A Novel Hydrated Iron Vanadate Cathode Material for Advanced Aqueous Nickel-Ion Batteries.

Aqueous nickel-ion batteries (ANIBs) as an emerging energy storage device attracted much attention owing to their multielectron redox reaction and dendrite-free Ni anode, yet their development is hindered by the divalent properties of Ni2+ and the lack of suitable cathode materials. Herein, a hydrated iron vanadate (Fe2V3O10.5∙1.5H2O, FOH) with a preferred orientation along the (200) plane is innovatively proposed and used as cathode material for ANIBs. The FOH cathode exhibits a remarkable capacity of 129.3 mAh g-1 at 50 mA g-1 and a super-high capacity retention of 95% at 500 mA g-1 after 700 cycles. The desirable Ni2+ storage capacity of FOH can be attributed to the preferentially oriented and tunnel structures, which offer abundant reaction active planes and a broad Ni2+ diffusion path, the abundant vacancies and high specific surface area further increase ion storage sites and accelerate ion diffusion in the FOH lattice. Furthermore, the Ni2+ storage mechanism and structural evolution in the FOH cathode are explored through ex situ XRD, ex situ Raman, ex situ XPS and other ex situ characteristics. This work opens a new way for designing novel cathode materials to promote the development of ANIBs.

Decreased histone expression in chronic rhinosinusitis with nasal polyps.

Background: Histones have been associated with human diseases. However, the implication of extranuclear histone proteins and their potential mechanism in the pathophysiology of chronic rhinosinusitis (CRS) have not been thoroughly investigated. This study was designed to evaluate the role of histones in patients with CRS by comparing histone expression between patients and controls. Methods: Nasal polyp (NP) tissues were obtained, and their comprehensive gene expression profiles were investigated by microarray analysis. Differences in expression were verified by reverse transcriptase polymerase chain reaction and immunohistochemical staining. Cell culture and flow cytometry were used to evaluate the role of histones in the pathogenesis of polyps. Results: Significant differences in the microarray analysis were observed between the patient and control groups (P < 0.01). It was found by flow cytometry that the histone (H2BK) can promote cell apoptosis in NPs. Conclusion: Our results indicate that reduced expression of H2BK may contribute to the imbalance process of cell proliferation and apoptosis in CRS with NP.

Charge-Reversal NaCl/G-Quartets for Aggregation-Induced Mitochondrial MicroRNA Imaging and Ion-Interference Therapy.

Mitochondrial therapy is a promising new strategy that offers the potential to achieve precise disease diagnosis or maximum therapeutic response. However, versatile mitochondrial theranostic platforms that integrate biomarker detection and therapy have rarely been exploited. Here, we report a charge-reversal nanomedicine activated by an acidic microenvironment for mitochondrial microRNA (mitomiR) detection and ion-interference therapy. The transporter liposome (DD-DC) was constructed from a pH-responsive polymer and a positively charged phospholipid, encapsulating NaCl nanoparticles with coloading of the aggregation-induced emission (AIE) fluorogens AIEgen-DNA/G-quadruplexes precursor and brequinar (NAB@DD-DC). The negatively charged nanomedicine ensured good blood stability and high tumor accumulation, while the charge-reversal to positive in response to the acidic pH in the tumor microenvironment (TME) and lysosomes enhanced the uptake by tumor cells and lysosome escape, achieving accumulation in mitochondria. The subsequently released Na+ in mitochondria not only contributed to the formation of mitomiR-494 induced G-quadruplexes for AIE imaging diagnosis but also led to an osmolarity surge that was enhanced by brequinar to achieve effective ion-interference therapy.

Fabrication of hyaluronic acid-altered gold complex delivery for head and neck squamous cell carcinoma therapy with high antitumor efficacy and low in vivo toxicity.

The use of multifunctional nanomedicines in the treatment of tumors is gaining popularity. Here, we constructed a nanodrug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to pH and near-infrared (NIR) dual stimuli. By precisely interacting with an overexpressed CD44 receptor in specific cancer cells, hyaluronic acid (HA) is coated on the Au-PDA NP surface for tumor-targeting abilities. When exposed to NIR radiation, polydopamine (PDA) and gold nanoshells exhibit exceptional photothermal performance that has the potential to both accelerate and kill HLAC 78 head and neck squamous cell carcinoma cells. Antitumor investigations conducted in vivo and in vitro demonstrated that nanomedicine had remarkable synergistic benefits with chemotherapy and photothermal treatment. Only 25.2% of the cells in the HA/Au-PDA@CZT with a NIR irradiation group were viable. Any group's lowest tumor volume was shown in the tumor mice subjected to HA/Au-PDA@CZT with NIR at 0.3 ± 0.1. Consequently, for synergistic chemo-photothermal therapy, our logically designed nanoplatform would be the potential for a head and neck squamous tumor-targeting drug delivery system.

Surgical treatment and prognosis of recurrent and radiotherapy insensitive nasopharyngeal carcinoma.

OBJECTIVE: To explore the effect of surgical treatment and related prognostic factors for recurrent Nasopharyngeal Carcinoma (NPC) after radiotherapy and the pathological types of nasopharyngeal carcinoma insensitive to radiotherapy. METHODS: A total of 70 NPC patients who underwent surgery at the Department of Otolaryngology, head and neck surgery, from January 2005 to December 2020 were retrospectively included: 41 males and 29 females, aged 21-75 years, 47 patients were pathologically classified as NPC (nonkeratinizing, undifferentiated type), 10 patients as adenoid cystic carcinoma, 13 patients as other types, 45 patients had received radiotherapy preoperatively, and 25 patients had not received radiotherapy preoperatively. All patients underwent surgical treatment under general anesthesia. Fifty-six patients underwent nasoendoscopic NPC resection, seven patients underwent open surgery, and seven patients underwent combined nasoendoscopic and open surgery. The median follow-up was 39 months. Tumor volume, extent of involvement, lymph node metastasis, imaging characteristics, surgical approach and efficacy, postoperative complications, and 2-, 3-, and 5-year postoperative survival rates were calculated for all patients. Statistical analysis was performed using spss22 Kaplan Meier survival analysis and Cox regression analysis were performed. RESULTS: Among the 70 patients, the overall 2-year survival rate was 93.4%, the 3-year survival rate was 90.8%, and the 5-year survival rate was 80.3%. Multivariate analysis showed that TNM stage and age at onset were independent prognostic factors for NPC outcome. CONCLUSION: Depending on the size and location of the tumor, endoscopic surgery, open surgery, and combined open surgery with nasoendoscopy may be considered for recurrent and radiotherapy insensitive NPC. LEVEL OF EVIDENCE: Level 4.

Surgical treatment and prognosis of recurrent and radiotherapy insensitive nasopharyngeal carcinoma

Abstract Objective To explore the effect of surgical treatment and related prognostic factors for recurrent Nasopharyngeal Carcinoma (NPC) after radiotherapy and the pathological types of nasopharyngeal carcinoma insensitive to radiotherapy. Methods A total of 70 NPC patients who underwent surgery at the Department of Otolaryngology, head and neck surgery, from January 2005 to December 2020 were retrospectively included: 41 males and 29 females, aged 21-75 years, 47 patients were pathologically classified as NPC (nonkeratinizing, undifferentiated type), 10 patients as adenoid cystic carcinoma, 13 patients as other types, 45 patients had received radiotherapy preoperatively, and 25 patients had not received radiotherapy preoperatively. All patients underwent surgical treatment under general anesthesia. Fifty-six patients underwent nasoendoscopic NPC resection, seven patients underwent open surgery, and seven patients underwent combined nasoendoscopic and open surgery. The median follow-up was 39 months. Tumor volume, extent of involvement, lymph node metastasis, imaging characteristics, surgical approach and efficacy, postoperative complications, and 2-, 3-, and 5-year postoperative survival rates were calculated for all patients. Statistical analysis was performed using spss22 Kaplan Meier survival analysis and Cox regression analysis were performed. Results Among the 70 patients, the overall 2-year survival rate was 93.4%, the 3-year survival rate was 90.8%, and the 5-year survival rate was 80.3%. Multivariate analysis showed that TNM stage and age at onset were independent prognostic factors for NPC outcome. Conclusion Depending on the size and location of the tumor, endoscopic surgery, open surgery, and combined open surgery with nasoendoscopy may be considered for recurrent and radiotherapy insensitive NPC. Level of Evidence: Level 4.

Application of prolonged submental perforator flap to repair the postoperative defect of upper airway malignancy.

OBJECTIVES: To explore the feasibility of making a submental perforator flap distal to the connecting line between the mastoid and the sternoclavicular joint under the guidance of neck-enhanced CT and repairing the postoperative defect of upper airway malignancy. MATERIALS AND METHODS: This study retrospectively analysed 19 cases of upper airway malignant tumours treated in our department from January 2021 to September 2022, including 17 males and 2 females, aged 43-70 years. SITE OF LESIONS: 15 cases were in the laryngopharynx, 2 cases in the nasal cavity and paranasal sinus and 2 cases on the soft palate. All the lesions were malignant and at stages T2-4N0-2M0. SURGICAL METHOD: The extended submental perforator flap (size 22-15 × 6-7 cm) was prefabricated distal to the connecting line between the mastoid and the sternoclavicular joint. After tumour resection, the flap was used to repair the postoperative defect. Fifteen cases of laryngopharyngeal malignant tumours were repaired using the extended submental perforator flap with the vascular pedicle located on the opposite side of the tumour body. Two cases of nasal cavity and paranasal sinus tumours were repaired using the extended submental perforator flap combined with the temporalis muscle flap. The soft palate was completely removed in two patients with soft palate cancer and repaired using the folded extended submental perforator flap. RESULTS: Before the surgery, the reflux vein was observed by neck-enhanced CT, including 12 cases returning to the internal jugular vein and 7 cases to the external jugular vein. All 19 cases in which flaps were used survived, and 1 case had a postoperative infection. All the patients had nasal feeding removed after surgery. The tracheal cannula was removed from the patients with laryngeal preservation, and the pronunciation was satisfactory. Among them, patients with soft palate cancer repair had mild nasal reflux symptoms with smooth breathing. During the follow-up period of 4-24 months, 18 patients had no tumour recurrence or metastasis, and 1 patient had cervical lymph node metastasis. CONCLUSIONS: This study highlights the use of a submental perforator flap distal to the connecting line between the mastoid and the sternoclavicular joint to repair postoperative defects for upper airway malignancy as an innovative surgical approach that provides more tissue and good arteriovenous blood supply to adjacent sites. This method has high clinical value and provides an effective option for repairing postoperative defects of upper airway malignancy.

Induction chemotherapy-based organ-preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer-Results of a matched-pair analysis.

BACKGROUND: We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy-based organ-preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy. METHODS: 351 patients who were treated with organ-preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression-free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS). RESULTS: No statistical difference was observed for 3-, 5-, and 10-year PFS and OS in two groups. In the organ-preservation group, the 3-, 5-, and 10-year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05). CONCLUSIONS: Survival outcomes did not significantly differ between the two groups. The organ-preservation approach allowed more than 70% of the survivors to retain their larynx function.

Dysregulated Polycomb Repressive Complex 2 contributes to chronic obstructive pulmonary disease by rewiring stem cell fate.

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self-renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 in mice with ovalbumin-induced lung inflammation led to epithelial cell differentiation patterns similar to those in COPD lung. We also identified cystathionine-ß-synthase as a possible upstream factor for PRC2 destabilization. Our findings suggest that PRC2 is integral to facilitating proper lung stem cell differentiation in humans and mice.

Hydrogen Peroxide Promotes the Production of Radiation-Derived EVs Containing Mitochondrial Proteins.

In spite of extensive successes, cancer recurrence after radiation treatment (RT) remains one of the significant challenges in the cure of localized prostate cancer (PCa). This study focuses on elucidating a novel adaptive response to RT that could contribute to cancer recurrence. Here, we used PC3 cell line, an adenocarcinoma from a bone metastasis and radio-resistant clone 695 cell line, which survived after total radiation dose of 66 Gy (2 Gy × 33) and subsequently regrew in nude mice after exposure to fractionated radiation at 10 Gy (2 Gy × 5). Clone 695 cells not only showed an increase in surviving fraction post-radiation but also an increase in hydrogen peroxide (H2O2) production when compared to PC3 cells. At the single cell level, confocal microscope images coupled with IMARIS rendering software demonstrate an increase in mitochondrial mass and membrane potential in clone 695 cells. Utilizing the Seahorse XF96 instrument to investigate mitochondrial respiration, clone 695 cells demonstrated a higher basal Oxygen Consumption Rate (OCR), ATP-linked OCR, and proton leak compared to PC3 cells. The elevation of mitochondrial function in clone 695 cells is accompanied by an increase in mitochondrial H2O2 production. These data suggest that H2O2 could reprogram PCa's mitochondrial homeostasis, which allows the cancer to survive and regrow after RT. Upon exposure to RT, in addition to ROS production, we found that RT induces the release of extracellular vesicles (EVs) from PC3 cells (p < 0.05). Importantly, adding H2O2 to PC3 cells promotes EVs production in a dose-dependent manner and pre-treatment with polyethylene glycol-Catalase mitigates H2O2-mediated EV production. Both RT-derived EVs and H2O2-derived EVs carried higher levels of mitochondrial antioxidant proteins including, Peroxiredoxin 3, Glutathione Peroxidase 4 as well as mitochondrial-associated oxidative phosphorylation proteins. Significantly, adding isolated functional mitochondria 24 h prior to RT shows a significant increase in surviving fractions of PC3 cells (p < 0.05). Together, our findings reveal that H2O2 promotes the production of EVs carrying mitochondrial proteins and that functional mitochondria enhance cancer survival after RT.

A combined microinvasive trans-submandibular and nasendoscopy surgical approach to dissect recurrent or radiotherapy-insensitive nasopharyngeal carcinoma.

Objective: To investigate a novel combined microinvasive trans-submandibular and nasendoscopy surgical approach for nasopharyngeal carcinoma involving the parapharyngeal space. Methods: Seven patients diagnosed with nasopharyngeal carcinoma involving the parapharyngeal space between May 2018 and April 2021, two males and five females, aged 37-63 years.Six of the 7 patients underwent submental flap preparation and dissection of the lymph nodes in the upper neck and parapharyngeal space on the lesion side. The nasopharynx lesions and tumor margins were dissected under nasal endoscopy. The medial boundary of internal carotid artery separated by open cervical approach was used as the lateral boundary of the tumor to realize en bloc resection of the tumor. Results: The patients were preoperatively diagnosed with T2~3N0M0 nasopharyngeal carcinoma, including mucoepidermoid carcinoma (n=2), papillary adenocarcinoma (n=1), and nonkeratinizing squamous cell carcinoma (n=4). The tumors were removed completely, and patients achieved primary healing of the incision. No recurrence and no serious complications were recorded during the 13-48 month follow-up. Conclusion: Complete resection of the tumor was obtained in the 7 patients without recurrence and serious complications during the follow-up. The findings of this cohort study suggest that, patients with recurrent nasopharyngeal carcinoma after radiotherapy and radiotherapy-insensitive types of nasopharyngeal carcinoma, the combined microinvasive trans-submandibular and nasendoscopy surgical approach may be considered as an surgical options. The results of this study provide an additional option for surgical treatment of NPC in the clinic.

The RelB-BLNK Axis Determines Cellular Response to a Novel Redox-Active Agent Betamethasone during Radiation Therapy in Prostate Cancer.

Aberrant levels of reactive oxygen species (ROS) are potential mechanisms that contribute to both cancer therapy efficacy and the side effects of cancer treatment. Upregulation of the non-canonical redox-sensitive NF-kB family member, RelB, confers radioresistance in prostate cancer (PCa). We screened FDA-approved compounds and identified betamethasone (BET) as a drug that increases hydrogen peroxide levels in vitro and protects non-PCa tissues/cells while also enhancing radiation killing of PCa tissues/cells, both in vitro and in vivo. Significantly, BET increases ROS levels and exerts different effects on RelB expression in normal cells and PCa cells. BET induces protein expression of RelB and RelB target genes, including the primary antioxidant enzyme, manganese superoxide dismutase (MnSOD), in normal cells, while it suppresses protein expression of RelB and MnSOD in LNCaP cells and PC3 cells. RNA sequencing analysis identifies B-cell linker protein (BLNK) as a novel RelB complementary partner that BET differentially regulates in normal cells and PCa cells. RelB and BLNK are upregulated and correlate with the aggressiveness of PCa in human samples. The RelB-BLNK axis translocates to the nuclear compartment to activate MnSOD protein expression. BET promotes the RelB-BLNK axis in normal cells but suppresses the RelB-BLNK axis in PCa cells. Targeted disruptions of RelB-BLNK expressions mitigate the radioprotective effect of BET on normal cells and the radiosensitizing effect of BET on PCa cells. Our study identified a novel RelB complementary partner and reveals a complex redox-mediated mechanism showing that the RelB-BLNK axis, at least in part, triggers differential responses to the redox-active agent BET by stimulating adaptive responses in normal cells but pushing PCa cells into oxidative stress overload.

Iron vacancies engineering of FexC@NC hybrids toward enhanced lithium-ion storage properties.

Defect engineering have profound influence on the energy storage properties of electrode hybrids by adjusting their intrinsic electronic characteristics. For iron carbide based materials, however, the effect of defect (especially cation vacancies) toward their electrochemical performance are still unclear. Herein, the feasible and scalable synthesis of FexC@NC with 3D honeycomb-like carbon architecture and abundant Fe vacancies via template etching is reported. Such structure enable outstanding lithium-ion storage properties owing to hierarchical pores, improved intrinsic electrochemical activity, as well as the introduction of more active sites. As a result, the FexC@NC-2 presents a high reversible specific capacity of 1079 mAh g-1after 1000 cycles. Moreover, an excellent cycling stability can be achieved via maintaining a high-capacity retention (689 mAh g-1, 98.4%) over 1000 cycles at 5 A g-1. This study provides a feasible strategy for developing high-performance hybrids with hierarchical pore and rich defects structures.

[Application of esophageal CT to establish the evaluation model of foreign body position in rigid esophagoscopic surgery].

Objective:Establish a correlation model with the true position of the foreign body in the esophageal foreign body surgery using the relevant diameter of the esophageal foreign body computed tomography（CT）. Methods:Thirty-three patients who were diagnosed with esophageal foreign bodies by esophageal CT in the emergency department of the Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, were selected to measure the CT-related diameters of the esophageal tube（airway length, hyoid anterior edge-mandibular distance, incisor extension line-Posterior nasal ridge, distance from foreign body to hard jaw, distance from foreign body to incisor, front and back nasal crest line-spine line included angle, front and back nasal crest line and airway length line included angle, the lowest point of mandible-highest point of hyoid bone-and Spine angle）, record the height and weight of the patient and calculate the body mass index（BMI）. During the operation, the patient's head is fully tilted back, and the rigid esophagus is inserted through the mouth, and the front end of the esophagus is recorded when it touches a foreign body. The method of multivariate linear analysis was used to calculate the CT diameter that correlated with the distance between the foreign body and the incisor during the operation. Results:The most common foreign body in the esophagus is jujube pit（14 cases）, followed by fish bones（13 cases）; the distance between the foreign body and the hard jaw, the incisor teeth measured by CT of the esophagus is less than the actual distance between the foreign body and the incisor during the operation（P<0.001）, the difference was statistically significant. Multiple linear regression analysis found that the patient's BMI（P=0.037） and the distance of the foreign body from the hard jaw（P<0.001） were correlated with the actual distance of the foreign body from the incisor during the operation. LR=3.708+0.130×BMI+0.857×Lct（cm）, R²=0.736, adjusted R²=0.719. Conclusion:The distance between the foreign body and the hard jaw measured by esophageal CT combined with the patient's BMI can predict the distance of the foreign body during rigid esophagoscopic surgery under general anesthesia and provide a certain reference value for the detection of foreign body during the operation.

Electrochemically Induced Structural and Morphological Evolutions in Nickel Vanadium Oxide Hydrate Nanobelts Enabling Fast Transport Kinetics for High-Performance Zinc Storage.

Suitable intercalation cathodes and fundamental insights into the Zn-ion storage mechanism are the crucial factors for the booming development of aqueous zinc-ion batteries. Herein, a novel nickel vanadium oxide hydrate (Ni0.25V2O5·0.88H2O) is synthesized and investigated as a high-performance electrode material, which delivers a reversible capacity of 418 mA h g-1 with 155 mA h g-1 retained at 20 A g-1 and a high capacity of 293 mA h g-1 in long-term cycling at 10 A g-1 with 77% retention after 10,000 cycles. More importantly, multistep phase transition and chemical-state change during intercalation/deintercalation of hydrated Zn2+ are illustrated in detail via in situ/ex situ analytical techniques to unveil the Zn2+ storage mechanism of the hydrated and layered vanadium oxide bronze. Furthermore, morphological development from nanobelts to hierarchical structures during rapid ion insertion and extraction is demonstrated and a self-hierarchical process is correspondingly proposed. The unique evolutions of structure and morphology, together with consequent fast Zn2+ transport kinetics, are of significance to the outstanding zinc storage capacity, which would enlighten the mechanism exploration of the aqueous rechargeable batteries and push development of vanadium-based cathode materials.

A Corrole-Based Covalent Organic Framework Featuring Desymmetrized Topology.

Herein, for the first time, we present the successful synthesis of a novel two-dimensional corrole-based covalent organic framework (COF) by reacting the unusual approximately T-shaped 5,10,15-tris(p-aminophenyl)corrole H3 TPAPC with terephthalaldehyde, which adopts desymmetrized hcb topology and consists of a staggered AB stacking structure with elliptical pores. The resultant corrole-based COF, TPAPC-COF, exhibits high crystallinity and excellent chemical stability. The combination of extended π-conjugated backbone and interlayer noncovalent π-π interactions endows TPAPC-COF with excellent absorption capability in the entire visible-light and even near-infrared regions. Moreover, this work suggests the promise of TPAPC-COF as a new class of photoactive material for efficient singlet-oxygen generation with potential photodynamic therapy application as demonstrated by in vitro anticancer studies.

Extracellular Vesicles Released by Cardiomyocytes in a Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers of Early Cardiac Injury.

Purpose: Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury.Experimental Design: Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content.Results: Treatment with DOX caused a significant increase in circulating EVs (DOX_EV) compared with saline-treated controls. DOX_EVs exhibited a higher level of 4-hydroxynonenal adducted proteins, a lipid peroxidation product linked to DOX-induced cardiotoxicity. Proteomic profiling of DOX_EVs revealed the distinctive presence of brain/heart, muscle, and liver isoforms of glycogen phosphorylase (GP), and their origins were verified to be heart, skeletal muscle, and liver, respectively. The presence of brain/heart GP (PYGB) in DOX_EVs correlated with a reduction of PYGB in heart, but not brain tissues. Manganese superoxide dismutase (MnSOD) overexpression, as well as pretreatment with cardioprotective agents and MnSOD mimetics, resulted in a reduction of EV-associated PYGB in mice treated with DOX. Kinetic studies indicated that EVs containing PYGB were released prior to the rise of cardiac troponin in the blood after DOX treatment, suggesting that PYGB is an early indicator of cardiac injury.Conclusions: EVs containing PYGB are an early and sensitive biomarker of cardiac injury. Clin Cancer Res; 24(7); 1644-53. ©2017 AACRSee related commentary by Zhu and Gius, p. 1516.

MicroRNA-154/ADAM9 axis inhibits the proliferation, migration and invasion of breast cancer cells.

Breast cancer is the leading cause for cancer-associated mortality in women. Although great progress has been made in the earlier diagnosis and systemic therapy of patients with breast cancer in recent years, recurrence or distant metastasis continue to present major barriers to the successful treatment of breast cancer. Therefore, fully understanding the molecular mechanisms underlying the progression of breast cancer may be critical for the development of effective therapeutic strategies against breast cancer. The aim of the present study was to explore the expression, function and molecular mechanisms of microRNA-154 (miR-154) in human breast cancer. It was demonstrated that miR-154 was significantly downregulated in breast cancer tissue and cell lines. The restoration of miR-154 expression suppressed the proliferation, migration and invasion of breast cancer cells. ADAM metallopeptidase domain 9 (ADAM9) was identified as a novel direct target for miR-154 in breast cancer. It was demonstrated that miR-154 acted as a tumor suppressor in breast cancer by targeting ADAM9. The results of the present study suggest that the restoration of miR-154 expression may be an effective therapeutic strategy for the treatment of breast cancer in the future.

A Naturally Generated Decoy of the Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance in Tumors.

Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 proapoptotic function. Conversely, PAF, which contains this VASA segment, competitively bound to Fbxo45 and rescued Par-4-mediated induction of cancer cell-specific apoptosis. Collectively, our findings identify a molecular decoy naturally generated during apoptosis that inhibits a ubiquitin ligase to overcome therapy resistance in tumors. Cancer Res; 77(15); 4039-50. ©2017 AACR.

[Study of visual analogue scale of nasal symptoms between chronic rhinosinusitis patients and doctors].

OBJECTIVE: To investigate the difference of the symptoms evaluation between CRS patients and doctors. METHOD: Seven symptoms including nasal obstruction, watery rhinorrhea, sneezing, rhinocnesmus, itching of eyes, hyposmia and facial pain were evaluated by visual analog scales (VAS) by the patients. The assigned rhinologist finished VAS evaluation of doctor based on the patient's description of their symptoms. Rank test was used to analyze the difference for each VAS scores of symptom between patients and doctor. Spearman test was used to analyze the effect of age in VAS scores and the effect of gender was analyzed by using Mann-Whitney test. RESULT: We found that the sum and every single patient's nasal symptoms VAS scores both showed statistical significantly difference (t = 4.51 P < 0.01). VAS scores of nasal blockage showed the significant difference between patients and doctor (r = 359.52 P < 0.01). Age of patients did not show correlation with VAS scores (r = -0.074 P > 0.05) also, gender of patients didn't show statistical significant (P > 0.05). CONCLUSION: There were differences between patient's and doctor's nasal symptoms VAS scores and the VAS scores of patients were higher than the doctor's. Age and gender of patient were not related to the VAS evaluation.