Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

ObjectiveTo investigate the effect and mechanism of Dendrobium mixture （DMix）-containing serum on high glucose-induced podocyte injury in mice. MethodThe MPC5 mouse glomerular podocytes were cultured in vitro， and the optimal glucose concentration for modeling， modeling time， and concentration of DMix-containing serum for administration were determined. The cells were classified into normal （5.5 mmol·L^-1 glucose+10% blank serum）， model （30 mmol·L^-1 glucose+10% blank serum）， DMix-containing serum （30 mmol·L^-1 glucose+10% DMix-containing serum）， ferroptosis inhibitor （Fer-1， 30 mmol·L^-1 glucose+10% blank serum+1 μmol·L^-1 Fer-1） groups. The corresponding kits were used to measure the levels of Fe²⁺ and lactate dehydrogenase （LDH） in cells. Enzyme-linked immunosorbent assay was employed to determine the content of glutathione （GSH） and lipid peroxide （LPO） in cells. Fluorescence probe was used to measure the reactive oxygen species （ROS） level. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Wilms' tumor-1 （WT-1）， desmin， long chain acyl-CoA synthase 4 （ACSL4）， and glutathione peroxidase 4 （GPX4） in podocytes. ResultCompared with the blank group， the intervention with 30 mmol·L^-1 glucose for 48 h reduced podocyte viability （P<0.01）， and the 10% DMix-containing serum showed the most significant improvement in podocyte viability （P<0.01）. Compared with the normal group， the model group presented elevated levels of Fe²⁺， LDH， LPO， and ROS， lowered GSH level， up-regulated mRNA and protein levels of desmin and ACSL4， and down-regulated mRNA and protein levels of WT-1 and GPX4 （P<0.01）. Compared with the model group， the DMix-containing serum lowered the Fe²⁺， LDH， LPO， and ROS levels， elevated the GSH level， down-regulated the mRNA and protein levels of desmin and ACSL4， and up-regulated the mRNA and protein levels of WT-1 and GPX4 in podocytes （P<0.05， P<0.01）. ConclusionDMix-containing serum exerts a protective effect on high glucose-induced podocyte injury by inhibiting ferroptosis.

Hepatocellular carcinoma （HCC） is a common tumor in the digestive tract， the formation mechanism of which remains to be fully elucidated. Although surgery， radiation， chemotherapy， targeted therapy， and immunotherapy have achieved significant results in the treatment of HCC， these methods are accompanied by a considerable number of adverse reactions and complications. In recent years， Chinese medicine has shown remarkable efficacy in the treatment of HCC， and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine， which exerts therapeutic effects via multiple components and multiple targets. However， the pathogenesis of HCC is exceptionally complex and not fully understood， which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Hedgehog， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and transforming growth factor-β （TGF-β）/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis， inhibiting cell proliferation and migration， and blocking the cell cycle via the above pathways. However， the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets， new perspectives， and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.

Objective:To investigate and analyze the use and duration of anti-seizure medications (ASMs) in patients with chronic epilepsy after autoimmune encephalitis (AE), as well as the effect of ASMs use on the formation of this epilepsy to provide relevant evidence for the choice of ASMs in patients with acute seizure or chronic epilepsy after AE.Methods:A retrospective follow-up study was performed on AE patients (including patients with antibody-negative autoimmune limbic encephalitis) diagnosed in the Affiliated Brain Hospital of Nanjing Medical University from December 1, 2013 to October 31, 2022. The dates of the first seizure onset and the chronic epilepsy formation (defined as 1 year after immunotherapy) were recorded. The initial time, types and numbers of ASMs used in acute symptomatic seizure (ASS) and the maintenance time, types and numbers of ASMs in chronic epilepsy period (the continuation or the combined therapy of ASMs) were collected, respectively. A Logistic regression model was used to analyze multi-influencing factors on the formation of chronic epilepsy after AE.Results:A total of 332 patients were enrolled in this study, of whom 32.5% (108/332) with antibody-negative autoimmune limbic encephalitis. In total, 54.8% (182/332) of patients were males, and the age of onset was (40.7±19.7) years. Finally, 81.0% (269/332) of participants manifested ASS, and 57.2% (190/332) developed chronic epilepsy up to the last follow-up. The follow-up time was 1-8 years, with a median of 2 years. All patients received ASMs treatment during ASS period. Among the ASS patients, 48.0% (129/269) were prescribed monotherapy of ASMs, and 52.0% (140/269) were given the combined therapy of ASMs. Of all the patients with ASMs, 70.3% (189/269) were given early ASMs treatment (within 24 hours of the seizure onset), and 29.7% (80/269) were given delayed ASMs treatment. Subsequently, 81.0% (218/269) of the ASS patients continued the ASMs treatment (>6 months), and 19.0% (51/269) stopped use of ASMs. In the chronic epilepsy stage, 79.5% (151/190) of thee epilepsy patients continued ASMs, of whom 37.1% (56/151) were treated with monotherapy, and 62.9% (95/151) were treated with combined therapy. The incidence of chronic epilepsy was 81.3% (65/80) in the delayed ASMs treatment group, higher than the 66.1% (125/189) in the early ASMs treatment group,with statistically significant difference (χ 2=6.189, P=0.013). There were no statistically significant differences in the ASMs types and whether combined therapy of ASMs was used between chronic epilepsy group and non-chronic epilepsy group. The Logistic regression model showed that delayed ASMs treatment ( OR=2.306,95% CI 1.032-6.387, P=0.018), positive anti-neuronal intracellular antibodies ( OR=2.626,95% CI 1.536-9.531, P=0.004,compared with anti- neuronal surface antibodies), abnormal brain magnetic resonance imaging ( OR=9.883,95% CI 3.608-27.071, P<0.001), elevated cerebrospinal fluid protein ( OR=2.874,95% CI 1.115-7.409, P=0.029), and abnormal electroencephalogram ( OR=9.287,95% CI 3.767-22.896, P<0.001) were independent risk factors for chronic epilepsy after AE. Conclusions:The development of chronic epilepsy after AE is associated with the occurrence of ASS and the delayed use of ASMs, but the type of ASMs or whether the combined ASMs therapy is used is not associated with the formation of chronic epilepsy after AE. It is concluded that early ASMs treatment for the AE patients with ASS may reduce the incidence of chronic epilepsy. For AE patients with ASS who have undergone early standardized treatment, long-term, combined ASMs treatment may not be necessary.

Objective:To explore the characteristics of SLCO1B1/ SLCO1B3 gene variants among children with Rotor syndrome (RS). Methods:Four children who were admitted to the Department of Hepatology of Hunan Children′s Hospital between January 2019 and January 2022 were selected as the study subjects. Trio-whole exome sequencing was carried out for the four families, and gel electrophoresis was used to verify an insertional variant of long-interspersed element-1 (LINE-1).Results:Genetic testing has identified three variants of the SLCO1B1 gene, including c. 1738C>T (p.R580*), c. 757C>T (p.R253*) and c. 1622A>C (p.Q541P), and two variants of the SLCO1B3 gene, including c. 481+ 22insLINE-1 and c. 1747+ 1G>A among the children. Three of them were found to harbor homozygous variants of the SLCO1B1/ SLCO1B3 genes, and one has harbored compound heterozygous variants. Sanger sequencing confirmed the existence of all variants, and gel electrophoresis has confirmed the existence of the LINE-1 insertional variant of about 6 kb within intron 6 of the SLCO1B3 gene in all children. Conclusion:The pathogenesis of the RS among the four children may be attributed to the variants of the SLCO1B1/ SLCO1B3 genes. The LINE-1 insertion variant of the SLCO1B3 gene may be common among Chinese RS patients.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective To explore the lipid-lowering effect of Qige Decoction before and after compatibility through the combination of pharmacodynamics and liver metabolomics,and to provide new research strategies for exploring the scientific notation of traditional Chinese medicine compatibility.Methods According to the pharmacodynamic strategy,three groups of drug administration were set up as Qige Decoction group,Astragali Radix-Puerariae Radix group,and Pericarpium Citri Tangerinae group.Four indices of blood lipids,serum biochemical indicators,and liver morphology and pathology were used to evaluate the intervention effect of Qige Decoction on hyperlipidemic rats.Liver metabolomics technology was used to analyze the effects of Qige Decoction on metabolites before and after compatibility,and multivariate statistical analysis was used to evaluate the differences between groups in terms of differential metabolites and metabolic pathways.Results Compared with the model group,the callback abilities of four indices of blood lipid in the Qige Decoction group were higher than those in Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group,among which the total cholesterol(TC)and triglyceride(TG)levels in the Qige Decoction group decreased(P＜0.05).A total of 86 potential biomarkers were identified by liver metabolomics,with 23,13,and 7 metabolites being significantly different in the Qige Decoction group,Astragali Radix-Puerariae Radix group,and Pericarpium Citri Tangerinae group,respectively(P＜0.05).Metabolic pathway analysis of 29 specific biomarkers with significant callback effects showed that they were related to glycerophospholipid metabolism,linoleic acid metabolism,α-linolenic acid metabolism,sphingolipid metabolism,arachidonic acid metabolism,and unsaturated fatty acid biosynthesis.Qige Decoction mainly regulates glycerophospholipid and linoleic acid metabolism,and uniquely acts on sphingolipid metabolism.Conclusion Qige Decoction has more lipid-lowering targets after compatibility,with better lipid-lowering effects than the Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group.This study provides experimental evidence and research strategies for further revealing the scientific notation of traditional Chinese medicine compatibility.

Objective:To correlate rs6677604 single nucleotide polymorphism (SNP) with mesangial C3 deposition and prognosis among patients with IgA nephropathy.Methods:A retrospective nested case-control study was conducted among 380 patients with IgA nephropathy who received treatment at Taizhou Central Hospital from July 2018 to July 2021. All patients were tested for rs6677604 SNP. Among them, 36 AG genotypes and 72 GG genotypes were selected. The clinical data (IgA, C4, C3 deposit scores, percutaneous kidney biopsy, interstitial fibrosis/glomerular atrophy, mesangial C3 deposition), tissue and circulating complement levels, and CFHR gene copy numbers were compared between two genotypes. Regular follow-ups were conducted for 2 years to analyze the prognosis of patients with different rs6677604 genotypes. Results:Patients with the rs6677604-AG genotype had scores of (1.34 ± 0.50) points for IgA, (1.47 ± 0.31) points for C4 deposit, and (2.65 ± 0.36) points for C3 deposit, all of which were significantly lower than those in patients with rs6677604-GG genotype [(1.77 ± 0.73) points, (2.17 ± 0.33) points, (3.00 ± 0.48) points, t = -3.17, -10.59, -3.86, all P < 0.05]. The deposition intensity of mesangial C3 was predominantly 2+. Circulating levels of C3, C4, and complement factor H were significantly higher in patients with rs6677604-AG genotype compared with patients with rs6677604-GG genotype ( t = 7.90, 9.87, 2.27, all P < 0.05). Circulating levels of IgA and Gd-IgA1 were significantly lower in patients with rs6677604-AG genotype compared with those with rs6677604-GG genotype ( t = -2.98, -2.08, both P < 0.05). All patients with rs6677604-AG genotype had 1 copy of the CFHR3 gene, with 33 cases (91.67%) having 1 copy and 3 cases (8.33%) having 2 copies of the CFHR1 gene. Both CFHR3 and CFHR1 genes in patients with rs6677604-GG genotype were 2 copies. There was no statistically significant difference in composite endpoint between patients with rs6677604-AG and rs6677604-GG genotypes over the 2-year period (χ 2 = 0.19, P = 0.656). Conclusion:RS6677604 SNP is correlated with circulating complement factor H levels and mesangial C3 deposition in patients with IgA nephropathy, and may have a regulatory effect on complement activation in IgA nephropathy.