1.Effect of Xiaoqinglong Decoction (小青龙汤) on Th2 Immune Responses and Nasal Mucosal TSLP/OX40L Pathway in Allergic Rhinitis Model Rats
Yimeng CHEN ; Yuye CHEN ; Guangchun YU ; Bei CHEN ; Jianwei ZHANG ; Shanshan DING ; Xiaoting YANG ; Baifan YU ; Yating CAI ; Xuejuan LIN ; Mengting ZHANG
Journal of Traditional Chinese Medicine 2026;67(9):994-1002
ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction (小青龙汤, XD) in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group, a model group, a loratadine group, low-, medium- and high-dose XD groups, and low-, medium- and high-dose Mahuang Decoction and Cang'erzi Powder (麻黄汤合苍耳子散, MDCP) groups. Except for the control group, rats were administered with ovalbumin (OVA) and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection, nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/(kg·d) of saline, whereas those in the loratadine group were administered with 0.9 mg/(kg·d) of loratadine. The low-, medium- and high-dose XD groups were administered XD at the dose of 2.7, 5.4, and 10.8 g/(kg·d), respectively. The low-, medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43, 4.86, and 9.72 g/(kg·d), respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage, nasal symptom scores were recorded for all group of rats. The next day, serum levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and interleukin-13 (IL-13) were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR (RT-qPCR) and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin (TSLP) and OX40 ligand (OX40L) in the nasal mucosa. ResultsCompared to the control group, total nasal symptom score in the model group significantly increased (P<0.01). HE staining revealed disrupted and adhered cilia, thickened basement membranes, and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE, IL-4, and IL-13, as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa, were significantly elevated in the model group (P<0.05 or P<0.01). Compared to the model group, the total nasal symptom scores in all drug intervention groups were significantly reduced; the serum total IgE levels in the loratadine group, the low- and medium-dose XD groups, and the low- and high-dose MDCP groups were significantly reduced; and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased (P<0.05 or P<0.01). Nasal mucosal structure was improved. Except for the low-dose MDCP group, all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa (P<0.01). All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L (P<0.05). The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA, and TSLP protein levels compared to the loratadine group (P<0.05). ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway, thereby attenuating Th2-mediated immune responses.
2.Effect of Xiaoqinglong Decoction (小青龙汤) on Th2 Immune Responses and Nasal Mucosal TSLP/OX40L Pathway in Allergic Rhinitis Model Rats
Yimeng CHEN ; Yuye CHEN ; Guangchun YU ; Bei CHEN ; Jianwei ZHANG ; Shanshan DING ; Xiaoting YANG ; Baifan YU ; Yating CAI ; Xuejuan LIN ; Mengting ZHANG
Journal of Traditional Chinese Medicine 2026;67(9):994-1002
ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction (小青龙汤, XD) in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group, a model group, a loratadine group, low-, medium- and high-dose XD groups, and low-, medium- and high-dose Mahuang Decoction and Cang'erzi Powder (麻黄汤合苍耳子散, MDCP) groups. Except for the control group, rats were administered with ovalbumin (OVA) and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection, nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/(kg·d) of saline, whereas those in the loratadine group were administered with 0.9 mg/(kg·d) of loratadine. The low-, medium- and high-dose XD groups were administered XD at the dose of 2.7, 5.4, and 10.8 g/(kg·d), respectively. The low-, medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43, 4.86, and 9.72 g/(kg·d), respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage, nasal symptom scores were recorded for all group of rats. The next day, serum levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and interleukin-13 (IL-13) were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR (RT-qPCR) and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin (TSLP) and OX40 ligand (OX40L) in the nasal mucosa. ResultsCompared to the control group, total nasal symptom score in the model group significantly increased (P<0.01). HE staining revealed disrupted and adhered cilia, thickened basement membranes, and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE, IL-4, and IL-13, as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa, were significantly elevated in the model group (P<0.05 or P<0.01). Compared to the model group, the total nasal symptom scores in all drug intervention groups were significantly reduced; the serum total IgE levels in the loratadine group, the low- and medium-dose XD groups, and the low- and high-dose MDCP groups were significantly reduced; and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased (P<0.05 or P<0.01). Nasal mucosal structure was improved. Except for the low-dose MDCP group, all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa (P<0.01). All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L (P<0.05). The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA, and TSLP protein levels compared to the loratadine group (P<0.05). ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway, thereby attenuating Th2-mediated immune responses.
3.Comparative Analysis of Clinical Efficacy of Traditional Chinese Medicine Manipulative Reduction Combined with Small Splint Fixation Versus Surgical Treatment for Type A Distal Radius Fracture
Yang SHAO ; Zihan WANG ; Jianwei WANG ; Guoda DAI ; Hengyan CUI ; Zhen HUA ; Tingchen ZHU ; Shaoshuo LI ; Jun MAO ; Fenghua CHEN ; Shuai TAO ; Mao WU
Journal of Traditional Chinese Medicine 2026;67(10):1078-1085
ObjectiveTo compare the clinical efficacy of traditional Chinese medicine (TCM) manipulative reduction combined with small splint fixation versus surgical treatment for type A distal radius fracture (DRF) and to explore the factors influencing the choice of treatment. MethodsA multi-center retrospective study was conducted, collecting data from 1237 type A DRF patients treated in 11 hospitals in Jiangsu province from September, 2023 to April, 2025. Among them, 851 patients in the TCM group received manipulative reduction combined with small splint fixation, and 386 patients in the surgical group underwent open reduction and internal fixation. Visual analog scale (VAS) scores for pain and radiographic indicators including palmar tilt, ulnar deviation, and radial height were compared before treatment, 5-7 days after treatment, and 4-6 weeks after treatment. The wrist joint function scores including Dienst and Gartland-Werley scores at 12 weeks after treatment were recorded. Subgroup analysis was conducted for the excellent rate of Dienst and Gartland-Werley scores, stratified by age (<50, 50-59, 60-69, ≥70 years old) and AO subtypes (A1, A2, A3). A multivariate logistic regression model was used to identify independent factors influencing treatment choice. ResultsOn 5-7 days after treatment, the surgical group had lower VAS scores than the TCM group, while 4-6 weeks after treatment, the TCM group showed lower VAS scores than the surgical group (P<0.01). In terms of radiographic indicators, except for the palmar tilt before treatment being higher in the surgical group than in the TCM group (P<0.01), there were no significant differences in palmar tilt, ulnar deviation, and radial height at other timepoints (P>0.05). Twelve weeks after treatment, the surgical group had a higher average Gartland-Werley score and the excellent rate than the TCM group (P<0.01). Subgroup analysis showed that in patients with A2 type DRF aged 50-59 and 60-69 years old, the excellent rates of Dienst and Gartland-Werley scores in the TCM group were higher than those in the surgical group (P<0.05). Multivariate logistic regression analysis revealed that age, palmar tilt, ulnar deviation, and the degree of swelling on the affected side were independent factors influencing the choice of treatment (P<0.05). ConclusionBoth TCM manipulative reduction combined with small splint fixation and surgical treatment for type A DRF can achieve good therapeutic effects. TCM manipulative reduction combined with small splint fixation has certain advantages in medium- and long-term pain relief, especially in elderly patients, where wrist joint function recovery is more stable. Age, palmar tilt, ulnar deviation, and swelling degree are the main factors influencing the treatment choice.
4.Clinical Efficacy and Radiographic Outcomes of Manipulative Reduction Combined with Small Splint Fixation for Distal Radius Fractures:A Retrospective Multicenter Study with Propensity Score Matching
Mao WU ; Guoda DAI ; Yang SHAO ; Shaoshuo LI ; Zhen HUA ; Hengyan CUI ; Tingchen ZHU ; Dipeng LI ; Jintao LIU ; Ming ZHOU ; Peimin WANG ; Liyong ZHANG ; Jianwei WANG
Journal of Traditional Chinese Medicine 2026;67(10):1086-1092
ObjectiveTo observe the clinical efficacy and radiographic outcomes of manipulative reduction combined with small splint fixation in the treatment of distal radius fractures. MethodsThe clinical data of 1051 patients with distal radius fractures were retrospectively collected from five hospitals included in the Jiangsu Diagnosis and Treatment Data Platform for Traditional Chinese Medicine(TCM) Dominant Diseases. Propensity score matching at a 1∶4 ratio was applied, resulting in 580 cases selected for final analysis, which comprised 448 patients in the TCM group(manipulative reduction plus small splint fixation) and 132 in the surgical treatment group(open reduction and internal fixation). Each group was further stratified into type A, B, and C subgroups based on AO fracture classification. Radiographic indicators including palmar tilt, radial inclination, and radial height were compared between groups before treatment and 1 day, 1 week, and 4-6 weeks after treatment, and pain visual analog scale(VAS) scores before treatment and 1 week and 4-6 weeks after treatment were also compared. Wrist joint function was assessed 12 weeks after treatment, using the Dienst wrist function score and the Gartland and Werley(G-W) wrist function score. Additionally, the radiographic indicators at different timepoints and the 12-week wrist function levels were compared between groups across different fracture types. ResultsNo statistically significant difference was observed in radiographic indicators and VAS scores at all timepoints before and after treatment, as well as wrist joint function grades assessed by the Dienst score and the G-W score at 12 weeks after treatment (P>0.05). Compared to those before treatment, both groups showed increased palmar tilt, radial inclination, and radial height 1 week and 4-6 weeks after treatment, and decreased VAS scores (P<0.05). Compared to those 1 week after treatment, both groups showed a decrease in palmar tilt, an increase in radial inclination and radial height, and a reduction in VAS score 4-6 weeks after treatment(P<0.05). In type A and B subgroups, the surgical treatment group had a higher radial inclination than the TCM group 4-6 weeks after treatment, while in the type C subgroup, a higher radial height was shown in the surgical treatment group than in the TCM group 4-6 weeks after treatment(P<0.05). In type C subgroup, there was significant difference between groups in the wrist joint function by G-W scores 12 weeks after treatment(P<0.05). ConclusionManipulative reduction combined with small splint fixation can maintain fracture alignment and alleviate pain in treating distal radius fractures, which achieves therapeutic outcomes comparable to surgical treatment. It is particularly suitable for type A and B fractures and can be considered an effective treatment option for distal radius fractures.
5.Construction and Clinical Validation of a Deep Learning-Based Automatic Measurement Model for Palmar Tilt and Radial Inclination in Distal Radius Fractures
Guoda DAI ; Jianwei WANG ; Mao WU ; Bin KANG ; Yang SHAO ; Hengyan CUI ; Shaoshuo LI ; Tingchen ZHU ; Zhen HUA ; Zhongming SHEN ; Jintao LIU ; Ming ZHOU
Journal of Traditional Chinese Medicine 2026;67(10):1093-1100
ObjectiveTo construct an automatic measurement model for palmar tilt and radial inclination suitable for traditional Chinese medicine (TCM) clinical scenarios, and to validate its accuracy and efficiency in TCM manipulative reduction settings. MethodsData on anteroposterior (AP) and lateral X-rays of distal radius fractures were collected from patients admitted to 18 TCM/ integrated TCM and western medicine hospitals in Jiangsu province between September 1st, 2023, and September 1st, 2024, via the Jiangsu Diagnosis and Treatment Big Data Platform for TCM Dominant Diseases. A medical image segmentation framework based on multi-scale feature fusion and edge-awareness was employed, combined with anatomical knowledge specific to TCM orthopedics, to optimize the feature extraction strategy of an artificial intelligence (AI) model. This framework enabled automatic segmentation of fracture regions and measurement of distal radius palmar tilt and radial inclination. The accuracy of the AI model in measuring radial inclination and volar tilt was validated, and the measurement time and average time gain rate of the AI model were compared to those of manual measurement. ResultsA total of 15,444 AP and lateral X-ray images of distal radius fractures were collected, and were divided into a training set (11,144 images, 5066 AP and 6078 lateral), a validation set (3700 images, 1840 AP and 1860 lateral), and an independent test set (600 images, 300 AP and 300 lateral) after preprocessing. In the measurement of 300 AP X-rays in the independent test set for radial inclination, when the degree error between AI measurement and manual measurement was <3° and <5°, AI measurement accuracy was 83% and 93%, respectively. In 300 lateral X-rays in the test set for palmar tilt, when AI measurements had an error of <3° and <5° compared to manual measurements, corresponding accuracy rate was 78% and 90%, respectively. For 50 X-ray images, AI measurement time was (1.37±0.05) min for radial inclination while manual measurement time was (22.57±2.52) min (P<0.001); in terms of palmar tilt, the AI measurement time was (1.33±0.14) min, shorter than (23.70±2.80) min for manual measurement time (P<0.001). Average time gain rates for manual and AI measurements were 93.93% and 94.39% respectively. ConclusionAn automatic measurement model for palmar tilt and radial inclination in distal radius fractures has been established, enabling more accurate and efficient assessment as well as providing a tool to support the quantitative evaluation of the efficacy of TCM manipulative reduction and large-sample clinical research.
6.Effects and mechanisms of action of Yiqi wenyang huwei decoction in improving bronchial asthma in rats
Yunqing YANG ; Jianyu XIE ; Wei TANG ; Chao YE ; Qiangqiang YU ; Peng SUN ; Yuping YANG ; Jianwei YU
China Pharmacy 2026;37(10):1264-1271
OBJECTIVE To investigate the effects and potential mechanism of Yiqi wenyang huwei decoction (YQWY) in improving airway inflammation and remodeling in rats with bronchial asthma (BA) based on the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response protein 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. METHODS Male SD rats were randomly divided into the normal group, the model group, the dexamethasone group (positive control, 0.5 mg/kg), and YQWY low-, medium- and high-dose groups (5, 10, 20 g/kg, calculated by the crude drug), with 8 rats in each group. Except for the normal group, rats in all other groups were sensitized twice with ovalbumin combined with aerosol challenge to establish a BA model. From day 14 to day 34 of the experiment, the rats in each group were administered the corresponding drug solution or normal saline intragastrically, once a day, 1 hour before aerosol challenge. At 24 hours after the final aerosol challenge, asthma symptom scores were assessed, serum levels of immunoglobulin E (IgE) were measured, and the levels of inflammatory cytokines (interleukin-4, interleukin-5, interleukin-13 and tumor necrosis factor-α) and the numbers of inflammatory cells (white blood cell, eosinophil, neutrophil, lymphocyte, monocyte and basophil) in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue were observed. The mRNA expressions of TLR4, MyD88 and NF-κB, as well as the protein expressions of TLR4, MyD88, NF-κB p65 and phosphorylated NF-κB p65 in lung tissue, were detected. RESULTS Compared with the model group, the pathological changes, such as inflammatory cell infiltration, abnormal deposition of collagen fibers, and goblet cell hyperplasia in the lung tissue of rats in each drug group, were alleviated to varying degrees. The asthma symptom scores (except for the YQWY low-dose group), the levels of IgE and inflammatory cytokines (except for interleukin-5 in the YQWY medium-dose group), the number of inflammatory cells (except for monocyte and basophil in the YQWY low-dose group), the mRNA expression of TLR4, MyD88 and NF-κB, as well as the protein expressions of TLR4, MyD88, NF-κB p65 and phosphorylated NF-κB p65 (except for MyD88 and NF-κB p65 proteins in the YQWY low-dose group as detected by Western blo t) were all significantly reduced or down-regulated ( P <0.05 or P <0.01). CONCLUSIONS YQWY can alleviate asthma-like manifestations in BA rats and improve their airway inflammation and remodeling; these effects may be related to the formula’s inhibition of the abnormal activation of the TLR4/MyD88/NF-κB signaling pathway.
7.Investigation and analysis of radioactivity detection capacity for food and drinking water in municipal and county-level disease control and prevention institutions in Shandong Province
Xinyun WANG ; Tao ZHOU ; Wei ZHANG ; Ke YANG ; Yi LIU ; Jianwei LIU ; Chundong XIA ; Bo TANG ; Xianpeng ZHANG
Chinese Journal of Radiological Health 2026;35(3):325-330
Objective To investigate the capacity of municipal and county-level Centers for Disease Control (CDC) in Shandong Province for γ radionuclides in food as well as gross α and gross β in drinking water, and to provide evidence for strengthening radiological laboratories. Method Data regarding radioactive detection capacity were collected from 16 prefecture-level cities and 136 county-level CDCs. Chi-square test and Fisher's exact tests were used to compare capacity differences across regions and between cities with and without nuclear power plants. Correlation analysis was used to evaluate the spatial equity of gross α and gross β detection capacity for drinking water. Result The detection capacity of gross α and gross β in drinking water varied significantly among counties (χ2=81.026, P<0.001),no significant difference was found between coastal and inland cities (χ2=2.021,P>0.155); Cities with nuclear power plants showed better detection capacity (χ2=20.253,P<0.01). The detection capacity for γ radionuclides in food was primarily concentrated in the prefecture-level cities that host nuclear power plants. Conclusion The overall detection capacity for radioactivity in drinking water was acceptable but spatially uneven. The capacity for monitoring radioactive contamination in food was generally weak. It is necessary to strengthen capacity building at the grassroots level.
8.Integrating Data Mining and Network Pharmacology to Explore the Optimization Strategy and Mechanism of Qishen Granules in Treating Coronary Heart Disease with Heart Failure
Jianwei YUE ; Jianglin XU ; Ligen DAO ; Jiale HE ; Jiangfeng ZHAO ; Jun WANG ; Zhi YANG ; Chun LI ; Wei WANG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(6):1454-1463
Objective To explore the optimization strategy of Qishen Granules in treating coronary heart disease with heart failure(CHD-HF)based on data mining and the pathogenic"toxin"theory,and to predict its active components and mechanisms using network pharmacology.Methods Literature on traditional Chinese medicine(TCM)for treating CHD-HF was collected from relevant databases,and prescriptions were screened and established into a database according to inclusion and exclusion criteria.Frequency,association rules,and hierarchical clustering analyses were performed using the Ancient and Modern Medical Case Cloud Platform.Network pharmacology techniques were applied to screen potential targets of the optimized combination for treating CHD-HF,and carry out the targets and pathways enrichment analysis.Results A total of 336 articles and 339 prescriptions involving 191 herbs were included,with 12 herbs used more than 100 times.The core drug combinations for treating CHD-HF included Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,etc,while commonly used detoxifying herbs included Leonuri Herb,Coptidis Rhizoma,etc.Association rule analysis yielded 10 two-item associations and 17 three-item associations;clustering analysis grouped the data into 5 categories.Based on data mining and the pathogenic"toxin"theory,the combination for treating CHD-HF was optimized to include Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Aconiti Lateralis Radix Praeparata,Glycyrrhizae Radix et Rhizoma,Coptidis Rhizoma,and Taraxaci Herba.Network pharmacology analysis identified 366 common targets between the optimized combination and CHD-HF,with 16 core targets screened out.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed significant enrichment in pathways such as cancer pathways,lipid and atherosclerosis,Rap1 signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway,Ras signaling pathway,and mitogen-activated protein kinase(MAPK)signaling pathway.Conclusion TCM treatment for CHD-HF primarily focuses on replenishing qi and warming yang,activating blood circulation and resolving fluid retention.Based on data mining results and the pathogenic"toxin"theory,the formulation strategy of Qishen Granules for treating CHD-HF was optimized,potentially exerting therapeutic effects through anti-inflammatory,anti-apoptotic,and anti-hypoxia physiological processes.
9.Clinical and genetic analysis of a child with Lamb-Shaffer syndrome due to a de novo variant of SOX5 gene.
Liming ZHANG ; Liye SHI ; Linfei LI ; Jianwei YANG ; Hongqi SUN ; Junmei YANG ; Yongxing CHEN
Chinese Journal of Medical Genetics 2025;42(1):89-93
OBJECTIVE:
To explore the clinical features of a child with Lamb-Shaffer syndrome (LAMSHF) due to a variant of SOX5 gene.
METHODS:
A child who was admitted to Children's Hospital Affiliated to Zhengzhou University in July 2022 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing (WES) was carried out on peripheral blood samples from the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-100).
RESULTS:
The child, an one-year-and-seven-month-old male, has manifested delayed development in speech and language, intelligence and movement, in addition with mild facial deformities and eye signs. Whole exome sequencing revealed that he has harbored a heterozygous c.1828_1829insGACT (p.Y610fs*1) frameshifting variant of the SOX5 gene. Sanger sequencing confirmed the variant to be de novo in origin. The variant was also unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_supporting).
CONCLUSION
The c.1828_1829insGACT (p.Y610fs*1) variant of the SOX5 gene probably underlay the pathogenesis of LAMSHF in this child. For children with delayed mental, language, intellectual, and motor development, genetic testing should be conducted to facilitate early diagnosis. Above finding has enriched the mutational spectrum of the SOX5 gene.
Humans
;
SOXD Transcription Factors/genetics*
;
Male
;
Infant
;
Exome Sequencing
;
Genetic Testing
;
Mutation
10.Genetic analysis of a case of Miller-McKusick-Malvaux syndrome type 1 caused by CUL7 gene variant and a literature review.
Liming ZHANG ; Xue WU ; Jianwei YANG ; Hongqi SUN ; Junmei YANG ; Yongxing CHEN
Chinese Journal of Medical Genetics 2025;42(3):343-348
OBJECTIVE:
To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant.
METHODS:
A child diagnosed with 3MS type 1 at the Children's Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020).
RESULTS:
The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. WES revealed compound heterozygous variants in the CUL7 gene: c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child's father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c.2686G>T (p.E896) was classified as a pathogenic (PVS1+PM2_Supporting+PM3), and c.1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+PM2_Supporting). Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%).
CONCLUSION
The compound heterozygous variants c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.
Humans
;
Cullin Proteins/genetics*
;
Female
;
Child
;
Limb Deformities, Congenital/genetics*
;
Exome Sequencing
;
Mutation
;
Child, Preschool
;
Dwarfism
;
Muscle Hypotonia
;
Spine/abnormalities*

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