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 ; X-linked Nuclear Protein/genetics* ; alpha-Thalassemia/genetics* ; X-Linked Intellectual Disability/genetics* ; Male ; Infant, Newborn ; Exome Sequencing ; Mutation

Objective:To analyze the epidemic situation of plague among animals in the foci of Meriones unguiculatus in Inner Mongolia Plateau, and to find out key influencing factors affecting the epidemic of the plague, and to provide theoretical basis for the prediction, early warning and risk assessment of the plague. Methods:The monitoring data including gerbils density, gerbils body flea index, plague epidemic intensity, etc., as well as environmental data including temperature, precipitation and El Ni?o activity (Southern Oscillation Index, SOI) from 19 banners (counties, cities and districts) in Ulanqab Plateau area, the foci of Meriones unguiculatus in Inner Mongolia Plateau were selected. The methods of correlation analysis, structural equation model and rank correlation were used to analyze the epidemic and key influencing factors of plague among animals in the foci. Results:The plague epidemic cycle in the foci of Meriones unguiculatus in Inner Mongolia Plateau was 5 to 10 years. The correlation analysis results showed that all the factors had influence on each other. Structural equation model screened out that the main influencing factors of plague epidemic were SOI, gerbils density and temperature. SOI had a negative effect on plague epidemic intensity (-0.022) and temperature (-0.029), while gerbils density had a positive effect on plague epidemic intensity (0.014), and temperature had a negative effect on plague epidemic intensity (-0.065). In rank correlation, when the gerbils density was at a high value, the probability of high plague epidemic intensity in that year was 4/9; when SOI was at a low value, the probability was 5/9; when the temperature was at a low value, the probability was 5/9. When the plague epidemic intensity was at a high value in that year, the probability of the plague epidemic intensity being high in the following year was 5/8; when the gerbils density was at a high value in that year, the probability was 4/9; when SOI was at a low value in that year, the probability was 4/9. Conclusion:Climate and biological factors can affect prevalence of plague, and countermeasures should be taken in advance to prevent plague outbreaks when El Ni?o phenomenon, low temperature, high density of gerbils, and high previous-year prevalence of plague appear.

Objective:To explore the promoted role of calcium-sensing receptor (CaSR) overexpression in proliferation and differentiation of immature white matter progenitor cells after ischemia in vitro. Methods:Periventricular white matter cells from 5-d-old rats were cultured in vitro and divided into control group, oxygen-glucose deprivation (OGD) group, OGD+gadolinium chloride (GdCl 3) group, and OGD+ CaSR silenced group. CaSR expression was agitated by GdCl 3, and CaSR gene expression was inhibited by gene silencing. CaSR mRNA levels 24, 48 and 72 h, and 7 and 14 d after OGD were detected by real-time fluorescence quantification-PCR (RT-qPCR); cell proliferation 48 h after OGD was detected by inverted microscope, and cell differentiation 24, 48, and 72 h, and 7 and 14 d was detected by double immunofluorescence staining. Results:(1) CaSR mRNA expressions: CaSR mRNA expressions in OGD group 48 and 72 h and 7 d after OGD were statistically higher than those in control group ( P<0.05). Forty-eight and 72 h, and 7 and 14 d after OGD, CaSR mRNA expressions in OGD+GDCL 3 group were statistically higher than those in control group and OGD group ( P<0.05); the CaSR mRNA expressions in the OGD+CaSR silenced group were significantly lower than those in the control group ( P<0.05). (2) Cell proliferation and differentiation: 48 h after OGD, the cell sphere diameter of OGD group ([75.26±26.07] μm) was significantly increased as compared with that of control group ([57.96±18.92] μm, P<0.05); the cell sphere diameter of OGD+GdCl 3 group ([91.92±21.82] μm) was significantly increased as compared with that of control group and OGD group ( P<0.05); and the cell sphere diameter of OGD+ CaSR silenced group ([24.09±8.34] μm) was significantly shorter than that of control group and OGD group ( P<0.05). At 48 and 72 h after OGD, the number of O4 +/CaSR + olidoendrocyte precursor cells (OPCs) in OGD group was significantly larger than that in control group, that in OGD+GdCl 3 group was significantly larger than that in control group and OGD group, and that in OGD+ CaSR silenced group was significantly smaller than that in control group and OGD group ( P<0.05). Conclusion:CaSR overexpression could promote the proliferation and differentiation of progenitor cells to OPCs.

Objective:To explore the correlation between the index of hemodynamics in perinatal period and retinopathy of prematurity(ROP), so as to provide basis for the better prevention and treatment of ROP.Methods:From May 2017 to April 2019, the preterm infants were admitted to the Neonatal Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University at birth and were hospitalized for more than 2 weeks, gestational age ≤ 35 weeks and birth weight ≤ 2 500 g. They were selected as the study objects.The perinatal data including heart rate, blood pressure, patent ductus arteriosus, ventricular septal defect, and NT-proBNP level on the 1 st, 7 th and 14 th day, respectively after birth were collected.They were divided into ROP group and non ROP group according to the results of the retinopathy screening report.The influencing factors of ROP were screened out by univariate analysis and multivariate regression analysis. Results:A total of 1 119 subjects were included, 105 infants with ROP were detected, and the prevalence of ROP was 9.4%.Among them, 12 cases of pre-threshold lesion type 1 and threshold lesions required treatment, accoun-ting for 1.07% of screened preterm infants .Univariate analysis and multivariate regression analysis revealed that gestational age, birth weight, total oxygen therapy time, and intrauterine growth restriction were all factors affecting ROP, and 2 hemodynamic related indicators, such as the level of NT-proBNP in plasma on the 14 th day after birth, and placenta previa or abruption were also related to ROP( OR=0.604, 0.647, 1.276, 2.361, 1.688 and 2.506, respectively, all P<0.05). Conclusion:The hemodynamic changes in perinatal period may be involved in the formation of ROP, and it is necessary to further clarify its mechanism.

Objective: To analyze the risk factors of adverse neurodevelopmental prognostic in very /extremely low birth weight infants (VLBWI/ELBWI). Methods: The 24 hours VLBWI/ELBWI admitted to the neonatal intensive care unit between January 2016 and October 2016 were enrolled.These infants were followed up and neurodevelopmental evaluation was performed at a corrected age of 12 months by using the Bayley Scales of Infant Development Ⅱ (BSID-Ⅱ). According to the neurodevelopmental outcomes, they were divided into normal and abnormal neurodeve-lopment groups.The data of prenatal, intrapartum and postpartum periods in the two groups were compared.Potential risk factors of neurodevelopmental impairment were analyzed with Logistic stepwise regression. Results: A total of 167 VLBWI/ELBWI were enrolled, among which 14 cases died during hospitalization or after giving up treatment.At the corrected age of 12 months, 140(91.5%) infants completed follow-up and 13(8.5%) were lost to follow-up.Among 140 infants who completed neurodevelopmental evaluation at the corrected age of 12 months, there were 86 males, 54 females, and in which 28 cases had extremely low birth weight, 112 cases with very low birth weight, with gestational age of (30.4±2.2) weeks (25.3-36.0 weeks). There were one hundred and twenty-five cases with normal neurodevelopmental outcomes and 15 cases with abnormal neurodevelopmental outcomes.The results of univariate analysis showed that birth weight<1 000 g, exposure to antenatal steroids, N -terminal brain natriuretic peptide (NT-proBNP) ≥35 000 ng/L and bronchopulmonary dysplasia (BPD) in the two groups were statistically significant(P<0.05). Logistic stepwise regression showed that NT-proBNP level≥35 000 ng/L may independently predict neurodevelopmental impairment among VLBWI/ELBWI (OR=22.774, 95%CI: 3.079-168.425, P=0.002). Exposure to antenatal steroids may be a protective factor for neurodevelopmental impairment (OR=0.125, 95%CI: 0.020-0.782, P=0.026). Conclusions Plasma NT-proBNP level ≥35 000 ng/L may independently predict neurodevelopmental impairment among VLBWI/ELBWI.Antenatal corticosteroids may be the protective factor of poor neurodevelopmental outcomes.

Magnesium ion (Mg²⁺ ) plays an important role in maintaining the life and health of the body.In preterm infants, the protective effect of prenatal Mg²⁺ supplementation on the nervous system of preterm infants has been widely recognized.Researchers begin to pay attention to the effects of serum Mg²⁺ level on the development of nervous system and effects of prenatal exposure to Mg²⁺ on the non-nervous system in preterm infants.The effects of Mg²⁺ on the development of neural and non-neural system in preterm infants were summarized.

Objective To explore the relationship between renal volume and function in the preterm and term newborns at different gestational ages.Methods This study was conducted at the First Affiliated Hospital of Zhengzhou University from October 2016 to March 2018.A total of 626 newborns with different gestational ages were included and the renal volume was determined by ultrasonography.Blood samples were taken for laboratory tests to detect renal function including urea,creatinine,uric acid and estimated glomerular filtration rate.Results A total of 352 preterm and 274 full term newborns were enrolled at birth.The mean gestational age of the neonates was (36.0 ± 3.5) weeks and the mean birth weight was (2.59 ±0.77) kg.The mean renal volume of the preterm infants was (19.57 ±4.30) cm3 and estimated glomerular filtration was (21.68 ± 5.99) mL/(min · 1.73 m2);the mean renal volume of the term infants was(23.03 ± 3.80) cm3 and estimated glomerular filtration was(46.60 ± 10.21) mL/(min · 1.73 m2).The renal volume and estimated glomerular filtration of term infants was significantly greater compared to the preterm infants (t =12.96,33.10,all P ＜ 0.001).The renal volume was highly linear positively correlated with gestational age,birth weight and birth length (r =0.546,0.605,0.592,all P ＜ 0.001).The renal volume was highly linear positively correlated with estimated glomerular filtration(r =0.396,P ＜ 0.001).The renal volume was negatively correlated with urea,creatinine and uric acid(r =-0.210,-0.280,-0.176,all P ＜ 0.001).Conclusions The renal volume increases with gestational age and birth weight in neonates.Estimated glomerular filtration increases with renal volume in neonates.The preterm infants have immaturity kidney size and poor development so that they need special medical care.

Objective To explore the testis development and epididymis in the preterm and term newborns so as to provide the scientific evidence for early clinical diagnosing early.Methods From October 2016 to March 2018,456 hospitalized neonates at Department of Neonatology,the First Affiliated Hospital of Zhengzhou University were recruited within 7 days at birth in this study.In these patients,224 cases were preterm newborns and 232 cases were term newborns.These gestational ages of newborns at birth were (36.18 ± 3.13) weeks (27-41 +6 weeks) and weighted (2.66 ± 0.67) kg(0.90-3.82 kg).The size of the testis and epididymis were measured by ultrasonography.Results The mean testicular volume of the preterm was (0.24 ± 0.07) mL.The mean length of epididymal head,thickness of epididymal head and body and tail of the preterm newborns were (4.17 ±0.59) mm,(2.58 ±0.39) mm,(1.78 ± 0.26) mm,(1.91 ± 0.24) mm,respectively.The mean testicular volume of the term newborns was (0.38 ± 0.13) mL,the mean length of epididymal head,thickness of epididymal head and body and tail of the term newborns were (4.49 ± 0.45) mm,(2.78 ± 0.34) mm,(1.95 ± 0.20) mm,(1.99 ± 0.16) mm,respectively.The mean testicular volume,length of epididymal head,thickness of epididymal head and body and tail of the preterm newborns were significantly lower compared with the term newborns (t =12.810,8.261,6.819,8.058,3.591,all P ＜0.001).The mean testicular volume of the newborns were highly linear positively correlated with gestational age,birth weight and birth length (r =0.538,0.591,0.533,all P ＜ 0.001).In the preterm newborns at postmenstrual age (PMA) of 37 weeks,the mean testicular volume,length of epididymal head,thickness of epididymal head and body and tail of the preterm newborns had no significant difference between the 2 groups (t =1.561,0.863,0.282,1.732,1.147,all P ＞ 0.05).Conclusions The testicular volume,the length of epididymal head,thickness of epididymal head and body increase with gestational age,birth weight and birth length in early neonates.The growth of reproductive system in the preterm newborns at PMA 37 weeks catch-up with term newborns.If this catch-up growth was incomplete at PMA 37 weeks,special attention should be given to monitor underlying diseases.

Hemangioendothelioma ; Humans ; Infant, Newborn ; Kasabach-Merritt Syndrome ; Sarcoma, Kaposi

ObjectiveTo explore the risk factors of obstructive hydrocephalus secondary to intracranial hemorrhage in premature infants.MethodsA total of 304 premature infants were selected who were diagnosed as sever intracranial hemor-rhage (grade III and IV) by cranial bedside ultrasound admitted to our hospital from Jun. 2013 to Sep. 2014. According to wheth-er the obstructive hydrocephalus was followed, all infants were divided into hydrocephalus group (n=59) and non-hydrocephalus group (n=185). The risk factors of obstructive hydrocephalus secondary to intracranial hemorrhage were analyzed and the lateral ventricle size was measured dynamically.ResultsThe univariate analysis showed the factors related with obstructive hydro-cephalus were as follows: gestational age≤32 weeks, birth weight< 1500g, severe asphyxia, cesarean section, RDS, neonatal infection, heart failure, PDA, acidosis, thrombocytopenia, coagulation abnormalities, and intracranial hemorrhage (gradeⅢ orⅣ) (allP<0.05). Multivariate logistic regression analysis showed that acidosis, thrombocytopenia, coagulation abnormalities, gesta-tional age≤ 32 weeks, severe asphyxia, intracranial hemorrhage (gradeⅢ orⅣ) were independent risk factors for obstructive hydrocephalus (OR: 1.76~20.46, allP<0.05). At each time point after birth, the ratio of posterior horn of lateral ventricle was signiifcantly higher in hydrocephalus group than that in non-hydrocephalus group (P<0.05). There were signiifcant differences in the changes of the posterior horn ratio of left or right lateral ventricle with time in hydrocephalus group (P=0.000), increasing at 14 days and reaching the peak at 28 days after birth.ConclusionsThe risk factors for obstructive hydrocephalus secondary to intracranial hemorrhage in neonates are important. Regular and dynamical monitoring of ventricle size by cranial ultrasound is needed in infants with sever intracranial hemorrhage.