Objective To construct a diagnostic and prognostic model for malignant pleural effusion (MPE) in patients with non-M1b stage (AJCC 7th edition) non-small cell lung cancer (NSCLC) by machine learning. Methods Retrospective analysis was conducted on patients diagnosed with NSCLC in the Surveillance, Epidemiology, and End Results database from 2010 to 2015, excluding those in the M1b stage. Two sets of data were collected: data 1 (patients with non-M1b stage NSCLC, n=47 392) was used to construct the MPE diagnostic model; and data 2 (patients with M1a stage NSCLC and MPE, n=2 422) was used to construct a prognostic model. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to screen feature variables, with a training set and validation set ratio of 7:3. Models were built using eight machine learning algorithms, with evaluation metrics including accuracy, precision, recall, F1 score, area under the ROC curve (AUC), decision curve, calibration curve, and precision recall curve (PR), with ROC-AUC as the main evaluation metric. Results The incidence of MPE in patients with non-M1b stage NSCLC was 5.12%, and the 1-year survival rate of patients with MPE was 32.5%. LASSO regression identified nine diagnostic-related variables and 12 prognostic-related variables. The AUC values of the models constructed by eight machine learning algorithms all exceeded 0.70. The random forest model performed the best in the diagnostic model (training set AUC=0.908, validation set AUC=0.897), and the XGBoost model showed the best performance in the prognostic model (training set AUC=0.905, validation set AUC=0.875). Other evaluation indicators showed good results and balanced distribution. SHAP feature importance analysis showed that tumor size, lymph node metastasis, and histological type were important influencing factors for the occurrence of MPE, and chemotherapy intervention was the most remarkably prognostic factor. Conclusion The random forest diagnostic model constructed in this study can effectively predict the risk of MPE in patients with non-M1b stage NSCLC, and the XGBoost prognostic model can predict the prognosis of M1a-stage NSCLC patients with concurrent MPE.

OBJECTIVE: To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA. METHODS: A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children's Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, i.e., 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children's Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00). RESULTS: There was a statistically significant difference in the gender and age distribution between the two groups of children (P < 0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes (P > 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children's samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. CONCLUSION DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.
Humans ; Arthritis, Juvenile/blood* ; Female ; Male ; Child ; Methotrexate/therapeutic use* ; Child, Preschool ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Transcriptome ; Adolescent ; RNA/genetics* ; Signal Transduction ; Gene Expression Profiling

Objective:To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA.Methods:A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children′s Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children′s Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00).Results:There was a statistically significant difference in the gender and age distribution between the two groups of children ( P<0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes ( P> 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children′s samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β; production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. Conclusion:DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.

Objective:To investigate the numbers of peripheral blood CD4 +T cell subpopulations in patients with elderly-onset rheumatoid arthritis (EORA) and its clinical significance. Methods:A total of 188 patients with newly diagnosed RA in the department of rheumatology and immunology of the Second Hospital of Shanxi Medical University from January 2020 to December 2023 were collected, including 48 cases of EORA (age of onset: ≥60 years old), 140 cases of young-onset rheumatoid arthritis (YORA) (18 years old ≤ age of onset < 60 years old). Meanwhile, 151 healthy controls (HC) were collected, of which 31 persons aged 60-85 years were included as HC group 1 (HC 1) and 120 individuals aged 18-59 years were included as HC group 2 (HC 2). Peripheral blood CD4 +T lymphocyte subsets of these participants were assessed by flow cytometry. Differences between groups were analyzed using independent-samples t test, Mann-Whitney U test or χ2 test. Results:Compared with healthy individuals, the absolute counts and percentages of peripheral blood Treg cells in patients with EORA were significantly decreased [absolute counts: 32.65 (23.04, 47.73) cells/μl vs. 23.03 (15.28, 32.12) cells/μl, Z=-3.35, P=0.001; percentages: 5.12%(4.13%, 6.16%) vs. 3.72% (2.79%, 4.82%), Z=-4.10, P<0.001], while the Th17/Treg cell ratio was increased [0.16 (0.12, 0.29) vs. 0.26 (0.18, 0.46), Z=-2.94, P=0.003], the differences are all significant. There was a tendency with higher absolute counts and percentages of Treg [absolute counts: 23.03 (15.28, 32.12) cells/μl vs. 20.97 (14.01, 30.64) cells/μl, Z=-0.58, P=0.561; percentages: 3.72%(2.79%, 4.82%) vs. 3.38% (2.39%, 4.71%), Z=-1.06, P=0.287] and lower Th17/Treg ratios [0.26 (0.18, 0.46) vs. 0.27 (0.19, 0.46), Z=-0.32, P=0.751] in EORA when compared to patients with YORA, but no significant differences were observed. Conclusion:Patients with EORA also have the reduced numbers of peripheral blood Treg cells and immune imbalance of Th17/Treg, suggesting that immune imbalance or dysfunction caused by defects in Treg cell counts and/or function contributes to the development of EORA, and that targeting Treg cells may be a promising therapeutic strategy for EORA.

Objective:To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA.Methods:A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children′s Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children′s Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00).Results:There was a statistically significant difference in the gender and age distribution between the two groups of children ( P<0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes ( P> 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children′s samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β; production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. Conclusion:DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.

Objective:To investigate the numbers of peripheral blood CD4 +T cell subpopulations in patients with elderly-onset rheumatoid arthritis (EORA) and its clinical significance. Methods:A total of 188 patients with newly diagnosed RA in the department of rheumatology and immunology of the Second Hospital of Shanxi Medical University from January 2020 to December 2023 were collected, including 48 cases of EORA (age of onset: ≥60 years old), 140 cases of young-onset rheumatoid arthritis (YORA) (18 years old ≤ age of onset < 60 years old). Meanwhile, 151 healthy controls (HC) were collected, of which 31 persons aged 60-85 years were included as HC group 1 (HC 1) and 120 individuals aged 18-59 years were included as HC group 2 (HC 2). Peripheral blood CD4 +T lymphocyte subsets of these participants were assessed by flow cytometry. Differences between groups were analyzed using independent-samples t test, Mann-Whitney U test or χ2 test. Results:Compared with healthy individuals, the absolute counts and percentages of peripheral blood Treg cells in patients with EORA were significantly decreased [absolute counts: 32.65 (23.04, 47.73) cells/μl vs. 23.03 (15.28, 32.12) cells/μl, Z=-3.35, P=0.001; percentages: 5.12%(4.13%, 6.16%) vs. 3.72% (2.79%, 4.82%), Z=-4.10, P<0.001], while the Th17/Treg cell ratio was increased [0.16 (0.12, 0.29) vs. 0.26 (0.18, 0.46), Z=-2.94, P=0.003], the differences are all significant. There was a tendency with higher absolute counts and percentages of Treg [absolute counts: 23.03 (15.28, 32.12) cells/μl vs. 20.97 (14.01, 30.64) cells/μl, Z=-0.58, P=0.561; percentages: 3.72%(2.79%, 4.82%) vs. 3.38% (2.39%, 4.71%), Z=-1.06, P=0.287] and lower Th17/Treg ratios [0.26 (0.18, 0.46) vs. 0.27 (0.19, 0.46), Z=-0.32, P=0.751] in EORA when compared to patients with YORA, but no significant differences were observed. Conclusion:Patients with EORA also have the reduced numbers of peripheral blood Treg cells and immune imbalance of Th17/Treg, suggesting that immune imbalance or dysfunction caused by defects in Treg cell counts and/or function contributes to the development of EORA, and that targeting Treg cells may be a promising therapeutic strategy for EORA.

Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

Sepsis-associated acute kidney injury (SA-AKI) is defined as the presence of acute kidney injury (AKI) in the context of sepsis. In the setting of genetic susceptibility, sepsis can lead to SA-AKI through various mechanisms. Based on differences in pathophysiological mechanisms, SA-AKI is categorized into different "endotypes" and manifests as distinct "subtypes". The combination of biomarkers and predictive models has the potential to early identify high-risk AKI patients and elucidate SA-AKI "endotypes". Volume resuscitation and blood purification are optimized strategies for SA-AKI treatment. Furthermore, clinical research on SA-AKI in children is promising.

Objective:To summarize the clinical features and genetic characteristics of Congenital bile acid synthetic disorder type 3 (BASD3) disorder caused by CYP7B1 gene variation.Methods:This was a case series study. Clinical data and genetic results of 2 cases of congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variations in the Department of Infectious Diseases, Children′s Hospital of Fudan University at Xiamen and Department of Pediatrics, Women and Children′s Hospital, School of Medicine, Xiamen University from January 2021 to December 2023 were retrospectively collected and analyzed. Literature up to December 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of " Congenital bile acid synthetic disorder type 3""Oxysterol 7-alpha-hydroxylase""Oxysterol 7α-Hydroxylase Deficiency""BASD3" and "CYP7B1 liver" both in Chinese and English. The main clinical features and genetic characteristics of BASD3 disorder caused by CYP7B1 gene variations were summarized.Results:Two BASD3 patients, 1 male and 1 female, were admitted at the ages of 3 months and 18 days, and 2 months and 7 days, respectively. Both patients presented with neonatal cholestasis and hepatomegaly. Biochemical evidence indicated direct hyper-bilirubinemia with elevated aminotransferase levels, while gamma-glutamyltransferase (GGT) and total bile acid levels were normal or nearly normal. Patient 1 was a compound heterozygotes of the CYP7B1 gene variants c.525-526insCAAGTTGG(p.Asp176GInfs*15) and c.334C>T(p.Arg112Ter). Patient 1 jaundice resolved and liver function tests normalized after oral administration of chenodeoxycholic acid (CDCA). Patient 2 was homozygous for variant c.334C>T(p.Arg112Ter) in CYP7B1 gene. Patient 2 was in liver failure status already and not reactive to oral CDCA administration. Patient 2 received living-related liver transplantation for enhanced abdominal CT revealed a liver tumor likely vascular origin. Literature review revealed no cases of BASD3 reported in Chinese literature, including 2 patients in this study, while 12 patients (9 males and 3 females) were reported in 9 English literatures. All of the 12 manifested jaundice and hepatosplenomegaly in infancy, with cirrhosis, liver failure, kidney enlargement, hypoglycemia, and spontaneous bleeding in some cases, polycystic kidney disease was demonstrated in 5 cases of them. The c.334C>T (p.Arg112Ter) of the CYP7B1 gene was homozygous in 4 cases and compound heterozygous in 2 cases. Among the 12 children, 6 cases received CDCA treatment, while 6 cases not. Four survived with their native liver in the 6 cases who received CDCA therapy, while none in the 6 cases not received CDCA therapy.Conclusions:BASD3 is a rare hereditary cholestatic disorder. Markedly elevated levels of conjugated bilirubin and aminotransferases, with normal or nearly normal GGT and total bile acid levels can serve as diagnostic clue. c.334C>T is the most common pathogenic variant of the CYP7B1 gene. Timely administration of CDCA may save the liver.

Objective To investigate the clinical application value of MRI Radiomics score(Radscore)combined with clinicopatho-logical features in predicting postoperative progression-free survival(PFS)of patients with endometrial cancer(EC).Methods A total of 127 patients with EC were selected.The radiomic features of the lesions were extracted from T2 WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images.The features were screened by random forest model and Radscore was calcu-lated.Simultaneously,clinical and pathological characteristics of patients were collected and incorporated,and multivariate Cox regression analysis was used to screen the risk factors related to PFS.The MRI Radscore and clinicopathological features were mapped to the nomogram,and the performance of nomogram was evaluated by receiver operating characteristic(ROC)curve and calibration curve.Results Multivariate Cox regression analysis showed that progesterone receptor(PR),human epididymis protein 4(HE4)and MRI Radscore were independent risk factors for predicting PFS in patients with EC(P＜0.05).The area under the curve(AUC)of the predicted PFS at 1,3 and 5 years after surgery were 0.91,0.804 and 0.776,respectively.Calibration curves showed that nomogram had a good fit in predicting PFS in patients with EC 1,3 and 5 years after surgery.Conclusion The nomogram con-structed based on multi-sequence MRI Radscore and clinicopathological features has favorable accuracy and stability in predicting postoperative PFS in individuals diagnosed with EC.