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Baishouwu (Cynanchum Auriculalum Royle ex Wight), a traditional Chinese herbal medicine, is used as a traditional anti-aging remedy in China. Previous studies suggested Baishouwu has multiple pharmacological actions. In this study, the total glycosides extracted from Baishouwu (CA/TG) were evaluated for its potential anti-tumor activity and mechanism on several human breast and prostate cancer cell lines. In [3H] thymidine incorporation assay. CA/TG inhibited the proliferation of cancer cells in a dose-dependent fashion. It also displayed anti-androgen activity on androgen sensitive cell line assessed by reporter gene assay. The morphological examination of CA/TG treated cells revealed overall shrinkage of nucleus, chromatin condensation and small nuclear fragments by DAPI staining, the characteristic pattern of DNA ladders were observed in cells exposed to CA/TG, indicating the involvement of apoptosis in its action. These results suggested that the CA/TG has preferred cytotoxicity against the cancer cells, and the action was due to its ability of preventing cell proliferation and inducing apoptosis. [ABSTRACT FROM AUTHOR]

Background: The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is a novel lipid measure for assessing the risk of cardiovascular disease. Lipid metabolism disorders are reportedly associated with hearing impairment. This study aimed to investigate the potential association between NHHR and hearing., Methods: The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) cycles of 2005-2010 and 2017-2018, including 4,296 participants aged 6-19 years. The NHHR was calculated from lipid profiles, and hearing was assessed using pure-tone audiometry. Weighted multivariate logistic regression analyses were used to investigate the association between the NHHR and hearing loss. Subgroup and sensitivity analyses were performed to verify the robustness of the results., Results: Univariate analysis revealed significant associations between the NHHR and hearing threshold at all categorized frequency (low, speech, or high-frequency) (P < 0.001). Three models were used: an unadjusted model, a model adjusted for age, sex, and race, and a model further adjusted for PIR, BMI, and diabetes. Multiple regression analysis confirmed these associations consistently across all models. When considered as a continuous variable, NHHR had a significant association with enhanced hearing thresholds at all categorized frequencies: low-frequency (β:0.56, 95% CI: 0.36-0.75), speech-frequency (β:0.55, 95% CI: 0.36-0.7), and high-frequency (β:0.55, 95% CI: 0.36-0.74). The adjusted models showed persistent positive correlations after controlling for covariates. The NHHR was consistently positively associated with hearing loss. The NHHR and auditory thresholds showed a general dose-response association across all frequencies., Conclusions: NHHR is a promising biomarker for predicting adolescent hearing threshold shifts and hearing loss. The study highlights the importance of early lipid monitoring and management as strategies to prevent or reduce hearing impairment., (© 2024. The Author(s).)

Objectives: The diagnosis of tuberculosis otitis media (TBOM) remains a great challenge. This study aims to suggest potential diagnostic clues and proper management of TBOM., Methods: The study is a retrospective review of TBOM cases that were treated at our department, between January 2015 and June 2023. Summarizing their clinical characteristics, diagnosis, and treatment. Additionally, a literature review is conducted., Results: Eight cases of TBOM, 6 female and 2 male patients, median age was 32 years old, were included in the study. TBOM mainly presents with symptoms of otorrhea, hearing loss, and occasional early-onset facial palsy. One case had a positive Purified Protein Derivative (PPD) before the operation. Middle ear tissue was pathologically biopsied in 7 cases, with 3 cases testing positive for Acid Fast Bacillus and 6 cases testing positive for Mycobacterium tuberculosis PCR. Middle ear surgery and Anti-tubercular treatment (ATT) were completed in all cases. The median follow-up was 11 months. No cases of TB relapse were observed., Conclusions: Proper suspicion and confirmation of TBOM is the primary clinical orientation. Middle ear surgery combination with ATT results in satisfactory outcomes. Hearing reconstruction should be performed after ATT is completed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To summarize the clinical features and postoperative efficacy of patients with oval window atresia accompanied by facial nerve aberration. Methods: The clinical data of patients with congenital middle ear malformation with facial nerve aberration admitted to our hospital from January 2015 to March 2023 were retrospectively analyzed. There were 97 cases (133 ears) in total. Among them, 39 patients (44 ears) had complete follow-up data, including 27 male patients and 12 females, aged 7-48 years old, with an average age of 17.8 years old. Of these, 14 cases (16 ears) were patients combined with facial nerve aberration, and 25 cases (28 ears) were without facial nerve aberration. The results of imaging examination, pure-tone audiometry, selection of surgical strategy, intraoperative findings and postoperative hearing improvement were summarized and analyzed. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Prism 9 software was used to statistically analyze the mean bone conductance and air-bone gap of patients before and after surgery. Results: All the 14 patients (16 ears) with middle ear malformation accompanied by facial nerve aberration and oval window atresia showed poor hearing and no facial palsy since childhood. High resolution CT (HRCT) examination of temporal bone, pure tone audiometry and Gelle test were performed before surgery. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Preoperative high-resolution CT (HRCT) examination of temporal bone found 12 ears with 4 or more deformities, accounting for 75.00%, in the group of patients with facial nerve malformation. The preoperative average bone conductive threshold was (15.3±10.4) dB and the average air-bone gap was (46.3±10.6) dB in pure-tone audiometry (0.5, 1, 2, 4kHz). According to the different degrees of facial nerve and ossicle malformation, we performed three different hearing reconstruction strategies for the 14 patients (16 ears) with facial nerve aberration and oval window atresia, including 7 ears of incus bypass artificial stape implantation, 7 ears of Malleostapedotomy (MS) and 2 ears of Malleus-cochlear-prothesis (MCP). After 3 months to 18 months of follow-up, all patients showed no facial paralysis. The postoperative mean bone conductive threshold was (15.7±7.9) dB and air-bone gap was (19.8±8.5) dB. There were significant differences in mean air-bone gap before and after operation ( t =7.766, P <0.05), and there was no significant difference between the mean bone conductive threshold before and after surgery ( t =0.225, P =0.824). There was no significant difference of mean reduction of air-bone gap between patients with and without facial nerve aberration ( t =1.412, P =0.165). There was no significant difference between the three hearing reconstruction strategies. There was no significant displacement of the Piston examined by U-HRCT. Conclusion: For patients of middle ear malformation whose facial nerve cover the oval window partially, incus bypass artificial stape implantation or Malleostapedotomy (MS) can be selected according to the specific condition of auditory ossis malformation, and for patients whose facial nerve completely covers the oval window area, Malleus-cochlear-prothesis (MCP) can be selected. Three types of stapes surgery are safe and reliable for patients with oval window atresia accompanied by facial nerve aberration. There was no significant difference in efficacy between them. Preoperative HRCT assessment of middle ear malformation is effective. There is no significant difference of surgical effect with or without facial nerve aberration. The U-HRCT can be used to evaluate the middle ear malformation before surgery and the Piston implantation status after surgery. Due to the risks of surgery, those who do not want to undergo surgery can choose artificial hearing AIDS, such as hearing aid, vibrating soundbridge, bone bridge or bone-anchored hearing aid.

Objective: To investigate the hemodynamic characteristics of transverse sinus with sigmoid sinus wall dehiscence (SSWD) of pulsatile tinnitus (PT) based on 4D flow MRI. Methods: Retrospective analysis was performed on all patients admitted to Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2021 for dehiscent sigmoid plate pulsatile tinnitus. A total of 26 patients (sides) who met the criteria and underwent 4D flow MRI were included. A total of 26 subjects (46 sides), matched 1∶1 according to gender and age, were included in the normal healthy control group. Nonparametric rank sum test, Student's t test, and ANOVA were performed by SPSS 19.0 software. Binary Logistic regression was applied to the data with statistical significance. Results: There were more patients with dominant drainage on the affected side in PT group than in control group (73.1% vs . 42.3%). The incidence of transverse with a focal intraluminal filling defect and tapered stenosis was higher than that in control group (21.7% vs . 69.2%; 17.4% vs . 42.3%). Average through-plane velocity and maximum through-plane velocity in PT group were higher than those in control group [(33.75±13.88) cm/s vs . (15.84±7.21) cm/s; (93.19±33.55) cm/s vs . (40.40±14.40) cm/s]. The middle part and proximal end of Flow avg (ml/s) in PT group were larger than those in control group [4.69 (2.87; 5.62) ml/s vs . 2.76 (1.67; 4.99) ml/s; 3.41 (2.16; 5.47) ml/s vs . 2.67 (1.68; 4.41) ml/s]. In control group, the velocity of transverse sinus changed relatively gently, while in PT group, the velocity of proximal sinus increased significantly. Binary Logistic regression showed that SSWD PT was independently correlated with proximal maximum flow velocity [ OR =1.086(1.029-1.146), P =0.003]. Conclusion: 4D flow MRI showed that the dominant drainage and higher velocity at the proximal end of the transverse sinus might be an important hemodynamic characteristics of dehiscent sigmoid plate pulsatile tinnitus.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Motivated by the novel phenomena observed in the layered material SrCu&#95;{2}(BO&#95;{3})&#95;{2}, the Shastry-Sutherland model (SSM) has been extensively studied as the minimal model for SrCu&#95;{2}(BO&#95;{3})&#95;{2}. However, the nature of its quantum phase transition from the plaquette valence-bond solid to antiferromagnetic phase is under fierce debate, posing a challenge to understand the underlying quantum criticality. Via the state-of-the-art tensor network simulations, we study the ground state of the SSM on large-scale size up to 20×20 sites. We identify the continuous transition nature accompanied by an emergent O(4) symmetry between the plaquette valence-bond solid and antiferromagnetic phase, which strongly suggests a deconfined quantum critical point (DQCP). Furthermore, we map out the phase diagram of an extended SSM that can be continuously tuned to the SSM, which demonstrates the same DQCP phenomena along a whole critical line. Our results indicate a compelling scenario for understanding the origin of the proposed proximate DQCP in recent experiments of SrCu&#95;{2}(BO&#95;{3})&#95;{2}.

Objective: To investigate the disease composition, clinical features, diagnosis, and treatment characteristics of vertigo in children. Methods: A total of 120 children with vertigo diagnosed and treated in the Department of Otorhinolaryngology, Children's Hospital, Capital Institute of Pediatrics in Beijing from February 2018 to February 2022 were retrospectively analyzed to explore the clinical characteristics of common peripheral vertigo in children and to summarize the experience of diagnosis and treatment. Results: The etiological composition of 120 cases of vertigo in children are as follows: 63 (52.5%) cases of vestibular migraine of childhood (VMC), 19 (15.8%) of recurrent vertigo of childhood (RVC), 11 (9.2%) of probable vestibular migraine of childhood (PVMC), 10 (8.3%) of secretory otitis media (SOM), 6 (5.0%) of persistent postural-perceptual dizziness (PPPD), 4 (3.3%) of benign paroxysmal positional vertigo (BPPV), 2 (1.7%) of vestibular neuritis (VN), 2 (1.7%) of Meniere's disease (MD), 2 (1.7%) of inner ear malformation (IEM), and 1 (0.8%) of vestibular paroxysmal syndrome (VP).The major cause of vertigo in children of different ages was different. SOM was the most important cause in preschool children, followed by RVC and VMC; VMC was the most important cause in school-age children, followed by RVC; and MD and BPPV were exclusive found in adolescents. The incidence rate of PPPD was higher in adolescents than in preschool and school-age children. Children with vertigo had good prognosis in general. Conclusions: VMC, RVC and SOM are the most common causes in vertigo in children, and their proportion was different in different aged children. Transforming abstract feelings into specific information is the skill required for collecting medical history of children with vertigo. Considering the age and cooperation of children, appropriate hearing and vestibular examination techniques are recommended. We should pay more attention to the mental health of children with vertigo and their parents.

Many BF 2 complexes of heteroaromatics are well known for their dual-state emission (DSE) properties. However, AIE and ACQ effects have also been observed in certain cases. To date, no rational explanations have been proposed for these uncommon photoluminescence (PL) behaviours. The current research prepared four BF 2 complexes of N -benzoyl 2-aminobenzothiazoles with diversified photoluminescence (PL) properties as model compounds and utilized quantum chemical calculation tools to address this issue. Theoretical calculations revealed that the electron-donating groups (EDGs) at the para -position of the exocyclic phenyl ring exert significant influence on their ground-state electronic structures and vertical excitation features. Potential energy curve (PEC) analysis showed that the exocyclic phenyl ring and NMe 2 could not function as effective rotors due to elevated energy barriers. Only the NPh 2 of BFBB-3 could spontaneously rotate ∼60° to induce the formation of an emissive twisted intramolecular charge transfer (TICT) state. The two-channel model involving both vibronic relaxation and S 0 /S 1 surface crossing revealed that the drastic narrowing of the S 1 /S 0 energy gap in the region approaching minimun energy conical intersection (MECI) led to the generation of a dark state in BFBB-1. The small energy barrier to access the dark-state region makes the resulting fast internal conversion a competitive channel for excited-state deactivation. In contrast, the presence of EDGs in BFBB-2 and 4 inhibits this pathway, thereby resulting in intense fluorescence emissions in solution. In addition, crystallographic analysis illustrated that the F atoms perpendicular to the polyheterocycle promoted a slipped face-to-face packing mode and enhanced intermolecular interactions. The efficiencies of their solid-state emissions are mainly affected by the degree of π-π overlaps.

As the most senstitive plant organs to environmental changes, leaves serve as crucial indicators of plant survival strategies. We measured the morphology, anatomical traits, gas exchange parameters, and chlorophyll fluorescence parameters of Quercus aquifolioides (evergreen broad-leaved) and Sorbus rehderiana (deciduous broad-leaved) at altitudes of 2600, 2800, 3000, 3200 and 3400 m on the eastern edge of the Qinghai-Tibet Plateau, China. We explored the similarity and difference in their responses to altitude change and the ecological adaptation strategy. The results showed that as the altitude increased, leaf dry matter content of Q. aquifolioides decreased, that of S. rehderiana increased, leaf size for both species gradually decreased, and the palisade coefficient of Q. aquifolioides showed a decreasing trend, contrasting with the increasing trend in S. rehderiana . As the altitude increased, the thickness of leaves, palisade tissue, spongy tissue, upper epidermis, and lower epidermis of both species increased significantly, with the increment of 22.4%, 4.9%, 45.1%, 23.3%, 19.6%, and 28.2%, 46.9%, 8.9%, 25.9%, 20.8% at altitude of 3400 m, respectively, compared with the altitude of 2600 m. The gas exchange and chlorophyll fluorescence parameters of S. rehderiana significantly increased with increasing altitude, while Q. aquifolioides showed the opposite trend. Leaf anatomical traits, gas exchange, and chlorophyll fluorescence parameters of both species displayed considerable plasticity. There were significant correlations among most leaf traits and between leaf traits and altitude. The survival strategy of Q. aquifolioides was more conservative in response to altitude changes, while that of S. rehderiana was more active. Both species adapted to different altitudes by adjusting their own traits.

Frustrated spin systems have traditionally proven challenging to understand, owing to a scarcity of controlled methods for their analyses. By contrast, under strong magnetic fields, certain aspects of spin systems admit simpler and universal description in terms of hardcore bosons. The bosonic formalism is anchored by the phenomenon of Bose-Einstein condensation (BEC), which has helped explain the behaviors of a wide range of magnetic compounds under applied magnetic fields. Here, we focus on the interplay between frustration and externally applied magnetic field to identify instances where the BEC paradigm is no longer applicable. As a representative example, we consider the antiferromagnetic J&#95;{1}-J&#95;{2}-J&#95;{3} model on the square lattice in the presence of a uniform external magnetic field, and demonstrate that the frustration-driven suppression of the Néel order leads to a Lifshitz transition for the hardcore bosons. In the vicinity of the Lifshitz point, the physics becomes unmoored from the BEC paradigm, and the behavior of the system, both at and below the saturation field, is controlled by a Lifshitz multicritical point. We obtain the resultant universal scaling behaviors, and provide strong evidence for the existence of a frustration and magnetic-field driven correlated bosonic liquid state along the entire phase boundary separating the Néel phase from other magnetically ordered states.

The square-lattice Hubbard and closely related t-J models are considered as basic paradigms for understanding strong correlation effects and unconventional superconductivity (SC). Recent large-scale density matrix renormalization group simulations on the extended t-J model have identified d-wave SC on the electron-doped side (with the next-nearest-neighbor hopping t&#95;{2}>0) but a dominant charge density wave (CDW) order on the hole-doped side (t&#95;{2}<0), which is inconsistent with the SC of hole-doped cuprate compounds. We re-examine the ground-state phase diagram of the extended t-J model by employing the state-of-the-art density matrix renormalization group calculations with much enhanced bond dimensions, allowing more accurate determination of the ground state. On six-leg cylinders, while different CDW phases are identified on the hole-doped side for the doping range δ=1/16-1/8, a SC phase emerges at a lower doping regime, with algebraically decaying pairing correlations and d-wave symmetry. On the wider eight-leg systems, the d-wave SC also emerges on the hole-doped side at the optimal 1/8 doping, demonstrating the winning of SC over CDW by increasing the system width. Our results not only suggest a new path to SC in general t-J model through weakening the competing charge orders, but also provide a unified understanding on the SC of both hole- and electron-doped cuprate superconductors.

The emergence of exotic quantum phenomena in frustrated magnets is rapidly driving the development of quantum many-body physics, raising fundamental questions on the nature of quantum phase transitions. Here we unveil the behaviour of emergent symmetry involving two extraordinarily representative phenomena, i.e., the deconfined quantum critical point (DQCP) and the quantum spin liquid (QSL) state. Via large-scale tensor network simulations, we study a spatially anisotropic spin-1/2 square-lattice frustrated antiferromagnetic (AFM) model, namely the J 1x -J 1y -J 2 model, which contains anisotropic nearest-neighbor couplings J 1x ,J 1y and the next nearest neighbor coupling J 2 . For small J 1y /J 1x , by tuning J 2 , a direct continuous transition between the AFM and valence bond solid phase is observed. With growing J 1y /J 1x , a gapless QSL phase gradually emerges between the AFM and VBS phases. We observe an emergent O(4) symmetry along the AFM-VBS transition line, which is consistent with the prediction of DQCP theory. Most surprisingly, we find that such an emergent O(4) symmetry holds for the whole QSL-VBS transition line as well. These findings reveal the intrinsic relationship between the QSL and DQCP from categorical symmetry point of view, and strongly constrain the quantum field theory description of the QSL phase. The phase diagram and critical exponents presented in this paper are of direct relevance to future experiments on frustrated magnets and cold atom systems., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Evidence suggests that damage to the ribbon synapses (RS) may be the main cause of auditory dysfunction in noise-induced hearing loss (NIHL). Oxidative stress is implicated in the pathophysiology of synaptic damage. However, the relationship between oxidative stress and RS damage in NIHL remains unclear. To investigate the hypothesis that noise-induced oxidative stress is a key factor in synaptic damage within the inner ear, we conducted a study using mice subjected to single or repeated noise exposure (NE). We assessed auditory function using auditory brainstem response (ABR) test and examined cochlear morphology by immunofluorescence staining. The results showed that mice that experienced a single NE exhibited a threshold shift and recovered within two weeks. The ABR wave I latencies were prolonged, and the amplitudes decreased, suggesting RS dysfunction. These changes were also demonstrated by the loss of RS as evidenced by immunofluorescence staining. However, we observed threshold shifts that did not return to baseline levels following secondary NE. Additionally, ABR wave I latencies and amplitudes exhibited notable changes. Immunofluorescence staining indicated not only severe damage to RS but also loss of outer hair cells. We also noted decreased T-AOC, ATP, and mitochondrial membrane potential levels, alongside increased hydrogen peroxide concentrations post-NE. Furthermore, the expression levels of 4-HNE and 8-OHdG in the cochlea were notably elevated. Collectively, our findings suggest that the production of reactive oxygen species leads to oxidative damage in the cochlea. This mitochondrial dysfunction consequently contributes to the loss of RS, precipitating an early onset of NIHL., Competing Interests: None., (AJTR Copyright © 2024.)

Synthesis-oriented design led us to the discovery of a series of novel cyanine-borondifluoride curcuminoid hybrids called Nanchang Red (NCR) dyes that overcome the intrinsic low synthetic yields of symmetrical cyanine-difluoroboronate (BF 2 )-hybridized NIR dyes. The hybridization endows NCR dyes with high molar extinction coefficients, efficient red-to-NIR emission, and enlarged Stokes shifts. Quantum chemical calculations revealed that the asymmetrical layout of the three key electron-withdrawing and electron-donating fragments results in a special pattern of partial charge separation and inconsistent degrees of charge delocalization on their π-conjugated backbones. While the nature of the hemicyanine fragment exerts significant influence on the excitation modes of NCR dyes, the borondifluoride hemicurcuminoid fragment is the major contributor to the enlarged Stokes shifts. Cell imaging experiments illustrated that a subtle change in the N-heterocycle of the hemicyanine fragment has a remarkable effect on the subcellular localization of NCR dyes. Unlike other previously reported cyanine-BF 2 hybridized dyes, which mainly target mitochondria, the benzothiazole and indole-based NCR dyes accumulate in both the endoplasmic reticulum (ER) and lipid droplets of HeLa cells, whereas the benzoxazole and quinoline-based NCR dyes stain the ER specifically., (© 2023 Wiley-VCH GmbH.)

The topological superconducting state is a highly sought-after quantum state hosting topological order and Majorana excitations. In this Letter, we explore the mechanism to realize the topological superconductivity (TSC) in the doped Mott insulators with time-reversal symmetry (TRS). Through large-scale density matrix renormalization group study of an extended triangular-lattice t-J model on the six- and eight-leg cylinders, we identify a d+id-wave chiral TSC with spontaneous TRS breaking, which is characterized by a Chern number C=2 and quasi-long-range superconducting order. We map out the quantum phase diagram with by tuning the next-nearest-neighbor (NNN) electron hopping and spin interaction. In the weaker NNN-coupling regime, we identify a pseudogaplike phase with a charge stripe order coexisting with fluctuating superconductivity, which can be tuned into d-wave superconductivity by increasing the doping level and system width. The TSC emerges in the intermediate-coupling regime, which has a transition to a d-wave superconducting phase with larger NNN couplings. The emergence of the TSC is driven by geometrical frustrations and hole dynamics which suppress spin correlation and charge order, leading to a topological quantum phase transition.

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

In the past decade, selenocyclization has been extensively exploited for the preparation of a wide range of selenylated heterocycles with versatile activities. Previously, selenium electrophile-based and FeCl 3 -promoted methods were employed for the synthesis of selenylated benzoxazines. However, these methods are limited by starting material availability and low atomic economy, respectively. Inspired by the recent catalytic selenocyclization approaches based on distinctive pathways, we rationally constructed an efficient and greener double-redox catalytic system for the access to diverse selenylated benzoxazines. The coupling of I 2 /I - and Fe 3+ /Fe 2+ catalytic redox cycles enables aerial O 2 to act as the driving force to promote the selenocyclization. Control and test redox experiments confirmed the roles of each component in the catalytic system, and a PhSeI-based pathway is proposed for the selenocyclization process.

Adeno-associated virus (AAV)-mediated gene transfer is an efficient method of gene over-expression in the vestibular end organs. However, AAV has limited usefulness for delivering a large gene, or multiple genes, due to its small packaging capacity (< 5 kb). Co-transduction of dual-AAV vectors can be used to increase the packaging capacity for gene delivery to various organs and tissues. However, its usefulness has not been well validated in the vestibular sensory epithelium. In the present study, we characterized the co-transduction of dual-AAV vectors in mouse utricles following inoculation of two AAV-serotype inner ear (AAV-ie) vectors via canalostomy. Firstly, co-transduction efficiencies were compared between dual-AAV-ie vectors using two different promoters: cytomegalovirus (CMV) and CMV early enhancer/chicken β-actin (CAG). In the group of dual AAV-ie-CAG vectors, the co-transduction rates for striolar hair cells (HCs), extrastriolar HCs, striolar supporting cells (SCs), and extrastriolar SCs were 23.14 ± 2.25%, 27.05 ± 2.10%, 57.65 ± 7.21%, and 60.33 ± 5.69%, respectively. The co-transduction rates in the group of dual AAV-ie-CMV vectors were comparable to those in the dual AAV-ie-CAG group. Next, we examined the co-transduction of dual-AAV-ie-CAG vectors in the utricles of neonatal mice and damaged adult mice. In the neonatal mice, co-transduction rates were 52.88 ± 3.11% and 44.93 ± 2.06% in the striolar and extrastriolar HCs, respectively, which were significantly higher than those in adult mice. In the Pou4f3 +/DTR mice, following diphtheria toxin administration, which eliminated most HCs and spared the SCs, the co-transduction rate of SCs was not significantly different to that of normal utricles. Transgene expression persisted for up to 3 months in the adult mice. Furthermore, sequential administration of two AAV-ie-CAG vectors at an interval of 1 week resulted in a higher co-transduction rate in HCs than concurrent delivery. The auditory brainstem responses and swim tests did not reveal any disruption of auditory or vestibular function after co-transduction with dual-AAV-ie vectors. In conclusion, dual-AAV-ie vectors allow efficient co-transduction in the vestibular sensory epithelium and facilitate the delivery of large or multiple genes for vestibular gene therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Guo, He, Liu, Xu, Yang, Su, Liu, Gong and Wang.)

Ischemic stroke causes brain inflammation and multi-organ injury, which is closely associated with the peroxisome proliferator-activated receptor-gamma (PPARγ) signaling pathway. Recent studies have indicated that ginsenoside Rb1 (GRb1) can protect the integrity of the blood-brain barrier after stroke. In the current study, a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established to determine whether GRb1 can ameliorate brain/lung/intestinal barrier damage via the PPARγ signaling pathway. Staining (2,3,5-triphenyltetrazolium chloride, hematoxylin, and eosin) and Doppler ultrasonography were employed to detect pathological changes. Endothelial breakdown was investigated with the leakage of Evans Blue dye and the expression of TJs (tight junctions) and AJs (adherent junctions). Western blot and immunofluorescence were used to determine the levels of cell junction proteins, PPARγ and NF-κB. Results showed that GRb1 significantly mitigated multi-organ injury and increased the expression of cerebral microvascular, pulmonary vascular, and intestinal epithelial connexins. In brain, lung, and intestinal tissues, GRb1 activated PPARγ, decreased the levels of phospho-NF-κB p65, and inhibited the production of proinflammatory cytokines, thereby maintaining barrier permeability. However, co-treatment with GRb1 and the PPARγ antagonist GW9662 reversed the barrier-protective effect of GRb1. These findings indicated that GRb1 can improve stroke-induced brain/lung/intestinal barrier damagevia the PPARγ pathway., (Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The nature of the zero-temperature phase diagram of the spin-1/2J 1 -J 2 Heisenberg model on a square lattice has been debated in the past three decades, and it remains one of the fundamental problems unsettled in the study of quantum many-body theory. By using the state-of-the-art tensor network method, specifically, the finite projected entangled pair state (PEPS) algorithm, to simulate the global phase diagram of the J 1 -J 2 Heisenberg model up to 24×24 sites, we provide very solid evidences to show that the nature of the intermediate nonmagnetic phase is a gapless quantum spin liquid (QSL), whose spin-spin and dimer-dimer correlations both decay with a power law behavior. There also exists a valence-bond solid (VBS) phase in a very narrow region 0.56≲J 2 /J 1 ≤0.61 before the system enters the well known collinear antiferromagnetic phase. We stress that we make the first detailed comparison between the results of PEPS and the well-established density matrix renormalization group (DMRG) method through one-to-one direct benchmark for small system sizes, and thus give rise to a very solid PEPS calculation beyond DMRG. Our numerical evidences explicitly demonstrate the huge power of PEPS for highly frustrated spin systems. Finally, an effective field theory is also proposed to understand the physical nature of the discovered gapless QSL and its relation to deconfined quantum critical point (DQCP)., (Copyright © 2022 Science China Press. Published by Elsevier B.V. All rights reserved.)

Lysosomes contribute to cellular homeostasis via processes including macromolecule degradation, nutrient sensing, and autophagy. Defective proteins related to lysosomal macromolecule catabolism are known to cause a range of lysosomal storage diseases; however, it is unclear whether mutations in proteins involved in homeostatic nutrient sensing mechanisms cause syndromic sensory disease. Here, we show that SLC7A14, a transporter protein mediating lysosomal uptake of cationic amino acids, is evolutionarily conserved in vertebrate mechanosensory hair cells and highly expressed in lysosomes of mammalian cochlear inner hair cells (IHCs) and retinal photoreceptors. Autosomal recessive mutation of SLC7A14 caused loss of IHCs and photoreceptors, leading to presynaptic auditory neuropathy and retinitis pigmentosa in mice and humans. Loss-of-function mutation altered protein trafficking and increased basal autophagy, leading to progressive cell degeneration. This study implicates autophagy-lysosomal dysfunction in syndromic hearing and vision loss in mice and humans.

Edaravone (EDA) injection has been extensively applied in clinics for treating stroke. Nevertheless, the metabolite signatures and underlying mechanisms associated with EDA remain unclear, which deserve further elucidation for improving the accurate usage of EDA. Ischemia stroke was simulated by intraluminal occlusion of the right middle cerebral artery for 1 h, followed by reperfusion for 24 h in mice. Brain infarct size, neurological deficits, and lactate dehydrogenase (LDH) levels were improved by EDA. Significantly differential metabolites were screened with untargeted metabolomics by cross-comparisons with pre- and posttreatment of EDA under cerebral ischemia/reperfusion (I/R) injury. The possibly involved pathways, such as valine, leucine, and isoleucine biosynthesis, and phenylalanine, taurine, and hypotaurine metabolisms, were enriched with differential metabolites and relevant regulatory enzymes, respectively. The network of differential metabolites was constructed for the integral exhibition of metabolic characteristics. Targeted analysis of taurine, an important metabolic marker, was performed for further validation. The level of taurine decreased in the MCAO/R group and increased in the EDA group. The inhibition of EDA on cerebral endothelial cell apoptosis was confirmed by TdT-mediated dUTP nick-end labeling (TUNEL) stain. Cysteine sulfinic acid decarboxylase (CSAD), the rate-limiting enzyme of taurine generation, significantly increased along with inhibiting endothelial cell apoptosis after treatment of EDA. Thus, CSAD, as the possible new therapeutic target of EDA, was selected and validated by Western blot and immunofluorescence. Together, this study provided the metabolite signatures and identified CSAD as an unrecognized therapeutic intervention for EDA in the treatment of ischemic stroke via inhibiting brain endothelial cell apoptosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ma, Zheng, Su, Zhang, Liu, Li, Zhang, Gong and Kou.)

Objective: To evaluate the imaging features of otosclerosis based on10 μm otology CT. Methods: Data of 27 patients with otosclerosis (51 sides) in Beijing Friendship Hospital, Capital Medical University from October 2020 to July 2021 were retrospectively collected, including 9 males and 18 females age ffrom 22 to 70 (42±12) years. All patients underwent 10 μm otology CT examination and surgical treatment. The types, amounts and involved sites of otosclerosis were analyzed and the sensitivity of 10 μm otology CT in diagnosing otosclerosis were evaluated. Results: Fenestral type accounted for 49.0% (25/51 sides), and diffuse type accounted for 51.0% (26/51 sides),and he retrofenestral type without fenestral lesion was not seen. Single lesions accounted for 45.1% (23/51 sides) and multiple lesions accounted for 54.9% (28/51 sides). The incidence of involvement of the fissula ante fenestram and annular ligaments were both 100%. The incidence of involvement of stapes footplate, vestibule, cochlea, round window, inner auditory canal wall, facial nerve canal, stapes muscle and semicircular canal was 60.8% (31 sides), 33.3% (17/51 sides), 21.6% (11/51 sides), 17.6% (9/51 sides), 13.7% (7/51 sides), 9.8% (5/51 sides), 7.8% (4/51 sides) and 5.9% (3/51 sides), respectively. The sensitivity of 10 μm otology CT in diagnosis of otosclerosis was 100%. Conclusion: 10 μm otology CT can fully display the imaging features of otosclerosis, and has the potential to be an effective routine method for otosclerosis.

Objective: To analysis the anatomical features of normal vestibular nerve canal based on 10 μm otology CT. Methods: Sixty-seven patients (103 ears) underwent 10 μm otology CT examinations in Department of Radiology, Beijing Friendship Hospital, Capital Medical University from September 2020 to March 2021 were retrospectively recruited. There were 24 males and 43 females, aged from 18 to 70 (40±17) years. According to the morphology of the inferior vestibular nerve canal, it can be divided into four types as follows: uniform straight type, curved type, ampullary type and direct connection. The anatomical variables of the superior vestibular nerve canal (external orifice, isthmus and internal orifice widths, canal length, angle with labyrinthine segment of the facial nerve) and inferior vestibular nerve canal (widths of the externaland internal orifice, canal length, angles with long axis of the vestibule and the modiolus) between the different sides, genders and canal morphologies were analyzed and compared, respectively. Results: 100% superior vestibular nerve canals and 75.7% (78/103) inferior vestibular nerve canals are clearly depicted by otology CT. The left-side ear presented with larger internal orifice diameter of the superior vestibular neve canal [(1.46±0.47) mm vs (1.31±0.41) mm], and a smaller angle between the inferior vestibular neve canal and the modiolus [(41.6±16.9)° vs (51.6±21.0)°] than the right-side ear (all P <0.05, respectively), respectively. Compared to females, males demonstrated larger internal orifice of the superior vestibular nerve canal [(1.55±0.37) mm vs (1.28±0.36) mm, P <0.05]. The uniform straight type of the inferior vestibular nerve canal was the most common type (62.1%, 64/103), followed by the direct connection (19.4%, 20/103), and the ampullary type was the least common type (4.9%, 5/103). There were significant differences in external diameter and angles with the long axis of the vestibule and the modiolus between the four morphologies of the superior vestibular nerve canal (all P <0.05, respectively). Conclusion: Ten μm otology CT is capable of depicting normal vestibular nerve canal clearly. Quantitative measurement of the normal vestibular nerve canal can provide references for the imaging diagnosis and preoperative evaluation of lesions in this area.

Objective: To evaluate the application of 10 μm otology CT on evaluation of isolated malleus fixation (IMF) in patients with conductive hearing loss. Methods: A total of 19 patients (25 sides) with idiopathic hearing loss, including 8 males and 11 females, aged between 4 to 50 years, who underwent 10 μm otology CT examination in Department of Radiology, Beijing Friendship Hospital, Capital Medical University from October 2020 to July 2021, were retrospectively collected. For those patients with idiopathic hearing loss, there were 5 cases (6 sides), including 2 males and 3 females, with an average age of 18-70 [65(20,68)] years, with bony connection between malleus and tympanum wall. Eighteen sex-and age-matched cases with normal hearing group, including 6 males and 12 females, with an average age of 20-68 (39±14) years, as the ratio of 1∶3, were included as the controls. The distances of the tegmen tympani between malleus head and horizontal semicircular canal, as well the distances between malleus head and horizontal semicircular canal were retrospectively measured and further compared between the two groups. Results: The incidence of IMF in patients with idiopathic conductive hearing loss without other etiologies was 24.0% (6/25). The specificity of 10 μm otology CT in diagnosing IMF was 100%. The distances of tegmen tympani between horizontal semicircular canal and malleus head in IMF patients were significantly smaller compared with the controls [-0.65(-1.21, -0.35) mm vs 1.34(0.04, 1.68) mm;0.92(0.51, 1.49) mm vs 2.82(1.76, 3.53) mm](both P <0.05, respectively). There was no significant difference in distances between malleus head and horizontal semicircular canal [-1.30 (-1.90, -0.46)mm vs -0.42 (-1.15, 0.05), P =0.057]. Conclusions: IMF is not uncommon in conductive hearing loss without other causes, which can be clearly shown by 10 μm otology CT. Its occurrence is related to the local downward shift of tegmen tympani above the malleus, without upwards displacement of the malleus.

Objective: To assess the changes of the spatial location of the malleus in patients with chronic otitis media (COM) using 10 μm otology CT. Methods: Forty-five patients with COM (COM group, 45 ears) and 55 patients without external and middle ear disease (control group, 89 ears), who underwent 10 μm otology CT examination in Department of Radiology, Beijing Friendship Hospital, Capital Medical University from October 2020 to March 2021, were retrospectively collected during the same period. In the COM group, there are 20 males and 25 females, aged from 20 to 78 (40±14) years. In the control group, 29 were males and 26 were females, with age of 19 to 57 (32±11) years. The shortest distance between the malleus head and the upper wall, the distance between the outer edge of the malleus neck and the scutum, the distance between the outer edge of the malleus neck and the pars flaccida of the tympanic membrane, the shortest distance between the malleus head and the anterior wall, the shortest distance between the anterior process and the anterolateral wall, the shortest distance between the tip of the malleus handle and the promontory, and the shortest distance between the malleus head and the tympanic segment of the facial nerve were measured and compared between the two groups. Results: Compared with the control group, the head-upper wall distance ( M ( Q 1 , Q 3 )) (0.81 (0.48, 1.21) mm vs 0.57 (0.33, 0.90) mm) and the neck-scutum distance (1.79 (1.54, 2.13) mm vs 1.65 (1.48, 1.83) mm) were larger in the COM group (all P <0.05), and the neck-tympanic membrane distance (1.32 (1.15, 1.49) mm vs 1.45 (1.31, 1.59) mm) and the handle-promontory distance (1.56 (1.33, 2.09) mm vs 2.10 (1.74, 2.43) mm) were reduced in the COM group (all P <0.05, respectively). The neck-tympanic membrane distance on the left was larger than those on the right in the COM group (1.39 (1.19, 1.51) mm vs 1.21 (0.87, 1.31) mm, P <0.05). Conclusion: There are changes in the relative position of the malleus in patients with COM, which are helpful for further understanding the imaging manifestations in patients with COM.

Objective: To evaluate the morphology of isthmus of the vestibular aqueduct (VA) and its relationship with the occurrence, course of Meniere's disease (MD) and the degree of hearing loss based on 10 μm otology CT. Methods: A total of 13 patients with MD in Beijing Friendship Hospital, Capital Medical University from October 2020 to July 2021, including 4 males and 9 females, age from 16 to 77 (56±16) years, were prospectively enrolled. All patients underwent 10 μm otology CT examination. The included lesion side was the MD affected group (14 sides), and the non-lesion side was the MD healthy group (12 sides). According to the 1∶2 side, 16 sex-and side matched cases (28 sides) without external and middle ear disease were included in the control group, including 4 males and 12 females, age from 16 to 77 (56±14) years. The horizontal semicircular canal showed on the largest plane was considered as the standard cross-section, and continuous observation was made on this image. According to the display type of isthmus of the VA, it was divided into Ⅰ to Ⅳ grades. Kruskal Wallis test was used to compare the morphological differences of VA isthmus among the affected group, the healthy group and the control group. The degree of hearing impairment was assessed by pure tone audiometry (PTA) results, which were divided into normal/mild/moderate/moderately severe/severe/extremely severe hearing impairment. Spearman correlation analysis was used to compare the correlation between the morphological rating of VA isthmus on the affected side and age, course of disease and the results of pure tone audiometry (PTA). Results: The proportions of VA isthmic morphology GRADE Ⅰ,Ⅱ,Ⅲ,Ⅳ in the MD affected group were 28.6% (4/14), 42.9% (6/14), 21.4% (3/14), 7.1% (1/14), those in the MD healthy group were 0 (0/12), 33.3% (4/12), 33.3% (4/12), 33.3% (4/12), and those in the control group were 0 (0/28), 7.1% (2/28), 64.2% (18/28), 28.6% (8/28). The VA isthmus scores [ M ( Q1, Q3 )] of MD affected group was lower than that of MD healthy group [2 (1, 3) vs 3 (2, 4)] and control group [2 (1, 3) vs 3 (3, 4)] (all P <0.05, respectively). The morphology of the VA isthmus on the affected side of MD was negatively correlated with age ( r =-0.81, P =0.002), and there was no correlation with the course of disease and degree of hearing impairment ( r =-0.40, r =-0.26; all P >0.05, respectively). Conclusion: The stenosis of the VA isthmus in MD was a possible anatomical factor for the occurrence of MD .

The vestibular sensory epithelium of humans and mice may degenerate into a layer of flat cells, known as flat epithelium (FE), after a severe lesion. However, the pathogenesis of vestibular FE remains unclear. To determine whether the epithelial-mesenchymal transition (EMT) participates in the formation of vestibular FE, we used a well-established mouse model in which FE was induced in the utricle by an injection of streptomycin into the inner ear. The mesenchymal and epithelial cell markers and cell proliferation were examined using immunofluorescence staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The function of the EMT was assessed through transcriptome microarray analysis. The results demonstrated that mesenchymal cell markers (α-SMA, S100A4, vimentin, and Fn1) were upregulated in vestibular FE compared with the normal utricle. Robust cell proliferation, which was absent in the normal status, was observed in the formation of FE. Microarray analysis identified 1,227 upregulated and 962 downregulated genes in vestibular FE. Gene Ontology (GO) analysis revealed that differentially expressed genes (DEGs) were highly associated with several EMT-related GO terms, such as cell adhesion, cell migration, and extracellular matrix. Pathway enrichment analysis revealed that DEGs were enriched in the EMT-related signaling pathways, including extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/Akt signaling pathway and cell adhesion molecule. Protein-protein interaction networks screened 20 hub genes, which were Akt, Casp3, Col1a1, Col1a2, Fn1, Hgf, Igf1,Il1b, Irs1, Itga2, Itga5, Jun, Mapk1, Myc, Nras, Pdgfrb, Tgfb1, Thbs1 , Trp53 , and Col2a1 . Most of these genes are reportedly involved in the EMT process in various tissues. The mRNA expression level of hub genes was validated using qRT-PCR. In conclusion, the present study indicates that EMT plays a significant role in the formation of vestibular FE and provides an overview of transcriptome characteristics in vestibular FE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 He, Wang, Guo, Chen, Liu and Gong.)

A bisthienylethene-dipyrimido[2,1- b ][1,3]benzothiazole ( BTE-2PBT ) triad has been designed and synthesized based on our recent discovery of PBTs as atypical propeller-shaped novel AIEgens. The triad not only maintains the photochromic properties of BTE moiety in solution, film, and solid state but also exhibits remarkable AIE properties. Moreover, the fluorescence of BTE-2PBT PMMA film could be modulated with high contrast by alternate UV and visible light irradiation. Photoerasing, rewriting, and non-destructive readout of fluorescent images on BTE-2PBT PMMA film well demonstrate its potential application as optical memory media.

Objective: To conclude the clinical features and the postoperative efficacy of congenital middle ear malformation treated with Malleostapedotomy (MS), and to explore the security and effectiveness of MS surgery. Methods: The clinical data of 17 patients (18 ears) with congenital middle ear malformation undergoing MS procedure were analyzed. There were 10 males (11 ears) and 7 females (7 ears), aged from 7 to 48 years. The imaging examination, pure-tone audiometry, intraoperative findings and postoperative hearing improvement of these patients were analyzed and summarized, and software SPSS23.0 was used for statistical analysis. Rusults All the 17 patients (18 ears) presented with hearing loss since childhood on the affected sides. Preoperative high resolution CT (HRCT) of the temporal bone revealed definite malformations in 9 ears (6 ears with incus long process dysplasia and 3 ears with anterior and posterior crus dysplasia). Before surgery, the mean bone conductive hearing threshold at 500, 1 000, 2 000 and 4 000 Hz was (15.6±10.2) dB HL, the mean air conductive hearing threshold was (60.6±9.7) dB HL, and the mean air-bone gap was (45.0±8.9) dB. During the surgery, all 18 ears were found to be accompanied by absence or hypoplasia of incus long process. 12 ears had stapes fixation, 6 ears had oval window atresia. All patients were treated with MS procedure by using Piston. The patients were followed up for 3 months to 1 year. The mean bone conductive hearing threshold was (14.7±8.8) dB HL. The mean air conductive hearing threshold was (37.7±11.6) dB HL, and the mean air-bone gap was (23.0±8.0) dB. There were statistically significant differences in the mean air conductive hearing threshold and mean air-bone gap before and after surgery ( P <0.05). While there were no statistically significant differences in the mean bone conductive hearing threshold before and after surgery ( P =0.550). Conclusions: MS procedure is safe and reliable in patients with congenital middle ear malformation of incus long process dysplasia, stapes fixation or oval window atresia. HRCT is useful in evaluating the major deformity of ossicular chain and facial nerve deformity. However, it is not enough to evaluate the joint of incus-stapes and oval window atresia. MS surgery in middle ear malformation requires advanced surgical experience and skills. The hearing improvement can be significant, even though some air-bone gap after surgery exist.

Objective: To study the clinical diagnosis and treatment strategies for vein-related pulsatile tinnitus patients with transverse sinus stenosis. Methods: The clinical data of patients with vein-related pulsatile tinnitus, from January 2015 to August 2019, were collected,whose digital subtraction angiography showing transverse sinus stenosis. Taking December 2019 as the last follow-up time, we analyzed the clinical characteristics, CT angiography and digital subtraction angiography results, lumbar puncture pressure and cerebrospinal fluid composition, and other auxiliary examination results (pure tone audiometry, fundus examination of papilledema, carotid ultrasonography, bone density screening, endocrinous test), as well as tinnitus handicap inventory, treatment options and follow-up results. Results: 83 patients were enrolled with female of 89.2% (74/83) and male of 10.8%(9/83); 65.1% (54/83) with right tinnitus, 31.3% (26/83) with left tinnitus, and 3.6% (3/83) with bilateral tinnitus; 67.5% (56/83) with right dominant sinus, 19.3% (16/83) with left dominant sinus, 13.3% (11/83) with bilateral equalization; Bilateral and ipsilateral stenosis accounted for 55.4% and 44.6% respectively; BMI was overweight or obese in 41 cases (49.4%, 41/83). Patients with tinnitus handicap inventory level three or above accounted for 79.5% (66/83). Eventually, 33 patients chose conservative observation (39.8%, 33/83), 40 patients (48.2%), 8 patients (9.6%) and 2 patients (2.4%) received sigmoid sinus-related surgery, interventional surgery, or emissary vein occlusion respectively. The mean follow-up time of 74 patients was 26.2 months. The data of 48 surgery patients showed that the pressure differences of venous sinus among the recurrent patients were more obvious; Interventional surgery with simultaneous stenting placement was effective. Tinnitus did not decrease in two patients with emissary vein occlusion. Analysis of 26 patients with lumbar puncture revealed eight cases of normal cranial pressure and 18 cases of high cranial pressure. The sinus pressure difference between the two groups was different ( P =0.025), but the difference of age of onset, concomitant symptoms, BMI, proportion of empty sella or papilledema was not statistically significant ( P >0.05). Conclusions: The evaluation of patients with vein-related pulsatile tinnitus requires a standardized procedure. Papilledema cannot be used as a sensitive indicator in patients with early intracranial hypertension. Venous sinus pressure difference may be one of the indicators of intracranial hypertension, and the lumbar puncture is the gold standard for the diagnosis. Weight loss can be used as a conservative treatment during the observation period. Significant sinus stenosis is a risk factor for recurrence in patients undergoing sigmoid sinus surgery. Interventional stenting is an effective treatment for tinnitus secondary to transverse sinus stenosis.

The frustrated magnet α-RuCl 3 constitutes a fascinating quantum material platform that harbors the intriguing Kitaev physics. However, a consensus on its intricate spin interactions and field-induced quantum phases has not been reached yet. Here we exploit multiple state-of-the-art many-body methods and determine the microscopic spin model that quantitatively explains major observations in α-RuCl 3 , including the zigzag order, double-peak specific heat, magnetic anisotropy, and the characteristic M-star dynamical spin structure, etc. According to our model simulations, the in-plane field drives the system into the polarized phase at about 7 T and a thermal fractionalization occurs at finite temperature, reconciling observations in different experiments. Under out-of-plane fields, the zigzag order is suppressed at 35 T, above which, and below a polarization field of 100 T level, there emerges a field-induced quantum spin liquid. The fractional entropy and algebraic low-temperature specific heat unveil the nature of a gapless spin liquid, which can be explored in high-field measurements on α-RuCl 3 .

Objective: To explore more refined classification methods of congenital middle ear cholesteatoma (CMEC) based on two existing staging systems. Subjects and Methods: This study involved a retrospective data review of 57 patients (61 ears involved) with CMEC requiring the surgical treatment. Patients were classified into different stages according to Nelson, Potsic, and Modified Nelson staging system. Preoperative data and intraoperative findings were recorded. Results: The mean age at operation was 15 ± 15.04 years with a median of 10 years. The main clinical manifestation was hearing loss (72.13%). CMEC mass was mainly located in the posterior portion of the tympanic cavity (65.57%). No patient was classified into Potsic stage II. The erosion of incus happened in all cases. Patients with Nelson type 2 and type 3 had erosions to the structures out of middle ear, such as dura mater, lateral semicircle canal, and facial canal. Postoperative follow-up time was more than 24 months. Recurrence occurred in four patients (6.56%), all of them in Nelson type 2, who had received canal wall down mastoidectomy (three cases) and canal wall up mastoidectomy (one case). Conclusions: Nelson staging system was more suitable for advanced CMEC patients than Potsic staging system. The rare case of Potsic stage II restricted the application of Potsic staging system. Moreover, since both of two staging systems do not distinguish the type of involved ossicles, the authors recommended to subdivide Nelson type 2 into type 2a and type 2b based on the erosion of the ossicular chain, as well as subdivide Nelson type 3 into type 3a and 3b based on the erosion of structures out of middle ear, which was named as Modified Nelson staging system.

Background: Fatigue is a very common but relatively neglected problem in patients with inflammatory bowel disease (IBD). The prevalence rate of IBD in China is the highest in Asia, but there is little research on fatigue in patients with IBD. Neither the relationship between fatigue and quality of life (QoL) nor the relationship between fatigue and work productivity (WP) in Chinese IBD patients has been reported., Aim: To investigate the prevalence of fatigue related to IBD in Eastern China, to identify the risk factors associated with fatigue, to assess the impact of fatigue on QoL, and to evaluate the relationship between fatigue and WP., Methods: A cross-sectional study was conducted in a Regional Tertiary IBD Diagnostic and Treatment Center in Eastern China. Clinical data of patients were collected, and disease activity was evaluated. Blood samples were analyzed to assess anemia, albumin, and inflammation. Fatigue was assessed using the multidimensional fatigue inventory. QoL and WP were measured using the short inflammatory bowel disease questionnaire and the work productivity and activity impairment general health questionnaire, respectively. The patients also completed assessments of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder 7-item Scale)., Results: A total of 311 IBD patients, comprising 168 Crohn's disease patients and 143 ulcerative colitis patients, were enrolled. The prevalence of fatigue in patients with IBD was 60.77%. In a univariate logistic regression analysis, factors such as disease activity, depression, anxiety, anemia, and IBD-related surgery were individually related to a significantly increased risk of fatigue in IBD patients. Multivariate logistic regression analysis indicated that depression [odds ratio (OR) = 8.078, 95% confidence interval (CI): 4.113-15.865], anxiety (OR = 2.373, 95%CI: 1.100-5.119), anemia (OR = 2.498, 95%CI: 1.290-4.834), and IBD-related surgery (OR = 2.035, 95%CI: 1.084-3.819) were related to fatigue in IBD patients. There was a negative correlation between fatigue and QoL ( r = -0.831; P < 0.0001) but a positive correlation between fatigue and WP loss., Conclusion: The prevalence of fatigue in IBD patients in Eastern China is remarkably high even in clinical remission. Factors such as depression, anxiety, anemia, and IBD-related surgery are major risk factors for fatigue in IBD patients. In addition, fatigue has a negative impact on QoL and is positively correlated with WP loss., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Vestibular hair cells (HCs) are mechanoreceptors for the detection of head movement. Vestibular HCs of adult mammals never completely regenerate after damage, resulting in vestibular dysfunction. Overexpression of Atoh1 is effective for inducing HC regeneration. However, method of clinical feasibility and improvement of regenerative extent are both in need. Here we used an adeno-associated virus (AAV) serotype 8 vector of two different titers to overexpress Atoh1 in the injured utricles of adult mice. One month after virus inoculation, abundant myosin VIIa-positive cells and immature stereocilia were observed. Quantitative analyses revealed that Atoh1 overexpression replenished vestibular HCs in a dose-dependent manner. Vectors of a higher titer increased the number of myosin VIIa-positive cells compared to those of lower titer. Moreover, only Atoh1 overexpression in the higher titer group enhanced stereocilium regeneration, which is an important step in the maturation of regenerated HCs. Although the current treatment failed to initiate functional recovery of the animals, our results prompt further improvements in the recovery of vestibular dysfunction by AAV., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A three-dimensional (3D) binodal 3,5-connected net, {[Cu(MTP)(H 2 O)](NO 3 )} n ( 1 ) with the Schläfli symbol of {3·7 2 }{3 2 ·7 5 ·8 3 } can be transformed into a two-dimensional (2D) kagóme network with the Schlafli symbol of {3 2 ·6 2 ·7 2 } in an irreversible single crystal-single crystal (SC-SC) guest-assisted linker exchange process. The product of this SC-SC represents the first luminescent probe for S 2- based on triazole ligand., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Coronavirus disease-2019 (COVID-19) is a new highly infectious disease caused by a novel coronavirus. Recently, the number of new cases infected pneumonia in the world continues to increase, which has aroused great concern from the international community. At present, there are no small-molecule specific anti-viral drugs for the treatment. The high mortality rate seriously threatens human health. Traditional Chinese medicine (TCM) is a unique health resource in China. The combination of TCM and Western medicine has played a positive and important role in combating COVID-19 in China. In this review, through literature mining and analysis, it was found that TCM has the potential to prevent and treat the COVID-19. Then, the network pharmacological studies demonstrated that TCM played roles of anti-virus, anti-inflammation and immunoregulation in the management of COVID-19 via multiple components acting on multiple targets and multiple pathways. Finally, clinical researches also confirmed the beneficial effects of TCM on the treatment of patients. This review may provide meaningful and useful information on further drug development of COVID-19 and other viral infectious diseases., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Sensorineural hearing loss and vertigo, resulting from lesions in the sensory epithelium of the inner ear, have a high incidence worldwide. The sensory epithelium of the inner ear may exhibit extreme degeneration and is transformed to flat epithelium (FE) in humans and mice with profound sensorineural hearing loss and/or vertigo. Various factors, including ototoxic drugs, noise exposure, aging, and genetic defects, can induce FE. Both hair cells and supporting cells are severely damaged in FE, and the normal cytoarchitecture of the sensory epithelium is replaced by a monolayer of very thin, flat cells of irregular contour. The pathophysiologic mechanism of FE is unclear but involves robust cell division. The cellular origin of flat cells in FE is heterogeneous; they may be transformed from supporting cells that have lost some features of supporting cells (dedifferentiation) or may have migrated from the flanking region. The epithelial-mesenchymal transition may play an important role in this process. The treatment of FE is challenging given the severe degeneration and loss of both hair cells and supporting cells. Cochlear implant or vestibular prosthesis implantation, gene therapy, and stem cell therapy show promise for the treatment of FE, although many challenges remain to be overcome.