1.Trend in disease burden of asthma attributable to tobacco in China from 1990 to 2021
MA Rongjiao ; HUANG Hanyan ; ZHU Manyu ; LIU Rui ; SHI Fang
Journal of Preventive Medicine 2026;38(1):89-92
Objective:
To investigate the trend in disease burden of asthma attributable to tobacco in China from 1990 to 2021, so as to provide the basis for improving intervention measures of asthma.
Methods:
Data on asthma-related mortality and disability-adjusted life years (DALY) attributable to tobacco among adults aged ≥30 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Age-standardized mortality and age-standardized DALY rate were calculated using the GBD world standard population structure to analyze the tobacco-attributable asthma burden. The average annual percent change (AAPC) was employed to evaluate temporal trends in the age-standardized mortality and DALY rate from 1990 to 2021.
Results:
In China, the age-standardized mortality and age-standardized DALY rate of asthma attributable to tobacco decreased from 0.73/100 000 and 22.20/100 000 in 1990 to 0.17/100 000 and 6.64/100 000 in 2021, showing downward trends (AAPC=-4.603% and -3.888%, both P<0.05). Among males, the tobacco-attributable age-standardized mortality and age-standardized DALY rate declined from 1.44/100 000 and 41.05/100 000 in 1990 to 0.36/100 000 and 12.79/100 000 in 2021 (AAPC=-4.369% and -3.810%, both P<0.05). Among females, the corresponding rates decreased from 0.21/105 and 5.37/105 to 0.03/105 and 1.08/105 (AAPC=-6.074% and -5.074%, both P<0.05). In 2021, males had higher tobacco-attributable age-standardized mortality and age-standardized DALY rate for asthma than females. Both the mortality and DALY rate of asthma attributable to tobacco increased with age, peaking in the age group ≥80 years at 7.84/100 000 and 112.07/100 000, respectively.
Conclusion
From 1990 to 2021, the disease burden of asthma attributable to tobacco showed a declining trend in China, with males and elderly population aged ≥80 years bearing a relatively heavier disease burden.
2.Efficiency and safety of haematopoietic stem cell collection in healthy donors
Rui HE ; Bangqiang ZHU ; Huiqin WEN ; Haijing WANG ; Maohong BIAN ; Yujie DIAO
Chinese Journal of Blood Transfusion 2025;38(2):209-213
[Objective] To explore the key factors affecting the efficiency and safety of hematopoietic stem cell apheresis. [Methods] The clinical data of 59 healthy donors who underwent allogeneic hematopoietic stem cell donation in the First Affiliated Hospital of Anhui Medical University from January 2021 to June 2024 were retrospectively analyzed. The number of CD34+ cells was used to evaluate the eligibility of stem cell collection. The effects of donor gender, age, patient weight, as well as the number of WBC, MNC, RBC, Hb, HCT, PLT, CD34+ cells, CD34+ percentage and instrument operating parameters on collection efficiency were analyzed. [Results] A total of 59 donors were enrolled, and 68 occasions of stem cell apheresis were performed, with a qualified collection rate of 56%. Donor gender, age, patient weight, total blood circulation volume, anticoagulant dosage, collection time, calcium gluconate dosage and RBC, Hb, HCT levels were not significantly correlated with the collection effect (P>0.05). Multivariate logistic regression analysis showed that the number of MNC cells, CD34+ cells and stem cell product volume were the key factors affecting the efficiency and safety. A total of 12 donors had mild adverse reactions during the collection process, and all of them were improved after treatment. [Conclusion] Optimizing apheresis strategy based on the three factors of MNC, WBC count and stem cell product volume on the day of collection will help to achieve high-quality collection and improve the success rate of transplantation.
3.Construction and Application Evaluation of an Integrated Traditional Chinese and Western Medicine Risk Prediction Model for Readmission in Patients with Stable Angina of Coronary Heart Disease:A Prospective Study Based on Real-World Clinical Data
Wenjie HAN ; Mingjun ZHU ; Xinlu WANG ; Rui YU ; Guangcao PENG ; Qifei ZHAO ; Jianru WANG ; Shanshan NIE ; Yongxia WANG ; Jingjing WEI
Journal of Traditional Chinese Medicine 2025;66(6):604-611
ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease (CHD) based on real-world clinical data, to establish a risk prediction model of integrated traditional Chinese and western medicine, in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD, who were divided into a training set and a validation set at a 7∶3 ratio. General information, traditional Chinese medicine (TCM)-related data, and laboratory test results were uniformly collected. After a one-year follow-up, patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination, calibration, and clinical decision curve analysis. ResultsA total of 682 patients were included, with 477 in the training set and 205 in the validation set, among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history [OR = 6.93, 95% CI (1.58, 30.45)], wiry pulse [OR = 2.58, 95% CI (1.42, 4.72)], weak pulse [OR = 3.97, 95% CI (2.06, 7.67)], teeth-marked tongue [OR = 4.38, 95% CI (2.32, 8.27)], blood stasis constitution [OR = 2.17, 95% CI (1.06, 4.44)], phlegm-stasis mutual syndrome [OR = 3.64, 95% CI (1.87, 7.09)], and elevated non-high-density lipoprotein cholesterol [OR = 1.30, 95% CI (1.01, 1.69)] as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability, with an area under the receiver operating characteristic curve (AUC) of 0.818 [95% CI (0.781, 0.852)] in the training set and 0.816 [95% CI (0.779, 0.850)] in the validation set. The Hosmer-Lemeshow test showed good calibration (χ² = 4.55, P = 0.80), and the model's predictive ability was stable. When the threshold probability exceeded 5%, the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure, teeth-marked tongue, weak pulse, wiry pulse, phlegm-stasis mutual syndrome, blood stasis constitution, and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors, which showed good discrimination, calibration, and clinical utility, providing a scientific basis for predicting readmission events in patients with stable angina.
4.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
5.Molecular classification of head and neck squamous cell carcinoma based on hypoxia-related genes and clinical significance of STC2
ZHU Jianing ; WANG Tiantian ; ZHANG Rui ; SONG Hongquan
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(5):345-358
Objective :
To construct a molecular classification system for head and neck squamous cell carcinoma (HNSCC) utilizing hypoxia-related gene (HAG) expression profiles, and to comprehensively examine the clinicopathological significance and biological functions of the hypoxia gene stanniocalcin 2 (STC2) in HNSCC.
Methods :
Transcriptomic data and clinical information of 546 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) database, and based on the expression profiles of 200 HRGs, HNSCC was classified subclasses using non-negative matrix factorization (NMF). HNSCC was classified into three subclasses (C1, C2, and C3), and the molecular characteristics and prognostic differences of the subclasses were assessed by comparing the tumor mutation load, functional enrichment analysis, drug sensitivity, and clinical features among the subclasses. LASSO-Cox regression was used to screen prognosis-related genes and construct prognostic models. Using oral squamous cell carcinoma (OSCC)-related data in the TCGA database, we analyzed the expression differences of STC2 in OSCC and control samples, and detected the mRNA and protein expression of STC2 in oral squamous carcinoma samples using qRT-PCR and immunohistochemistry. We knocked down STC2 in CAL-27 cells and verified the knockdown efficiency by qRT-PCR and Western blot. CCK-8 assay and cell scratch assay were used to assess the effect of STC2 on cell proliferation and migration ability.
Results:
Based on HRGs expression profiles, HNSCC was categorized into three subclasses (C1, C2, and C3). Subclass C1 had moderate hypoxic activity and good prognosis; subclass C2 had the highest hypoxic activity, poor prognosis, and poor sensitivity to CTLA-4 inhibitors (P<0.05); subclass C3 had the lowest hypoxic activity and moderate prognosis, and STC2 belonged to subclass C3. The frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and tumor protein p53 (TP 53) mutations was higher in HNSCC. C1 genomic gain and deletion burden were significantly higher than C3 subclass (P<0.05) and C2 genomic gain than C3 subclass (P<0.05). The C2 subclass was significantly enriched in hypoxia-associated pathways, such as glycine metabolism and base excision repair (P<0.05). The C1, C2, and C3 subclasses were significantly positively correlated in terms of sex (male) (Cramer’s V=0.15), radiation exposure (Cramer’s V=0.12), medication (Cramer’s V=0.18), and pathological grading (G1/G2) (Cramer’s V=0.25) (P<0.05). Nine prognosis-related genes were screened by LASSO-Cox regression, among which high expression of STC2 was positively correlated with poorer overall survival (OS) in HNSCC patients (P<0.01). Bioinformatics analysis showed that STC2 mRNA expression was higher in OSCC than in normal controls (P<0.05). qRT-PCR and immunohistochemistry confirmed that both mRNA and protein expression of STC2 were significantly upregulated in OSCC tissues and cells (P<0.01). In vitro experiments showed that STC2 expression was knocked down to approximately 80% in CAL-27 cells (P<0.001), and the STC2 knockdown group had a reduced value-added rate (P<0.001) and a reduced percentage of scratch closure (P<0.05) compared with the control group.
Conclusion
We successfully constructed a molecular typing system for HNSCC based on the expression profiles of HRGs and categorized HNSCC into three subclasses with significant prognostic differences, among which the C2 subclass had the highest hypoxic activity and the poorest prognosis. STC2 was highly expressed in HNSCC and suggested a poor prognosis, demonstrating that it may be a potential target for HNSCC treatment.
6.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
7.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
8.Diagnosis and Treatment of Lung Cancer Complicated with Sepsis from Perspective of "Yang Wei Yin Xian" Theory
Qinghua LIU ; Rui ZHU ; Jun YAN
Cancer Research on Prevention and Treatment 2025;52(5):423-428
"Yang Wei Yin Xian" originates from "Jin Kui Yao Lue". It denotes the slight pulse at the cun pulse and the yin pulse in the yang position, which indicates a deficiency of yang qi in the upper focus. The ulnar vein is a cord, and the yin position corresponds to the yin vein, which is excessive yin pathogen in the lower jiao. Lung cancer complicated with sepsis is common in clinical practice; it is characterized by a high mortality rate and poor conventional treatment outcomes. This article discusses "Yang Wei Yin Xian" and its relationship with lung cancer complicated by sepsis, evaluates the selection of TCM prescriptions and efficacy mechanisms of "Yang Wei Yin Xian" theory, and provides a reference for the use of this theory to guide clinical treatment.
9.Impact of Onset-to-Door Time on Endovascular Therapy for Basilar Artery Occlusion
Tianlong LIU ; Chunrong TAO ; Zhongjun CHEN ; Lihua XU ; Yuyou ZHU ; Rui LI ; Jun SUN ; Li WANG ; Chao ZHANG ; Jianlong SONG ; Xiaozhong JING ; Adnan I. QURESHI ; Mohamad ABDALKADER ; Thanh N. NGUYEN ; Raul G. NOGUEIRA ; Jeffrey L. SAVER ; Wei HU
Journal of Stroke 2025;27(1):140-143
10.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.


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