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 investigate the role and mechanism of ferroptosis in cochlear hair cell injury induced by exposure to ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate(GenX).Methods Mouse cochlear hair cell line HEI-OC1 was assigned to control,GenX,ferrostatin-1(Fer-1),and GenX+Fer-1 groups.CCK-8 assay was used to assess the cytotoxicity of GenX and the rescue effect of Fer-1 co-treatment.Western blotting and qRT-PCR were employed to measure the protein and transcriptional expression of ferroptosis markers,cochlear function indicators,blood labyrinth barrier markers,and ferroptosis-related pathway.FerroOrange,Bodipy(C11),mitochondrial membrane potential assay kit(JC-1),and adenosine triphosphate(ATP)assay were applied to detect Fe2? accumulation,lipid peroxidation,mitochondrial membrane dysfunction,and cellular ATP levels,respectively.Results Exposure to 200 μmol/L GenX for 12 h significantly reduced the viability of HEI-OC1 cells(P<0.01),down-regulated the protein levels of glutathione peroxidase 4(Gpx4),solute carrier family 7 member 11(Slc7a11),and ferroptosis suppressor protein 1(Fsp1)(P<0.05),whereas up-regulated acyl-coa synthetase long-chain family member 4(Acsl4)(P<0.01),and decreased the expression of cochlear hair-cell function genes and blood labyrinth barrier genes(P<0.05).These changes were accompanied with Fe2+accumulation,elevated lipid peroxidation,mitochondrial membrane damage,and reduced ATP production(P<0.001).Addition of Fer-1 restored cell viability(P<0.05),restored the expression of ferroptosis related proteins(P<0.05),and improved the expression of several hair-cell function and blood labyrinth barrier genes(P<0.05).In parallel,the GenX+Fer-1 group exhibited reduced Fe2? accumulation,lower lipid peroxidation,attenuated mitochondrial membrane damage,and increased ATP level(P<0.001).Conclusion GenX induces iron-metabolism dysregulation and lipid peroxidation,and then leads to differentiation impairment of cochlear hair cells and barrier functions via the ferroptotic System Xc?-Gpx4-Fsp1 axis.

The cultivation of innovation ability is not only the essential requirement of graduate education,but also the strate-gic demand of the development of the communist party and our country,and is of great significance to the realization of the Chinese dream of the great rejuvenation of the Chinese nation.Curriculum ideology and politics should run through the whole process of post-graduate innovation ability training.However,the curriculum ideology and politics and postgraduate innovation ability training lack deep integration.It's important for postgraduates'growth and scientific research innovation that the curriculum ideology and politics covers the whole process of scientific research activities.Therefore,this paper focuses on the design and specific implementation schemes of the curriculum ideology and politics on the postgraduate innovative ability training at the respiratory disease research team in the department of medical immunology.It makes a basis for optimizing postgraduate curriculum ideology and politics teaching in the future,which also provides ideas for cultivating innovative talents with both morality and ability in medical specialty.

Objective To explore the intrinsic relationship between imaging features of the bony structure in varus-type knee osteoarthritis(KOA).Methods A total of 99 patients diagnosed with varus-type KOA were retrospectively selected.All patients underwent standard weight-bearing full-length X-ray radiographs of both lower extremities and 3D CT scans of the knee joints.The images were observed and analyzed at the picture archiving and communication system(PACS)workstation.The hip-knee-ankle(HKA)angle and tibial medial plateau settlement value were measured,the size of osteophyte was measured and graded,and the distribution of subchondral pseudocysts was counted.Correlation analysis was performed on the above imaging indicators,and scatter plots were drawn for linear correlations.Results There was a correlation between the HKA angle and the tibial medial plateau settlement value,with a correlation coefficient(r)of-0.548.The osteophyte grades in each subregion were correlated with the HKA angle,with r of-0.324,-0.307,-0.534,-0.581,-0.468,-0.245,-0.265,-0.244,-0.706,-0.741,-0.726,-0.326,-0.712,-0.218,respectively.There was correlation between the osteophyte grades in the medial patella,medial femoral subregion,and medial tibial subregion and the tibial medial settlement value,with r of 0.227,0.263,0.295,0.242,0.297,0.361,and 0.407,respectively.No correlation was found between the osteophyte grades in other subregions and the tibial medial settlement value.There was an overall correlation between osteophyte grades and subchondral pseudocysts,with a r of 0.245,but with regional differences.No correlation was found between the medial femoral osteophyte grades and subchondral pseudocysts,while correlations were observed in other zones,with r of 0.213,0.230,0.200,and 0.147,respectively.Conclusion KOA is a disease of the entire knee joint.The imaging features of its bony structure,including the HKA angle,tibial medial plateau settlement value,osteophyte grades,and subchondral pseudocysts,have both intrinsic relationship and regional differences,which are influenced by anatomical structures.

Objective:To investigate the effect of circular RNA bromodomain PHD finger transcription factor (circBPTF) targeting microRNA (miR)-224-3p on the damage of human retinal vascular endothelial cells (HRECs) induced by high glucose.Methods:HRECs were divided into control group and high glucose group, which were cultured with medium containing 5.5 mmol/L glucose and 30 mmol/L glucose for 48 hours, respectively.HRECs were transfected with siRNA negative control (si-NC), siRNA of circBPTF (si-circBPTF), miRNA mimic control (miR-NC), and miR-224-3p by Lipofectamine 2000, followed by cultured in 30 mmol/L glucose medium for 48 hours and were recorded as si-NC group, si-circBPTF group, miR-NC group and miR-224-3p group, respectively.HRECs were transfected with si-circBPTF and anti-miR-NC or si-circBPTF and anti-miR-224-3p by double transfection method, and then treated with 30 mmol/L glucose medium for 48 hours and were recorded as anti-miR-NC group and anti-miR-224-3p group, respectively.The expression of circBPTF and miR-224-3p was detected by real-time fluorescence quantitative PCR.Cell apoptosis was detected by flow cytometry.Reactive oxygen species (ROS) level was determined by 2′, 7′-dichlorodihydrofluorescein diacetate probe.Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric method.Expression of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9 proteins was detected by Western blot.The interaction between circBPTF and miR-224-3p was identified by the dual luciferase reporter method.Results:Compared with the control group, the apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, ROS level, MDA content, and circBPTF relative expression were significantly increased and SOD activity and miR-224-3p expression were decreased in the high glucose group (all P<0.05).Compared with the si-NC group, circBPTF relative expression, ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, and cell apoptosis rate were significantly reduced and SOD activity was significantly increased in the si-circBPTF group (all P<0.05).Compared with the miR-NC group, miR-224-3p relative expression and SOD activity were significantly enhanced and ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression and cell apoptosis rate were significantly reduced in the miR-224-3p group (all P<0.05).The relative luciferase activity of HRECs after co-transfection of wild type circBPTF and miR-224-3p mimic was 0.43±0.04, which was significantly decreased compared with 0.99±0.06 after co-transfection of wild type circBPTF and miR-NC ( t=23.297, P<0.05).Compared with anti-miR-NC group, the relative expression of miR-224-3p and SOD activity were significantly decreased and ROS level, MDA content, cell apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, and cleaved-caspase-9/caspase-9 protein expression were significantly increased in the anti-miR-224-3p group (all P<0.05). Conclusions:Interfering with circBPTF can inhibit high glucose induced HRECs apoptosis and oxidative stress damage by targeting miR-224-3p.

Objective:s To investigate the risk factors for delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in patients with acute carbon monoxide poisoning (ACOP) and to develop predictive models based on machine learning algorithms.Methods:Patients with ACOP hospitalized at the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2024 were included, with the occurrence of DEACMP as the outcome measure. The dataset was randomly divided into training and validation sets at a ratio of 7:3. Lasso regression was used to select features influencing the outcome in training sets. Nine machine learning models—including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM)—were constructed. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) calculated for each model. Calibration curves were used to assess accuracy, and decision curve analysis (DCA) was applied to evaluate clinical utility. The SHapley Additive exPlanations (SHAP) method was employed to visualize and interpret the best-performing model.Results:A total of 264 ACOP patients were included, of whom 54 (20.5%) developed DEACMP. Lasso regression identified eight key feature variables. Based on these factors, predictive models were constructed, showing good AUC stability across the nine machine learning models in both training (0.92–0.99) and validation sets (0.85–0.91). The RF model performed best, with an AUC of 0.99 in the training set and 0.90 in the validation set; its calibration curve and DCA curve also demonstrated excellent performance. SHAP analysis of the RF model revealed the importance ranking of factors from highest to lowest as follows: Glasgow Coma Scale (GCS) score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, diastolic blood pressure (DBP), and drinking history.Conclusions:The RF model exhibited the highest predictive performance for DEACMP occurrence in ACOP patients. The influencing factors, ranked in order of importance from highest to lowest, are as follows: GCS score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, DBP, and drinking history.

Objective:To compare the impact of manual right arm blood pressure measurement with computer-controlled blood pressure meter (CCBPM) on the detection rate of hypertension among elderly individuals.Method:This was a cross-sectional study. Elderly residents undergoing routine health check-up in a village in Jiangxi Province from April to June 2024 were enrolled. Manual blood pressure measurements were performed on the right arm using an electronic sphygmomanometer, while standardized dual-arm synchronized blood pressure assessments were conducted using the CCBPM. Blood pressure data were recorded from three sources: manual measurement on the right arm; the first CCBPM measurement on the arm with higher systolic blood pressure (CCBPM single); and the mean blood pressure of the arm with higher systolic blood pressure from two (if the difference between the first two measurements was less than 5 mmHg, 1 mmHg=0.133 kPa) or three (if the difference exceeded 5 mmHg) CCBPM measurements (CCBPM mean). Hypertension detection rates from these three datasets were compared. Subgroup analysis was performed according to age (60-74 years old as the elderly group,≥75 years old as the senior group) and gender. Intra-group correlation coefficient ( ICC) was analyzed to evaluate the consistency of blood pressure data of different blood pressure measurement methods, and Kappa value was analyzed to evaluate the consistency of hypertension classification determined by different blood pressure measurement methods. Results:A total of 1 498 participants were enrolled, aged (71.30±6.83) years old, including 678 males (45.26%). The blood pressure and heart rate measured by the artificial right arm blood pressure measurement were higher than those measured by CCBPM single (blood pressure: (140.09±17.19)/(82.40±10.93) mmHg vs. (135.31±18.98)/(81.23±10.51) mmHg; heart rate: (75.76±11.72) beats/min vs.(72.94±11.21) beats/min) and CCBPM mean (blood pressure: (140.09±17.19)/(82.40±10.93) mmHg vs. (134.64±18.39)/(80.28±9.78) mmHg; heart rate: (75.76±11.72) beats/min vs. (72.87±10.70) beats/min, all P<0.05). The detection rate of hypertension determined by CCBPM mean was significantly lower than that of artificial right arm (40.25% (603/1 498) vs.54.34% (814/1 498)) and CCBPM single (40.25% (603/1 498) vs. 44.79% (671/1 498), all P<0.05). Subgroup analysis showed that that the detection rate of hypertension determined by CCBPM mean was lower than that measured by artificial right arm regardless of gender and age (all P<0.05). The consistency of blood pressure data between artificial right arm and the CCBPM mean was moderate (systolic blood pressure: ICC=0.70; diastolic blood pressure: ICC=0.62), with less consistent classification ( Kappa=0.37). The consistency of blood pressure data between CCBPM single and CCBPM mean is extremely high (systolic blood pressure: ICC=0.94; diastolic blood pressure: ICC=0.91), with highly consistent classification ( Kappa=0.74). Conclusions:Artificial right arm blood pressure measurement in physical examinations may overestimate the hypertension detection rate, and the standardized dual-arm synchronized blood pressure measurement using CCBPM can reduce irregular blood pressure measurement.

Cleft lip and palate, as one of the most common congenital deformities of the oral and maxillofacial region, not only affects the physiological functions of patients, but also has a profound impact on their psychological well-being. Traditional sequential treatment for cleft lip and palate aims to restore primary functions and typically concludes intervention after orthodontic treatment. However, this management protocol often fails to meet patients′ expectations for esthetic outcomes. In the process of dental esthetic restoration, it is essential to adhere to the principles of comprehensive planning, sequential treatment, and tooth preservation, while formulating individualized treatment strategies. This article delves into the main challenges and corresponding therapeutic measures in dental esthetic restoration following sequential treatment for cleft lip and palate patients. It systematically analyzes the causes, clinical manifestations, and treatment methods for esthetic defects in dental arch space, dental hard tissues, and periodontal soft tissues. The study proposes that dental esthetic restoration can be implemented during three critical phases of sequential treatment: the mixed dentition stage, early permanent dentition stage, and adulthood stage to reduce the complexity of subsequent treatments, thereby preserving more dental and periodontal tissues. Through multidisciplinary collaboration and the application of digital technology, not only has the efficiency and predictability of treatment been enhanced, but more economical and effective treatment options have also been provided for patients. The aim is to offer clinicians comprehensive treatment insights, promoting a shift in the treatment philosophy for cleft lip and palate patients from "function-oriented" to a multidimensional approach that equally emphasizes" function-aesthetics-psychosocial aspects", ultimately achieving a comprehensive improvement in patients′ quality of life.

Objective:To investigate the effect of circular RNA bromodomain PHD finger transcription factor (circBPTF) targeting microRNA (miR)-224-3p on the damage of human retinal vascular endothelial cells (HRECs) induced by high glucose.Methods:HRECs were divided into control group and high glucose group, which were cultured with medium containing 5.5 mmol/L glucose and 30 mmol/L glucose for 48 hours, respectively.HRECs were transfected with siRNA negative control (si-NC), siRNA of circBPTF (si-circBPTF), miRNA mimic control (miR-NC), and miR-224-3p by Lipofectamine 2000, followed by cultured in 30 mmol/L glucose medium for 48 hours and were recorded as si-NC group, si-circBPTF group, miR-NC group and miR-224-3p group, respectively.HRECs were transfected with si-circBPTF and anti-miR-NC or si-circBPTF and anti-miR-224-3p by double transfection method, and then treated with 30 mmol/L glucose medium for 48 hours and were recorded as anti-miR-NC group and anti-miR-224-3p group, respectively.The expression of circBPTF and miR-224-3p was detected by real-time fluorescence quantitative PCR.Cell apoptosis was detected by flow cytometry.Reactive oxygen species (ROS) level was determined by 2′, 7′-dichlorodihydrofluorescein diacetate probe.Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric method.Expression of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9 proteins was detected by Western blot.The interaction between circBPTF and miR-224-3p was identified by the dual luciferase reporter method.Results:Compared with the control group, the apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, ROS level, MDA content, and circBPTF relative expression were significantly increased and SOD activity and miR-224-3p expression were decreased in the high glucose group (all P<0.05).Compared with the si-NC group, circBPTF relative expression, ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, and cell apoptosis rate were significantly reduced and SOD activity was significantly increased in the si-circBPTF group (all P<0.05).Compared with the miR-NC group, miR-224-3p relative expression and SOD activity were significantly enhanced and ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression and cell apoptosis rate were significantly reduced in the miR-224-3p group (all P<0.05).The relative luciferase activity of HRECs after co-transfection of wild type circBPTF and miR-224-3p mimic was 0.43±0.04, which was significantly decreased compared with 0.99±0.06 after co-transfection of wild type circBPTF and miR-NC ( t=23.297, P<0.05).Compared with anti-miR-NC group, the relative expression of miR-224-3p and SOD activity were significantly decreased and ROS level, MDA content, cell apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, and cleaved-caspase-9/caspase-9 protein expression were significantly increased in the anti-miR-224-3p group (all P<0.05). Conclusions:Interfering with circBPTF can inhibit high glucose induced HRECs apoptosis and oxidative stress damage by targeting miR-224-3p.