HER2-positive breast carcinomas with a PIK3CA mutation are less likely to achieve a pCR after neoadjuvant anthracycline-taxane-based chemotherapy plus anti-HER2 treatment, even if a dual anti-HER2 treatment is given.

The coronavirus disease 2019 (COVID-19) pandemic is a global disaster, and recent studies have shown its association with increasing mental health problems such as post-traumatic stress disorder (PTSD), depression, anxiety, and stress. Nursing students, especially nursing interns, may be shunned, harassed, and even blamed as potential COVID-19 spreaders, though they were an important reserve force against COVID-19 and other diseases. Of note, the psychological influences of COVID-19 on nursing students remained unclear. The aim of this study was to evaluate the mental health of nursing students during the COVID-19 pandemic. A cross-sectional online survey was conducted on nursing students in a vocational college from April 12 to 23, 2020. The Impact of Event Scale–Revised, 21-item Depression, Anxiety and Stress Scale, and Pittsburgh Sleep Quality Index were used to assess the degree of symptoms of PTSD, depression, anxiety, stress, and insomnia, respectively. Multivariable logistic regression analysis was performed to determine the potential risk factors for the psychological symptoms. A total of 1,780 college nursing students were asked to participate in this online survey, with 1,532 complete responses. In total, 682 (44.5%) college nursing students reported having PTSD, 358 (22.8%) students reported insomnia, and few students reported depression (n = 45, 2.9%), anxiety (n = 44, 2.9%), and stress (n = 17, 1.1%) symptoms. As compared with junior, female, and rural nursing students, the senior, male, and urban nursing students had higher rates of PTSD, depression, anxiety, stress, respectively, whereas male nursing students had a higher insomnia rate. Multivariable analysis showed that senior nursing students had higher risks of PTSD, depression, anxiety; being male was associated with higher risks of PTSD, depression, anxiety, stress, and insomnia; and urban nursing students had higher risks of PTSD, depression, anxiety, and stress. In summary, a considerable number of nursing students reported mental symptoms of PTSD and insomnia, though few reported mental symptoms of depression, anxiety, and stress. Furthermore, senior, male, and urban nursing students are at risk for developing mental symptoms. Appropriate psychological interventions should be implemented to assure the mental health of nursing students.

Low‐intensity ultrasound‐microbubble (LIUS‐MB) treatment is a promising antivascular therapy for tumors. We sought to determine whether LIUS‐MB treatment with an appropriate ultrasound pressure could achieve substantial and persistent cessation of tumor perfusion without having significant effects on normal tissue. Further, we investigated the mechanisms underlying this treatment. Murine S‐180 sarcomas, thigh muscles, and skin tissue from 60 tumor‐bearing mice were subjected to sham therapy, an ultrasound application combined with microbubbles in four different ultrasound pressures (0.5, 1.5, 3.0, 5.0 MPa), or ultrasound at 5.0 MPa alone. Subsequently, contrast‐enhanced ultrasonic imaging and histological studies were performed. Tumor microvessels, tumor cell necrosis, apoptosis, tumor growth, and survival were evaluated in 85 mice after treatment with the selected ultrasound pressure. We found that twenty‐four hours after LIUS‐MB treatment at 3.0 MPa, blood perfusion and microvessel density of the tumor had substantially decreased by 84 ± 8% and 84%, respectively (p < 0.01). Similar reductions were not observed in the muscle or skin. Additionally, an extreme reduction in the number of immature vessels was observed in the tumor (reduced by 90%, p < 0.01), while the decrease in mature vessels was not significant. Further, LIUS‐MB treatment at 3.0 MPa promoted tumor cell necrosis and apoptosis, delayed tumor growth, and increased the survival rate of tumor‐bearing mice (p < 0.01). These findings indicate that LIUS‐MB treatment with an appropriate ultrasound pressure could selectively and persistently reduce tumor perfusion by depleting the neovasculature. Therefore, LIUS‐MB treatment offers great promise for clinical applications in antivascular therapy for solid tumors.

Objective: Ultrasound molecular imaging (UMI) of glycoprotein (GP) IIb/IIIa receptor on activated platelets offers a unique means of identifying high-risk atherosclerosis. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) targeted to GP IIb/IIIa could be used to detect and quantify activated platelets on the surface of advanced plaques.Methods and Results: A mouse model of advanced atherosclerosis was generated by maintaining apolipoprotein E-deficient (ApoE-/-) mice on a hypercholesterolemic diet (HCD). The three other experimental groups consisted of ApoE-/- and wild-type (C57BL/6) mice fed a normal chow diet and C57BL/6 mice on an HCD diet. Plaque formation was confirmed by histological and immunohistochemical methods using light, fluorescence, and electron microscopy. Mice were injected with a lipid MB-conjugated cyclic Arg-Gly-Asp peptide or nonspecific control peptide, and the abdominal aorta was examined by UMI. The accumulation of GP IIb/IIIa and activated platelets on the surface of atherosclerotic plaques was highest in the ApoE-/-+HCD group, followed by ApoE-/-+chow, C57BL/6+HCD, and C57BL/6+chow groups (P<0.05). Notably, GP IIb/IIIa expression was associated with the vulnerability index and necrotic center/fiber cap ratio (P<0.05), and contrast video intensity from adhered cyclic Arg-Gly-Asp-modified MBs (MB-cRGDs) was correlated with GP IIb/IIIa expression on the plaque surface (P<0.05).Conclusion: GP IIb/IIIa of activated platelets on the atherosclerotic endothelium is a biomarker for high-risk plaques that can be quantified by UMI using MB-cRGDs, providing a noninvasive means for detecting high-risk plaques and preventing acute cardiovascular events.

With the rapid development of cancer-targeted nanotechnology, a variety of nanoparticle-based drug delivery systems have clinically been employed in cancer therapy. However, multidrug resistance significantly impacts the therapeutic efficacy. Physical non-drug therapy has emerged as a new and promising strategy. This study aimed to determine whether novel folate-nanobubbles (F-NBs), combined with therapeutic ultrasound (US), could act as a safe and effective physical targeted cancer therapy. Using folate-conjugated N-palmitoyl chitosan (F-PLCS), we developed novel F-NBs and characterised their physicochemical properties, internalization mechanism, targeting ability, therapeutic effects, and killing mechanism. The results showed that the novel F-NBs selectively accumulated in FR-positive endothelial cells and tumour cells via FR coupled with clathrin- and caveolin-mediated endocytosis in vitro and in vivo. In addition, the F-NBs killed target cells by an intracellular explosion under US irradiation. Hoechst/PI staining demonstrated that apoptosis and necrosis accounted for a large proportion of cell death in vivo. F-NBs combined with US therapy significantly inhibited tumour growth and improved the overall survival of tumour-bearing mice. Under US irradiation, the novel F-NBs selectively killed FR-positive tumour cells in vitro and in vivo via intracellular explosion and therefore is a promising alternative for targeted cancer treatment.

Although a white spot syndrome virus (WSSV) subunit vaccine could significantly enhance the immune response and benefit the shrimp host, its practical application is currently not feasible because of drawbacks in existing expression systems. We generated a transgenic Dunaliella salina (D. salina) strain by introducing the WSSV VP28 gene to produce a novel oral WSSV subunit vaccine. Following transformation of D. salina, VP28 gene expression was assessed by reverse transcription polymerase chain reaction (RT-PCR) assays, enzyme-linked immunosorbent assays (ELISAs), and western blot analysis. The RT-PCR results indicated that the VP28 gene was successfully expressed in D. salina cells. The presence of recombinant VP28 proteins with natural bioactivity was confirmed by western blot analysis and ELISA. Animal vaccination experiments indicated that transgenic D. salina can induce protection against WSSV by oral delivery in crayfish. Our findings indicate that the VP28 gene can be successfully expressed in transgenic D. salina and can be applied as an oral vaccine to protect crayfish against WSSV. We have demonstrated that it is feasible to produce an oral vaccine using D. salina, and thereby provide a new method for controlling other viral diseases in crustaceans.

Cyclic RGD-modified MBs targeted to GP IIb/IIIa with CEU are capable of detecting inflammation-activated platelets and thrombosis in large arteries, thus providing a potential tool for identification of vulnerable atherosclerotic plaques.

Purpose<i>PIK3CA</i>, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. <i>PIK3CA</i>mutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of <i>PIK3CA</i> mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.Materials and MethodsA total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of <i>PIK3CA</i> mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues.ResultsSeven of 90 tumors (7.8%) were detectable with a <i>PIK3CA</i> H1047R mutation. Overall, <i>PIK3CA</i> H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056).ConclusionTNBC with a <i>PIK3CA</i> H1047R mutation was less likely to achieve pCR after anthracyclinebased neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.