Classification and clinical significance of immunogenic cell death-related genes in Plasmodium falciparum infection determined by integrated bioinformatics analysis and machine learning.

BACKGROUND: Immunogenic cell death (ICD) is a type of regulated cell death that plays a crucial role in activating the immune system in response to various stressors, including cancer cells and pathogens. However, the involvement of ICD in the human immune response against malaria remains to be defined. METHODS: In this study, data from Plasmodium falciparum infection cohorts, derived from cross-sectional studies, were analysed to identify ICD subtypes and their correlation with parasitaemia and immune responses. Using consensus clustering, ICD subtypes were identified, and their association with the immune landscape was assessed by employing ssGSEA. Differentially expressed genes (DEGs) analysis, functional enrichment, protein-protein interaction networks, and machine learning (least absolute shrinkage and selection operator (LASSO) regression and random forest) were used to identify ICD-associated hub genes linked with high parasitaemia. A nomogram visualizing these genes' correlation with parasitaemia levels was developed, and its performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In the P. falciparum infection cohort, two ICD-associated subtypes were identified, with subtype 1 showing better adaptive immune responses and lower parasitaemia compared to subtype 2. DEGs analysis revealed upregulation of proliferative signalling pathways, T-cell receptor signalling pathways and T-cell activation and differentiation in subtype 1, while subtype 2 exhibited elevated cytokine signalling and inflammatory responses. PPI network construction and machine learning identified CD3E and FCGR1A as candidate hub genes. A constructed nomogram integrating these genes demonstrated significant classification performance of high parasitaemia, which was evidenced by AUC values ranging from 0.695 to 0.737 in the training set and 0.911 to 0.933 and 0.759 to 0.849 in two validation sets, respectively. Additionally, significant correlations between the expressions of these genes and the clinical manifestation of P. falciparum infection were observed. CONCLUSION: This study reveals the existence of two ICD subtypes in the human immune response against P. falciparum infection. Two ICD-associated candidate hub genes were identified, and a nomogram was constructed for the classification of high parasitaemia. This study can deepen the understanding of the human immune response to P. falciparum infection and provide new targets for the prevention and control of malaria.

Efficacy analysis of C5V chemotherapy combined with transcatheter subcutaneous radiofrequency ablation in the treatment of children with advanced (Stage III/IV) hepatoblastoma.

Objectives: To evaluate the clinical efficacy of C5V chemotherapy combined with transcatheter subcutaneous radiofrequency ablation in the treatment of children with advanced (stage III/IV) hepatoblastoma. Methods: Eighty children with advanced (Stage III/IV) hepatoblastoma were admitted in Hebei Children's Hospital from May 2019 to September 2021 randomly divided into two groups: control group and experimental group, with 40 cases in each group. Children in the control group received C5V chemotherapy, while those in the experimental group received C5V chemotherapy combined with transcatheter subcutaneous radiofrequency ablation. After treatment, the treatment effect, adverse drug reactions, AFP, ALT, AST, HBG and other indicators of the two groups were compared and analyzed. And the difference in survival rate and recurrence rate between the two groups was compared and analyzed. Results: The total efficacy of the experimental group was 67.5%, which was significantly better than 45% of the control group (p=0.04). The incidence of adverse drug reactions in the experimental group was 50%, while that in the control group was 35% (p=0.15). After treatment, AFP, ALT and AST in the experimental group were significantly lower than those in the control group, while the HBG was slightly higher than that of the control group (p=0.03). Moreover, the overall survival rate of the experimental group was significantly higher than that of the control group, and the recurrence rate was significantly lower than that of the control group. Conclusion: C5V chemotherapy combined with transcathetal subcutaneous radio fascial ablation is a safe and effective regimen for children with advanced (stage III/IV) hepatoblastoma, boasting definite efficacy and no increase in adverse reactions.

[Diethylstilbestrol affects LGR8 expression in mouse gubernaculum testis].

OBJECTIVE: To investigate the impact of prenatal exposure to diethylstilbestrol (DES) on the specific receptor LGR8 of insulin-like factor 3 (INSL3) in the mouse gubernaculum testis, and that of exoestrogens on descensus testis in mice. METHODS: A total of 120 pregnant KM mice aged 8 to 10 weeks were assigned to a normal, a blank control and 4 DES groups of equal number, the blank controls injected subcutaneously with dimethyl sulfoxide plus normal saline, and the DES groups with DES at 0.1, 1, 10 and 100 microg/kg body weight, respectively, from embryonic day 9 (ED9) through ED17. Immunohistochemistry and RT-PCR were used to detect the expressions of LGR8 protein and mRNA in the gubernaculum testis of the ED18 fetuses and PND20 (postnatal day 20) offspring of the mice. RESULTS: Histological analysis showed that the gubernaculum testis of the ED18 fetuses were well developed in both the normal and control groups, with an inner mesenchymal core and muscular outer layer. In contrast, the gubernaculum testis were poorly developed in the experimental groups, morphologically abnormal and without visible dividing line between the mesenchymal tissue and the muscular outer layer. No obvious differences were found in the gubernaculum testis development of the neonates between the normal and experimental groups. Positive immunostaining was seen in the mesenchymal core and muscular outer layer, but mainly in the latter. The expression of LGR8 was weaker in the experimental groups than in the normal group (P < 0.05), but that of LGR8 mRNA was increased in the high-dose (10 and 100 microg/kg) DES groups (P < 0.05). No obvious mutations were observed in the PCR products in any of the experimental groups. CONCLUSION: Prenatal exposure to diethylstilbestrol affected the expression of LGR8 mRNA in the mouse gubernaculum testis, which suggests that diethylstilbestrol may induce cryptorchidism by interfering with the INSL3-LGR8 signaling system and consequently the development of the gubernaculum testis.

Association Between 12 Polymorphisms of VEGF/Hypoxia/Angiogenesis Pathway Genes and Risk of Urogenital Carcinomas: A Meta-Analysis Based on Case-Control Studies.

Objective: Previous studies indicated potential associations between polymorphisms in genes of VEGF/hypoxia/angiogenesis pathway and risk of urogenital carcinomas However, the results were controversial and inconclusive. Here, we conducted an in-depth meta-analysis to investigate the precise associations between polymorphisms in VEGF/hypoxia/angiogenesis related genes and risk of urogenital carcinomas. Methods: We searched PubMed, Web of Science, EMBASE, and Cochrane Library to identify all eligible publications. Pooled odds ratios (ORs) corresponding with the 95% confidence intervals (CIs) were calculated to evaluate their associations. Subgroup analysis was conducted to further ascertain such relationship and investigate sources of heterogeneity. Results: In the end, a total of 96 case-control studies fulfilled the inclusion criteria were enrolled for 12 polymorphisms in 4 VEGF/hypoxia/angiogenesis related genes. The pooled results showed eNOS-rs2070744 polymorphism conferred a significantly increased overall risk of urogenital carcinomas in allele, homozygote, and recessive models, respectively. In addition, eNOS-Intron 4a/b VNTR polymorphism was identified related to an increased risk of urogenital carcinomas in recessive model. And VEGF-rs699947 polymorphism was also identified an increased risk of renal cell carcinoma (RCC) in allelic, heterozygote, dominant, homozygote, and recessive models. Conclusion: To conclude, eNOS-rs2070744 and eNOS-Intron 4a/b VNTR polymorphisms are risk factors for urogenital carcinomas. VEGF-rs699947 polymorphism was also identified as an increased risk factor for renal carcinoma.

[Effect of nutritional support on immunity function in the acquired immune deficiency syndrome patients].

OBJECTIVE: To investigate the effect of nutritional support on immunity function in the acquired immune deficiency syndrome (AIDS) patients. METHODS: Sixty-five AIDS patients were randomly divided into treatment group (n=35) and control group (n=30). In the treatment group, the patients received enteral nutrition (EN) treatment or EN supplemented with parenteral nutrition (EN+PN) on top of routine treatment according to the daily condition of the sufferers. The control group received routine treatment only. CD3, CD4 and CD8 cell, CD4/CD8, C3, C4, immunoglobulin G (IgG), IgM, IgA were determined on the 0 and 30th day of the treatment, and they were analyzed with covariance analysis. RESULTS: CD4 cell in the treatment group was significantly raised compared with before examination (P<0.05). Other immunity indexes were not correlated. All clinical indexes showed no change in the control group (all P>0.05). CONCLUSION: The nutritional support can raise the immunity function in the AIDS patient.