1.Cost-effectiveness analysis of insulin degludec and insulin aspart in Chinese patients with type 2 diabetes mellitus
Jiali QIN ; Yawen ZHANG ; Lei ZHANG ; Shan JIANG ; Xiaoyan YOU ; Xiaomei WANG ; Xianying WANG
China Pharmacy 2025;36(22):2809-2814
OBJECTIVE To evaluate the long-term cost-effectiveness of insulin degludec and insulin aspart (IDegAsp) in patients with type 2 diabetes mellitus (T2DM) in China. METHODS A cost-effectiveness analysis was conducted from the perspective of the Chinese healthcare system, using the CORE diabetes model to simulate long-term (20-year) health and economic outcomes. Baseline cohort characteristics and treatment effect data were derived from the CREATE study. The prices of glucose- lowering drugs were obtained from medical insurance payment standards and the average winning bid prices in the follow-up round of the specialized centralized procurement for insulin, while the daily dosages were derived from the CREATE study. The costs of complications and utility values were obtained from published literature, with a discount rate of 5%. One-way sensitivity analysis, scenario analysis, and probabilistic sensitivity analysis were performed to verify the robustness of the results. RESULTS Patients switching from previous once-daily basal insulin regimens to IDegAsp therapy gained an incremental 0.190 quality-adjusted life year (QALY) with direct medical cost savings of 42 163.58 yuan. For those switching from premixed insulin therapies, IDegAsp treatment provided 0.130 incremental QALY and reduced direct healthcare costs by 41 129.11 yuan. The outcome was significantly influenced by the discount rate and the cost of complications. Probabilistic sensitivity analysis and scenario analysis confirmed the robustness of these findings. CONCLUSIONS Switching from previous daily basal insulin or premixed insulin regimens to IDegAsp in Chinese patients with T2DM can improve patients’ long-term health outcomes and achieve cost savings, making it a more cost-effective treatment option.
2.Correlation between mental health status and metabolic syndrome in health checkup population
Honghai HE ; Xiaolian ZHANG ; Xiaoyan HAO ; Ying CHE ; Wei ZHAO ; Hongli WANG ; Lei TIAN ; Hua WU ; Peng WANG
Chinese Journal of Health Management 2025;19(2):127-133
Objective:To analyze the correlation between mental health status and metabolic syndrome (MetS) in health checkup people.Methods:It was a cross-sectional study, 2 920 participants who received health checkup in the Health Examination Center of Peking University Third Hospital from January 2019 to December 2023 were selected using cluster sampling method. Their general information, physical examination, biochemical indicators, body composition, and self-evaluation scores on the Symptom Checklist-90 (SCL-90) were collected. According to the inclusion and exclusion criteria, a total of 2 813 study subjects were included, and divided into the MetS group and the non-MetS group based on whether they had MetS. The differences in general demographic information, body composition, blood biochemistry, and SCL-90 scores between the two groups were compared. Binary Logistic regression analysis was used to explore the correlation between mental health status and MetS.Results:Of the 2 813 subjects included, 1 576 were males (56.0%) and 1 237 were females (44.0%), with an average age of (41.7±11.0) years, the MetS group had 586 cases (20.8%) and the non-MetS group had 2 227 cases (79.2%). The MetS group had higher levels of age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), fasting blood glucose, glycosylated hemoglobin (HbA 1c), free thyroxine(FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), waist-to-hip ratio, visceral fat area, body fat percentage, uric acid/creatinine, homocysteine (Hcy), aspartate aminotransferases (AST), and alanine transaminase (ALT) levels, as well as higher scores for somatization, hostility, paranoia, and other factor compared to the non-MetS group (all P<0.05), while high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) levels were lower than those in the non-MetS group (all P<0.05). The proportion of male, and the positive rates of SCL-90, somatization, interpersonal sensitivity, hostility, paranoia and other factor in the MetS group were higher than those in the non-MetS group (all P<0.05). Multifactorial analysis showed that individuals with a positive SCL-90 assessment had a 1.34 times higher risk of MetS than those with a negative assessment ( OR=1.34, 95% CI: 1.06-1.68; P=0.014). Among them, individuals with positive somatization ( OR=2.02, 95% CI: 1.25-3.28; P=0.004) and hostility ( OR=1.61, 95% CI: 1.02-2.56; P=0.042) had increased risk of MetS. Conclusion:Poor mental health status increases the risk of MetS.
3.Construction and effect evaluation of group health management mode for functional community
Ying CHE ; Gaili HE ; Honghai HE ; Peng WANG ; Lei TIAN ; Wei ZHAO ; Zhenge ZHANG ; Xiaoyan HAO
Chinese Journal of Health Management 2025;19(10):815-822
Objective:To construct a health management mode for functional community groups and evaluate its health management effect.Methods:This study was a non-randomized controlled trial. A cluster sampling method was adopted to select 3 352 subjects who completed three health examinations at the Physical Examination Center of Peking University Third Hospital from January 2022 to October 2024 and received health management for two consecutive years from a certain functional community (an enterprise) in Beijing as the research subjects. A health management mode for functional community groups was constructed, and a cohort of the population was established. A health management platform was built, and the research subjects were included in the health management system. Comprehensive interventions were carried out using multiple methods, including disease risk assessment, daily monitoring and reminders, exercise and nutrition assessment and intervention, personal health consultation, and health science popularization knowledge push. The subjects were classified and analyzed based on general information such as age and gender. The changes in systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were assessed using One-way Repeated Measures Analysis of Variance before the intervention and at 1 and 2 years after the intervention. The changes in triglycerides were assessed using Generalized Estimating Equations before the intervention and at 1 and 2 years after the intervention.Results:The systolic blood pressure, total cholesterol, and LDL-C levels of the total population showed a linear decreasing trend after the intervention (all P0.001). The HDL-C level showed an overall upward trend after the intervention [(1.45±0.32) vs (1.39±0.30) vs (1.47±0.33) mmol/L, F=12.746, P0.001]. However, there was no linear change trend in diastolic blood pressure, fasting blood glucose, and triglycerides after the intervention (all P0.05). The systolic blood pressure, total cholesterol and LDL-C levels of both men and women showed a linear decreasing trend after the intervention. For men, systolic blood pressure [(128.6±16.1) vs (127.6±16.3) vs (126.5±15.5) mmHg (1 mmHg=0.133 kPa); F=33.488, P0.001], total cholesterol [(5.29±1.02) vs (5.07±1.00) vs (4.94±1.03) mmol/L; F=286.525, P0.001], and LDL-C [(3.45±0.86) vs (3.43±0.84) vs (3.33±0.83) mmol/L; F=55.419, P0.001] all decreased. For women, systolic blood pressure [(118.9±15.6) vs (117.5±15.6) vs (117.2±15.8) mmHg; F=34.188, P0.001], total cholesterol [(5.13±0.94) vs (4.96±0.90) vs (4.85±0.90) mmol/L; F=274.080, P0.001], and LDL-C [(3.13±0.79) vs (3.10±0.76) vs (3.10±0.75) mmol/L; F=6.861, P=0.009] also decreased. The HDL-C level of men showed an overall upward trend after the intervention [(1.30±0.26) vs (1.25±0.25) vs (1.32±0.28) mmol/L; F=6.866, P0.05]. For men and women, diastolic blood pressure, fasting blood glucose and triglyceride levels showed no linear change trend after the intervention (all P0.05). The systolic blood pressure and total cholesterol levels of all age groups showed a linear decreasing trend after the intervention(all P0.001). In the 50-59 age group, diastolic blood pressure showed a linear decreasing trend after intervention [(81.6±11.6) vs (80.1±11.6) vs (79.9±11.6) mmHg; F=7.043, P0.05]. In the 40-49 age group, triglyceride showed an overall decreasing trend after intervention [1.29(0.91-2.01) vs 1.27(0.88-1.91) vs 1.27(0.92-1.89) mmol/L; Wald χ 2=10.062, P0.05]. In the 30-39 age group, LDL-C showed a linear decreasing trend after intervention [(3.23±0.80) vs (3.20±0.79) vs (3.19±0.77) mmol/L; F=7.702, P0.05]. In the 40-49 age group, LDL-C also showed a linear decreasing trend after intervention [(3.39±0.84) vs (3.36±0.82) vs (3.30±0.80) mmol/L; F=22.801, P0.001]. In the 50-59 age group, LDL-C showed a linear decreasing trend after intervention [(3.38±0.92) vs (3.32±0.91) vs (3.15±0.88) mmol/L; F=27.920, P0.001]. In the 30-39 age group, HDL-C showed an overall increasing trend after intervention [(1.46±0.33) vs (1.39±0.31) vs (1.48±0.34) mmol/L; F=10.047, P0.05]. In the 40-49 age group, HDL-C also showed an overall increasing trend after intervention [(1.45±0.30) vs (1.40±0.30) vs (1.47±0.32) mmol/L; F=10.118, P0.05]. However, there was no linear change trend in fasting blood glucose and triglyceride levels in all age groups after intervention ( F=1.169, 2.643, 0.663, 0.001, all P0.05). Conclusion:The functional community group health management mode constructed in this study has a good effect.
4.Exploration on the Protective Effects and Mechanisms of Modified Shenqi Dihuang Decoction on Podocytes in db/db Mice Based on ROS/NLRP3/GSDMD Signaling Pathway
Guiyan SUN ; Mingzhe LI ; Yan SHI ; Xiaoyan ZHUANG ; Xiaonan DUAN ; Moyan ZHANG ; Zhihan LEI ; Chunhui ZHANG ; Guanqi YANG ; Yufeng YANG ; Jing LYU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(11):123-132
Objective To explore the protective effect and possible mechanism of modified Shenqi Dihuang Decoction on podocytes in db/db mice based on ROS/NLRP3/GSDMD signaling pathway.Methods Fifty 8-week-old male db/db mice(SPF grade)were randomly divided into the model group,losartan group and TCM low-,medium-and high-dosage groups,with 10 mice in each group.Ten heterozygous db/m mice served as the blank group.Interventions were administered respectively for 12 weeks.The body mass,random blood glucose,serum creatinine,blood urea nitrogen and 24 h urinary protein content were detected,HE,PAS,PASM,Masson and Sirius red staining was used to observe the morphology of renal tissue,transmission electron microscopy was used to observe the ultrastructure of renal tissue,fluorescent probes were used to observe the release of ROS in renal tissue,immunofluorescence staining was used to detect the expression of Nephrin,NLRP3,Cleaved Caspase-1 and GSDMD-N in renal tissue,and Western blot was used to detect the expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18,Nephrin,Podocin,PODXL,WT-1 and Desmin proteins.Results Compared with the blank group,the body mass and random blood glucose of the model group mice significantly increased(P<0.05),and the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein were significantly increased(P<0.05);glomerular hypertrophy,dilation of renal glomeruli and tubules,thickening of basement membrane,matrix proliferation in mesangial area,abnormal deposition of collagen fibers in renal interstitium,accompanied by damage to renal tubular epithelial structure and focal glomerulosclerosis,significant increase in type Ⅰ collagen deposition,extensive fusion of podocyte processes,and scattered electron dense material in the basement membrane or subepithelial layer;the ROS content in renal tissue significantly increased(P<0.05),and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin significantly increased(P<0.05),the protein expression of Nephrin,Podocin,PODXL and WT1 significantly decreased(P<0.05).Compared with the model group,the body mass and random blood glucose of mice in each dosage of TCM group were relatively stable,the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein decreased;the pathological damage to renal tissue was reduced,the ultrastructure of podocytes was improved,and the density of podocytes increased;the ROS content decreased,and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin decreased,while the protein expression of Nephrin,Podocin,WT1 and PODXL increased.With the dosage of modified Shenqi Dihuang Decoction increased,the improvement effect gradually strengthened,and the differences in TCM high-dose group was statistically significant(P<0.05).Conclusion Modified Shenqi Dihuang Decoction can protects podocytes in db/db mice,potentially by modulating the ROS/NLRP3/GSDMD signaling pathway.
5.Application Value of 18F-FDG PET/CT Metabolic Parameters in Prognosis of Nasopharyngeal Carcinoma
Shanshan HE ; Nana LUO ; Xiaoyan HU ; Lei LI ; Yin NI ; Dasheng QIU
Cancer Research on Prevention and Treatment 2025;52(9):741-746
Objective To investigate the value of 18F-FDG PET/CT metabolic parameters in the prognostic assessment of nasopharyngeal cancer patients. Methods The clinical data and PET/CT metabolic parameters of 185 nasopharyngeal cancer patients were retrospectively analyzed. The collected parameters were SUVmax, MTV, TLG, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG). The ROC curve was used to determine the optimal cut-off values of PET/CT metabolic parameters. Univariate and multivariate Cox regression models were used to screen the independent prognostic factors. Kaplan–Meier curves were used to analyze the survival differences. Results The results of univariate Cox regression analysis showed that age, pathologic type, WTLG, TMTV, MTV, and TLG were closely associated with OS and PFS; and SUVmax was associated with PFS (P<0.05). Multivariate Cox regression analysis results showed that age, TMTV, and WTLG were the independent prognostic factors for OS and PFS (P<0.05). The combination of WTLG with T/N staging (AUC=0.781 and 0.781) and TMTV with T/N staging (AUC=0.800 and 0.790) yielded greater predictive accuracy than that of WTLG and TMTV alone (AUC=0.724 and 0.719) or T/N staging (AUC=0.593 and 0.575). Conclusion TMTV and WTLG are important prognostic predictors of nasopharyngeal carcinoma. TLG and MTV of primary lesions are prognostic factors for patients’ PFS and OS. SUVmax has limited prognostic value. Systemic metabolic indexes (TMTV and WTLG), when combined with T/N staging, can optimize prognostic stratification.
6.BTVT ameliorates offspring blood-brain barrier damage induced by prenatal and lactational neodymium oxide exposure via the gut-brain axis.
Xiaoyan DU ; Xiaocheng GAO ; Jing CAO ; Xin ZHAO ; Zhi HUO ; Shaoqing ZHAO ; Qingqing LIANG ; Lei GAO ; Yang DENG
Journal of Central South University(Medical Sciences) 2025;50(4):615-624
OBJECTIVES:
Exposure to rare earth elements (REEs) has been linked to various systemic diseases, but their impact on the offspring blood-brain barrier (BBB) via the gut-brain axis remains unclear. This study aims to investigate the effects of maternal exposure to neodymium oxide (Nd2O3) on the BBB integrity of offspring rats, and to evaluate the potential protective role of bifidobacterium tetrad viable tablets (BTVT) against Nd2O3-induced intestinal and BBB damage.
METHODS:
Healthy adult SD rats were mated at a 1:1 male-to-female ratio, with the day of vaginal plug detection marked as gestational day 0. A total of 60 pregnant rats were randomly assigned to the following groups: Control, 50 mg/(kg·d) Nd2O3, 100 mg/(kg·d) Nd2O3, 200 mg/(kg·d) Nd2O3, and 200 mg/(kg·d) Nd2O3 + BTVT group. Treatments were administered by daily oral gavage throughout pregnancy and lactation. On postnatal day 21 (weaning), offspring feces, brain, and colon tissues were collected. Hematoxylin and eosin (HE) staining was used to assess structural changes in brain and intestinal tissues. Short-chain fatty acids (SCFAs) in feces were quantified by gas chromatography-mass spectrometry (GC-MS). Evans Blue (EB) dye extravasation assessed BBB permeability. Gene and protein expression levels of tight junction proteins occludin and zonula occludens-1 (ZO-1) were measured by reverse transcription PCR (RT-PCR) and Western blotting (WB), respectively. Neodymium levels in brain tissue were determined via inductively coupled plasma mass spectrometry (ICP-MS).
RESULTS:
HE staining revealed that maternal Nd2O3 exposure caused mucosal edema, increased submucosal spacing, and lymphocyte infiltration in offspring colon, as well as neuronal degeneration and vacuolization in brain tissue. BTVT intervention alleviated these changes. GC-MS analysis showed that levels of acetic acid, propionic acid, butyric acid, and isobutyric acid significantly decreased, while valeric acid and isovaleric acid increased in offspring of Nd2O3-exposed mothers (P<0.05). BTVT significantly restored levels of acetic, propionic, and isobutyric acids and reduced valeric acid content (P<0.05). EB permeability was significantly elevated in Nd2O3-exposed offspring brains (P<0.05), but reduced with BTVT treatment (P<0.05). RT-PCR and WB showed downregulation of occludin and ZO-1 expression following Nd2O3 exposure (P<0.05), which was reversed by BTVT (P<0.05). ICP-MS results indicated significantly increased brain neodymium levels in offspring from all Nd2O3-exposed groups (P<0.05), while BTVT significantly reduced neodymium accumulation compared to the 200 mg/(kg·d) Nd2O3 group (P<0.05).
CONCLUSIONS
Maternal exposure to Nd2O3 during pregnancy and lactation disrupts intestinal health and BBB integrity in offspring, elevates brain neodymium accumulation, and induces neuronal degeneration. BTVT effectively mitigates Nd2O3-induced intestinal and BBB damage in offspring, potentially through modulation of the gut-brain axis.
Animals
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Female
;
Blood-Brain Barrier/pathology*
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Pregnancy
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Rats, Sprague-Dawley
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Rats
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Male
;
Neodymium/toxicity*
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Prenatal Exposure Delayed Effects/prevention & control*
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Lactation
;
Maternal Exposure/adverse effects*
;
Brain
7.Expert consensus on pulpotomy in the management of mature permanent teeth with pulpitis.
Lu ZHANG ; Chen LIN ; Zhuo CHEN ; Lin YUE ; Qing YU ; Benxiang HOU ; Junqi LING ; Jingping LIANG ; Xi WEI ; Wenxia CHEN ; Lihong QIU ; Jiyao LI ; Yumei NIU ; Zhengmei LIN ; Lei CHENG ; Wenxi HE ; Xiaoyan WANG ; Dingming HUANG ; Zhengwei HUANG ; Weidong NIU ; Qi ZHANG ; Chen ZHANG ; Deqin YANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Jingzhi MA ; Shuli DENG ; Xiaoli XIE ; Xiuping MENG ; Jian YANG ; Xuedong ZHOU ; Zhi CHEN
International Journal of Oral Science 2025;17(1):4-4
Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans
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Calcium Compounds/therapeutic use*
;
Consensus
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Dental Pulp
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Dentition, Permanent
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Oxides/therapeutic use*
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Pulpitis/therapy*
;
Pulpotomy/standards*
8.Expert consensus on management of instrument separation in root canal therapy.
Yi FAN ; Yuan GAO ; Xiangzhu WANG ; Bing FAN ; Zhi CHEN ; Qing YU ; Ming XUE ; Xiaoyan WANG ; Zhengwei HUANG ; Deqin YANG ; Zhengmei LIN ; Yihuai PAN ; Jin ZHAO ; Jinhua YU ; Zhuo CHEN ; Sijing XIE ; He YUAN ; Kehua QUE ; Shuang PAN ; Xiaojing HUANG ; Jun LUO ; Xiuping MENG ; Jin ZHANG ; Yi DU ; Lei ZHANG ; Hong LI ; Wenxia CHEN ; Jiayuan WU ; Xin XU ; Jing ZOU ; Jiyao LI ; Dingming HUANG ; Lei CHENG ; Tiemei WANG ; Benxiang HOU ; Xuedong ZHOU
International Journal of Oral Science 2025;17(1):46-46
Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans
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Root Canal Therapy/adverse effects*
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Consensus
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Root Canal Preparation/adverse effects*
9.Application value of chromosomal microarray analysis for the detection of low-level mosaicisms in amniotic fluid samples and analysis of rare cases.
Huiyuan SHAO ; Zongyu MIAO ; Hong WU ; Lei LI ; Xiaoyan LIU ; Yuping WANG ; Lihua JIANG
Chinese Journal of Medical Genetics 2025;42(4):441-445
OBJECTIVE:
To assess the value of chromosomal microarray analysis (CMA) for the detection of low-level mosaicisms in amniotic fluid samples, and to retrospectively analyze the rare cases of mosaicisms.
METHODS:
Chromosomal karyotype of the fetus was determined by G-banding analysis of cultured amniotic fluid cells. CMA was used to detect copy number variation of fetal chromosomes, and fluorescence in situ hybridization (FISH) was used to determine the proportion of fetal chromosomal mosaicisms in uncultured amniotic fluid cells.
RESULTS:
Among 825 prenatal samples, 4 cases of true fetal mosaicisms were detected, which yielded an incidence of 0.48%. Two cases were sex chromosomal mosaicisms, and two were autosomal mosaicisms, which involved chromosomes 8 and 9, respectively. All cases were verified by G-banding analysis of cultured amniotic fluid cells, CMA, and/or FISH.
CONCLUSION
CMA has a great value for detecting low-level mosaicisms in amniotic fluid samples, though the positive results need to be verified by other techniques and should be interpreted with caution. The review of rare cases can provide a basis for prenatal genetic counseling.
Humans
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Female
;
Amniotic Fluid/metabolism*
;
Pregnancy
;
Mosaicism/embryology*
;
Prenatal Diagnosis/methods*
;
Adult
;
In Situ Hybridization, Fluorescence
;
Microarray Analysis/methods*
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Karyotyping
;
Retrospective Studies
;
Male
10.Clinical and genetic analysis of a patient with Loeys-Dietz syndrome caused by a SMAD3 gene variant.
Lei SUN ; Yueli WANG ; Yanlong REN ; Renhua WU ; Junqing ZHANG ; Shu ZHOU ; Xiaoyan LI
Chinese Journal of Medical Genetics 2025;42(4):480-485
OBJECTIVE:
To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS).
METHODS:
A adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X).
RESULTS:
Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c.206+2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the proband's mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+PM2_Supporting).
CONCLUSION
The heterozygous splice site variant c.206+2T>G of the SMAD3 gene probably underlay the disease in this patient. Above discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.
Adult
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Humans
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Male
;
Exome Sequencing
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Loeys-Dietz Syndrome/genetics*
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Mutation
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Pedigree
;
Smad3 Protein/genetics*

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