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1.
Hum Pathol ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38782102

ABSTRACT

There is no universally accepted method for evaluating lymph node metastasis (LNM) in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. Different protocols recommend evaluating the percentage of residual viable tumor (RVT%) and metastatic tumor size (MTS). Our aim was to determine the prognostic significance of RVT% and MTS, and identify the more effective parameter for pathological evaluating LNM. Two independent cohorts were collected (derivation, n=84; external validation, n=42). All patients exhibited metastatic cancer or treatment response in lymph nodes post-surgery. In the derivation cohort, we assessed the mean and largest values of MTS and RVT% in LNM, estimating their optimal cutoffs for event-free survival (EFS) using maximally selected rank statistics. Validation was subsequently conducted in the external validation cohort. The quality of prognostic factors was evaluated using the Area Under Curve (AUC). A positive association was identified between RVT% and MTS, but an absolute association could not be conclusively established. In the derivation cohort, neither the largest MTS (cutoff=6mm, p=0.28), largest RVT% (cutoff=75%, p=0.23), nor mean RVT% (cutoff=55%, p=0.06) were associated with EFS. However, mean MTS (cutoff=4.5mm) in lymph nodes was statistically associated with EFS (p=0.018), validated by the external cohort (p=0.017). The prognostic value of MTS exceeded that of ypN staging in both cohorts, as evidenced by higher AUC values. The mean value of MTS can effectively serve as a parameter for the pathological evaluation of lymph nodes, with a threshold of 4.5mm, closely linked to EFS. Its prognostic value outperforms that of ypN staging.

2.
ACS Omega ; 9(18): 19911-19922, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38737087

ABSTRACT

In this study, an existing ternary membrane system based on nonsolvent-induced phase separation (NIPS) with a phase-field model was optimized. To study and analyze the effects of different additives on the formation of the skin layer and the effects of the three solvents on membrane characterization under the same conditions, two-dimensional simulations of the relevant parameters of a poly(vinylidene fluoride) (PVDF) membrane system were performed. The specific application of quaternary substances in ternary membrane systems was elaborated by determining the cohesive energy density between the additives and solvents, followed by the interaction parameters χ under the joint effect of the two. The results showed that the PVDF microporous membrane formed a dense surface layer at the mass transfer exchange interface, and with an increase in the poly(ethylene glycol) (PEG) concentration, the phase separation of the skin layer was predominantly transformed from liquid-solid partitioning to liquid-liquid partitioning; the number of membrane pores increased with increasing poly(vinylpyrrolidone) (PVP) concentration. The N,N-dimethylacetamide (DMAc) solvent system had the most stable thermodynamic properties; the dimethyl sulfoxide (DMSO) solvent system had mostly large pores running through the membrane and exhibited a porous structure. Related experiments also validated the model. Therefore, this model can be applied to other PVDF ternary membrane systems to better understand the structural development of microporous PVDF membranes under different conditions.

3.
BMC Womens Health ; 24(1): 310, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38802808

ABSTRACT

BACKGROUND: To demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS). CASE PRESENTATION: A 71-year-old woman with the left invasive breast cancer was treated with hormone therapy for six months and underwent the 18F-FDG PET/CT examination for efficacy evaluation. 18F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18F-FDG uptake, bone expansion of cystic lesions in the bilateral ribs, ectopic calcifications and dilated right ureter. She had no known family history. Then, the patient underwent surgical excision of the all skin nodules and the postoperative pathology were multiple basal cell carcinomas. Finally, the comprehensive diagnosis of NBCCS was made. The patient was still in follow-up. Additionally, we have summarized the reported cases (n = 3) with 18F-FDG PET/CT from the literature. CONCLUSIONS: It is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences.


Subject(s)
Basal Cell Nevus Syndrome , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Humans , Female , Positron Emission Tomography Computed Tomography/methods , Aged , Basal Cell Nevus Syndrome/diagnostic imaging , Basal Cell Nevus Syndrome/diagnosis , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Breast Neoplasms/diagnosis , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Radiopharmaceuticals
4.
ACS Nano ; 18(11): 7796-7824, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38456414

ABSTRACT

Sodium-ion batteries (SIBs) are considered as an alternative to and even replacement of lithium-ion batteries in the near future in order to address the energy crisis and scarcity of lithium resources due to the wide distribution and abundance of sodium resources on the earth. The exploration and development of high-performance anode materials are critical to the practical applications of advanced SIBs. Among various anode materials, bimetallic oxides (BMOs) have attracted special research attention because of their abundance, easy access, rich redox reactions, enhanced capacity and satisfactory cycling stability. Although many BMO anode materials have been reported as anode materials in SIBs, very limited studies summarized the progress and prospect of BMOs in practical applications of SIBs. In this review, recent progress and challenges of BMO anode materials for SIBs have been comprehensively summarized and discussed. First, the preparation methods and sodium storage mechanisms of BMOs are discussed. Then, the challenges, optimization strategies, and sodium storage performance of BMO anode materials have been reviewed and summarized. Finally, the prospects and future research directions of BMOs in SIBs have been proposed. This review aims to provide insight into the efficient design and optimization of BMO anode materials for high-performance SIBs.

5.
Plants (Basel) ; 13(5)2024 Feb 25.
Article in English | MEDLINE | ID: mdl-38475473

ABSTRACT

Cadmium (Cd) hampers plant growth and harms photosynthesis. Glutamate (Glu) responds to Cd stress and activates the Ca2+ signaling pathway in duckweed, emphasizing Glu's significant role in Cd stress. In this study, we overexpressed phosphoserine aminotransferase (PSAT), a crucial enzyme in Glu metabolism, in duckweed. We investigated the response of PSAT-transgenic duckweed to Cd stress, including growth, Glu metabolism, photosynthesis, antioxidant enzyme activity, Cd2+ flux, and gene expression. Remarkably, under Cd stress, PSAT-transgenic duckweed prevented root abscission, upregulated the expression of photosynthesis ability, and increased Chl a, Chl b, and Chl a + b levels by 13.9%, 7%, and 12.6%, respectively. Antioxidant enzyme activity (CAT and SOD) also improved under Cd stress, reducing cell membrane damage in PSAT-transgenic duckweeds. Transcriptomic analysis revealed an upregulation of Glu metabolism-related enzymes in PSAT-transgenic duckweed under Cd stress. Moreover, metabolomic analysis showed a 68.4% increase in Glu content in PSAT duckweed exposed to Cd. This study sheds novel insights into the role of PSAT in enhancing plant resistance to Cd stress, establishing a theoretical basis for the impact of Glu metabolism on heavy metal tolerance in plants.

6.
Comput Biol Med ; 173: 108353, 2024 May.
Article in English | MEDLINE | ID: mdl-38520918

ABSTRACT

The grading diagnosis of intracranial tumors is a key step in formulating clinical treatment plans and surgical guidelines. To effectively grade the diagnosis of intracranial tumors, this paper proposes a dual path parallel hierarchical model that can automatically grade the diagnosis of intracranial tumors with high accuracy. In this model, prior features of solid tumor mass and intratumoral necrosis are extracted. Then the optimal division of the data set is achieved through multi-feature entropy weight. The multi-modal input is realized by the dual path structure. Multiple features are superimposed and fused to achieve the image grading. The model has been tested on the actual clinical medical images provided by the Second Affiliated Hospital of Dalian Medical University. The experiment shows that the proposed model has good generalization ability, with an accuracy of 0.990. The proposed model can be applied to clinical diagnosis and has practical application prospects.


Subject(s)
Brain Neoplasms , Humans , Entropy , Brain Neoplasms/diagnostic imaging , Image Interpretation, Computer-Assisted/methods
7.
Biochem Pharmacol ; 223: 116132, 2024 May.
Article in English | MEDLINE | ID: mdl-38492782

ABSTRACT

Cisplatin is an effective chemotherapeutic drug for different cancers, but it also causes severe and permanent hearing loss. Oxidative stress and mitochondrial dysfunction in cochlear hair cells (HCs) have been shown to be important in the pathogenesis of cisplatin-induced hearing loss (CIHL). CDGSH iron sulfur domain 1 (CISD1, also known as mitoNEET) plays a critical role in mitochondrial oxidative capacity and cellular bioenergetics. Targeting CISD1 may improve mitochondrial function in various diseases. However, the role of CISD1 in cisplatin-induced ototoxicity is unclear. Therefore, this study was performed to assess the role of CISD1 in cisplatin-induced ototoxicity. We found that CISD1 expression was significantly increased after cisplatin treatment in both HEI-OC1 cells and cochlear HCs. Moreover, pharmacological inhibition of CISD1 with NL-1 inhibited cell apoptosis and reduced mitochondrial reactive oxygen species accumulation in HEI-OC1 cells and cochlear explants. Inhibition of CISD1 with small interfering RNA in HEI-OC1 cells had similar protective effects. Furthermore, NL-1 protected against CIHL in adult C57 mice, as evaluated by the auditory brainstem response and immunofluorescent staining. Mechanistically, RNA sequencing revealed that NL-1 attenuated CIHL via the PI3K and MAPK pathways. Most importantly, NL-1 did not interfere with the antitumor efficacy of cisplatin. In conclusion, our study revealed that targeting CISD1 with NL-1 reduced reactive oxygen species accumulation, mitochondrial dysfunction, and apoptosis via the PI3K and MAPK pathways in HEI-OC1 cell lines and mouse cochlear explants in vitro, and it protected against CIHL in adult C57 mice. Our study suggests that CISD1 may serve as a novel target for the prevention of CIHL.


Subject(s)
Antineoplastic Agents , Hearing Loss , Mitochondrial Diseases , Ototoxicity , Mice , Animals , Cisplatin/toxicity , Cisplatin/metabolism , Antineoplastic Agents/toxicity , Phosphatidylinositol 3-Kinases/metabolism , Reactive Oxygen Species/metabolism , Ototoxicity/prevention & control , Hearing Loss/chemically induced , Hearing Loss/prevention & control , Apoptosis , Membrane Proteins/metabolism , Iron-Binding Proteins/pharmacology
8.
Clin Imaging ; 108: 110100, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38341881

ABSTRACT

PURPOSE: To investigate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer (BC) with second primary malignancies (SPMs). MATERIALS AND METHODS: 149 BC patients (149/1419, 10.5 %) ultimately diagnosed with SPMs were included in the study. The following data were evaluated: age, location, the treatment of the first BC, the interval between the first BC and SPMs, the maximum diameter of SPMs, the maximum standardized uptake value (SUVmax) of SPMs, and SPMs metastases. The overall survival (OS) and progression-free survival (PFS) of follow-up patients were analyzed. The diagnostic efficiency of 18F-FDG PET/CT for SPMs and consistency with the pathological findings were calculated. RESULTS: The most common SPMs of BC was lung cancer (81/149, 54.4 %), particularly early-stage lung adenocarcinoma. There were the shorter maximum diameter of SPMs, the lower SUVmax of SPMs, and the fewer SPMs metastases in the lung cancer group than non-lung cancer group (P<0.001). The OS and PFS of the follow-up patients in the lung cancer group were longer than non-lung cancer group (P<0.001). The SPMs metastases was independent prognostic indicator of OS. The pathological grouping and the SPMs metastases were independent prognostic indicators of PFS. 18F-FDG PET/CT efficacy in diagnosing SPMs in BC patients was high. Compared with the pathological findings, the consistency was good (P = 0.010). CONCLUSION: Applying 18F-FDG PET/CT in BC patients might be helpful in detecting SPMs and partially predicting patient prognosis, in addition to its primary function in the diagnosis and staging of BC.


Subject(s)
Breast Neoplasms , Lung Neoplasms , Neoplasms, Second Primary , Humans , Female , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Breast Neoplasms/diagnostic imaging , Neoplasms, Second Primary/diagnostic imaging , Prognosis , Lung Neoplasms/diagnostic imaging , Retrospective Studies , Radiopharmaceuticals
9.
Ann Diagn Pathol ; 69: 152268, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38301396

ABSTRACT

BACKGROUND: Major pathological response (MPR) is proposed as a surrogate endpoint for survival in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. However, the criteria for estimating MPR differ between the recommendations of the International Association for the Study of Lung Cancer (IASLC) and the immune-related pathologic response criterion (irPRC). IASLC's criteria focus solely on evaluating the primary tumor, while irPRC's criteria encompass both the primary tumor and lymph node metastasis. Our objective is to compare the prognostic value of different criteria for estimating MPR. METHODS: We conducted a retrospective study on a cohort of 235 patients with NSCLC after neoadjuvant chemoimmunotherapy. The survival endpoint was event-free survival (EFS). The MPR status of each patient was evaluated using both IASLC's criteria and irPRC's criteria. The prognostic value was compared using the Area Under Curve (AUC). RESULTS: The MPR rates were 63.4 % (149/235) and 57.4 % (135/235) according to IASLC's and irPRC's criteria, respectively. Inconsistent cases, characterized by MPR status according to IASLC's criteria but non-MPR status according to irPRC's criteria, constituted 6.0 % (14/235) of the overall cohort and 15.2 % (14/92) of patients with pretreatment N positive disease. Interestingly, all inconsistent patients showed no recurrence during the study period. Although both MPR statuses according to IASLC (p = 0.00039) and irPRC (p = 0.0094) were associated with improved EFS, IASLC's criteria (AUC = 0.65) were superior to irPRC's criteria (AUC = 0.62) with a higher AUC value. CONCLUSION: IASLC's criteria for estimating MPR were superior to irPRC's criteria in predicting EFS for NSCLC after neoadjuvant chemoimmunotherapy.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Neoadjuvant Therapy , Retrospective Studies , Immunotherapy
10.
Cancer Gene Ther ; 31(4): 507-516, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38316961

ABSTRACT

Thyroid cancer is a prevalent endocrine malignancy with increasing incidence in recent years. Although most thyroid cancers grow slowly, they can become refractory, leading to a high mortality rate once they exhibit recurrence, metastasis, resistance to radioiodine therapy, or a lack of differentiation. However, the mechanisms underlying these malignant characteristics remain unclear. Circular RNAs, a type of closed-loop non-coding RNAs, play multiple roles in cancer. Several studies have demonstrated that circular RNAs significantly influence the development of thyroid cancers. In this review, we summarize the circular RNAs identified in thyroid cancers over the past decade according to the hallmarks of cancer. We found that eight of the 14 hallmarks of thyroid cancers are regulated by circular RNAs, whereas the other six have not been reported to be correlated with circular RNAs. This review is expected to help us better understand the roles of circular RNAs in thyroid cancers and accelerate research on the mechanisms and cure strategies for thyroid cancers.


Subject(s)
RNA, Circular , Thyroid Neoplasms , Humans , RNA, Circular/genetics , Iodine Radioisotopes , Thyroid Neoplasms/genetics , Thyroid Neoplasms/therapy
11.
Cancers (Basel) ; 15(12)2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37370781

ABSTRACT

(1) Background: Chromatin structure typing has been used for prognostic risk stratification among cancer survivors. This study aimed to ascertain the prognostic values of ploidy, nucleotyping, and tumor-stroma ratio (TSR) in predicting disease progression for patients with early-stage non-small cell lung cancer (NSCLC), and to explore whether patients with different nucleotyping profiles can benefit from adjuvant chemotherapy. (2) Methods: DNA ploidy, nucleotyping, and TSR were measured by chromatin structure typing analysis (Matrix Analyser, Room4, Kent, UK). Cox proportional hazard regression models were used to assess the relationships of DNA ploidy, nucleotyping, and TSR with a 5-year disease-free survival (DFS). (3) Results: among 154 early-stage NSCLC patients, 102 were non-diploid, 40 had chromatin heterogeneity, and 126 had a low stroma fraction, respectively. Univariable analysis suggested that non-diploidy was associated with a significantly lower 5-year DFS rate. After combining DNA ploidy and nucleotyping for risk stratification and adjusting for potential confounders, the DNA ploidy and nucleotyping (PN) high-risk group and PN medium-risk group had a 4- (95% CI: 1.497-8.754) and 3-fold (95% CI: 1.196-6.380) increase in the risk of disease progression or mortality within 5 years of follow-up, respectively, compared to the PN low-risk group. In PN high-risk patients, adjuvant therapy was associated with a significantly improved 5-year DFS (HR = 0.214, 95% CI: 0.048-0.957, p = 0.027). (4) Conclusions: the non-diploid DNA status and the combination of ploidy and nucleotyping can be useful prognostic indicators to predict long-term outcomes in early-stage NSCLC patients. Additionally, NSCLC patients with non-diploidy and chromatin homogenous status may benefit from adjuvant therapy.

12.
ACS Chem Neurosci ; 14(10): 1896-1904, 2023 05 17.
Article in English | MEDLINE | ID: mdl-37146126

ABSTRACT

Cochlear calcium (Ca2+) waves are vital regulators of the cochlear development and establishment of hearing function. Inner supporting cells are believed to be the main region generating Ca2+ waves that work as internal stimuli to coordinate the development of hair cells and the mapping of neurons in the cochlea. However, Ca2+ waves in interdental cells (IDCs) that connect to inner supporting cells and spiral ganglion neurons are rarely observed and poorly understood. Herein, we reported the mechanism of IDC Ca2+ wave formation and propagation by developing a single-cell Ca2+ excitation technology, which can easily be accomplished using a two-photon microscope for simultaneous microscopy and femtosecond laser Ca2+ excitation in any target individual cell in fresh cochlear tissues. We demonstrated that the store-operated Ca2+ channels in IDCs are responsible for Ca2+ wave formation in these cells. The specific architecture of the IDCs determines the propagation of Ca2+ waves. Our results provide the mechanism of Ca2+ formation in IDCs and a controllable, precise, and noninvasive technology to excite local Ca2+ waves in the cochlea, with good potential for research on cochlear Ca2+ and hearing functions.


Subject(s)
Calcium Signaling , Cochlea , Intracellular Calcium-Sensing Proteins , Single-Cell Analysis , Cochlea/cytology , Cochlea/growth & development , Intracellular Calcium-Sensing Proteins/physiology , Single-Cell Analysis/methods , Microscopy, Fluorescence, Multiphoton , Animals , Mice , Mice, Inbred C57BL
13.
Nucl Med Commun ; 44(6): 502-508, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37036299

ABSTRACT

PURPOSE: To assess the characteristics of fibrotic-foci-like lung adenocarcinoma on 18 F-fluorodeoxyglucose PET/computed tomography ( 18 F-FDG PET/CT) and high-resolution computed tomography (HRCT). MATERIAL AND METHODS: This was a retrospective study with 20 cases in the fibrotic-foci-like lung adenocarcinoma group; the control group was old fibrotic-foci of the lung with 20 cases. The following 18 F-FDG PET/CT and HRCT features were evaluated: the maximum standardized uptake value (SUVmax); the tumor-to-background ratios of SUVmax (TBRmax); the long-to-short diameter ratio (L/S); anatomic location; location type; internal characteristics; marginal characteristics and surrounding structures. In the fibrotic-foci-like lung adenocarcinoma group, a comparison of 18 F-FDG uptake between the metastatic group ( n  = 10) and the non-metastatic group ( n  = 10) was performed. Finally, the comparison of diagnostic accuracy for fibrotic-foci-like lung adenocarcinoma between 18 F-FDG PET/CT and HRCT was performed. RESULTS: The SUVmax [2.6 (1.7-7.9) vs. 1.0 (0.7-1.4)], TBRmax [2.9 (2.1-9.9) vs. 1.3 (1.2- 1.7)], L/S [2.4 (1.7-3.8) vs. 4.0 (3.2-6.3)], ground-glass opacity (GGO) [13/20 (65.0%) vs. 4/20 (20.0%)], and vessel convergence [7/20 (35.0%) vs. 1/20 (5.0%)] were found to be statistically significant differences between the fibrotic-foci-like lung adenocarcinoma group and the old fibrotic-foci group ( P  < 0.05). SUVmax [7.9 (4.7-8.8) vs. 1.7 (1.2-2.2)] and TBRmax [9.9 (6.5-11.0) vs. 2.1 (1.6-2.9)] were found to be statistically significant differences between the metastatic group and the non-metastatic group ( P  < 0.05). 18 F-FDG PET/CT showed the higher diagnostic accuracy for fibrotic-foci-like lung adenocarcinoma than HRCT [95.0% (19/20) vs. 65.0% (13/20), P  < 0.05]. CONCLUSION: The specific characteristics of fibrotic-foci-like lung adenocarcinoma on 18 F-FDG PET/CT and HRCT were high 18 F-FDG uptake, GGO, and vessel convergence, which could be distinguished from old fibrotic-foci of the lung.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography/methods , Retrospective Studies , Adenocarcinoma of Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology
14.
J Dermatol ; 50(7): 856-868, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37020415

ABSTRACT

The pathogenesis of granulomatous rosacea (GR), the only variant of rosacea, is unclear. To investigate the differences between GR and non-granulomatous rosacea (NGR) in clinical characteristics, histopathological changes and gene expression for the purpose of providing new ideas on the pathogenesis of rosacea. A total of 30 GR and 60 NGR patients were included. Their clinical and histopathological information was collected retrospectively, and the characteristics of immune cell infiltration were investigated by multiple immunohistochemical staining. RNA sequencing and transcriptome analysis were performed on three pairs of skin samples from GR and NGR patients, respectively. Then, the expressions of candidate genes that were potentially associated with granuloma formation were verified by immunohistochemical staining. It was found that GR patients were more prone to the occurrence of rosacea in the forehead, periocular and perioral skin (p = 0.001, p < 0.001, p = 0.001), and presented more severe papules and pustules when compared with NGR patients (p = 0.032). For histopathological features, the inflammatory cells primarily infiltrated around hair follicles in the GR group and around blood vessels in the NGR group. In addition, the neutrophils were richer (p = 0.036) and the expression levels of CD4+ , CD8+ and CD68+ cells were higher (p = 0.047, p < 0.001, p < 0.001) in the GR group than in the NGR group. In addition, the GR group had apparent collagen hyperplasia (p = 0.026). A total of 420 differentially expressed genes (DEGs) were detected, and bioinformatics analysis showed that the DEGs were enriched in neutrophil activation, adaptive immune response and other biological processes. Lastly, the candidate genes related to neutrophil activation and collagen hyperplasia, i.e., Cathepsin S (CTSS), Cathepsin Z (CTSZ) and matrix metalloproteinases 9 (MMP9), were confirmed to be highly expressed in the GR group. The clinical and histopathological features of GR exhibited a very diverse pattern compared with NGR, and the underlying mechanisms may be related to neutrophil activation and collagen hyperplasia.


Subject(s)
East Asian People , Rosacea , Humans , Hyperplasia/pathology , Neutrophils/immunology , Retrospective Studies , Rosacea/ethnology , Rosacea/genetics , Rosacea/immunology , Rosacea/pathology , Skin/pathology
15.
Biochem Pharmacol ; 209: 115440, 2023 03.
Article in English | MEDLINE | ID: mdl-36720354

ABSTRACT

Cisplatin is commonly used to treat cancers and is associated with a significant risk of irreversible sensorineural hearing loss. However, no effective preventive strategies are available for cisplatin-induced HL. Therefore, significant efforts have been made to discover new drugs protecting cochlear hair cells from cisplatin-induced damage. We found that a new phytochemical, aucubin, attenuated cisplatin-induced apoptosis, the production of reactive oxygen species, and mitochondrial dysfunction in House Ear Institute Organ of Corti 1 cells and cochlear hair cells. Moreover, aucubin attenuated cisplatin-induced sensorineural hearing loss and hair cells loss in vivo. Furthermore, RNA sequencing analysis revealed that the otoprotective effects of aucubin were mainly mediated by increased STAT3 phosphorylation via the PI3K/AKT pathway. Inhibition of the STAT3 signaling pathway with the inhibitor S3I-201 or siRNA disrupted the protective effects of aucubin on cisplatin-induced apoptosis. In conclusion, we identified an otoprotective effect of aucubin. Therefore, aucubin could be used to prevent cisplatin-induced ototoxicity.


Subject(s)
Antineoplastic Agents , Hearing Loss, Sensorineural , Hearing Loss , Ototoxicity , Mice , Animals , Cisplatin/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Hearing Loss/chemically induced , Hearing Loss/drug therapy , Hearing Loss/prevention & control , Ototoxicity/metabolism , Cochlea/metabolism , Hair Cells, Auditory , Apoptosis , Reactive Oxygen Species/metabolism , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sensorineural/metabolism , Antineoplastic Agents/pharmacology
16.
Article in Chinese | MEDLINE | ID: mdl-36543410

ABSTRACT

At present, the main treatment for vestibular schwannomas is surgery. Considering the risk of multiple complications from surgery and the subjective and objective conditions of patients, a non-surgical treatment modality, namely stereotactic radiotherapy, has gradually been included in the treatment of vestibular schwannomas. Studies have shown that Gamma Knife therapy has a more prominent therapeutic effect on smaller tumors and can alleviate facial nerve disorders caused by space occupying of tumor mass. Cyberknife not only has a better effect on tumor control, but also has an ideal retention rate for patients' auditory function. Proton beam therapy has also been gradually applied to the treatment of vestibular schwannomas, but the effect of treatment remains to be further studied. Drug therapy includes a variety of target inhibitors and anti-angiogenic drugs. At present, drug treatment focuses more on preclinical research. This article reviews the clinical research of various radiotherapy and the progress of drug treatment.


Subject(s)
Facial Nerve Diseases , Neuroma, Acoustic , Radiosurgery , Humans , Neuroma, Acoustic/pathology , Neuroma, Acoustic/radiotherapy , Treatment Outcome , Hearing/physiology , Radiosurgery/adverse effects , Retrospective Studies
17.
Article in English | MEDLINE | ID: mdl-36293922

ABSTRACT

Migrants workers are important participants in and contributors to economic and social construction, but they still face the reality of being marginalized. Based on data from the China Migrants Dynamic Survey in 2018, this paper systematically investigated the impact of public health services on the multidimensional poverty of migrant workers. The research found that, first, the current mean of the multidimensional poverty deprivation value of migrant workers is 0.1806, which is one dimension of poverty that exists on average. In addition, migrant workers do not have high access to public health services. The proportions of migrant workers who have not established residents' health files and who have not received public health education are 74.22% and 29.92%, respectively. Second, public health services can significantly alleviate the multidimensional poverty of migrant workers. After mitigating the potential endogeneity problem by the IV-2SLS method and conducting robustness tests by the PSM method, the conclusion is still robust. Further research found that the impact of public health services on the multidimensional poverty alleviation of migrant workers is heterogeneous. The improvement of public health services has the greatest effect on the multidimensional poverty alleviation of the new generation of migrant female workers in the western region. The research in this paper helps to examine and clarify the policy significance of public health services for the multidimensional poverty alleviation of migrant workers and provides empirical evidence for the use of public health services to tackle the poverty problem.


Subject(s)
Transients and Migrants , Female , Humans , Poverty , Health Services , Health Services Accessibility , China
18.
Front Neurosci ; 16: 933520, 2022.
Article in English | MEDLINE | ID: mdl-35911992

ABSTRACT

Objective: To explore the composition of vestibular disorders presenting with the acute vestibular syndrome (AVS). Methods: We performed a case analysis of 209 AVS patients between January 2016 and December 2020. These patients were grouped into different disorder categories according to the relevant diagnostic criteria. Results: We classified the 209 patients into 14 disorder categories, including 110 cases of vestibular neuritis, 30 of idiopathic sudden sensorineural hearing loss with vertigo, 17 of the first attack of continuous vertigo with migraine, 15 of Ramsay Hunt syndrome, 11 of acute labyrinthitis secondary to chronic otitis media, 8 of vestibular schwannoma, 6 of posterior circulation infarction and/or ischemia, 3 of cerebellar abscess secondary to chronic otitis media, 3 of AVS caused by trauma or surgery, 2 of AVS with down-beating nystagmus, 1 of multiple sclerosis of the medulla oblongata, 1 of epidermoid cyst of the posterior cranial fossa, 1 of a probable acute otolithic lesion, and 1 of AVS without measurable vestibular dysfunction. Conclusion: When a group of disorders present with AVS, characteristic clinical manifestations and imaging help with an accurate diagnosis.

19.
Front Mol Neurosci ; 15: 916458, 2022.
Article in English | MEDLINE | ID: mdl-35706425

ABSTRACT

Objective: Cisplatin is a broad-spectrum anti-tumour drug commonly used in clinical practice. However, its ototoxicity greatly limits its clinical application, and no effective method is available to prevent this effect. Endoplasmic reticulum stress (ERS) is reportedly involved in cisplatin ototoxicity, but the exact mechanism remains unclear. Therefore, this study aimed to investigate the role of eukaryotic translation initiation factor 2α (eIF2α) signalling and its dephosphorylation inhibitor salubrinal in cisplatin ototoxicity. Methods: We evaluated whether salubrinal could protect against cisplatin-induced damage in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and mouse cochlear explants. By knocking down eIF2α, we elucidated the vital role of eIF2α in cisplatin-induced damage in HEI-OC1 cells. Whole-mount immunofluorescent staining and confocal microscopy of mouse cochlear explants and HEI-OC1 cells were performed to analyse cisplatin-induced damage in cochlear hair cells and the auditory cell line. Results: Data suggested salubrinal attenuated cisplatin-induced hair cell injury by inhibiting apoptosis. In addition, salubrinal significantly reduced ERS levels in hair cells via eIF2α signalling, while eIF2α knockdown inhibited the protective effect of salubrinal. Significance: Salubrinal and eIF2α signalling play a role in protecting against cisplatin-induced ototoxicity, and pharmacological inhibition of eIF2α-mediated ERS is a potential treatment for cisplatin-induced damage in the cochlea and HEI-OC1 cells.

20.
Am J Pathol ; 192(9): 1230-1249, 2022 09.
Article in English | MEDLINE | ID: mdl-35750260

ABSTRACT

Vestibular schwannomas (VSs), which develop from Schwann cells (SCs) of the vestibular nerve, are the most prevalent benign tumors of the cerebellopontine angle and internal auditory canal. Despite advances in treatment, the cellular components and mechanisms of VS tumor progression remain unclear. Herein, single-cell RNA-sequencing was performed on clinically surgically isolated VS samples and their cellular composition, including the heterogeneous SC subtypes, was determined. Advanced bioinformatics analysis revealed the associated biological functions, pseudotime trajectory, and transcriptional network of the SC subgroups. A tight intercellular communication between SCs and tumor-associated fibroblasts via integrin and growth factor signaling was observed and the gene expression differences in SCs and fibroblasts were shown to determine the heterogeneity of cellular communication in different individuals. These findings suggest a microenvironmental mechanism underlying the development of VS.


Subject(s)
Neuroma, Acoustic , Cell Communication , Fibroblasts/metabolism , Humans , Neuroma, Acoustic/genetics , Neuroma, Acoustic/metabolism , Neuroma, Acoustic/pathology , RNA-Seq , Schwann Cells/metabolism , Tumor Microenvironment/genetics
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