1.The Mesencephalic Locomotor Region for Locomotion Control
Xing-Chen GUO ; Yan XIE ; Xin-Shuo WEI ; Wen-Fen LI ; Ying-Yu SUN
Progress in Biochemistry and Biophysics 2025;52(7):1804-1816
Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.
2.Analysis of Acupoint Selection Rules of Acupuncture and Moxibustion in the Treatment of Female Menopausal Obesity
Min XU ; Yan TAN ; Wen-Ying SHI ; Chao KE ; Lu CAO ; Heng-Fen ZHANG ; Wei ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1262-1269
Objective To explore the acupoint selection rules of acupuncture and moxibustion for the treatment of female menopausal obesity and to provide reference for clinical acupuncture treatment of female menopausal obesity based on data mining techniques.Methods Clinical literature on acupuncture treatment of female menopausal obesity was searched by computer in CNKI,Wanfang,VIP,SinoMed,and PubMed database,and the time limit of searching was from the establishment of database to the date of 1 August 2023,and the literature was screened and extracted according to the inclusion and exclusion criteria.The association rule analysis was performed using IBM SPSS Moderler 18.0 software,and cluster analysis was performed using IBM SPSS Statistics 27.0 software.Results A total of 50 literature meeting the requirements were screened out,and 83 groups of acupoint prescriptions were extracted.Descriptive analysis showed that the intervention measures of acupuncture and moxibustion in the treatment of female menopausal obesity were mainly acupoint catgut embedding,electroacupuncture and auricular acupuncture.The top 7 acupoints with the highest frequency were Sanyinjiao(SP6),Zusanli(ST36),Shenshu(BL23),Tianshu(ST25),Guanyuan(RN4),Zhongwan(RN12)and Qihai(RN6).Stomach meridian of foot yangming,conception vessel,bladder meridian of foot taiyang and spleen meridian of foot taiyin are the most commonly selected meridians.In terms of specific acupoints,the main acupoints are intersection points,front-mu points and back-shu points.The acupoints are mainly distributed in the chest and abdomen,lower limbs and waist and back.By using data mining technology,the core acupoint pair of acupuncture and moxibustion for menopausal obesity is'Zusanli-Sanyinjiao',and the core acupoint prescription is'Zusanli,Sanyinjiao,Zhongwan,Tianshu,Shenshu,Guanyuan,Qihai';cluster analysis found 7 types of clinical acupoint clustering.Conclusion Acupuncture and moxibustion for the treatment of female menopausal obesity focuses on tonifying the essence of the kidney and restoring the qi mechanism and characteristics of acupoint selection of spleen and stomach qi.
3.Association of sleep duration and risk of frailty among the elderly over 80 years old in China: a prospective cohort study.
Wen Fang ZHONG ; Fen LIANG ; Xiao Meng WANG ; Pei Liang CHEN ; Wei Qi SONG ; Ying NAN ; Jia Xuan XIANG ; Zhi Hao LI ; Yue Bin LYU ; Xiao Ming SHI ; Chen MAO
Chinese Journal of Preventive Medicine 2023;57(5):607-613
Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q1, Q3) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.
Aged
;
Humans
;
Aged, 80 and over
;
Frailty/epidemiology*
;
Sleep Duration
;
Prospective Studies
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Sleep/physiology*
;
China/epidemiology*
4.Antimicrobial susceptibility of Gram-positive organisms:Results from China antimicrobial resistance surveillance trial(CARST)program,2021-2022
Yun LI ; Bo ZHENG ; Feng XUE ; Xiu-Zhen ZHANG ; Yun-Jian HU ; Yu-Fen JIN ; Jian-Hong ZHAO ; Shi-Yang PAN ; Wei GUO ; Feng ZHAO ; Yun-Song YU ; Xuan CAI ; Wen-En LIU ; De-Hua LIU ; Ying FEI ; Jia-Yun LIU ; Feng-Yan PEI ; Ling MENG ; Ping JI ; Jin TANG ; Kai XU ; Lei ZHU ; Cun-Wei CAO ; He-Ping XU ; Shan WANG ; Lan-Qing CUI ; Jia ZHANG ; Yao-Yao LIU
The Chinese Journal of Clinical Pharmacology 2023;39(23):3509-3524
Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4%and 79.9%respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100%susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1%and 92.9%.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6%.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2%,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5%)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8%based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8%,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.
5.Antimicrobial susceptibility of Gram-negative organisms:Results from China antimicrobial resistance surveillance trial(CARST)program,2021-2022
Yun LI ; Bo ZHENG ; Feng XUE ; Xiu-Zhen ZHANG ; Yun-Jian HU ; Yu-Fen JIN ; Jian-Hong ZHAO ; Shi-Yang PAN ; Wei GUO ; Feng ZHAO ; Yun-Song YU ; Xuan CAI ; Wen-En LIU ; De-Hua LIU ; Ying FEI ; Jia-Yun LIU ; Feng-Yan PEI ; Ling MENG ; Ping JI ; Jin TANG ; Kai XU ; Lei ZHU ; Cun-Wei CAO ; He-Ping XU ; Shan WANG ; Lan-Qing CUI ; Jia ZHANG ; Yao-Yao LIU
The Chinese Journal of Clinical Pharmacology 2023;39(23):3525-3544
Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0%and 21.0%,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75%.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80%.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3%and 72.1%and multidrug-resistant(MDR)detection rates were 41.1%and 77.3%,extensively drug-resistant(XDR)were 12.0%and 71.8%,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35%.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.
6.Impact of asthma action plan-based remote joint management model on asthma control in children.
Cai Feng ZHANG ; Yan GAO ; Yi QIN ; Xiao Yin HU ; Jia Ning LU ; Si Jing ZHAO ; Wen Chun LIN ; Ying Fen LIU ; Gen Quan YIN ; Wen Hui JIANG ; Hui Feng FAN ; Li DENG
Chinese Journal of Pediatrics 2023;61(9):820-826
Objective: To compare the effects of the China Children's Asthma Action Plan (CCAAP)-based remote joint management model with traditional management model on the control of childhood asthma. Methods: A retrospective cohort study was conducted to analyze the general data and asthma control assessment data of 219 children with asthma who attended the respiratory department of Guangzhou Women's and Children's Medical Center from April 2021 to October 2021 and were followed up for 1 year or more. According to the follow-up management model, the CCAAP-based remote joint management model was used in the observation group and the traditional management model was used in the control group, and the propensity score matching method was applied to match the data of children in the two management models for comparison. Paired-samples t-test, Wilcoxon signed-rank test, McNemar χ2-test or χ2-test or nonparametric tests were used to compare the general data and asthma control assessment data between the two matched groups of children. Results: Among 219 children with asthma, 145 were male and 74 were female, aged at consultation (7.2±2.4) years. There were 147 cases in the observation group and 72 cases in the control group, and 27 cases in each of the observation and control groups were successfully matched. The number of asthma exacerbation aura, acute exacerbations, and emergency room visits or hospitalizations for asthma exacerbations were lower in the observation group than in the control group after pairing (1 (0, 2) vs. 3 (1, 5) times, 0 (0,0) vs. 0 (0, 1) times, 0 (0,0) vs. 1 (0, 1) times, Z=-3.42, -2.58, -3.17, all P<0.05). The use of peak flowmeters was higher in children aged 5 years and older in the observation group than in the control group after pairing (100% (22/22) vs. 13% (3/23), χ2=54.00,P<0.001). The ratio of actual to predicted 1st second expiratory volume of force after follow-up in the observation group after pairing was higher than that before follow-up in the observation group and after follow-up in the control group ((95±11)% vs. (85±10)%, (95±11)% vs. (88±11)%, t=-3.40, 2.25, all P<0.05). The rate of complete asthma control after follow-up was higher in both the observation and control groups after pairing than before follow-up for 12 months in both groups (93% (25/27) vs. 41% (11/27), 52% (14/27) vs. 41% (11/27), H=56.19, 45.37, both P<0.001), and the rate of complete control of asthma in children in the observation group was higher than that in the control group at 3 and 12 months of follow-up management (56% (15/27) vs. 25% (5/20), 93% (25/27) vs. 52% (14/27), χ2=47.00, 54.00, both P<0.001). The number of offline follow-up visits, inhaled hormone medication adherence scores, and caregiver's asthma perception questionnaire scores were higher in the observation group than in the control group after pairing (6 (4, 8) vs. 4 (2,5), (4.8±0.3) vs. (4.0±0.6) score, (19.3±2.6) vs. (15.2±2.7) score, Z=6.58, t=6.57, 5.61, all P<0.05), and the children in the observation group had lower school absences, caregiver absences, asthma attack visit costs, and caregiver PTSD scores than the control group (0 (0,0) vs.3 (0, 15) d, 0 (0,0) vs. 3 (0, 10) d, 1 100 (0, 3 700) vs. 5 000 (1 000, 10 000) yuan, 1.3 (1.1, 1.9) vs. 2.0 (1.2, 2.7) score, Z=-2.89, -2.30, 2.74, 2.73, all P<0.05). Conclusion: The CCAAP-based joint management model of asthma control is superior to the traditional management model in the following aspects: it can effectively improve asthma control, self-monitoring, and lung function in children; it can improve treatment adherence and caregivers' asthma awareness; and it can reduce the duration of absenteeism from school, the cost of asthma exacerbation visits, and caregiver's negative psychology.
Humans
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Child
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Female
;
Male
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Retrospective Studies
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Asthma/therapy*
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China
;
Hospitalization
;
Hospitals
7.Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma.
Meng ZHANG ; Pan WU ; Yan Long DUAN ; Ling JIN ; Jing YANG ; Shuang HUANG ; Ying LIU ; Bo HU ; Xiao Wen ZHAI ; Hong Sheng WANG ; Yang FU ; Fu LI ; Xiao Mei YANG ; An Sheng LIU ; Shuang QIN ; Xiao Jun YUAN ; Yu Shuang DONG ; Wei LIU ; Jian Wen ZHOU ; Le Ping ZHANG ; Yue Ping JIA ; Jian WANG ; Li Jun QU ; Yun Peng DAI ; Guo Tao GUAN ; Li Rong SUN ; Jian JIANG ; Rong LIU ; Run Ming JIN ; Zhu Jun WANG ; Xi Ge WANG ; Bao Xi ZHANG ; Kai Lan CHEN ; Shu Quan ZHUANG ; Jing ZHANG ; Chun Ju ZHOU ; Zi Fen GAO ; Min Cui ZHENG ; Yonghong ZHANG
Chinese Journal of Pediatrics 2022;60(10):1011-1018
Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Burkitt Lymphoma/drug therapy*
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Child
;
Disease-Free Survival
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Female
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Humans
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Lactate Dehydrogenases
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Lymphoma, B-Cell/drug therapy*
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Male
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Prognosis
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Retrospective Studies
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Rituximab/therapeutic use*
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Treatment Outcome
8.Applying Four-Chamber View and Three-Vessel Trachea View Combined With HD-Flow to Screening Fetal Cardiovascular Malformations in First-Trimester Pregnancy
Yu-jun HUANG ; Yun-xiao ZHU ; Dong-mei LIN ; Ying TAN ; Kun YUAN ; Wen-fen LIU
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(1):146-151
ObjectiveTo evaluate the value of four-chamber view (4CV) and three-vessel trachea view (3VTV) combined with HD-flow in screening for fetal cardiovascular mailformations (CVMs) in unselected population during early pregnancy (11~13+6 weeks). MethodsFrom May 2018 to December 2019, 1145 fetuses were ultrasonic scanned routinely at 11~13+6 weeks at our hospital. The 4CV and 3VTV of fetal hearts were assessed by Power Doppler with flow direction (high definition flow, HD-flow),and the sonographic findings and follow-up outcomes were documented. Suspected CVMs were confirmed by the postpartum echocardiography or autopsy results. The sensitivities, specificities, PPVs and NPVs of diagnostic tests were compared among the two views and combined views. ResultsThere were 948 fetuses included in this study, with 19 cases of CVMs. The sonographic findings of 12 cases (12/19) with 22 CVMs were consistent entirely with the follow-up outcomes, including 7 cases of complex CVMs. In 1 case (1/19) with complex CVM, the diagnosis was not entirely consistent to the autopsy result. The 6 cases (6/19) of abnormal atrioventricular septum were not detected in early pregnancy. In the 19 cases of CVMs, abnormalities were found by displaying 4CV in 8 cases, by displaying 3VTV in 11 cases, and by displaying 4CV combined with 3VTV in 13 cases. The sensitivity of 4CV, 3VTV, 4CV+3VTV was 31.5%, 57.9%, 68.4%, with significant difference between 4CV and 4CV+3VTV(P=0.016) .The specificity and PPVs were all 100% (P>0.05). The NPVs of them were 98.6%, 99.1% and 99.4%, with no statistical difference (P>0.05). ConclusionsDisplaying the 4CV combined with 3VTV of fetal heart in the first-trimester ultrasound examination resulted in higher detect ratio of fetal cardiovascular malformations rather than scanning only with the 4CV, especially for those serious CVMs with poor prognosis, which is important for clinical management appropriately.
9.Phenotypes and ATP7B gene variants in 316 children with Wilson disease.
Zhi Kun LU ; Jing CHENG ; Si Min LI ; Yun Ting LIN ; Wen ZHANG ; Xiu Zhen LI ; Hui Ying SHENG ; Xiao Jian MAO ; Hui Fen MEI ; Rui Dan ZHENG ; Cui Li LIANG ; Min Yan JIANG ; Yong Lan HUANG ; Li LIU ; Chun Hua ZENG
Chinese Journal of Pediatrics 2022;60(4):317-322
Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.
Ceruloplasmin/metabolism*
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Child
;
Child, Preschool
;
Copper/metabolism*
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Copper-Transporting ATPases/genetics*
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Female
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Hepatolenticular Degeneration/genetics*
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Humans
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Male
;
Mutation
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Phenotype
;
Retrospective Studies
10.Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development.
Hu LIN ; Hao YANG ; Jun Fen FU ; Jin Na YUAN ; Ke HUANG ; Wei WU ; Guan Ping DONG ; Hong Juan TIAN ; De Hua WU ; Da Xing TANG ; Ding Wen WU ; Li Ying SUN ; Ya Lei PI ; Li Jun LIU ; Li Ping SHI ; Wei GU ; Lu Gang HUANG ; Yi Hua WANG ; Lin Qi CHEN ; Hong Ying LI ; Yang YU ; Hai Yan WEI ; Xin Ran CHENG ; Xiao Ou SHAN ; Yu LIU ; Xu XU ; Shu LIU ; Xiao Ping LUO ; Yan Feng XIAO ; Yu YANG ; Gui Mei LI ; Mei FENG ; Xiu Qi MA ; Dao Xiang PAN ; Jia Yan TANG ; Rui Min CHEN ; Mireguli MAIMAITI ; De Yun LIU ; Xin Hai CUI ; Zhe SU ; Zhi Qiao DONG ; Li ZOU ; Yan Ling LIU ; Jin WU ; Kun Xia LI ; Yuan LI
Chinese Journal of Pediatrics 2022;60(5):435-441
Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics*
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Child
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China/epidemiology*
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Cryptorchidism/genetics*
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Disorders of Sex Development/genetics*
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Female
;
Genital Diseases, Male
;
Genotype
;
Humans
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Hypospadias/genetics*
;
Male
;
Membrane Proteins/genetics*
;
Penis/abnormalities*
;
Phenotype
;
Retrospective Studies
;
Steroid 21-Hydroxylase/genetics*

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