Objective:To explore the active ingredients of shengxian and jinshuiliujun decoction with the method of network pharmacology, and to verify the experimental mechanism of its treatment of silicosis.Methods:In May 2023, the active ingredients and targets of drugs in shengxian and jinshuiliujun decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The target of silicosis disease was screened by databases such as Genecards, Disease Gene Network (DisGeNET), Comparative Toxicogenomics Database (CTD), etc. The screened drug targets and disease targets were intersected to obtain the target set of shengxian and jinshuiliujun decoction for the treatment of silicosis. Protein-protein interaction (PPI) network analysis was performed on the target set through STRING database, and core target genes were screened. GO enrichment analysis and KEGG pathway analysis of intersection genes were performed based on Metascape database, and molecular docking verification of key components and targets of shengxian and jinshuiliujun decoction was carried out. Twenty-four adult male SD rats with SPF grade were randomly divided into control group, model group and TCM intervention group, with 8 rats in each group. The dust-stained rat model was prepared by non-tracheal exposure of 1 ml silica suspension (50 mg/ml) in one go, and TCM intervention group was given shengxian and jinshuiliujun decoction[6 g/ (kg·d) ] on the second day. The CT of the lungs of each group was observed 28 days after the dust-stained rat model. Paraffin sections of rat lung tissues were prepared and stained with Hematoxylin-Eosin (HE) and Masson. Western blot was used to verify the expression of core target-related proteins in rat lung tissues after the intervention of shengxian and jinshuiliujun decoction for 28 days, and the differences in protein expression between groups were compared by one-way analysis of variance.Results:A total of 205 active ingredients and 3345 active compounds were selected from shengxian and jinshuiliujun decoction, corresponding to 281 targets, among which 240 targets were related to silicosis. Serine/threonine kinase 1 (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF) and interleukin (IL) 6 may be the key targets of shengxian and jinshuiliujun decoction in the treatment of silicosis. Through enrichment analysis, 30 GO entries and 20 potential signaling pathways were screened according to P-value, including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) and cancer signaling pathways. Molecular docking showed that the active compounds of shengxian and jinshuiliujun decoction had good binding with the core target proteins, and the strongest binding properties were beta-sitosterol and TNF-α (-10.45 kcal/mol). In animal experiments, the inflammatory infiltration and fibrosis of lung tissue of rats in TCM intervention group were significantly improved. Compared with control group, the levels of TNF-α, IL-1β, IL-6 and NF-κB in lung tissue of model group were significantly increased ( P<0.05). Compared with model group, the lung injury of rats in TCM intervention group was significantly improved, and the expressions of TNF-α, IL-1β, IL-6 and NF-κB were significantly decreased ( P<0.05) . Conclusion:Shengxian and jinshuiliujun decoction in the treatment of silicosis may play an anti-fibrosis role by inhibiting the NF-κB signal transduction pathway mediated by inflammatory factors such as TNF-α and IL-1β, which provides a reference for further exploring the material basis and mechanism of its action.

Objective:To explore the genetic etiology of pediatric intensive care unit (PICU) mortality cases and summarize their clinical characteristics.Methods:This was a retrospective cohort study. The study population consisted of 234 children who died within 7 d after admitted to the PICU of Children′s Hospital of Fudan University from January 2017 to December 2021. The clinical diagnoses, laboratory test results, and genetic testing results were collected. These patients were divided into the pathogenic gene variation positive (PGVP) group and the pathogenic gene variation negative (PGVN) group according to the results of genetic testing. The Mann-Whitney U test and Pearson′s chi-square test or Fisher′s exact probability method were used to compare the clinical characteristics between the groups. Results:A total of 234 cases were enrolled, including 139 (59.4%) males and 95 (40.6%) females. The age at death was 1.0 (0.4, 3.7) years old and the length of PICU stay was 16 (6, 33) days. There were 62 cases (26.5%) PGVP, and the mutated pathogenic genes included immune genes (23 cases (37.1%)), metabolic genes (11 cases (17.7%)), neuromuscular genes (11 cases (17.7%)), cardiovascular genes (4 cases (6.5%)), and genes of other systems (13 cases (21.0%)). The age at death in PGVP cases was significantly lower than in PGVN cases (0.6 (0.3, 1.4) vs. 1.3(0.5, 4.3) years old, Z=3.85, P<0.001). Compared with the PGVN group, the PGVP group had a higher incidence of family history and chronic complex conditions (CCC) than the PGVN group (6.5% (4/62) vs. 0.6% (1/172) and 93.5% (58/62) vs. 76.2% (131/172), χ2=8.87, P=0.018 and 0.003, respectively). Children in the PGVP group were admitted with higher incidence of severe infection, decreased consciousness or coma, moderate-to-severe anemia, thrombocytopenia, protracted diarrhea, and abnormalities in muscle strength or tone than those in the PGVN group (74.2%(46/62) vs. 45.9%(79/172), 50.0%(31/62) vs. 35.5%(61/172), 32.3%(20/62) vs. 18.0%(31/172), 21.0%(13/62) vs. 10.5%(18/172), 25.8%(16/62) vs. 4.1%(7/172), 16.1%(10/62) vs. 5.2%(9/172), χ2=14.63, 4.04, 5.41, 4.37, 24.30, 7.25, all P<0.05). Pathogenic genes that occurred more than twice included IL2RG (5 cases), SMN1 (4 cases), and SH2D1A (3 cases, including 2 single gene varients and 1 copy number varient). Conclusions:Among the deceased cases in the PICU, the main genetic causes are immune-related, metabolic, and neuromuscular genetic disorders. Critically ill children with a family history, CCC, and early features such as severe infections, decreased consciousness or coma, moderate to severe anemia, thrombocytopenia, protracted diarrhea, or abnormalities in muscle strength or tone should be closely monitored and undergo early genetic testing.

Objective:To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) .Methods:The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups.Results:The baseline parameters were balanced between the two groups ( P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant ( P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups ( P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% ( P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) ( P=0.198) . Conclusion:The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.

Objective:To explore the active ingredients of shengxian and jinshuiliujun decoction with the method of network pharmacology, and to verify the experimental mechanism of its treatment of silicosis.Methods:In May 2023, the active ingredients and targets of drugs in shengxian and jinshuiliujun decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The target of silicosis disease was screened by databases such as Genecards, Disease Gene Network (DisGeNET), Comparative Toxicogenomics Database (CTD), etc. The screened drug targets and disease targets were intersected to obtain the target set of shengxian and jinshuiliujun decoction for the treatment of silicosis. Protein-protein interaction (PPI) network analysis was performed on the target set through STRING database, and core target genes were screened. GO enrichment analysis and KEGG pathway analysis of intersection genes were performed based on Metascape database, and molecular docking verification of key components and targets of shengxian and jinshuiliujun decoction was carried out. Twenty-four adult male SD rats with SPF grade were randomly divided into control group, model group and TCM intervention group, with 8 rats in each group. The dust-stained rat model was prepared by non-tracheal exposure of 1 ml silica suspension (50 mg/ml) in one go, and TCM intervention group was given shengxian and jinshuiliujun decoction[6 g/ (kg·d) ] on the second day. The CT of the lungs of each group was observed 28 days after the dust-stained rat model. Paraffin sections of rat lung tissues were prepared and stained with Hematoxylin-Eosin (HE) and Masson. Western blot was used to verify the expression of core target-related proteins in rat lung tissues after the intervention of shengxian and jinshuiliujun decoction for 28 days, and the differences in protein expression between groups were compared by one-way analysis of variance.Results:A total of 205 active ingredients and 3345 active compounds were selected from shengxian and jinshuiliujun decoction, corresponding to 281 targets, among which 240 targets were related to silicosis. Serine/threonine kinase 1 (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF) and interleukin (IL) 6 may be the key targets of shengxian and jinshuiliujun decoction in the treatment of silicosis. Through enrichment analysis, 30 GO entries and 20 potential signaling pathways were screened according to P-value, including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) and cancer signaling pathways. Molecular docking showed that the active compounds of shengxian and jinshuiliujun decoction had good binding with the core target proteins, and the strongest binding properties were beta-sitosterol and TNF-α (-10.45 kcal/mol). In animal experiments, the inflammatory infiltration and fibrosis of lung tissue of rats in TCM intervention group were significantly improved. Compared with control group, the levels of TNF-α, IL-1β, IL-6 and NF-κB in lung tissue of model group were significantly increased ( P<0.05). Compared with model group, the lung injury of rats in TCM intervention group was significantly improved, and the expressions of TNF-α, IL-1β, IL-6 and NF-κB were significantly decreased ( P<0.05) . Conclusion:Shengxian and jinshuiliujun decoction in the treatment of silicosis may play an anti-fibrosis role by inhibiting the NF-κB signal transduction pathway mediated by inflammatory factors such as TNF-α and IL-1β, which provides a reference for further exploring the material basis and mechanism of its action.

OBJECTIVE To investigate the mechanisms by which Pinggan Yishen Decoction(PGYSD)contributes to alleviating target organ damage in spontaneously hypertensive rats.METHODS The chemical components of PGYSD were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)and were analyzed by target a-nalysis and functional enrichment combined with network pharmacology methods to predict the potential mechanism of PGYSD in trea-ting hypertension and its target organ damage.Spontaneously hypertensive rats were randomly divided into the model group,low-dose PGYSD group(2 g·kg-1),high-dose PGYSD group(5 g·kg-1),and valsartan group(7.2 mg·kg-1),with 6 rats in each group.Wistar-Kyoto rats were used as the control group,and the control group and the model group were gavaged with normal saline for 8 consecutive weeks.HE and Masson staining were used to observe the pathological damage and fibrosis degree of rat heart and tho-racic aorta.Immunohistochemical staining and Western blot were used to detect the expression level of EGFR in the heart,liver and kidney of rats.Immunofluorescence staining was used to detect the co-localization of EGFR and EEA1 in the heart,liver and kidney of rats.RESULTS Twenty-six components of PGYSD were detected by UPLC-Q-TOF/MS.Network pharmacology revealed that EG-FR,PIK3R1 and EP300 may be key therapeutic targets of action of PGYSD for the treatment of hypertension and its target organ dam-age,and that the treatment of hypertension and its target organ damage by PGYSD may be closely related to EGFR tyrosine kinase in-hibitor resistance,lipids and atherosclerosis and HIF-1 signaling pathway.The high-dose group of PGYSD significantly reduced sys-tolic blood pressure and mean blood pressure in rats(P<0.05,P<0.01),attenuated pathological damage and fibrosis in the heart and thoracic aorta(P<0.01,P<0.001),significantly reduced the expression level of EGFR in the liver and kidney of rats(P<0.01),and treated fibrosis in liver and kidney,reduced the co-localization of EGFR and EEA1 in the kidney of rats(P<0.001),attenuated fibro-sis in kidney.CONCLUSION The paper integrates UPLC-Q-TOF/MS,network pharmacology and spontaneously hypertensive rat model and preliminarily explores the effect mechanism of PGYSD in the treatment of hypertension and its target organ damage,provi-ding a scientific basis for further mechanism research and clinical application of PGYSD in the treatment of hypertension.

Objective To investigate the accuracy and feasibility of shear wave elastography(SWE)combined with superb microvascular imaging(SMI)for the differential diagnosis of benign and malignant thyroid nodules.Methods A total of 190 patients with thyroid nodu-les detected in the Ultrasound Department of our hospital from January 2021 to December 2022 who underwent ultrasound-guided fine-needle aspiration biopsy or exhibited postoperative histopathological improvement were selected as the study subjects.Among them,a total of 224 thyroid nodules(74 benign and 150 malignant nodules)were detected,all of whom underwent thyroid ultrasonography,SWE,and SMI.The parameters related to the Young's modulus of the tissue as well as the condition of fine blood flow and perforating vessels were calculated.Using histopathological results as the gold standard to construct receiver operating characteristic(ROC)curves,observe the effectiveness of SWE combined with SMI in the differential diagnosis of thyroid nodules,and compare the efficacy of different examination methods in the diagnosis of thyroid nodules.Results There were significant differences in the internal composition,echo,margin,cal-cification,and aspect ratio between the benign and malignant thyroid nodules(all P<0.05);however,there was no significant difference in the average diameter of the benign and malignant nodules(P>0.05).There were statistically significant differences in maximum elas-ticity,mean elasticity,elasticity ratio,microvascular score,peak shear wave velocity,and average shear wave velocity between the benign and malignant thyroid nodules(all P<0.05).The ROC curve showed that the area under the curve of the maximum elastic value was the highest,while the optimal diagnostic threshold was 29.52 kPa.The optimal diagnostic threshold for the microvascular flow score was 2.3 points.In terms of diagnostic efficacy,SWE combined with SMI showed the highest sensitivity(94.67%)and specificity(94.59%).Conclusion SWE combined with SMI can further improve the diagnostic efficiency of benign and malignant thyroid nodules and achieve quantitative evaluation and dynamic observation of lesions,which has application and promotion value.

Objective: To investigate the prognostic utility of radiomics features extracted from 18 F-fluorodeoxyglucose (FDG) PET/CT combined with clinical factors and metabolic parameters in predicting progression-free survival (PFS) and overall survival (OS) in individuals diagnosed with extranodal nasal-type NK/T cell lymphoma (ENKTCL). Materials and Methods: A total of 126 adults with ENKTCL who underwent 18 F-FDG PET/CT examination before treatment were retrospectively included and randomly divided into training (n = 88) and validation cohorts (n = 38) at a ratio of 7:3.Least absolute shrinkage and selection operation Cox regression analysis was used to select the best radiomics features and calculate each patient’s radiomics scores (RadPFS and RadOS). Kaplan–Meier curve and Log-rank test were used to compare survival between patient groups risk-stratified by the radiomics scores. Various models to predict PFS and OS were constructed, including clinical, metabolic, clinical + metabolic, and clinical + metabolic + radiomics models. The discriminative ability of each model was evaluated using Harrell’s C index. The performance of each model in predicting PFS and OS for 1-, 3-, and 5-years was evaluated using the time-dependent receiver operating characteristic (ROC) curve. Results: Kaplan–Meier curve analysis demonstrated that the radiomics scores effectively identified high- and low-risk patients (all P < 0.05). Multivariable Cox analysis showed that the Ann Arbor stage, maximum standardized uptake value (SUVmax), and RadPFS were independent risk factors associated with PFS. Further, β2-microglobulin, Eastern Cooperative Oncology Group performance status score, SUVmax, and RadOS were independent risk factors for OS. The clinical + metabolic + radiomics model exhibited the greatest discriminative ability for both PFS (Harrell’s C-index: 0.805 in the validation cohort) and OS (Harrell’s C-index: 0.833 in the validation cohort). The time-dependent ROC analysis indicated that the clinical + metabolic + radiomics model had the best predictive performance. Conclusion The PET/CT-based clinical + metabolic + radiomics model can enhance prognostication among patients with ENKTCL and may be a non-invasive and efficient risk stratification tool for clinical practice.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

Objective: To analyze the current nutritional composition of commonly consumed prepackaged foods among children in Chengdu and to provide a scientific basis for health education among children and adolescents. Methods: Based on the 3 day and 24 hour dietary data of children aged 6-12 in Chengdu of the Southwest China Childhood Nutrition and Growth Cohort from 2021 to 2022, the nutritional information of prepackaged foods was collected by combining offline and online methods. All foods were classified step by step, and the nutrient content of each 100 g or 100 mL food was counted and graded. Results: A total of 1 902 children s prepackaged foods in 23 sub categories of 10 major categories were investigated. Nuts and seeds, snack foods, instant foods and other dairy products had higher total energy(2 476, 2 027, 1 728, 1 816 kJ/100 g), with the nutrient reference value percentage(NRV%) exceeding 20%. Fish, poultry, meat, eggs and their products had the highest protein content(22.8 g/ 100 g ) with an NRV% of 38%, nuts and seeds had the highest fat content(47.5 g/100 g) with an NRV% of 79%, confectionery and jelly had the highest carbohydrate content(82.1 g/100 g) with an NRV% of 27%, and seasoning flour products had the highest sodium content with an NRV% up to 118%. Seasoning flour products and instant foods were mostly high sodium, high fat and high carbohydrate food. Baked and puffed foods were almost high fat and high carbohydrate. Fish, poultry, meat, eggs, beans and their products were rich in protein but mostly high in sodium. Beverages and cold drinks were low in other nutrients except carbohydrate. Conclusion The nutrient content of various prepackaged foods commonly consumed by children in Chengdu are quite different. Most of the foods consumed by children are high sodium, high fat and/or high carbohydrate. Nutrition education should be strengthened to help children choose healthy foods.

Abstract OBJECTIVE To explore the material basis and mechanism of Crataegi Fructus in improving metabolic hypertension(MH) by using network pharmacology and molecular docking technique.METHODS The components of Crataegi Fructus were collected by HERB, ETCM database and literature survey; screening all ingredients of Crataegi Fructus to improve MH targets through databases such as SwissTargetPrediction and GeneCards; build "active ingredient-target-disease" network of Crataegi Fructus with Cytoscape software; DAVID was used to analyze GO enrichment and KEGG pathway. The core components and core targets were verified by molecular docking with Autodock software. RESULTS The total of 89 active components were screened from Crataegi Fructus and acted on 84 targets. Among them, the core active components of Crataegi Fructus to improve MH were maslinic acid, fomefficinic acid B, linolenic acid, linoleic acid, methyl-n-nonylketone, apigenin, ursolic acid, etc. The core targets were CYP19A1, PPARA, ESR1, PTGS2, PPARG, NR3C1, MMP9, TNF, etc. The mechanism of action mainly involved multiple signaling pathways such as inflammation, glycolipid metabolism, and vascular endothelial function. Molecular docking showed that the core active ingredients of Crataegi Fructus had high affinity with core targets. CONCLUSION Crataegi Fructus may regulate multiple signaling pathways such as TNF, IL-17, AGE-RAGE, HIF-1, cGMP-PKG through multi-component regulation, thereby inhibiting inflammatory response, improving glucose and lipid metabolism abnormalities, and improving vascular endothelial function, so as to comprehensively exert the role of improving MH in various aspects.