1.Investigating Effect of Xianglian Huazhuo Prescription on Cell Cycle and Proliferation in Rats with Chronic Atrophic Gastritis Through TGF-β1/Smads Signaling Pathway
Yican WANG ; Jie WANG ; Yirui CHENG ; Xiaojing LI ; Yibin MA ; Qiuhua LIU ; Ziwei LIU ; Yuxi GUO ; Pengli DU ; Yanru CAI ; Yao DU ; Zheng ZHI ; Bolin LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):128-136
ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription (XLHZ) in treating chronic atrophic gastritis (CAG) by regulating cell cycle and inhibiting proliferation, using bioinformatics technology and animal experiments. MethodsDifferential expressed genes (DEGs) related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis (WGCNA) was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction (PPI) analysis of genes was conducted using the Protein Interaction Platform (STRING) database to search the super hub gene (hub 2.0), and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group, and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine (MNNG) + sodium salicylate". The successfully modeled rats were randomly divided into the model group, XLHZ-H, XLHZ-M, and XLHZ-L groups (36, 18, 9 g·kg-1, respectively), and Morodan group (1.4 g·kg-1). Each group was given corresponding intervention for 60 days. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β1, Smad2 and Smad3 proteins, S/G2/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue, and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified, including TGF-β1, suggesting the involvement of the TGF-β1 signaling pathway in the CAG pathogenesis. Compared with the normal group, the expressions of TGF-β1, Smad2, geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased (P<0.05), and the expression of Smad3 protein was decreased (P<0.05). Compared with the model group, the expressions of TGF-β1 and geminin in the gastric mucosa were decreased in the drug groups (P<0.05). The XLHZ-M group, XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 (P<0.05). The protein expression of Smad3 was significantly increased in XLHZ-M, XLHZ-H, and Morodan groups (P<0.05). Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators, and positively correlated with other indicators (P<0.01). ConclusionXLHZ may inhibit TGF-β1/Smads signaling pathway, regulate cell cycle, and inhibit proliferation in the treatment of CAG.
2.Investigating Effect of Xianglian Huazhuo Prescription on Cell Cycle and Proliferation in Rats with Chronic Atrophic Gastritis Through TGF-β1/Smads Signaling Pathway
Yican WANG ; Jie WANG ; Yirui CHENG ; Xiaojing LI ; Yibin MA ; Qiuhua LIU ; Ziwei LIU ; Yuxi GUO ; Pengli DU ; Yanru CAI ; Yao DU ; Zheng ZHI ; Bolin LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):128-136
ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription (XLHZ) in treating chronic atrophic gastritis (CAG) by regulating cell cycle and inhibiting proliferation, using bioinformatics technology and animal experiments. MethodsDifferential expressed genes (DEGs) related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis (WGCNA) was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction (PPI) analysis of genes was conducted using the Protein Interaction Platform (STRING) database to search the super hub gene (hub 2.0), and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group, and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine (MNNG) + sodium salicylate". The successfully modeled rats were randomly divided into the model group, XLHZ-H, XLHZ-M, and XLHZ-L groups (36, 18, 9 g·kg-1, respectively), and Morodan group (1.4 g·kg-1). Each group was given corresponding intervention for 60 days. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β1, Smad2 and Smad3 proteins, S/G2/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue, and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified, including TGF-β1, suggesting the involvement of the TGF-β1 signaling pathway in the CAG pathogenesis. Compared with the normal group, the expressions of TGF-β1, Smad2, geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased (P<0.05), and the expression of Smad3 protein was decreased (P<0.05). Compared with the model group, the expressions of TGF-β1 and geminin in the gastric mucosa were decreased in the drug groups (P<0.05). The XLHZ-M group, XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 (P<0.05). The protein expression of Smad3 was significantly increased in XLHZ-M, XLHZ-H, and Morodan groups (P<0.05). Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators, and positively correlated with other indicators (P<0.01). ConclusionXLHZ may inhibit TGF-β1/Smads signaling pathway, regulate cell cycle, and inhibit proliferation in the treatment of CAG.
3.Xianglian Huazhuo Prescription Regulates Nrf2/NQO1/HO-1 Signaling Pathway to Affect Oxidative Stress in Treatment of Chronic Atrophic Gastritis
Xiaojing LI ; Jie WANG ; Qiuhua LIU ; Yican WANG ; Yibin MA ; Yanru CAI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):76-85
ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription alleviates chronic atrophic gastritis (CAG) through modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1) pathway of oxidative stress (OS) based on animal experiments. MethodsFifty rats were modeled for CAG by gavage of 2% sodium salicylate (10 mL·kg-1), free access to 180 mg·L-1 N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and periodic diet intervention (72 h cycle: 24 h fasting + 48 h free access to food). The modeled rats were grouped by a random number method as follows: low-, medium-, and high-dose (9, 18,36 g·kg-1, respectively) Xianglian Huazhuo prescription, Moradan, and model, with 10 rats in each group. The general state of all rats was observed. Hematoxylin-eosin (HE) staining was employed to observe the pathological changes of the gastric mucosal tissue. The ultrastructure of cells was observed under transmission electron microscopy. Biochemical methods were adopted to determine the levels of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the rat serum. The mRNA and protein levels of Kelch-like ECH-associated protein 1 (Keap1), Nrf2, NQO1, and HO-1 in the gastric mucosal tissue of rats from each group were measured by Real-time polymerase chain reaction (Real-time PCR) and Western blot, respectively. Reactive oxygen species (ROS) staining was employed to detect the fluorescence intensity of ROS in the gastric mucosal tissue of rats in each group. ResultsCompared with the normal group, the modeled rats were sluggish, had yellowing and sparse hair, short and dark tail, loose stool, and reduced food intake, and showed the gastric mucosa characterized by atrophy, thinning, congestive edema, declined gland density and disarrangement, and apparent inflammatory cell infiltration, irregular nucleus morphology, nuclear condensation, mitochondria with decreased number, declined density, and abnormal morphology, vacuolization, declined serum T-SOD level (P<0.05), elevated serum MDA level (P<0.05), downregulated mRNA and protein levels of Nrf2, NQO1, and HO-1 (P<0.05), upregulated mRNA and protein levels of Keap1 (P<0.05), and enhanced mean fluorescence intensity of ROS (P<0.05). Compared with the model group, each treatment group exhibited improved general state, alleviated histopathological changes in gastric mucosa, improved ultrastructural characteristics of cells, elevated T-SOD level and declined MDA level in the serum (P<0.05), upregulated mRNA and protein levels of Nrf2, NQO1, and HO-1, downregulated mRNA and protein levels of Keap1 (P<0.05), and attenuated mean fluorescence intensity of ROS (P<0.05). ConclusionXianglian Huazhuo prescription can improve the general status, ameliorate pathological changes of gastric mucosa, and repair the cell ultrastructure to varying degrees, demonstrating a definite therapeutic effect on CAG. It may restrain OS and safeguard the natural physiological function of gastric mucosa in CAG rats by regulating the Nrf2/NQO1/HO-1 signaling pathway.
4.Xianglian Huazhuo Prescription Regulates Nrf2/NQO1/HO-1 Signaling Pathway to Affect Oxidative Stress in Treatment of Chronic Atrophic Gastritis
Xiaojing LI ; Jie WANG ; Qiuhua LIU ; Yican WANG ; Yibin MA ; Yanru CAI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):76-85
ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription alleviates chronic atrophic gastritis (CAG) through modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1) pathway of oxidative stress (OS) based on animal experiments. MethodsFifty rats were modeled for CAG by gavage of 2% sodium salicylate (10 mL·kg-1), free access to 180 mg·L-1 N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and periodic diet intervention (72 h cycle: 24 h fasting + 48 h free access to food). The modeled rats were grouped by a random number method as follows: low-, medium-, and high-dose (9, 18,36 g·kg-1, respectively) Xianglian Huazhuo prescription, Moradan, and model, with 10 rats in each group. The general state of all rats was observed. Hematoxylin-eosin (HE) staining was employed to observe the pathological changes of the gastric mucosal tissue. The ultrastructure of cells was observed under transmission electron microscopy. Biochemical methods were adopted to determine the levels of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the rat serum. The mRNA and protein levels of Kelch-like ECH-associated protein 1 (Keap1), Nrf2, NQO1, and HO-1 in the gastric mucosal tissue of rats from each group were measured by Real-time polymerase chain reaction (Real-time PCR) and Western blot, respectively. Reactive oxygen species (ROS) staining was employed to detect the fluorescence intensity of ROS in the gastric mucosal tissue of rats in each group. ResultsCompared with the normal group, the modeled rats were sluggish, had yellowing and sparse hair, short and dark tail, loose stool, and reduced food intake, and showed the gastric mucosa characterized by atrophy, thinning, congestive edema, declined gland density and disarrangement, and apparent inflammatory cell infiltration, irregular nucleus morphology, nuclear condensation, mitochondria with decreased number, declined density, and abnormal morphology, vacuolization, declined serum T-SOD level (P<0.05), elevated serum MDA level (P<0.05), downregulated mRNA and protein levels of Nrf2, NQO1, and HO-1 (P<0.05), upregulated mRNA and protein levels of Keap1 (P<0.05), and enhanced mean fluorescence intensity of ROS (P<0.05). Compared with the model group, each treatment group exhibited improved general state, alleviated histopathological changes in gastric mucosa, improved ultrastructural characteristics of cells, elevated T-SOD level and declined MDA level in the serum (P<0.05), upregulated mRNA and protein levels of Nrf2, NQO1, and HO-1, downregulated mRNA and protein levels of Keap1 (P<0.05), and attenuated mean fluorescence intensity of ROS (P<0.05). ConclusionXianglian Huazhuo prescription can improve the general status, ameliorate pathological changes of gastric mucosa, and repair the cell ultrastructure to varying degrees, demonstrating a definite therapeutic effect on CAG. It may restrain OS and safeguard the natural physiological function of gastric mucosa in CAG rats by regulating the Nrf2/NQO1/HO-1 signaling pathway.
5.Study on residents′ preference for traditional Chinese medicine health management services in community health service institutions
Xiaojing MA ; Hang XU ; Yuna PAN ; Jianping REN
Chinese Journal of Hospital Administration 2025;41(8):636-642
Objective:To investigate Beijing residents′ preferences, marginal willingness to pay (mWTP), and utilization probabilities regarding the traditional Chinese medicine (TCM) health management services provided by community health service institutions, and to provide references for promoting the application and dissemination of TCM health management at the grassroots level.Methods:A questionnaire was designed based on a discrete choice experiment involving six attributes influencing residents′ utilization of TCM health management services: medical insurance coverage, technical effectiveness, service provider, physician seniority, treatment modality, and individual average out-of-pocket cost. A multi-stage stratified random sampling method was used to select 800 residents from three community health service institutions across three administrative districts of Beijing. The survey was conducted from November to December 2024. A mixed logit model was employed to analyze the factors influencing service utilization preferences, mWTP, and utilization probabilities.Results:A total of 733 valid questionnaires were included in the analysis. All six attributes significantly influenced residents′ service utilization preferences ( P<0.05). Residents showed stronger preferences for services with lower individual average out-of-pocket costs ( β=-0.214), combination therapies involving both internal medication and external treatments ( β=0.314), provision by senior-level professionals ( β= 0.522), fixed service providers ( β=0.851), longer treatment courses with better efficacy ( β=1.323), and services covered by medical insurance ( β=1.843). When services were covered by insurance, featured longer courses with better efficacy, and involved fixed service providers, the probability of service utilization increased to 76.52%. Heterogeneity in service utilization preferences was observed across different ages, genders and chronic health conditions ( P<0.05). Conclusions:Medical insurance coverage, technical efficacy and doctor service continuity are the most influential factors affecting residents′ service utilization. Optimizing the combination of TCM health management service attributes can enhance residents′ willingness to utilize these services. It is recommended to develop multi-tiered medical security strategies, selectively include high-value TCM health management services into insurance coverage, strengthen physician-patient trust, and design differentiated " disease prevention" service packages for residents with different characteristics to improve overall population health.
6.Study on the dynamic changes of brain oxygen saturation in premature infant brain injury and its correlation with amplitude integrated EEG parameters and neurodevelopment
Huanhuan MA ; Xiaojing LIU ; Zhimei SI ; Jingjing XU ; Xuemin QIE
The Journal of Practical Medicine 2025;41(16):2461-2469
Objective To investigate the expression of regional cerebral oxygen saturation(rSO2)in preterm infants with brain injury(BIPI)and its relationship with amplitude-integrated electroencephalogram(aEEG)parameters and neurodevelopment.Methods Retrospectively,116 cases of BIPI(Bilateral Intra-ventricular Perforation)born in the hospital between February 2022 and February 2023 were selected as the study subjects.According to the Expert Consensus on the Diagnosis and Prevention of Premature Infant Brain Injury,these cases were categorized into mild,moderate,and severe groups,with 59,35,and 22 cases,respectively.The study compared the general characteristics of premature infants with different brain injury levels.Regression analysis was conducted to identify the factors affecting brain injury in premature infants,and correlation analyses were performed on aEEG scores,rSO2,and GMS scores.ROC curve analysis was used to evaluate the value of combining brain oxygen saturation monitoring with aEEG in predicting abnormal whole-body motor quality assessment.Results On the 3rd and 7th days after birth,severe brain-injured premature infants had significantly lower rSO2 and aEEG scores compared to those with mild and moderate brain injuries(P<0.05).At 7 days,these infants also had lower scores for graph continuity,sleep-wake cycles,lower boundary amplitude,bandwidth,total score,rSO2,gestational age,and birth weight,and a higher proportion of abnormal developmental outcomes(PR+CS)(P<0.05).Multivariate logistic regression analysis revealed that the 3-day aEEG total score(OR=0.448,95%CI:0.094~0.890),7-day aEEG total score(OR=0.384,95%CI:0.058~0.726),3-day rSO2(OR=0.574,95%CI:0.398~0.750),and 7-day rSO2(OR=0.431,95%CI:0.115~0.777)were all protective factors for brain injury in premature infants,P<0.05.Correlation analysis showed that brain oxygen saturation was negatively correlated with aEEG scores and overall motor quality.The prediction value for abnormal overall motor quality using 7-day rSO2,aEEG,and the combination of 7-day rSO2 and 7-day aEEG scores was as follows:the positive predictive value for rSO2 was 86.46%,the negative predictive value was 96.85%,the sensitivity was 92.31%,the specificity was 92.21%,and the cut-off value was 0.845;The positive predictive value(PPV)of aEEG was 78.26%,the negative predictive value(NPV)was 96.86%,the sensitivity was 89.74%,and the specificity was 92.21%,with a cut-off value of 0.820.The positive predictive value(PPV)of 7-day rSO2 combined with 7-day aEEG score was 89.04%,the NPV was 96.88%,the sensitivity was 94.90%,and the specificity was 93.51%,with a cut-off value of 0.884,P<0.05.ROC curve analysis showed that the AUC of 7-day rSO2+7-day aEEG score was 0.895,De-long test P<0.005,indicating high predictive value for overall exercise quality.Conclusion Combined with rSO2 and EEG,the prediction of overall motor quality is better,which may have clinical value for excluding high-risk children.
7.Evaluation of Right Ventricular Function in Cardiac Amyloidosis by Two-Dimensional Speckle Tracking Imaging
Huiying CHEN ; Xiaojing MA ; Juan XIA ; Yafeng HE ; Jingjing WANG ; Jinlong ZHONG
Chinese Journal of Medical Imaging 2025;33(6):638-644
Purpose To investigate the value of two-dimensional speckle tracking in evaluating right ventricular function in cardiac amyloidosis(CA).Materials and Methods A total of 25 patients with CA,30 patients with hypertrophic cardiomyopathy(HCM)and 30 healthy controls were retrospectively selected from July 2021 to October 2023 in Wuhan Asia Heart Hospital.The regional difference was represented by the formula apical ratio.The parameters of conventional echocardiography,two-dimensional strain and apical ratio of the three groups were analyzed and compared.Results Only segmental strain was different in right ventricular structure and function between CA group and HCM group,and the differences were statistically significant(all P<0.05).In the CA group,the strain gradient of the right ventricle from the apex of the heart to the base was the same as that of the left ventricle,that was,the"apex preservation"pattern,which was not seen in the HCM group and the control group.Comparison of the right ventricular free wall longitudinal strain-apical ratio,right ventricle four-chamber longitudinal strain-apical ratio,left ventride global longitudinal strain-apical ratio among the three groups,it was found that the levels of CA group were higher than HCM group and control group,and the differences were statistically significant(H=40.40,43.18,55.43,all P<0.05).The right ventricular free wall longitudinal strain-apical ratio had the highest CA recognition value,the area under the curve was 0.935,sensitivity was 96%and specificity was 83%.Conclusion Two-dimensional speckle tracking can accurately evaluate the right ventricular function impairment in CA patients and provide a new choice for clinical evaluation and identification of CA patients.
8.Analysis of diagnostic biomarkers for ischemic stroke and experimental validation of targeted cuproptosis related genes
Ying CHEN ; Xiaojing GUO ; Xueni MO ; Wei MA ; Shangzhi WU ; Xiangling LI ; Tingting XIE
Chinese Journal of Tissue Engineering Research 2025;29(35):7562-7570
BACKGROUND:Studies have shown that immune cells are involved in all processes of ischemic stroke,in which cuproptosis also plays a key role.OBJECTIVE:To screen diagnostic biomarkers related to the progression of ischemic stroke through bioinformatics,and analyze and validate cuproptosis-related genes closely related to the occurrence and development of ischemic stroke.METHODS:The GSE16561 microarray was obtained from the GEO database,containing data from 39 cases of ischemic stroke(ischemic stroke group)and 24 controls(control group).Differentially expressed genes from the ischemic stroke microarray data were analyzed.Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed.By using LASSO and Random Forest methods,key genes affecting the occurrence and development of ischemic stroke were screened,and a diagnostic model was established and validated.Differential gene analysis was performed through immune cell infiltration and weighted gene co expression network.The differentially expressed immune-related genes were intersected with cuproptosis genes to obtain the hub genes related to cuproptosis immunity.In vitro cell experiments were conducted to divide rat hippocampal neurons into a normal group and an ischemic stroke group,and qPCR experiments were performed to verify the results.RESULTS AND CONCLUSION:(1)573 differentially expressed genes were obtained by differential analysis.Differentially expressed genes were mainly enriched in biological processes,such as positive regulation of immune response,and signaling pathways such as lipid and atherosclerosis.(2)Machine learning methods were used to screen diagnostic genes such as MFN2,PKM2,CREG1,and FOXO3A,which may have some diagnostic value for ischemic stroke.(3)Immune infiltration analysis revealed resting plasma cells,NK cells,macrophages,etc.,indicating that immune cells play a certain role in the pathogenesis of ischemic stroke.(4)Weighted gene co-expression network analysis combined with immune infiltration analysis obtained 118 key module genes,which were intersected with cuproptosis genes to obtain 2 cuproptosis and immune characteristic genes.The correlation analysis between four diagnostic genes and Hub genes showed that the expression of FOXO3A and MFN2,PKM2 and BCL2L1,MTF1 and MFN2,ATP7B and BCL2L1 were correlated.(5)The qPCR results showed significant differences in the genes MTF1 and ATP7B between the ischemic stroke group and the blank group.To conclude,ATP7B and MTF1 can serve as characteristic genes for cuproptosis in ischemic stroke.It is possible to improve ischemic stroke by intervening in ATP7B and MTF1 to regulate cuproptosis.
9.Relationship between RNase3 Gene Polymorphism and Its Expression Level with Airway Inflammation and Glucocorticoid Efficacy in Children with Bronchial Asthma
Huimin MA ; Xiaojing ZHOU ; Donge LU ; Yujiao YAN
Journal of Modern Laboratory Medicine 2025;40(2):164-168
Objective To explore the relationship between ribonuclease A3(RNase3)gene polymorphism and its expression level with airway inflammation and glucocorticoid efficacy in children with bronchial asthma(BA).Methods A total of 110 children with bronchial asthma admitted to Handan Maternal and Child Health Hospital June 2022 to June 2024 were selected as the study objects.According to the severity of the condition at admission,they were divided into mild group(n=64),moderate to severe group(n=46),and children who underwent physical examination in the hospital during the same period were selected as the control group(n=82).Molecular weight array gene analysis(MassArray)was used to detect the genotyping of RNase3 gene rs2073342 locus.Quantitative real-time PCR(RT-PCR)was used to detect the expression level of RNase3 mRNA.The clinical data of the children were collected,and the differences of genotype and allele frequency were compared.The relationship between RNase3 gene polymorphism and BA susceptibility was analyzed by unconditioned Logistic regression.Results Compared with the mild group,IL-6(21.49±3.01ng/L vs 13.21±2.84ng/L)and PCT(19.16±4.02μg/L vs 9.94±3.15μg/L)in the moderate and severe group were significantly increased(t=-14.568,-12.952),while FVC,PEF and FEV1 were significantly decreased(t=2.534,3.304,2.011),and the differences were statistically significant(all P<0.05).The genotype distribution of RNase3 gene rs2073342 in both control and study groups was consistent with Hardy-Weinberg balance law(χ2=0.402,0.689,all P>0.05),indicating population representation.Compared with the control group and the mild group,the CC,CA genotype frequencies were higher in moderate to severe group(χ2=35.008,23.079),Compared with the control group,the frequency of CC and CA genotypes in mild group was higher(χ2=7.325),the differences were statistically significant(all P<0.05).Compared with mild group,RNase3 mRNA expression in peripheral blood mononuclear cells of children with C gene BA at rs2073342 in moderate to severe group was higher,and the difference was statistically significant(t=-19.622,P<0.05).In the same group,the mRNA expression level of RNase3 in peripheral blood mononuclear cells of the children with C gene BA at rs2073342 was higher than that of the children without C gene(t=4.169,22.608,all P<0.05).Unconditional Logistic regression results showed that RNase3 gene carrying allele C or dominant model(CC vs CA+AA)was a risk factor for severe disease in BA children(P<0.05).The total effective rate of genotype AA carriers was the highest after glucocorticoid therapy,and the therapeutic effect of genotype AA carriers was significantly better than that of genotype AC and CC,and the difference was statistically significant(χ2=11.858,P<0.05).Conclusion The expression of RNase3 mRNA in peripheral blood of BA children increased significantly with the exacerbation of the disease.Carrier of allele C or dominant model(CC vs CA+AA)is a risk factor for severe disease in BA children.Genotype AA carriers had better therapeutic effect.
10.Role of fecal calprotectin testing in predicting endoscopic remission in Crohn′s disease treated with infliximab
Qiong GUO ; Chen CHEN ; Xiaojing ZHAO ; Jingjing MA ; Chunhua JIAO ; Nana TANG ; Hongjie ZHANG
Chinese Journal of Digestion 2025;45(7):469-476
Objective:To explore the relationship between early fecal calprotectin (FC) level and the long-term efficacy of infliximab (IFX) in the treatment of Crohn′s disease (CD) and predictive the value.Methods:From January 2018 to December 2023, at the First Affiliated Hospital with Nanjing Medical University, the clinical data of patients with moderate-to-severe CD who received IFX as first-line therapy were retrospectively collected. The main outcomes were clinical and endoscopic remission at week 52 after IFX treatment, and the secondary outcome was clinical response at week 14 after IFX treatment. The predictive value of FC levels at week 0 (at baseline when first administered) and week 14 of treatment was evaluated for the clinical and endoscopic remission at week 52 after IFX treatment. Multivariate logistic regression was performed to investigate the factors predicting endoscopic remission. The optimal cutoff value was calculated, model was established, the data was divided into training set and validation set at a ratio of 7∶3 using the random number table method and the corresponding column chart was drawn. Receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the discrimination and calibration of the model, respectively. Mann-Whitney U test was used for statistical comparison. Results:A total of 165 patients with CD were enrolled, of whom 150 cases (90.9%) achieved clinical response after induction therapy, and 15 cases (9.1%) were primary non-response. Among the 150 patients with clinical response, 112 cases (74.7%) achieved clinical remission at week 52 after treatment, while 38 cases (25.3%) did not achieve clinical remission. Endoscopic evaluation was performed at week 52 after treatment in 139 patients, of whom 54 cases (38.8%) achieved endoscopic remission and 85 cases (61.2%) did not. At week 14 of treatment, there was no statistically significant difference in FC level between the patients achieved and did not achieve clinical response (263.24 (93.96, 675.28) μg/g vs. 556.35 (245.77, 953.56) μg/g, P>0.05). At week 52 after treatment, the FC level of patients who achieved clinical remission was lower than that of patients did not achieve(103.20(44.11, 456.57) μg/g vs. 531.26(222.06, 998.40) μg/g) and the decreased value of FC at week 52 and week 0 after treatment of patients achieved clinical remission was more than that of patients did not achieve clinical remission (443.34 (82.25, 788.95) μg/g vs. 269.91 (-79.20, 522.54) μg/g), and the differences were statistically significant ( U=1 078.00, 2 677.00; P<0.001, =0.018). At week 52 after treatment, the FC level of patients achieved endoscopic remission was lower than that of patients did not achieve endoscopic remission (52.80(31.93, 83.47) μg/g vs. 506.18(217.44, 778.02) μg/g), and the decreased value of FC at week 52 and week 0 after treatment of patients achieved endoscopic remission was more than that of patients did not achieve endoscopic remission (428.85(140.20, 863.60) μg/g vs. 309.61(-62.37, 683.82) μg/g), and the differences were statistically significant ( U=500.00, 2 812.00; P<0.001, =0.025). The FC level at week 14 of treatment could predict the clinical and endoscopic remission at week 52 after treatment (area under the curve (AUC) =0.663, 0.773; 95% confidence interval (95% CI): 0.566 to 0.760, 0.694 to 0.852; P=0.006, <0.001). The optimal cutoff value of FC at week 14 of treatment for predicting endoscopic remission at week 52 after treatment was 246.13 μg/g, with a sensitivity of 0.741 and a specificity of 0.671. The results of multivariate logistic regression analysis revealed that FC ≤ 246.13 μg/g at week 14 of treatment ( OR=4.576, 95% CI: 2.021 to 10.363, P<0.001), baseline albumin ( OR=1.093, 95% CI: 1.006 to 1.188, P=0.035), and baseline platelet-to-lymphocyte ratio (PLR) ( OR=0.995, 95% CI: 0.990 to 1.000, P=0.046) were independent influencing factors of endoscopic remission at week 52 after treatment. A predictive model for endoscopic remission at week 52 after IFX treatment was established based on FC ≤ 246.13 μg/g at week 14 of treatment, baseline albumin and PLR. The results of ROC analysis showed that this model had good discriminative ability, with an AUC of 0.780 (95% CI: 0.700 to 0.878) in the validation set, with a sensitivity of 0.812 and a specificity of 0.760. The results of calibration curve analysis demonstrated that the average absolute error of the prediction model in the validation set was 0.038, and the consistency between the predicted probability and the actual probability was good. Conclusion:FC ≤ 246.13 g/g at week 14 of IFX treatment has good predictive value for endoscopic remission at week 52 after treatment in CD patients.

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