Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Objective:To analyze a novel intronic variant in the SPTB gene and explore its effect on SPTB mRNA splicing.Methods:Clinical data of a child diagnosed with hereditary spherocytosis (HS) and admitted to the First Affiliated Hospital of Xi′an Jiaotong University in February 2022 were analyzed retrospectively. Whole genome sequencing was used to identify disease-causing variantions and the results were validated with Sanger sequencing, mRNA sequencing was used to determine the SPTB gene′s mRNA expression level, and bioinformatics tools were used for splicing site prediction and analysis.Results:The proband is a 2-month-old Han male child, clinically presenting with anemia and jaundice. In the past, jaundice appeared early and was severe during the neonatal period, with significantly elevated indirect bilirubin (203.5 μmol/L), accompanied by moderate anemia. This family consisted of four generations, eight of whom suffered from splenomegaly, jaundice, and anemia. In their peripheral blood, the percentage of microglobular erythrocytes was between 5% and 10%. Under scanning electron microscopy analysis of the proband's father's peripheral red blood cells, about 6% exhibited a mouth-shaped morphology, about 4% were spherical, and about 3% were oval. Following the splenectomy, the father′s anemia and jaundice recovered to normal level. Whole genome sequencing analysis of the proband identified a heterozygous variant in the SPTB gene (NM_ 001355436.2 (SPTB):c.6022+4_6022+18delinsTGGCTCCTCCGTGAAGGGACAGTCCTGC), which was verified to be co-segregating with the disease in this family line by Sanger sequencing. The results of the SPTB gene mRNA expression level detection showed that the expression levels of the SPTB variant gene were statistically increased in the proband and affected family members (father, grandmother, cousin, second cousin, great-grandmother, great-aunt) (all P<0.05). The SPTB gene′s intron can undergo selective splicing, as demonstrated by analysis using the bioinformatics program ESE Finder. Additionally, predictions from the SpliceAI and SpliceTool software indicated that activation of a new covert splicing donor can result in a code-shift variantion that introduces an early termination codon and nonsense-mediated degradation of the mRNA, which prevents the synthesis of proteins. Conclusion:A new variantion site c.6022+4_6022+18delinsTGGCTCCTCCGTGAAGGGACAGTCCTGC was found in SPTB gene. This variantion was the pathogenic factor of HS. By affecting the splicing process, this variantion triggers the nonsense mediated mRNA degradation pathway, resulting in inactivation of gene function.

Background Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants widely distributed in the environment. Epidemiological studies have shown that PFAS exposure is closely associated with liver dysfunction and an increased risk of liver cancer. Some animal and cell experiments have also revealed its hepatotoxicity and potential carcinogenicity; however, the related carcinogenic mechanism has not yet been fully elucidated. Objective To explore the potential molecular mechanism of PFAS-induced liver cancer, identify the key causal genes, and specifically evaluate the causal association and expression changes of KMT2C in this process, as well as the binding stability between KMT2C and PFAS, and to provid a theoretical basis for mechanistic studies and molecular target discovery in PFAS-related liver cancer. Methods Toxicity prediction was performed on six representative PFAS. Potential target genes of PFAS were identified by integrating results from SwissTargetPrediction, STITCH, and TargetNet databases. Liver cancer-related genes were retrieved from GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The intersection of PFAS targets and liver cancer-related genes was used to obtain core genes. A compound-gene-disease regulatory network was constructed, and a protein–protein interaction network was established using STRING database. A core gene network was visualized based on node degree values. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore biological functions and enriched signaling pathways. Subsequently, two-sample Mendelian randomization was employed to assess potential causal relationships between candidate genes and hepatocellular carcinoma, enabling the identification of key genes. Molecular docking analysis using AutoDock was conducted to evaluate the binding stability between KMT2C and PFAS, and TCGA data were used to validate the differential expression of KMT2C between hepatocellular carcinoma and adjacent normal tissues. Results PFAS exhibited multisystem toxicity and posed significant risks of liver injury and carcinogenesis. A total of 266 PFAS target genes and 2923 liver cancer-related genes were identified, with 61 intersecting genes obtained. The enrichment analysis revealed that these intersecting genes were primarily involved in epigenetic regulation, nuclear receptor signaling pathways, and apoptosis-related pathways including TGF-β FoxO and Notch, suggesting their roles in diverse tumor-related biological processes. The two-sample Mendelian randomization results showed a significant negative causal association between KMT2C and hepatocellular carcinoma (OR=0.68, P <0.05). The molecular docking results demonstrated that all tested PFAS exhibited favorable binding to the KMT2C protein, with binding energies below –5.0 kcal·mol⁻¹. KMT2C was significantly upregulated in hepatocellular carcinoma tissues (unpaired P=0.025; paired P=8.38 × 10⁻⁴). Conclusion The KMT2C protein is found to stably bind with all six PFAS, exhibiting strong structural affinity. A causal relationship is identified between KMT2C and the development of hepatocellular carcinoma. TCGA data indicate that KMT2C is significantly upregulated in hepatocellular carcinoma tissues, and it may serve as a key regulatory target in PFAS-related liver cancer.

Objective To explore the work experiences and needs of nutrition specialist nurses,so as to provide a basis in career development and management practices among the nutrition specialist nurses.Methods A method of descriptive phenomenological research was adopted in this study.Purposive sampling was used to select 12 nutrition specialist nurses who came from different regions across the country with over one year of clinical working experiences as well as had completed the specialist training and been qualified by the Nutrition Committee of Guangdong Nursing Association between January and February 2024.Semi-structured on-line interviews were conducted among the participants and the data acquired from the interviews were analysed and summarised.Themes were extracted using NVivo12 and Colaizzi's seven-step analysis from the data from interview.Results Three main themes and eight sub-themes were identified regarding the work experience of nutrition specialist nurses:growth and gains(continuously learning in nutrition therapy-related knowledge to enhance professional skills;actively practice in nutrition therapy to achieve the self-worth);sense of responsibility and mission(increased awareness of responsibility and proactive services;sense of mission to cultivate talents and promotion of the development of nutrition nursing discipline);challenges(lack of an established role in nutrition nursing,conflict in responsibilities;insufficient communication in a medical team regarding nutrition therapy;limited resource to support the development of nutrition nursing;and the professional knowledge and skills unable to fully meet the job demands).Conclusion Hospitals managers should strengthen the support and training for nutrition specialist nurses,clarify their roles,leverage their professional value and promote the career development.

Objective To explore the work experiences and needs of nutrition specialist nurses,so as to provide a basis in career development and management practices among the nutrition specialist nurses.Methods A method of descriptive phenomenological research was adopted in this study.Purposive sampling was used to select 12 nutrition specialist nurses who came from different regions across the country with over one year of clinical working experiences as well as had completed the specialist training and been qualified by the Nutrition Committee of Guangdong Nursing Association between January and February 2024.Semi-structured on-line interviews were conducted among the participants and the data acquired from the interviews were analysed and summarised.Themes were extracted using NVivo12 and Colaizzi's seven-step analysis from the data from interview.Results Three main themes and eight sub-themes were identified regarding the work experience of nutrition specialist nurses:growth and gains(continuously learning in nutrition therapy-related knowledge to enhance professional skills;actively practice in nutrition therapy to achieve the self-worth);sense of responsibility and mission(increased awareness of responsibility and proactive services;sense of mission to cultivate talents and promotion of the development of nutrition nursing discipline);challenges(lack of an established role in nutrition nursing,conflict in responsibilities;insufficient communication in a medical team regarding nutrition therapy;limited resource to support the development of nutrition nursing;and the professional knowledge and skills unable to fully meet the job demands).Conclusion Hospitals managers should strengthen the support and training for nutrition specialist nurses,clarify their roles,leverage their professional value and promote the career development.

Objective:To analyze a novel intronic variant in the SPTB gene and explore its effect on SPTB mRNA splicing.Methods:Clinical data of a child diagnosed with hereditary spherocytosis (HS) and admitted to the First Affiliated Hospital of Xi′an Jiaotong University in February 2022 were analyzed retrospectively. Whole genome sequencing was used to identify disease-causing variantions and the results were validated with Sanger sequencing, mRNA sequencing was used to determine the SPTB gene′s mRNA expression level, and bioinformatics tools were used for splicing site prediction and analysis.Results:The proband is a 2-month-old Han male child, clinically presenting with anemia and jaundice. In the past, jaundice appeared early and was severe during the neonatal period, with significantly elevated indirect bilirubin (203.5 μmol/L), accompanied by moderate anemia. This family consisted of four generations, eight of whom suffered from splenomegaly, jaundice, and anemia. In their peripheral blood, the percentage of microglobular erythrocytes was between 5% and 10%. Under scanning electron microscopy analysis of the proband's father's peripheral red blood cells, about 6% exhibited a mouth-shaped morphology, about 4% were spherical, and about 3% were oval. Following the splenectomy, the father′s anemia and jaundice recovered to normal level. Whole genome sequencing analysis of the proband identified a heterozygous variant in the SPTB gene (NM_ 001355436.2 (SPTB):c.6022+4_6022+18delinsTGGCTCCTCCGTGAAGGGACAGTCCTGC), which was verified to be co-segregating with the disease in this family line by Sanger sequencing. The results of the SPTB gene mRNA expression level detection showed that the expression levels of the SPTB variant gene were statistically increased in the proband and affected family members (father, grandmother, cousin, second cousin, great-grandmother, great-aunt) (all P<0.05). The SPTB gene′s intron can undergo selective splicing, as demonstrated by analysis using the bioinformatics program ESE Finder. Additionally, predictions from the SpliceAI and SpliceTool software indicated that activation of a new covert splicing donor can result in a code-shift variantion that introduces an early termination codon and nonsense-mediated degradation of the mRNA, which prevents the synthesis of proteins. Conclusion:A new variantion site c.6022+4_6022+18delinsTGGCTCCTCCGTGAAGGGACAGTCCTGC was found in SPTB gene. This variantion was the pathogenic factor of HS. By affecting the splicing process, this variantion triggers the nonsense mediated mRNA degradation pathway, resulting in inactivation of gene function.

Objective To explore the feasibility of predicting expression level of Ki-67 in lung adenocarcinoma via multi-parameter of spectral CT.Methods The data of 226 patients with lung adenocarcinoma confirmed by pathology were analyzed retrospectively.The conventional and spectral CT parameters of the lesions were analyzed.According to Ki-67 expression level,all patients were divided into low expression group and high expression group.The parameters with statistical significance were identified as independent variables for multivariate logistic regression analysis to establish a logistic regression model for predicting the expression level of Ki-67.Receiver operating characteristic(ROC)curve was used to assess the diagnostic performance for each model,respectively.Results There were significant differences in the clinical factors of gender,smoking and chest pain between high and low Ki-67 expression groups.In spectral CT parameters,CT40 keV,CT100 keV,Z-effective(Zeff)and iodine concentration(IC)in the high expression group in arterial phase were significantly higher than those in the low expression group.Logistic regression analysis showed that CT100 keV was the independent risk factor for Ki-67 expression level.Both the spectral CT model and the combined model had high value in predicting the expression level of Ki-67 in lung adenocarcinoma,and the combined model had better diagnostic efficacy.Conclusion Spectral CT parameters combined with clinical factors have a certain value in predicting the expression level of Ki-67 in lung adenocarcinoma.

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.
Musa/genetics* ; Phylogeny ; Fungal Proteins ; Cell Nucleus ; Histones ; Stress, Physiological/genetics*

Objective To understand the distribution of ecological suitability of Scutellaria baicalensis Georgi;To screen the main ecological factors affecting its distribution;To predict its suitable planting area in China.Methods A total of 231 batches of Scutellaria baicalensis Georgi were collected through the fourth national survey of TCM resources.The environment information of sampling points were recorded,and 55 ecological factors were analyzed by MaxEnt model and GIS.Results Rainfall,vegetation type and soil types had a greater influence on the distribution of Scutellaria baicalensis Georgi.The ecological suitable areas of Scutellaria baicalensis Georgi mainly concentrated in the eastern part of Shaanxi Province,the western part of Hebei Province and most areas of Chengde,the most part of Shanxi Province,the western part of Beijing,the western part of Liaoning Province,the central and eastern part of Shandong Province,the junction of Jiangsu and Anhui Province,the northern part of Yunnan Province,and the eastern and southern part of Sichuan Province.Conclusion The ecological suitability areas of Scutellaria baicalensis Georgi were classified in this study,and the results could provide reference for the selection of cultivation areas of Scutellaria baicalensis Georgi.

Objective:To observe the impact of core stability training in the sling exercise therapy pattern on the balance of stroke survivors.Methods:Sixty stroke survivors were randomly divided into a control group ( n=30) and an experimental group ( n=30). In addition to routine rehabilitation training, the control group received traditional core stability training, while the experimental group underwent core stability training applying the sling exercise therapy pattern. Before and after 4 weeks of training, the standing balance of both groups was evaluated using the Prokin balance trainer, with the length and area of motion recorded when performing the balance test with the eyes open and closed. Surface electromyography was used to record the average EMG (AEMG) values of the bilateral erector spinae and multifidus muscles during the balance testing. Results:After the 4 weeks of training the length and the area of progression of the center of the pressure were both significantly smaller for both groups than before the training with the eyes both open and closed. The average length and area in the experimental group were significantly less than among the controls. The AEMG values recorded during the balance tests were significantly higher than those before the intervention for both groups, with the multifidus muscle averages on the affected side significantly greater in the experimental group than among the controls when performing the balance test with the eyes closed.Conclusion:Core stability training in the sling exercise therapy pattern is superior to conventional core stability training because it can better improve the balance of stroke survivors.