Photothermal Temperature-Modulated Cancer Metastasis Harnessed Using Proteinase-Triggered Assembly of Near-Infrared II Photoacoustic/Photothermal Nanotheranostics.

Here we demonstrate that cancer metastasis could be modulated by the judicious tuning of physical parameters such as photothermal temperature in nanoparticle-mediated photothermal therapy (PTT). This is supported by theranostic nanosystem design and characterization, in vitro and in vivo analyses, and transcriptome-based gene profiling. In this work, the highly efficient near-infrared II (NIR-II) photoacoustic image (PA)-guided PTT are selectively activated using our developed matrix metalloproteinase (MMP)-triggered in situ assembly of gold nanodandelions (GNDs@gelatin). Unlike other "always-on" NIR PTT agents lacking specific bioactivation and suffering from the intrinsic nonspecific pseudosignals and treatment-related side effects such as metastasis, our GNDs@gelatin possesses important advantages while deployed in cancer PTT that include the following: (1) The theranostic effects could be "turned on" only after specific MMP-2/-9 activity and with acidity in the tumor microenvironment. (2) The quantitative PA diagnosis allows for precise PTT planning for better cancer treatment. (3) GNDs@gelatin could noninvasively quantify MMP activity and efficiently harness NIR-I (808 nm) and NIR-II (1064 nm) energies for tumor ablation. (4) The multibranched nanostructures reabsorb scattered laser photons, thus enhancing the surface plasmons for the pronounced photothermal conversion of aggregated GNDs@gelatin in situ. (5) It is noteworthy that in situ tumor eradication at higher PTT temperature (>55 °C) mediated by GNDs@gelatin could induce subsequent metastasis, which could be otherwise abolished at lower PTT temperatures (50 °C > T > 43 °C). (6) Furthermore, the gene profiling using transcriptome-based microarray including GO and KEGG analyses revealed that 315 differentially expressed genes were identified in higher PTT temperature treated tumors compared with lower PTT temperature ones. These were enriched into some well-known cancer-related pathways, such as cell migration pathway, signal transductions, cell proliferation, wound healing, PPAR signaling, and metabolic pathways. These observations suggest a new perspective of "moderate-is-better" in nanoparticle-mediated PTT for maximizing its therapeutic/prognosis benefits and translational potential with metastasis inhibition.

The influence of chronic renal insufficiency on multi-therapeutic modalities for breast cancer: a single-center experience.

BACKGROUND: Due to the presence of other comorbidities and multi-therapeutic modalities in breast cancer, renally cleared chemotherapeutic regimens may cause nephrotoxicity. The aim of this retrospective study is to compare the chemotherapy types and outcomes in breast cancer patients with or without chronic renal disease. PATIENTS AND METHODS: We retrospectively enrolled 62 female patients with breast cancer and underlying late stages (stage 3b, 4, and 5) of chronic kidney disease (CKD) treated from 2000 to 2017. They were propensity score-matched 1:1 with patients in our database with breast cancer and normal renal function (total n = 124). RESULTS: The main subtype of breast cancer was luminal A and relatively few patients with renal impairment received chemotherapy and anti-Her-2 treatment. The breast cancer patients with late-stage CKD had a slightly higher recurrent rate, especially at the locally advanced stage. The 5-year overall survival was 90.1 and 71.2% for patients without and with late-stage CKD, but the breast cancer-related mortality rate was 88.9 and 24.1%, respectively. In multivariate analyses, dose-reduced chemotherapy was an independent negative predictor of 5-year recurrence-free survival and late-stage CKD was associated with lower 5-year overall survival rate. CONCLUSIONS: Breast cancer patients with late-stage CKD may receive insufficient therapeutic modalities. Although the recurrence-free survival rate did not differ significantly by the status of CKD, patients with breast cancer and late-stage CKD had shorter overall survival time but a lower breast cancer-related mortality rate, indicated that the mortality was related to underlying disease.

Radiation-induced skin and heart toxicity in patients with breast cancer treated with adjuvant proton radiotherapy: a comparison with photon radiotherapy.

This study aimed to investigate the dose parameters and incidence of radiotherapy (RT)-associated toxicity in patients with left breast cancer (LBC) treated with proton-RT, compared with photon-RT. We collected data from 111 patients with LBC who received adjuvant RT in our department between August 2021 and March 2023. Among these patients, 24 underwent proton-RT and 87 underwent photon-RT. In addition to the dosimetric analysis for organs at risk (OARs), we measured NT-proBNP levels before and after RT. Our data showed that proton-RT improved dose conformity and reduced doses to the heart and lungs and was associated with a lower rate of increased NT-proBNP than did photon-RT. Regarding skin toxicity, the Dmax for 1 c.c. and 10 c.c. and the average dose to the skin-OAR had predictive roles in the risk of developing radiation-induced dermatitis. Although pencil beam proton-RT with skin optimization had a dose similar to that of skin-OAR compared with photon-RT, proton-RT still had a higher rate of radiation dermatitis (29%) than did photon RT (11%). Using mice 16 days after irradiation, we demonstrated that proton-RT induced a greater increase in interleukin 6 and transforming growth factor-ß1 levels than did photon-RT. Furthermore, topical steroid ointment reduced the inflammatory response and severity of dermatitis induced by RT. In conclusion, we suggest that proton-RT with skin optimization spares high doses to OARs with acceptable skin toxicity. Furthermore, prophylactic topical steroid treatment may decrease radiation dermatitis by alleviating proton-induced inflammatory responses in vivo.

Lysosomal-targeted doxorubicin delivery using RBC-derived vesicles to overcome drug-resistant cancer through mitochondrial-dependent cell death.

Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Nanoparticles as drug delivery systems (DDSs) show promise for MDR cancer therapy. However, current DDSs require sophisticated design and construction based on xenogeneic nanomaterials, evoking feasibility and biocompatibility concerns. Herein, a simple but versatile biological DDS (bDDS) composed of human red blood cell (RBC)-derived vesicles (RDVs) with excellent biocompatibility was surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs that remarkably suppressed MDR in uterine sarcoma through a lysosomal-mitochondrial axis-dependent cell death mechanism. Dox-gluRDVs can efficiently deliver and accumulate Dox in lysosomes, bypassing drug efflux transporters and facilitating cellular uptake and retention of Dox in drug-resistant MES-SA/Dx5 cells. The transfer of lysosomal calcium to the mitochondria during mitochondria-lysosome contact due to lysosomal Dox accumulation may result in mitochondrial ROS overproduction, mitochondrial membrane potential loss, and activation of apoptotic signaling for the superior anti-MDR activity of Dox-gluRDVs in vitro and in vivo. This work highlights the great promise of RDVs to serve as a bDDS of Dox to overcome MDR cancers but also opens up a reliable strategy for lysosomal-mitochondrial axis-dependent cell death for fighting against other inoperable cancers.

A Dual Concentration-Tailored Cytokine-Chemo Nanosystem to Alleviate Multidrug Resistance and Redirect Balance of Cancer Proliferation and Apoptosis.

Background: Cancer multidrug resistance (MDR) is an important factor that severely affects the chemotherapeutic efficacy. Among various methods to bypass MDR, usage of cytokines, such as tumor necrosis factor alpha (TNFα) is attractive, which exerts antitumor effects of immunotherapeutic response and apoptotic/proinflammatory pathways. Nevertheless, the challenges remain how to implement targeted delivery of TNFα to reduce toxicity and manifest the involved signaling mechanism that subdues MDR. Methods: We synthesized a multifunctional nanosytem, in which TNFα covalently bound to doxorubicin (Dox)-loaded pH-responsive mesoporous silica nanoparticles (MSN) through bi-functional polyethylene glycol (TNFα-PEG-MSN-Hydrazone-Dox) as a robust design to overcome MDR. Results: The salient features of this nanoplatform are: 1) by judicious tailoring of TNFα concentration conjugated on MSN, we observed it could lead to a contrary effect of either proliferation or suppression of tumor growth; 2) the MSN-TNFα at higher concentration serves multiple functions, besides tumor targeting and inducer of apoptosis through extrinsic pathway, it inhibits the expression level of p-glycoprotein (P-gp), a cell membrane protein that functions as a drug efflux pump; 3) the enormous surface area of MSN provides for TNFα functionalization, and the nanochannels accommodate chemotherapeutics, Dox; 4) targeted intracellular release of Dox through the pH-dependent cleavage of hydrazone bonds induces apoptosis by the specific intrinsic pathway; and 5) TNFα-PEG-MSN-Hydrazone-Dox (MSN-Dox-TNFα) could infiltrate deep into the 3D spheroid tumor model through disintegration of tight junction proteins. When administered intratumorally in a Dox-resistant mouse tumor model, MSN-Dox-TNFα exhibited a synergistic therapeutic effect through the collective performances of TNFα and Dox. Conclusion: We hereby develop and demonstrate a multifunctional MSN-Dox-TNFα system with concentration-tailored TNFα that can abrogate the drug resistance mechanism, and significantly inhibit the tumor growth through both intrinsic and extrinsic apoptosis pathways, thus making it a highly potential nanomedicine translated in the treatment of MDR tumors.

Illuminating and Radiosensitizing Tumors with 2DG-Bound Gold-Based Nanomedicine for Targeted CT Imaging and Therapy.

Although radiotherapy is one of the most important curative treatments for cancer, its clinical application is associated with undesired therapeutic effects on normal or healthy tissues. The use of targeted agents that can simultaneously achieve therapeutic and imaging functions could constitute a potential solution. Herein, we developed 2-deoxy-d-glucose (2DG)-labeled poly(ethylene glycol) (PEG) gold nanodots (2DG-PEG-AuD) as a tumor-targeted computed tomography (CT) contrast agent and radiosensitizer. The key advantages of the design are its biocompatibility and targeted AuD with excellent sensitivity in tumor detection via avid glucose metabolism. As a consequence, CT imaging with enhanced sensitivity and remarkable radiotherapeutic efficacy could be attained. Our synthesized AuD displayed linear enhancement of CT contrast as a function of its concentration. In addition, 2DG-PEG-AuD successfully demonstrated significant augmentation of CT contrast in both in vitro cell studies and in vivo tumor-bearing mouse models. In tumor-bearing mice, 2DG-PEG-AuD showed excellent radiosensitizing functions after intravenous injection. Results from this work indicate that 2DG-PEG-AuD could greatly potentiate theranostic capabilities by providing high-resolution anatomical and functional images in a single CT scan and therapeutic capability.

Patients' attitudes regarding genetic counseling before germline BRCA1/2 pathogenic variants testing in Taiwan: A single-country, multi-center, patient-reported outcome study.

Germline pathogenic variants of BRCA1 or BRCA2 cause hereditary breast and ovarian cancer syndromes. The present study investigated the participants' understanding and awareness of germline BRCA1/2 pathogenic variants before genetic counseling, the expectations and obstacles for genetic testing from the perspective of participants and their families, and their attitudes towards genetic testing after counseling. In this single-country, multicenter, non-interventional, patient-reported outcome study, untested cancer patients and their families who visited genetic counseling clinics or who wanted to receive pre-test genetic counseling were eligible to fill in the questionnaire after pre-test counseling for germline BRCA1/2 testing. Demographic information, clinical characteristics, and information collected from the questionnaires, including the understanding of BRCA1/2 pathogenic variants before genetic counseling, understanding of BRCA1/2 pathogenic variants and feelings after genetic counseling, willingness to share results of genetic testing with family, and willingness to receive genetic testing, were summarized using descriptive statistics. A total of 88 participants were enrolled. The proportion of slight understanding of BRCA1/2 pathogenic variants increased from 11.4% to 67.0%, and the proportion of full understanding increased from 0% to 8.0%. After genetic counseling, most participants were willing to undergo genetic testing (87.5%) and share the results with their families (96.6%). The main factors that may affect participants' willingness to undergo BRCA1/2 testing were management (61.2%) and testing costs (25.9%). After pre-test counseling, there was a high acceptance of BRCA1/2 testing and in-family information sharing in Taiwanese patients with cancer and their families, which may serve as a reference for implementing genetic counseling in Taiwan.

Multimodal Magnetic Resonance and Photoacoustic Imaging of Tumor-Specific Enzyme-Responsive Hybrid Nanoparticles for Oxygen Modulation.

Multimodal imaging contrast agents for cancer that can not only perform diagnostic functions but also serve as tumor microenvironment-responsive biomaterials are encouraging. In this study, we report the design and fabrication of a novel enzyme-responsive T1 magnetic resonance imaging (MRI) contrast agent that can modulate oxygen in the tumor microenvironment via the catalytic conversion of H2O2 to O2. The T1 contrast agent is a core-shell nanoparticle that consists of manganese oxide and hyaluronic acid (HA)-conjugated mesoporous silica nanoparticle (HA-MnO@MSN). The salient features of the nanoparticle developed in this study are as follows: 1) HA serves as a targeting ligand for CD44-expressing cancer cells; 2) HA allows controlled access of water molecules to the MnO core via the digestion of enzyme hyaluronidase; 3) the generation of O2 bubbles in the tumor by consuming H2O2; and 4) the capability to increase the oxygen tension in the tumor. The r 1 relaxivity of HA-MnO@MSN was measured to be 1.29 mM-1s-1 at a magnetic field strength of 9.4 T. In vitro results demonstrated the ability of continuous oxygen evolution by HA-MnO@MSN. After intratumoral administration of HA-MnO@MSN to an HCT116 xenograft mouse model, T1 weighted MRI contrast was observed after 5 h postinjection and retained up to 48 h. In addition, in vivo photoacoustic imaging of HA-MnO@MSN demonstrated an increase in the tumor oxygen saturation over time after i. t. administration. Thus, the core-shell nanoparticles developed in this study could be helpful in tumor-targeted T1 MR imaging and oxygen modulation.

Using "Integrated Reminders of Nursing Written Assignment" to Reduce the Interruptions in Nursing Care.

Nursing interruptions can suspend the nursing process and distracting the nurses' attention. In a nursing information system, there are lots of pop-up windows to notify the nurses to complete the nursing records. These notifications can also interrupt the original work. We proposed an "Integrated Reminders of Nursing Written Assignment" system to reduce the number of interruptions from the nursing information system. The result showed that the number of pop-up windows decreased from 489.48 to 0 per shift. The completeness of the nursing records raised from 97.3% to 100%. The "Integrated Reminders of Nursing Written Assignment" can effectively reduce the frequency of nursing interruptions and improve the quality of nursing records.

Discrepancy of Breast and Axillary Pathologic Complete Response and Outcomes in Different Subtypes of Node-positive Breast Cancer after Neoadjuvant Chemotherapy.

Few studies have analyzed the discrepancy between breast pathologic complete response (B-pCR) and axillary node pCR (N-pCR) rates and their impact on survival outcomes in different intrinsic subtypes of early breast cancer after neoadjuvant chemotherapy (NAC). We retrospectively reviewed B-pCR, N-pCR, and total (breast and axillary node) pCR (T-pCR) after NAC to assess the discrepancy and outcomes between 2005 and 2017. A total of 968 patients diagnosed with cT1-4c, N1-2, and M0 breast cancer were enrolled in the study. The median age was 49 years and the median follow-up time was 45 months. Of these patients, 213 achieved T-pCR, 31 achieved B-pCR with axillary node pathologic non-complete response (N-non pCR), 245 achieved N-pCR with breast pathologic non-complete response (B-non pCR), and 479 achieved total (breast and axillary node) pathologic non-complete response (T-non pCR) after NAC. The highest B-pCR and N-pCR rates were found in the hormone receptor-negative, human epidermal growth factor receptor 2-positive HR(-)HER2(+) subtype, while the lowest B-pCR rate was found in the HR(+)HER2(-) subtype. The N-pCR rate was correlated to the B-pCR rate (P<0.001), but was higher than the B-pCR rate in all subtypes. The 5-year overall survival (OS) rates for patients with T-pCR, B-pCR, and N-pCR were 91.2%, 91.7%, and 91.9%, respectively. For non-pCR, non-pCR, and non-pCR, the 5-year OS rates were 73.6%, 78.9%, and 74.7%, respectively (P<0.0001). B-non pCR patients had a lower risk of recurrence than T-non pCR or N-non-pCR patients, although there were no differences in OS among them. In conclusion, the N-pCR rate was higher than the B-pCR rate after NAC in all intrinsic subtypes, and N-non pCR or T-non pCR patients had the worst outcomes.

Factors affecting locoregional recurrence in breast cancer patients undergoing surgery following neoadjuvant treatment.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been the standard treatment for locally advanced breast cancer for the purpose of downstaging or for conversion from mastectomy to breast conservation surgery (BCS). Locoregional recurrence (LRR) rate is still high after NAC. The aim of this study was to determine predictive factors for LRR in breast cancer patients in association with the operation types after NAC. METHODS: Between 2005 and 2017, 1047 breast cancer patients underwent BCS or mastectomy after NAC in Chang Gung Memorial Hospital, Linkou. We obtained data regarding patient and tumor characteristics, chemotherapy regimens, clinical tumor response, tumor subtypes and pathological complete response (pCR), type of surgery, and recurrence. RESULTS: The median follow-up time was 59.2 months (range 3.13-186.75 months). The mean initial tumor size was 4.89 cm (SD ± 2.95 cm). Of the 1047 NAC patients, 232 (22.2%) achieved pCR. The BCS and mastectomy rates were 41.3% and 58.7%, respectively. One hundred four patients developed LRR (9.9%). Comparing between patients who underwent BCS and those who underwent mastectomy revealed no significant difference in the overall LRR rate of the two groups, 8.8% in BCS group vs 10.7% in mastectomy group (p = 0.303). Multivariate analysis indicated that independent factors for the prediction of LRR included clinical N2 status, negative estrogen receptor (ER), and failure to achieve pCR. In subgroups of multivariate analysis, only negative ER was the independent factor to predict LRR in mastectomy group (p = 0.025) and hormone receptor negative/human epidermal growth factor receptor 2 positive (HR-/HER2 +) subtype (p = 0.006) was an independent factor to predict LRR in BCS patients. Further investigation according to the molecular subtype showed that following BCS, non-pCR group had significantly increased LRR compared with the pCR group, in HR-/HER2 + subtype (25.0% vs 8.3%, p = 0.037), and HR-/HER2- subtype (20.4% vs 0%, p = 0.002). CONCLUSION: Clinical N2 status, negative ER, and failure to achieve pCR after NAC were independently related to the risk of developing LRR. Operation type did not impact on the LRR. In addition, the LRR rate was higher in non-pCR hormone receptor-negative patients undergoing BCS comparing with pCR patients.

Annealing-modulated nanoscintillators for nonconventional X-ray activation of comprehensive photodynamic effects in deep cancer theranostics.

Photodynamic therapy (PDT), which involves the generation of reactive oxygen species (ROS) through interactions of a photosensitizer (PS) with light and oxygen, has been applied in oncology. Over the years, PDT techniques have been developed for the treatment of deep-seated cancers. However, (1) the tissue penetration limitation of excitation photon, (2) suppressed efficiency of PS due to multiple energy transfers, and (3) insufficient oxygen source in hypoxic tumor microenvironment still constitute major challenges facing the clinical application of PDT for achieving effective treatment. We present herein a PS-independent, ionizing radiation-induced PDT agent composed of yttrium oxide nanoscintillators core and silica shell (Y2O3:Eu@SiO2) with an annealing process. Our results revealed that annealed Y2O3:Eu@SiO2 could directly induce comprehensive photodynamic effects under X-ray irradiation without the presence of PS molecules. The crystallinity of Y2O3:Eu@SiO2 was demonstrated to enable the generation of electron-hole (e--h+) pairs in Y2O3 under ionizing irradiation, giving rise to the formation of ROS including superoxide, hydroxyl radical and singlet oxygen. In particular, combining Y2O3:Eu@SiO2 with fractionated radiation therapy increased radio-resistant tumor cell damage. Furthermore, photoacoustic imaging of tumors showed re-distribution of oxygen saturation (SO2) and reoxygenation of the hypoxia region. The results of this study support applicability of the integration of fractionated radiation therapy with Y2O3:Eu@SiO2, achieving synchronously in-depth and oxygen-insensitive X-ray PDT. Furthermore, we demonstrate Y2O3:Eu@SiO2 exhibited radioluminescence (RL) under X-ray irradiation and observed the virtually linear correlation between X-ray-induced radioluminescence (X-RL) and the Y2O3:Eu@SiO2 concentration in vivo. With the pronounced X-RL for in-vivo imaging and dosimetry, it possesses significant potential for utilization as a precision theranostics producing highly efficient X-ray PDT for deep-seated tumors.

Biodegradable Polymers for Gene-Delivery Applications.

Gene-based therapies have emerged as a new modality for combating a myriad of currently incurable diseases. However, the fragile nature of gene therapeutics has significantly hampered their biomedical applications. Correspondingly, the development of gene-delivery vectors is of critical importance for gene-based therapies. To date, a variety of gene-delivery vectors have been created and utilized for gene delivery. In general, they can be categorized into viral- and non-viral vectors. Due to safety issues associated with viral vectors, non-viral vectors have recently attracted much more research focus. Of these non-viral vectors, polymeric vectors, which have been preferred due to their low immunogenicity, ease of production, controlled chemical composition and high chemical versatility, have constituted an ideal alternative to viral vectors. In particular, biodegradable polymers, which possess advantageous biocompatibility and biosafety, have been considered to have great potential in clinical applications. In this context, the aim of this review is to introduce the recent development and progress of biodegradable polymers for gene delivery applications, especially for their chemical structure design, gene delivery capacity and additional biological functions. Accordingly, we first define and categorize biodegradable polymers, followed by describing their corresponding degradation mechanisms. Various types of biodegradable polymers resulting from natural and synthetic polymers will be introduced and their applications in gene delivery will be examined. Finally, a future perspective regarding the development of biodegradable polymer vectors will be given.

Precision control of the large-scale green synthesis of biodegradable gold nanodandelions as potential radiotheranostics.

Herein, we report a new type of biodegradable, high surface-area gold nanodandelions (GNDs). This report possesses important features and some are the first of its kind: (1) the large scale green synthesis of GNDs with high monodispersity and a circa 100% yield with consistent chemistry, manufacturing and controls (CMC); (2) cellular/physiological degradability of GNDs leading to its disassembly into debris, which is indicative of the potential for possible body clearance; (3) precision control of the chemicophysical properties of the GNDs including shape, petal number and size, all can be judiciously fine-tuned by the synthetic parameters; (4) highly efficient radiotheranostics of GNDs encompassing better enhanced computed tomography (CT) contrast and pronounced X-ray induced reactive oxygen species (ROS) generation than conventional spherical gold nanoparticles (AuNP). It is noteworthy that the GNDs demonstrate a unique combinational effect of radiosensitization (production of superoxide anions and hydroxyl radicals) and type II photodynamic interaction (generation of singlet oxygen). Given the above, our reported GNDs are promising in clinical translation as radiotheranostics.

Impact of age on pathological complete response and locoregional recurrence in locally advanced breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard approach for downstaging of locally advanced breast cancer and can improve breast conservation rates. A pathological complete response (pCR) after NAC associated with favorable long-term outcomes has been described. There is still a high locoregional recurrence (LRR) rate after NAC and the influence of age on LRR after NAC is unclear. This study analyzed the relationship between age and LRR after NAC. METHODS: Two hundred and sixty-three patients with invasive breast cancer who received NAC followed by mastectomy or breast conserving surgery (BCS) were enrolled. Concurrent weekly epirubicin and docetaxel was the NAC regimen. RESULTS: Twenty-nine patients (11%) achieved a pCR after NAC. In univariate analysis, age <50 years, luminal B (HER2 positive) subtype, HER2 overexpression subtype, and triple-negative subtype were factors to predict a pCR. In multivariate analysis, age <50 years, luminal B (HER2 positive) type, HER2 overexpression, and triple-negative subtype were the independent factors to predict a pCR. No patients in the pCR group developed LRR compared with 31 patients in the non-pCR group. Eleven patients (6.9%) in the younger group (age <50 years) developed LRR compared with 20 patients (19.4%) in the older group (age ≥50 years). In multivariate analysis, younger age (<50 years) was the only independent prognostic factor for a LRR-free survival. CONCLUSION: Younger age can predict a pCR and is an independent prognostic factor for LRR in locally advanced breast cancer patients after NAC as concurrent epirubicin and docetaxel.

Microwave-Synthesized Platinum-Embedded Mesoporous Silica Nanoparticles as Dual-Modality Contrast Agents: Computed Tomography and Optical Imaging.

Nanoparticle-based imaging contrast agents have drawn tremendous attention especially in multi-modality imaging. In this study, we developed mesoporous silica nanoparticles (MSNs) for use as dual-modality contrast agents for computed tomography (CT) and near-infrared (NIR) optical imaging (OI). A microwave synthesis for preparing naked platinum nanoparticles (nPtNPs) on MSNs (MSNs-Pt) was developed and characterized with physicochemical analysis and imaging systems. The high density of nPtNPs on the surface of the MSNs could greatly enhance the CT contrast. Inductively coupled plasma mass spectrometry (ICP-MS) revealed the MSNs-Pt compositions to be ~14% Pt by weight and TEM revealed an average particle diameter of ~50 nm and covered with ~3 nm diameter nPtNPs. To enhance the OI contrast, the NIR fluorescent dye Dy800 was conjugated to the MSNs-Pt nanochannels. The fluorescence spectra of MSNs-Pt-Dy800 were very similar to unconjugated Dy800. The CT imaging demonstrated that even modest degrees of Pt labeling could result in substantial X-ray attenuation. In vivo imaging of breast tumor-bearing mice treated with PEGylated MSNs-Pt-Dy800 (PEG-MSNs-Pt-Dy800) showed significantly improved contrasts in both fluorescence and CT imaging and the signal intensity within the tumor retained for 24 h post-injection.

Clinical outcome of revision cartilage tympanoplasty.

We retrospectively reviewed 32 ears from 30 adult patients with chronic otitis media who underwent revision tympanoplasty using cartilage graft (performed by a single surgeon) from January 10, 2011, to May 10, 2016. All procedures were performed using an endaural incision for both temporalis fascia graft and tragal cartilage graft harvesting. The overall surgical success rate was 93.3%. The average preoperative hearing level was 43.1 ± 17.3 dBHL, and the average postoperative hearing level was 39.2 ± 18.2 dBHL, representing a significant improvement. The average air-bone gap was 19.4 ±7.6 dB preoperatively and 16.9 ± 9.9 dB postoperatively. Also of note, the improvement in air-bone gap reached the level of significance at 500 Hz (p = 0.023). We conclude that using cartilage graft in revision tympanoplasty is a safe and reliable technique with good surgical outcomes. Using one single endaural incision for both fascia and cartilage harvesting is simple while achieving aesthetic wound healing.

Lectin-functionalized mesoporous silica nanoparticles for endoscopic detection of premalignant colonic lesions.

Colorectal cancer (CRC) is one of the leading causes of cancer-deaths worldwide. Methods for the early in situ detection of colorectal adenomatous polyps and their precursors - prior to their malignancy transformation into CRC - are urgently needed. Unfortunately at present, the primary diagnostic method, colonoscopy, can only detect polyps and carcinomas by shape/morphology; with sessile polyps more likely to go unnoticed than polypoid lesions. Here we describe our development of polyp-targeting, fluorescently-labeled mesoporous silica nanoparticles (MSNs) that serve as targeted endoscopic contrast agents for the early detection of colorectal polyps and cancer. In vitro cell studies, ex vivo histopathological analysis, and in vivo colonoscopy and endoscopy of murine colorectal cancer models, demonstrate significant binding specificity of our nanoconstructs to pathological lesions via targeting aberrant α-L-fucose expression. Our findings strongly suggest that lectin-functionalized fluorescent MSNs could serve as a promising endoscopic contrast agent for in situ diagnostic imaging of premalignant colonic lesions.

An Efficient User Interface Design for Nursing Information System Based on Integrated Patient Order Information.

A user friendly interface can enhance the efficiency of data entry, which is crucial for building a complete database. In this study, two user interfaces (traditional pull-down menu vs. check boxes) are proposed and evaluated based on medical records with fever medication orders by measuring the time for data entry, steps for each data entry record, and the complete rate of each medical record. The result revealed that the time for data entry is reduced from 22.8 sec/record to 3.2 sec/record. The data entry procedures also have reduced from 9 steps in the traditional one to 3 steps in the new one. In addition, the completeness of medical records is increased from 20.2% to 98%. All these results indicate that the new user interface provides a more user friendly and efficient approach for data entry than the traditional interface.