ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology， molecular docking， and in vitro cell experiments. MethodsIn this study， the canonical SMILES of magnoflorine was obtained from the PubChem database， and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database， while the disease targets of colon cancer were obtained from the DisGeNET， GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken， and a protein-protein interaction （PPI） network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology （GO） and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally， cellular experiments including CCK-8 assays， EdU experiments， cell scratch assays， and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 （STAT3） in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.

Objective:To investigate influences of tetrandrine(Tet)on proliferation,apoptosis and immune escape of melanoma cells by regulating cyclic GMP-AMP synthase(cGAS)-stimulator of interferon gene(STING)signal pathway.Methods:MV3 cells were divided into NC group,Tet-L group(5 μmol/L),Tet-M group(10 μmol/L),Tet-H group(15 μmol/L),RU.521(cGAS inhibi-tor)group(1 μmol/L),Tet-H+RU.521 group(15 μmol/L+1 μmol/L).Proliferation of MV3 cells was detected by CCK-8 and plate cloning test;apoptosis of MV3 cells was detected by flow cytometry;Western blot was used to detect expressions of proliferating cell nuclear antigen(PCNA),Bcl-2-associated X protein(Bax),TGF-β,cGAS,STING proteins in MV3 cells.Cells in above groups were co-cultured with NK cells for 48 h through Transwell chamber,and named NC co-culture group,Tet-L co-culture group,Tet-M co-culture group,Tet-H co-culture group,RU.521 co-culture group,Tet-H+RU.521 co-culture group,respectively.ELISA was used to detect levels of IFN-γ and Granzyme B in supernatant of co-cultured cells;change of NK cell killing activity was detected.Results:Compared with NC group,A450,cloning rate,PCNA and TGF-β protein expressions of MV3 cells in Tet-L group,Tet-M group and Tet-H group were decreased,apoptosis rate,Bax,cGAS,STING protein expressions were increased,which was in a dose dependent man-ner,change trend of corresponding indexes in RU.521 group was contrary to the above(P<0.05);compared with NC co-culture group,levels of IFN-γ,Granzyme B and NK cell killing activity in supernatant of Tet-L co-culture group,Tet-M co-culture group and Tet-H co-culture group were increased,which was in a dose-dependent manner,change trend of corresponding indexes in RU.521 co-culture group was opposite to the above(P<0.05);RU.521 attenuated inhibition of high-dose Tet on MV3 cell proliferation,immune escape and its promotion on apoptosis.Conclusion:Tet may inhibit melanoma cell proliferation,immune escape and promote cell apoptosis by activating cGAS-STING signal pathway.

Objective:To evaluate the prognostic value of droplet digital PCR(ddPCR)in conjunction with multiparametric flow cytometry(MFC)for measurable residual disease(MRD)detection in predicting relapse risk in patients with acute myeloid leukemia(AML).Methods:In this retrospective cohort study,we have analyzed 78 newly diagnosed patients with AML who underwent combined MRD monitoring using MFC and ddPCR at The Affiliated Hospital of Hebei University(January 2018-January 2025).Clinical outcomes-including MRD negativity rates,cumulative incidence of relapse(CIR),relapse-free survival(RFS),and overall survival(OS)-were systematically evaluated.Prognostic discrim-ination between the MRD-negative and MRD-positive subgroups was compared across standalone and combined detection approaches.Results:With a median follow-up of 17 months(range:2.4-86.7)and a median of one mutation tracked per patient(range:1-3),both MFC-MRD and ddPCR-MRD negative subgroups demonstrated superior 2-year RFS compared with MRD-positive counterparts.Notably,com-bined MFC/ddPCR monitoring enhanced prognostic discrimination,with MRD-negative patients achieving significantly prolonged 2-year RFS compared with MRD-positive patients.MFC-MRD negativity independently predicted improved 2-year OS.Conclusion:ddPCR-based multi-gene MRD profiling provides significant independent prognostic value in patients with AML.The synergistic application of MFC and ddPCR enables superior predictive accuracy for relapse risk and survival outcomes,supporting its integration into standardized MRD monitoring protocols.

Objective:To explore clinical and genetic features of persistent asymptomatic microscopic hematuria in children.Methods:A retrospective case analysis of 135 individuals admitted to Xi ′an Children′s Hospital with persistent asymptomatic microscopic haematuria between January 2016 to December 2023 was conducted. The demographic characteristics, kidney pathology and gene results of 135 individuals were analyzed. One hundred and thirty-five individuals were divided into 2 groups (positive group and negative group) according to family history of glomerulogenic hematuria in first-degree relatives. The differences of hematuria remission, proteinuria and gene variation were compared between the 2 groups. Two independent sample t test, Wilcoxon rank sum test, Pearson Chi-square, Yates′ corrected Chi-squared test or Fisher exact test were used for comparison between groups. Results:All 135 children, with 48 males and 87 females, were 8.5 (6.5, 9.5) years old at first presentation. Kidney biopsy was performed in 73 cases (54.1%). Kidney pathology showed mild lesions in 41 cases (56.2%), thin basement membrane disease (TBMD) in 24 cases (32.9%), typical pathological features of Alport syndrome in 5 cases (6.8%), and other manifestations in 3 cases (4.1%). The positive group comprised 52 individuals, whereas the negative group consisted of 83 individuals. The positive group demonstrated a higher susceptibility in proteinuria and gene variation, while the negative group exhibited a greater rate of hematuria remission ( χ2=5.00, 5.27, 8.52, all P<0.05). Whole exome sequencing was performed in 80 individuals and 18 individuals (22.5%) had a pathogenic or likely pathogenic variant in COL4A3-5. COL4A5 was the most common gene afected, accounting for 11 cases. The 135 individuals were followed up for 4.2 (2.9, 5.1) years, of which 31 cases (22.9%) had complete hematuria remission at 2.1 (1.4, 2.7) years. Up to March 2024, there were also 7 individuals (5.2%) with varying degrees of proteinuria, and 3 individuals (2.2%) with proteinuria progressed to chronic kidney insufficiency. Conclusions:The most common kidney pathological types in children with persistent asymptomatic microscopic hematuria are minor lesions and TBMD. Children with microscopic hematuria whose first-degree relatives have a family history of hematuria are more likely to have proteinuria and gene variants. COL4A3-5 genetic screening could be considered a priority in these children.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To observe the efficacy and safety of adrenocorticotropic hormone (ACTH) therapy in children with steroid dependent nephrotic syndrome (SDNS)/frequently relapsed nephrotic syndrome (FRNS).Methods:The clinical data of children with SDNS/FRNS who received treatment with prednisone acetate tablets were retrospectively collected from June 2019 to June 2023 in the Nephrology Department of Xi′an Children′s Hospital. The children were divided into glucocorticoid+ACTH group and glucocorticoid group, according to whether ACTH was used or not. The differences in cortisol, total cholesterol and 24 hour urinary protein quantity between 2 groups of children at baseline and follow-up endpoints were compared, and the effectiveness (the proportion of no recurrence and discontinuation of glucocorticoid) and occurrence of adverse reactions were evaluated.Results:A total of 39 patients with SDNS/FRNS were included in this study, with 21 cases in the glucocorticoid+ACTH group and 18 cases in the glucocorticoid group. Among the 39 children, there were 33 cases of SDNS and 6 cases of FRNS, respectively. The proportion of baseline low cortisol levels was 76.9% (30/39). The proportion of cortisol levels returning to normal after ACTH treatment in the glucocorticoid+ACTH group was 76.2% (16/21). The baseline and follow-up endpoint for cortisol levels in the glucocorticoid+ACTH group were 28.0(19.8, 51.5) μg/L and 79.9(58.9, 113.0) μg/L, respectively. The baseline and follow-up endpoint for cortisol levels in the glucocorticoid group were 21.0(15.8, 37.4) μg/L and 25.3(18.2, 51.4) μg/L, respectively. In the 2 groups of cortisol levels, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=11.595, P=0.001), there was a statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=19.462, P<0.001), and the difference was statistically significant in the time effect of the glucocorticoid+ACTH group ( Wald χ2=21.100, P<0.001). The baseline and follow-up endpoint for total cholesterol in the glucocorticoid+ACTH group were 4.95(4.23, 5.26) mmol/L and 4.38(4.04, 5.24) mmol/L, respectively. The baseline and follow-up endpoint for total cholesterol in the glucocorticoid group were 4.80 (4.17, 5.28) mmol/L and 5.74 (5.04, 6.88) mmol/L, respectively. In the 2 groups of total cholesterol, there was statistically significant difference in the interaction effect between time and group ( Wald χ 2=9.842, P=0.002), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ 2=12.187, P<0.001), the difference was statistically significant between the 2 groups in the time effect at baseline and the follow-up endpoint (glucocorticoid+ACTH group: Wald χ 2=6.488, glucocorticoid group: Wald χ2=7.112; all P<0.05). The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid+ACTH group were 115 (105, 128) mg/d and 121 (113, 128) mg/d, respectively. The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid group were 118 (113, 125) mg/d and 138 (119, 2 100) mg/d, respectively. In the 2 groups of 24 hour urinary protein quantity, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=7.743, P=0.005), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=7.779, P=0.005), and the difference was statistically significant in the time effect of the glucocorticoid group ( Wald χ2=13.331, P<0.001). The proportion of no recurrence (17/21) and discontinuation of oral glucocorticoid (16/21) in the glucocorticoid+ACTH group were higher than those in the glucocorticoid group (the proportion were both 6/18), and the differences between the 2 groups were statistically significant (the chi square values were 9.084 and 7.240, respectively; all P<0.01). No adverse reactions occurred in the glucocorticoid group. The incidence of adverse reactions in the glucocorticoid+ACTH group was 14.3% (3/21), of which 2 cases developed generalized urticaria and 1 case developed hypertension. Conclusions:ACTH has a good efficacy and safety in children with SDNS/FRNS. The results of this study need to be further validated by increasing the sample size and conducting multicenter studies.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(＜1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.

Objective:To observe the efficacy and safety of adrenocorticotropic hormone (ACTH) therapy in children with steroid dependent nephrotic syndrome (SDNS)/frequently relapsed nephrotic syndrome (FRNS).Methods:The clinical data of children with SDNS/FRNS who received treatment with prednisone acetate tablets were retrospectively collected from June 2019 to June 2023 in the Nephrology Department of Xi′an Children′s Hospital. The children were divided into glucocorticoid+ACTH group and glucocorticoid group, according to whether ACTH was used or not. The differences in cortisol, total cholesterol and 24 hour urinary protein quantity between 2 groups of children at baseline and follow-up endpoints were compared, and the effectiveness (the proportion of no recurrence and discontinuation of glucocorticoid) and occurrence of adverse reactions were evaluated.Results:A total of 39 patients with SDNS/FRNS were included in this study, with 21 cases in the glucocorticoid+ACTH group and 18 cases in the glucocorticoid group. Among the 39 children, there were 33 cases of SDNS and 6 cases of FRNS, respectively. The proportion of baseline low cortisol levels was 76.9% (30/39). The proportion of cortisol levels returning to normal after ACTH treatment in the glucocorticoid+ACTH group was 76.2% (16/21). The baseline and follow-up endpoint for cortisol levels in the glucocorticoid+ACTH group were 28.0(19.8, 51.5) μg/L and 79.9(58.9, 113.0) μg/L, respectively. The baseline and follow-up endpoint for cortisol levels in the glucocorticoid group were 21.0(15.8, 37.4) μg/L and 25.3(18.2, 51.4) μg/L, respectively. In the 2 groups of cortisol levels, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=11.595, P=0.001), there was a statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=19.462, P<0.001), and the difference was statistically significant in the time effect of the glucocorticoid+ACTH group ( Wald χ2=21.100, P<0.001). The baseline and follow-up endpoint for total cholesterol in the glucocorticoid+ACTH group were 4.95(4.23, 5.26) mmol/L and 4.38(4.04, 5.24) mmol/L, respectively. The baseline and follow-up endpoint for total cholesterol in the glucocorticoid group were 4.80 (4.17, 5.28) mmol/L and 5.74 (5.04, 6.88) mmol/L, respectively. In the 2 groups of total cholesterol, there was statistically significant difference in the interaction effect between time and group ( Wald χ 2=9.842, P=0.002), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ 2=12.187, P<0.001), the difference was statistically significant between the 2 groups in the time effect at baseline and the follow-up endpoint (glucocorticoid+ACTH group: Wald χ 2=6.488, glucocorticoid group: Wald χ2=7.112; all P<0.05). The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid+ACTH group were 115 (105, 128) mg/d and 121 (113, 128) mg/d, respectively. The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid group were 118 (113, 125) mg/d and 138 (119, 2 100) mg/d, respectively. In the 2 groups of 24 hour urinary protein quantity, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=7.743, P=0.005), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=7.779, P=0.005), and the difference was statistically significant in the time effect of the glucocorticoid group ( Wald χ2=13.331, P<0.001). The proportion of no recurrence (17/21) and discontinuation of oral glucocorticoid (16/21) in the glucocorticoid+ACTH group were higher than those in the glucocorticoid group (the proportion were both 6/18), and the differences between the 2 groups were statistically significant (the chi square values were 9.084 and 7.240, respectively; all P<0.01). No adverse reactions occurred in the glucocorticoid group. The incidence of adverse reactions in the glucocorticoid+ACTH group was 14.3% (3/21), of which 2 cases developed generalized urticaria and 1 case developed hypertension. Conclusions:ACTH has a good efficacy and safety in children with SDNS/FRNS. The results of this study need to be further validated by increasing the sample size and conducting multicenter studies.

Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(＜1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.