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 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.

Objective To summarize the assessment standards of organ donation after cardiac death (DCD) donor lungs application and donor lung function maintenance experience.Method From Jan.2013 to June 2015,139 cases of DCD donors were subjected to rigorous assessment and effective donor lung function maintenance,and 11 donor lungs for lung transplantation were obtained.The donor lung cold ischemia time was (526.8-± 12.6) min (312 to 675 min).Double lung transplantation was performed on 9 cases,and 2 cases received single lung transplantation.Result Perioperatively,1 lung transplant recipient died of pulmonary infection.The survived 10 recipients had no rejection after operation,and obtained good quality of life during discharge to the final follow-up.Condusion The effect of donor lung transplantation using organ donation is satisfactory.The assessment standards and functional maintenance of donor lung are important factors to guarantee the success of lung transplantation.

Objective To investigate the effects of anti?PD?L1 monoclonal antibody and EGFR?TKI on expression of soluble PD?L1 and function of T lymphocytes in EGFR?mutated lung cancer cells. Methods Flow cytometry was used to analyze the expression of membrane PD?LI. ELISA was performed to detect the level of sPD?L1 in the supernatant of cultured EGFR?mutated and wild type lung cancer cells before and after erlotinib treatment. After treated with anti?PD?L1 monoclonal antibody alone and in combination with erlotinib, the proliferation of T lymphocytes in co?culture system was measured using Cell Counting Kit?8 ( CCK?8) assay. The expression levels of PD?LI and IFN?γin tumor cells and T lymphocytes treated with erlotinib in co?culture system were analyzed by flow cytometry and ELISA, respectively. Results PD?L1 was highly expressed in EGFR?mutated lung cancer PC9 cells (78.7±3.1)% and HCC827 cells (82. 7±2.6)%.After treated with erlotinib, the expression rates of membrane PD?L1 in PC9 and HCC827 cells were down?regulated (64.7%±3.1% and 73.0%±2.6%, respectively),significantly lower than that in the two cell lines without erlotinib treatment ( P<0.05) , and the expression levels of sPD?L1 in the supernatant of PC9 and HCC827 cells were also down?regulated ( 0. 680 ± 0. 120) ng/ml and ( 0. 903 ± 0. 047) ng/ml, respectively, significantly lower than that in the two cell lines without erlotinib treatment ( P<0. 01 ) . However, no significant changes of membrane PD?L1 and sPD?L1 expression were found in EGFR wild type lung cancer cells ( H1299 and A549) before and after erlotinib treatment. In the co?culture system composed of T cells and EGFR?mutated lung cancer cells, treatment with erlotinib alone promoted the proliferation of T lymphocytes (P<0.05), and combined treatment of anti?PD?L1 monoclonal antibody with erlotinib had a stronger effect ( P<0.05) . In the co?culture system composed of T cells and EGFR wild type cell lines, the proliferation of T cells was not changed after using erlotinib alone or combination of erlotinib and anti?PD?L1 monoclonal antibody ( P>0.05) . Before and after treatment with erlotinib, the secretion levels of IFN?γwere (856.0± 70. 3) pg/ml and ( 1 697. 3 ± 161. 0) pg/ml, respectively, showing a significant difference ( P<0.001). The expression rates of membrane PD?L1 were (76.2±0.5)% and (50.9±0.9)%, respectively, also showing a significant difference ( P<0.001) . However, no significant changes in the expression of IFN?γ and membrane PD?L1 were found in the co?culture system composed of T cells and A549 cells. Conclusions Anti?PD?L1 monoclonal antibody combined with EGFR?TKI can effectively promote the proliferation and secretion function of T lymphocytes in the microenvironment of EGFR?mutated lung cancer cells.

Objective To investigate the effects of anti?PD?L1 monoclonal antibody and EGFR?TKI on expression of soluble PD?L1 and function of T lymphocytes in EGFR?mutated lung cancer cells. Methods Flow cytometry was used to analyze the expression of membrane PD?LI. ELISA was performed to detect the level of sPD?L1 in the supernatant of cultured EGFR?mutated and wild type lung cancer cells before and after erlotinib treatment. After treated with anti?PD?L1 monoclonal antibody alone and in combination with erlotinib, the proliferation of T lymphocytes in co?culture system was measured using Cell Counting Kit?8 ( CCK?8) assay. The expression levels of PD?LI and IFN?γin tumor cells and T lymphocytes treated with erlotinib in co?culture system were analyzed by flow cytometry and ELISA, respectively. Results PD?L1 was highly expressed in EGFR?mutated lung cancer PC9 cells (78.7±3.1)% and HCC827 cells (82. 7±2.6)%.After treated with erlotinib, the expression rates of membrane PD?L1 in PC9 and HCC827 cells were down?regulated (64.7%±3.1% and 73.0%±2.6%, respectively),significantly lower than that in the two cell lines without erlotinib treatment ( P<0.05) , and the expression levels of sPD?L1 in the supernatant of PC9 and HCC827 cells were also down?regulated ( 0. 680 ± 0. 120) ng/ml and ( 0. 903 ± 0. 047) ng/ml, respectively, significantly lower than that in the two cell lines without erlotinib treatment ( P<0. 01 ) . However, no significant changes of membrane PD?L1 and sPD?L1 expression were found in EGFR wild type lung cancer cells ( H1299 and A549) before and after erlotinib treatment. In the co?culture system composed of T cells and EGFR?mutated lung cancer cells, treatment with erlotinib alone promoted the proliferation of T lymphocytes (P<0.05), and combined treatment of anti?PD?L1 monoclonal antibody with erlotinib had a stronger effect ( P<0.05) . In the co?culture system composed of T cells and EGFR wild type cell lines, the proliferation of T cells was not changed after using erlotinib alone or combination of erlotinib and anti?PD?L1 monoclonal antibody ( P>0.05) . Before and after treatment with erlotinib, the secretion levels of IFN?γwere (856.0± 70. 3) pg/ml and ( 1 697. 3 ± 161. 0) pg/ml, respectively, showing a significant difference ( P<0.001). The expression rates of membrane PD?L1 were (76.2±0.5)% and (50.9±0.9)%, respectively, also showing a significant difference ( P<0.001) . However, no significant changes in the expression of IFN?γ and membrane PD?L1 were found in the co?culture system composed of T cells and A549 cells. Conclusions Anti?PD?L1 monoclonal antibody combined with EGFR?TKI can effectively promote the proliferation and secretion function of T lymphocytes in the microenvironment of EGFR?mutated lung cancer cells.

Objective To summarize the evaluation standard of cardiac death organ donation from Chinese first category donor heart application and experience of donor heart function maintenance.Method From Jan.2013 to Jan.2015,donor hearts for heart transplantation were obtained in 18 cases of Chinese first category cardiac death organ donors from 109 cases of organ donation donors through rigorous assessment and effective donor heart function maintenance.The diagnosis of brain death was based on the diagnosis of brain death criteria (adult) by the neurological department of internal medicine,department of neurosurgery,and intensive care unit with brain death qualification.Organ donation work followed the basic principles of voluntary,free,fair,equitable and technical access.Result Eighteen case of heart transplantations were all operated with double lumen venous anastornosis.The cold ischemia time was (125.5+ 18.7) min (61-60 min),and cardiopulmonary bypass time was (130.4+ 12.5) min (99-193 min).In 18 heart transplantations,16 cases survived,and 2 eases died of acute right heart failure.During the follow-u period,the quality of life in the survival recipients was satisfactory.Conclusion Using cardiac death organ donation from Chinese first category donor heart transplantation has achieved good results.The accurate assessment of donor hearts and effective donor heart function maintenance are the key factors to guarantee the success of heart transplantation.