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 explore the effect of immobility on the quality of life in older adults.Methods:This cross-sectional study included 244 consecutive elderly patients aged 60 years and older who were admitted to the Department of Geriatrics at Xuanwu Hospital of Capital Medical University from May 2022 to March 2023.Among the participants, 52.5%(128/244)were male and 47.5%(116/244)were female, with a mean age of 69.2±7.4 years.All participants underwent a series of assessments, including the Short Physical Performance Battery(SPPB), grip strength measurement, gait speed evaluation, and the Timed Up and Go test(TUG).The Barthel Index was employed to assess activities of daily living, while the Medical Outcomes Study 36-Item Short Form Health Survey(SF-36)was used to evaluate quality of life.A score of SPPB ≤ 9 was used to diagnose immobility.Results:A total of 60 older adults met the criteria for immobility.Compared to the non-immobility group, the quality-of-life scores for older adults in the immobility group were significantly lower across various dimensions, including physical functioning, role-physical, bodily pain, general health, vitality, social functioning, physical component summary, and the total SF-36 score(all P<0.05).Furthermore, a positive correlation was identified between the SPPB scores and the quality-of-life scores across the dimensions of physical functioning, bodily pain, general health, vitality, social functioning, mental health, reported health transition, physical component summary, and the total SF-36 score among patients in the immobility group(all P<0.05).Additionally, older adults in the immobility group exhibited lower grip strength, slower gait speed, and longer TUG times, as well as a higher incidence of emergencies and falls over the past year(all P<0.05). Conclusions:The poorer quality of life and physical function, along with higher rates of emergencies and falls among older adults with immobility, indicate the necessity of addressing the health consequences that immobility inflicts on this population.

Objective:To investigate the efficacy and safety of a combination of programmed death receptor 1 (PD-1) inhibitor and multi-target tyrosine kinase inhibitor anlotinib in second-line treatment of non-small cell lung cancer (NSCLC).Methods:A prospective randomized controlled study was conducted. Using the random number table method, 118 NSCLC patients who were admitted to Shaanxi Provincial Cancer Hospital from June 2021 to June 2023 were randomly divided into the control group and the observation group, with 59 patients in each group. The observation group was treated with PD-1 inhibitor combined with anlotinib, while the control group was treated with PD-1 inhibitor. There were 36 males and 23 females in the observation group, with an age of (56±5) years; there were 34 males and 25 females in the control group, with an age of (56±5) years. There was no statistically significant difference in general clinicopathological data between the two groups (all P > 0.05). The short-term clinical efficacy [objective response rate (ORR) and disease control rate (DCR)], tumor-related factor levels [vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase (TIMP), and tumor necrosis factor β1 (TNF-β1)], inflammatory status [plasma fibrinogen-to-albumin ratio (FAR)], lung function [forced vital capacity (FVC) and peak expiratory flow (PEF)] before and after treatment, the European Organization for Research and Treatment on Cancer (EORTC) core questionnaire for quality of life assessment (QLQ-C30) score, and occurrence of adverse reactions were compared between two groups of patients. Results:The ORR and DCR of the observation group were 33.90% (20/59) and 69.49% (41/59), respectively; the ORR and DCR of the control group were 10.17% (6/59) and 44.07% (26/59), respectively; the comparison of ORR and DCR between the two groups showed statistically significant differences ( χ2 values were 9.67 and 7.77, both P < 0.05). There was no statistically significant difference in the levels of tumor-related factors between the observation group and the control group before treatment (all P > 0.05); after 4 cycles of treatment, the levels of VEGF and MMP-2 in the observation group were lower than those in the control group, while the levels of TIMP and TNF-β1 were higher than those in the control group, and the differences were statistically significant (all P < 0.001). The FAR of the observation group and the control group before treatment were (0.15±0.06) g/L and (0.16±0.06) g/L, respectively, with no statistically significant difference ( t = 0.90, P = 0.367); after 4 cycles of treatment, the FAR were (0.07±0.01) g/L and (0.11±0.04) g/L, respectively, with statistically significant difference ( t = 7.45, P < 0.001). Before treatment, there was no statistically significant difference in FVC and PEF between the observation group and the control group (both P > 0.05); after 4 cycles of treatment, the FVC and PEF in the observation group were higher than those in the control group, and the differences were statistically significant (both P < 0.001). There were no statistically significant differences in the EORTC QLQ-C30 scores of functional dimension, symptom dimension and global health status/quality of life dimension between the observation group and the control group before treatment (all P > 0.05); after 4 cycles of treatment, the scores of functional dimension and global health status/quality of life dimension in the observation group were higher than those in the control group, while the symptom dimension score was lower than that in the control group, and the differences were statistically significant (all P < 0.001). The incidence of adverse reactions in the observation group was 6.78% (4/59), while in the control group it was 10.17% (6/59), and the difference was not statistically significant ( P = 0.741). Conclusions:The combination of PD-1 inhibitor and anlotinib in second-line treatment of NSCLC has good clinical efficacy, it can reduce the inflammatory response, improve the lung function and quality of life, and has good safety.

Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans ; Large Language Models ; Tomography, X-Ray Computed

Objective To investigate the effect of human umbilical vein endothelial cells(HUVECs)on the proliferation and stem-ness of human dental pulp stem cells(hDPSCs)silencing with integrin α6(ITGA6).Methods ITGA6 silencing lentivirus was used to interfere the ITGA6 expression of hDPSCs,and its silencing efficiency was detected.Then HUVECs were added to the chambers to co-culture,and the experiments were divided into four groups(sh-NC,sh-ITGA6,sh-NC+HUVECs and sh-ITGA6+HUVECs).hDP-SCs in the sh-NC and sh-ITGA6 groups were transfected with sh-NC and sh-ITGA6 respectively.hDPSCs transfected with sh-NC and sh-ITGA6 were co-cultured with HUVECs in the sh-NC+HUVECs group and sh-ITGA6+HUVECs group respectively.The proliferation capacity of hDPSCs of each group was examined by CCK-8 and EdU on day 7.Immunofluorescence detected the expression of Stro-1,and Real-time PCR was used to detect the expression of Oct4 and Nanog.Results ①Fluorescence microscopy showed that the trans-fection efficiency was about 80％.Real-time PCR and Western blot results showed that sh-ITGA6 lentivirus effectively interfered with ITGA6 expression in hDPSCs.②CCK-8 results showed that on day 5 of co-culture,the proliferation ability of the sh-ITGA6+HUVECs group was superior to that of the sh-ITGA6 group(P＜0.05);on day 7,the proliferation ability of the sh-NC+HUVECs and sh-ITGA6+HUVECs group was superior to that of the sh-NC and sh-ITGA6 group(P＜0.05).EdU results showed that the DNA synthesis ability of hDPSCs in the co-culture group was significantly stronger than that in the single-culture group(P＜0.05).③Immunofluorescence stai-ning revealed that the expression of Stro-1 in the co-culture group was significantly stronger than that in the single-culture group.④Re-al-time PCR results showed that the expression of Oct4 in the co-culture group was higher than that in the single-culture group(P＜0.05);the expression of Nanog in hDPSCs with sh-ITGA6 was elevated by the addition of HUVECs co-culture(P＜0.05).Conclusion HUVECs significantly enhance the proliferation and stemness of hDPSCs silencing integrin α6.

Objective:To evaluate the clinical value of multi-track specialized nursing based on the transtheoretical model (TTM) in the care of patients with myasthenia gravis (MG) .Methods:A total of 108 patients with MG admitted to Shanxi Provincial People's Hospital from September 2022 to September 2023 were selected by convenience sampling and randomly divided into a control group and an observation group ( n=54 each) using a random number table. The control group received routine nursing care, while the observation group received multi-track specialized nursing based on the TTM in addition to routine care. The intervention lasted for six months. Barthel Index, Connor-Davidson Resilience Scale (CD-RISC), General Self-Efficacy Scale (GSES), 36-item Short Form Health Survey (SF-36), and Fatigue Severity Scale (FSS) were measured before intervention, and at 3 and 6 months after intervention. Results:At both 3 and 6 months post-intervention, the observation group showed higher scores in Barthel Index, CD-RISC, GSES, and SF-36, and lower FSS scores compared to the control group. The differences were all statistically significant ( P<0.05) . Conclusions:The multi-track specialized nursing model based on the TTM can improve rehabilitation outcomes in patients with MG, enhance psychological resilience and self-efficacy, improve quality of life, and alleviate fatigue.

Objective:To explore the effect of immobility on the quality of life in older adults.Methods:This cross-sectional study included 244 consecutive elderly patients aged 60 years and older who were admitted to the Department of Geriatrics at Xuanwu Hospital of Capital Medical University from May 2022 to March 2023.Among the participants, 52.5%(128/244)were male and 47.5%(116/244)were female, with a mean age of 69.2±7.4 years.All participants underwent a series of assessments, including the Short Physical Performance Battery(SPPB), grip strength measurement, gait speed evaluation, and the Timed Up and Go test(TUG).The Barthel Index was employed to assess activities of daily living, while the Medical Outcomes Study 36-Item Short Form Health Survey(SF-36)was used to evaluate quality of life.A score of SPPB ≤ 9 was used to diagnose immobility.Results:A total of 60 older adults met the criteria for immobility.Compared to the non-immobility group, the quality-of-life scores for older adults in the immobility group were significantly lower across various dimensions, including physical functioning, role-physical, bodily pain, general health, vitality, social functioning, physical component summary, and the total SF-36 score(all P<0.05).Furthermore, a positive correlation was identified between the SPPB scores and the quality-of-life scores across the dimensions of physical functioning, bodily pain, general health, vitality, social functioning, mental health, reported health transition, physical component summary, and the total SF-36 score among patients in the immobility group(all P<0.05).Additionally, older adults in the immobility group exhibited lower grip strength, slower gait speed, and longer TUG times, as well as a higher incidence of emergencies and falls over the past year(all P<0.05). Conclusions:The poorer quality of life and physical function, along with higher rates of emergencies and falls among older adults with immobility, indicate the necessity of addressing the health consequences that immobility inflicts on this population.

Objective:To evaluate the clinical value of multi-track specialized nursing based on the transtheoretical model (TTM) in the care of patients with myasthenia gravis (MG) .Methods:A total of 108 patients with MG admitted to Shanxi Provincial People's Hospital from September 2022 to September 2023 were selected by convenience sampling and randomly divided into a control group and an observation group ( n=54 each) using a random number table. The control group received routine nursing care, while the observation group received multi-track specialized nursing based on the TTM in addition to routine care. The intervention lasted for six months. Barthel Index, Connor-Davidson Resilience Scale (CD-RISC), General Self-Efficacy Scale (GSES), 36-item Short Form Health Survey (SF-36), and Fatigue Severity Scale (FSS) were measured before intervention, and at 3 and 6 months after intervention. Results:At both 3 and 6 months post-intervention, the observation group showed higher scores in Barthel Index, CD-RISC, GSES, and SF-36, and lower FSS scores compared to the control group. The differences were all statistically significant ( P<0.05) . Conclusions:The multi-track specialized nursing model based on the TTM can improve rehabilitation outcomes in patients with MG, enhance psychological resilience and self-efficacy, improve quality of life, and alleviate fatigue.

Objective To investigate the effect of human umbilical vein endothelial cells(HUVECs)on the proliferation and stem-ness of human dental pulp stem cells(hDPSCs)silencing with integrin α6(ITGA6).Methods ITGA6 silencing lentivirus was used to interfere the ITGA6 expression of hDPSCs,and its silencing efficiency was detected.Then HUVECs were added to the chambers to co-culture,and the experiments were divided into four groups(sh-NC,sh-ITGA6,sh-NC+HUVECs and sh-ITGA6+HUVECs).hDP-SCs in the sh-NC and sh-ITGA6 groups were transfected with sh-NC and sh-ITGA6 respectively.hDPSCs transfected with sh-NC and sh-ITGA6 were co-cultured with HUVECs in the sh-NC+HUVECs group and sh-ITGA6+HUVECs group respectively.The proliferation capacity of hDPSCs of each group was examined by CCK-8 and EdU on day 7.Immunofluorescence detected the expression of Stro-1,and Real-time PCR was used to detect the expression of Oct4 and Nanog.Results ①Fluorescence microscopy showed that the trans-fection efficiency was about 80％.Real-time PCR and Western blot results showed that sh-ITGA6 lentivirus effectively interfered with ITGA6 expression in hDPSCs.②CCK-8 results showed that on day 5 of co-culture,the proliferation ability of the sh-ITGA6+HUVECs group was superior to that of the sh-ITGA6 group(P＜0.05);on day 7,the proliferation ability of the sh-NC+HUVECs and sh-ITGA6+HUVECs group was superior to that of the sh-NC and sh-ITGA6 group(P＜0.05).EdU results showed that the DNA synthesis ability of hDPSCs in the co-culture group was significantly stronger than that in the single-culture group(P＜0.05).③Immunofluorescence stai-ning revealed that the expression of Stro-1 in the co-culture group was significantly stronger than that in the single-culture group.④Re-al-time PCR results showed that the expression of Oct4 in the co-culture group was higher than that in the single-culture group(P＜0.05);the expression of Nanog in hDPSCs with sh-ITGA6 was elevated by the addition of HUVECs co-culture(P＜0.05).Conclusion HUVECs significantly enhance the proliferation and stemness of hDPSCs silencing integrin α6.