1.Signals mining and analysis of inebilizumab adverse events
Jiayi ZHANG ; Chen LIU ; Xiaotong ZHANG
China Pharmacy 2026;37(2):215-219
OBJECTIVE To mine and analyze adverse event signals associated with inebilizumab, and to provide reference for safe and rational clinical use. METHODS Reports of adverse event related to inebilizumab were collected from the FDA adverse event reporting system (FAERS) database, from Q2 2020 to Q4 2024. Adverse events were standardized and categorized according to the preferred term (PT) and system organ class (SOC) of the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. Signals were mined using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) method. RESULTS A total of 783 adverse event reports with inebilizumab as the primary suspected drug were identified, involving 297 patients. Most reports originated from the United States and Japan, with physicians being the primary reporters. Female patients outnumbered males, and the most common age group was 45-64 years. Using the ROR method and BCPNN method, a total of 29 valid adverse event signals were detected, involving 12 SOCs and comprising 225 adverse event reports. The five most frequently reported PTs were headache, nausea, fatigue, infectious pneumonia and arthralgia. The five PTs with the strongest signal intensity were: B-cell recovery, decreased blood immunoglobulin G, spinal compression fracture, COVID-19 and acute respiratory distress syndrome. Among the 29 valid signals for adverse event, 19 were not documented in the drug package inserts, involving 10 SOCs and comprising 107 adverse event reports. These encompassed nervous system disorders, general disorders and administration site conditions, eye disorders, among others. CONCLUSIONS Inebilizumab treatment not only causes adverse events documented in the product information, such as infections, immunoglobulin reduction and infusion-related reactions but also leads to potential signals, including B-cell recovery, spinal compression fracture. When using this drug in clinical practice, the patient’s risk of infection and baseline immune status should be assessed, relevant indicators should be closely monitored, and targeted preventive measures should be considered when necessary.
2.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
3.Clinical application value of intracavitary PRP infusion combined with IVF-FET in patients with chronic endometritis
Xiaotong ZHANG ; Xiaoyuan HAO ; Rui FANG ; Shuyao HU ; Linkun MA ; Yaqi ZHAO ; Wei HAN
Chinese Journal of Blood Transfusion 2025;38(3):382-387
[Objective] To evaluate the clinical application value of intrauterine perfusion with platelet-rich plasma (PRP) combined with in vitro fertilization-frozen-thawed embryo transfer (IVF-FET) in patients with chronic endometritis (CE). [Methods] A randomized controlled trial (RCT) was conducted, enrolling 60 CE patients undergoing artificial cycle frozen embryo transfer at our hospital from January 2022 to January 2024. Participants were randomly divided into three groups: Group A (routine frozen embryo transfer, n=20), Group B (routine frozen embryo transfer + one PRP intrauterine perfusion, n=20), and Group C (routine frozen embryo transfer + two PRP intrauterine perfusions, n=20). Endometrial thickness during the transformation and transplantation phases, uterine artery pulsatility index (PI), resistance index (RI), systolic peak velocity/end-diastolic velocity (S/D) ratio during transplantation, serum levels of IL-2, IL-4, IL-6, IL-10, and TNF-α during transplantation, as well as biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and early miscarriage rate were compared across groups. [Results] No significant differences in endometrial thickness were observed among the three groups during the transformation phase (P>0.05). During the transplantation phase, endometrial thickness in Groups C and B was significantly higher than in Group A[9.54 (8.96-10.22) and 8.90 (8.34-9.72) vs 8.37 (7.89-8.75) mm, P<0.05], with Group C showing greater thickness than Group B (Z=3.733, P<0.05). Endometrial thickness in Groups C and B during transplantation was significantly increased compared to their respective transformation phases (Z=2.191, 2.462; P<0.05). Groups C and B exhibited lower PI, RI, and S/D values than Group A[PI:1.87 (1.77-1.97), 1.94 (1.88-2.15) vs 2.43 (2.35-2.49); RI:0.75 (0.73-0.77), 0.78 (0.75-0.81) vs 0.84 (0.83-0.86); S/D:2.61 (2.33-3.42), 3.01 (2.20-3.93) vs 3.72 (3.06-4.49); P<0.05]. Group C demonstrated lower PI and RI than Group B (P<0.05). IL-2 levels in Groups C and B were higher than in Group A[3.88 (2.71-5.01), 3.59 (2.73-4.38) vs 3.16 (2.11-3.25) ng/L, P<0.05], while IL-4, IL-6, IL-10, and TNF-α levels were significantly lower (IL-4: Z=1.428, 2.421; IL-6: Z=1.754, 2.435; IL-10: Z=1.754, 2.854; TNF-α: Z=1.961, 1.765; P<0.05). Group C had lower IL-6 levels than Group B (Z=3.976, P<0.05). Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate in Group C were significantly higher than in Group A (75% vs 40%, 70% vs 35%, 60% vs 20%, P<0.05). No significant differences in early miscarriage rates were observed among the groups (χ2=3.750, P>0.05). [Conclusion] Intrauterine autologous PRP perfusion in CE patients enhances pregnancy and live birth rates, improves pregnancy outcomes post-FET, and demonstrates superior efficacy in endometrial repair and receptivity with two PRP perfusions compared to a single perfusion. This provides a safe and effective therapeutic option for optimizing outcomes in CE patients with prior implantation failure.
4.Advances in artificial intelligence for integrated diagnostic approaches based on radiomics and pathomics in breast cancer
Liu JINGJING ; Xu XIAOTONG ; Zhang YI ; Zhang JIN
Chinese Journal of Clinical Oncology 2025;52(18):920-925
Breast cancer is the most common malignant tumor in women worldwide,and its incidence rate is increasing annually.Early dia-gnosis is essential for improving patient prognosis.In recent years,artificial intelligence(AI)technology has emerged as a transformative tool,providing new directions for accurate diagnostic and prognostic assessments.This article systematically reviews research progress in the ap-plication of AI to breast cancer screening,multimodal imaging techniques for diagnosis,pathological diagnosis,treatment,and prognostic modeling.Through machine learning and deep learning algorithms,AI has demonstrated significant advantages in the enhancement of dia-gnostic accuracy,efficiency,and accessibility,including improvement of the detection rate of small lesions,reduction in the radiologists'workload,and optimization of treatment decisions.Despite challenges,including the integration of explainable technology in clinical trans-formation,lack of data standardization,complexity of multimodal data,and risk of model generalization,AI is expected to play a more prom-inent role in the precise diagnosis and intelligent therapy for breast cancer,thereby contributing to the full realization of the goal of preci-sion medicine.
5.MED15-TFE3 renal cell carcinoma: a clinicopathological and molecular analysis
Xiaotong WANG ; Rusong ZHANG ; Rui LI ; Xuan WANG ; Ru FANG ; Qiuyuan XIA ; Qiu RAO
Chinese Journal of Pathology 2025;54(1):16-22
Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.
6.Analysis of influenza vaccination intention and influencing factors among urban and rural residents aged ≥50 in Zhejiang Province, in 2024
Yusui ZHAO ; Jinhang XU ; Yue XU ; Xiaotong YAN ; Dingming YAO ; Heni CHEN ; Xiujing HU ; Xuehai ZHANG
Chinese Journal of Health Management 2025;19(1):36-42
Objective:To analyze the intention to receive influenza vaccination and its associated factors among urban and rural residents aged≥50 in Zhejiang Province, China, in 2024.Methods:This cross-sectional study was conducted between March and May 2024 through a multi-stage intercept survey in 35 counties (cities, districts) selected from a total of 90 in Zhejiang Province, involving 175 communities/villages. The survey targeted residents visiting local hospitals and community health service centers/community health clinics. The questionnaire included basic demographic information, knowledge related to influenza prevention and treatment, chronic disease status, history of influenza vaccination, and intention to vaccinate. Urban and rural residents were classified based on their registered residence, according to the "Rules for Compilation of Statistical Regional Code and Urban-Rural Division Code" issued by the National Bureau of Statistics. Chi-square tests, ANOVA, and multivariate logistic regression models were used to analyze the factors influencing the intention to receive the influenza vaccine.Results:A total of 10 500 participants were surveyed, comprising 4 885 rural residents (46.52%) and 5 615 urban residents (53.48%). Of these, 3 430 rural residents (70.21%) and 3 718 urban residents (66.22%) expressed intention to receive the influenza vaccine. Multivariate logistic regression analysis revealed that for rural residents aged≥50, younger age groups (50-59 years: OR=1.747, 95% CI: 1.290-2.366; 60-69 years: OR=1.838, 95% CI: 1.401-2.411), history of influenza vaccination ( OR=6.721, 95% CI: 5.152-8.767), doctor′s recommendation for vaccination ( OR=3.788, 95% CI: 3.078-4.662), and higher scores on knowledge related to influenza prevention and treatment ( OR=1.090, 95% CI: 1.054-1.128) were significant promoting factors for vaccination intent. For urban residents aged≥50, belonging to the 60-69 age group ( OR=1.264, 95% CI: 1.023-1.563), history of influenza vaccination ( OR=5.392, 95% CI: 4.309-6.748), doctor′s recommendation for vaccination ( OR=5.307, 95% CI: 4.420-6.371), and higher scores on knowledge related to influenza prevention and treatment ( OR=1.051, 95% CI: 1.021-1.082) were significant promoting factors for vaccination intent. Conclusions:The intention to receive the influenza vaccination is notably high among residents aged≥50 in both urban and rural areas of Zhejiang Province, yet there remains potential for improvement. Age, history of influenza vaccination, doctor recommendation, and knowledge related to influenza prevention and treatment are significant factors influencing the intention to receive the influenza vaccination.
7.Pneumococcal vaccination rate and influencing factors among residents aged≥50 in Zhejiang Province
Xiaotong YAN ; Yue XU ; Xuehai ZHANG ; Yusui ZHAO ; Dingming YAO ; Qiaohong LÜ ; Heni CHEN ; Jinhang XU
Chinese Journal of Health Management 2025;19(7):543-549
Objective:To analyze the pneumococcal vaccination rate and the influencing factors among residents aged≥50 in Zhejiang Province.Methods:This cross-sectional study was conducted between March and May 2024. A multi-stage intercept survey was used to intercept and survey 10 500 residents who visited or underwent physical examinations at 175 community health service centers/clinics in 35 counties (cities, districts) of Zhejiang Province. The questionnaire included basic demographic characteristics, history of pneumonia, chronic disease conditions, pneumococcal vaccination status, doctor recommendation, reasons for vaccination/non-vaccination, and channels for obtaining pneumococcal vaccine information. Participants were grouped based on demographic characteristics, chronic diseases conditions, history of pneumonia and doctor recommendations. The chi-square test was used to assess differences in vaccination rates among demographic groups while binary logistic regression models were used to identify factors affecting the vaccination rate.Results:Among the 10 500 surveyed participants, 1 724 (16.42%) had received pneumococcal vaccination. Binary logistic regression analysis revealed significantly higher vaccination rates among those who received a doctor recommendation compared to those without (26.25% vs 7.59%; OR=4.414, 95% CI: 3.851-5.059). Participants benefiting from the free vaccination policy showed higher vaccination rates than those who didn′t (47.59% vs 5.18%; OR=12.527, 95% CI: 10.723-14.634). The top three reasons for getting vaccinated against pneumonia were the free vaccination policy (65.43%), community promotion (52.15%), and family recommendations (42.34%). The top three sources through which respondents learned about the pneumococcal vaccine were television (64.64%), doctors (59.81%) and family members (50.92%). Conclusion:The pneumococcal vaccination rate among residents aged≥50 years in Zhejiang Province is relatively high but still needs further improvement, with vaccination rates closely associated with factors such as free vaccination policy and doctor recommendation.
8.Cross-cultural adaptation and validation of the postoperative recovery in children scale for dental treatment under general anesthesia (PRiC-DTGA) in Chinese children
Xiaotong SHI ; Bing LIU ; Ze FAN ; Yao ZHANG ; Tiantian LIU ; Zhenzhen GAO ; Haopeng ZHANG ; Hui ZHANG
Chinese Journal of Stomatology 2025;60(10):1128-1136
Objective:To translate and adapt the postoperative recovery in children (PRiC) scale, developing a Chinese version for children undergoing dental treatment under general anesthesia (PRiC-DTGA) with validated psychometric properties.Methods:The PRiC scale underwent forward-backward translation using Brislin′s model. A convenience sample of DTGA patients from the Department of Anesthesiology, School of Stomatology, The Fourth Mility Force Medical University was enrolled for a cross-sectional survey on postoperative complications. Delphi expert consultation informed cultural adaptation based on survey findings to develop the PRiC-DTGA Chinese version. Psychometric validation included reliability and validity testing in a separate DTGA cohort at the same center (April-October 2024).Results:Results from the cross-sectionalsurvey of 231 children showed that 82.7% (191/231) of them hadat least one postoperative complication within 72 hours, and these complications were mainly mild local symptoms. Additionally, 358 copies of the Chinese version of the PRiC-DTGA scale were distributed; 21 invalid questionnaires with incomplete information were excluded, and a total of 337 cases were included inthe study. The final PRiC-DTGA comprised 22 items across three dimensions including physical comfort, social ability, and negative emotional. Exploratory factor analysis (EFA) confirmed all factor loadings>0.4. Confirmatory factor analysis (CFA) demonstrated adequate fit: χ 2/df=1.665, tucker-Lewis index (TLI)=0.924, comparative fit index (CFI)=0.896, standardized root mean square residual (SRMR)=0.041, and root mean square error of approximation (RMSEA)=0.044 (90% CI: 0.035-0.053). Reliability was strong with Cronbach′s α (total scale)=0.853, subscale α=0.632-0.723, split-half reliability=0.824. Validity indices met standards: scale-content validity index (S-CVI)=0.909, Item-CVI range=0.944-1.000, average variance extracted (AVE)=0.473-0.501, composite reliability (CR)=0.830-0.913. Conclusions:The systematically adapted PRiC-DTGA demonstrates robust reliability and validity, serving as an effective tool for assessing postoperative recovery quality in Chinese children following DTGA.
9.Efficacy of CEA, CA125, CA199, CA724, and G-17 in diagnosing early gastric cancer
Xiaotong ZHANG ; Lansheng ZHANG ; Yaqi ZHAO ; Wei HAN
Cancer Research and Clinic 2025;37(3):206-210
Objective:To explore the clinical values of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), carbohydrate antigen 724 (CA724) and gastrin 17 (G-17) detections in the early diagnosis of gastric cancer patients.Methods:A retrospective case-control study was conducted. A total of 120 patients with gastric diseases who were admitted to General Hospital of Xuzhou Mining Group from January 2019 to December 2021 were selected. According to the pathological results of gastroscopy examination, the patients were divided into gastric ulcer group (23 cases), atrophic gastritis group (58 cases) and early gastric cancer group (39 cases). The healthy control group consisted of 30 healthy individuals who underwent physical examination during the same period. All participants were detected for serum levels of CEA, CA125, CA199, CA724, and G-17. The levels of various indicators in each group were compared. Using the pathological results of gastroscopy as the gold standard, the receiver operating characteristic (ROC) curve was used to analyze the efficacy of various indicators in distinguishing early gastric cancer from healthy individuals, gastric ulcer and atrophic gastritis.Results:The serum levels of CA125 [ M ( Q1, Q3)] [19.94 (8.29, 22.99) U/ml vs. 6.03 (4.07, 10.48) U/ml, 7.49 (4.96, 12.19) U/ml, 7.54 (6.20, 11.91) U/ml], CA199 [32.09 (15.68, 41.97) U/ml vs. 19.19 (10.01, 30.05) U/ml, 21.00(16.01, 32.71) U/ml, 18.95 (13.90, 32.76) U/ml], CA724 [19.55 (3.91, 26.25) U/ml vs. 4.61 (3.06, 5.24) U/ml, 4.09 (3.37, 5.00) U/ml, 4.88 (3.92, 5.46) U/ml] and G-17 [21.01 (14.67, 24.00) pmol/L vs. 11.80 (10.07, 16.58) pmol/L, 12.74 (11.09, 14.69) pmol/L, 12.08 (8.40, 15.10) pmol/L] in the early gastric cancer group were higher than those in the gastric ulcer group, atrophic gastritis group and healthy control group, and the differences were statistically significant (all P < 0.05). The CEA level in the early gastric cancer group, gastric ulcer group and atrophic gastritis group was all higher than that in the healthy control group [4.38 (3.22, 7.56) ng/ml, 4.51 (3.37, 5.51) ng/ml, 4.49 (4.13, 5.09) ng/ml vs. 3.95 (2.16, 4.44) ng/ml], and the differences were statistically significant (all P < 0.05). ROC curve analysis showed that among all indicators, the area under the curve (AUC) of G-17 for distinguishing early gastric cancer from healthy individuals was the largest [0.825 (95% CI: 0.728-0.922)], the optimal critical value was 18.21 pmol/L, and the specificity was the highest (96.7%); the AUC of CA125 and CA724 was also relatively high, with values of 0.768 (95% CI: 0.653-0.884) and 0.744 (95% CI: 0.622-0.866), respectively, and the optimal critical values were 15.41 and 39.60 U/ml, respectively, with the corresponding sensitivities of 71.8%, which was the highest among several indicators. Among all indicators, CA125 had the largest AUC for distinguishing early gastric cancer from gastric ulcer, which was 0.829 (95% CI: 0.729-0.930), with an optimal critical value of 11.60 U/ml, and the corresponding sensitivity was also the highest (74.4%); the AUC of CEA and CA724 was 0.534 (0.391-0.677) and 0.786 (0.668-0.903), respectively; the optimal critical values were 7.20 ng/ml and 6.34 U/ml, respectively; the corresponding specificity was 100.0%. Among the various indicators, the AUC of G-17 for distinguishing early gastric cancer from atrophic gastritis was the largest [0.813 (95% CI: 0.710-0.915)]. The specificity of each indicator at the optimal critical value was relatively high (≥ 94.8%), among which the optimal critical values of CEA and CA125 were 7.170 ng/ml and 15.55 U/ml, respectively, with the corresponding specificity of 100.0%; the AUC of CA724 was 0.783 (95% CI: 0.671-0.895), the optimal critical value was 6.40 U/ml, and the corresponding sensitivity was 71.8%, which was the highest among the several indicators. Conclusions:CEA, CA125, CA199, CA724, and G-17 have high sensitivity and detection rate in the differential diagnosis of early gastric cancer, gastric ulcer and atrophic gastritis, and have certain clinical values in the diagnosis of early gastric cancer and potential for clinical auxiliary diagnosis.
10.Curcumin ameliorates the pathogenesis of IgA nephropathy by regulating intestinal mucosal immunity through inhibition of Toll-like receptor 9/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway
Ziyang YE ; Qi DUAN ; Feng WU ; Xiaotong LI ; Sijie ZHANG ; Yafeng LI
Chinese Journal of Nephrology 2025;41(5):358-371
Objective:To explore the role of curcumin (Cur) in improving IgA nephropathy (IgAN) and its related mechanisms.Methods:Fifty 7-month-old miR-23b knockout (miR-23b -/-) mice weighing (25±5) g were used to establish an IgAN disease model, and were randomly divided into IgAN group, IgAN+Cur (150 mg/kg) group and IgAN+Cur (300 mg/kg) group using simple randomisation. Sixteen healthy 7-month-old weighing (25±3) g C57BL/6J wild-type mice served as the normal control group. IgAN+Cur (150 mg/kg) and IgAN+Cur (300 mg/kg) groups were respectively gavaged continuously with 150 mg/kg Cur and 300 mg/kg Cur for 8 weeks, and the normal control and IgAN groups were gavaged continuously with an equal dose of 0.9% sodium chloride solution for 8 weeks. The samples of urine, serum, intestinal fluid, intestinal tissues, kidney tissues and liver tissues were collected from each group. In vitro experiments, human cloned colon adenocarcinoma (Caco-2) cells were divided into blank control (Ctrl), Ctrl+Cur (10 μmol/L), Ctrl+ Cur (60 μmol/L), tumor necrosis factor-α(TNF-α), TNF-α+Cur (10 μmol/L) and TNF-α+Cur (60 μmol/L) groups. Enzyme-linked immunosorbent assay was used to detect serum alanine transaminase, aspartate transaminase, secretory IgA (sIgA), creatinine, blood urea nitrogen, 24 h urine microalbumin, as well as sIgA, TNF-α, interleukin(IL)-6 and IL-1β in the intestinal fluids. HE staining was used to observe the effect of Cur on liver tissues, the hyperplasia of glomerular mesangial zone in kidney tissues and the morphological and structural changes of intestinal epithelial barrier, and the histopathological damage scores were performed respectively. PAS staining was used to observe the changes of glomerular basement membrane and mesangial matrix. Immunofluorescence was used to observe the deposition of immune complexes in the glomerular mesangial zone. Real-time quantitative PCR was used to detect the mRNA expression levels of B-cell activating factor ( BAFF) and a proliferation inducing ligand ( APRIL). Western blotting was used to detect the protein expression levels of tight junction proteins zonula occluden-1 (ZO-1) and occludin in the mouse intestinal tissues. The potential targets of Cur in IgAN were predicted. Western blotting was used to detect the protein expression levels of tight junction proteins, as well as Toll-like receptor 9 (TLR9), myeloid differentiation primary response protein (MyD88), nuclear factor-κB p65 (NF-κB p65) and p-NF-κB p65. Results:Genetic identification results revealed that all IgAN model mice exhibited the miR-23b -/- genotype, confirming successful model establishment. Seven-month-old mice were subsequently selected for Cur treatment. Histopathological analysis demonstrated no significant differences in hepatic tissue morphology across groups, with comparable liver histopathological injury scores and unaltered liver function parameters, thereby validating the safety of Cur administration. Compared with the normal control group, IgAN mice displayed elevated levels of serum sIgA, serum creatinine, blood urea nitrogen and 24 h urine microalbumin (all P<0.05). Renal pathological results revealed severe mesangial hypercellularity in glomeruli, higher glomerular injury scores, and notable glomerular mesangial deposits of IgA, IgG and complement C3 in IgAN mice (all P<0.05). Additionally, intestinal pathological alterations were observed, including structural changes in intestinal epithelium and Peyer's patches, accompanied by significantly higher intestinal histopathological injury scores in IgAN mice ( P<0.05). Intestinal epithelial expression levels of ZO-1 and occludin were significantly reduced, while sIgA, TNF-α, IL-1β and IL-6 in intestinal fluid were elevated (all P<0.05). Serum FITC fluorescence intensity was markedly increased, and intestinal tissue exhibited upregulated mRNA expression of BAFF and APRIL (all P<0.05). Following Cur treatment, serum sIgA level and renal function indices in mice showed partial recovery (all P<0.05). Renal pathological improvements included alleviated mesangial hypercellularity, reduced glomerular injury scores, and diminished glomerular immune complex deposition (all P<0.05). Intestinal pathologies, including epithelial and Peyer's patch lesions, were mitigated, with decreased intestinal histopathological injury scores ( P<0.05). Additionally, intestinal tight junction protein expression levels were upregulated, intestinal fluid sIgA level was reduced, inflammatory markers were attenuated, serum FITC fluorescence intensity was declined, and intestinal BAFF and APRIL mRNA expression levels were downregulated (all P<0.05). In vitro experiments demonstrated that TNF-α exposure reduced tight junction protein expression in Caco-2 cells, whereas Cur treatment reversed the effect (all P<0.05). Target prediction analysis revealed that Cur effectively bound to TLR9 structural domain in IgAN. Experimental validation confirmed that Cur treatment suppressed the upregulated protein expression levels of TLR9, MyD88, NF-κB p65 and p-NF-κB p65 in intestinal tissues of IgAN mice (all P<0.05). Conclusion:Cur has a significant effect in the treatment of IgAN and can regulate intestinal mucosal immunity by inhibiting the TLR9/MyD88/NF-κB signaling pathway, thereby reducing renal injury and protecting the kidneys.

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