Objective:To evaluate the changes in brain network function indicators in premature infants with language developmental disorders by resting state functional magnetic resonance imaging (rs-fMRI).Methods:Premature infants admitted to Changzhou Children's Hospital Affiliated to Nantong University from January 2021 to December 2023 were selected as the study subjects to evaluate language development. Language development assessment was conducted using the Gesell developmental scales during follow-up until 12 months of corrected gestational age. According to the evaluation results, the subjects were divided into language development disorders group (31 cases) and normal language development group (19 cases). rs-fMRI was performed on all premature infants with corrected gestational age of 40-42 weeks. The amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis were performed on MRI data. Regions of interest (ROI) were obtained as seed points based on previous literature, then functional connectivity (FC) was extracted between these ROIs for inter-group comparison. Independent sample t-test, non parametric test, chi-square test, and Fisher's exact test were performed on the data using SPSS 23.0 software. Results:(1)There were statistically significant differences in birth weight, gestational age, moderate to severe respiratory distress syndrome, sepsis, and maternal education level between the two groups of premature infants (all P<0.05).(2)The FC values of left temporal gyrus-left angular gyrus (1.220±0.155, 1.139±0.118), left insula-left trigone (0.520±0.199, 0.411±0.152), and left angular gyrus-left marginal gyrus (1.588±0.333, 1.330±0.437) in language development disorders group were higher than those in normal language development group ( t=-2.089, -2.186, -2.359, all P<0.05). There was no statistically significant difference in the FC values of ROI-ROI between the two groups in the right hemisphere of the brain (all P>0.05). The FC values of left superior temporal gyrus-right insula (0.588±0.257, 0.398±0.305) and left superior temporal gyrus-right marginal gyrus (1.550±0.393, 1.374±0.213) in language development disorders group were higher than those in the normal language development group ( t=-2.363, 2.057, both P<0.05). Conclusions:Functional connectivity between local brain regions in preterm infants with language development is significantly enhanced. The change of local brain network functional connectivity has certain predictive value for the language developmental outcome of preterm infants.

Objective:To summarize the clinical and genetic characteristics of 23 children with pathogenic ACAN gene variants, enhance the understanding of this disorder, and explore possible regulatory mechanisms. Methods:A retrospective case series summary.The clinical characteristics and genetic analysis results of 23 children with ACAN gene variants treated in the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Soochow University from January 2016 and September 2024 were analyzed retrospectively.Transcriptome sequencing was performed on peripheral blood samples from 3 of affected children and 3 age-matched healthy children as controls.Differentially expressed genes (DEGs) in the peripheral blood transcriptome profiles were identified.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to explore the potential signaling pathways involved. Results:Among the 23 cases, there were 13 males and 10 females, aged from 2 years and 8 months to 12 years old, with 11 cases presenting advanced bone age.Thirteen cases were treated with growth hormone (GH), including 6 cases who received concomitant gonadotropin-releasing hormone analogue therapy.The treatment duration ranged from 3 to 70 months, resulting in varying degrees of height improvement in all treated patients.Transcriptomic analysis identified 811 DEGs, with 516 up-regulated and 295 down-regulated.GO and KEGG enrichment analyses revealed that the heterozygous ACAN variants were significantly associated with FcγR-mediated phagocytosis, nuclear factor-κB signaling pathway, the intestinal immune network for IgA production, rheumatoid arthritis, and systemic lupus erythematosus signaling pathways. Conclusions:The predominant clinical manifestations of patients with ACAN gene variants are short stature and advanced bone age.Although GH provocation tests may indicate normal GH levels, GH therapy can be effective in improving height.Immune-related factors may play a role in the pathogenesis of this disorder.

Objective:To evaluate the changes in brain network function indicators in premature infants with language developmental disorders by resting state functional magnetic resonance imaging (rs-fMRI).Methods:Premature infants admitted to Changzhou Children's Hospital Affiliated to Nantong University from January 2021 to December 2023 were selected as the study subjects to evaluate language development. Language development assessment was conducted using the Gesell developmental scales during follow-up until 12 months of corrected gestational age. According to the evaluation results, the subjects were divided into language development disorders group (31 cases) and normal language development group (19 cases). rs-fMRI was performed on all premature infants with corrected gestational age of 40-42 weeks. The amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis were performed on MRI data. Regions of interest (ROI) were obtained as seed points based on previous literature, then functional connectivity (FC) was extracted between these ROIs for inter-group comparison. Independent sample t-test, non parametric test, chi-square test, and Fisher's exact test were performed on the data using SPSS 23.0 software. Results:(1)There were statistically significant differences in birth weight, gestational age, moderate to severe respiratory distress syndrome, sepsis, and maternal education level between the two groups of premature infants (all P<0.05).(2)The FC values of left temporal gyrus-left angular gyrus (1.220±0.155, 1.139±0.118), left insula-left trigone (0.520±0.199, 0.411±0.152), and left angular gyrus-left marginal gyrus (1.588±0.333, 1.330±0.437) in language development disorders group were higher than those in normal language development group ( t=-2.089, -2.186, -2.359, all P<0.05). There was no statistically significant difference in the FC values of ROI-ROI between the two groups in the right hemisphere of the brain (all P>0.05). The FC values of left superior temporal gyrus-right insula (0.588±0.257, 0.398±0.305) and left superior temporal gyrus-right marginal gyrus (1.550±0.393, 1.374±0.213) in language development disorders group were higher than those in the normal language development group ( t=-2.363, 2.057, both P<0.05). Conclusions:Functional connectivity between local brain regions in preterm infants with language development is significantly enhanced. The change of local brain network functional connectivity has certain predictive value for the language developmental outcome of preterm infants.

Objective:To verify the prognostic value of perineural invasion and lymphovascular tumor embolus for patients with gastric cancer undergoing gastrectomy and postoperative chemotherapy, and establish a prognostic prediction nomogram model.Methods:According to 7∶3 radio, 781 gastric cancer patients were randomly divided into training cohort and internal validation cohort. One hundred fifty patients were utilized as the external validation cohort. Univariate and multivariate analysis were performed to evaluate the prognostic value of perineural invasion and lymphovascular tumor embolus, and construct the dynamic nomogram. The concordance index (C-index), net reclassification index and integrated discrimination improvement index, receiver operating characteristic curve, calibration curves and decision curve analysis were used to evaluate the nomogram.Results:Perineural invasion ( HR=1.486, 95% CI: 1.150-1.919, P<0.01) and lymphovascular tumor embolus ( HR=1.321, 95% CI: 1.030-1.693, P<0.05) were independent prognostic risk factors for patients with gastric cancer after gastrectomy and postoperative chemotherapy. C-index (training cohort: 0.734, internal validation cohort: 0.755, external validation cohort: 0.715), net reclassification index (training cohort: 0.228 for 3-year and 0.213 for 5-year OS prediction; internal validation cohort: 0.211 for 3-year and 0.279 for 5-year OS prediction; external validation cohort: 0.220 for 3-year and 0.440 for 5-year OS prediction) and integrated discrimination improvement index (training cohort: 0.051 for 3-year and 0.041 for 5-year OS prediction; internal validation cohort: 0.027 for 3-year and 0.036 for 5-year OS prediction; external validation cohort: 0.063 for 3-year and 0.153 for 5-year OS prediction) indicated that the nomogram performed better than the traditional TNM staging system ( P<0.05). Conclusions:Perineural invasion and lymphovascular tumor embolus are independent prognostic risk factors of gastric cancer patients after postoperative chemotherapy. The novel dynamic nomogram model based on perineural invasion and lymphovascular tumor embolus provides better assistance in evaluating prognosis of gastric cancer patients.

Objective:To assess the effects of allergens on interleukin-18 (IL-18), IL-18 binding protein a (IL-18BPa), and IL-18 receptor α (IL-18Rα) expression levels in different monocyte subtypes of the peripheral blood samples of allergic asthma (AA) patients, and the correlations between the percentage of IL-18 +classical monocytes and plasma levels of pro-inflammatory cytokines. Methods:A cross-sectional study. Blood samples were collected from 28 healthy controls and 33 patients experiencing acute attack of AA based on a positive skin prick test of Henan Provincial People′s Hospital from February 2023 to April 2024. Flow cytometry was used to assess the effects of allergens on IL-18, IL-18BPa, and IL-18Rα expression levels in the classical, intermediate, and non-classical monocytes of the peripheral blood samples of AA patients. Kruskal-Wallis test and Pairwise test were used to analyze statistical significance between groups. Plasma tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) levels were estimated using Bioplex assays. Pearson correlation test was used to determine the association between the percentage of IL-18 +classical monocytes and the plasma levels of IL-1β and TNF-α. Results:Compared with healthy controls, the percentages of classical and non-classical monocytes in the peripheral blood of AA patients were reduced by 20.2% ( Z=-3.89, P<0.001) and 45.8% ( Z=-4.01, P<0.001), respectively. Allergens increased the percentages of classical, intermediate, and non-classical monocytes in AA patients in vitro by 13.1%-61.5% (all P<0.05). Compared with healthy controls, the percentages of IL-18 expression in classical monocytes of AA patients was elevated by 1.08-fold ( Z=-6.40, P<0.001), whereas the percentages of IL-18 expression in intermediate and non-classical monocytes were reduced by 52.7% ( Z=-6.40, P<0.001) and 3.23% ( Z=-3.13, P=0.001), respectively. Allergens upregulated IL-18 expression by 16.4%-67.8% in the classical and intermediate monocytes of AA patients (all P<0.05). Compared with healthy controls, IL-18BPa expression level was lower in the three monocyte subtypes of AA patients (all P<0.05). However, allergens upregulated IL-18BPa expression by 8.9% and 13.3% in the classical monocytes (both P<0.05). Compared with healthy controls, IL-18Rα expression was elevated by 1.29-fold in the classical monocytes of AA patients ( Z=-6.40, P<0.001). Allergens upregulated IL-18Rα expression by 17.6%-39.2% in the three monocyte subtypes of AA patients (all P<0.05). Plasma levels of IL-1β and TNF-α in the AA patients were increased compared to those in healthy controls (all P<0.001), and correlated with the percentage of IL-18 +classical monocytes ( r=0.451, 0.714; both P<0.05). Conclusions:Allergens may participate in the inflammatory response of AA by inducing the differentiation of monocytes and the expression levels of IL-18, IL-18BPa and IL-18Rα in different blood monocytes subtypes. Classical monocytes are the potential source of elevated plasma IL-18 level in AA patients.

Objective:To investigate the effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in blood CD4+Th17 cells of patients with allergic rhinitis and asthma syndrome(ARA)and plasma levels of IL-17A and IL-17F in ARA patients.Methods:ARA patients(n=25)and healthy volunteers(n=22)in the First Affiliated Hospital of Jinzhou Medical University and Henan Provincial People's Hospital were recruited,and blood samples of the subjects were collected.Proportions of CD4+Th17 cells,and effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in Th17 cells were determined by flow cytometry.Levels of IL-17A and IL-17F were examined by Bioplex system.Correlation between levels of free plasma free IL-18(fIL-18)and IL-17A,and per-centage of Th17 cells was further analyzed.Results:Proportion of IL-18+cells in Th17 cells was increased in ARA patients by 26.0%(P<0.01),and house dust mite allergen induced 1.22-fold elevation in expression of IL-18 in Th17 cells(P<0.05).In addition,Arte-misiae sieversiana wild pollen allergen enhanced expressions of IL-18 and IL-18Rα in Th17 cells of ARA patients(P<0.05).Plasma levels of IL-17A and IL-17F were increased by 2.2 and 1.1 folds,respectively(P<0.05)in ARA patients,and they correlated well with other(R=0.712,P<0.01).Moreover,the increased level of fIL-18 was moderately correlated with the increased level of IL-17A and the elevated proportion of Th17 cells in ARA patients(r=0.607,r=0.652,P<0.05).Conclusion:The increased plasma fIL-18 in ARA patients may be derived from Th17 cells.Allergens may be involved in pathogenesis of ARA by inducing elevated IL-18 and IL-18Rα expressions in Th17 cells.

Objective:To investigate the effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in blood CD4+Th17 cells of patients with allergic rhinitis and asthma syndrome(ARA)and plasma levels of IL-17A and IL-17F in ARA patients.Methods:ARA patients(n=25)and healthy volunteers(n=22)in the First Affiliated Hospital of Jinzhou Medical University and Henan Provincial People's Hospital were recruited,and blood samples of the subjects were collected.Proportions of CD4+Th17 cells,and effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in Th17 cells were determined by flow cytometry.Levels of IL-17A and IL-17F were examined by Bioplex system.Correlation between levels of free plasma free IL-18(fIL-18)and IL-17A,and per-centage of Th17 cells was further analyzed.Results:Proportion of IL-18+cells in Th17 cells was increased in ARA patients by 26.0%(P<0.01),and house dust mite allergen induced 1.22-fold elevation in expression of IL-18 in Th17 cells(P<0.05).In addition,Arte-misiae sieversiana wild pollen allergen enhanced expressions of IL-18 and IL-18Rα in Th17 cells of ARA patients(P<0.05).Plasma levels of IL-17A and IL-17F were increased by 2.2 and 1.1 folds,respectively(P<0.05)in ARA patients,and they correlated well with other(R=0.712,P<0.01).Moreover,the increased level of fIL-18 was moderately correlated with the increased level of IL-17A and the elevated proportion of Th17 cells in ARA patients(r=0.607,r=0.652,P<0.05).Conclusion:The increased plasma fIL-18 in ARA patients may be derived from Th17 cells.Allergens may be involved in pathogenesis of ARA by inducing elevated IL-18 and IL-18Rα expressions in Th17 cells.

ObjectiveBased on analytic hierarchy process（AHP）-criteria importance through intercriteria correlation（CRITIC） hybrid weighting method， grey relational analysis and backpropagation artificial neural network（BP-ANN）， to optimize the water extraction process of Qizhi prescription， so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL₉（3⁴） orthogonal test was employed， and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components， including astragaloside Ⅳ， polygalaxanthone Ⅲ， calycosin-7-O-β-D-glucoside， tenuifolin， and 3，6′-disinapoylsucrose， as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times， extraction time， and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis， variance analysis， and grey relational analysis. Meanwhile， a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription， and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components（astragaloside Ⅳ， tenuifolin， calycosin-7-O-β-D-glucoside， polygalaxanthone Ⅲ， and 3，6′-disinapoylsucrose） and dry extract yield were 25.7%， 20.82%， 16.41%， 12.45%， 15.96% and 8.67%， respectively. The optimized extraction process parameters were extracted 3 times with 8， 6， 6 times the amount of water， each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results， and the mean square error（MSE） of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible， which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix， and the average comprehensive score of the validation test was 90.85 with the relative standard deviation（RSD） of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules， and the optimized extraction process can effectively improve the extraction efficiency of active ingredients， which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.

Reasonable and standardised placebo setting for acupoint application pastes is a key factor for clinical trials to verify the safety and effectiveness of acupoint application. By sorting out the current design status of placebo in the allocation concealment and blind design， paste components， paste location， paste duration in the current clinical trials of acupoint application pastes， it is proposed that there are problems such as low application rate of blinding and non-standardised reporting， insufficient standardisation of placebo settings and lack of systematic research， and lack of uniform standards of the placebo evaluation method. Based on the action mechanism of acupoint application， the idea of setting placebo for acupoint application paste is proposed in terms of replacing the application material， controlling the physicochemical effect produced by transdermal absorption of drugs， and setting the permeability of placebo， in order to enrich the methodological content of the placebo setting for acupoint application， and providing more scientific and reliable clinical evidence of acupoint application.

Virus-related lymphoma exhibits a dual nature as both a hematologic malignancy and a viral infectious disease， making it more resistant to treatment and associated with poorer prognosis. This paper analyzes the understanding and therapeutic advantages of traditional Chinese medicine （TCM） in virus-related lymphoma. It proposes a TCM-based approach centered around syndrome differentiation， using standardized measurements of the overall TCM condition， multi-omics research of hematologic tumors， and artificial intelligence technologies to identify the "pre-condition" of virus-related lymphoma. A risk warning model will be established to early identify high-risk populations with viral infections that may develop into malignant lymphoma， thereby establishing a risk warning system for virus-related lymphoma. At the same time， a TCM health management approach will be applied to manage and regulate virus-related lymphoma， interrupting its progression and forming a human-centered， comprehensive， continuous health service model. Based on this， a standardized， integrated clinical prevention and treatment decision-making model for virus-related lymphoma， recognized by both Chinese and western medicine， will be established to provide TCM solutions for primary prevention of major malignant tumors.