Comparing the double-echo steady-state with water excitation and constructive interference in steady state sequence techniques for identifying extracranial facial nerve and tumor positions in patients with parotid tumors.

BACKGROUND AND PURPOSE: Reliable preoperative visualization of facial nerve morphology and understanding the spatial relationship between the facial nerve and tumor in the parotid gland can help clinicians perform safe and effective surgeries. Hence, this study aimed to compare the image quality of extracranial facial nerves obtained using double-echo steady-state with water excitation (DESS-WE) and constructive interference in steady state (CISS) sequences and evaluate their diagnostic efficacy in the localization of parotid tumors. MATERIALS AND METHODS: In total, 32 facial nerves of 16 healthy volunteers and 25 facial nerves of 25 patients with parotid tumors were included in this retrospective study. All participants underwent noncontrast-enhanced extracranial facial nerve magnetic resonance imaging with DESS-WE and CISS with a 3T MR scanner equipped with a 64-channel head and neck coil. Image quality was subjectively evaluated using a 5-point Likert scale by two radiologists. Inter- and intra-rater agreements were assessed using the Cohen kappa coefficient (κ). Receiver operating characteristic analysis was performed, and the diagnostic efficacies of DESS-WE and CISS images in localizing parotid tumors were calculated. RESULTS: For healthy volunteers (11 men and 5 women; median age, 26 years), image quality scores for CISS were significantly higher than those for DESS-WE for the discrimination of the temporofacial and cervicofacial trunks (both, p <0.001). In patients with parotid tumors (12 men and 13 women; median age, 58 years), CISS performed better than DESS-WE in terms of visualizing the spatial relationship of the facial nerve to the tumor and diagnostic confidence (both, p<0.001). Regarding the localization of parotid tumors, CISS showed excellent performance, comparable to that of DESS-WE (area under the curve, 0.981 versus 0.942, p = 0.1489). CONCLUSIONS: CISS achieved diagnostic performance comparable to DESS-WE in parotid tumor localization, with favorable image quality and more reliable morphological visualization of the facial nerve. ABBREVIATIONS: 3D = three-dimensional; CISS = constructive interference in steady state; DESS-WE = double-echo steady-state with water excitation; IQS = image quality score; AUC = area under the curve.

Type-I Photodynamic Therapy Induced by Pt-Coordination of Type-II Photosensitizers into Supramolecular Complexes.

Platinum supramolecular complexes based on photosensitizers have garnered great interest in photodynamic therapy (PDT) due to Pt (II) centers as chemotherapeutic agents to eliminate tumor cells completely, which greatly improve the antitumor efficacy of PDT. However, in comparison to precursor photosensitizer ligand, the formed platinum supramolecular complexes typically exhibit inferior outcomes in terms of reactive oxygen species (ROS) generation. How to boost ROS generation in the formed platinum supramolecular complexes for enhanced PDT is an enticing yet highly challenging task. Here we report a Pt-coordination-based dimeric photosensitizer complex (Cz-BTZ-Py)2Pt(OTf)2. It is found that comparing with photosensitizer ligand Cz-BTZ-Py, the formed supramolecular complex exhibit redshifts of absorption wavelength as well as enhanced ROS generation efficiency. Moreover, type-I ROS generation (O2⋅-) is produced in the formed platinum supramolecular complexes mainly due to a reduced energy gap ΔEST resulting from exciton coupling between two photosensitizer ligands. And type-I ROS (O2⋅-) generation significantly amplifies the photodynamic therapy (PDT) outcomes. In vitro evaluation shows excellent photochemotherapy performance of (Cz-BTZ-Py)2Pt(OTf)2 nanoparticles. We anticipate this work would provide a novel approach to design type-I photosensitizers for efficient PDT.

Effect of Ascosphaera apis Infestation on the Activities of Four Antioxidant Enzymes in Asian Honey Bee Larval Guts.

Ascosphaera apis infects exclusively bee larvae and causes chalkbrood, a lethal fungal disease that results in a sharp reduction in adult bees and colony productivity. However, little is known about the effect of A. apis infestation on the activities of antioxidant enzymes in bee larvae. Here, A. apis spores were purified and used to inoculate Asian honey bee (Apis cerana) larvae, followed by the detection of the host survival rate and an evaluation of the activities of four major antioxidant enzymes. At 6 days after inoculation (dpi) with A. apis spores, obvious symptoms of chalkbrood disease similar to what occurs in Apis mellifera larvae were observed. PCR identification verified the A. apis infection of A. cerana larvae. Additionally, the survival rate of larvae inoculated with A. apis was high at 1−2 dpi, which sharply decreased to 4.16% at 4 dpi and which reached 0% at 5 dpi, whereas that of uninoculated larvae was always high at 1~8 dpi, with an average survival rate of 95.37%, indicating the negative impact of A. apis infection on larval survival. As compared with those in the corresponding uninoculated groups, the superoxide dismutase (SOD) and catalase (CAT) activities in the 5- and 6-day-old larval guts in the A. apis−inoculated groups were significantly decreased (p < 0.05) and the glutathione S-transferase (GST) activity in the 4- and 5-day-old larval guts was significantly increased (p < 0.05), which suggests that the inhibition of SOD and CAT activities and the activation of GST activity in the larval guts was caused by A. apis infestation. In comparison with that in the corresponding uninoculated groups, the polyphenol oxidase (PPO) activity was significantly increased (p < 0.05) in the 5-day-old larval gut but significantly reduced (p < 0.01) in the 6-day-old larval gut, indicating that the PPO activity in the larval guts was first enhanced and then suppressed. Our findings not only unravel the response of A. cerana larvae to A. apis infestation from a biochemical perspective but also offer a valuable insight into the interaction between Asian honey bee larvae and A. apis.

Localization Evaluation of Primary Middle Ear Cholesteatoma With Fusion of Turbo Spin-Echo Diffusion-Weighted Imaging and High-Resolution Computed Tomography.

OBJECTIVE: The aim of the study is to evaluate the application of high-resolution computed tomography (HRCT) and turbo spin-echo diffusion-weighted imaging (TSE-DWI) fusion imaging for localization of middle ear cholesteatomas. METHODS: Eighty-six patients with clinically suspected middle ear cholesteatomas were enrolled prospectively. Ear TSE-DWI and HRCT scans were performed using a postprocessing workstation to generate a TSE-DWI-CT fusion image. Subsequently, all the enrolled patients received surgical treatment. According to the STAM system (difficult access sites [S], the tympanic cavity [T], the attic [A], and the mastoid [M]), the agreement between the localization of lesions evaluated by HRCT, TSE-DWI, and TSE-DWI-CT fusion images and the intraoperatively recorded localization were computed using Cohen κ statistic. RESULTS: Based on the pathological results, the enrolled patients were divided into a cholesteatoma (n = 50) and a noncholesteatoma group (n = 36). The area under the receiver operator characteristic curve for diagnosis of cholesteatoma with TSE-DWI-CT fusion imaging was identical to that using the TSE-DWI images (0.924 vs 0.924, P > 0.05), but was significantly higher than that with HRCT imaging (0.924 vs 0.767, P = 0.0005). Furthermore, the diagnostic sensitivity and specificity of TSE-DWI-CT fusion imaging for cholesteatomas were 96.0% and 88.9%, respectively. Depending on whether the cholesteatoma extended to the mastoid, TSE-DWI-CT fusion imaging demonstrated good agreement with the intraoperative record for localization of lesions (κ = 0.808) and had a high accuracy of localization by the STAM system. CONCLUSIONS: Turbo spin-echo-DWI-CT fusion images have a very high diagnostic value for the preoperative localization of cholesteatomas.

Preparation and Antioxidant Activities of High Fischer's Ratio Oligopeptides from Goat Whey.

This study aimed to obtain high Fischer's ratio oligopeptides from goat whey (HFO) and investigate antioxidant property of it. Hydrolysis of goat whey was done with the approach of sequential digestion of pepsin and flavourzyme. With the adsorption of aromatic amino acids by activated carbon, HFO with a Fischer's ratio of 27.070 and a molecular weight of 200-1,000 Da were obtained, and the branched-chain amino acids accounted for 22.87%. Then the antioxidant activity of HFO was evaluated. At the concentrations of 2.0 mg/mL and 0.50 mg/mL, HFO scavenged 77.27% and 99.63% of 1,1-diphenyl-2-picrylhydrazyl and 3-ethylbenzthiazoline-6-sulphonate free radicals respectively. The scavenging rate of HFO against hydroxyl radicals reached 92.31% at the concentration of 0.25 mg/mL. Animal experiments demonstrated that HFO could moderate the changes of malondialdehyde, superoxide dismutase and glutathione peroxidase caused by CCl4-induced oxidative stress in vivo. This study indicated that HFO from goat whey was capable of oxidation resistance both in vivo and in vitro, which provided a scientific basis for the high-value processing and application of goat milk whey.

Photothermal agents based on small organic fluorophores with intramolecular motion.

Photothermal therapy (PTT) has attracted great attention due to its noninvasive and low side effects. Photothermal agents (PTAs) which could convert absorbing light into heat play a critical role in PTT. For conventional small organic PTAs, the photothermal conversion ability is mainly achieved by intermolecular noncovalent interactions such as π-π interactions. However, in terms of organic fluorophores with rotator or vibrator segments, the balance between fluorescence emission and heat generation is mainly regulated by intramolecular motions which could be mediated by molecular engineering. Following this designing principle, various fluorophores with intramolecular motions for effective PTT have been reported. In this review, we highlight the recent progress of PTAs based on small organic fluorophores with intramolecular motions for enhanced PTT. Designing tactics of these fluorophores to afford long-wavelength absorption, high photothermal conversion ability, and effective accumulation capability are emphasized. Finally, one-for-all phototheranostics achieved by mediating intramolecular motions of these fluorophores are highlighted. We hope this review could pave a new avenue to developing fluorophores with intramolecular motion as PTAs to advance their clinical transition. STATEMENT OF SIGNIFICANCE: Recent progress of photothermal agents (PTAs) based on small organic fluorophores with intramolecular motion is summarized in this review. Molecular engineering of these small organic fluorophores to afford long-wavelength absorption, high photothermal conversion ability, and effective accumulation at tumor sites for enhanced photothermal therapy (PTT) is highlighted. Strategies to tune the intramolecular motions of these fluorophores to achieve multimodal phototherapy are emphasized as well.

Rational design of a small organic photosensitizer for NIR-I imaging-guided synergistic photodynamic and photothermal therapy.

Developing a small molecular photosensitizer to achieve multimodal phototherapy has recently garnered attention as a promising strategy for efficient cancer treatment. However, synthesis of a multifunctional small molecular photosensitizer has remained challenging. Here we report an aggregation-induced-emission (AIE)-featured luminogen (AIEgen) TPA-BTZ decorated with long and branched alkyl chains. TPA-BTZ shows long-wavelength emission at ca. 800 nm in the NIR-I region. Moreover, upon laser irradiation, TPA-BTZ could produce O2˙- and 1O2via both type I and type II mechanisms for enhanced photodynamic therapy (PDT). The propeller-like structure triphenylamine (TPA) rotators not only endow TPA-BTZ with AIE characteristics but also facilitate heat generation by intramolecular rotation for photothermal therapy (PTT). More importantly, long and branched alkyl chains can create intermolecular spatial isolation in the fabricated TPA-BTZ@PEG2000 nanoparticles (NPs) to allow sufficient intramolecular motion for photothermal conversion. Due to these unique features, in vitro and in vivo evaluations demonstrate that the TPA-BTZ@PEG2000 NPs exhibited long-term NIR-imaging ability, superior tumoricidal activity, and suppressed tumor growth. This research provides new insights for developing new AIEgens for NIR imaging-guided multimodal phototherapy.

[The value of turbo spin-echo diffusion weighted imaging in the diagnosis of temporal bone cholesteatoma].

Objective:The aim of this study is to evaluate the diagnostic value of turbo spin-echo（TSE） diffusion weighted imaging（DWI） in temporal bone cholesteatoma. Method:A prospective evaluated of 76 patients with suspected sacral cholesteatoma was performed using a Philips Ingenia 3.0T superconducting magnetic resonance scanner and a 32-channel head coil with turbo spin-echo diffusion weighted imaging（TSE-DWI） sequence and conventional magnetic resonance scan, and underwent surgery within the next two weeks. The pathological result is the gold standard, and the imaging diagnosis and surgery are performed. The intraoperative observation and pathological results were compared. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of TSE-DWI sequence in the diagnosis of temporal bone cholesteatoma were calculated. Result:Of the 76 patients with suspected temporal bone cholesteatoma, TSE-DWI scan was performed, 44 cases were diagnosed as cholesteatoma and 32 cases were non-cholesteatoma. Based on the pathology results, 46 cases were diagnosed as cholesteatoma, 30 cases were non-cholesteatoma. The accuracy of TSW-DWI sequence in the diagnosis of cholesteatoma was 89.47%, 3 cases were false negative and 5 cases was false positive. The sensitivity, specificity, positive predictive value and negative predictive value of TSE-DWI in the diagnosis of temporal bone cholesteatoma were 89.13%, 90.00%, 93.18%, and 84.38%, respectively. Conclusion:The TSE-DWI sequence has high signal-to-noise ratio and can improve the diagnostic accuracy and specificity. TSE-DWI sequence is of great value in clinical diagnosis and treatment.

Association between smoking and in-hospital mortality in patients with acute myocardial infarction: results from a prospective, multicentre, observational study in China.

INTRODUCTION: Smoking is a well-established risk factor for cardiovascular disease. However, the effect of smoking on in-hospital mortality in patients with acute myocardial infarction (AMI) who are managed by contemporary treatment is still unclear. METHODS: A cohort study was conducted using data from the China AMI registry between 2013 and 2016. Eligible patients were diagnosed with AMI in accordance with the third universal definition of MI. Propensity score (PS) matching and multivariable logistic regression were used to control for confounders. Subgroup analysis was performed to examine whether the association between smoking and in-hospital mortality varies according to baseline characteristics. RESULTS: A total of 37 614 patients were included. Smokers were younger and more frequently men with fewer comorbidities than non-smokers. After PS matching and multivariable log regression analysis were performed, the difference in in-hospital mortality between current smokers versus non-smokers was reduced, but it was still significant (5.1% vs 6.1%, p=0.0045; adjusted OR 0.78, 95% CI 0.69 to 0.88, p<0.001). Among all subgroups, there was a trend towards lower in-hospital mortality in current or ex-smokers compared with non-smokers. CONCLUSIONS: Smoking is associated with lower in-hospital mortality in patients with AMI, even after multiple analyses to control for potential confounders. This 'smoker's paradox' cannot be fully explained by confounding alone. TRIAL REGISTRATION NUMBER: NCT01874691.

Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/ß-catenin and Jak2/Stat3 pathways.

Captopril (Cap) as angiotensin-converting enzyme inhibitor (ACEi) is commonly used to treat hypertension and some types of congestive heart failure. However, few studies reported on whether Cap exerts a protective effect on myocardial apoptosis induced by transverse aortic constriction (TAC). This study aimed at investigating the possible mechanism of Cap on myocardial apoptosis induced by pressure overload. Results showed that Cap significantly decreased heart-to-body weight ratios (HBWR). Cap markedly improved cardiac function, and reduced inner diameter of ascending aorta (Asc Ao) in TAC mice as shown by echocardiography. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that Cap treatment also markedly decreased the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Cardiac pathological changes and fibrosis have been improved after Cap treatment as shown by hematoxylin-eosin (H&E) staining and Masson's trichrome staining. Moreover, Terminal deoxynucleotidyl transferase-mediated dexoxyuridine triphosphate nick-end labeling (TUNEL) staining result indicated Cap treatment also significantly inhibited cardiac apoptosis. Western Blot results showed that Cap obviously decreased the expression of cleaved capase-3, Bax, phosphorylated Jak2 (p-Jak2), phosphorylated Stat3 (p-Stat3), Wnt3a and ß-catenin proteins, as well as increased Bcl-2 expression. In conclusion, Cap showed a protective effect on TAC-induced cardiac apoptosis, which could be attributed to the inhibition of Wnt3a/ß-catenin signaling pathway. Cap also attenuated myocardial hypertrophy induced by TAC via suppression of Jak2/Stat3 pathway.

Rhein ameliorates adenomyosis by inhibiting NF-κB and ß-Catenin signaling pathway.

In the present study, we examined the effects of rhein on pituitary gland implantation-induced adenomyosis, an animal model which mimics human adenomyosis. Oral administration of rhein dose-dependently attenuated hyperplastic and hypertrophic myometrium and improved adenomyosis. The activation of NF-κB and ß-catenin signaling pathway was observed in the ectopic endometria. While, rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived Rac1. As Rac1 activation controlled nuclear localization of ß-catenin during canonical Wnt signaling, we found that the degradation complex of ß-catenin was improved by rhein. In addition, ß-catenin nuclear translocation and its downstream genes were markedly suppressed by different doses of rhein. At the same time, decreased activation of epithelial-mesenchymal transition (EMT)-associated proteins including Snail and ZEB1 was detected in rhein-treated mice, indicating that the activation of Wnt signaling pathway was suppressed by rhein. The in vitro study verified a negative regulation of rhein on ß-catenin in stromal cells. Stimulation of IL-1ß significantly increased the nuclear translocation of ß-catenin and improved its target genes expressions. While, rhein remarkably abolished the enhancement in a dose dependent manner. Taken together, our results demonstrated the ability of rhein to inhibit Wnt/ß-catenin activation and its potential use in the treatment of adenomyosis and other abnormal activation of ß-catenin -associated diseases.

YiQiFuMai Powder Injection Attenuates Ischemia/Reperfusion-Induced Myocardial Apoptosis Through AMPK Activation.

The YiQiFuMai powder injection (YQFM), a traditional Chinese medicine (TCM) prescription re-developed based on the well-known TCM formula Sheng-maisan, showed a wide range of pharmacological activities in cardiovascular diseases in clinics. However, its role in protection against myocardial ischemia/reperfusion (MI/R) injury has not been elucidated. The present study not only evaluated the cardioprotective effect of YQFM from MI/R injury but also investigated the potential molecular mechanisms both in vivo and in vitro. The myocardium infarct size, production of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac function, TUNEL staining, and caspase-3 activity were measured. Cell viability was determined, and cell apoptosis was measured by Hoechst 33342 staining and flow cytometry. Mitochondrial membrane potential (ΔΨm) was measured, and ATP content was quantified by bioluminescent assay. Expression of apoptosis-related proteins, including Caspase-3, Bcl-2, Bax, AMPKα, and phospho-AMPKα, was analyzed by western blotting. AMPKα siRNA transfection was also applied to the mechanism elucidation. YQFM at a concentration of 1.06 g/kg significantly reduced myocardium infarct size and the production of LDH, CK in serum, improved the cardiac function, and also produced a significant decrease of apoptotic index. Further, combined treatment with compound C partly attenuated the anti-apoptotic effect of YQFM. In addition, pretreatment with YQFM ranging from 25 to 400 µg/mL markedly improved cell viability and decreased LDH release. Moreover, YQFM inhibited H9c2 apoptosis, blocked the expression of caspase-3, and modulated Bcl-2 and Bax proteins, leading to an increased mitochondrial membrane potential and cellular ATP content. Mechanistically, YQFM activated AMP-activated protein kinase (AMPK) signaling pathways whereas pretreatment with AMPK inhibitor Compound C and application of transfection with AMPKα siRNA attenuated the anti-apoptotic effect of YQFM. Our results indicated that YQFM could provide significant cardioprotection against MI/R injury, and potential mechanisms might suppress cardiomyocytes apoptosis, at least in part, through activating the AMPK signaling pathways.