Objective:To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes.Methods:A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children′s Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out.Results:CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%).Conclusion:The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.

Sjogren's syndrome is a chronic inflammatory autoimmune disease characterized by invasion of exocrine glands such as lacrimal gland and salivary gland and high lymphocyte infiltration. Interstitial cystitis is a chronic cystitis disease with frequent micturition, urgency, nocturia and/or pelvic pain as its main clinical manifestations, and its pathological changes are bladder submucosal ulcer and fibrosis as its main manifestations. Sjogren's syndrome complicated with interstitial cystitis is not uncommon. Anti-muscarinic type 3 acetylcholine receptor (M3R) antibody will not only cause gland dysfunction, but also play an important role in the pathogenesis of interstitial cystitis. The pathogenesis may include: ①Immune inflammation accompanied by mast cells and neurogenic inflammation with up-regulation of bladder sensory nerve. ②The detrusor contraction function is impaired, which induces ATP release and stimulates sensory nerve outflow.

OBJECTIVE: To investigate the perinatal clinical phenotype and genetic characteristics of two fetuses with ring chromosome 21 mosaicisms. METHODS: Two fetuses who were diagnosed at the Xiamen Maternal and Child Health Care Hospital in November 2021 were selected as the study subjects. Clinical data of the two fetuses were collected. Conventional G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out for the fetuses and their parents. RESULTS: Prenatal ultrasonography of fetus 1 has revealed absence of nasal bone, ventricular septal defect, persistent left superior vena cava, and mild tricuspid regurgitation. Chromosomal karyotyping was 46,X?,dic r(21;21)(p12q22;q22p12)[41]/45,X?,-21[9]. CMA has revealed a 30.00 Mb quadruplication at 21q11.2q22.3 and a 3.00 Mb deletion at 21q22.3. For fetus 2, ultrasonography has revealed pointed echo of the nasal bone. The fetus was found to have a karyotype of 46,X?,r(21)(p12q22)[83]/45,X?,-21[14]/46,X?,dic r(21;21)(p12q22;q22p12)[3]. CMA has revealed a 5.10 Mb quadruplication at 21q22.12q22.3 and a 2.30 Mb deletion at 21q22.3. CONCLUSION The perinatal phenotype of the two fetuses with ring chromosome 21 mosaicisms is related to the duplication of chromosomal segments near the breakpoints of the chromosomal deletions. The combined chromosomal karyotyping and CMA has enabled prenatal diagnosis and genetic counseling for these families.
Pregnancy ; Female ; Humans ; Mosaicism ; Ring Chromosomes ; Vena Cava, Superior ; Chromosome Aberrations ; Prenatal Diagnosis ; Microarray Analysis ; Fetus/diagnostic imaging*

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

OBJECTIVE: To explore the genetic basis for a case of recurrent fetal congenital hydrocephalus. METHODS: Next-generation sequencing was carried out for the fetus, the gravida and two of her sisters. RESULTS: The fetus was found to harbor a c.1765T>C (p.Tyr589His) mutation in exon 14 of the L1CAM gene, which was derived from the gravida. CONCLUSION Male fetuses with recurrent hydrocephalus should be subjected to testing of the L1CAM gene to facilitate genetic counseling and prenatal diagnosis.
DNA Mutational Analysis ; Female ; Fetus ; Genetic Diseases, X-Linked ; diagnosis ; genetics ; Humans ; Hydrocephalus ; diagnosis ; genetics ; Male ; Mutation ; Neural Cell Adhesion Molecule L1 ; genetics ; Pedigree ; Pregnancy

Objective: To explore the genetic basis for a case of recurrent fetal congenital hydrocephalus. Methods: Next-generation sequencing was carried out for the fetus, the gravida and two of her sisters. Results: The fetus was found to harbor a c. 1765T>C (p.Tyr589His) mutation in exon 14 of the L1CAM gene, which was derived from the gravida. Conclusion Male fetuses with recurrent hydrocephalus should be subjected to testing of the L1CAM gene to facilitate genetic counseling and prenatal diagnosis.

Objective To investigate the effects and mechanisms of glutamine (Gln) supplementation on oxidative stress,autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Eighty SD rats were randomly divided into 4 groups:sham operation group (group Sham),Sham + glutamine supplementation group (group Sham+ GLN),traumatic brain injury group (group TBI),and TBI + glutamine supplementation group (group TBI+ GLN).We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1,3,7 and 14 after TBI.The apoptosis neurons in TBI cerebral cortex were determined by TUNEL staining.The expression of reactive oxygen species (ROS) was tested by ROS kits.Oxidative stress and autophagy related cytokines (HO-1,NQO1,Nrf2,LC3-Ⅱ and Beclin-1) were tested with Western blotting.Results Compared with the TBI group,the neurological function was improved [(9.79±0.43) vs.(8.43±0.30),F =6.775,P =0.010] and the apoptosis rate decreased (19.88％ ± 1.60％ vs.15.35％ ± 1.28％,P =0.013) in the TBI+ GLN group after 7-day treatment.Compared with the Sham group,the protein expression of ROS increased (P=0.000),and the expression of anti-oxidative stress factors (HO-1,NQO1) and Nrf2 pathway significantly decreased in the TBI group.After glutamine supplementation was given,the expression of ROS decreased and the expressions of HO-1 and NQO1 increased.The Nrf2 pathway and autophagy response also were activated with the expressions of Nrf2,LC3-Ⅱ and Beclin-1 increasing.Conclusion Glutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI,thus has the protective effect on nerves by inhibiting TBI-induced oxidative stress response,activating Nrf2 pathway and autophagy response.

Objective To investigate the effects of enteral nutrition added with glutamine on the incidences of gastrointestinal complications,intestinal mucosal barrier function and inflammatory responses in patients with acute severe traumatic brain injury (sTBI).Methods A prospective case control study was made on 107 patients with sTBI hospitalized from January 2016 to June 2017.The patients were divided into experimental group added with glutamine (n =54) and control group without glutamine (n =53) according to the random number table.The general data of the patients were recorded.After treatment,the incidences of gastrointestinal complications in both groups were compared.The serum levels of intestinal mucosal barrier function indices,namely,diamine oxidase (DAO),Dlactate acid,and intestinal fat acid binding protein (I-FABP) were evaluated by enzymology spectrophotometer method.Meanwhile,the serum levels of C-reactive protein (CRP),tumor necrosis factor-α (TNF-α),and interleukin-6 (IL-6) were also tested with enzyme-linked immunosorbent assay (ELISA).Glasgow coma scale (GCS),acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ),and hospital stay in both groups were compared.Results The two group were comparable with respect to gender,age,injury reasons,body mass index,preoperative GCS,preoperative APACHE Ⅱ,injury type and injury time (P ＞ 0.05).The experimental group had lower incidences of stress ulcer,gastric retention and diarrhea compared with the control group 14 days after treatment (P ＜ 0.05).Within 14 days after treatment,the serum levels of DAO,D-lactate acid and I-FABP were significantly decreased in the experimental group at days 7 and 14 after treatment (P ＜ 0.05).The serum levels of CRP,TNF-α and IL-6 in the experimental group were significantly decreased after treatment (P ＜ 0.05).The experimental group had better prognosis compared with the control group (P ＜ 0.05),with higher GCS scores [(9.3 ± 0.7) points vs.(8.2 ± 0.7) points],lower APACHE Ⅱ scores [(15.3 ± 1.1) points vs.(17.7 ± 1.2) points] at day 14,and shorter hospital stay [(19.1 ± 2.2) days vs.(25.3 ± 2.4) days] (P ＜ 0.01).Conclusions Enteral nutrition added with glutamine can effectively reduce the incidence of gastrointestinal complications,as well as alleviate the intestinal mucosal barrier function damage and the inflammatory responses at early stage after sTBI,which possibly improves prognosis.

OBJECTIVE: This research developed a practical, multi-dimensional attention deficit hyperactivity disorder (ADHD) rating scale (i.e., the Symptoms and Functional Impairment Rating Scale, SFIRS) for Chinese children, aged 6–12 years, with ADHD. METHODS: The structural validity, criterion validity, internal consistency, and test-retest reliability of the scale were evaluated. Item screening was conducted with 412 ADHD patients and 322 developmentally typical controls. RESULTS: The scale includes 44 items, divided among Hyperactivity-Impulsivity, Self-Control, Inattention, Self-Management, Academic Performance, and Social Interaction. The six-factor model showed good data fit, with each factor significantly correlated with its corresponding criterion (r=0.690–0.841). The Cronbach's α of the full scale was 0.976. Total score test-retest reliability was r=0.816 (p < 0.01). CONCLUSION: The SFIRS thus demonstrated good reliability and validity and may be used to assess ADHD among children aged 6–12 years in China.
Asian Continental Ancestry Group ; Attention Deficit Disorder with Hyperactivity ; Behavior Rating Scale ; Child ; China ; Executive Function ; Humans ; Interpersonal Relations ; Mass Screening ; Reproducibility of Results ; Self Care ; Self-Control

A non-magnetic MEG compatible device has been developed that provides continuous force and velocity information. Combined with MEG, this device may find utility in characterizing brain regions associated with force and velocity relative to individual digits or movement pattern. 15 healthy right-handed participants were given visual cues to perform random finger movements on the prototype finger sensor for 21 s and then rest for 21 s (7 times). Respective finger flexion data were obtained, during 151-channel MEG brain scanning, by feeding the signal from finger sensor into four input Analog to Digital Converter (ADC) channels in the MEG hardware. The source activity was reconstructed in beta band using a Linearly Constrained Minimum Variance (LCMV) beamformer in the beta band. The ADC channels were used as regressors for a continuous time General Linear Model (GLM) and a Region of Interest (ROI) was identified to examine activity. MEG analysis showed bilateral activation in the primary motor cortex region. Because individual digits could be isolated in the ADC data, somatotopy of the fingers were observed consistent with the homunculus except pinky finger. The total span was calculated to be 5.5662 mm. The study confirms that the finger sensor is magnetically compatible with MEG measurements and may potentially provide a means to study complex sensorimotor functions. Improved isolation of individual digit information along with the use of machine learning algorithms can help retrieve more accurate results.
Brain ; Cues ; Fingers* ; Linear Models ; Machine Learning ; Motor Cortex