Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Objective:To evaluate the efficacy of bevacizumab in reducing dyspnea, avoiding tracheostomy, and assessing the overall safety and effectiveness of the treatment in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP).Methods:This study included 19 patients with JORRP treated with Bevacizumab at the Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, from March 2022 to June 2024. The age of patients ranged from 1.0 to 27.0 years (10.47±8.45 years), with age at onset ranging from 0.5 to 15.0 years (3.66±3.70 years). The cohort included 11 males and 8 females. Bevacizumab was administered intravenously at a dose of 10 mg/kg every three weeks for three sessions. Efficacy was evaluated by comparing the standardized lesion volume pre-and post-treatment, with statistical analysis performed using R software (4.3.1).Results:Among the 19 patients, 11 presented with dyspnea before treatment. All patients experienced varying degrees of dyspnea relief within 72 hours following the initial treatment, and only one patient had mild dyspnea by the second treatment session three weeks later. The average reduction rates at 24 and 48 hours post-initia treatment were 25.75% and 47.16%, respectively. Following three treatment cycles, the average cumulative reduction rate was 67.47%, significantly higher than after the first treatment ( Z=3.38, P=0.002). Throughout the treatment period, no adverse events that of grade 2 or higher were noted. Conclusions:Bevacizumab can rapidly alleviate dyspnea symptoms and significantly reduce lesion volume in JORRP patients, exhibiting satisfactory overall safety and effectiveness. However additional large-scale prospective studies are warranted to validate its long-term safety and efficacy.

Objective:To investigate the clinical characteristics and risk factors of airway mucus plugging in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:This was a retrospective cross-sectional study. A total of 322 hospitalized AECOPD patients admitted to the First Affiliated Hospital of Anhui Medical University from February 2023 to February 2025 were enrolled. Based on chest high-resolution computed tomography (HRCT) findings of airway mucus plugging, patients were classified into mucus plugging and non-mucus plugging groups. General and clinical data were collected, including age, sex, disease duration, smoking and alcohol history, comorbidities, number of acute exacerbations in the past year, routine blood tests, biochemical indices, pulmonary function, and pathogen detection. The incidence of airway mucus plugging in AECOPD patients was calculated, and differences in baseline characteristics, laboratory parameters, and pulmonary function between the two groups were compared. Logistic regression was used to identify independent risk factors for mucus plugging, and receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of relevant indicators.Results:Of the 322 enrolled patients, 87(27.02%) were found to have airway mucus plugging. Univariate analysis revealed statistically significant differences between the mucus plug group and the non-plug group in the following parameters (all P<0.05): body mass index (BMI), disease duration, smoking status, Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, modified British Medical Research Council (mMRC) dyspnea scale, COPD Assessment Test (CAT) score, frequency of acute exacerbations, neutrophil percentage, absolute lymphocyte count, lymphocyte percentage, albumin, C-reactive protein (CRP), activated partial thromboplastin time, fibrinogen, fibrin(ogen) degradation products, D-dimer, Aspergillus infection rate, percentage of forced expiratory volume in 1 second to predicted value (FEV 1%pred), ratio of FEV 1 to forced vital capacity (FEV 1/FVC), and percentage of maximal mid-expiratory flow to predicted value (MMEF 75/25%pred). Multivariate logistic regression analysis identified the following as independent risk factors for airway mucus plugs (all P<0.05): elevated CRP ( OR=1.022, 95% CI: 1.013-1.036), decreased albumin ( OR=0.891, 95% CI: 0.825-0.959), Aspergillus infection ( OR=1.774, 95% CI: 1.366-2.317), and reduced MMEF 75/25%pred value ( OR=0.978, 95% CI: 0.964-0.990). ROC curve analysis showed that the combined predictive model incorporating CRP, albumin, Aspergillus infection, and MMEF 75/25%pred had an area under the ROC curve (AUC) of 0.776(95% CI: 0.714-0.838), which was superior to each individual indicator alone, with AUCs of 0.721 for CRP, 0.687 for albumin, 0.579 for Aspergillus infection, and 0.631 for MMEF 75/25%pred. Conclusions:AECOPD patients with airway mucus plugging exhibit higher inflammatory markers, poorer nutritional status, a higher likelihood of Aspergillus infection, worse pulmonary function, and poorer prognosis. Aspergillus infection, elevated CRP, decreased albumin, and reduced MMEF 75/25%pred are independent risk factors for mucus plugs in AECOPD.

Objective:To investigate the clinical characteristics and risk factors of airway mucus plugging in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:This was a retrospective cross-sectional study. A total of 322 hospitalized AECOPD patients admitted to the First Affiliated Hospital of Anhui Medical University from February 2023 to February 2025 were enrolled. Based on chest high-resolution computed tomography (HRCT) findings of airway mucus plugging, patients were classified into mucus plugging and non-mucus plugging groups. General and clinical data were collected, including age, sex, disease duration, smoking and alcohol history, comorbidities, number of acute exacerbations in the past year, routine blood tests, biochemical indices, pulmonary function, and pathogen detection. The incidence of airway mucus plugging in AECOPD patients was calculated, and differences in baseline characteristics, laboratory parameters, and pulmonary function between the two groups were compared. Logistic regression was used to identify independent risk factors for mucus plugging, and receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of relevant indicators.Results:Of the 322 enrolled patients, 87(27.02%) were found to have airway mucus plugging. Univariate analysis revealed statistically significant differences between the mucus plug group and the non-plug group in the following parameters (all P<0.05): body mass index (BMI), disease duration, smoking status, Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, modified British Medical Research Council (mMRC) dyspnea scale, COPD Assessment Test (CAT) score, frequency of acute exacerbations, neutrophil percentage, absolute lymphocyte count, lymphocyte percentage, albumin, C-reactive protein (CRP), activated partial thromboplastin time, fibrinogen, fibrin(ogen) degradation products, D-dimer, Aspergillus infection rate, percentage of forced expiratory volume in 1 second to predicted value (FEV 1%pred), ratio of FEV 1 to forced vital capacity (FEV 1/FVC), and percentage of maximal mid-expiratory flow to predicted value (MMEF 75/25%pred). Multivariate logistic regression analysis identified the following as independent risk factors for airway mucus plugs (all P<0.05): elevated CRP ( OR=1.022, 95% CI: 1.013-1.036), decreased albumin ( OR=0.891, 95% CI: 0.825-0.959), Aspergillus infection ( OR=1.774, 95% CI: 1.366-2.317), and reduced MMEF 75/25%pred value ( OR=0.978, 95% CI: 0.964-0.990). ROC curve analysis showed that the combined predictive model incorporating CRP, albumin, Aspergillus infection, and MMEF 75/25%pred had an area under the ROC curve (AUC) of 0.776(95% CI: 0.714-0.838), which was superior to each individual indicator alone, with AUCs of 0.721 for CRP, 0.687 for albumin, 0.579 for Aspergillus infection, and 0.631 for MMEF 75/25%pred. Conclusions:AECOPD patients with airway mucus plugging exhibit higher inflammatory markers, poorer nutritional status, a higher likelihood of Aspergillus infection, worse pulmonary function, and poorer prognosis. Aspergillus infection, elevated CRP, decreased albumin, and reduced MMEF 75/25%pred are independent risk factors for mucus plugs in AECOPD.

Objective:To evaluate the efficacy of bevacizumab in reducing dyspnea, avoiding tracheostomy, and assessing the overall safety and effectiveness of the treatment in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP).Methods:This study included 19 patients with JORRP treated with Bevacizumab at the Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, from March 2022 to June 2024. The age of patients ranged from 1.0 to 27.0 years (10.47±8.45 years), with age at onset ranging from 0.5 to 15.0 years (3.66±3.70 years). The cohort included 11 males and 8 females. Bevacizumab was administered intravenously at a dose of 10 mg/kg every three weeks for three sessions. Efficacy was evaluated by comparing the standardized lesion volume pre-and post-treatment, with statistical analysis performed using R software (4.3.1).Results:Among the 19 patients, 11 presented with dyspnea before treatment. All patients experienced varying degrees of dyspnea relief within 72 hours following the initial treatment, and only one patient had mild dyspnea by the second treatment session three weeks later. The average reduction rates at 24 and 48 hours post-initia treatment were 25.75% and 47.16%, respectively. Following three treatment cycles, the average cumulative reduction rate was 67.47%, significantly higher than after the first treatment ( Z=3.38, P=0.002). Throughout the treatment period, no adverse events that of grade 2 or higher were noted. Conclusions:Bevacizumab can rapidly alleviate dyspnea symptoms and significantly reduce lesion volume in JORRP patients, exhibiting satisfactory overall safety and effectiveness. However additional large-scale prospective studies are warranted to validate its long-term safety and efficacy.

Objective:To observe the efficacy of vocal cord botulinum toxin type A injection in the treatment of refractory laryngeal contact granuloma and to analyze the factors affecting the curative effect.Methods:Fifty-two patients with refractory laryngeal contact granuloma who received vocal cord botulinum toxin type A injection under topical anesthesia from May 2021 to May 2023 were analyzed retrospectively. Among them, 51 were males and 1 was female, aged 22-66 (48.98±8.87)years old. All patients were followed up for a minimum of 12 months. Outcome measures in terms of patient cure rate, total effective rate, complications and recurrence rate were calculated. The median [ M ( Q1, Q3)] was used to represent non-normally distributed measurement data, and Logistic regression analysis was used to determine independent risk factors affecting efficacy. Results:The cure rate of 52 patients with refractory laryngeal contact granuloma treated by vocal cord botulinum toxin type A injection was 78.8% (41/52), and the total effective rate (including cure, marked and effective) was 90.4% (47/52). The median number of injections was 1[1,2]. Following a single injection, the cure rate was 69.2% (36/52), and the median treatment duration for cured patients was 3 [3,3] months. Hoarseness occurred in 88.5% (46/52) of patients, with recovery within 3 months in all cases. Additionally, 21.2% (11/52) of the patients experienced cough, sore throat, dyspnea, all of whom recovered within 3 months. One patient among the 41 cured cases was lost to follow-up, and the recurrence rate at the 12th month was 17.5% (7/40). Multivariate regression analysis indicated that age, granuloma size, history of PPI treatment, previous corticosteroid injections, prior surgical excision, pharyngeal reflux, chronic cough, pharyngeal reflux, chronic cough and vocal overuse were not independent risk factors for cure and recurrence.Conclusion:Vocal cord botulinum toxin type A injection is an alternative for the treatment of refractory laryngeal contact granuloma, which offers benefits such ashigh cure rate, short treatment cycle and less injection times.

Objective To explore the effect of Naikan cognitive-music reminiscence therapy on coping style in female patients with chronic schizophrenia.Methods In May, 2020, 72 female patients with chronic schizophrenia from Beijing Huilongguan Hospital were assigned into control group (n = 48) and music group (n = 24) after trait matching. Both groups accepted routine medicine, while the control group accepted Naikan cognitive therapy, and the music group accepted Naikan cognitive therapy combined music reminiscence, for twelve weeks. They were blind assessed with Simplified Coping Style Questionnaire, Self-rating Depression Scale and Self-rating Anxiety Scale before and after intervention.Results There were five cases in the control group removed for erroneous response. The main effects of group were not significant for all the assessments (F < 0.567, P > 0.05). The main effect of time was significant for negative coping style score (F = 6.968, P = 0.01), and the interaction effects were significant for positive coping style score and Self-rating Depression Scale score (F > 4.227, P < 0.05).Conclusion Combining with music reminiscence, Naikan cognitive therapy may be advantageous for the coping style of female patients with chronic schizophrenia.

Objective To understand phthalic acid esters pollution of daily consumed food in Guangzhou City，and evaluate the hazard of phthalic acid esters exposure in residents dietary. Methods Detected the content of phthalic acid esters in 10 types of food by gas chromatography-mass spectroscopy（GC-MS）methods .It combined with a survey on dietary nutrients intake of Guangzhou residents was conducted．Hazard index on the dietary exposure assessment of chemicals in food was applied. Results It showed that the highest levels of DBP，DEHP and DIBP，from the mixed diet samples in Guangzhou were 1.256，1.418，0.576 mg/kg respectively；and the exposure level of DBP，DEHP and DIBP were 2.431、5.981、2.408μg/kg.d ;HQ was respectively 0.243、0.125、0.025. HI was 0.393. Conclusion The dietary contamination of phthalic acid esters for Guangzhou was kept at a low level.But the pollution of 3 kinds of mixed samples such as meats，eggs，aquatic and products may be a certain risk of health that should attract more attention.

Objective:To evaluate the influence of transcatheter aortic valve replacement (TAVR) on left atrial strain by two-dimensional speckle tracking echocardiography.Methods:Thirty-five patients, who were admitted for TAVR in Zhongshan Hospital of Fudan University from September 2015 to July 2018, were recruited. Echocardiography was performed 1 day before and 12 months after TAVR. Traditional ultrasound results, including aortic valve area (AVA), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), peak velocity of tricuspid regurgitation (Vtr), peak velocity of the lateral wall of mitral annulus in early diastolic period (e′) and the ratios of peak mitral orifice velocity in early diastolic period to e′ (E/e′), were recorded. Two-dimensional speckle tracking imaging derived left atrial strain, which included reservoir (LASr), conduction (LAScd) and contraction (LASct), were recorded as well. The differences between pre-operation and post-operation were analyzed.Results:Compared to pre-operation, aortic valve area was increased ( P<0.001). Left ventricular systolic function was improved significantly (LVEDV and LVESV were decreased, LVEF was increased, all P<0.001). As to the left ventricular diastolic function, although LAVI and Vtr were decreased (both P<0.05), e′ and E/e′ were hardly changed (both P>0.05). Meanwhile, left atrial strain, including LASr, LAScd and LASct, were improved significantly 1 year post-TAVR (all P<0.01). Conclusions:Left atrial strain is able to evaluate the left atrial function of reservoir, conduction and contraction.Left atrial strain can be a promising tool of assessing left atrial function in patients underwent TAVR.