Radionuclides can be hazardous by absorbed through the skin, respiratory and digestive tracts. Chelating agents and adsorbents already could effectively remove them, however traditional chelators have side effects such as nephrotoxicity, teratogenicity, and embryotoxicity. As a new type of nuclide adsorbent, polysaccharide has the advantages of safety, biocompatibility, and high clearance rate. In this paper, the main types and perniciousness of radionuclides, and the latest research of polysaccharides in radionuclide removal were summarized. The application of polysaccharide as an effective adsorption molecule for radio nuclides in nuclear wars, nuclear accidents and other sudden nuclear events is promising.

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.

Metastatic lung cancer continues to cause a high number of deaths due to high malignancy and poor prognosis, and the efficacy of typical chemotherapy or immunotherapy is less than ideal due to the low pulmonary accumulation and targeting of therapeutics. Here, a submicron-sized biomimetic liposome was formulated for the lung-targeted co-delivery of bacterial superantigen and paclitaxel. Recombinant staphylococcal enterotoxin C2 (rSEC2), a bacterial superantigen, was expressed with the Escherichia coli system and showed potent immunostimulatory activities to mediate tumor cell death. The submicron-sized (∼800 nm) biomimetic liposomes, namely 4T1 cell membrane-hybrid rSEC2 paclitaxel liposomes (TSPLs), exhibited high lung-accumulation efficiency and tumor homologous effect due to the suitable particle size and membrane hybridization of cancer cell membranes with phospholipids. Intravenous TSPLs remarkably inhibited metastatic lung cancer with limited systemic immune responses. TSPLs reversed the immunosuppressive state and increased the proportion of local CD4⁺ and CD8⁺ T cells in the lung; moreover, paclitaxel increased tumor cell apoptosis and reduced tumor burden. In summary, the high lung cancer targeting was achieved by particle size control and cell membrane hybridization, and the highly efficient anticancer effect was achieved by the co-delivery of superantigens and chemotherapeutic drugs.

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.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

OBJECTIVE: To explore whether hydrocortisone can improve the prognosis of patients with severe community-acquired pneumonia (sCAP) by Meta-analysis. METHODS: Randomized controlled trial (RCT) on hydrocortisone in the treatment of sCAP were extracted from the database including PubMed, Cochrane library, Web of Science, and Embase, and the search time was up to April 29, 2023. The patients in the standard treatment group received standard treatment such as antibiotics and supportive care, while those in the hydrocortisone group received hydrocortisone treatment on the basis of standard treatment. Meta-analysis was used to compare the mortality, duration of mechanical ventilation, mechanical ventilation rate and incidence of adverse reactions (hyperglycemia, gastrointestinal bleeding, secondary infection) between the two groups. The risk of literature bias was assessed. The studies that might have publication bias were corrected by the subtraction and complementation method. At the same time, trial sequential analysis (TSA) was conducted. RESULTS: A total of 5 RCTs involving 1 031 patients were finally enrolled, including 494 patients in the standard treatment group and 537 patients in the hydrocortisone group. Among the 5 studies, the research site of 2 studies was in the mixed ward. Considering the inclusion characteristics of the study population, there was doubt whether its research object was sCAP patients, which might have a certain impact on the results and introduce potential bias. Meta-analysis showed that the mortality in the hydrocortisone group was significantly lower than that in the standard treatment group [6.0% vs. 14.0%; odds ratio (OR) = 0.38, 95% confidence interval (95%CI) was 0.25-0.59, P < 0.01; I² = 9%]. The studies that were asymmetric were corrected by the reduction and supplementation method. Even after filling the missing studies, hydrocortisone could still reduce the death risk of the patient (OR = 0.49, 95%CI was 0.32-0.73, P < 0.01; I² = 31%). TSA showed that the average mortality of the standard treatment group was about 14.0%, and that of the hydrocortisone group was about 6.0%, with a relative risk reduction (RRR) = 57%. The calculated sample size was 699 cases, and the actual sample size was 1 031 cases. The actual sample size exceeded the required sample size, and the Z-curve crossed the O'Brien-Fleming boundary and the curve corresponding to P = 0.05, it meant that hydrocortisone could effectively reduce the mortality of sCAP. Compared with the standard treatment group, no statistical difference in the duration of mechanical ventilation was found in the hydrocortisone group [mean difference (MD) = -3.26, 95%CI was -6.72-0.21, P = 0.07; I² = 0%], but the 8-day mechanical ventilation rate was significantly lowered (19.5% vs. 55.4%; OR = 0.24, 95%CI was 0.12-0.45, P < 0.01; I² = 0%), and also no significantly difference was found in the incidence of hyperglycemia (54.3% vs. 44.6%, OR = 1.26, 95%CI was 0.56-2.84, P = 0.58; I² = 61%), gastrointestinal bleeding (2.5% vs. 3.6%; OR = 0.70, 95%CI was 0.34-1.46, P = 0.34; I² = 0%) and secondary infection (9.2% vs. 11.5%; OR = 0.46, 95%CI was 0.06-3.35, P = 0.45; I² = 53%). CONCLUSION Hydrocortisone can reduce the mortality rate of sCAP patients, decrease their need for mechanical ventilation, and does not increase the risk of hyperglycemia, gastrointestinal bleeding, or secondary infections.
Humans ; Hydrocortisone/therapeutic use* ; Community-Acquired Infections/drug therapy* ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; Community-Acquired Pneumonia

OBJECTIVE To explore the prognostic significance of the prognostic nutrition index(PNI)in patients with hypopharyngeal cancer undergoing surgical treatment.METHODS Clinical and pathological data of 117 patients with hypopharyngeal carcinoma who underwent surgical treatment at the center of Otolaryngology Head and Neck Surgery of Beijing Friendship Hospital,Capital Medical University from May 2014 to June 2022 were collected.The prognostic significance of hematological indicators such as PNI and neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and systemic immune inflammation index(SⅡ)were investigated.The time-dependent receiver operating characteristic(tROC)curves were used to analyze the sensitivity and specificity of various hematological indicators and to determine their optimal cutoffvalues.The Kaplan-Meier method was used to plot the postoperative survival curve,and the Cox regression model was used to analyze the correlation between PNI and overall survival(OS)and disease-free survival(DFS).RESULTS 117 patients were enrolled in this cohort,of which 109 were clinically classified as advanced stage(Ⅲ-Ⅳ).63 cases underwent surgery to preserve laryngeal function.The 5-year OS is 46.07％.According to the analysis of the tROC curve,the optimal cutoffvalue for PNI is 46.75.PNI is correlated with tumor T staging,NLR,PLR,and SⅡ.Kaplan Meier univariate analysis showed that PNI was significantly correlated with OS and DFS(P<0.05).In addition,tumor N-stage,postoperative complications,adverse pathological prognostic factors,NLR,PLR,and SⅡ were all significantly correlated with OS(P<0.05).Tumor N-stage,laryngeal preservation,postoperative complications,NLR,and SⅡ were significantly correlated with DFS(P<0.05).The Cox multivariate analysis results indicated that PNI,tumor N-stage,and postoperative complications were independent factors affecting OS and DFS.CONCLUSION Preoperative PNI,tumor N-stage,and postoperative complications are independent risk factors for OS and DFS in patients with hypopharyngeal carcinoma.PNI,as a prognostic indicator for predicting hypopharyngeal cancer patients,is superior to other hematological indicators.

Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P＞0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.

Objective:To evaluate the value of the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) in evaluating right ventricular function of patients with hypertrophic cardiomyopathy (HCM) and heart failure with preserved ejection fraction (HFpEF).Methods:A total of 74 patients with HCM and HFpEF and 22 healthy individuals who visited the First Affiliated Hospital of Zhengzhou University from January 2021 to January 2023 were included in this study. The HCM patients with HFpEF were divided into three groups based on the tertiles of the TAPSE/PASP (low group: <0.280 0 mm/mmHg; middle group: 0.280 0-0.476 2 mm/mmHg; high group: >0.476 2 mm/mmHg). Conventional echocardiographic parameters were collected, and two-dimensional speckle tracking technology was used to obtain right ventricular strain parameters. The differences in parameters among the groups were compared, and the correlations between TAPSE/PASP and clinical parameters and right ventricular function parameters were analyzed.Results:The results of difference analysis showed that there were significant differences in 6-minute walking test, New York Heart Association grade (NYHA grade), incidence of atrial fibrillation, left atrial area (LAA), left ventricular global longitudinal strain (LVGLS), TAPSE, PASP, right ventricular fractional area change (RVFAC), right ventricular global longitudinal strain (RVGLS), right ventricular free wall strain (RVFWST) and cardiac magnetic resonance right ventricular ejection fraction (CMR-RVEF) among the three groups. The results of correlation analysis and multiple linear regression analysis showed that the TAPSE/PASP was positively correlated with 6-minute walking distance, RVFAC, tricuspid annulus peak systolic velocity (RV s′), and CMR-RVEF ( r=0.449, 0.284, 0.358, 0.577; all P<0.05). It was negatively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP), NYHA grade, LAA, mitral early diastolic peak velocity / mitral annulus early diastolic peak velocity (LV E/e′), LVGLS, RVGLS, RVFWST and tricuspid early diastolic peak velocity / tricuspid annulus early diastolic peak velocity (RV E/e′) (r/ rs=-0.336, -0.349, -0.468, -0.452, -0.444, -0.339, -0.405, -0.320; all P<0.05). The LAA and CMR-RVEF correlated independently with TAPSE/PASP(all P<0.05). Conclusions:The TAPSE/PASP can provide an early, simple, rapid, and convenient evaluation of right ventricular function in patients with HCM and HFpEF, so as to guide clinical treatment and monitoring disease progression.

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4⁺/CD8a⁺ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.