1.Allogeneic lung transplantation in miniature pigs and postoperative monitoring
Yaobo ZHAO ; Ullah SALMAN ; Kaiyan BAO ; Hua KUI ; Taiyun WEI ; Hongfang ZHAO ; Xiaoting TAO ; Xinzhong NING ; Yong LIU ; Guimei ZHANG ; He XIAO ; Jiaoxiang WANG ; Chang YANG ; Feiyan ZHU ; Kaixiang XU ; Kun QIAO ; Hongjiang WEI
Organ Transplantation 2026;17(1):95-105
Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO2) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.
2.Effect of Zhengan Xifengtang on Intestinal Mucosal Barrier in Spontaneously Hypertensive Rats via FXR-MLCK/p-MLC Pathway
Meilong SI ; Hua JIN ; Yu WANG ; Qiuju ZHANG ; Tao LIU ; Yun YONG ; Xuan BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):1-10
ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats (SHRs) through the pathways of farnesoid X receptor (FXR)-myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group, amlodipine besylate group (0.5 mg·kg-1·d-1), and high, middle and low dose groups of Zhengan Xifengtang (34.5, 17.25, 8.625 g·kg-1·d-1); eight age-matched male Wistar-Kyoto (WKY) rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks, and the blood pressure of the rats was measured regularly. After the intervention, the rats were euthanized to collect tissue samples. Hematoxylin and eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay (ELISA) was employed to measure plasma lipopolysaccharide (LPS) and diamine oxidase (DAO) levels in each group of rats. Immunofluorescence (IF) assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 (ZO-1), Occludin, Claudin-1, junctional adhesion molecule-1 (JAM-1), mucin-2 (MUC2), FXR, MLCK, and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of ZO-1, Occludin, Claudin-1, JAM-1, MUC2, FXR, MLCK, and MLC in colon tissue. ResultsCompared with the normal group, the blood pressure in the model group increased significantly (P<0.01), the colonic mucosal structure was seriously damaged, and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly (P<0.01), the relative fluorescence intensity of FXR in colon decreased, while that of p-MLC increased (P<0.01). The protein and mRNA expressions of ZO-1, Claudin-1, JAM-1, Occludin, MUC2 and FXR decreased significantly (P<0.01), whereas the protein expression of MLCK and p-MLC increased significantly (P<0.01). Additionally, the mRNA expression of MLCK and MLC increased significantly (P<0.01). Compared with the model group, the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure (P<0.01). The damage of colonic mucosa structure was alleviated, the infiltration of inflammatory cells decreased, and the number of goblet cells increased. LPS and DAO levels were decreased (P<0.05, P<0.01). In the colon, the relative fluorescence intensity of FXR increased, while that of p-MLC decreased (P<0.05, P<0.01). The protein and mRNA expression levels of ZO-1, Claudin-1, JAM-1, Occludin, and FXR increased significantly (P<0.05, P<0.01), while the protein expression of MLCK and p-MLC decreased significantly (P<0.05, P<0.01). Furthermore, the mRNA expression of MLCK and MLC decreased significantly (P<0.05, P<0.01), and the protein expression of MUC2 increased significantly (P<0.05, P<0.01). The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly (P<0.05, P<0.01). ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein, thereby reducing intestinal mucosal permeability, promoting mucosal barrier repair, decreasing LPS release into the blood, and ultimately lowering blood pressure.
3.Effect of Zhengan Xifengtang on Intestinal Mucosal Barrier in Spontaneously Hypertensive Rats via FXR-MLCK/p-MLC Pathway
Meilong SI ; Hua JIN ; Yu WANG ; Qiuju ZHANG ; Tao LIU ; Yun YONG ; Xuan BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):1-10
ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats (SHRs) through the pathways of farnesoid X receptor (FXR)-myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group, amlodipine besylate group (0.5 mg·kg-1·d-1), and high, middle and low dose groups of Zhengan Xifengtang (34.5, 17.25, 8.625 g·kg-1·d-1); eight age-matched male Wistar-Kyoto (WKY) rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks, and the blood pressure of the rats was measured regularly. After the intervention, the rats were euthanized to collect tissue samples. Hematoxylin and eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay (ELISA) was employed to measure plasma lipopolysaccharide (LPS) and diamine oxidase (DAO) levels in each group of rats. Immunofluorescence (IF) assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 (ZO-1), Occludin, Claudin-1, junctional adhesion molecule-1 (JAM-1), mucin-2 (MUC2), FXR, MLCK, and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of ZO-1, Occludin, Claudin-1, JAM-1, MUC2, FXR, MLCK, and MLC in colon tissue. ResultsCompared with the normal group, the blood pressure in the model group increased significantly (P<0.01), the colonic mucosal structure was seriously damaged, and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly (P<0.01), the relative fluorescence intensity of FXR in colon decreased, while that of p-MLC increased (P<0.01). The protein and mRNA expressions of ZO-1, Claudin-1, JAM-1, Occludin, MUC2 and FXR decreased significantly (P<0.01), whereas the protein expression of MLCK and p-MLC increased significantly (P<0.01). Additionally, the mRNA expression of MLCK and MLC increased significantly (P<0.01). Compared with the model group, the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure (P<0.01). The damage of colonic mucosa structure was alleviated, the infiltration of inflammatory cells decreased, and the number of goblet cells increased. LPS and DAO levels were decreased (P<0.05, P<0.01). In the colon, the relative fluorescence intensity of FXR increased, while that of p-MLC decreased (P<0.05, P<0.01). The protein and mRNA expression levels of ZO-1, Claudin-1, JAM-1, Occludin, and FXR increased significantly (P<0.05, P<0.01), while the protein expression of MLCK and p-MLC decreased significantly (P<0.05, P<0.01). Furthermore, the mRNA expression of MLCK and MLC decreased significantly (P<0.05, P<0.01), and the protein expression of MUC2 increased significantly (P<0.05, P<0.01). The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly (P<0.05, P<0.01). ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein, thereby reducing intestinal mucosal permeability, promoting mucosal barrier repair, decreasing LPS release into the blood, and ultimately lowering blood pressure.
4.The decade of otoendoscope in China.
Yu SUN ; Xiuyong DING ; Yunfeng WANG ; Wuqing WANG ; Wei WANG ; Wenlong SHANG ; Wen ZHANG ; Jie ZHANG ; Yang CHEN ; Zhaoyan WANG ; Haidi YANG ; Qiong YANG ; Yu ZHAO ; Zhaohui HOU ; Yong CUI ; Lingyun MEI ; Youjun YU ; Hua LIAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(12):1103-1109
5.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
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Practice Guidelines as Topic
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Drugs, Chinese Herbal/therapeutic use*
6.Profiling the chemical differences of diterpenoid alkaloids in different processed products of Aconiti Lateralis Radix Praeparata by UHPLC-LTQ-Orbitrap mass spectrometry combined with untargeted metabolomics and mass spectrometry imaging.
Yang YU ; Changliang YAO ; Jianqing ZHANG ; Yong HUANG ; Shuai YAO ; Hua QU ; Tong ZHANG ; Dean GUO
Chinese Journal of Natural Medicines (English Ed.) 2025;23(8):1009-1015
Aconiti Lateralis Radix Praeparata (Fuzi) represents a significant traditional Chinese medicine (TCM) that exhibits both notable pharmacological effects and toxicity. Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components, primarily diterpenoid alkaloids. To comprehensively analyze the chemical variations between different Fuzi products, ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was employed to systematically characterize Shengfuzi, Heishunpian and Baifupian. A total of 249 diterpenoid alkaloids present in Shengfuzi were identified, while only 111 and 61 in Heishunpian and Baifupian were detected respectively, indicating substantial differences among these products. An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers. Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples, 8 robust markers distinguishing these products were identified, including AC1-propanoic acid-3OH, HE-glucoside, HE-hydroxyvaleric acid-2OH, dihydrosphingosine, N-dodecoxycarbonylvaline and three unknown compounds. Additionally, the MS imaging (MSI) technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi, revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian. The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products. This research provides valuable insights into the material basis for future investigations of different Fuzi products.
Diterpenes/chemistry*
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Alkaloids/chemistry*
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Chromatography, High Pressure Liquid/methods*
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Aconitum/chemistry*
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Drugs, Chinese Herbal/chemistry*
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Metabolomics
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Mass Spectrometry/methods*
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Plant Roots/chemistry*
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Molecular Structure
7.Dynamic Monitoring and Correlation Analysis of General Body Indicators, Blood Glucose, and Blood Lipid in Obese Cynomolgus Monkeys
Yanye WEI ; Guo SHEN ; Pengfei ZHANG ; Songping SHI ; Jiahao HU ; Xuzhe ZHANG ; Huiyuan HUA ; Guanyang HUA ; Hongzheng LU ; Yong ZENG ; Feng JI ; Zhumei WEI
Laboratory Animal and Comparative Medicine 2025;45(1):30-36
ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P<0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P<0.05), with this increasing trend persisting in the third year (P<0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P<0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.
8.Integrating data mining and network pharmacology to decode the therapeutic principles of contemporary Xin'an medicine for chronic glomerulonephritis
Xulei HU ; Xiaowei DUAN ; Le WANG ; Zhengyang ZHU ; Yong LYU ; Hua JIN ; Dong WANG ; Lei ZHANG ; Kejun REN
Chinese Journal of Pharmacoepidemiology 2025;34(6):676-689
Objective To systematically summarize medication patterns and explore the potential mechanisms of core herbal combinations in treating chronic glomerulonephritis(CGN)based on data mining and network pharmacology,and to provide a reference for clinical treatment strategies.Methods Electronic book databases were searched to screen the CGN prescription from the works of contemporary Xin'an medical practitioners.Frequency statistics,association rule analysis,and clustering algorithms via the traditional Chinese medicine(TCM)Inheritance Support Platform V3.5 were applied to identify high-frequency herbs(frequency of use>10%)and core combinations.Active ingredients and potential targets were predicted using TCMSP,PubChem,and SwissTargetPrediction databases.Disease-related targets were retrieved from OMIM and GeneCards,after obtaining the intersecting targets,followed by protein-protein interaction(PPI)network construction(STRING platform),Cytoscape topological analysis,and GO and KEGG pathway enrichment(DAVID).Results A total of 151 prescriptions related to the treatment of CGN were included,involving 213 flavours of TCM,including 42 varites of high frequency drugs,mainly in the categories of supplementing deficiency,eliminating dampness and diuresis and clearing heat.Theherb properties were mainly cold,warm,and neutral,with flavors of sweet,bitter,and pungent.Herbs primarily targeted the liver,lung,kidney,and spleen meridians.Thecore combination"Astragali Radix,Dioscorea Rhizome,Atractylodis Macrocephalae Rhizoma,Imperata Rhizome,Pyrrosiae Folium,Poria"was identified,with key active ingredients including quercetin,stigmasterol,and β-sitosterol.Core targets involved IL6,EGFR,TNF,AKT1,and PIK3CA,while enriched pathways included PI3K-Akt and AGE-RAGE signaling.Conclusion Contemporary Xin'an practitioners primarily treat CGN by tonifying the spleen,nourishing the kidney,and clearing damp-heat.Thecore herbal combination exerts synergistic effects through multi-target intervention in immune-inflammatory pathways,oxidative stress,and fibrotic pathways,highlighting the holistic therapeutic advantages of TCM formulas via multi-component synergistic regulation and multi-target interactions.This study provides a theoretical foundation for further experimental validation and clinical applications.
9.Study of 12 blood donors with c.389T>C variant of ABO*A1.01 allele and weak expression of A from Xi'an area.
Qinqin ZUO ; Liangzi ZHANG ; Hua XU ; Yong ZHANG
Chinese Journal of Medical Genetics 2025;42(4):406-410
OBJECTIVE:
To carry out serological and molecular tests on 12 blood donors and family members of one proband with discrepancy results for ABO serological typing.
METHODS:
Twelve blood donors with ABO discrepancies identified by the Blood Center of Shaanxi Province from March 2015 to December 2023 and family members of one proband were selected as the study subjects. Serological blood typing was carried out to determine their blood phenotype. ABO genotype of the samples was determined by direct sequencing of amplicons of exons 1 to 7 and cloning sequencing of amplicons of exons 6 and 7. This study has been approved by the Ethics Committee of Blood Center of Shaanxi Province (202328).
RESULTS:
Serological results showed that 5 samples were Aweak, 4 samples were Aweak with anti-A1 antibody, and 3 samples were AweakB with anti-A1. Direct sequencing and cloning sequencing results showed that all 12 samples had the haplotype ABO*A1.01/c.389T>C, and family studies showed that the allele could be stably inherited. Glycosyltransferase activity in the plasma was decreased in all samples.
CONCLUSION
The c.389T>C variant of the ABO*A1.01 allele can alter the encoded amino acid p.Leu130Pro, which weakens the activity of A glycosyltransferase, ultimately leading to the weak expression of A antigen.
Humans
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ABO Blood-Group System/genetics*
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Blood Donors
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Alleles
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Male
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Female
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Exons
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Genotype
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China
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Adult
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Base Sequence
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Haplotypes
10.Clinical features and genetic analysis of a child with Progressive familial intrahepatic cholestasis type 8 due to compound heterozygous variants of KIF12 gene.
Dayan SUN ; Shixuan ZHANG ; Junmin LIAO ; Shuangshuang LI ; Dingding WANG ; Ya'nan ZHANG ; Yichao GU ; Kaiyun HUA ; Jinshi HUANG ; Yong ZHAO
Chinese Journal of Medical Genetics 2025;42(12):1437-1445
OBJECTIVE:
To explore the clinical phenotype and genetic characteristics of a child with Progressive familial intrahepatic cholestasis type 8 (PFIC8). METHODS A child with PFIC diagnosed at Beijing Children's Hospital Affiliated to Capital Medical University in September 2025 was selected as the study subject. Peripheral venous blood samples were collected from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Beijing Children's Hospital Affiliated to Capital Medical University (Ethics No.: 2023-E-126-Y).
RESULTS:
The proband, a 2-month-old female infant, had manifested jaundice of the skin and sclera, and slightly distended abdomen. She had no visible abdominal wall varicose veins, soft abdomen, and no palpable masses. Biliary atresia was ruled out by intraoperative cholangiography. WES revealed that she has harbored compound heterozygous variants of KIF12 gene, namely c.809C>T (p.Ala270Val) and c.1313G>A (p.Arg438Lys), which were verified by Sanger sequencing to have derived from her mother and father, respectively. According to the ACMG guidelines, both variants were classified as variants of uncertain significance (VUS). Based on the pre-defined search strategy, 10 articles were retrieved, which involved 25 PFIC cases, including 5 from China. Together with the proband of this study, the 26 PFIC patients have primarily presented with high GGT cholestasis, with the genetic cause in all cases attributed to variants of the KIF12 gene.
CONCLUSION
The c.809C>T and c.1313G>A compound heterozygous variants of the KIF12 gene probably underlay the pathogenesis of cholestatic liver disease in this child. Above findings have enriched the mutational and phenotypic spectra of PFIC8.
Humans
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Kinesins/genetics*
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Female
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Cholestasis, Intrahepatic/genetics*
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Infant
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Heterozygote
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Mutation
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Exome Sequencing
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Male

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