original dissected quadrat. The 3-year recurrence-free survival rates in intraductal papilloma and intraductal papilloma accompanied with atypical ductal hyperplasia were 97.7% and 93.5%, respectively, the recurrence-free survival curves showed a significant difference (P=0.011). Multivariate analysis indicated that atypical ductal hyperplasia was a major prognostic factor affecting the recurrence-free survival of intraductal papilloma (RR=0.183, 95%CI=0.054 to 0.777, P=0.020). Four cases (3.1%) of intraductal papillary carcinoma had local recurrence. The logistic analysis showed that patient aged >45 years, clinical manifestations of a breast lump, maximum tumor diameter greater than 2 cm are possible clinical manifestation of malignant breast intraductal papillary tumors (RR=1.735, 95%CI=1.007-2.990, P=0.047; RR=2.849, 95%CI=1.207-6.711, P=0.017; RR=3.792, 95%CI=2.162-6.653, P<0.001). Conclusions: Intraductal papillary tumors have a certain recurrence rate. Age, clinical features and tumor size may be predictive factors of intraductal papillary carcinoma.

Lung microdialysis study of florfenicol in pigs after single intramuscular administration.

For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been considered as the gold standard for estimating the antibacterial efficacy. In this study, the pharmacokinetics of florfenicol (FF) in porcine lung interstitial fluid was investigated after single intramuscular administration at two different doses (20 and 50 mg/kg). Twelve pigs underwent thoracotomy under general anesthesia. Then, the CMA/30 probe was implanted into the lung and perfused at 1 µL/min. The microdialysis (MD) samples were collected on a preset schedule and analyzed by high-performance liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis was performed. FF exhibited rapid distribution and slow elimination in porcine lung interstitial fluid. The main pharmacokinetic parameters at 20 and 50 mg/kg were 4.88 ± 0.54 and 10.36 ± 2.52 µg/mL for the maximum concentration (Cmax ), 3.25 ± 0.32 and 3.50 ± 0.27 h for the time to Cmax (Tmax ), 9.47 ± 6.84 and 7.75 ± 3.23 h for the half-life (t1/2 ), 0.10 ± 0.06 and 0.10 ± 0.04 1/h for the terminal elimination rate constant (λz ), 13.85 ± 7.97 and 11.42 ± 2.79 h for the mean residence time (MRT), 37.77 ± 8.13 and 71.15 ± 16.99 h·µg/mL for the area under the curve from time 0 to 18.25 h (AUC0-18.25 ), and 51.18 ± 20.11 and 88.78 ± 27.58 h·µg/mL for the area under the curve from time 0 to infinity (AUC0-∞ ), respectively.

The effect of maternal infection on cognitive development and hippocampus neuronal apoptosis, proliferation and differentiation in the neonatal rats.

Many epidemiological reports stated a strong association between maternal infection and development of cerebral palsy, which is a major cause of cognitive impairment. The pathophysiological mechanism of intrauterine inflammation is complex. Recently, it was demonstrated that inflammation has a modulating effect on adult neurogenesis. In this study, we discovered the effect of maternal infection to hippocampal neuronal apoptosis, proliferation and differentiation, and cognitive development in the developing brains of neonatal rats. Morris water maze test was used to assess learning and memory. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to determine neuronal apoptosis, immunostaining was conducted to assess neurogenesis, and Western blot for extracellular signal-regulated kinase (ERK), cyclic AMP responsive element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Results demonstrated that maternal infection increased neuronal apoptosis and significantly impaired spatial learning and memory ability. Maternal infection significantly increased cell proliferation, accompanied by an increased expression of ERK (P3-P7), CREB (P3-P7) and BDNF (P3). On P28, there was no significant difference of cell survival and differentiation in two groups. These results suggest that variation in ERK activity and subsequent expression of its downstream targets, including CREB and BDNF might contribute, at least partially, to modulation of inflammation related cell proliferation, survival and differentiation. Maternal infection increased hippocampal neuronal apoptosis and affected cell proliferation and differentiation in neonatal rats, which may be regarded as an etiological factor in cognitive development impairment.