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Background Tumor growth rate (TGR) is a dynamic biomarker for evaluating therapeutic response and prognosis in unresectable hepatocellular carcinoma (uHCC) with triple therapy, yet its clinical utility and role in guiding treatment optimization require further validation. Methods This study included 68 uHCC patients receiving transarterial chemoembolization (TACE) with systemic combination therapy. Propensity score matching (PSM) was applied to balance baseline confounders. Cubic spline models explored nonlinear associations between TGR and survival risk and found the ideal cut-off points. Kaplan-Meier (KM) analysis compared overall survival (OS) and progression-free survival (PFS) between TGR subgroups, Cox multivariate regression evaluated the independent prognostic value of TGR. Results Cox analysis confirmed TGR0 as an independent prognostic factor for OS (hazard ratio (HR) 1.035, 95% confidence interval (CI): 1.013–1.057, p  = 0.020) and PFS (HR 1.033, 95%CI: 1.014–1.053, p  = 0.001). After stratified for TGR0/TGR1 and matched, the low-TGR0 group showed significantly longer median OS (not reached vs. 13.09 months, p  = 0.002) and PFS (12.11 vs. 4.38 months, p  = 0.006) than the high-TGR0 group. In the subgroup analysis, after propensity score matching(PSM), the low-TGR1 group demonstrated a more favorable prognosis compared with high-TGR1(mOS: not reached vs. 16.97 months, p  = 0.024; mOS1: not reached vs. 11.78 months, p  = 0.022). Conclusions Dynamic TGR monitoring identifies heterogeneous therapeutic responses, guiding timely personalized treatment adjustments and prognostic stratification in uHCC.

Questionnaires have been used in the past 2 decades to predict the diagnosis of vertigo and assist clinical decision-making. A questionnaire-based machine learning model is expected to improve the efficiency of diagnosis of vestibular disorders. This study aims to develop and validate a questionnaire-based machine learning model that predicts the diagnosis of vertigo. In this multicenter prospective study, patients presenting with vertigo entered a consecutive cohort at their first visit to the ENT and vertigo clinics of 7 tertiary referral centers from August 2019 to March 2021, with a follow-up period of 2 months. All participants completed a diagnostic questionnaire after eligibility screening. Patients who received only 1 final diagnosis by their treating specialists for their primary complaint were included in model development and validation. The data of patients enrolled before February 1, 2021 were used for modeling and cross-validation, while patients enrolled afterward entered external validation. A total of 1693 patients were enrolled, with a response rate of 96.2% (1693/1760). The median age was 51 (IQR 38-61) years, with 991 (58.5%) females; 1041 (61.5%) patients received the final diagnosis during the study period. Among them, 928 (54.8%) patients were included in model development and validation, and 113 (6.7%) patients who enrolled later were used as a test set for external validation. They were classified into 5 diagnostic categories. We compared 9 candidate machine learning methods, and the recalibrated model of light gradient boosting machine achieved the best performance, with an area under the curve of 0.937 (95% CI 0.917-0.962) in cross-validation and 0.954 (95% CI 0.944-0.967) in external validation. The questionnaire-based light gradient boosting machine was able to predict common vestibular disorders and assist decision-making in ENT and vertigo clinics. Further studies with a larger sample size and the participation of neurologists will help assess the generalization and robustness of this machine learning method.

Cisplatin is widely used for chemotherapy of a variety of malignancies. However, the clinical application of cisplatin is hampered by the resultant irreversible hearing loss due to hair cell apoptosis. To date, no practical regimen to resolve this has been developed. Meanwhile, the role of microRNA in protecting hair cells from cisplatin-induced apoptosis in the inner ear has not been extensively investigated. In this study, we monitored miR-183, -96, and -182 turnover in the cochlea during cisplatin treatment in vitro . We found that overexpression of miR-182, but not miR-183 and -96, improved hair cell survival after 3  μ M cisplatin treatment in vitro . We demonstrated that overexpression of miR-182 repressed the intrinsic apoptotic pathway by inhibiting the translation of FOXO3a. Our study offers a new therapeutic target for alleviating cisplatin-induced hair cell apoptosis in a rapid and tissue-specific manner.

Background Chemoresistance is a primary clinical challenge for the management of small cell lung cancer. Additionally, transcriptional regulation by super enhancer (SE) has an important role in tumor evolution. The functions of SEs, a key class of noncoding DNA cis -regulatory elements, have been the subject of many recent studies in the field of cancer research. Methods In this study, using chromatin immunoprecipitation-sequencing and RNA-sequencing (RNA-seq), we aimed to identify SEs associated with chemoresistance from H69AR cells. Through integrated bioinformatics analysis of the MEME chip, we predicted the master transcriptional factors (TFs) binding to SE sites and verified the relationships between TFs of SEs and drug resistance by RNA interference, cell counting kit 8 assays, quantitative real-time reverse transcription polymerase chain reaction. Results In total, 108 SEs were screened from H69AR cells. When combining this analysis with RNA-seq data, 45 SEs were suggested to be closely related to drug resistance. Then, 12 master TFs were predicted to localize to regions of those SEs. Subsequently, we selected forkhead box P1 (FOXP1), interferon regulatory factor 1 (IRF1), and specificity protein 1 (SP1) to authenticate the functional relationships of master TFs with chemoresistance via SEs. Conclusions We screened out SEs involved with drug resistance and evaluated the functions of FOXP1, IRF1, and SP1 in chemoresistance. Our findings established a large group of SEs associated with drug resistance in small cell lung cancer, revealed the drug resistance mechanisms of SEs, and provided insights into the clinical applications of SEs.

Generally, deciduous and evergreen trees coexist in subtropical forests, and both types of leaves are attacked by numerous insect herbivores. However, trees respond and defend themselves from herbivores in different ways, and these responses may vary between evergreen and deciduous species. We examined both the percentage of leaf area removed by herbivores as well as the percentage of leaves attacked by herbivores to evaluate leaf herbivore damage across 14 subtropical deciduous and evergreen tree species, and quantified plant defenses to varying intensities of herbivory. We found that there was no significant difference in mean percentage of leaf area removed between deciduous and evergreen species, yet a higher mean percentage of deciduous leaves were damaged compared to evergreen leaves (73.7% versus 60.2%). Although percent leaf area removed was mainly influenced by hemicellulose concentrations, there was some evidence that the ratio of non-structural carbohydrates:lignin and the concentration of tannins contribute to herbivory. We also highlight that leaf defenses to varying intensities of herbivory varied greatly among subtropical plant species and there was a stronger response for deciduous trees to leaf herbivore (e.g., increased nitrogen or lignin) attack than that of evergreen trees. This work elucidates how leaves respond to varying intensities of herbivory, and explores some of the underlying relationships between leaf traits and herbivore attack in subtropical forests.

The utricle is one of the five sensory organs in the mammalian vestibular system, and while the utricle has a limited ability to repair itself, this is not sufficient for the recovery of vestibular function after hair cell (HC) loss induced by ototoxic drugs. In order to further explore the possible self-recovery mechanism of the adult mouse vestibular system, we established a reliable utricle epithelium injury model for studying the regeneration of HCs and examined the toxic effects of 3,3′-iminodiproprionitrile (IDPN) on the utricle in vivo in C57BL/6J mice, which is one of the most commonly used strains in inner ear research. This work focused on the epithelial cell loss, vestibular dysfunction, and spontaneous cell regeneration after IDPN administration. HC loss and supporting cell (SC) loss after IDPN treatment was dose-dependent and resulted in dysfunction of the vestibular system, as indicated by the swim test and the rotating vestibular ocular reflex (VOR) test. EdU-positive SCs were observed only in severely injured utricles wherein above 47% SCs were dead. No EdU-positive HCs were observed in either control or injured utricles. RT-qPCR showed transient upregulation of Hes5 and Hey1 and fluctuating upregulation of Axin2 and β-catenin after IDPN administration. We conclude that a single intraperitoneal injection of IDPN is a practical way to establish an injured utricle model in adult C57BL/6J mice in vivo. We observed activation of Notch and Wnt signaling during the limited spontaneous HC regeneration after vestibular sensory epithelium damage, and such signaling might act as the promoting factors for tissue self-repair in the inner ear.

Otitis media with effusion (OME) is a non-suppurative inflammation of the middle ear that is characterized by middle ear effusion and hearing loss. However, the mechanisms of OME are not fully understood. The aim of this study was to determine the function and the mechanism of the IL-17 cytokine in the pathogenesis of OME and to investigate IL-17 as a potential strategy for the treatment of OME. In this study, the OME rat model was induced by ovalbumin (OVA) as previously described. The severity of OME was determined with an oto-endoscope, by histochemical analysis, and by acoustic immittance. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of RNA-sequencing (RNA-seq) data was carried out to analyze the signaling pathways related to the pathogenesis of OME, which indicated that IL-17 is involved in OME. The anti-IL-17A monoclonal antibody was administrated by nasal drip to block IL-17 to treat OME in the rat model. The rats were finally injected intraperitoneally with the inhibitor of Notch signaling pathway to study the mechanisms of IL-17-induced inflammation. Serum and lavage fluid were collected for the detection of related cytokines, and middle ear tissue was collected for Western blot, quantitative real-time PCR (qRT-PCR), and immunohistochemical and immunofluorescence analysis. KEGG analysis of RNA-seq data suggested that the IL-17 signaling pathway might be involved in the onset of OME. IL-17 expression was confirmed to be increased in both the serum and the middle ear of the rat model. The monoclonal antibody against IL-17 neutralized IL-17, inhibited the inflammation in the middle ear, and reduced the overall severity of OME in vivo. Furthermore, the Notch signaling pathway was activated upon IL-17 upregulation in OME and was suppressed by IL-17 blockage. However, there was no change in IL-17 expression after Notch inhibitor treatment, which reduced the severity of OME in the rat middle ear. IL-17 plays a key role in the pathogenesis of the OVA-induced OME rat model. IL-17 induced inflammatory responses via the Notch signaling pathway and targeting IL-17 might be an effective approach for OME therapy.

microRNAs are regulatory molecules regarded as important in the pathogenesis of different types of tumors. microRNA-216a (miR-216a-5p) has been identified as a tumor suppressor in multiple malignancies. However, the role of miR-216a-5p in the pathogenesis of small cell lung cancer (SCLC) remains obscure. The objective of this study was to investigate the role of the miR-216a-5p/Bcl-2 axis in SCLC pathogenesis. All the experimental methods used were as follows: microarray analysis, cell culture, transient, and stable gene transfection; real-time fluorescence PCR; Western blot; flow cytometry for cell cycle analysis; in vitro proliferation assay; in vitro wound healing experiment; in vivo xenograft model in nude mice; and dual luciferase reporter assay. All statistical analyses were carried out using GraphPad Prism 7 software. Statistical significance was analyzed by Student's -test or one-way ANOVA. <0.05 (typically compared with the negative control group) was considered as significant and is marked with an asterisk in the figures. In this study, we observed that miR-216a-5p is downregulated in SCLC cell lines compared to that in the normal human bronchial epithelial cell line 16-HBE. In vitro and in vivo experiments demonstrate that upregulation of miR-216a-5p significantly decreased cell growth and migration and its downregulation increased SCLC cell proliferation and migration and influenced the cell cycle. Using bioinformatics analyses, we predicted that the important antiapoptotic gene is targeted by miR-216a-5p, and we identified a functional miR-216a-5p binding site in the 3'-UTR of using luciferase reporter assay. Furthermore, we determined that suppression of miR-216a-5p modulated the expression of , Bax, and Bad proteins ( family proteins), while knockdown abrogated the effect of miR-216a-5p downregulation on cell proliferation, cell migration, and the cell cycle. Taken together, these findings suggest that miR-216a-5p regulates SCLC biology via family proteins. Therefore, our study highlights the role of the miR-216a-5p/ axis in SCLC pathogenesis.

This paper proposes a nonelliptic extended English teaching ability evaluation algorithm based on an adaptive random matrix model. The algorithm models a nonelliptical expansion target as multiple elliptical sub-objectives, and the expansion state of each sub-target is described by an inverse Wishart distribution. The new method is combined to improve the robustness problem caused by the initialization after the algorithm expansion. This research uses the smart teacher education platform to conduct research and analysis on the evaluation of teaching practice ability of intern normal students. From the perspective of data evaluation, we explore the influence of normal students’ curriculum training on the teaching practice ability of normal students. By analyzing the correlation between normal students’ course grades and practice grades, this paper explores the influence of normal students’ prepractice training on normal students’ teaching practice ability. This paper explores the influence of the training of normal students’ course learning on the teaching practice ability of normal students. The results show that the learning level of normal students’ professional courses has a significant impact on the development of normal students’ practice performance and teaching practice ability; the impact of normal students’ pedagogical course level on normal students’ practice performance and teaching practice ability is relatively low.

Ultrasound-assisted emulsification-microextraction coupled to HPLC was applied to the determination of propoxur in environmental and beverage samples. Carbon tetrachloride (the extraction solvent) is added to the aqueous sample, and the liquids are sonificated at 60 °C, upon which an emulsion is formed. This is followed by centrifugation the lower phase being analyzed by HPLC. The extraction solvent, its volume, extraction time, temperature and salt concentration were optimized. Linear range (0.01–10 µg mL -1 ), correlation coefficient (0.9965), detection limit (1 ng mL -1 at a SNR of 3), and precision (4.5% RSD, n  = 5) were determined. The technique was applied to the determination of propoxur in environmental and beverage samples and no target analyte was found in these samples. Therefore, samples were spiked and recoveries of 93–106% and RSDs of 1.5–6.2% were obtained.