Constructing and validating pan-apoptosis-related features for predicting prognosis and immunotherapy response in hepatocellular carcinoma.

The study aimed to develop a prognostic model for Hepatocellular Carcinoma (HCC) based on pan-apoptosis-related genes, a novel inflammatory programmed cell death form intricately linked to HCC progression. Utilizing transcriptome sequencing and clinical data from the TCGA database, we identified six crucial pan-apoptosis-related genes through statistical analyses. These genes were then employed to construct a prognostic model that accurately predicts overall survival rates in HCC patients. Our findings revealed a strong correlation between the model's risk scores and tumor microenvironment (TME) status, immune cell infiltration, and immune checkpoint expression. Furthermore, we screened for drugs with potential therapeutic efficacy in high- and low-risk HCC groups. Notably, PPP2R5B gene knockdown was found to inhibit HCC cell proliferation and clonogenic capacity, suggesting its role in HCC progression. In conclusion, this study presents a novel pan-apoptosis gene-based prognostic risk model for HCC, providing valuable insights into patient TME status and guiding the selection of targeted therapies and immunotherapies.

MiR-143-5p regulates the proangiogenic potential of human dental pulp stem cells by targeting HIF-1α/RORA under hypoxia: A laboratory investigation in pulp regeneration.

AIM: Angiogenesis is a key event in the successful healing of pulp injuries, and hypoxia is the main stimulator of pulpal angiogenesis. In this study, we investigated the effect of hypoxia on the proangiogenic potential of human dental pulp stem cells (hDPSCs) and the role of miR-143-5p in the process. METHODOLOGY: Human dental pulp stem cells were isolated, cultured and characterized in vitro. Cobalt chloride (CoCl2) was used to induce hypoxia in hDPSCs. CCK-8 and Transwell assays were used to determine the effect of hypoxia on hDPSCs proliferation and migration. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB) and ELISA were performed to assess the mRNA and protein levels of HIF-1α and angiogenic cytokines in hDPSCs. The effect of hypoxia on hDPSCs proangiogenic potential was measured in vitro using Matrigel tube formation and chick chorioallantoic membrane (CAM) assays. Recombinant lentiviral vectors were constructed to stably overexpress or inhibit miR-143-5p in hDPSCs, and the proangiogenic effects were assessed using qRT-PCR, WB, and tube formation assays. miR-143-5p target genes were identified and verified using bioinformatics prediction tools, dual-luciferase reporter assays and RNA pull-down experiments. Finally, a subcutaneous transplantation model in nude mice was used to determine the effects of hypoxia treatment and miR-143-5p overexpression/inhibition in hDPSCs in dental pulp regeneration. RESULTS: Hypoxia promotes hDPSCs proliferation, migration and proangiogenic potential. The in vivo experiments showed that hypoxia treatment (50 and 100 µM CoCl2) promoted pulp angiogenesis and dentine formation. In contrast to the levels of proangiogenic factors, miR-143-5p levels decreased with increasing CoCl2 concentration. miR-143-5p inhibition significantly promoted proangiogenic potential of hDPSCs, whereas miR-143-5p overexpression inhibited angiogenesis in vitro. Dual-luciferase reporter assay identified retinoic acid receptor-related orphan receptor alpha (RORA) as an miR-143-5p target gene in hDPSCs. RNA pull-down experiments demonstrated that HIF-1α and RORA were pulled down by biotin-labelled miR-143-5p, and the levels of HIF-1α and RORA bound to miR-143-5p in the hypoxia group were lower than those in the normoxia group. Inhibition of miR-143-5p expression in hDPSCs promoted ectopic dental pulp tissue regeneration. CONCLUSIONS: CoCl2-induced hypoxia promotes hDPSCs-driven paracrine angiogenesis and pulp regeneration. The inhibition of miR-143-5p upregulates the proangiogenic potential of hDPSCs under hypoxic conditions by directly targeting HIF-1α and RORA.

Application of digital virtual simulated design in the prosthodontic rehabilitation of a child with a novel EDA mutation in ectodermal dysplasia: A clinical report.

This clinical report presents a 7-year-old patient with ectodermal dysplasia and a newly identified ectodysplasin A (EDA) gene mutation (c.965 T>C). A removable partial denture combined with a complete denture was provided after considering the relevant factors. Based on digital smile design, resin crowns were fabricated to restore the cone-shaped teeth esthetically. Facial scan parameters and maxillofacial landmark localization on cone beam computed tomography (CBCT) images were combined for the registration of jaw relation, and a Gothic arch was subsequently 3-dimensionally printed for verification. Ultimately, dentures with accurate occlusion and satisfactory retention were delivered for this young patient with inadequate bone volume and poor fit that markedly improved his esthetics and function.

Measurement of thresholds using Chirp-ABR in children with auditory neuropathy spectrum disorder and sensorineural hearing loss.

AIM: This study explored the value of Chirp-auditory brainstem response (ABR) thresholds in assessing the hearing threshold of children diagnosed with auditory neuropathy spectrum disorder (ANSD). METHODS: A total of 20 children with ANSD (40 ears, aged 1.5-7.0 years, median age 4.5 years) and 31 children with sensorineural hearing loss (SNHL) (52 ears, aged 0.9-8.0 years, median age 3.7 years) were included. Besides, 25 normal children (50 ears, aged 0.8-7.5 years, median age 4.6 years) were used as controls. Chirp-ABR and behavioral audiometry were performed simultaneously among three groups of children, allowing for a comparison of the thresholds obtained through both methods. RESULTS: In ANSD children, the correlation (r-values) between the thresholds obtained from Chirp-ABR and behavioral audiometry at 500-4000 Hz were 0.84, 0.67, 0.59, and 0.60, respectively. The average threshold differences between two methods ranged from 9.7 to 13.3 dB at 500-4000 Hz. Notably, 20 % ears (8/40) exhibited considerable discrepancies (>30 dB) in thresholds at certain frequencies. For SNHL children, the r-values between two methods were 0.84, 0.89, 0.92, and 0.93, respectively. The average threshold differences between two methods were 5.7-8.2 dB at 500-4000 Hz. Similarly, in normal children, the average threshold differences between two methods ranged from 6.1 dB to 7.7 dB, the r-values were 0.81, 0.78, 0.80, and 0.80 at 500-4000 Hz, respectively. CONCLUSION: Chirp-ABR threshold is not suitable to predict the behavioral audiometry threshold in ANSD children. When there is a significant discrepancy (>30 dB) between Chirp-ABR thresholds and behavioral audiometry thresholds in hearing loss, ANSD should be highly suspected.

Effects of edaravone dexborneol on functional outcome and inflammatory response in patients with acute ischemic stroke.

BACKGROUND: Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating the impact of edaravone dexborneol on functional outcomes and systematic inflammatory response in AIS patient. METHODS: All participants were recruited from the AISRNA study (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 and December 2022. The AIS patients were divided into two groups based on whether they received the treatment of edaravone dexborneol (37.5 mg/12 hours, IV) within 48 h after stroke onset. Inflammatory response was determined by detecting levels of cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, and IL-1ß) within 14 days after stroke onset. RESULTS: Eighty-five AIS patients were included from the AISRNA study. Patients treated with edaravone dexborneol showed a significantly higher proportion of modified Rankin Scale score < 2 compared to those who did not receive this treatment (70.7% versus 47.8%; P = 0.031). Furthermore, individuals receiving edaravone dexborneol injection exhibited lower expression levels of interleukin (IL)-1ß, IL-6, and IL-17, along with higher levels of IL-4 and IL-10 expression during the acute phase of ischemic stroke (P < 0.05). These trends were not observed for IL-2, IL-5, IL-8, IL-12p70, tumor necrosis factor-α, interferon-γ [IFN-γ], and IFN-α (P > 0.05). CONCLUSIONS: Treatment with edaravone dexborneol resulted in a favorable functional outcome at 90 days post-stroke onset when compared to patients without this intervention; it also suppressed proinflammatory factors expression while increasing anti-inflammatory factors levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www. CLINICALTRIALS: gov/ct2/show/NCT04175691 .

Theaflavin -3,3'-digallate/ethanol: a novel cross-linker for stabilizing dentin collagen.

Objectives: To study the ability of theaflavin-3,3'-digallate (TF3)/ethanol solution to crosslink demineralized dentin collagen, resist collagenase digestion, and explore the potential mechanism. Methods: Fully demineralized dentin blocks were prepared using human third molars that were caries-free. Then, these blocks were randomly allocated into 14 separate groups (n = 6), namely, control, ethanol, 5% glutaraldehyde (GA), 12.5, 25, 50, and 100 mg/ml TF3/ethanol solution groups. Each group was further divided into two subgroups based on crosslinking time: 30 and 60 s. The efficacy and mechanism of TF3's interaction with dentin type I collagen were predicted through molecular docking. The cross-linking, anti-enzymatic degradation, and biomechanical properties were studied by weight loss, hydroxyproline release, scanning/transmission electron microscopy (SEM/TEM), in situ zymography, surface hardness, thermogravimetric analysis, and swelling ratio. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy were utilized to explore its mechanisms. Statistical analysis was performed using one and two-way analysis of variance and Tukey's test. Results: TF3/ethanol solution could effectively crosslink demineralized dentin collagen and improve its resistance to collagenase digestion and biomechanical properties (p < 0.05), showing concentration and time dependence. The effect of 25 and 50 mg/ml TF3/ethanol solution was similar to that of 5% GA, whereas the 100 mg/mL TF3/ethanol solution exhibited better performance (p < 0.05). TF3 and dentin type I collagen are mainly cross-linked by hydrogen bonds, and there may be covalent and hydrophobic interactions. Conclusion: TF3 has the capability to efficiently cross-link demineralized dentin collagen, enhancing its resistance to collagenase enzymatic hydrolysis and biomechanical properties within clinically acceptable timeframes (30 s/60 s). Additionally, it exhibits promise in enhancing the longevity of dentin adhesion.

Nucleus-targeting DNase I self-assembly delivery system guided by pirarubicin for programmed multi-drugs release and combined anticancer therapy.

The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy.

Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Expert consensus on irrigation and intracanal medication in root canal therapy.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.

Tonsil microbiome in pediatric patients with post tonsillectomy hemorrhage for tonsillar hypertrophy.

OBJECTIVE: This study aimed to compare the tonsillar microbiota between post tonsillectomy patients with bleeding and without bleeding, and to investigate the potential role of tonsillar microbiota in the development of post-tonsillectomy hemorrhage (PTH). METHODS: Nineteen tonsillar tissues from PTH patients and 21 tissues from control patients were collected. Metagenomic sequencing was used to compare the microbiota in PTH and control groups. Alpha diversity indices were used to compare the richness and evenness of the microbiota between the two groups. PCoA and NMDS analyses were used to evaluate beta diversity. LDA analysis was conducted to identify significantly abundant genera. RESULTS: No significant difference in alpha diversity indices was found between PTH and control patients. The dominant bacteria in the tonsillar microbiota were Haemophilus, Streptococcus, and Fusobacterium. PCoA and NMDS analyses showed significant differences in beta diversity between PTH and control patients. PTH patients had a significantly higher relative abundance of Neisseria, Capnocytophaga, and Veillonella. Capnocytophaga was also identified as a significantly abundant genus by LDA analysis. CONCLUSION: This study demonstrates that there is a difference in the tonsillar microbiota between PTH and control patients. The results suggest that Neisseria, Capnocytophaga, and Veillonella may be associated with the development of PTH. These findings provide new insights into the potential role of the tonsillar microbiota in the development of PTH, and may help to develop new strategies for preventing and treating this potentially life-threatening complication.

Expert consensus on digital guided therapy for endodontic diseases.

Digital guided therapy (DGT) has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades. The concept of DGT for endodontic diseases is categorized into static guided endodontics (SGE), necessitating a meticulously designed template, and dynamic guided endodontics (DGE), which utilizes an optical triangulation tracking system. Based on cone-beam computed tomography (CBCT) images superimposed with or without oral scan (OS) data, a virtual template is crafted through software and subsequently translated into a 3-dimensional (3D) printing for SGE, while the system guides the drilling path with a real-time navigation in DGE. DGT was reported to resolve a series of challenging endodontic cases, including teeth with pulp obliteration, teeth with anatomical abnormalities, teeth requiring retreatment, posterior teeth needing endodontic microsurgery, and tooth autotransplantation. Case reports and basic researches all demonstrate that DGT stand as a precise, time-saving, and minimally invasive approach in contrast to conventional freehand method. This expert consensus mainly introduces the case selection, general workflow, evaluation, and impact factor of DGT, which could provide an alternative working strategy in endodontic treatment.

[Clinical analysis of 102 cases of pediatric vocal fold nodules].

Objective:To evaluate the impact of vocal fold nodules on the quality of life of children, and to compare the efficacy between conservative management（voice hygiene education, etc.） and laryngeal microsurgery. Methods:A retrospective study was performed on 102 children with vocal fold nodules, who received treatment in Children's Hospital of Fudan University during the period from January 2020 to December 2022. According to the regime, the patients were divided into conservative management group and surgical treatment group; Cases are divided into pre-school age group （2-5 years old） and school-age group （6-12 years old） based on age. The pediatric voice-related quality of life （pVRQOL） was used to evaluate the impact of vocal fold nodules on the quality of life of children and differences in efficacy between two treatment regimens. Results:The pVRQOL scores of vocal fold nodule grades 1, 2, and 3 were 91.58±8.17, 78.87±12.49, 72.50±12.08, respectively. There were statistical differences between grade 1 and grade 2, and between grade 2 and grade 3. There were statistical differences between grade 1 grade 2, grade 2 and grade 3 （P<0.001）, suggesting that the higher the rating of vocal cord nodules, the lower the pVRQOL score of patients was. The pVRQOL score of the school-age group was 69.83±11.11, which is lower than that of the preschool group（87.59±8.63）, and the difference was statistically significant （P=0.042）. Vocal fold nodules had a significant impact on the pVRQOL score of school-age children. In the conservative management group, the pVRQOL scores before and after treatment were 83.99±12.66 and 87.26±9.58, respectively, and there was significant difference between the two groups（P=0.046）. Indirect voice therapy such as voice hygiene education could improve children's pVRQOL scores and was more effective for school-age children（P<0.001）. The microsurgical treatment had a more significant improvement in the pVRQOL score of children. Conclusion:The higher the rating of vocal fold nodules, the greater the impact on the quality of life of patients. Vocal fold nodules had a greater impact on the quality of life of school-age children than that of preschool children. Voice hygiene education could improve the quality of life of children, which was more evident in the school-age group. Compared with voice hygiene therapy, laryngeal microsurgery had a more significant effect on improving the pVRQOL score of patients. It is recommended to undergo laryngeal microsurgery for the treatment of vocal fold nodules for the requirement of improving the quality of life related to voice. During the 6-month follow-up period after surgery in this study, the short-term efficacy of laryngeal microsurgery in treating vocal cord nodules in children is clear, but the long-term efficacy needs further research.

[New progress in the surgical treatment of laryngeal cyst in infants and children].

Laryngeal cyst is a cystic lesion occurring in the laryngeal cavity. Large laryngeal cyst in infants and young children can cause laryngeal wheezing and other upper airway obstruction symptoms. In severe cases, it can be even life-threatening and requires timely surgical treatment. Currently, there is a lack of unified clinical treatment strategy for this disease.This article summarizes the surgical methods, the advantages and disadvantages of various surgical methods for laryngeal cysts in recent years. It is recommended that needle aspiration, partial cyst wall resection, radical cyst dissection, transoral robotic surgery or external approach cyst resection should be selected through full communication and evaluation to clarify the extent of the lesion scope and the advantages and disadvantages of surgery.

Clinical Features and Outcomes of Omicron-Associated Croup in Children.

Objective: This study was aimed to describe the clinical features and outcomes of Omicron-associated croup in children. Methods: A total of 105 children aged 3-60 months (median age 11 months) with coronavirus disease 2019 (COVID-19) and cough were admitted to our hospital from December 16, 2022, to December 31, 2022. Their clinical features, treatment, and outcomes were reviewed. These children were followed up for 8 months. Results: Among the cases, 5 had complex medical histories, while the other children were generally healthy. Out of the cases, 41 (38.3%), 57 (54.4%), and 7 (6.7%) had mild, moderate, and severe laryngeal obstruction, respectively. They developed croup after 1-5 days of fever (median 2 days). The majority (90.5%) of COVID-19 children with croup did not have pneumonia, and most of them (64.8%) had decreased eosinophil counts. Additionally, most other blood routine indicators were normal. Five other viral infections (chlamydia pneumoniae, respiratory syncytial virus, adenovirus, coxsackie virus, and mycoplasma pneumoniae) were tested in 51 cases, and all results were negative. All cases recovered from croup after receiving prompt nebulization therapy and/or intravenous drip of hormone. The hospitalization rate was 6.7%. During the 8-month follow-up period, 71 cases experienced repeated fever due to various infections, but only 4 cases (4/105, 3.8%) had repeated croup. Conclusion: Omicron is a risk factor for croup, with most cases presenting mild to moderate laryngeal obstructions. Co-viral infection testing is unnecessary for such cases. The symptoms of Omicron-associated croup may be more severe than croup associated with other viruses; however, unnecessary hospitalizations can be avoided, leading to reduced healthcare expenses.

Efficient expansion and delayed senescence of hUC-MSCs by microcarrier-bioreactor system.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are widely used in cell therapy due to their robust immunomodulatory and tissue regenerative capabilities. Currently, the predominant method for obtaining hUC-MSCs for clinical use is through planar culture expansion, which presents several limitations. Specifically, continuous cell passaging can lead to cellular aging, susceptibility to contamination, and an absence of process monitoring and control, among other limitations. To overcome these challenges, the technology of microcarrier-bioreactor culture was developed with the aim of ensuring the therapeutic efficacy of cells while enabling large-scale expansion to meet clinical requirements. However, there is still a knowledge gap regarding the comparison of biological differences in cells obtained through different culture methods. METHODS: We developed a culture process for hUC-MSCs using self-made microcarrier and stirred bioreactor. This study systematically compares the biological properties of hUC-MSCs amplified through planar culture and microcarrier-bioreactor systems. Additionally, RNA-seq was employed to compare the differences in gene expression profiles between the two cultures, facilitating the identification of pathways and genes associated with cell aging. RESULTS: The findings revealed that hUC-MSCs expanded on microcarriers exhibited a lower degree of cellular aging compared to those expanded through planar culture. Additionally, these microcarrier-expanded hUC-MSCs showed an enhanced proliferation capacity and a reduced number of cells in the cell cycle retardation period. Moreover, bioreactor-cultured cells differ significantly from planar cultures in the expression of genes associated with the cytoskeleton and extracellular matrix. CONCLUSIONS: The results of this study demonstrate that our microcarrier-bioreactor culture method enhances the proliferation efficiency of hUC-MSCs. Moreover, this culture method exhibits the potential to delay the process of cell aging while preserving the essential stem cell properties of hUC-MSCs.

Neighboring Platinum Atomic Sites Activate Platinum-Cobalt Nanoclusters as High-Performance ORR/OER/HER Electrocatalysts.

The rational design of efficient and multifunctional electrocatalysts for energy conversion devices is one of the major challenges for clean and renewable energy transition. Herein, the local electronic structure of cobalt-platinum nanoclusters is regulated by adjacent platinum atomic site encapsulated in N-doped hollow carbon nanotubes (PtSA -PtCo NCs/N-CNTs) by pyrolysis of melamine-orientation-induced zeolite imidazole metal-organic frameworks (ZIF-67) with thimbleful platinum doping. The introduction of melamine can reactivate adjacent carbon atoms and initiate the oriented growth of nitrogen-doped carbon nanotubes. The systematic analysis suggests the significant role of thimbleful neighboring low-coordinated Pt─N2 in altering the localized electronic structure of PtCo nanoclusters. The optimized PtSA -PtCo NCs/N-CNTs-900 exhibit excellent hydrogen evolution reaction (HER)/oxygen evolution reaction (OER)/oxygen reduction reaction (ORR)/ catalytic performance reaching the current density of 10 mA cm-2 in 1 m KOH under the low 47 (HER) and 252 mV (OER) overpotentials, and a high half-wave potential of 0.86 and 0.89 V (ORR) in 0.1 m KOH and 0.1 m HClO4 , respectively. Remarkably, the PtSA -PtCo NC/N-CNT-900 also presents outstanding catalytic performances toward water splitting and rechargeable Zn-air batteries. The theoretical calculations reveal that optimal regulation of the electronic structure of PtCo nanoclusters by thimbleful neighboring Pt atomic reduces the reaction energy barrier in electrochemical process, facilitating the ORR/OER/HER performance.

Antioxidants Improve the Proliferation and Efficacy of hUC-MSCs against H2O2-Induced Senescence.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are broadly applied in clinical treatment due to convenient accessibility, low immunogenicity, and the absence of any ethical issues involved. However, the microenvironment of inflammatory tissues may cause oxidative stress and induce senescence in transplanted hUC-MSCs, which will further reduce the proliferation, migration ability, and the final therapeutic effects of hUC-MSCs. Beta-nicotinamide mononucleotide (NMN) and coenzyme Q10 (CoQ10) are famous antioxidants and longevity medicines that could reduce intracellular reactive oxygen species levels by different mechanisms. In this study, hUC-MSCs were treated in vitro with NMN and CoQ10 to determine if they could reduce oxidative stress caused by hydrogen peroxide (H2O2) and recover cell functions. The effects of NMN and CoQ10 on the cell proliferation, the mRNA levels of the inflammatory cytokine TNFα and the anti-inflammatory cytokine IL10, and the differentiation and cell migration ability of hUC-MSCs before and after H2O2 treatment were investigated. The findings revealed that NMN and CoQ10 reduced H2O2-induced senescence and increased hUC-MSCs' proliferation in the late phase as passage 12 and later. The TNFα mRNA level of hUC-MSCs induced by H2O2 was significantly decreased after antioxidant treatment. NMN and CoQ10 all reduced the adipogenic differentiation ability of hUC-MSCs. CoQ10 improved the chondrogenic differentiation ability of hUC-MSCs. Furthermore, NMN was found to significantly enhance the migration ability of hUC-MSCs. Transcriptomic analysis revealed that NMN and CoQ10 both increased DNA repair ability and cyclin expression and downregulated TNF and IL-17 inflammatory signaling pathways, thereby contributing to the proliferative promotion of senecent stem cells and resistance to oxidative stress. These findings suggest that antioxidants can improve the survival and efficacy of hUC-MSCs in stem cell therapy for inflammation-related diseases.

An integrative analysis of the tumor suppressors and oncogenes from sexual dimorphism and gene expression alteration features in thyroid cancer.

BACKGROUND: The incidence of thyroid cancer has risen rapidly over the last decades. Although mortality rates are relatively low compared to other cancers, the rate of new cases started to increase in the early 2000s. While tumor suppressors and oncogenes were recently identified in thyroid cancer, the potential roles of these genes in thyroid cancer remain unclear. OBJECTIVE: Analyze the roles and functions of tumor suppressors and oncogenes in thyroid cancer. METHODS: Thyroid cancer data were collected from public databases, such as the UCSC Xena database of TCGA thyroid cancer, TISIDB, and UALCAN. The genes frequently associated with unfavorable thyroid cancer were examined and validated. The association of these target genes with thyroid tumorigenesis, stages, subtypes, and survival rates were analyzed. Additionally, the genes aberrantly expressed in thyroid cancer and significantly involved in thyroid tumorigenesis, stages, subtypes, and survival rates were identified. RESULTS: Female sex was identified as a risk factor for thyroid cancer. The expression of PAPSS2, PDLIM3, COPZ2, ALDH1B1, ANTXR1, GUF1, and SENP6 negatively correlated with thyroid cancer prognosis. CONCLUSION: Female sex was a risk factor for thyroid cancer. In addition, our analysis suggested that PAPSS2, PDLIM3, COPZ2, ALDH1B1, ANTXR1, GUF1, and SENP6 are negatively correlated with the prognosis of thyroid cancer. The expression of ANTXR1, GUF1, and PDLIM3 was weakly associated with thyroid cancer's immune and molecular subtypes.

Short-term outcomes of infants with hyperbilirubinemia-associated auditory neuropathy spectrum disorder in neonatal intensive care unit.

OBJECTIVES: Hyperbilirubinemia is a high-risk factor for auditory neuropathy spectrum disorder (ANSD) as well as hearing loss in general. This study described the outcomes of hyperbilirubinemia-associated ANSD infants diagnosed in hearing screening in the neonatal intensive care unit (NICU). METHODS: A total of 578 children with hyperbilirubinemia admitted to the NICU between October 2020 and October 2021 were included in this study. The distortion product otoacoustic emission (DPOAE) and automatic auditory brainstem response (AABR) were combined for hearing screening, and those who failed the DPOAE or/and AABR underwent an auditory brainstem response (ABR) test. Infants with ANSD were followed up for 12 months. RESULTS: Forty infants (40/578, 6.9%) failed the DPOAE or/and AABR tests, of which, 13 (13/578, 2.2%) were diagnosed as ANSD, and 27 (27/578, 4.7%) were diagnosed as having sensorineural hearing loss (SNHL). Of the 13 ANSD infants followed up for 12 months, 7 recovered, 3 improved, 3 did not recover, and 1 was lost, equating to improved or recovered hearing in 75% (9/12) of ANSD infants at 12 months of age. Moreover, the maximum bilirubin in recovered or improved ANSD infants was 408.6 ± 129.0 µmol/L, while the maximum bilirubin in unrecovered ANSD infants was 749.3 ± 323.0 µmol/L. Furthermore, poorly differentiated and absent ABR waveforms were observed in 6 and 14 ears at 1 month, 2 ears were lost, 6 (6/6, 100.0%) and 6 (6/12, 50.0%) ears were recovered or improved at 12 months of age. CONCLUSION: s: The incidence of hyperbilirubinemia associated-ANSD was 2.2% of infants screened in the NICU. ANSD caused by hyperbilirubinemia may be transient, with most infants improving or recovering hearing by 12 months of age. Infants with poorly differentiated ABR waveforms and low bilirubin concentration are more likely to recover and hearing aids are not recommended in hyperbilirubinemia-associated ANSD below 12 months of age.

Deep learning for the screening of primary ciliary dyskinesia based on cranial computed tomography.

Objective: To analyze the cranial computed tomography (CT) imaging features of patients with primary ciliary dyskinesia (PCD) who have exudative otitis media (OME) and sinusitis using a deep learning model for early intervention in PCD. Methods: Thirty-two children with PCD diagnosed at the Children's Hospital of Fudan University, Shanghai, China, between January 2010 and January 2021 who had undergone cranial CT were retrospectively analyzed. Thirty-two children with OME and sinusitis diagnosed using cranial CT formed the control group. Multiple deep learning neural network training models based on PyTorch were built, and the optimal model was trained and selected to observe the differences between the cranial CT images of patients with PCD and those of general patients and to screen patients with PCD. Results: The Swin-Transformer, ConvNeXt, and GoogLeNet training models had optimal results, with an accuracy of approximately 0.94; VGG11, VGG16, VGG19, ResNet 34, and ResNet 50, which are neural network models with fewer layers, achieved relatively strong results; and Transformer and other neural networks with more layers or neural network models with larger receptive fields exhibited a relatively weak performance. A heat map revealed the differences in the sinus, middle ear mastoid, and fourth ventricle between the patients with PCD and the control group. Transfer learning can improve the modeling effect of neural networks. Conclusion: Deep learning-based CT imaging models can accurately screen for PCD and identify differences between the cranial CT images.