Outcomes of coronary artery bypass grafting (CABG) in patients with OSA-COPD overlap syndrome versus COPD alone: an analysis of US Nationwide Inpatient Sample.

BACKGROUND: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are associated with unfavorable outcomes following coronary artery bypass grafting (CABG). The purpose of this study was to compare in-hospital outcomes of patients with COPD alone versus OSA-COPD overlap after CABG. METHODS: Data of adults ≥ 18 years old with COPD who received elective CABG between 2005 and 2018 were extracted from the US Nationwide Inpatient Sample (NIS). Patients were divided into two groups: with OSA-COPD overlap and COPD alone. Propensity score matching (PSM) was employed to balance the between-group characteristics. Logistic and linear regression analyses determined the associations between study variables and inpatient outcomes. RESULTS: After PSM, data of 2,439 patients with OSA-COPD overlap and 9,756 with COPD alone were analyzed. After adjustment, OSA-COPD overlap was associated with a significantly increased risk of overall postoperative complications (adjusted odd ratio [aOR] = 1.12, 95% confidence interval [CI]: 95% CI: 1.01-1.24), respiratory failure/prolonged mechanical ventilation (aOR = 1.27, 95%CI: 1.14-1.41), and non-routine discharge (aOR = 1.16, 95%CI: 1.03-1.29), and AKI (aOR = 1.14, 95% CI: 1.00-1.29). Patients with OSA-COPD overlap had a lower risk of in-hospital mortality (adjusted odd ratio [aOR] = 0.53, 95% CI: 0.35-0.81) than those with COPD only. Pneumonia or postoperative atrial fibrillation (AF) risks were not significantly different between the 2 groups. Stratified analyses revealed that, compared to COPD alone, OSA-COPD overlap was associated with increased respiratory failure/prolonged mechanical ventilation risks among patients ≥ 60 years, and both obese and non-obese subgroups. In addition, OSA-COPD overlap was associated with increased risk of AKI among the older and obese subgroups. CONCLUSION: In US adults who undergo CABG, compared to COPD alone, those with OSA-COPD are at higher risks of non-routine discharge, AKI, and respiratory failure/prolonged mechanical ventilation, but a lower in-hospital mortality. No increased risk of AF was noted.

In Situ Visualization of RNA-Specific Sialylation on Living Cell Membranes to Explore N-Glycosylation Sites.

The small RNAs on living cell membranes were recently found to be N-glycosylated and terminated with sialic acids, although the glycosylation sites and potential functions remain unclear. Herein, we designed a second-generation hierarchical coding strategy (HieCo 2) for in situ visualization of cell surface RNA-specific sialylation. After covalently binding DNA codes to sialic acids and then binding a DNA code to a target RNA via sequence specificity, cascade decoding processes were performed with subsequent signal amplification that enabled sensitive in situ visualization of low-abundance Y5 RNA-specific sialic acids on living cell membranes. The proposed strategy unveils the number of glycosylation sites on a single RNA and reveals the binding preference of glycosylated RNAs to different sialic acid binding-immunoglobulin lectin-type receptors, demonstrating a new route for exploration of the glycosylated RNA-related biological and pathological processes.

In situ SERS imaging of protein-specific glycan oxidation on living cells to quantitatively visualize pathogen-cell interactions.

Glycan oxidation on the cell surface occurs in many specific life processes including pathogen-cell interactions. This work develops a surface-enhanced Raman scattering (SERS) imaging strategy for in situ quantitative monitoring of protein-specific glycan oxidation mediated pathogen-cell interactions by utilizing Raman reporter DTNB and aptamer co-assembled platinum shelled gold nanoparticles (Au@Pt-DTNB/Apt). Using Fusarium graminearum (FG) and MCF-7 cells as models, Au@Pt-DTNB/Apt can specifically bind to MUC1 protein on the cell surface containing heavy galactose (Gal) and N-acetylgalactosamine (GalNAc) modification. When FG interacts with cells, the secreted galactose oxidase (GO) can oxidize Gal/GalNAc, and the generated reactive oxygen species (ROS) further oxidizes DTNB to produce TNB for greatly enhancing the SERS signal. This strategy can quantitatively visualize for the first time both the protein-specific glycan oxidation and the mediated pathogen-cell interactions, thus providing key quantitative information to distinguish and explore the pathogen-resistance and pharmacological mechanisms of different drugs.

In situ evaluation of in vivo sialylation with a dual-color imaging strategy.

This work designs a functional dendrimer probe to conveniently identify newly generated sialic acid groups in vivo with a dual-color imaging strategy, which achieves in situ semiquantitative evaluation of the sialylation difference between tumor and normal tissues to reveal sialylation-related biological events and promote clinical tumor diagnosis.

Crosslinked albumin-manganese nanoaggregates with sensitized T1 relaxivity and indocyanine green loading for multimodal imaging and cancer phototherapy.

Albumin-manganese-based nanocomposites (AMNs) characterized by simple preparation and good biocompatibility have been widely used for in vivo T1-weighted magnetic resonance imaging (MRI) and cancer theranostics. Herein, an aggregation and crosslinking assembly strategy was proposed to achieve the sensitization to T1 relaxivity of the albumin-manganese nanocomposite. At a relatively low Mn content (0.35%), the aggregation and crosslinking of bovine serum albumin-MnO2 (BM) resulted in a dramatic increase of T1 relaxivity from 5.49 to 67.2 mM-1 s-1. Upon the loading of indocyanine green (ICG) into the crosslinked BM nanoaggregates (C-BM), the T1 relaxivity of the C-BM/ICG nanocomposite (C-BM/I) was further increased to 97.3 mM-1 s-1, which was much higher than those reported previously even at high Mn contents. Moreover, the presence of C-BM greatly enhanced the photoacoustic (PA) and photothermal effects of ICG at 830 and 808 nm, respectively, and the second near infrared fluorescence (NIR-II FL) of ICG also showed better stability. Therefore, the synthesized C-BM/ICG nanocomposite exhibited remarkable performance in in vivo multimodal imaging of tumors, such as T1-weighted MRI, NIR-II FL imaging and PA imaging, and cancer phototherapy with little side effects. This work provided a highly efficient and promising multifunctional nanoprobe for breaking through the limits of cancer theranostics, and opened a new avenue for the development of high-relaxivity AMNs and multimodal imaging methodology.

Orthogonal excitations of lanthanide nanoparticle up/down conversion emissions via switching NIR lights for in-vivo theranostics.

With multiple emissions ranging from NIR-IIb to visible lights, near-infrared light-excited lanthanide nanoparticle (LnNP) is an ideal in-vivo theranostic platform to achieve imaging guided phototherapy. However, current reported LnNPs typically demonstrate simultaneous up and downconversion emissions with fixed single excitation light, which impairs therapeutic efficiency and generates side effect during navigation. Here we develop a lanthanide-based conversion switching nanoparticle (CSNP) with independent activation of 1550 nm NIR-IIb downconversion emission under 808 nm excitation and 345/450 nm upconversion emission under 980 nm excitation. CSNP is modified with Cy-GSH to quench NIR-IIb emission and photosensitizer hypocrellin A. In vivo delivery of CSNP is traced via 808 nm irradiation, and Cy-GSH changes structure in response to glutathione to activate NIR-IIb imaging. This indicates the tumor position and timing to switch for 980 nm irradiation to activate hypocrellin A for photodynamic therapy. Orthogonal activation of CSNP up/down conversion emissions demonstrates high tumor-to-normal tissue ratio in vivo and good therapeutic result, would have promising potential as a theranostics platform.

O-GlcNAcylation mapping of single living cells by in situ quantitative SERS imaging.

O-GlcNAcylation is involved in many biological processes including cancerization. Nevertheless, its in situ quantification in single living cells is still a bottleneck. Here we develop a quantitative SERS imaging strategy for mapping the O-GlcNAcylation distribution of single living cells. O-GlcNAcylated compounds (OGCs) can be quantified through their in situ azide labeling and then a click reaction competing with azide and Raman reporter labeled 15 nm-gold nanoparticles (AuNPs) for linking to dibenzocyclooctyne labeled 40 nm-AuNPs to produce OGC-negatively correlated SERS signals. The calibration curve obtained in vitro can be conveniently used for detecting OGCs in different areas of single living cells due to the negligible effect of cell medium on the click linkage and Raman signal. This method has been successfully applied in mapping O-GlcNAcylation distribution in different cell lines and monitoring O-GlcNAcylation variation during cell cycling, which demonstrate its great practicability and expansibility in glycosylation related analysis.

Tumor suppression via diverting intracellular sialylation with multifunctional nanoparticles.

Sialylation plays an important role in tumor-related physiological processes. Therefore, intervention of sialylation has great potential to explore new paths for tumor therapy. In view of the immune modulation of sialic acid (SA) on tumors, this work designs a multifunctional mesoporous silica nanoparticle (MFMSN) to divert intracellular sialylation for tumor suppression. The galactose groups covered on MFMSN act as sialylation substrates to bind intracellular SAs competitively, which inhibits the SA expression on the tumor cell surface. The diverted intracellular sialylation can be visualized on living cells and in vivo by specifically binding the sialylated galactose with a phenylboronic acid labeled ssDNA probe released from the pore of MFMSN to induce DNA strand displacement, which recovers the fluorescence of the dsDNA probe covered on MFMSN surface. The diverting of sialylation efficiently suppresses tumor growth in mice, demonstrating the great potential of the designed strategy for revealing SA-related biological processes and clinical cancer therapy.

Tug-of-war: molecular dynamometers against living cells for analyzing sub-piconewton interaction of a specific protein with the cell membrane.

Protein-membrane interactions play important roles in signal transductions and functional regulation of membrane proteins. Here, we design a molecular dynamometer (MDM) for analyzing protein-membrane interaction on living cells. The MDM is constructed by assembling an artificial lipid bilayer and alkylated Cy3-DNA azide (azide-Cy3-Cx) on a silica bubble. After a functional aptamer is covalently anchored onto the corresponding target protein on a living cell through UV irradiation, azide-Cy3-Cx is conjugated with the aptamer through a click reaction to produce a "tug-of-war" between the MDM and the cell due to the buoyancy of the silica bubble. This induces the detachment of the protein from the cell membrane or the alkane terminal from the MDM enabling sub-piconewton embedding force measurement by changing the alkane chain length and simple fluorescence analysis. The successful analysis of embedding force variation of a protein on the cell membrane upon post-translational modifications demonstrates the practicability and expansibility of this method for mechanics-related research in biological systems.

Association of Insomnia, Depressive Disorders, and Mood Disorders as Risk Factors With Breast Cancer: A Nationwide Population-Based Cohort Study of 232,108 Women in Taiwan.

BACKGROUND: Insomnia, depressive disorders, and to a more general view, mood disorders are raising people's concerns and causing disability of life. Herein, we try to seek the association of such illnesses with subsequent breast cancer. METHODS: This population-based, retrospective cohort study used data from the Taiwan National Health Insurance Research Database. This study included 232,108 women diagnosed with insomnia, depressive disorders, and mood disorders from January 1, 2000 to December 31, 2013. Physician diagnosed insomnia, depressive disorders, or mood disorders using outpatient and inpatient records before diagnosis of breast cancer. Cox proportional hazards regression analysis is adjusted for women with insomnia, depressive disorders, mood disorders, and other factors like insured amount, urbanization, and comorbidities such as having subsequent breast cancer. RESULTS: Sleep medication was associated with a significantly increased incidence rate of breast cancer (aHR = 1.23 (95% CI = 1.13, 1.35), p < 0.001). Insomnia was associated with significant increased hazard of breast cancer (aHR = 1.16 (95% CI = 1.07, 1.27), p < 0.001). Annual insured amount >20,000 (TWD), high urbanization area, and hyperlipidemia were associated with increased hazard of breast cancer (aHR = 1.13 (95% CI = 1.01, 1.27), p = 0.04; aHR = 1.41 (95% CI = 1.17, 1.71), p < 0.001; aHR = 1.14 995% CI = 1.02, 1.29), p = 0.02, respectively). There was a positive correlation between depressive disorders and increased incidence rate of breast cancer but not statistically significant (aHR = 1.11 (95% CI = 0.99, 1.25), p = 0.08). Mood disorders were not associated with increased hazard (aHR = 1.11 (95% CI = 0.91, 1.34), p = 0.31). CONCLUSION: In this study, women with insomnia had increased risk of breast cancer, particularly those in high urbanization or with high insured amounts. Sleep medication (benzodiazepine (BZD) or non-BZD) and hyperlipidemia were independently associated with a higher hazard ratio of breast cancer. Insomnia along with sleep medication did not yield more hazards than each alone. Mood disorders appeared to be not associated with subsequent breast cancer. However, depressive disorders, the subgroups of mood disorders, could possibly increase the incidence rate of breast cancer though not statistically significant.

A pore-forming protein-induced surface-enhanced Raman spectroscopic strategy for dynamic tracing of cell membrane repair.

The plasma membrane repair holds significance for maintaining cell survival and homeostasis. To achieve the sensitive visualization of membrane repair process for revealing its mechanism, this work designs a perforation-induced surface-enhanced Raman spectroscopy (SERS) strategy by conjugating Raman reporter (4-mercaptobenzoic acid) loaded gold nanostars with pore-forming protein streptolysin O (SLO) to induce the SERS signal on living cells. The SERS signal obviously decreases with the initiation of membrane repair and the degradation of SLO pores due to the departure of gold-nanostar-conjugated SLO. Thus, the designed strategy can dynamically visualize the complete cell membrane repair and provide a sensitive method to demonstrate the SLO endocytosis- and exocytosis-mediated repairing mechanism. Using DOX-resistant MCF-7 cells as a model, a timely repair-blocking technology for promoting the highly efficient treatment of drug-resistant cancer cells is also proposed. This work opens an avenue for probing the plasma membrane repairing mechanisms and designing the precision therapeutic schedule.

A giant malignant phyllodes tumor of breast post mastectomy with metastasis to stomach manifesting as anemia: a case report and review of literature.

BACKGROUND: Phyllodes tumors (PTs) are well known for local recurrence and progression. Less than 10% of these tumors grow larger than 10 cm. Distant metastases have been reported in up to 22% of malignant PTs, with most metastases being discovered in the lungs. PTs of the breast rarely metastasize to the gastrointestinal tract, and reported cases are scarce. To date, a review of the English literature revealed only 3 cases, including our case, of PTs metastasis to stomach. CASE PRESENTATION: An 82-year-old female patient had 10-year-duration of palpable huge tumor on left breast which was in rapid growth in recent months. Total mastectomy of left breast was performed thereafter, and pathology diagnosis was malignant phyllodes tumor. Adjuvant radiotherapy was suggested while she declined out of personal reasons initially. For PTs recurred locally on left chest wall 2 months later, and excision of the recurrent PTs was performed. She, at length, completed adjuvant radiation therapy since then. Six months later, she was diagnosed of metastasis to stomach due to severe anemia with symptom of melena. Gastrostomy with tumor excision was performed for uncontrollable tumor bleeding. CONCLUSION: For PTs presenting as anemia without known etiologies, further studies are suggested to rule out possible gastrointestinal tract metastasis though such cases are extremely rare. Management of metastatic gastric tumor from PTs should be done on a case-to-case basis, surgical intervention may be needed if there is persistent active bleeding despite medical treatment. Adjuvant radiotherapy is recommended in borderline and malignant PTs with tumor-free margin < 1 cm and high-risk malignant tumors. Adjuvant chemotherapy or target therapy may be helpful for metastatic PTs. Molecular and genomic techniques may predict clinical outcomes of benign and borderline PTs more precisely.

Functional Dual-Color Indicator To Achieve in Situ Visualization of Intracellular Glycosylation.

A functional dual-color indicator is designed for in situ visualization of intracellular glycosylation. Using O-GlcNAcylation as model, the indicator is constructed on a poly-GlcNAc-coated gold nanoparticle (AuNP) by assembling dye labeled lectin (FSWGA) and then another dye-labeled GlcNAc (FGlcNAc) through the two opposite subunits of FSWGA. These dyes possess negligible overlapping emission and can be quenched by AuNP. In the presence of intracellular dissociated GlcNAc residue and O-GlcNAcylated proteins, the assembled FGlcNAc and the conjugate of FSWGA with FGlcNAc are released from AuNP through the dynamic competitive conjugation, which lights up the fluorescence of two dyes, respectively, and provides a simple technique for simultaneously monitoring the level of O-GlcNAcylated proteins and the total amount of GlcNAc groups in living cells. The practicality of the protocol for visually monitoring the biological pathway between intracellular O-GlcNAcylation and cell surface differentiation-related proteins demonstrates a convenient and powerful tool for research of glycosylation equilibrium and related biological processes.

Quantitative Screening of Cell-Surface Gangliosides by Nondestructive Extraction and Hydrophobic Collection.

A screening strategy involving designed extractors and collectors was used for the nondestructive quantitation of gangliosides on cell surfaces. The extractors were constructed by functionalizing maleimide silica bubbles with a DNA probe, which contains an endonuclease cleavage site and a boronic acid end to extract cell-surface sialic acid-containing compounds through simple centrifugation. After the extractors containing the extracted compounds were incubated with endonuclease, the released oligonucleotide-gangliosides were selectively collected by silanized collector bubbles through hydrophobic interactions. The in vitro fluorescent signals from the collectors were used for the quantitation of cell-surface gangliosides. By combining with sialidase cleavage, a protocol for the identification of ganglioside subtypes was developed. The successful monitoring of the regeneration of cell-surface gangliosides demonstrates the potential of this strategy in probing related biological processes.

Intra-abdominal bleeding with hemorrhagic shock: a case of adrenal myelolipoma and review of literature.

Background: Adrenal myelolipoma is an uncommon, benign, and hormonally non-functioning tumor that is composed of mature adipose tissue and normal hematopoietic tissue. Most cases to date are asymptomatic or have epigastric pain. Acute hemorrhage is the most dramatic manifestation of adrenal myelolipoma; though, it is a rare entity. Hemorrhagic shock due to adrenal myelolipoma, to our knowledge, was much less mentioned so far. Persistent bleeding and uncontrollable hypotension are considered to be absolute indications for immediate surgical operation. Case presentation: Herein we presented a 32-year-old male patient with initial symptoms of nausea, vomiting, and epigastric pain progressing to altered consciousness and hypotension during ER course. Hemorrhagic shock due to a giant adrenal myelolipoma, R't was diagnosed. Emergent exploratory laparotomy was executed, and en bloc excision of tumor was done. Conclusion: Adrenal myelolipoma might be diagnosed as a adjunction to other main causes of illness; furthermore, adrenal myelolipoma could be asymptomatic in lifetime. In our case, however, manifesting as hemorrhage shock was challenging to diagnose step by step; instead, maintaining vital organs perfusion and identifying bleeding sources were to be done. Management of myelolipoma should be done on a case-to-case basis.