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.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

Objective:To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province,and to analyze the genotypes and hematological phenotypes.Methods:Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province,whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations.The mutations of β-globin gene clusters were confirmed by polymerase chain reaction(PCR)and Sanger DNA sequencing technology.Results:The 3.5 kb deletion in β-globin gene cluster(NC_000011.10:g.5224302-5227791 del3490bp)was detected in 4 patients'samples,of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation.These 2 patients displayed moderate anemia phenotype,while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype.Conclusion:Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia,compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia.In areas with a high incidence of thalassemia,suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.

Objective:To investigate the incidence,clinical characteristics,and complications of Torque teno virus(TTV)in children after hematopoietic stem cell transplantation(HSCT).Methods:A total of 40 children with hematological diseases who underwent HSCT were selected,and metagenomic next-generation sequencing(mNGS)technology was used to detect the gene sequences of pathogenic microorganisms in the blood.Combined with clinical data,the characteristics of TTV infection were analyzed.Results:Among the 40 pediatric patients post-HSCT,the TTV positive rate was 42.5％(17/40).There were no statistically significant differences between the TTV-positive group and the TTV-negative group in sex,age,white blood cell count(WBC),red blood cell count(RBC),hemoglobin,platelet count,neutrophil count,lymphocyte count,and high-sensitivity C-reactive protein(all P＞0.05).The incidence of TTV infection was significantly higher in children who underwent haploidentical HSCT and in those with bone marrow stem cells(BMSC)as the transplant source(P＜0.05).However,there were no significant differences in the TTV infection rate among patients with different disease types,different HLA matching statuses,or different engraftment times of neutrophils and platelets(all P＞0.05).Among 17 children infected with TTV,13(76.5％)had co-infections with other viruses,mainly including cytomegalovirus(58.8％,10/17),human polyomavirus(41.2％,7/17),and Epstein-Barr virus(17.6％,3/17).In children with TTV infection,the most common complications were sepsis(82.4％),graft-versus-host disease(GVHD)(70.6％),pulmonary infection(41.2％),and hemorrhagic cystitis(17.6％).The incidence of GVHD in the TTV-positive group was significantly higher than that in the TTV-negative group(P＜0.05).Conclusion:TTV infection is common in children undergoing HSCT,and it is prone to be complicated with cytomegalovirus infection and GVHD,which has an important influence on the clinical outcomes.

Objective:To investigate the incidence,clinical characteristics,and complications of Torque teno virus(TTV)in children after hematopoietic stem cell transplantation(HSCT).Methods:A total of 40 children with hematological diseases who underwent HSCT were selected,and metagenomic next-generation sequencing(mNGS)technology was used to detect the gene sequences of pathogenic microorganisms in the blood.Combined with clinical data,the characteristics of TTV infection were analyzed.Results:Among the 40 pediatric patients post-HSCT,the TTV positive rate was 42.5％(17/40).There were no statistically significant differences between the TTV-positive group and the TTV-negative group in sex,age,white blood cell count(WBC),red blood cell count(RBC),hemoglobin,platelet count,neutrophil count,lymphocyte count,and high-sensitivity C-reactive protein(all P＞0.05).The incidence of TTV infection was significantly higher in children who underwent haploidentical HSCT and in those with bone marrow stem cells(BMSC)as the transplant source(P＜0.05).However,there were no significant differences in the TTV infection rate among patients with different disease types,different HLA matching statuses,or different engraftment times of neutrophils and platelets(all P＞0.05).Among 17 children infected with TTV,13(76.5％)had co-infections with other viruses,mainly including cytomegalovirus(58.8％,10/17),human polyomavirus(41.2％,7/17),and Epstein-Barr virus(17.6％,3/17).In children with TTV infection,the most common complications were sepsis(82.4％),graft-versus-host disease(GVHD)(70.6％),pulmonary infection(41.2％),and hemorrhagic cystitis(17.6％).The incidence of GVHD in the TTV-positive group was significantly higher than that in the TTV-negative group(P＜0.05).Conclusion:TTV infection is common in children undergoing HSCT,and it is prone to be complicated with cytomegalovirus infection and GVHD,which has an important influence on the clinical outcomes.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the in vivo fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) were much more significant than that in rodents. We demonstrated that anti-PEG IgM (partially) and complement (mostly) determined the elimination of sLip and linked the distinct interspecies performances with the diverse complement capacity among species. Based on the data from animals and clinical patients, it was revealed that the fate of sLip in large animals was closer to that in humans, for the sufficient complement capacity could expose the potential adverse reactions caused by anti-PEG antibodies. Our results suggested that the distinctive interspecies performances of sLip were highly related to the physiological variabilities among species, which should not be overlooked in the innovation and translation of nanomedicines.