BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Obesity is a chronic low-grade inflammation and a risk factor for diseases such as diabetes， hypertension， dyslipidemia， and malignant tumors， demonstrating an increasingly grim development situation. The nuclear factor-kappa B （NF-κB） signaling pathway is a key signaling pathway involved in the immune response and inflammatory response. In obese individuals， the expression of NF-κB is overactivated， which leads to abnormal inflammatory responses in the body. Therefore， it is expected to alleviate inflammation and treat obesity by regulating the NF-κB signaling pathway， which has been proven effective by a large number of studies. The available studies on the NF-κB signaling pathway mostly focus on tumors， and there is no systematic review of the mechanism of this pathway in mediating obesity and the traditional Chinese medicine （TCM） treatment. We reviewed the research progress in the pathological and physiological processes of obesity mediated by NF-κB signaling pathway and TCM treatment， aiming to give insights into the clinical treatment of obesity with TCM and provide reference targets and research directions for exploring the biological foundations and the development of new TCM preparations.

Objective To explore the mechanism of Shanggan granules in suppressing pulmonary inflammation in mice infected with H1N1 influenza virus.Methods A mouse model of pulmonary influenza virus infection was established by nasal inoculation with H1N1 influenza virus.Mice were divided into a normal control group,model group,positive control group,and low-,medium-,and high-dose Shanggan granules groups.Mice were treated for 7 days and then sacrificed,and the body weight and lung wet weight were measured.Pathological changes in the lung tissues were detected by hematoxylin/eosin(HE)staining.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,and transforming growth factor-β(TGF-β)levels in lung tissues were detected by enzyme-linked immunosorbent assay,and superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected using appropriate kits.Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)inflammatory signaling pathways were detected by real-time polymerase chain reaction,and TANK-binding kinase 1(TBK1)/interferon regulatory factor(IRF)signaling pathway proteins were detected by Western blot.Results Both Shanggan granules and oseltamivir phosphate reduced the lung wet weight(P＜0.05,P＜0.001)in mice infected with influenza virus H1N1 compared with the model group,decreased the infiltration of inflammatory cells in lung tissue,reduced levels of the inflammatory factors TNF-α,IL-6,IL-8,and TGF-β(P＜0.05,P＜0.01,P＜0.001),decreased levels of SOD and GSH-Px in lung tissue(P＜0.05,P＜0.01),and increased MDA levels(P＜0.05,P＜0.01).Shanggan granules and oseltamivir phosphate also reduced TLR4,MyD88,and p38 mRNA levels(P＜0.05,P＜0.01)and expression of TBK1/IRF3/7/NF-κB signaling pathway proteins(P＜0.05,P＜0.01,P＜0.001).Conclusions Shanggan granules may effectively reduce lung injury,lung inflammation,and oxidative stress,via a mechanism related to the down-regulation of TLR4/NF-κB inflammatory signaling pathways.

Objective:To explore the feasibility and preliminary efficacy of domestic single-port robotic surgical system in the surgical treatment of thyroid cancer. Methods:Thyroid cancer patients who underwent domestic single-port robotic surgery in the Department of Head and Neck Surgery of Sichuan Cancer Hospital from June 2024 to January 2025 were prospectively included. Clinical data, oncological characteristics, and perioperative indicators were systematically collected. Results:A total of 7 patients were included, including 3 males and 4 females, with an age of （34.57±10.26） years. All procedures were successfully completed without conversion to open surgery. Operative time was（180.00±30.41） minutes. Blood loss was（5.00[15.00 ]）mL. Postoperative drainage volume was （167.86±130.95） mL. The postoperative pathological results were all thyroid papillary carcinoma. There were no system failures, no device-related complications and adverse events were observed during the operation and perioperative period. No tumor recurrence or metastasis was observed during the follow-up period. Conclusion:Preliminary data indicate that the domestic single-port robotic surgical system is safe and feasible for the surgical treatment of thyroid cancer, providing a practical basis for subsequent multi-disease, multi-center, and large-sample studies.
Humans ; Thyroid Neoplasms/surgery* ; Robotic Surgical Procedures/instrumentation* ; Male ; Female ; Adult ; Thyroidectomy/methods* ; Operative Time ; Middle Aged ; Prospective Studies

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.

Background Noise-induced hearing loss (NIHL) is a prevalent occupational health problem in workplace settings, with non-steady noise exposure being particularly widespread. Although kurtosis-adjusted equivalent sound level (\begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}) methods based on linear regression are available to assess hearing damage, the complexity of kurtosis effects necessitates introducing new metrics through nonlinear regression to improve predictive accuracy for hearing loss from non-steady noise exposure. Objective To examine the adjustment terms [\begin{document}$ \mathrm{lg}(\beta _{N}/{\beta }_{G}) $\end{document}] and coefficients (λ) of \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} using nonlinear regression and evaluate the method’s effectiveness in assessing occupational hearing loss associated with non-steady noise exposure. Methods A cross-sectional study design was employed, enrolling 1034 manufacturing workers and evaluating noise exposure to estimate hearing loss metrics. Quantile regression analysis quantified the proportional contributions of influencing factors for noise-induced permanent threshold shift at 3, 4, and 6 kHz frequencies (NIPTS₃₄₆). \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} was computed using multiple linear regression and nonlinear least squares optimization. Paired t-tests analyzed predictive efficacy before and after kurtosis adjustment to evaluate its impact on ISO 1999 NIPTS₃₄₆ predictions. Chow tests compared the similarity of logistic regression curves for high-frequency noise-induced hearing loss (HFNIHL) incidence between non-steady noise (\begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}) and steady noise (\begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document}), thereby validating the effectiveness of \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}. Results The quantile regression analysis showed that kurtosis was a significant indicator of occupational hearing loss risk from non-steady noise (contribution rate was 27.5%, P<0.05). The linear regression and nonlinear least squares methods obtained six different combinations of coefficients (λ) and adjustment terms [\begin{document}$ \mathrm{lg}(\beta _{N}/{\beta }_{G}) $\end{document}]. Incorporating these \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} adjustments into the ISO 1999 predictive model significantly reduced NIPTS underestimation (from 14.2 dB HL with \begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document} to 11.5–5.6 dB HL with \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}, P < 0.001). The model \begin{document}$ {{{L'}}_{\text{EX,}\text{8}\text{ h}\text{,6}}=L}_{\mathrm{E}\mathrm{X},8\;\mathrm{h}}+7.9\mathrm{lg}({{\beta }_{N}}/{10}) $\end{document} achieved the most significant improvement, reducing underestimation by 8.7 dB HL. The logistic curve analysis further demonstrated that all \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} dose-response relationships for non-steady noise aligned more closely with the steady noise group than \begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document}, with \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}\text{,6}} $\end{document} showing the smallest divergence (difference: 4.1%). Conclusions \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} demonstrates superior efficacy in assessing the risk of occupational hearing loss induced by non-steady noise exposure. The \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} metric, constructed by calculating adjustment terms and coefficients through nonlinear regression analysis, exhibits greater effectiveness than linear regression methods in evaluating occupational hearing loss associated with non-steady noise exposure.

Background Temporal kurtosis (without frequency weighting, i.e., Z-weighted kurtosis) can evaluate noise-induced hearing loss (NIHL). However, few studies have considered the function of frequency weighting (A- or C-weighted) kurtosis on NIHL. Objective To study the significance of A- and C-weighted kurtosis adjustment for equivalent sound level (L'_{EX,8 h}) in evaluating occupational hearing loss. Methods A cross-sectional survey was used to select 973 noise-exposed workers in seven industries as the subjects. The noise exposure of all workers was assessed by distributions of A-, C-, and Z-weighted kurtosis (e.g., K_A, K_C, and K_Z) and respective adjusted equivalent sound level (e.g., L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z). The significance of A- and C-weighted kurtosis in evaluating NIHL was evaluated by correlations between three types of L'_{EX,8 h} and NIHL, and improvement of noise-induced permanent threshold shift (NIPTS) underestimation predicted by the ISO prediction model (Acoustics—Estimation of noise-induced hearing loss, ISO 1999-2013). Results The median K_A, K_C, and K_Z were 68.33, 28.22, and 19.82, respectively. The binary logistic regression showed that L_{EX, 8 h}-K_A, L_{EX, 8 h}-K_C, and L'_{EX, 8 h}-K_Z were risk factors for NIHL (OR>1, P<0.001). The receiver operating characteristic (ROC) curve showed that when the outcome variable was noise-induced hearing impairment (NIHI), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.625, 0.628, and 0.625, respectively. When the outcome variable was high-frequency noise-induced hearing loss (HFNIHL), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX, 8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.624, 0.623, and 0.622, respectively (P<0.05). The order of underestimation improvement values predicted by L'_{EX,8 h} for NIPTS₁₂₃₄ was: L'_{EX,8 h}-K_A (4.68 dB HL)>L'_{EX,8 h}-K_C (4.38 dB HL)>L'_{EX,8 h}-K_Z (4.28 dB HL) (P<0.001). The order of underestimation improvement values predicted by L'_{EX,8 h}-K for NIPTS₃₄₆ was: L'_{EX,8 h}-K_A (7.20 dB HL)>L'_{EX,8 h}-K_C (6.83 dB HL)>L'_{EX,8 h}-K_Z (6.71 dB HL) (P<0.001). Conclusion The adjustment of A- and C-weighted kurtosis to equivalent sound level L_{EX,8 h} can effectively improve the accuracy of the ISO 1999 prediction model in NIPTS prediction, and compared with the C-weighted, the A-weighted kurtosis can improve the result of the ISO 1999 prediction model in terms of underestimating NIPTS.

background Current assessment of noise-induced hearing loss relies on the hearing threshold statistical distribution table of ISO 7029-2017 standard (ISO 7029), which is based on foreign population data and lacks a hearing threshold distribution table derived from pure-tone audiometry data of the Chinese population, hindering accurate evaluation of hearing loss in this group. Objective To establish a statistical distribution table of hearing threshold level (HTL) for otologically normal Chinese adults and to provide a scientific basis for revising the diagnostic criteria of occupational noise-induced deafness in China. Methods A total of 1271 otologically normal Chinese adults aged 18-60 years were divided into four groups with 10-year age intervals. Based on the pure tone audiometry data and power function operation formula, the relevant parameters of the median and percentile calculation formula of ISO 7029 were adjusted. Based on the adjusted parameters, a statistical distribution table of HTL of normal Chinese adults in otology was preliminarily constructed according to the calculation formula of ISO 7029. A nonparametric rank sum test was used to compare the difference between the adjusted median deviation value and the ISO 7029 calculation. Results Except for a few frequencies (2000, 3000, and 8000 Hz), the value of parameter α adjusted for the auditory threshold deviation of the Chinese population (α_CHN-md) increased with the increase of frequency, while the value of parameter β adjusted for the auditory threshold deviation of the Chinese population (β_CHN-md) decreased with the increase of frequency. The preliminary distribution table of otologically normal Chinese adults' median hearing threshold deviation (ΔH_CHN-md) showed that the hearing threshold deviation increased with age and frequency. At 8000 Hz, the increase in ΔH_CHN-md with age was the greatest for both men and women, from 0 dB to 23 dB and 21 dB respectively. The minimal threshold elevation was noted at 500, 1000, and 2000 Hz, which increased from 0 dB to 2 dB. In otologically normal Chinese adults, the maximum increase of ΔH_CHN-md with frequency was observed at age of 50 years, which increased from 2 dB at 500 Hz to 23 dB at 8000 Hz in men and from 2 dB at 500 Hz to 21 dB at 8000 Hz in women. The comparison results with the ISO 7029 calculation showed that the trend was consistent. The median hearing threshold deviation value of the adjusted Chinese population was lower than that of the ISO 7029 calculation (ΔH_md). However, they had no significant statistical difference (P>0.05). For otologically normal normal Chinese men and women, the maximum difference of ΔH_md between the 50-year-old group and the ISO calculation at 8000 Hz was 7 dB and 9 dB, respectively. Conclusion This preliminary analysis of hearing threshold deviations in otologically normal Chinese adults suggests that current standards may potentially underestimate hearing loss at frequencies below 8000 Hz while possibly overestimating it at 8000 Hz. These findings require further validation through expanded sample sizes to more accurately assess the characteristics of hearing thresholds in the Chinese population and their discrepancies with existing standards.