Prognostic value of multi-PLD ASL-based cerebral perfusion ASPECTS in acute ischemic stroke.

Introduction: We aimed to verify the application value of the Alberta Stroke Program Early CT Score (ASPECTS) based on multiple post-labeling delay (multi-PLD) arterial spin labeling (ASL) for outcome assessment in acute ischemic stroke (AIS) patients. Method: The endpoint was modified Rankin scale score at 90 days (90-day mRS). Patients were divided into the good outcome (0-2) and poor outcome (3-6) groups. The independent samples t-test, Mann-Whitney U-test, and χ2-test were used to compare clinical and imaging parameters between groups. We used partial correlation analysis to evaluate the relationships between ASPECTS and outcomes. Multivariate logistic regression analysis was used to examine potential independent prognostic indicators. The receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the independent prognostic indicators in predicting outcomes. Results: Fifty-five AIS patients were included. The good outcome group had a lower baseline National Institutes of Health Stroke Scale (NIHSS; Z = -3.413, P < 0.001) and infarct core volume (ICV; Z = -3.114, P = 0.002) as well as higher cerebral blood flow (CBF)-ASPECTS (Z = -3.835, P < 0.001) and cerebral blood volume (CBV)-ASPECTS (Z = -4.099, P < 0.001). Higher CBF-ASPECTS (r = -0.459, P = 0.001), and CBV-ASPECTS (r = -0.502, P < 0.001) were associated with a lower 90-day mRS. The baseline NIHSS, CBF-ASPECTS, and CBV-ASPECTS were identified as independent prognostic indicators. The AUCs of the baseline NIHSS, CBF-ASPECTS, and CBV-ASPECTS were 83.3, 87.4, and 89.9%, respectively. Combining NIHSS with CBF-ASPECTS and CBV-ASPECTS, the AUC significantly improved to 96.3%. The combined three factors showed a significant difference compared to the baseline NIHSS (Z = 2.039, P = 0.041) and CBF-ASPECTS (Z = 2.099, P = 0.036), but no difference with CBV-ASPECTS (Z = 1.176, P = 0.239). Conclusions: The ASPECTS based on multi-PLD ASL is a valuable tool for identifying independent prognostic indicators and assessing clinical outcomes in AIS patients. The baseline NIHSS, combined with CBF-ASPECTS and CBV-ASPECTS, enhances the predictive efficacy of clinical outcomes in AIS patients. The CBV-ASPECTS alone can offer comparable predictive efficacy to the combination.

Metabolomics analysis of physicochemical properties associated with freshness degradation in frozen Antarctic krill (Euphausia superba).

This study aimed to determine the effect of different frozen temperatures during storage on the quality of Antarctic krill (Euphausia superba) and assess the change at the metabolite level via a combination of physicochemical property analysis, liquid chromatography-tandem mass spectrometry (LC-MS) based non-targeted metabolomics profiling. Regarding samples stored at -20 °C, the expressions of 7055 metabolites were elevated, while 2313 were downregulated. Lipids and lipid molecules had the highest proportion of differential metabolites. A total of 432 discriminatory metabolites with Kyoto Encyclopedia of Genes and Genomes (KEGG) IDs was obtained. We also observed that the concentrations of differential bitter free amino acids (FAAs) and oxidation products of arachidonic and linoleic acid increased. Moreover, as the storage temperature increased, the freshness, umami, and sweetness components were considerably reduced. Furthermore, results indicated that the color, pH and water-holding capacity (WHC) were potential indicators of quality deterioration, while inosinic acid was a probable biomarker for umami degradation of frozen Antarctic krill. In conclusion, this study demonstrates that storage at lower temperatures can be beneficial for maintaining the freshness of Antarctic krill from macro and micro perspectives.

Research on Nonlinear Behavior of Local High-Performance Concrete Beam-Column Connections.

The seismic performance index of prefabricated structures is generally obtained via experimental analysis. However, in experimental research, it is impossible that every influencing factor can be taken into account. Therefore, the finite element analysis method can be used as a supplementary method for experimental research to carry out parametric analysis of joints. Based on this test, a hysteretic model of steel bars is developed on the ABAQUS platform; meanwhile, the model is used to simulate the seismic analysis of the proposed local reinforced joints. The hysteresis curve obtained via simulation exhibits a high degree of coincidence with the experimental results. Based on the validated model, a detailed parameter analysis of prefabricated local reinforced concrete frame joints is carried out. The analysis results illustrate that the axial pressure ratio at the top of the column has a minimal impact on the joint's performance. Decreasing the stirrup ratio within the core region, enlarging the diameter of the PC steel bar, and increasing the concrete strength that is poured in the keyway and the core region can raise the cumulative energy consumption of the joints, thereby reducing the damage degree of other units and improving the maximum bearing capability of the joints.

Inhibitory effects of pH, salinity, and tea polyphenols concentration on the specific spoilage organisms isolated from lightly-salted large yellow croaker (Pseudosciaena crocea).

Proteus vulgaris and Hafnia alvei were identified as specific spoilage organisms (SSOs) isolated from the refrigerated lightly-salted large yellow croaker (Pseudosciaena crocea). In this work, the inhibitory effects of pH, salinity, and tea polyphenols concentration on both strains were investigated. Modified Gompertz models were used to estimate the kinetic parameters µm (maximum specific growth rate) and λ (duration of lag phase) of the two strains under different conditions, demonstrating that their growth rates decreased with the decrease of pH as well as the increase of salinity and tea polyphenols concentration, and the growths of both strains stopped while the salinity and tea polyphenols concentration increased to 0.05 and 5%, respectively. Response surface methodology (RSM) based on a three-level three-factor Box-Behnken Design (BBD) was employed to optimize the combination of these three antibacterial factors. The results showed that the optimum inhibitory conditions were: tea polyphenols concentration 0.05%, salinity 3.46%, and pH 6.96 to inhibit the growth of P. vulgaris; tea polyphenols concentration 0.05%, salinity 3.45%, and pH 6.94 to inhibit H. alvei. Validation experiments were performed and demonstrated that under these conditions, the growth of the two SSOs could be 100% inhibited. This research provided references for the inhibition of the SSOs of lightly-salted large yellow croaker and the extension of its shelf life.

Long noncoding RNA FGF14-AS2 inhibits breast cancer metastasis by regulating the miR-370-3p/FGF14 axis.

Long noncoding RNAs (lncRNAs) have emerged as important regulators in cancers, including breast cancer. However, the overall biological roles and clinical significance of most lncRNAs are not fully understood. This study aimed to elucidate the potential role of a novel lncRNA FGF14-AS2 and the mechanisms underlying metastasis in breast cancer. The lncRNA FGF14-AS2 was significantly downregulated in breast cancer tissues; patients with lower FGF14-AS2 expression had advanced clinical stage. In vitro and in vivo assays of FGF14-AS2 alterations revealed a complex integrated phenotype affecting breast cancer cell migration, invasion, and tumor metastasis. Mechanistically, FGF14-AS2 functioned as a competing endogenous RNA of miR-370-3p, thereby leading to the activation of its coding counterpart, FGF14. Clinically, we observed increased miR-370-3p expression in breast cancer tissues, whereas FGF14 expression was decreased in breast cancer tissues compared to the adjacent normal breast tissues. FGF14-AS2 expression was significantly negatively correlated with miR-370-3p expression, and correlated positively to FGF14 expression. Collectively, our findings support a model in which the FGF14-AS2/miR-370-3p/FGF14 axis is a critical regulator in breast cancer metastasis, suggesting a new therapeutic direction in breast cancer.

Combining the tumor abnormal protein test with tests for carcinoembryonic antigens, cancer antigen 15-3, and/or cancer antigen 125 significantly increased their diagnostic sensitivity for breast cancer.

BACKGROUND: The tumor abnormal protein (TAP) test is used to screen for many cancers, but its use for breast cancer has not been studied. METHODS: Tests for carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), and TAP were administered to 261 women with operable benign breast disease and 348 with breast cancer. The cutoff value used for TAP was the mean + 3 standard deviations for benign breast disease patients (275.64 µm). Sensitivities and specificities of single biomarker tests and combined tests were compared. The combined tests were defined as positive if any single biomarker was positive, and negative otherwise. RESULTS: The single biomarker test sensitivities were similar: CEA, 7.18%; CA125, 4.89%; CA15-3, 7.47%; and TAP, 4.89%. For the combinations TAP + CEA + CA125, TAP + CEA + CA15-3, TAP + CA125 + CA15-3, and TAP + CEA + CA125 + CA15-3, the sensitivities were 16.67%, 17.82%, 16.38%, and 21.84%, respectively, and the specificities were 93.49%, 97.70%, 93.87%, and 92.72%. CONCLUSIONS: The 4-test combination showed the highest sensitivity (21.84%) and may be auxiliary used in early screening. TAP + CEA + CA15-3 showed high specificity (97.70%) and so could be used for confirming breast cancer.

Biological effect of ribosomal protein L32 on human breast cancer cell behavior.

Breast cancer (BC) is the most common malignancy among women worldwide. However, identifying effective biomarkers for the diagnosis and treatment of BC is challenging. Based on our previously developed 'humanized' mouse model of BC, microarray expression analysis was performed and multiple differentially expressed genes, including ribosomal protein (RP) L32, were screened. Recent reports have revealed that RPs are relevant to the development and progression of cancer. However, the expression and function of RPL32 in BC remains unknown. Therefore, in the present study, the role of RPL32 in the development of BC was explored. Immunohistochemical staining and reverse transcription­quantitative PCR were used, and it was found that RPL32 was upregulated in human BC tissues and cells. Cell Counting Kit­8, cell invasion and migration assays were performed, which demonstrated that RPL32 knockdown using lentivirus­delivered small interfering RNA inhibited the migration and invasion of BC cells in vitro and in vivo (nude mouse model). Moreover, western blotting showed that RPL32 knockdown decreased the expression levels of matrix metalloproteinase (MMP)­2 and MMP­9. Thus, the present findings indicated a potential oncogenic role of RPL32, suggesting that it may be a novel target for molecular targeted therapy in patients with BC.

Implanting totally implantable venous access ports in the upper arm is feasible and safe for patients with early breast cancer.

PURPOSE: Totally implantable venous access ports are widely used in chemotherapy for malignant tumors. This retrospective study investigated the safety, technical feasibility, and device-related complications of totally implantable venous access ports implanted in the upper arm. METHODS: Between May 2016 and June 2018, 570 women with early breast cancer received chemotherapy and were successfully implanted with a totally implantable venous access port in the upper arm. Device-related complications were collected and influencing factors were analyzed for major complications. RESULTS: Only one case underwent premature port removal before the end of chemotherapy. Device-related complications were observed in 32 cases, including 31 late complications. The rate of complications was 0.263/1000 catheter-days. Infection and thrombosis were the most common complications, occurring in 13 and 8 cases, respectively. Other complications were catheter occlusion, catheter dislocation, arrhythmia, and so on. Patients with higher body mass index were significantly more prone to infection and those who experienced catheter-related thrombosis had longer implantation times and higher body mass indices. CONCLUSION: Implanting totally implantable venous access ports in the upper arm is feasible and safe for patients with early breast cancer, with a low rate of complications, providing good alternative to central venous ports.

Non-doctoral factors influencing the surgical choice of Chinese patients with breast cancer who were eligible for breast-conserving surgery.

BACKGROUND: The rate of breast-conserving surgery (BCS) is low in China. Many patients choose mastectomy even when informed that there is no difference in the overall survival rate compared with that of BCS plus radiotherapy. This study aimed to investigate the factors that influenced the surgical choice in patients eligible for BCS. METHODS: Female patients with breast carcinoma were enrolled in a single center from March 2016 to January 2017. They made their own decision regarding the surgical approach. Univariate analysis was employed to determine the factors associated with the different breast surgical approaches. Significant factors (defined as P < 0.05) were then incorporated into multivariate logistic regression models to determine the factors that independently influenced patients' decision. RESULTS: Of the 271 patients included, 149 were eligible for BCS; 65 chose BCS and 84 chose mastectomy. On the basis of univariate analysis, patients with younger age, higher income and education, shorter admission to surgery interval, and shorter confirmed diagnosis to surgery interval were more likely to choose BCS than mastectomy (P < 0.05). Meanwhile, patients who resided in rural regions, did not have general medicare insurance, and were diagnosed with breast cancer preoperatively were more inclined to choose mastectomy than BCS (P < 0.05). The multivariate model revealed three independent influencing factors: age at diagnosis (P = 0.009), insurance status (P = 0.035), and confirmed diagnosis to surgery interval (P = 0.037). In addition, patients receiving neoadjuvant chemotherapy (NCT) were more inclined to choose mastectomy. CONCLUSION: Surgical choice of patients eligible for BCS was affected by several factors, and age at diagnosis, confirmed diagnosis to surgery interval, and insurance status were independent factors.

Efficacy of two-weekly nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy for breast cancer.

Aim: Compare the two-weekly regimens of nanoparticle albumin-bound paclitaxel (nab-P) with solvent-based paclitaxel (sb-P) as neoadjuvant chemotherapy for breast cancer. Materials & methods: Patients (n = 162) with operable early breast cancer received four cycles of dose-dense epirubicin and cyclophosphamide followed by four two-weekly cycles of nab-P (n = 83) or sb-P (n = 79), with trastuzumab when needed. Results: Across all the patients, the ypT0 ypN0 and ypT0/is ypN0 pathological complete response rates in the nab-P group were not superior to those in the sb-P group. However, pathological complete response rates for triple-negative breast cancer were significantly better with nab-P than with sb-P. Meanwhile, nab-P also induced more peripheral sensory neuropathy. Conclusion: The two-weekly nab-P regimen is a good neoadjuvant chemotherapy choice for triple-negative breast cancer.

Long-acting formulation of a new muscarinic receptor antagonist for the treatment of overactive bladder.

A new muscarinic receptor antagonist, 5-hydroxymethyl tolterodine (5-HMT), was successfully encapsulated into PLGA microspheres. With an increase of PLGA concentration from 15% to 40%, encapsulation efficiency of 5-HMT increased from 55.39% to 76.32%, and the particle size of microsphere increased from 34.33 to 70.48 µm. Increasing the homogenisation speed from 850 to 2300 rpm, the particle size was reduced about 65%.The in vitro and in vivo studies in beagle dogs show that the release profile of 5-HMT-loaded microspheres (5-HMT MS) prepared with 503H is characterised by a low initial burst followed by slow release that lasted for 2 weeks. A C(max) of 1.617 ± 0.392 ng/mL was found on the sixth day. When evaluated for inhibition of the carbachol-induced contraction of rat urinary bladder, 5-HMT MS showed a much longer and more potent effect than tolterodine tablets. The mean urination time of the rats in the 5-HMT MS group was significantly decreased (p < 0.05 or p < 0.01) to less than 2 weeks.

Effects of formulation parameters on encapsulation efficiency and release behavior of risperidone poly(D,L-lactide-co-glycolide) microsphere.

A 4-week sustained release risperidone biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microsphere for the therapy of schizophrenia, the effects of formulation parameters on encapsulation efficiency and release behavior were studied. The risperidone PLGA microspheres were prepared by O/W solvent evaporation method and characterized by HPLC, SEM, laser particle size analysis, GC and HPLC-MS. The results indicated that the morphology of the risperidone PLGA microspheres presented a spherical shape with smooth surface, the particle size was distributed from 32 to 92 microm and the drug encapsulation efficiency was influenced by homogeneous rotation speed, intrinsic viscosity, carboxylic terminal group, the polymer concentration in the oil phase and the molecular weight of the polymer. These changes were also reflected in drug release. When the Mw of the polymers increased from ca. 28000 to ca. 90000, the initial burst release of risperidone PLGA microspheres decreased from 13 to 0.8% and the sustained-release could be extended to 4 weeks. Pharmacokinetic study on beagle dogs showed that the 4-week sustained release profile of the risperidone loaded microspheres prepared with 75253A was verified. The PLGA 75253A and 75255A show the potential as excipients for the monthly sustained release risperidone PLGA microspheres due to higher encapsulation efficiency and almost zero-order release kinetics of release profile.