1.Exploration of the antidepressant machanism of Shugan hewei tang based on metabolomics of PFC-NAc-VTA neural circuit
Xinyue QU ; Junjie HU ; Juan LI ; Min ZHANG ; Xian ZHOU ; Songlin LIU ; Xin CHEN
China Pharmacy 2025;36(10):1172-1178
OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang (SGHWT) based on the metabolomics of prefrontal cortex (PFC)-nucleus accumbens (NAc)-ventral tegmental area (VTA) neural circuit. METHODS Male SD rats were randomly divided into blank group, model group, SGHWT low-, medium- and high-dose groups [3.67, 7.34, 14.68 g/(kg·d), by raw material], and fluoxetine group [1.58 mg/(kg·d), positive control], with 12 rats in each group. Except for the blank group, the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups, and the corresponding drug solution or normal saline was administered via gavage during modeling, once a day, for 6 consecutive weeks. After the last administration, the body weight, sucrose preference rate, total moving distance, frequency into the center and immobility time of rats in each group were detected. Samples of PFC, NAc and VTA areas of rats in the blank group, model group, SGHWT medium-dose group and fluoxetine positive control groups were collected,and their histomorphological features were observed, and non-targeted metabolomics analysis (except for fluoxetine group)were performed and validated. RESULTS Compared with model group, the cytolysis, structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group, while their body weight, sucrose preference rate, total moving distance and frequency into the center were all significantly higher or longer (P<0.05), and immobility time was significantly shorter (P<0.05). The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified, with 40, 35 and 24 in the PFC, NAc and VTA regions respectively, mainly involved in amino acid, lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, saturated fatty acid biosynthesis, among which alanine, aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 (NMDAR1) in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats, the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.
2.Rapid Identification of Different Parts of Nardostachys jatamansi Based on HS-SPME-GC-MS and Ultra-fast Gas Phase Electronic Nose
Tao WANG ; Xiaoqin ZHAO ; Yang WEN ; Momeimei QU ; Min LI ; Jing WEI ; Xiaoming BAO ; Ying LI ; Yuan LIU ; Xiao LUO ; Wenbing LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):182-191
ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi, so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GC-MS) combined with Smart aroma database and National Institute of Standards and Technology(NIST) database were used to characterize the aroma components in different parts of N. jatamansi, and the aroma components were quantified according to relative response factor(RRF) and three internal standards, and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis(OPLS-DA) and cluster thermal analysis based on variable importance in the projection(VIP) value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose, and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data, and the rapid identification model of different parts of N. jatamansi was established by principal component analysis(PCA), discriminant factor alysis(DFA), soft independent modeling of class analogies(SIMCA) and statistical quality control analysis(SQCA). ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi, of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components, the contents of five components(ethyl isovalerate, 2-pentylfuran, benzyl alcohol, nonanal and glacial acetic acid,) in the aboveground part of N. jatamansi were significantly higher than those in the underground part(P<0.01), the contents of β-ionone, patchouli alcohol, α-caryophyllene, linalyl butyrate, valencene, 1,8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part(P<0.01). Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82, and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted, respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%, the validation score of the SIMCA model for discrimination of the two parts was 99, and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose(PCA, DFA, SIMCA and SQCA) can realize the rapid identification of different parts of N. jatamansi. Combining the two results, it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.
3.Correlation between body fat distribution measured by quantitative CT and body mass index in adults receiving physical examination
Yang ZHOU ; Yongbing SUN ; Qi QIAO ; Xin QI ; Yawei DU ; Zhonglin LI ; Zhi ZOU ; Xiaoling WU ; Jing ZHOU ; Min QU ; Xiaolin ZHANG ; Yong WANG ; Shewei DOU ; Hongming LIU ; Fengshan YAN ; Jiadong ZHU ; Yongli LI
Chinese Journal of Health Management 2024;18(5):354-360
Objective:To analyze the correlation between body fat distribution measured by quantitative CT (QCT) and body mass index in adults receiving physical examination.Methods:It was a cross-sectional study. From January to December 2021, 3 205 adults undergoing physical examination who met the inclusion criteria and underwent chest CT and QCT examination in the health management discipline of Henan Provincial People′s Hospital were selected as the research objects. The general data were collected; and the subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate were measured by QCT. According to body mass index, the subjects were divided into normal group (18.5-<24.0 kg/m 2, 1 343 cases), overweight group (24.0-<28.0 kg/m 2, 1 427 cases) and obesity group (≥28.0 kg/m 2, 435 cases). One-way analysis of variance and χ2 test were used to compare the differences of QCT indexes among the three groups. Pearson and Spearman correlation analysis were used to evaluate the correlation between QCT indexes and body mass index. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic effect of QCT on obesity and fatty liver. Results:Subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate in obese group were all significantly higher than those in overweight group and normal group [males, (147.60±46.44) vs (104.33±27.68), (73.46±22.65) cm 2; (297.46±54.70) vs (229.40±53.12), (159.57±49.68) cm 2; (445.06±70.24) vs (333.73±62.91), (233.02±61.87) cm 2; 11.30% (7.90%, 15.55%) vs 8.75% (6.50%, 11.70%), 6.60% (4.80%, 8.70%); 100.0% vs 96.0%, 64.0%; 92.9% vs 86.7%, 73.3%; females, (213.96±48.61) vs (155.85±35.31), (107.24±31.01) cm 2; (185.41±43.88) vs (142.48±41.75), (96.56±36.50) cm 2; (399.37±68.07) vs (298.33±56.86), (203.80±57.53) cm 2; 9.80% (6.90%, 13.30%) vs 7.30% (5.05%, 9.80%), 5.40%(3.50%, 7.20%); 96.4% vs 74.8%, 28.9%; 87.3% vs 75.6%, 56.5%], and were all positively correlated with body mass index (males, r/ rs=0.709, 0.738, 0.831, 0.402, 0.464, 0.225; females, r/ rs=0.798, 0.695, 0.841, 0.416, 0.605, 0.276) (all P<0.001). In both male and female subjects, the detection rates of obesity based on QCT were significantly higher than those based on body mass index (male, 86.9% vs 16.6%; female, 49.3% vs 8.9%), and the detection rates of fatty liver based on QCT were significantly higher than those based on ultrasound (male, 83.6% vs 57.1%; female, 65.2% vs 27.6%) (all P<0.001). ROC curve showed that when the visceral fat area of 142 cm 2 was used as the cut-off value for the diagnosis of obesity in male subjects, the sensitivity and specificity was 100% and 15.8%, respectively; and when the cut-off value of liver fat content 5.0% was used to diagnose fatty liver, the sensitivity and specificity was 88.9% and 25.1%, respectively. When the visceral fat area of 115 cm 2 was set as the cut-off value for the diagnosis of obesity in female subjects, the sensitivity and specificity was 96.4% and 55.3%, respectively; when the liver fat content of 5.0% was set as the cut-off value for the diagnosis of fatty liver, the sensitivity and specificity was 83.7% and 43.2%, respectively. Conclusions:The indexes of abdominal fat and liver fat measured by QCT in adults receiving physical examination are all positively correlated with body mass index. The effect of QCT in the diagnosis of obesity and fatty liver are both better than body mass index and ultrasound.
4.Quantitative CT study of fat distribution in normal weight population
Yang ZHOU ; Qi QIAO ; Yongbing SUN ; Xin QI ; Yawei DU ; Zhonglin LI ; Zhi ZOU ; Xiaoling WU ; Jing ZHOU ; Min QU ; Xiaolin ZHANG ; Yong WANG ; Shewei DOU ; Hongming LIU ; Fengshan YAN ; Gong ZHANG ; Jiadong ZHU ; Yongli LI
Chinese Journal of Health Management 2024;18(6):410-415
Objective:To analyze the distribution of body fat with quantitative computed tomography (QCT) in people with normal body mass index (BMI).Methods:A cross-sectional study was conducted in the physical examination population who underwent chest CT and QCT examination in the Department of Health Management, Henan Provincial People′s Hospital from January to December in 2021, and 1 395 physical examination subjects who met the inclusion criteria were selected as the research subjects. The subjects were divided into five groups according to their age. The general data of the subjects were collected. The total abdominal fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), total abdominal muscle area (TMA) and muscle fat content (MFC) in the subjects were measured by QCT. One-way analysis of variance, Welch test and Kruskal-Wallis test were used to compare the above QCT measurement indexes between the two genders among different age groups with normal BMI. Pearson correlation analysis was used to analyze the correlation between VFA and sarcopenia indexes. Multivariate linear regression was used to analyze the relationship between VFA and linear correlation variables in the related indicators of sarcopenia.Results:There were significant differences in TFA, VFA, TMA and SMI among different age groups in subjects with normal BMI (all P<0.05). Pearson correlation analysis showed that VFA was negatively correlated with TMA in some age groups (male: 18-39 years group: r=-0.351; 40-49 years group: r=-0.278; 60-69 years group: r=-0.245; female:40-49 years group: r=-0.251; 50-59 years group: r=-0.270;≥70 years group: r=-0.391; all P<0.01); it was negatively correlated with SMI (male: 18-39 years group: r=-0.352; 40-49 years group: r=-0.340; 50-59 years group: r=-0.266; 60-69 years group: r=-0.316; female: 40-49 years group: r=-0.240; 50-59 years group: r=-0.284; all P<0.001); it was positively correlated with MFC (male: 18-39 years group: r=0.342; 40-49 years group: r=0.291; female: 50-59 years group: r=0.133; 60-69 years group: r=0.284; all P<0.05). Multivariate linear regression analysis showed that VFA was independently and negatively correlated with SMI in both men and women after adjusting for age interference factors (male B=-1.881, t=-6.025, P<0.001; female B=-0.603, t=-2.887, P=0.004), and it was independently positively correlated with MFC (male B=1.230, t=4.271, P<0.001;female B=0.893, t=3.836, P<0.001). There was an independent negative correlation between VFA and TMA in male subjects ( B=0.263, t=2.478, P=0.013). Conclusions:VFA is correlated with TMA, SMI and MFC in people with normal BMI. Regardless of gender, SMI has a negative effect on VFA, and MFC has a positive effect on VFA.
5.Analysis of related factors of frailty in very elderly patients with multimorbidity
Tingwen WENG ; Min ZONG ; Liyan SHEN ; Yaping WANG ; Cheng QIAN ; Yajian LI ; Xinkai QU ; Songbai ZHENG ; Jing YAO
Chinese Journal of Geriatrics 2024;43(7):857-862
Objective:To investigate the factors contributing to frailty in very elderly patients with multimorbidity.Methods:This cross-sectional study enrolled 119 very elderly patients with multimorbidity who were hospitalized in the Department of Geriatrics of Huadong Hospital Affiliated to Fudan University from August 2022 to March 2023.The study aimed to understand the basic status of multimorbidity by collecting general information, the number and types of diseases, and frailty status.The subjects were divided into frail and non-frail groups through comprehensive geriatric assessment.Various factors including gender, age, Tinetti balance gait score, risk of sarcopenia, dementia, depression, risk of deep vein thrombosis, dysphagia, comorbidity index, medication count, Basic Activities of Daily Living(BADL)score, Instrumental Activities of Daily Living(IADL)score, Nutritional Risk Screening 2002(NRS-2002)score, Norton pressure injury risk assessment score, and Social Support Rating Scale(SSRS)score were compared.The correlation between each factor and the occurrence of frailty was analyzed using univariate analysis and multivariate Logistic regression analysis.Results:A total of 119 elderly inpatients with multimorbidity, with an average age of 90.8±5.9 years old, were included in the study.The incidence of frailty was 68.9%(82 cases).Univariate analysis revealed significant statistical differences between the frail group and the non-frail group in various factors including age( t=-3.131, P=0.002), Tinetti score( Z=-5.544, P<0.001), risk of sarcopenia( χ2=39.205, P<0.001), dysphagia( χ2=5.937, P=0.015), Charlson comorbidity index( Z=-2.565, P=0.010), medication count( Z=-3.325, P<0.001), BADL( Z=-5.871, P<0.001), IADL( Z=-5.062, P<0.001), Norton score( Z=-5.922, P<0.001), and SSRS social support( Z=-2.637, P=0.008).Multivariate logistic regression analysis showed that the Tinetti score( OR=0.843, 95% CI: 0.737-0.966, P=0.014), decreased muscle strength( OR=11.226, 95% CI: 2.157-58.432, P=0.004), sarcopenia( OR=18.084, 95% CI: 2.041-106.211, P=0.009), Norton score( OR=0.462, 95% CI: 0.254-0.838, P=0.011), and medication count( OR=1.153, 95% CI: 1.000-1.329, P=0.049)were independently associated with frailty. Conclusions:In very elderly patients with multimorbidities, the occurrence of frailty is notably increased.Frailty is linked to multiple risks including falls, muscle weakness/sarcopenia, pressure ulcer risk, and polypharmacy, and these risks are independent of other factors.
6.Identification and phylogenetic analysis of one clinical isolate of Ochrobactrum teleogrylli from human blood
Jianlong LIU ; Dexing HAN ; Shunguang LI ; Ya LIU ; Chunrong SONG ; Xiaowei CHEN ; Min FU ; Qiong HU ; Pinghua QU
Chinese Journal of Microbiology and Immunology 2024;44(8):680-688
Objective:To analyze the biological characteristics, phylogeny and the taxonomic status of strain 7712 (=CGMCC 1.17031=NBRC 113783=KCTC 15766) isolated from a clinical blood sample.Methods:Strain 7712 was identified by the cultural properties, cellular and colonial morphology, physiological and biochemical reactions, matrix-assisted laser desorption ionization time-of-flight mass spectrometry system, and genome correlation index analysis. The genomic phylogenetic tree was construct to analyze the taxonomic position. The virulence factors and resistance genes of strain 7712 and related strains were then compared by the online virulence factor database and online comprehensive antibiotic research database respectively.Results:Strain 7712 was urease negative, gram-negative nonfermenters, which was identified as Ochrobactrum anthropi by VITEK GN card. The 16S rRNA gene analysis showed that the strain was closely related to the members of genera Ochrobactrum and Brucella. The phylogenetic tree showed that strain 7712 was clustered together with Ochrobactrum teleogrylli LCB8 T and Ochrobactrum haematophilum CCUG 38531 T, along with genus Brucella and other Ochrobactrum species. The genome relatedness indexes analysis showed that the average nucleotide identity between strain 7712 and Ochrobactrum teleogrylli LCB8 T was 98.16%, which was higher than the threshold for prokaryotic species. Genetic prediction showed that strain 7712 carried several virulence-related genes and resistance-related genes, of which the existence of OCH gene might be responsible to the resistance to cephalosporin. Conclusions:A case of human infection caused by Ochrobactrum teleogrylli is identified, which would help promote the understanding of biodiversity of genus Ochrobactrum.
7.Comparison the WHO classification and the International Consensus Classification for myelodysplastic syndromes/neoplasms and acute myeloid leukemia
Yigang LIU ; Huiting QU ; Li LI ; Jing WANG ; Xiaosheng FANG ; Qian WANG ; Zie WANG ; Hui SUN ; Min HUANG ; Jian ZHANG ; Zhifen ZHANG ; Xiaoling ZHEN ; Wenbo ZHAO ; Huanling WU
Chinese Journal of Laboratory Medicine 2024;47(8):844-851
The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.
8.Study on the influencing factors of coronary CT angiography combined with CT-FFR on myocardial ischemia in coronary heart disease
China Modern Doctor 2024;62(25):66-69
Objective To explore the imaging features of myocardial ischemia in patients with coronary heart disease by coronary CT angiography(CCTA)combined with coronary CT angiography derived fractional flow reserve(CT-FFR),and to find out the influencing factors of myocardial ischemia in patients with coronary heart disease.Methods A total of 86 patients who received CCTA examination in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medicine University from January to November 2023 were retrospectively selected.According to the measured CT-FFR value,they were divided into ischemia group(CT-FFR≤0.80,45 cases)and non-ischemia group(CT-FFR>0.80,41 cases).The plaque characteristics of two groups were compared,and the influencing factors of myocardial ischemia in patients with coronary heart disease were investigated by multivariate Logistic regression analysis.Results The proportion of diabetes mellitus in ischemia group was significantly higher than that in non-ischemia group(P<0.05).A total of 150 coronary arteries showed plaque,with the majority located in the left anterior descending artery(114).A total of 212 plaques were analyzed,including 68 plaques in ischemic group and 144 plaques in non-ischemic group.The proportion of calcified plaque in non-ischemic group was significantly higher than that in ischemic group(P<0.05).The degree of vascular stenosis,the volume of plaque,the proportion of lipid components and the volume of fibrous lipid components in ischemic group were significantly higher than those in non-ischemic group,and the volume of plaque fiber components was significantly lower than that in non-ischemic group(P<0.05).Multivariate Logistic regression analysis showed that the degree of vascular stenosis(OR=1.054,P=0.026)and plaque volume(OR=1.027,P=0.048)were influencing factors of myocardial ischemia in patients with coronary heart disease.Conclusion The degree of vascular stenosis and volume of plaque are both factors affecting myocardial ischemia in patients with coronary heart disease,and targeted treatment can be carried out for these patients.
9.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
10.Clinical phenotypes and genotypes of congenital fibrinogen disorder:an analysis of 16 children
Min WANG ; Tian-Ping CHEN ; Ao-Shuang JIANG ; Ying-Hui ZHAO ; Cheng-Lin ZHU ; Nan WEI ; Yu-Ting JIN ; Li-Jun QU
Chinese Journal of Contemporary Pediatrics 2024;26(8):840-844
Objective To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder(CFD).Methods A retrospective analysis was conducted on the clinical data of 16 children with CFD.Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA,FGB,and FGG genes,and sequencing was performed to analyze mutation characteristics.Results Among the 16 children,there were 9 boys(56%)and 7 girls(44%),with a median age of 4 years at the time of attending the hospital.Among these children,9(56%)attended the hospital due to bleeding events,and 7(44%)were diagnosed based on preoperative examination.The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events(P<0.05).Genetic testing was conducted on 12 children and revealed a total of 12 mutations,among which there were 4 novel mutations,i.e.,c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene.There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene,with relatively severe bleeding symptoms.There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes,and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.Conclusions The clinical phenotypes of children with CFD are heterogeneous,and the severity of bleeding is associated with the level of fibrinogen activity,but there is a weak association between clinical phenotype and genotype.

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