The nervous system not only affects the core processes of tumors such as proliferation, metastasis and angiogenesis, but is also closely related to symptoms such as tumor-related pain and cachexia. Meanwhile, tumor cells can invade adjacent tissues through nerve pathways to induce perineural invasion, which promotes tumor development. This article reviews the research progress in role of the nervous system in tumor occurrence and development from perspectives of tumor perineural invasion, neurotrophic factors, autonomic and sensory nerves, and influence of the neuroimmune system in tumors, in order to provide new perspective and method for tumor treatment.

Objective:To report the clinical data of a patient with 18q-deletion syndrome primarily presenting with intellectual disability, seizures, and white matter lesions, and to summarize the phenotypic and genetic characteristics of this syndrome.Methods:The clinical data, auxiliary examinations, and genetic test results of a patient diagnosed with 18q-deletion syndrome in the Department of Neurology, General Hospital of Northern Theater Command in October 2023 were retrospectively collected. Additionally, literatures related to "18q-syndrome" "18q-deletion syndrome" were searched in the CNKI, Wanfang Database, and PubMed databases. Combining a review of relevant literature, the clinical phenotypes and genetic features of 18q-deletion syndrome were summarized.Results:The patient was a 17-year-old male presenting with seizures, severe intellectual disability (Mini-Mental State Examination score of 11), and white matter lesions on brain magnetic resonance imaging. Whole-exome sequencing and chromosomal microarray analysis confirmed an approximately 11.3 Mb copy number deletion in the 18q22.1-q23 region, involving dosage-sensitive genes such as TSHZ1, MBP, NETO1, and ZNF407, leading to a diagnosis of 18q- deletion syndrome. A literature review identified 18 previously reported cases of 18q-deletion syndrome, totaling 19 cases including this patient. The main clinical manifestations included facial dysmorphism (10/19), intellectual disability (9/19), mental and/or motor developmental delay (9/19), congenital heart disease (8/19), seizures (6/19) and white matter lesions (5/19). Pathogenic genes involved included TCF4, SMAD4, TSHZ1, ZNF407, ZNF516, and MBP. Conclusions:18q-deletion syndrome is caused by partial deletion of the long arm of chromosome 18, with neurological manifestations such as seizures, intellectual disability, and white matter lesions, exhibiting high phenotypic variability. Genetic testing aids in definitive diagnosis.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective:To report the clinical data of a patient with 18q-deletion syndrome primarily presenting with intellectual disability, seizures, and white matter lesions, and to summarize the phenotypic and genetic characteristics of this syndrome.Methods:The clinical data, auxiliary examinations, and genetic test results of a patient diagnosed with 18q-deletion syndrome in the Department of Neurology, General Hospital of Northern Theater Command in October 2023 were retrospectively collected. Additionally, literatures related to "18q-syndrome" "18q-deletion syndrome" were searched in the CNKI, Wanfang Database, and PubMed databases. Combining a review of relevant literature, the clinical phenotypes and genetic features of 18q-deletion syndrome were summarized.Results:The patient was a 17-year-old male presenting with seizures, severe intellectual disability (Mini-Mental State Examination score of 11), and white matter lesions on brain magnetic resonance imaging. Whole-exome sequencing and chromosomal microarray analysis confirmed an approximately 11.3 Mb copy number deletion in the 18q22.1-q23 region, involving dosage-sensitive genes such as TSHZ1, MBP, NETO1, and ZNF407, leading to a diagnosis of 18q- deletion syndrome. A literature review identified 18 previously reported cases of 18q-deletion syndrome, totaling 19 cases including this patient. The main clinical manifestations included facial dysmorphism (10/19), intellectual disability (9/19), mental and/or motor developmental delay (9/19), congenital heart disease (8/19), seizures (6/19) and white matter lesions (5/19). Pathogenic genes involved included TCF4, SMAD4, TSHZ1, ZNF407, ZNF516, and MBP. Conclusions:18q-deletion syndrome is caused by partial deletion of the long arm of chromosome 18, with neurological manifestations such as seizures, intellectual disability, and white matter lesions, exhibiting high phenotypic variability. Genetic testing aids in definitive diagnosis.

The nervous system not only affects the core processes of tumors such as proliferation, metastasis and angiogenesis, but is also closely related to symptoms such as tumor-related pain and cachexia. Meanwhile, tumor cells can invade adjacent tissues through nerve pathways to induce perineural invasion, which promotes tumor development. This article reviews the research progress in role of the nervous system in tumor occurrence and development from perspectives of tumor perineural invasion, neurotrophic factors, autonomic and sensory nerves, and influence of the neuroimmune system in tumors, in order to provide new perspective and method for tumor treatment.

This study investigated the full-genome molecular characteristics of a rotavirus vaccine-derived strain,G1P[8]geno-type A group rotavirus RVA/Human-wt/CHN/HN1140/2021/G1P[8](referred to as HN1140).The gene fragments of the HN1140 strain were amplified with reverse transcription-polymerase chain reaction(RT-PCR)combined with whole-genome primers to obtain the full genome sequence.Genotyping was performed with the online genotyping tool RotaC 2.0,and similarity and genetic evolution analyses for each gene segment were conducted in DNAstar5.1 and MEGA11.0 software.The genotype of the HN1140 strain was deter-mined to be G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis demonstrated that all 11 genomic segments clus-tered closely with the RotaTeq vaccine strains,sharing 99.7%-100%nucleotide sequence similarity.Notably,VP1,VP2,VP6,and NSP2-NSP5 segments showed 100%nucleotide identity with RotaTeq strains.Comparative genomic analysis identified 13 nucleotide and 8 amino acid substitutions between HN1140 and RotaTeq strains,localized within the VP7,VP4,VP1,VP2,VP3,and NSP1 segments.The HN1140 strain exhibited the genotype G1-P[8]-A3-T6-H3,which was consistent with the typical profile of a vaccine-derived reassortant.This strain demonstrated high genetic similarity to RotaTeq vaccine strains,with nucleotide sequence identity ranging from 99.7%to 100%.These findings suggested that HN1140 evolved from RotaTeq vaccine strains through genetic reassortment.

This study investigated the full-genome molecular characteristics of a rotavirus vaccine-derived strain,G1P[8]geno-type A group rotavirus RVA/Human-wt/CHN/HN1140/2021/G1P[8](referred to as HN1140).The gene fragments of the HN1140 strain were amplified with reverse transcription-polymerase chain reaction(RT-PCR)combined with whole-genome primers to obtain the full genome sequence.Genotyping was performed with the online genotyping tool RotaC 2.0,and similarity and genetic evolution analyses for each gene segment were conducted in DNAstar5.1 and MEGA11.0 software.The genotype of the HN1140 strain was deter-mined to be G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis demonstrated that all 11 genomic segments clus-tered closely with the RotaTeq vaccine strains,sharing 99.7%-100%nucleotide sequence similarity.Notably,VP1,VP2,VP6,and NSP2-NSP5 segments showed 100%nucleotide identity with RotaTeq strains.Comparative genomic analysis identified 13 nucleotide and 8 amino acid substitutions between HN1140 and RotaTeq strains,localized within the VP7,VP4,VP1,VP2,VP3,and NSP1 segments.The HN1140 strain exhibited the genotype G1-P[8]-A3-T6-H3,which was consistent with the typical profile of a vaccine-derived reassortant.This strain demonstrated high genetic similarity to RotaTeq vaccine strains,with nucleotide sequence identity ranging from 99.7%to 100%.These findings suggested that HN1140 evolved from RotaTeq vaccine strains through genetic reassortment.

Objective:To explore the effects of hyperoxic environments on renal metabolites to understand the potential mechanisms that contribute to pathologic retinal vascular neovascularization and renal injury through metabolomic studies in a mouse model of oxygen-induced retinopathy (OIR) model.Methods:Sixteen C57/B6J mice pups born to day 7 (P7) were randomly and equally divided into an OIR model group and a normal control group using a randomized numerical table of mother mice.Mice were reared standardly from birth until day 7 (P7), then mice and their mother mice in the OIR group were placed in a hyperoxic (75±2)% chamber until day 12 (P12) and then reared normally.Mice in the normal control group were reared normally throughout.Mice in two groups were killed by carbon dioxide euthanasia on postnatal day 17 (P17). The mice retinal wholemount from the two groups were made and stained with isolectin B4 (IB4) to observe the morphology of retinal vessels, central non-perfusion area and pathological neovascularization.The kidney tissue of P17 mice was analyzed by liquid chromatograph mass spectrometer.After anticoagulant treatment, the whole blood of mice was centrifuged and precipitated, and the obtained plasma without cellular components was analyzed by targeted metabonomics.Mass spectral information was interpreted using metabolomics data processing software Progenesis QI v2.3.Overall differences in metabolic profiles were distinguished by unsupervised principal component analysis and orthogonal partial least squares analysis (OPLS-DA). The fold change and P values of metabolites were compared between the two groups.The variable importance of projection value>1 and P value<0.05 was used to screen out differential metabolites.Metabolic pathway enrichment analysis of differential metabolites was performed based on the KEGG database.The feeding and use of animals were strictly in accordance with the requirements of the Ethics Committee of Jinan University, and the research protocol was reviewed and approved by the Ethics Committee of Jinan University (No.20200401-54). Results:The IB4 staining of retinal wholemounts showed that the retinal blood vessels were evenly distributed in the P17 mice from control group.The peripheral retinal vessels were tortuous and disordered with a large non-perfusion area in central region in P17 mice from OIR group, and a large number of neovascularization clusters were formed at the junction of the nonperfusion area and the vascular area of the retina, showing strong fluorescent staining.The relative area of retinal nonperfusion area in OIR group was (25.16±3.50)%, which was significantly larger than (0.63±0.30)% in normal control group ( t=12.07, P<0.001). The OPLS-DA parameter R2X cum (0.578), interpretation rate R2Y cum (0.978) and prediction rate Q2 cum (0.857) values were all greater than 0.5, indicating that the OPLS-DA model had a good predictive ability.A total of 26 main differential metabolites were found, among which 17 were up-regulated and 9 were down-regulated, including glycerophospholipids (PC 20∶4(5Z, 8Z, 11Z, 14Z)/0∶0, PC 22∶6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/0∶0, PC 14∶1(9Z)/20∶2(11Z, 14Z), PE P-18∶0/20∶4(6E, 8Z, 11Z, 14Z)(5OH[S]), amino acid metabolites (arginine, ornithine, pipecolic acid, and hydroxylysine), purines (guanine, hypoxanthine, hydroxypurinol), and fatty acids (methyl 15-palmitate, 2, 6, 8, 12-tetramethyl-2, 4-tridecadien-1-ol), and so on.Differential metabolites were mainly enriched in ABC transporters (L-arginine, taurine, inositol, adenosine, N-acetyl-D-glucosamine, L-glutamine), aminoacyl-tRNA biosynthesis (L-isoleucine, L-proline, L-arginine, L-histidine, L-glutamine), arginine biosynthesis (L-arginine, L-ornithine, L-glutamine) metabolic pathways.The plasma targeted metabonomics showed that the differential amino acid metabolites were mainly enriched in metabolic pathways such as aminoacyl-tRNA biosynthesis, arginine biosynthesis and metabolism, and ABC transporters. Conclusions:ABC transporter, aminoacyl-tRNA biosynthesis, and arginine biosynthesis metabolic pathways in OIR mice may participate in the pathological changes of renal injury and neovascularization in retinopathy of prematurity.

Objective:To evaluate the efficacy and safety of lenvatinib combined with camrelizumab as the second-line treatment for advanced intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with advanced ICC undergoing the second-line treatment of lenvatinib combined with camrelizumab in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from June 2021 to June 2022 were screened and analyzed. A total of 12 patients were enrolled, including seven males and five females, aged (67.5±8.6) years. Response evaluation criteria in solid tumor 1.1 was used to evaluate the efficacy of treatment. The safety assessment adopts the Adverse Event Evaluation Standard 5.0. Kaplan-Meier method was conducted to plot survival curves.Results:Among the 12 patients (after 1-7 cycles of immune and targeted therapy), three achieved partial response, four achieved stable disease, and five were defined as progression disease. Adverse events of different degrees occurred in seven cases, among which three patients had adverse events of grade ≥ 3: one with hypertension, which was managed after antihypertensive and symptomatic treatment; one with elevated serum total bilirubin, which was improved after reducing the dose of lenvatinib; one with liver dysfunction, which was considered as immune-related liver toxicity and alleviated after discontinuing camrelizumab. The 1-month, 3-month, and 6-month survival rates and progression-free survival rates of the patients were 100.0%, 91.7%, 66.7%, and 83.3%, 41.7%, and 25.0%, respectively. The median overall survival of patients was 14.7 months (95% CI: 9.2-21.2) and the median time to progression was 8.0 months (95% CI: 4.1-11.9). Conclusion:Combination of lenvatinib and camrelizumab could bring survival benefits with controllable adverse events as the second-line treatment of patients with advanced ICC.

Objective:A genome-wide molecular characterization of FJ21351116, a strain of G3P[8]-E2 2021 collected in Fujian, China, was performed.Methods:Whole genome sequencing of FJ21351116 was performed using a high-sensitivity group A rotavirus whole genome sequencing method. Genomic characteriza-tion of the virus was assessed by nucleic acid sequence analysis using MEGA 11.0, Geneious 9.0.2 and DNASTAR software. Neutralization epitopes of VP7 and VP4 (VP8*) were analyzed using BioEdit v. 7.0.9.0 and PyMOL v. 2.5.2.Results:In this study, FJ21351116 was shown to be a G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype, and the result of phylogenetic tree showed that the VP7, VP4, VP3, and NSP2-NSP5 genes of the FJ21351116 strain were related to the equine-like DS-1-like G3P[8] genes that have been detected in Japan in recent years. VP6, VP1, VP2, and NSP1 genes are closely related to G2P[4] in most countries, especially in Singapore, suggesting that this strain was formed by genetic reassortment during the evolution of equine-like G3P[8] and G2P[4]. Evolutionary relationships between the VP7/VP4 genes of FJ21351116 and Rotarix and RotaTeq vaccines suggest that the multiple mutations in both VP7 and VP4 (VP8*) neutralizing antigenic epitopes and vaccine amino acid sites. It is hypothesized that the Rotarix and RotaTeq vaccines may be less effective against equine DS-1-like G3P[8] RVA, and the sequence differences with Rotarix are higher than those with RotaTeq.Conclusions:In this study, we found a rare case of DS-1-like G3P [8] RVA strain in China. Currently, horse-like DS-1-like G3P [8] RVA is relatively rare in China and may be poorly protected by vaccine strains, emphasizing the importance of continuous monitoring of RVA strains and the development of efficient and full-coverage RVA vaccines.