Differentiating Definite and Probable Ménière Disease: A Comprehensive Evaluation of Audio-Vestibular Function Testing Combined with Inner Ear MRI.

OBJECTIVES: To evaluate the differences between audio-vestibular function testing and inner ear gadolinium magnetic resonance imaging (MRI) in distinguishing definite Ménière disease (DMD) and probable Ménière disease (PMD), and to provide a reference for early clinical diagnosis and intervention. METHODS: A total of 116 patients diagnosed with DMD (n = 80) and PMD (n = 36) were enrolled. The differences in the results of pure tone audiometry, caloric test, and tympanic injection of gadolinium for contrast-enhanced MRI between the two groups were compared and analyzed. Parameters that could differentiate between the two conditions were identified, and the sensitivity and specificity and the area under the curve (AUC) of individual and combined indices in the differential diagnosis of DMD and PMD were evaluated. RESULTS: The hearing threshold and hearing asymmetry rate of the DMD group were significantly higher than those of the PMD group (p < 0.001), 98.8% and 30.6%, respectively. The abnormal rates of canal paresis (CP) and severity of endolymphatic hydrops in the DMD group were higher than those in the PMD group (p < 0.05). When combined with high-frequency hearing thresholds, hearing asymmetry, hearing curve type, endolymphatic hydrops, and abnormal CP, the diagnostic accuracy of DMD was improved compared to using high-frequency alone (p < 0.05). CONCLUSION: This study showed that PMD and DMD may represent two different stages in the development of MD disease. The comprehensive assessment of audio-vestibular function testing and inner ear MRI proves beneficial for early diagnosis, potentially contributing to the preservation of inner ear function.

Systemic inflammatory markers in ageing, Alzheimer's disease and other dementias.

Systemic inflammation with alterations in inflammatory markers is involved in aging and Alzheimer's disease. However, few studies have investigated the longitudinal trajectories of systemic inflammatory markers during aging and Alzheimer's disease, and specific markers contributing to Alzheimer's disease remain undetermined. In this study, a longitudinal cohort (cohort 1: n = 290; controls, 136; preclinical Alzheimer's disease, 154) and a cross-sectional cohort (cohort 2: n = 351; controls, 62; Alzheimer's disease, 63; vascular dementia, 58; Parkinson's disease dementia, 56; behavioural variant frontotemporal dementia, 57; dementia with Lewy bodies, 55) were included. Plasma levels of inflammatory markers were measured every 2 years during a 10-year follow-up in the longitudinal cohort and once in the cross-sectional cohort. The study demonstrated that the inflammatory markers significantly altered during both aging and the development of Alzheimer's disease. However, only complement C3, interleukin-1ß, and interleukin-6 exhibited significant changes in participants with preclinical Alzheimer's disease, and their longitudinal changes were significantly associated with the development of Alzheimer's disease compared to controls over the 10-year follow-up. In the cross-sectional cohort, complement C3 demonstrates specificity to Alzheimer's disease, while interleukin-1ß and interleukin-6 were also altered in other dementias. The study provides a new perspective on the involvement of inflammatory markers in the aging process and the development of Alzheimer's disease, implying that regulating inflammation may have a pivotal role in promoting successful aging and in the prevention and treatment of Alzheimer's disease.

Effect of artificial natural light on the development of myopia among primary school-age children in China: a three-year longitudinal study.

AIM: To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age children. METHODS: This is a prospective, randomized control, intervention study. A total of 1840 students from 39 classes in 4 primary schools in Foshan participated in this study. The whole randomization method was adopted to include classes as a group according to 1:1 randomized control. Classrooms in the control group were illuminated by usual light, and classrooms in the intervention group were illuminated by artificial natural light. All students received uncorrected visual acuity and best-corrected visual acuity measurement, non-cycloplegic autorefraction, ocular biometric examination, slit lamp and strabismus examination. Three-year follow-up, the students underwent same procedures. Myopia was defined as spherical equivalent refraction ≤ -0.50 D and uncorrected visual acuity <20/20. RESULTS: There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±0.53y. The three-year cumulative incidence rate of myopia was 26.4% (207 incident cases among 784 eligible participants at baseline) in the control group and 21.2% (164 incident cases among 774 eligible participants at baseline) in the intervention group [difference of 5.2% (95%CI, 3.7% to 10.1%); P=0.035]. There was also a significant difference in the three-year change in spherical equivalent refraction for the control group (-0.81 D) compared with the intervention group [-0.63 D; difference of 0.18 D (95%CI, 0.08 to 0.28 D); P<0.001]. Elongation of axial length was significantly different between in the control group (0.77 mm) and the intervention group [0.72 mm; difference of 0.05 mm (95%CI, 0.01 to 0.09 mm); P=0.003]. CONCLUSION: Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.

Delivering synaptic protein mRNAs via extracellular vesicles ameliorates cognitive impairment in a mouse model of Alzheimer's disease.

BACKGROUND: Synaptic dysfunction with reduced synaptic protein levels is a core feature of Alzheimer's disease (AD). Synaptic proteins play a central role in memory processing, learning, and AD pathogenesis. Evidence suggests that synaptic proteins in plasma neuronal-derived extracellular vesicles (EVs) are reduced in patients with AD. However, it remains unclear whether levels of synaptic proteins in EVs are associated with hippocampal atrophy of AD and whether upregulating the expression of these synaptic proteins has a beneficial effect on AD. METHODS: In this study, we included 57 patients with AD and 56 healthy controls. We evaluated their brain atrophy through magnetic resonance imaging using the medial temporal lobe atrophy score. We measured the levels of four synaptic proteins, including synaptosome-associated protein 25 (SNAP25), growth-associated protein 43 (GAP43), neurogranin, and synaptotagmin 1 in both plasma neuronal-derived EVs and cerebrospinal fluid (CSF). We further examined the association of synaptic protein levels with brain atrophy. We also evaluated the levels of these synaptic proteins in the brains of 5×FAD mice. Then, we loaded rabies virus glycoprotein-engineered EVs with messenger RNAs (mRNAs) encoding GAP43 and SNAP25 and administered these EVs to 5×FAD mice. After treatment, synaptic proteins, dendritic density, and cognitive function were evaluated. RESULTS: The results showed that GAP43, SNAP25, neurogranin, and synaptotagmin 1 were decreased in neuronal-derived EVs but increased in CSF in patients with AD, and the changes corresponded to the severity of brain atrophy. GAP43 and SNAP25 were decreased in the brains of 5×FAD mice. The engineered EVs efficiently and stably delivered these synaptic proteins to the brain, where synaptic protein levels were markedly upregulated. Upregulation of synaptic protein expression could ameliorate cognitive impairment in AD by promoting dendritic density. This marks the first successful delivery of synaptic protein mRNAs via EVs in AD mice, yielding remarkable therapeutic effects. CONCLUSIONS: Synaptic proteins are closely related to AD processes. Delivery of synaptic protein mRNAs via EVs stands as a promising effective precision treatment strategy for AD, which significantly advances the current understanding of therapeutic approaches for the disease.

The value of gadolinium-enhanced MRI in predicting the development of sudden hearing loss into Ménière's disease.

OBJECTIVE: To compare the clinical features of sudden hearing loss (SHL) in patients with and without endolymphatic hydrops (EH), and to investigate the association between SHL with EH and Ménière's disease (MD). METHODS: The clinical data of 63 SHL patients with first symptoms were evaluated retrospectively. Patients were separated into two groups based on the results of gadolinium-enhanced magnetic resonance imaging: EH and non-EH groups. Independent sample t-test and U-test were used to compare groups for continuous variables, and the chi-squared test, corrected chi-squared test and Bonferroni correction test were used to compare groups for binary and ordinal variables. The binary logistic regression model was utilised for univariate and multivariate analysis of follow-up patient prognosis. RESULTS: The EH and non-EH groups contained 32 and 31 patients, respectively. The EH group had a higher prevalence of low-tone descending hearing loss. Fifty-one patients were followed for more than 2 years. In the EH group, 11 and 15 patients were diagnosed with sudden sensorineural hearing loss (SSNHL) and MD, respectively, while in the non-EH group, 24 patients were diagnosed with SSNHL and only one with MD. EH, low-tone descending hearing loss and vertigo were risk factors for the diagnosis of MD in a subgroup univariate regression analysis of patients experiencing SHL. EH was found to be a risk factor for the progression of SHL into MD in a multifactor regression analysis. CONCLUSIONS: Patients with SHL who have EH are more likely to present with low-tone descending hearing loss. EH is a risk factor for the subsequent development of MD.

Development and validation of a blood routine-based extent and severity clinical decision support tool for ulcerative colitis.

Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin's model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin's model was free with open access at http://jinmodel.com:3000/ . Jin's model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.

Plasma biomarkers predict Alzheimer's disease before clinical onset in Chinese cohorts.

Plasma amyloid-ß (Aß)42, phosphorylated tau (p-tau)181, and neurofilament light chain (NfL) are promising biomarkers of Alzheimer's disease (AD). However, whether these biomarkers can predict AD in Chinese populations is yet to be fully explored. We therefore tested the performance of these plasma biomarkers in 126 participants with preclinical AD and 123 controls with 8-10 years of follow-up from the China Cognition and Aging Study. Plasma Aß42, p-tau181, and NfL were significantly correlated with cerebrospinal fluid counterparts and significantly altered in participants with preclinical AD. Combining plasma Aß42, p-tau181, and NfL successfully discriminated preclinical AD from controls. These findings were validated in a replication cohort including 51 familial AD mutation carriers and 52 non-carriers from the Chinese Familial Alzheimer's Disease Network. Here we show that plasma Aß42, p-tau181, and NfL may be useful for predicting AD 8 years before clinical onset in Chinese populations.

The Hyperproliferation Mechanism of Cholesteatoma Based on Proteomics: SNCA Promotes Autophagy-Mediated Cell Proliferation Through the PI3K/AKT/CyclinD1 Signaling Pathway.

Cholesteatoma is a chronic inflammatory ear disease with abnormal keratinized epithelium proliferation and tissue damage. However, the mechanism of keratinized epithelium hyperproliferation in cholesteatoma remains unknown. Hence, our study sought to shed light on mechanisms affecting the pathology and development of cholesteatoma, which could help develop adjunctive treatments. To investigate molecular changes in cholesteatoma pathogenesis, we analyzed clinical cholesteatoma specimens and paired ear canal skin with mass spectrometry-based proteomics and bioinformatics. From our screen, alpha-synuclein (SNCA) was overexpressed in middle ear cholesteatoma and might be a key hub protein associated with inflammation, proliferation, and autophagy in cholesteatoma. SNCA was more sensitive to lipopolysaccharide-induced inflammation, and autophagy marker increase was accompanied by autophagy activation in middle ear cholesteatoma tissues. Overexpression of SNCA activated autophagy and promoted cell proliferation and migration, especially under lipopolysaccharide inflammatory stimulation. Moreover, inhibiting autophagy impaired SNCA-mediated keratinocyte proliferation and corresponded with inhibition of the PI3K/AKT/CyclinD1 pathways. Also, 740Y-P, a PI3K activator reversed the suppression of autophagy and PI3K signaling by siATG5 in SNCA-overexpressing cells, which restored proliferative activity. Besides, knockdown of SNCA in RHEK-1 and HaCaT cells or knockdown of PI3K in RHEK-1 and HaCaT cells overexpressing SNCA both resulted in attenuated cell proliferation. Our studies indicated that SNCA overexpression in cholesteatoma might maintain the proliferative ability of cholesteatoma keratinocytes by promoting autophagy under inflammatory conditions. This suggests that dual inhibition of SNCA and autophagy may be a promising new target for treating cholesteatoma.

Phylogenetic relationships and biogeography of Asia Callicarpa (Lamiaceae), with consideration of a long-distance dispersal across the Pacific Ocean -insights into divergence modes of pantropical flora.

There are about 140 species of Callicarpa L. 1753 (Lamiaceae), with more species richness in tropical to subtropical Asia and the New World. The genus might provide an insight into the amphi-Pacific disjunction pattern of tropical and subtropical vegetation. This study has greatly improved the phylogenetic underpinning for Callicarpa, derived from more inclusive taxonomic samplings, and employing data on both two-nuclear and eight-chloroplast regions. To address time and patterns of diversification in Callicarpa, we conducted divergence time and biogeographic analyses, and inferred shifts in the distribution areas across the phylogenetic clades. Our phylogenetic results show that Callicarpa is monophyletic with respect to the groups considered, and eight well-supported primary clades were discerned in the combined analyses. Our estimates indicated that the crown group of Callicarpa originates around the Late-Eocene (ca. 36.23 Ma) and diversification within most clades is concentrated in the Miocene and continued to the Pleistocene. In addition, our biogeographic analyses suggested that the probable ancestor of the Callicarpa crown clade originated in East Asia and Southeast Asia. Multiple dispersal and vicariance events contributed to the current distribution of the taxa. Furthermore, this genus expanded eastward out of East and Southeast Asia to the New World by long-distance dispersal, which inspired us to better understand the amphi-Pacific disjunct distribution.

The value of 3D quantitative scoring of endolymphatic hydrops in the diagnosis and differential diagnosis of Ménière's disease.

Objective: We aimed to explore the application of three-dimensional (3D) quantitative scoring of endolymphatic hydrops (EH) based on gadolinium-contrast MRI in both the diagnosis and differential diagnosis of Ménière's disease (MD). Methods: Local threshold method based on signal intensities was used to quantitatively measure volumes, and the degree of EH was scored by 3D quantitative scoring. The receiver-operating characteristic (ROC) curve was used to compare the diagnostic efficacy of this method against conventional evaluation methods. The scores of MD, sudden sensorineural hearing loss (SSNHL), delayed endolymphatic hydrops (DEH), and vestibular migraine (VM) group were compared and correlated with clinical examination results, including pure tone audiometry (PTA), electrocochleogram, and caloric test. Results: The sensitivity and specificity of 3D quantitative scoring were 94.1% and 92.2%, while conventional evaluation methods were 84.3% and 88.2%, respectively. Cochlear score (CR), vestibular score (VR), semicircular canal score (SR), and total scores (TR) in MD group were significantly higher than those in SSNHL group. The rate of diagnosis of MD was significantly higher in the MD group (92.2%) than VM group (27.3%). In MD, PTA was significantly correlated with CR and SR, the ratio of summating potential to action potential (-SP/AP) of electrocochleogram was significantly correlated with CR, VR, and SR, also canal paresis (CP) value of caloric test was significantly correlated with SR. Conclusion: 3D quantitative scoring demonstrated better diagnostic efficacy than conventional evaluation methods for Ménière's disease, and it may be an effective clinical tool to distinguish MD from SSNHL and VM. The clinical practicality of inner ear-enhanced MRI was further confirmed. Level of Evidence: IV.

Why is the beautyberry so colourful? Evolution, biogeography, and diversification of fruit colours in Callicarpa (Lamiaceae).

Fruit colour is essential to seed dispersal, speciation, and biological diversity in global ecosystems. The relationship between fruit-colour variation and species diversification has long been of interest in evolutionary biology, but remains poorly understood at the genus level. Here, we used Callicarpa, a typical representative of pantropical angiosperm, to analyse whether fruit colours are correlated with biogeographic distribution, dispersal events, and diversification rate. We estimated a time-calibrated phylogeny for Callicarpa and reconstructed ancestral fruit colour. Utilizing phylogenetic methods, we estimated the major dispersal events across the phylogenetic tree and the most likely fruit colours related to each dispersal event, and tested whether the dispersal frequencies and distances of the four fruit colours between major biogeographical areas were equal. We then tested whether fruit colours are correlated with latitude, elevation, and diversification rate. Biogeographical reconstructions showed that Callicarpa originated in the East Asia and Southeast Asia during the Eocene (∼35.53 Ma) and diverse species diverged mainly in the Miocene and lasted into the Pleistocene. Large-scale dispersal events were significantly associated with violet-fruited lineages. Furthermore, different fruit colours were markedly correlated with different latitudes and elevations (e.g., violet fruits were correlated with higher latitudes and elevations; red fruits and black fruits with lower latitudes; white fruits with higher elevations). Notably, violet fruits were statistically associated with highest diversification rates, driving fruit colour variation among different regions globally. Our results contribute to further understanding why fruit colour is so variable at the genus level of angiosperms in different areas around the world.

Callicarpa stoloniformis (Lamiaceae), a new species from Southeast China based on morphological characters and phylogenetic evidence.

Callicarpa stoloniformis sp. nov. (Lamiaceae) is described as a new species from Fujian Province of China on the basis of both morphological and molecular data. The new species is morphologically most close to C. hainanensis. However, it can be distinguished from the latter by its unique procumbent life form, adventitious roots at nodes, papery leaves, cup-shaped or campanulate calyx, truncate or shallow fissure calyx lobes, and smaller fruits. In addition, the new species is also similar with C. basitruncata, a species only known from the original description and the photograph of holotype, but it can differ from the latter by its procumbent shrub, purple terete branchlets with apparent linear lenticels, adventitious roots at nodes, and papery larger leaves with prominently cordate leaf base. Original photographs, illustration, distribution map, and a comparative morphological table, as well as an identification key of the related taxa are provided.

A blood mRNA panel that differentiates Alzheimer's disease from other dementia types.

BACKGROUND: Messenger RNAs (mRNAs) have been reported to be associated with Alzheimer's disease (AD). In this study, we investigated whether plasma-based mRNAs could distinguish AD from cognitively normal controls and other types of dementia, including vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Plasma mRNA expression was measured in three independent datasets. Dataset 1 (n = 40; controls, 20; AD, 20) was used to identify the differentially expressed mRNAs. Dataset 2 (n = 122; controls: 60; AD: 62) was used to develop a diagnostic AD model using an mRNA panel. Furthermore, we applied the model to Dataset 3 (n = 334; control, 57; AD, 58; VaD, 55; PDD, 54; bvFTD, 55; DLB, 55) to verify its ability to identify AD and other types of dementia. RESULTS: Dataset 1 showed 22 upregulated and 21 downregulated mRNAs. A panel of six mRNAs distinguished AD from the control group in Dataset 2. The panel was used to successfully differentiate AD from other types of dementia in Dataset 3. CONCLUSIONS: An AD-specific panel of six mRNAs was created that can be used for AD diagnosis.

A novel aged mouse model of recurrent intracerebral hemorrhage in the bilateral striatum.

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

A Group of Long Non-coding RNAs in Blood Acts as a Specific Biomarker of Alzheimer's Disease.

Long non-coding RNAs (lncRNAs) have been identified to be involved in the pathogenesis of Alzheimer's disease (AD). In this study, we evaluated whether lncRNAs can be used to discriminate AD patients from controls and patients with other dementias, such as vascular, Parkinson's disease, behavioral variant frontotemporal, and dementia with Lewy body. In this study, we used three datasets to measure the blood lncRNA levels. A pilot study (dataset 1, n = 40; controls, 20; AD, 20) was used to screen for differentially expressed lncRNAs. Dataset 2 (n = 174; controls, 86; AD, 88) was used to identify a lncRNA panel for the diagnostic model. Dataset 3 (n = 333; control, 60; AD, 54; vascular dementia, 53; Parkinson's disease dementia, 55; behavioral variant frontotemporal dementia, 56; and dementia with Lewy body, 55) was used to validate the diagnostic model. In dataset 1, 12 upregulated and 15 downregulated lncRNAs were identified. In dataset 2, a panel of seven lncRNAs was found to have the ability to differentiate AD patients from controls. Finally, this panel was applied to dataset 3 to successfully distinguish AD from other dementias. This study proposes a panel of seven lncRNAs as specific and promising biomarker for AD diagnosis.

Proteomic profiling of circulating plasma exosomes reveals novel biomarkers of Alzheimer's disease.

BACKGROUND: Neuronal- and astrocyte-derived exosomes have been identified as an optimal source for screening biomarkers for Alzheimer's disease (AD). However, few studies focus on the bulk exosome population isolated from plasma of AD. This study investigated whether proteins in bulk exosomes can aid in the diagnosis of AD. METHODS: The plasma exosomes were collected by ultracentrifuge. Protein samples were extracted from exosomes. Cerebrospinal fluid levels of amyloid ß (Aß)42 and phosphorylated tau (P-tau)181 were measured for diagnostic purposes. A pilot study (controls, 20; AD, 20) followed by a second dataset (controls, 56; AD, 58) was used to establish a diagnostic model of AD. Mass spectrometry-based proteomics was performed to profile the plasma exosomal proteome. Parallel reaction monitoring was used to further confirm the differentially expressed proteins. RESULTS: In total, 328 proteins in plasma exosomes were quantified. Among them, 31 proteins were altered in AD patients, and 12 were validated. The receiver operating characteristic curve analysis revealed a combination of six proteins (upregulated: Ig-like domain-containing protein (A0A0G2JRQ6), complement C1q subcomponent subunit C (C1QC), complement component C9 (CO9), platelet glycoprotein Ib beta chain (GP1BB), Ras suppressor protein 1 (RSU1); downregulated: disintegrin and metalloproteinase domain 10 (ADA10)) has the capacity to differentiate AD patients from healthy controls with high accuracy. Linear correlation analysis showed that the combination was significantly correlated with cognitive performance. CONCLUSIONS: The combination of plasma exosomal proteins A0A0G2JRQ6, C1QC, CO9, GP1BB, RSU1, and ADA10 acts as a novel candidate biomarker to differentiate AD patients from healthy individuals.

A preliminary study of further attempt at the development, testing and application of an independent primary screening stool card.

Stool characteristics are of great value to assess diseases, but patients knew little. E-learning applied in health popularization and patient education is booming. In China, WeChat applets has advantages of abundant users, convenient access and low cost, which may be a great media in patient education on stool. This preliminary study aims to develop and evaluate a stool card WeChat applet. We collected stools images during 2020 to 2022 in the Department of Gastroenterology and Hepatology in the Second Affiliated Hospital of Harbin Medical University, constructed a stool card applet named the Doctor Friend Primary Screening Stool Card (DFPSSC) and evaluated it. Eligible participants were divided into the applet, traditional paper media and control group. We implement a series of tests to evaluate the effectiveness. 20 clinicians and participants using the DFPSSC completed a questionnaire to evaluate the usability. We developed the DFPSSC for an E-learning approach. Of 108 volunteers, 97 completed the DFPSSC learning. No significant pretest differences were found among the three groups (P = 0.303). Applet group had significantly higher posttest scores than pretest scores in intervention (P < 0.001, d = 1.68) and simulation (P = 0.006) test, and it had higher scores than other two group (P < 0.001). 63% participants and 59% clinicians strongly agree or agree to the usability of DFSSC. This preliminary study verified that the DFPSSC can effectively improve participants' knowledge of feces, making it an effective clinical tool for patient education and the avoidance of treatment delay.

Transplanted hair follicle mesenchymal stem cells alleviated small intestinal ischemia-reperfusion injury via intrinsic and paracrine mechanisms in a rat model.

Background: Small intestinal ischemia-reperfusion (IR) injury is a common intestinal disease with high morbidity and mortality. Mesenchymal stem cells (MSCs) have been increasingly used in various intestinal diseases. This study aimed to evaluate the therapeutic effect of hair follicle MSCs (HFMSCs) on small intestinal IR injury. Methods: We divided Sprague-Dawley rats into three groups: the sham group, IR group and IR + HFMSCs group. A small intestinal IR injury rat model was established by clamping of the superior mesenteric artery (SMA) for 30 min and reperfusion for 2 h. HFMSCs were cultured in vitro and injected into the rats through the tail vein. Seven days after treatment, the intrinsic homing and differentiation characteristics of the HFMSCs were observed by immunofluorescence and immunohistochemical staining, and the paracrine mechanism of HFMSCs was assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Results: A small intestinal IR injury model was successfully established. HFMSCs could home to damaged sites, express proliferating cell nuclear antigen (PCNA) and intestinal stem cell (ISC) markers, and promote small intestinal ISC marker expression. The expression levels of angiopoietin-1 (ANG1), vascular endothelial growth factor (VEGF) and insulin growth factor-1 (IGF1) in the IR + HFMSCs group were higher than those in the IR group. HFMSCs could prevent IR-induced apoptosis by increasing B-cell lymphoma-2 (Bcl-2) expression and decreasing Bcl-2 homologous antagonist/killer (Bax) expression. Oxidative stress level detection showed that the malondialdehyde (MDA) content was decreased, while the superoxide dismutase (SOD) content was increased in the IR + HFMSCs group compared to the IR group. An elevated diamine oxidase (DAO) level reflected the potential protective effect of HFMSCs on the intestinal mucosal barrier. Conclusion: HFMSCs are beneficial to alleviate small intestinal IR injury through intrinsic homing to the small intestine and by differentiating into ISCs, via a paracrine mechanism to promote angiogenesis, reduce apoptosis, regulate the oxidative stress response, and protect intestinal mucosal function potentially. Therefore, this study suggests that HFMSCs serve as a new option for the treatment of small intestinal IR injury.

Magnetic resonance imaging of endolymphatic hydrops in Ménière's disease: A comparison of the diagnostic value of multiple scoring methods.

Objectives: To compare three methods of scoring endolymphatic hydrops in patients with Ménière's disease in order to assess the correlation between endolymphatic hydrops and auditory characteristics. Methods: A retrospective study of 97 patients with unilateral definite Ménière's disease (DMD) who underwent contrast-enhanced three-dimensional fluid attenuated inversion recovery (3D FLAIR) MRI. Each patient was scored by the Inner Ear Structural Assignment Method (IESAM), the Saccule to utricle area ratio (SURI), and the Four Stage Vestibular Hydrops Grading (FSVH), according to their corresponding axial images. Cohen's Kappa and intra-class correlation coefficient were used for consistency testing, combined with binary logistic regression analysis, to compare the sensitivity and specificity of the three methods. The degree of hydrops in different stages of MD was compared. The correlation between endolymphatic hydrops in the inner ear sub-units and hearing thresholds was further analyzed. Results: The intra- and inter-reader reliability for the scoring of endolymphatic hydrops were excellent. The IESAM had a high diagnostic value for identifying definite Ménière's disease (sensitivity: 86.6%, specificity: 97.9%). The hearing thresholds were correlated with the degree of endolymphatic hydrops. Stages 3 and 4 were more significant for the severity of hydrops than stage 1. Within the subgroups of the Ménière's disease patients, compared with the non-hydrops group and the pure vestibular hydrops (V group), the cochlear combined vestibular hydrops group (CV group) had significantly higher auditory thresholds. The amplitude ratio of electrocochleogram was significantly higher in the affected ear than in the healthy ear. Conclusion: The IESAM is a more sensitive and specific diagnostic scoring method for the diagnosis of DMD. Diagnostic imaging may improve the detection of inner ear hydrops which is correlated with severity of hearing loss. A comprehensive evaluation of the inner ear sub-unit structures maybe necessary.

A circular RNA blood panel that differentiates Alzheimer's disease from other dementia types.

BACKGROUND: Circular RNAs (circRNAs) have been demonstrated to be associated with Alzheimer's disease (AD). Here, we conducted a study to explore whether circRNAs have the ability to differentiate AD from cognitively normal controls and other types of dementia, such as vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Three datasets were included in this study to measure blood circRNAs. The pilot study (Dataset 1, n = 40; controls, 20; AD, 20) was used to screen differentially expressed circRNAs. Dataset 2 (n = 124; controls, 61; AD, 63) was recruited for the establishment of the diagnostic model using a circRNA panel. Further, the Dataset 3 (n = 321; control, 58; AD, 60; VaD, 50; PDD, 51; bvFTD, 52; DLB, 50) was used to verify the diagnostic model. RESULTS: In Dataset 1, 22 upregulated and 19 downregulated circRNAs were revealed. In Dataset 2, a six-circRNA panel was found to be able to distinguish patients with AD from controls. Then this panel was applied to Dataset 3 and successfully differentiated AD from other types of dementia. CONCLUSION: This study suggested that a six-circRNA panel is AD-specific and a promising biomarker of AD.