Mendelian randomization analysis does not reveal a causal association between migraine and Meniere's disease.

Background: According to observational research, migraine may increase the risk of Meniere's disease (MD). The two have not, however, been proven to be causally related. Methods: Using Mendelian random (MR) analysis, we aimed to evaluate any potential causal relationship between migraine and MD. We extracted single-nucleotide polymorphisms (SNPs) from large-scale genome-wide association studies (GWAS) involving European individuals, focusing on migraine and MD. The main technique used to evaluate effect estimates was inverse-variance weighting (IVW). To assess heterogeneity and pleiotropy, sensitivity analyses were carried out using weighted median, MR-Egger, simple mode, weighted mode, and MR-PRESSO. Results: There was no discernible causative link between genetic vulnerability to MD and migraine. The migraine dose not increase the prevalence of MD in the random-effects IVW method (OR = 0.551, P = 0.825). The extra weighted median analysis (OR = 0.674, P = 0.909), MR-Egger (OR = 0.068, P = 0.806), Simple mode (OR = 0.170, P = 0.737), and Weighted mode (OR = 0.219, P= 0.760) all showed largely consistent results. The MD dose not increase the prevalence of migraine in the random-effects IVW method (OR = 0.999, P = 0.020). The extra weighted median analysis (OR = 0.999, P = 0.909), MR-Egger (OR = 0.999, P = 0.806), Simple mode (OR = 0.999, P = 0.737), and Weighted mode (OR = 1.000, P = 0.760). Conclusion and significance: This Mendelian randomization study provides casual evidence that migraine is not a risk factor for MD and MD is also not a risk factor for migraine.

The mediation effect of mental resilience between stress and coping style among parents of children with cochlear implants: Cross-sectional study.

PURPOSE: This study aimed to examine the relationship of stress, mental resilience, and coping style, and the mediation effect of mental resilience between stress and coping style among parents of children with cochlear implants. DESIGN AND METHODS: A cross-sectional design was used. A total of 231 parents of children with cochlear implants were recruited from May 1, 2022, to February 28, 2023 at a comprehensive tertiary hospital and a cochlear implant rehabilitation center in China. Parenting Stress Index-Short Form (PSI-SF), the Connor-Davidson Resilience Scale (CD-RISC) and the Simplified Coping Style Questionnaire(SCSQ) were used to measure stress, mental resilience, and coping style respectively. RESULTS: The mean score observed for PSI-SF, CD-RISC, active coping, and passive coping was 87.85 ± 24.59, 55.63 ± 16.11, 21.36 ± 6.73, and 9.05 ± 4.52, respectively. Mental resilience was a significant mediator explaining the effect of stress on active coping (ß = -0.294; 95% bias-corrected bootstrap CI: -0.358 to -0.164). CONCLUSIONS: Attention should be paid to the status of stress, mental resilience and coping style in parents of children with cochlear implants. Mental resilience mediated stress and coping style. PRACTICE IMPLICATIONS: This study provides a theoretical basis for establishing an active coping care program for parents of children with cochlear implants. There is a need to identify strategies that can help increase the level of mental resilience of parents of children with cochlear implants and more subjective and objective social support should be provided to reduce their stress and to encourage active coping style.

Lung Abscess Caused by Tannerella forsythia Infection: A Case Report.

Background: Tannerella forsythia is a gram-negative anaerobic bacterium commonly found in the oral cavity. It is among the common pathogenic bacteria associated with gingivitis, chronic periodontitis, and aggressive periodontitis. However, there is currently no literature discussing lung abscesses primarily caused by T. forsythia infection. Presentation: This article presents the case of a 55-year-old male with a massive lung abscess. The patient underwent ultrasound-guided percutaneous drainage, and the sample was sent for pathogen metagenomic next-generation sequencing (mNGS) testing. The test indicated that the lung abscess was primarily caused by T. forsythia infection. A literature review was conducted to understand the characteristics of this pathogen as well as its clinical features and suitable treatment approaches. Conclusion: Currently, there is no literature specifically mentioning T. forsythia as a primary pathogen causing lung abscesses. This anaerobic bacterium is commonly found in the oral cavity and is difficult to cultivate using routine culture methods. mNGS emerges as a value diagnostic method for identifying this pathogen. Treatment recommendations include drainage and antibiotic selection encompassing common periodontal pathogens such as red complex bacteria and Actinomyces.

Flexible High-Entropy Poly(vinyl alcohol) Dielectric Films Were Prepared at a Low Temperature and Applied to an Indium Gallium Zinc Oxide Thin-Film Transistor.

In recent years, more and more attention has been paid to flexible thin-film transistors (TFTs). Therefore, we combined HfMgTiYZrOx high-entropy metal oxide and poly(vinyl alcohol) (PVA) organic material to prepare a flexible dielectric layer. We fabricated metal-insulator-metal (MIM) and TFT devices and carried out flexible tests. The test results show that the mixed dielectric layer attains a leakage current of 3.6 × 10-11 A under the bending radius of 5 mm. In the application of the TFT, the device still has good performance after 10 000 bends with a mobility of 3.1 cm2 V-1 s-1, an Ion/Ioff of 1.4 × 107, a threshold voltage of 3.3 V, and a threshold swing of 0.20 V/decade. In addition, the average transmittance of the hybrid dielectric layer in the visible range is 90.8%. Therefore, high-entropy PVA hybrid films have high transparency, low leakage current, and good bending resistance and have broad application prospects in transparent and flexible devices.

cdh23 affects congenital hearing loss through regulating purine metabolism.

Introduction: The pathogenic gene CDH23 plays a pivotal role in tip links, which is indispensable for mechanoelectrical transduction in the hair cells. However, the underlying molecular mechanism and signal regulatory networks that influence deafness is still largely unknown. Methods: In this study, a congenital deafness family, whole exome sequencing revealed a new mutation in the pathogenic gene CDH23, subsequently; the mutation has been validated using Sanger sequencing method. Then CRISPR/Cas9 technology was employed to knockout zebrafish cdh23 gene. Startle response experiment was used to compare with wide-type, the response to sound stimulation between wide-type and cdh23-/-. To further illustrate the molecular mechanisms underlying congenital deafness, comparative transcriptomic profiling and multiple bioinformatics analyses were performed. Results: The YO-PRO-1 assay result showed that in cdh23 deficient embryos, the YO-PRO-1 signal in inner ear and lateral line neuromast hair cells were completely lost. Startle response experiment showed that compared with wide-type, the response to sound stimulation decreased significantly in cdh23 mutant larvae. Comparative transcriptomic showed that the candidate genes such as atp1b2b and myof could affect hearing by regulating ATP production and purine metabolism in a synergetic way with cdh23. RT-qPCR results further confirmed the transcriptomics results. Further compensatory experiment showed that ATP treated cdh23-/- embryos can partially recover the mutant phenotype. Conclusion: In conclusion, our study may shed light on deciphering the principal mechanism and provide a potential therapeutic method for congenital hearing loss under the condition of CDH23 mutation.

Achieving ideal transistor characteristics in conjugated polymer semiconductors.

Organic thin-film transistors (OTFTs) with ideal behavior are highly desired, because nonideal devices may overestimate the intrinsic property and yield inferior performance in applications. In reality, most polymer OTFTs reported in the literature do not exhibit ideal characteristics. Supported by a structure-property relationship study of several low-disorder conjugated polymers, here, we present an empirical selection rule for polymer candidates for textbook-like OTFTs with high reliability factors (100% for ideal transistors). The successful candidates should have low energetic disorder along their backbones and form thin films with spatially uniform energetic landscapes. We demonstrate that these requirements are satisfied in the semicrystalline polymer PffBT4T-2DT, which exhibits a reliability factor (~100%) that is exceptionally high for polymer devices, rendering it an ideal candidate for OTFT applications. Our findings broaden the selection of polymer semiconductors with textbook-like OTFT characteristics and would shed light upon the molecular design criteria for next-generation polymer semiconductors.

[Advances in the study of fluctuating sensorineural hearing loss].

Fluctuating sensorineural hearing loss（FSNHL） is a special type of sensorineural hearing loss, which can be manifested in many clinical diseases. In this paper, some clinical diseases associated with FSNHL are summarized, such as Meniere's disease, large vestibular aqueduct syndrome, acute low frequency sensorineural hearing loss, delayed endolymphatic hydrops, autoimmune inner ear disease and syndromes leading to FSNHL. The pathogenesis, diagnosis and treatment of FSNHL were summarized in order to improve clinicians' understanding of FSNHL, reduce the probability of misdiagnosis of related diseases and improve the prognosis of patients.

Nrf2 regulates the expression of NOX1 in TNF-α-induced A549 cells.

Acute lung injury causes severe inflammation and oxidative stress in lung tissues. In this study, we analyzed the potential regulatory role of nuclear factor erythroid-2-related factor 2 (Nrf2) on NADPH oxidase 1 (NOX1) in tumor necrosis factor-α (TNF-α)-induced inflammation and oxidative stress in human type II alveolar epithelial cells. In this study, A549 cells were transfected with Nrf2 siRNA and overexpression vectors for 6 h before being induced by TNF-α for 24 h. TNF-α upregulated the expression of NOX1 and Nrf2 in A549 cells. Furthermore, overexpression of Nrf2 could reduce TNF-α-induced NF-κB mRNA and protein expression after transfection with the Nrf2 siRNA vector, and the levels of IL-6, IL-8, ROS, and malondialdehyde (MDA) in TNF-α-induced A549 cells increased, while the level of total antioxidation capability (T-AOC) decreased. On the other hand, the overexpression of Nrf2 decreased the levels of IL-6, IL-8, ROS, and MDA, while increasing T-AOC. The mRNA and protein levels of NOX1 were dramatically increased by TNF-α, while those changes were notably suppressed by Nrf2 overexpression. Further studies demonstrated that Nrf2 suppressed NOX1 transcription by binding to the -1199 to -1189 bp (ATTACACAGCA) region of the NOX1 promoter in TNF-α-stimulated A549 cells. Our study suggests that Nrf2 may bind to and regulate NOX1 expression to antagonize TNF-α-induced inflammatory reaction and oxidative stress in A549 cells.

Beliefs and perceptions of electronic cigarettes among medical staff in respiratory departments of Fujian Province, China, in 2021.

INTRODUCTION: Due to the popularity of e-cigarettes, more and more patients ask about e-cigarettes, and it is particularly important to understand doctors' beliefs and perceptions on e-cigarettes. The aim was to evaluate the belief and perception of electronic cigarettes among medical staff in the respiratory department of medical institutions located in Fujian Province. METHODS: The electronic questionnaires were conveyed to the medical staff of the respiratory department in Fujian Province during March to April 2021. Descriptive statistics were calculated for all questions, and the relationship between relevant factors and the perception of e-cigarette-related statements was analyzed by logistic regression analysis. RESULTS: Among 1028 medical staff in the respiratory departments of Fujian Province, 90.5% of medical staff agreed that electronic cigarettes are harmful to the human body; 61.4% of medical staff agreed that e-cigarettes cannot be regarded as a type of smoking cessation treatment; 71.7% of medical staff agreed that e-cigarettes could be a 'gateway' to other tobacco use; and 69.2% of medical staff agreed that electronic cigarettes are in 'Three No' states. The multivariate logistic regression analysis showed that the respondents' perception of 'e-cigarettes cannot be regarded as a type of smoking cessation treatment' were related to gender, professional title and whether they participated in the cessation clinic. CONCLUSIONS: The medical staff of the respiratory department in Fujian Province put more emphasis on the adverse effects of e-cigarettes on health, but lack the cognition of the effect of e-cigarette smoking cessation. In order to better carry out smoking cessation work, it is necessary to strengthen the training of respiratory medical staff at all levels of medical institutions on e-cigarette knowledge.

Vestibular function in children with cochlear implant: Impact and evaluation.

Over the last 30 years, cochlear implant (CI) has been dedicated to improving the rehabilitation of hearing impairments. However, CI has shown potential detrimental effects on vestibular function. For children, due to atypical symptoms and difficulty in cooperating with vestibular function tests, systematic and objective assessments of vestibular function with CI have been conducted sparsely. This review focuses on the impact of vestibular function in children with CI and summarized the evaluation of vestibular function in children. In addition, some recommended strategies are summarized and proposed.

The effects of epithelial-mesenchymal transitions in COPD induced by cigarette smoke: an update.

Cigarette smoke is a complex aerosol containing a large number of compounds with a variety of toxicity and carcinogenicity. Long-term exposure to cigarette smoke significantly increases the risk of a variety of diseases, including chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is a unique biological process, that refers to epithelial cells losing their polarity and transforming into mobile mesenchymal cells, playing a crucial role in organ development, fibrosis, and cancer progression. Numerous recent studies have shown that EMT is an important pathophysiological process involved in airway fibrosis, airway remodeling, and malignant transformation of COPD. In this review, we summarized the effects of cigarette smoke on the development and progression of COPD and focus on the specific changes and underlying mechanisms of EMT in COPD induced by cigarette smoke. We spotlighted the signaling pathways involved in EMT induced by cigarette smoke and summarize the current research and treatment approaches for EMT in COPD, aiming to provide ideas for potential new treatment and research directions.

Exosomes derived from adipose-derived stem cells alleviate cigarette smoke-induced lung inflammation and injury by inhibiting alveolar macrophages pyroptosis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a frequently encountered disease condition in clinical practice mainly caused by cigarette smoke (CS). The aim of this study was to investigate the protective roles of human adipose-derived stem cells-derived exosomes (ADSCs-Exo) in CS-induced lung inflammation and injury and explore the underlying mechanism by discovering the effects of ADSCs-Exo on alveolar macrophages (AMs) pyroptosis. METHODS: ADSCs were isolated from human adipose tissues harvested from three healthy donors, and then ADSCs-Exo were isolated. In vivo, 24 age-matched male C57BL/6 mice were exposed to CS for 4 weeks, followed by intratracheal administration of ADSCs-Exo or phosphate buffered saline. In vitro, MH-S cells, derived from mouse AMs, were stimulated by 2% CS extract (CSE) for 24 h, followed by the treatment of ADSCs-Exo or phosphate buffered saline. Pulmonary inflammation was analyzed by detecting pro-inflammatory cells and mediators in the bronchoalveolar lavage fluid. Lung histology was assessed by hematoxylin and eosin staining. Mucus production was determined by Alcian blue-periodic acid-Schiff staining. The profile of AMs pyroptosis was evaluated by detecting the levels of pyroptosis-indicated proteins. The inflammatory response in AMs and the phagocytic activity of AMs were also investigated. RESULTS: In mice exposed to CS, the levels of pro-inflammatory cells and mediators were significantly increased, mucus production was markedly increased and lung architecture was obviously disrupted. AMs pyroptosis was elevated and AMs phagocytosis was inhibited. However, the administration of ADSCs-Exo greatly reversed these alterations caused by CS exposure. Consistently, in MH-S cells with CSE-induced properties modelling those found in COPD, the cellular inflammatory response was elevated, the pyroptotic activity was upregulated while the phagocytosis was decreased. Nonetheless, these abnormalities were remarkably alleviated by the treatment of ADSCs-Exo. CONCLUSIONS: ADSCs-Exo effectively attenuate CS-induced airway mucus overproduction, lung inflammation and injury by inhibiting AMs pyroptosis. Therefore, hADSCs-Exo may be a promising cell-free therapeutic candidate for CS-induced lung inflammation and injury.

Large mediastinal mass diagnosed as Nocardia infection by endobronchial ultrasound-guided transbronchial needle aspiration in a ceramic worker: A case report.

Background: Nocardia is a ubiquitous soil saprophyte transmitted through airborne or direct cutaneous inoculation routes. Although Nocardia is more common in immunocompromised patients, Nocardia may also arise in apparently immunocompetent patients. Case presentation: We report a rare case of Nocardia infection presenting as a large mediastinal mass in an immunocompetent ceramic worker. A 54-year-old man with no previous history of immune dysfunction, a ceramic worker by profession, was referred and admitted to our hospital because of a persistent fever for 19 days. Chest CT showed a large middle mediastinal mass. However, conventional anti-infective treatment was ineffective. Under the guidance of the Virtual bronchoscopic navigation (VBN) system, he underwent Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The purulent exudate obtained by EBUS-TBNA was further identified as Nocardia by weak acid-fast and metagenomic next-generation sequencing (mNGS). He was subsequently treated with intravenous imipenem/amikacin, switched to intravenous imipenem and oral trimethoprim/sulfamethoxazole, and the clinical symptoms were significantly improved. Conclusions: Even in immunocompetent patients, Nocardiosis cannot be excluded. For the public, especially soil contact workers, precautions should be taken to avoid Nocardia infection from occupational exposure. This rare case may provide a diagnosis and treatment reference for clinicians.

FERMT3 mediates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/ß-catenin signaling.

BACKGROUND: Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated. METHODS: The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT. RESULTS: Based on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/ß-catenin signaling. CONCLUSIONS: In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/ß-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

Cochlear implantation in prelingually deafened patients: Evaluation in hearing, speech ability, and quality of life. / äººå·¥è€³èœ—æ¤å ¥æœ¯æé«˜è¯­å‰è‹æ‚£è€ å¬è§‰è¨€è¯­èƒ½åŠ›åŠç”Ÿæ´»è´¨é‡.

OBJECTIVES: The main purpose of cochlear implantation for prelingual deafness is to restore the deaf children's auditory function, obtain normal speech development, learning and social ability, and improve the quality of life. Previous studies mostly focused on the improvement of simple hearing or speech ability. This study aims to evaluate the changes of hearing and speech ability and family life quality of patients after cochlear implantation, and to explore the effect of cochlear implantation on hearing and speech rehabilitation of patients. METHODS: In February 2021, using the convenient sampling method, 171 patients who have completed cochlear implantation were selected from the database of cochlear implantation follow-up center of a class III Tertiary hospital in Hunan Province. Questionnaires were used to investigate the patients' parents, which were Categories of Auditory Performance (CAP), Speech/Spatial and Qualities of Hearing Scale-Parents' Version (SSQ-P), and Children using Hearing Implants Quality of Life (CuHI-QoL). T-test and analysis of variance were used to explore the postoperative auditory and speech ability of patients at different ages in different periods (<2.5-year group, 2.5-4.5-year group and >4.5-year group), and Pearson correlation analysis was used to explore the correlation. Multiple linear regression was used to explore the relationship between the dimension of patients' quality of life and the scores of scale for evaluating auditory ability (CAP, speech perception, spatial hearing, and other hearing characteristics). RESULTS: The values of CAP and SSQ-P in the <2.5-year group were lower than those in the 2.5-4.5-year and >4.5-year groups (all P<0.05). Pearson correlation analysis showed that postoperative years and CuHI-QoL scores (parental expectations and patients' quality of life) were positively correlated with score of CAP, SSQ-P and its dimension, respectively (all P<0.05). The results of multiple linear regression analysis showed the CAP scores and speech perception were the influencing factors for the quality of life (R2=0.170, P<0.01). CONCLUSIONS: Two and a half years after operation is the rapid growth period of patients' hearing and language ability, and the growth rate becomes slow after stabilization. With the extension of postoperative years, the patients' hearing and speech ability becomes stronger, and the quality of life is better.

Comprehensive analysis of prognostic value and immune infiltration of kindlin family members in non-small cell lung cancer.

BACKGROUND: Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated. METHODS: We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan­Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR. RESULTS: The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC. CONCLUSIONS: The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.

Nuclear factor-kappaB regulates the transcription of NADPH oxidase 1 in human alveolar epithelial cells.

OBJECTIVE: Acute lung injury (ALI) is characterized by inflammation and oxidative stress. Nuclear factor-kappaB (NF-κB) mediates the expression of various inflammation-related genes, including the NADPH oxidase family. This study aimed to identify the potential regulatory role of NF-κB on NADPH oxidases in tumor necrosis factor-α (TNF-α)-induced oxidative stress in human alveolar epithelial cells. METHODS: A549 cells were treated with TNF-α for 24 h to establish ALI cell models. RT-PCR, western blot, assessment of oxidative stress, Alibaba 2.1 online analysis, electrophoretic mobility shift assays and luciferase reporter analysis were employed to identify the potential regulatory role of NF-κB on NADPH oxidases in TNF-α-induced oxidative stress in human alveolar epithelial cells. RESULTS: The expression of NF-κB/p65 was notably upregulated in TNF-α-stimulated A549 cells. NF-κB knockdown by siRNA significantly inhibited the TNF-α-induced oxidative stress. Moreover, NF-κB/p65 siRNA could inhibit the activation of NOX1, NOX2 and NOX4 mRNA and protein expression in TNF-α-stimulated A549 cells. The next study demonstrated that NF-κB activated the transcription of NOX1 by binding to the -261 to -252 bp (NOX1/κB2, TAAAAATCCC) region of NOX1 promoter in TNF-α-stimulated A549 cells. CONCLUSION: Our data demonstrated that NF-κB can aggravate TNF-α-induced ALI by regulating the oxidative stress response and the expression of NOX1, NOX2 and NOX4. Moreover, NF-κB could promote the NOX1 transcriptional activity via binding its promoter in TNF-α-stimulated A549 cells.

Anti-diabetic effects of the soluble dietary fiber from tartary buckwheat bran in diabetic mice and their potential mechanisms.

BACKGROUND: Tartary buckwheat has beneficial effects on glucose and lipid metabolism of patients with type 2 diabetes mellitus. However, the physiological effects of a soluble dietary fiber (SDF) from tartary buckwheat have rarely been studied, especially in vivo. OBJECTIVE: This study aimed to examine the hypoglycemic and hypolipidemic effects of SDF from tartary buckwheat bran on high-fat diet/streptozotocin-induced diabetic mice. DESIGN: The SDF of tartary buckwheat bran was collected according to the Association of Official Analytical Chemists method 991.43. Diabetic mice were treated with high-fat diets supplemented with 0.5, 1, and 2% SDF for 8 weeks. Parameters related to glucose and lipid metabolism and relevant mechanisms, including the excretion of short-chain fatty acids and the glycemic signaling pathway in the liver, were investigated. In addition, the structural characterization of a purified polysaccharide from SDF of tartary buckwheat bran was illustrated. RESULT: Supplementation with SDF in the diet resulted in reduced levels of fasting blood glucose, improved oral glucose tolerance, increased levels of liver glycogen and insulin, as well as improved lipid profiles in both the serum and liver, in diabetic mice. The amelioration of glucose and lipid metabolism by SDF was accompanied by an increase in the short-chain fatty acid levels in the cecum and co-regulated by hepatic adenosine-5'-monophosphate-activated protein kinase (AMPK) phosphorylation. A neutral tartary buckwheat polysaccharide with an average molecular weight of 19.6 kDa was purified from the SDF, which consisted mainly of glucose with α-glycosidic bonds. CONCLUSIONS: The SDF of tartary buckwheat bran exhibits hypoglycemic and hypolipidemic effects in diabetic mice, contributing to the anti-diabetic mechanisms of tartary buckwheat.

General and mild modification of food-derived extracellular vesicles for enhanced cell targeting.

Food-derived extracellular vesicles (FDEVs) have attracted increasing attention as potential delivery vehicles for therapeutic agents due to their desirable features such as excellent biocompatibility, easy accessibility and cost effectiveness. However, the intrinsic targeting capability of FDEVs is unsatisfactory compared to artificial nanoparticles or other source-derived EVs, which calls for efficient surface engineering strategies to equip them with specific ligands. Here we report a general and mild modification method via reduction of disulfide groups to maleimide reactive thiols. Taking milk-derived EVs (mEVs) as a model system, we demonstrated the feasibility for tethering various ligands on the surface without compromising the vesicular structures. Building an ultra-sensitive nano-flow cytometer (nFCM), the heterogeneous nature of the functionalized samples was revealed, and a magnetic separation approach was proposed accordingly to remove the as-observed non-EV particles. The cellular uptake and cytotoxicity experiments provided direct evidence showing an enhanced cell targeting and cargo delivery capability of the ligand conjugated mEVs. In addition, the in vivo imaging further proved the applicability of transferrin conjugation for increased tumor enrichment of mEVs. Collectively, this general and mild ligand conjugation method enables an efficient surface functionalization of FDEVs, which is of vital importance for enhanced targeting delivery.

[An analysis of surgical management of difficulties during cochlear implant with inner ear anomalies].

Objective:The purpose of this study is to review the difficulties that can occur during cochlear implant surgery in patients with inner ear abnormalities and the management. Method:A retrospective analysis was made on 186 cases of cochlear implant with inner ear malformation, the types of inner ear malformations included 6 cases（3.23%） of isolated semicircular dysplasia, 137 cases（73.66%） of isolated large vestibular aqueducts, 26 cases（13.98%） of Mondini malformations, 6 cases（3.23%） of incomplete septal type Ⅲ, 3 cases（1.61%） of internal auditory stenosis, 7 cases（3.76%） of cochlear dysplasia and 1 case（0.54%） of incomplete septal typeⅠ. Two hundred patients with normal inner ear structures were randomly selected as the control group. The data collected included the types of inner ear abnormalities, intraoperative manifestations, clinical management strategies, and postoperative speech rehabilitation, and the literature was reviewed. Result:148 patients（77.49%） with inner ear malformation underwent successful surgery, electrode insertion was incomplete in 6 patients（3.14%）, and cerebrospinal fluid blowout occurred in 29 patients（15.18%）, it was difficult to locate the window because of the abnormal structure of the window in 8 cases（4.19%）. In 191 patients, the facial recess approach was adopted intraoperatively, and 17.8% of the patients had significant structural abnormalities of the facial nerve, significantly more than the group with normal inner ear structure. Only 1 patient showed delayed facial nerve paralysis 1 week after surgery, and recovered well after treatment. 6.81% of the patients adopted the expanded round window approach, which was significantly lower than that of the group with normal inner ear structure（28%）. There was no significant difference between patients with inner ear malformation and patients with extremely severe deafness with normal inner ear structure who received cochlear implant in speech rehabilitation. Conclusion:Cochlear implant is safe, feasible and effective for patients with inner ear malformation. For patients with inner ear malformation, special attention should be paid to the preoperative imaging reading to predict the possible risks during the operation. The safest surgical plan, including the type of electrode and the manner in which the window is opened, must be prepared before the operation, and the operation must be performed or directed by an experienced surgeon who can adjust the optimal surgical plan according to what is seen during the operation.