Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Objective: To construct a risk prediction model for pediatric metabolic dysfunction associated steatotic liver disease (MASLD), so as to provide practical tool for the early identification of high risk children. Methods: A healthy cohort of children in Southwest China was established from January 2021 to April 2025. A nested case-control study design was used to include 507 cases MASLD group and 507 cases in non MASLD group. Data on physical measurements, blood biochemical parameters, and liver ultrasound indicators were collected. Conditional Logistic regression was used to analyze the relationship between individual variables and MASLD, Lasso regression was applied for multivariable screening, and a high risk prediction model was constructed and presented in the form of a nomogram. Internal validation was performed using 10 repeated ten fold cross validations to assess model discrimination, accuracy, sensitivity, and specificity. Results: Logistic regression analysis showed that MASLD was associated with central obesity ( OR=22.11, 95%CI =15.62-31.29), apolipoprotein B ( OR=30.24, 95%CI =12.42-73.63), increased hepatorenal echo ( OR=326.00, 95%CI =183.87-578.01), hepatomegaly ( OR=24.98, 95%CI =16.66-37.46) (all P <0.05). The Lasso regression jointly selected 6 key variables, including hepatorenal echo, central obesity, hepatomegaly, right liver lobe inclination, body mass index, and alanine amino transferase. The results of cross validation showed that the average area under the curve (AUC) was 0.999 5, the average accuracy was 98.74%, and the sensitivity and specificity were 98.21% and 99.22% respectively, indicating a good predictive effect of the model. Conclusion The risk prediction model for high risk MASLD among children based on ultrasound and clinical indicators has good prediction effect, which is helpful for the early identification and risk stratification of pediatric MASLD.

Objective To enhance the gamma spectrometry analysis and detection capabilities of personnel in measuring radionuclides in bio-ash, and ensure the accuracy and precision of gamma spectrometer in our laboratory for the analysis of radionuclides in bio-ash. Methods The laboratory participated in the 2024 national interlaboratory comparison for radionuclide measurement in bio-ash. Radionuclides ²⁴¹Am, ¹³⁷Cs, and ⁴⁰K in four different bio-ash samples were measured. Based on the measurement methods specified in GB/T 16145—2022, sample measurement, result calculation, and uncertainty evaluation were performed using spectrometry analysis software and sourceless efficiency calibration software. The measurement results and performance evaluation of the laboratory in the comparison were analyzed, and factors affecting gamma-spectrometry measurement and result interpretation were discussed. Results The relative deviation (D) of the measurement results for radionuclides ²⁴¹Am and ¹³⁷Cs in the four bio-ash samples ranged from −10.2% to 2.0% and −1.7% to 0.3%, respectively. The P statistic ranged from 7.0% to 12.5% and 5.0% to 10.8%, respectively. These results met the criteria of |D| ≤ 20% (MARB), |D| ≤ 2.58P, and P ≤ 20% (MARB). The ζ-scores for the measurement of ⁴⁰K in the four bio-ash samples ranged from 0.8 to 1.3, satisfying the criterion of |ζ| < 2. All measurement results in this laboratory in the comparison were satisfactory. Conclusion The laboratory uses a high-purity germanium gamma spectrometer to measure radionuclides in bio-ash. The self-absorption correction method, analysis method, and uncertainty evaluation are appropriate, which can ensure the accuracy and precision of the measurement results. The measurement results are accurate and reliable.

ObjectiveTo investigate the expression patterns of key steroidogenic enzymes （CYP11A1， HSD3B1， and CYP19A1） in placental tissues from preeclampsia （PE） patients and evaluate​ their potential as biomarkers for PE. MethodsA case-control study was conducted using placental tissues from PE patients （PE group， n=3） and normotensive pregnant women （control group， n=3）. RNA sequencing was performed to identify differentially expressed genes （DEGs）， followed by validation of target gene expression using Western blot， qRT-PCR， and immunohistochemistry. Steroid hormone levels in placental tissues and serum were measured by ELISA. Spearman correlation analysis was used to assess associations between protein expression and clinical parameters， and receiver operating characteristic （ROC） curve analysis was performed to evaluate the predictive value of target genes for PE. ResultsThe results showed that 501 DEGs （P<0.05 and |Log₂Fold Change| >1） were identified in PE placental tissues， with KEGG enrichment analysis revealing significant involvement in steroid hormone biosynthesis pathways. Compared with the control group， PE placental tissues exhibited significantly decreased protein and mRNA expression of HSD3B1 and CYP19A1 （P<0.01）， while CYP11A1 expression was upregulated （P<0.05）. Serum estradiol （E2） and progesterone （P4） levels were significantly reduced in the PE group （P<0.01）， whereas testosterone （T） levels were elevated （P<0.05）. Correlation analysis demonstrated that CYP11A1 expression was positively associated with systolic blood pressure （SBP）， diastolic blood pressure （DBP）， and soluble fms-like tyrosine kinase-1 （sFlt-1） （P<0.01）， but negatively correlated with placental growth factor （PLGF） （P<0.01）. Conversely， HSD3B1 and CYP19A1 expression showed inverse correlations with these clinical parameters （P<0.01）. ROC analysis revealed that CYP11A1， HSD3B1， and CYP19A1 each had an area under the curve （AUC） of 0.778 for predicting PE， with 95%CI ranging from 0.614 to 0.942 （P=0.004）. The sensitivity was 94.4%， and the specificity was 66.7%. ConclusionThese findings suggest that dysregulated expression of steroidogenic enzymes in PE placental tissues contributes to hormonal imbalance， thereby playing a role in PE pathogenesis. Furthermore， CYP11A1， HSD3B1， and CYP19A1 may serve as potential diagnostic biomarkers for PE.

ObjectiveTo investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsAnimal experiments were conducted with 50 female SD rats， which were randomized into a sham operation group （10 rats） and a modeling group （40 rats）. An autologous endometrial transplantation method was used for the modeling of EMs. The 36 successfully modeled rats were randomly allocated into four groups （n=9 each）： The model group， the low-dose （7.87 g·kg^-1） Luoshi Neiyi prescription group， the high-dose （15.74 g·kg^-1） Luoshi Neiyi prescription group， and the dienogest （0.20 mg·kg^-1） group. The physiological status and ectopic lesion volumes of rats in each group were observed. Hematoxylin-eosin （HE） staining was used to observe the morphology of the eutopic endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory factors including interleukin-1β （IL-1β） and prostaglandin E₂ （PGE₂） in the serum of EMs rats. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor A （VEGFA） in the eutopic endometrial tissue. Western blot was adopted to determine the protein levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated nuclear factor-κB （p-NF-κB）/NF-κB， MMP-9， and VEGFA in the eutopic endometrial tissue. In the cell experiments， the cell-counting kit-8 （CCK-8） assay was employed to screen the optimal concentration of Luoshi Neiyi prescription-containing serum， and a scratch assay was performed to assess the migration ability of iheESCs cells. Interventions with Luoshi Neiyi prescription-containing serum， resatorvid （TAK-242， a TLR4 inhibitor）， and lipopolysaccharides （LPS， a TLR4 agonist） were conducted， and Western blot was used to detect the expression of proteins related to the TLR4/NF-κB signaling pathway. ResultsThis experiment successfully replicated 36 EMs rat models. Compared with the sham operation group， the model group exhibited visible ectopic lesions on the abdominal wall and an increase in the writhing response score （P<0.01）. Furthermore， HE staining revealed the model group exhibited a thickened eutopic epithelium， stromal cell disarrangement， and evident infiltration of inflammatory cells. In addition， the model group showed elevated serum levels of IL-1β and PGE₂ （P<0.05， P<0.01）， increased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.01）， and up-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. Compared with the model group， all treatment groups exhibited a reduction in the ectopic lesion volume （P<0.01）. Furthermore， the writhing response scores were decreased in the high-dose Luoshi Neiyi prescription group and the dienogest group （P<0.05， P<0.01）. The pathological state of the ectopic endometrial tissue was alleviated to varying degrees in the treatment groups. Low-dose Luoshi Neiyi prescription reduced serum PGE₂ levels， and high-dose Luoshi Neiyi prescription and dienogest decreased serum IL-1β and PGE₂ levels in EMs rats （P<0.05， P<0.01）. The treatment groups showed decreased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01） and down-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. The cell experiments showed that 5%， 10%， and 20% Luoshi Neiyi prescription-containing sera significantly reduced the viability and inhibited the migration of iheESCs. Compared with the control group， 5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups and the TAK-242 group showed reduced protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA （P<0.01）. Compared with the control group， the LPS group showed increased expression of the above proteins （P<0.01）. Compared with the LPS group， the LPS+5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups showed reduced expression of the above proteins （P<0.05， P<0.01）. ConclusionLuoshi Neiyi prescription may modulate the TLR4/NF-κB signaling pathway to reduce the inflammatory response and histopathological damage in the eutopic endometrium and suppress the adhesive， invasive， and angiogenic biological processes in the ectopic endometrial tissue， thereby exerting its therapeutic effect on EMs.

ObjectiveTo investigate the effects and potential mechanisms of Babaodan （BBD） against acetaminophen （APAP）-induced acute liver injury （ALI） based on transcriptomics. MethodsA total of 36 male C57BL/6 mice were randomly divided into 6 groups （n=6 per group）： normal group， model group， N-acetylcysteine group （NAC， 120 mg·kg^-1）， and BBD low-， medium-， and high-dose groups （BBD-L， BBD-M， BBD-H groups， 75， 150， 300 mg·kg^-1， respectively）. Except for the normal group， all other groups were subjected to APAP-induced ALI. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured in each group. Hepatic levels or activities of malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） were detected using commercial kits. Hematoxylin-eosin （HE） staining was performed to evaluate the degree of liver histopathological damage. Transcriptomic analysis was employed to screen differentially expressed genes （DEGs）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify differential pathways involved in BBD intervention against ALI. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were applied to validate the expression of differential genes and related pathway proteins. Additionally， glucose （GLU） consumption， as well as lactate （LD） and adenosine triphosphate （ATP） content were assessed across all mouse groups. ResultsPharmacodynamic evaluation showed that， compared with the normal group， the model group exhibited significantly elevated serum levels of ALT， AST， TC， TG， and LDL-C （P<0.01）， significantly increased MDA level （P<0.01）， and significantly decreased GSH-Px level （P<0.05）. Compared with the model group， BBD intervention at different doses significantly reduced the serum levels of ALT， AST， TC， TG， and LDL-C （P<0.05， P<0.01）， increased GSH-Px level （P<0.05， P<0.01）， significantly decreased MDA level （P<0.01）， and ameliorated hepatic histopathological injury. Liver transcriptomic analysis revealed that， following high-dose BBD intervention， the core genes were mainly enriched in pathways related to inflammatory responses and energy metabolic reprogramming， including the interleukin-17 （IL-17） signaling pathway， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， fructose and mannose metabolism， and glycolysis. Real-time PCR validation demonstrated that， compared with the normal group， the mRNA expression levels of glycolysis-related genes ［hexokinase 1 （HK1）， hexokinase 2 （HK2）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 4 （PFKFB4）， pyruvate kinase M （PKM）， and lactate dehydrogenase A （LDHA）］， as well as inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］ were significantly upregulated in the model group （P<0.05， P<0.01）. Compared with the model group， the BBD-H group showed significantly decreased mRNA expression of HK1， HK2， PFKFB3， PFKFB4， PKM， LDHA， TNF-α， IL-6， and IL-1β （P<0.05， P<0.01）. Western blot results indicated that， compared with the normal group， the model group had significantly increased expression of glycolysis-related proteins ［glucose transporter 1 （GLUT1）， HK1， PFKFB3， and PKM］， inflammatory proteins ［interleukin-18 （IL-18）， TNF-α， and IL-1β］， and phosphorylated （p）-PI3K and p-Akt proteins （P<0.05， P<0.01）. Compared with the model group， the BBD-H group exhibited significantly decreased expression of GLUT1， HK1， PFKFB3， PKM， IL-18， TNF-α， IL-1β， p-PI3K， and p-Akt （P<0.05， P<0.01）. Metabolic indicator measurements showed that， compared with the model group， the BBD-H group showed significantly reduced GLU consumption， LD and ATP content （P<0.05， P<0.01）. ConclusionBBD may alleviate APAP-induced ALI through dual regulation of metabolic reprogramming and inflammatory responses， potentially via inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the effects and potential mechanisms of Babaodan （BBD） against acetaminophen （APAP）-induced acute liver injury （ALI） based on transcriptomics. MethodsA total of 36 male C57BL/6 mice were randomly divided into 6 groups （n=6 per group）： normal group， model group， N-acetylcysteine group （NAC， 120 mg·kg^-1）， and BBD low-， medium-， and high-dose groups （BBD-L， BBD-M， BBD-H groups， 75， 150， 300 mg·kg^-1， respectively）. Except for the normal group， all other groups were subjected to APAP-induced ALI. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured in each group. Hepatic levels or activities of malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） were detected using commercial kits. Hematoxylin-eosin （HE） staining was performed to evaluate the degree of liver histopathological damage. Transcriptomic analysis was employed to screen differentially expressed genes （DEGs）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify differential pathways involved in BBD intervention against ALI. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were applied to validate the expression of differential genes and related pathway proteins. Additionally， glucose （GLU） consumption， as well as lactate （LD） and adenosine triphosphate （ATP） content were assessed across all mouse groups. ResultsPharmacodynamic evaluation showed that， compared with the normal group， the model group exhibited significantly elevated serum levels of ALT， AST， TC， TG， and LDL-C （P<0.01）， significantly increased MDA level （P<0.01）， and significantly decreased GSH-Px level （P<0.05）. Compared with the model group， BBD intervention at different doses significantly reduced the serum levels of ALT， AST， TC， TG， and LDL-C （P<0.05， P<0.01）， increased GSH-Px level （P<0.05， P<0.01）， significantly decreased MDA level （P<0.01）， and ameliorated hepatic histopathological injury. Liver transcriptomic analysis revealed that， following high-dose BBD intervention， the core genes were mainly enriched in pathways related to inflammatory responses and energy metabolic reprogramming， including the interleukin-17 （IL-17） signaling pathway， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， fructose and mannose metabolism， and glycolysis. Real-time PCR validation demonstrated that， compared with the normal group， the mRNA expression levels of glycolysis-related genes ［hexokinase 1 （HK1）， hexokinase 2 （HK2）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 4 （PFKFB4）， pyruvate kinase M （PKM）， and lactate dehydrogenase A （LDHA）］， as well as inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］ were significantly upregulated in the model group （P<0.05， P<0.01）. Compared with the model group， the BBD-H group showed significantly decreased mRNA expression of HK1， HK2， PFKFB3， PFKFB4， PKM， LDHA， TNF-α， IL-6， and IL-1β （P<0.05， P<0.01）. Western blot results indicated that， compared with the normal group， the model group had significantly increased expression of glycolysis-related proteins ［glucose transporter 1 （GLUT1）， HK1， PFKFB3， and PKM］， inflammatory proteins ［interleukin-18 （IL-18）， TNF-α， and IL-1β］， and phosphorylated （p）-PI3K and p-Akt proteins （P<0.05， P<0.01）. Compared with the model group， the BBD-H group exhibited significantly decreased expression of GLUT1， HK1， PFKFB3， PKM， IL-18， TNF-α， IL-1β， p-PI3K， and p-Akt （P<0.05， P<0.01）. Metabolic indicator measurements showed that， compared with the model group， the BBD-H group showed significantly reduced GLU consumption， LD and ATP content （P<0.05， P<0.01）. ConclusionBBD may alleviate APAP-induced ALI through dual regulation of metabolic reprogramming and inflammatory responses， potentially via inhibition of the PI3K/Akt signaling pathway.

Objective To propose a whole-life cycle management model for valvular heart disease (VHD), systematically elucidate its underlying logic and implementation pathways, and concurrently review and analyze its preliminary application outcomes. Methods Since 2020, West China Hospital of Sichuan University has established a management system encompassing "assessment-decision-intervention-follow-up", including: (1) a risk-stratified, tiered management pathway; (2) six core functions ("promotion, screening, prevention, diagnosis, treatment, and rehabilitation") coordinated by disease-specific managers; (3) an intelligent decision support information platform; and (4) a collaborative network of multidisciplinary teams and regional academic alliances. To evaluate the effectiveness of this management model, we retrospectively included three cohorts: (1) the population screened by echocardiography from 2020 to 2024, analyzing the detection rate of aortic valve disease and risk stratification; (2) patients enrolled in the whole-life cycle management from April 2021 to December 2024, assessing follow-up outcomes, hospital satisfaction, and changes in quality of life; (3) patients who underwent transcatheter aortic valve replacement (TAVR) from January 2022 to January 2024, evaluating the one-year all-cause mortality rate, perioperative complications, and improvements in New York Heart Association (NYHA) classification. Results Between 2020 and 2024, a total of 583 874 individuals underwent echocardiographic screening. A total of 48 089 patients with aortic valve disease were identified, including 3 401 (7.1%) high-risk patients, 18 657 (38.8%) moderate-risk patients, and 26 031 (54.1%) low-risk patients. Among them, 2 417 patients were enrolled in whole-life cycle management. Patient satisfaction scores showed a yearly increase, rising from 73.89 points before 2020 to 93.74 points in 2024. The 1-year mortality rate in the TAVR cohort decreased to 5.3%, significantly lower than the 8.2% observed under early standard management between 2014 and 2019 (P<0.01). Conclusion Through process optimization and resource integration, the VHD whole-life cycle management model has demonstrated significant effectiveness in standardizing diagnostic and follow-up procedures, enhancing patient satisfaction and quality of life, and reducing mortality. These outcomes highlight its practical value for broader implementation in China.

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China