1.Network meta-analysis of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke
Yuanyuan YANG ; Shanshan ZHOU ; Xiaofei CHENG ; Luye FENG ; Jiqin TANG
Chinese Journal of Tissue Engineering Research 2026;30(4):1008-1018
OBJECTIVE:Most of the existing studies are based on traditional Meta-analysis to study the efficacy of single stimulation protocols such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor dysfunction in stroke patients,and it is not possible to clarify which stimulation protocol is the optimal choice.This study used network meta-analysis to systematically evaluate the clinical efficacy of different regimens of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke.METHODS:CNKI,WanFang,VIP,CBM,PubMed,Medline and Web of Science databases were searched to collect randomized controlled trials on different regimens of non-invasive brain stimulation for lower limb motor dysfunction after stroke from inception to October 1,2024.Data extraction was performed on the included studies.RevMan 5.4.1 software was used for traditional meta-analysis and the quality of the included studies was evaluated.Stata 17.0 software was used for network meta-analysis.RESULTS:(1)A total of 39 studies involving 2 920 patients were included,involving 6 treatment methods:conventional rehabilitation training,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation.(2)The results of network meta-analysis showed that high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training in the Fugl-Meyer assessment for lower extremity motor function.(3)In terms of improving Berg balance scale score,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,and intermittent theta burst stimulation were significantly different from conventional rehabilitation training(P<0.05),and there was a significant difference between high-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation(P<0.05).(4)In improving modified Barthel index and Barthel index,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training.(5)Under the cumulative ranking chart,high-frequency repetitive transcranial magnetic stimulation showed the best efficacy in Fugl-Meyer assessment for lower extremity motor function,Berg balance scale score,modified Barthel index and Barthel index,followed by low-frequency repetitive transcranial magnetic stimulation.CONCLUSION:Both high-and low-frequency repetitive transcranial magnetic stimulation can improve the lower limb motor function and balance function of patients with stroke,and can improve the activities of daily living of patients to varying degrees.Moreover,the effect of high-frequency repetitive transcranial magnetic stimulation is better than that of low-frequency repetitive transcranial magnetic stimulation.
2.Network meta-analysis of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke
Yuanyuan YANG ; Shanshan ZHOU ; Xiaofei CHENG ; Luye FENG ; Jiqin TANG
Chinese Journal of Tissue Engineering Research 2026;30(4):1008-1018
OBJECTIVE:Most of the existing studies are based on traditional Meta-analysis to study the efficacy of single stimulation protocols such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor dysfunction in stroke patients,and it is not possible to clarify which stimulation protocol is the optimal choice.This study used network meta-analysis to systematically evaluate the clinical efficacy of different regimens of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke.METHODS:CNKI,WanFang,VIP,CBM,PubMed,Medline and Web of Science databases were searched to collect randomized controlled trials on different regimens of non-invasive brain stimulation for lower limb motor dysfunction after stroke from inception to October 1,2024.Data extraction was performed on the included studies.RevMan 5.4.1 software was used for traditional meta-analysis and the quality of the included studies was evaluated.Stata 17.0 software was used for network meta-analysis.RESULTS:(1)A total of 39 studies involving 2 920 patients were included,involving 6 treatment methods:conventional rehabilitation training,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation.(2)The results of network meta-analysis showed that high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training in the Fugl-Meyer assessment for lower extremity motor function.(3)In terms of improving Berg balance scale score,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,and intermittent theta burst stimulation were significantly different from conventional rehabilitation training(P<0.05),and there was a significant difference between high-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation(P<0.05).(4)In improving modified Barthel index and Barthel index,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training.(5)Under the cumulative ranking chart,high-frequency repetitive transcranial magnetic stimulation showed the best efficacy in Fugl-Meyer assessment for lower extremity motor function,Berg balance scale score,modified Barthel index and Barthel index,followed by low-frequency repetitive transcranial magnetic stimulation.CONCLUSION:Both high-and low-frequency repetitive transcranial magnetic stimulation can improve the lower limb motor function and balance function of patients with stroke,and can improve the activities of daily living of patients to varying degrees.Moreover,the effect of high-frequency repetitive transcranial magnetic stimulation is better than that of low-frequency repetitive transcranial magnetic stimulation.
3.Clinical Efficacy and Mechanism of Danggui Liuhuang Tang in Reducing Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus with Yin Deficiency and Fire Excess Syndrome
Yuanying XU ; Shanshan YU ; Xinyan JIN ; MAREYANMU·ROSE ; Cheng CHEN ; Wenjun SHA ; Tao LEI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):163-172
ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang (DGLHT) on patients with type 2 diabetes mellitus (T2DM) complicated by atherosclerotic cardiovascular disease (ASCVD) at high risk, focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation (FMD), atherogenic index of plasma (AIP), and triglyceride-glucose index (TyG), and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B (MyD88/NF-κB) signaling pathway. MethodsThe clinical study was a single-center, double-blind, and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT, while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks, with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD, AIP, TyG, and small dense low-density lipoprotein cholesterol (sdLDL-C) index were compared. Human umbilical vein endothelial cells (HUVECs) were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction (Real-time PCR) and Western blot . ResultsAfter 12 weeks of treatment, the AIP in the treatment group significantly decreased compared with that before the treatment (P<0.05). Compared with the control group, the treatment group showed significant improvements in FMD and TyG (P<0.05). Additionally, the treatment group demonstrated significant reductions in two-hour postprandial glucose (2 hPG), glycated albumin (GA), triglycerides (TG), apolipoprotein E (Apo E), and sdLDL-C (P<0.05). Analysis of traditional Chinese medicine (TCM) syndrome efficacy indicated that in the treatment group, Yin deficiency and fire excess syndromes, including dry throat and mouth (P<0.05), excessive thirst (P<0.01), tidal fever and night sweats (P<0.05), and dry stools (P<0.05), improved. Compared with the control group, the treatment group showed significant improvements in symptoms of dry throat and mouth (P<0.05) and excessive thirst (P<0.01). TCM syndrome scores significantly decreased (P<0.01), and the overall efficacy rate was 56.67%, significantly higher than the 10.34% observed in the control group (P<0.01). At the cellular level, increasing concentrations of DGLHT led to decreased messenger ribonucleic acid (mRNA) levels of pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1β) in lipopolysaccharide (LPS)-stimulated HUVECs (P<0.01), with significant reductions in the high-concentration group (P<0.01). DGLHT may inhibit the expressions of MyD88 and phosphorylated (p)-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.
4.Research progress on application of vision technology in negative emotion assessment for chronic disease patients
Huixia WU ; Huifang CHENG ; Shanshan HUANG ; Yuansi HUANG ; Xiangyu LIU
Chinese Journal of Nursing 2025;60(5):635-640,后插1
Chronic disease patients often experience negative emotions such as anxiety and depression,and the accurate assessment of these emotions is crucial for developing effective care plans and interventions.Traditional assessments of negative emotions are limited by subjectivity,error and accessibility issues,making precise identification and evaluation difficult.In recent years,vision technology has demonstrated unique advantages in emotion recognition due to its accuracy,speed,consistency,objectivity nature.This paper reviews the development process of computer vision technology,the content and effects of its application in negative emotion assessment for chronic disease patients,and the current challenges,in order to provide references for the evaluation of chronic disease patients'negative emotions.
5.A cohort study on the impact of stressful life events on social activity participation among middle-aged and elderly adults
Yujing ZHANG ; Shanshan LI ; Yuming ZHANG ; Xuchao REN ; Siyi ZUO ; Ziqi ZHANG ; Linyuan CHENG ; Zijie ZHAI ; Pan XU ; Dong LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(1):60-65
Objective:To analyze the impact of stressful life events on the social activity participation of middle-aged and elderly adults in China, providing a scientific basis for improving their quality of life.Methods:This study was conducted in January 2024.Data were derived from the China health and retirement longitudinal study (CHARLS) conducted from 2011 to 2020. SPSS 25.0 software was used for statistical analysis.Ordered Logistic regression analysis was employed to explore the association between stressful life events experienced over the past decade and the level of social activity participation, with stratified analysis by age, gender, and place of residence.Results:A total of 10 838 middle-aged and elderly adults were included in this study. The proportions of individuals with no social activity participation, low social activity participation, and high social activity participation were 52.07%(5 643/10 838), 24.21%(2 624/10 838), and 23.72%(2 571/10 838), respectively. After adjusting for sociodemographic characteristics and health-related behaviors, individuals who experienced stressful life events were 15.2% less likely to participate in social activities compared to those who did not ( RR=0.848, 95% CI=0.786-0.915).Stratified analysis revealed that the decrease in the likelihood of social activity participation following stressful life events was significantly greater in urban residents than that in rural residents ( Pinteraction=0.004). Conclusion:Experiencing stressful life events over the past decade may reduce the level of social activity participation among middle-aged and elderly adults. It is recommended to strengthen psychological counseling for this population and encourage active social engagement.
6.Effect of joint management of type 2 diabetes mellitus between specialty department and community health under National Diabetes Prevention and Control Center (DPCC) model
Ying HUANG ; Yi QIAN ; Xuchi WU ; Zhongyu ZHOU ; Cong WANG ; Lin WANG ; Caiyan HUANG ; Zhuangsen CHEN ; Yanrong ZHANG ; Shanshan WANG ; Lu WANG ; Jie WAN ; Ruihong YANG ; Huiya WANG ; Yan CHEN ; Cheng HE ; Kun FENG ; Dewen YAN
Journal of Chinese Physician 2025;27(3):338-342
Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.
7.The value of the Caprini risk assessment model for predicting deep vein thrombosis in the lower extremities of patients with a spinal cord injury
Cheng WANG ; Xia CHEN ; Xinmeng ZHA ; Shanshan ZHU ; Tingting ZHANG ; Jinlong ZHANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(4):331-336
Objective:To evaluate the Caprini risk assessment model (Caprini RAM) for predicting lower extremity deep vein thrombosis (DVT) after a spinal cord injury (SCI).Methods:Five hundred and one SCI patients were divided into low- (0-1 points, n=130), medium- (2 points, n=43), and high-risk (≥3 points, n=328) groups according to their Caprini scores. The data covering all 501 included gender, age, cause of injury, injury site, American Spinal Injury Association classification, smoking history, surgical history, concurrent pulmonary or urinary tract infections, indwelling catheterization, comorbid type 2 diabetes or hypertension, D-dimer level, fibrinogen level, prothrombin time (PT), activated partial thromboplastin time, international normalized ratio), red blood cell (RBC) count, white blood cell count, platelet (PLT) count and neutrophil percentage. DVTs were detected using lower extremity ultrasound. The Caprini scores were treated as both categorical and continuous variables alongside the other risk factors in multivariate logistic regressions predicting DVT incidence. Generalized additive models were used for curve fitting and threshold saturation analysis, and log-likelihood ratio tests were applied to evaluate the linear relationships observed between Caprini scores and DVT incidence. Results:When the Caprini score was used as a categorical variable, a high risk score ( OR=7.264), age ( OR=1.050), D-dimer ( OR=1.11) , PT ( OR=1.494), PLT count ( OR=1.004) and lung infection ( OR=1.83) were found to be significant independent predictors of DVT. RBC was a protective factor ( OR=0.509). When the Caprini score was used as a continuous variable, lung infection lost its predictive utility. After adjusting for the risk and protective factors, the Caprini scores and the incidence of DVT showed a significant curvilinear increasing association, with a breakpoint of 3. When the Caprini score was less than 3, the incidence of DVT increased 1.83 times with a 1 point increase in the Caprini score. Beyond 3 the multiplier was 1.06. Conclusions:With the independent risk factors accounted for, Caprini scores demonstrate a curvilinear increasing relationship with DVT risk. Clinically, special attention should be given to SCI patients with Caprini scores ≥3.
8.Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats
Lin ZHENG ; Wenjun JIN ; Shanshan LUO ; Rui HUANG ; Jie WANG ; Yuting CHENG ; Zheqing AN ; Yue XIONG ; Zipeng GONG ; Jian LIAO
Chinese Journal of Tissue Engineering Research 2025;29(6):1159-1167
BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P<0.05),and trabecular separation was elevated(P<0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P<0.05),and the level of osteocalcin was decreased(P<0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P<0.05);protein expression of β-Catenin and Frizzled9 was decreased(P<0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P<0.05)and a decrease in trabecular separation(P<0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P<0.05)and the serum level of osteocalcin was elevated(P<0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P<0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P<0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P<0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.
9.A cohort study on the impact of stressful life events on social activity participation among middle-aged and elderly adults
Yujing ZHANG ; Shanshan LI ; Yuming ZHANG ; Xuchao REN ; Siyi ZUO ; Ziqi ZHANG ; Linyuan CHENG ; Zijie ZHAI ; Pan XU ; Dong LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(1):60-65
Objective:To analyze the impact of stressful life events on the social activity participation of middle-aged and elderly adults in China, providing a scientific basis for improving their quality of life.Methods:This study was conducted in January 2024.Data were derived from the China health and retirement longitudinal study (CHARLS) conducted from 2011 to 2020. SPSS 25.0 software was used for statistical analysis.Ordered Logistic regression analysis was employed to explore the association between stressful life events experienced over the past decade and the level of social activity participation, with stratified analysis by age, gender, and place of residence.Results:A total of 10 838 middle-aged and elderly adults were included in this study. The proportions of individuals with no social activity participation, low social activity participation, and high social activity participation were 52.07%(5 643/10 838), 24.21%(2 624/10 838), and 23.72%(2 571/10 838), respectively. After adjusting for sociodemographic characteristics and health-related behaviors, individuals who experienced stressful life events were 15.2% less likely to participate in social activities compared to those who did not ( RR=0.848, 95% CI=0.786-0.915).Stratified analysis revealed that the decrease in the likelihood of social activity participation following stressful life events was significantly greater in urban residents than that in rural residents ( Pinteraction=0.004). Conclusion:Experiencing stressful life events over the past decade may reduce the level of social activity participation among middle-aged and elderly adults. It is recommended to strengthen psychological counseling for this population and encourage active social engagement.
10.Clinical feature and genetic analysis of a case of X-linked alpha-thalassemia mental retardation syndrome neonate caused by ATRX gene variant and literature review.
Qianya XU ; Xinru CHENG ; Shanshan ZHANG ; Aojie CAI ; Qian ZHANG
Chinese Journal of Medical Genetics 2025;42(2):162-169
OBJECTIVE:
To explore the clinical phenotype and genetic etiology of a neonate with X-linked alpha-thalassemia mental retardation syndrome (ATR-X) caused by ATRX gene variant, and review related literature on children with ATR-X caused by ATRX gene variants.
METHODS:
A case of ATR-X neonate who was transferred to the First Affiliated Hospital of Zhengzhou University on February 11, 2022 for poor effect of treatment in the neonatology department of the hospital where he was born for 4 days due to "postnatal slow response, groaning, and cyanosis of the skin for 30 min" was selected as the study subject. 3 mL of peripheral blood was collected from the child and their parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used to verify the pathogenic gene variations in the child's family. The pathogenicity of genetic variant sites was assessed based on the Standards and Guidelines for the Interpretation of Sequence Variants by American College of Medical Genetics and Genomics (ACMG). The amino acid sequence conservation analysis of relevant variant proteins was conducted by the Universal Protein Resource Database (UniProt) and visual analysis of these variant proteins was performed by Swiss online protein three-dimensional modeling database (SWISS-MODEL). Using keywords such as "ATRX gene" and " X-linked alpha-thalassemia mental retardation syndrome" both in Chinese and English, relevant literature on ATR-X children caused by ATRX gene variants was retrieved from the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases, and the clinical phenotypes of ATR-X patients reported in the retrieved literature were analyzed. The literature retrieval time was set from the establishment of each database to December 31st, 2023. This study followed the research procedures approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-1360-002), and informed consent of clinical study was signed by the guardian of the child.
RESULTS:
The child in this study presented with symptoms such as delayed response, feeding difficulties accompanied by vomiting, low body temperature, hypotonia in all extremities, apnea, abnormal hearing screening, and a Neonatal Behavioral Neurological Assessment (NBNA) score of 19 (lower than the normal range).Hemoglobin (Hb) electrophoresis suggested the presence of α-thalassemia. The results of WES and Sanger sequencing revealed a hemizygous missense variant c.668G>A (p.C223Y) in exon 9 of the ATRX gene in the child of the study, neither of the parents of the child carried this variant, indicating that it is a de novo variant. Based on the Standards and Guidelines for the Interpretation of Sequence Variants released by ACMG, this gene variant was assessed as pathogenic (PS2+PM2_Supporting+PP3_Strong+PP4_Strong). The results of amino acid sequence analysis revealed that the pathogenic variant site normally encodes cysteine, which is highly conserved among various animal species. This pathogenic variant can lead to alterations in the hydrogen bonding structure of ATRX protein, thereby affecting its structural stability. Based on the clinical manifestations and genetic testing results of the child in this study, a diagnosis of ATR-X syndrome was established Based on the literature retrieval strategy established in this study, 13 relevant articles concerning ATR-X syndrome in children caused by ATRX gene variants were retrieved, including 5 Chinese articles and 8 English articles, involving a total of 311 ATR-X children. Including the child in this study, the total number of ATR-X children reaches 312. All 312 children were male and presented with mental retardation. Among them, 45.8% (143/312) had coexisting α-thalassemia, 45.2% (141/312) had abnormal genital appearance, 44.2% (138/312) had facial malformations, and 30.8% (96/312) had hypotonia. Other phenotypes included microcephaly, skeletal dysplasia, among others.
CONCLUSION
The ATR-X child in this study exhibit a range of clinical phenotypes, including delayed growth and development, facial malformation, abnormal genital appearance, apnea, vomiting symptoms, among others. The de novo variant of ATRX gene c.668G>A (p.C223Y) was identified as the genetic etiology. This study contributes to the expansion of the clinical phenotype spectrum and genetic variation spectrum of ATR-X children.
Humans
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X-linked Nuclear Protein/genetics*
;
alpha-Thalassemia/genetics*
;
X-Linked Intellectual Disability/genetics*
;
Male
;
Infant, Newborn
;
Exome Sequencing
;
Mutation

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