A rapid PCR-free next-generation sequencing method for comprehensive diagnosis of chromosome disease syndromes in prenatal samples.

The aim of this study is to investigate the application performance of rapid copy number variation sequencing (rCNV-seq) technology for the detection of chromosomal abnormalities during prenatal diagnosis. Samples were collected from 424 pregnant women who were at high-risk for noninvasive prenatal screening in Kunming Maternal and Child Care Hospital from January 2018 to May 2022. rCNV-seq technique was used to detect fetal chromosome abnormalities and compare the results with that of chromosomal karyotype analysis. The Result showed that 330 (77.83%, 330/424) cases indicated chromosomal abnormalities among 424 high-risk pregnant women who underwent rCNV-seq. Moreover, 94 (22.17%, 94/424) cases were discovered to have copy number variations. Among the 330 fetuses with chromosomal abnormalities, common autosomal aneuploidy was observed in 203 cases (47.87%, 203/424) and sex chromosome aneuploidy was observed in 91 cases (21.46%, 91/424). Moreover, the abnormalities in multiple chromosomes were discovered in 33 cases (7.78%, 33/424), and the rare autosomal aneuploidy was observed in 3 cases (0.71%, 3/424). There were 63 fetuses (14.86%, 63/424) with pathogenic CNVs among the 94 fetuses with variable copy numbers. Of the 245 pregnant women who voluntarily selected G-band karyotyping, 1 fetus with copy number variation had normal karyotype results, and the remaining women were consistent with rCNV-seq. Our study revealed that rCNV-seq has higher accuracy in detecting common trisomy and can also detect chromosomal microdeletions or microduplications that cannot be detected by G-banding karyotype analysis. There is no effective treatment for chromosomal diseases, so it is particularly important to prevent chromosomal diseases through genetic counseling and prenatal diagnosis of chromosomal diseases.

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature.

With the emergence of targeted inhibition strategies for Hedgehog signaling in cancer, multiple Hedgehog signaling pathway-related biomarkers have become the focus of research. SsGSEA algorithm was employed to analyze the Hedgehog pathway scores of samples in TCGA-HNSC dataset and divide them into two groups. Weighted co-expression network analysis was performed to identify modules strongly associated with the Hedgehog pathway. Differentially up-regulated genes in tumor samples in comparison to the normal ones were screened by Limma, in which genes belonging to modules strongly related to Hedgehog pathway were further filtered by LASSO reduction and multivariate Cox regression analysis to develop a model. ESTIMATE and CIBERSORT were served to characterize the tumor microenvironment (TME). TIDE assessed immunotherapy response. Hedgehog pathway activity was significantly higher in head and neck squamous cell carcinoma (HNSCC) tissues than in normal tissues and was correlated with HNSCC survival, glycan, cofactors and vitamins, drug metabolism, and matrix scores. Six genes (SLC2A3, EFNB2, OAF, COX4I2, MT2A and TXNRD1) were captured to form a Hedgehog associated 6-gene signature, and the resulting risk score was an independent indicator of HNSCC prognosis. It was significantly positively correlated with stromal score, metabolism, angiogenesis and inflammatory response. Patients in low-risk group with a low TIDE score had higher immunotherapy sensitivity relative to those in high-risk group. This study revealed novel findings of the Hedgehog pathway in HNSCC progression and opened up a Hedgehog pathology-related signature to help identify risk factors contributing to HNSCC progression and help predict immunotherapy outcomes.

Clinical impact and in vitro characterization of ADNP variants in pediatric patients.

BACKGROUND: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability. METHODS: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells. RESULTS: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells. LIMITATIONS: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants. CONCLUSIONS: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS.

Corrigendum: The incidence and clinical characteristics of fragile X syndrome in China.

[This corrects the article DOI: 10.3389/fped.2023.1064104.].

Plasma microRNAs as potential biomarkers in diagnosis of acute venous thromboembolism.

OBJECTIVE: To assess the potential use of plasma microRNAs (miRNAs) in diagnosis of acute venous thromboembolism (VTE). METHODS: Using BGISEQ-500 sequencing technology, we analyzed the miRNA profile of paired plasma samples from the acute and chronic phases of four patients with unprovoked VTE. Using real-time quantitative polymerase chain reaction (RT-qPCR), we verified nine upregulated named miRNAs in the acute phase in the plasma samples of 54 patients with acute VTE and 39 controls. We then compared the relative expression of the 9 candidate miRNAs between the acute VTE and control group, and plotted the receiver operating characteristic (ROC) curves of the differentially expressed miRNAs. We chose the miRNA with the greatest area under curve (AUC) to evaluate the effect of miRNA on coagulation and platelet function in the plasma samples of 5 healthy volunteers. RESULTS: The plasma levels of miR-374b-3p, miR-660-5p, miR-378a-3p, miR-425-5p, miR-3613-5p, miR-130b-3p, miR-183-5p, and miR-103b were higher in patients with acute VTE than in the controls, with AUCs of 0.6776, 0.6614, 0.6648, 0.6885, 0.8048, 0.6871, 0.7298, and 0.7498, respectively, and P values of 0.0036, 0.0081, 0.0069, 0.0020,<0.0001, 0.0022, 0.0002, and < 0.0001, respectively. There were no significant differences in miR-193b-5p level between the acute VTE group and the control group. Fibrinogen (Fib), thrombin- antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), and TAT/plasmin-α2-plasmin inhibitor complex (PIC) were decreased in the miR-3613-5p group when compared with the control group (P < 0.05) and the mean platelet aggregation rate was increased in the miR-3613 group (P < 0.05). CONCLUSION: miRNAs can be potential biomarkers for diagnosing acute VTE, and miR-3613-5p may be involved in the formation, coagulation, and platelet functions in acute VTE.

Epitaxial growth of hexahedral Fe2O3@SnO2 nano-heterostructure for improved lithium-ion batteries.

Fe2O3 is one of the most important lithium storage materials and has attracted increasing interest owing to its good capacity in theory, abundant reserves, and better security. The utilization of Fe2O3 materials is hampered by their inferior cycle performance, low rate performance, and restricted composite variety. Herein, the heterostructure of Fe2O3@SnO2 with hexahedral structure was manufactured by two- step hydrothermal strategy, while the SnO2 nanopillars were epitaxially grown in six faces, not in the twelve edges of hexahedral Fe2O3 cubes, which comes from maximizing lattice matching on the six surfaces of Fe2O3. Furthermore, the experimental results prove that the hexahedral Fe2O3@SnO2 heterostructure exhibits remarkably enhanced electrochemical reversibility and reaction kinetics and delivers an impressive initial discharge capacity (1742 mA h g-1 at 4 A g-1), great rate performance (565 mA h g-1 at 5 A g-1), and stable long-term durability (661 mA h g-1 after 4000 cycles at 4 A g-1) as an anode for LIBs. The result of the finite element mechanical simulation further indicates that the SnO2 nanopillars grow on the six surfaces but not on the twelve edges of the hexahedral Fe2O3 cube, which would provide great rate performance and long-term stability. This study underlines the merits of the heterostructure and offers a useful design routine for superior electrode materials in LIBs.

Targeted sequencing and clinical strategies in children with autism spectrum disorder: A cohort study.

Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with genetic and clinical heterogeneity. Owing to the advancement of sequencing technologies, an increasing number of ASD-related genes have been reported. We designed a targeted sequencing panel (TSP) for ASD based on next-generation sequencing (NGS) to provide clinical strategies for genetic testing of ASD and its subgroups. Methods: TSP comprised 568 ASD-related genes and analyzed both single nucleotide variations (SNVs) and copy number variations (CNVs). The Autism Diagnostic Observation Schedule (ADOS) and the Griffiths Mental Development Scales (GMDS) were performed with the consent of ASD parents. Additional medical information of the selected cases was recorded. Results: A total of 160 ASD children were enrolled in the cohort (male to female ratio 3.6:1). The total detection yield was 51.3% for TSP (82/160), among which SNVs and CNVs accounted for 45.6% (73/160) and 8.1% (13/160), respectively, with 4 children having both SNVs and CNV variants (2.5%). The detection rate of disease-associated variants in females (71.4%) was significantly higher than that in males (45.6%, p = 0.007). Pathogenic and likely pathogenic variants were detected in 16.9% (27/160) of the cases. SHANK3, KMT2A, and DLGAP2 were the most frequent variants among these patients. Eleven children had de novo SNVs, 2 of whom had de novo ASXL3 variants with mild global developmental delay (DD) and minor dysmorphic facial features besides autistic symptoms. Seventy-one children completed both ADOS and GMDS, of whom 51 had DD/intellectual disability (ID). In this subgroup of ASD children with DD/ID, we found that children with genetic abnormalities had lower language competence than those without positive genetic findings (p = 0.028). There was no correlation between the severity of ASD and positive genetic findings. Conclusion: Our study revealed the potential of TSP, with lower cost and more efficient genetic diagnosis. We recommended that ASD children with DD or ID, especially those with lower language competence, undergo genetic testing. More precise clinical phenotypes may help in the decision-making of patients with genetic testing.

A multicenter clinical study on parent-implemented early intervention for children with global developmental delay.

Objective: Early identification and intervention for children with global developmental delay (GDD) can significantly improve their prognosis and reduce the possibility of developing intellectual disability in the future. This study aimed to explore the clinical effectiveness of a parent-implemented early intervention program (PIEIP) for GDD, providing a research basis for the extended application of this intervention strategy in the future. Methods: During the period between September 2019 and August 2020, children aged 3 to 6 months diagnosed with GDD were selected from each research center as the experimental group and the control group. For the experimental group, the PIEIP intervention was conducted for the parent-child pair. Mid-term and end-stage assessments were performed, respectively, at 12 and 24 months of age, and parenting stress surveys were completed. Results: The average age of the enrolled children was 4.56 ± 1.08 months for the experimental group (n = 153) and 4.50 ± 1.04 months for the control group (n = 153). The comparative analysis of the variation in the progress between the two groups by independent t-test showed that, after the experimental intervention, the developmental quotient (DQ) of locomotor, personal-social, and language, as well as the general quotient (GQ) of the Griffiths Mental Development Scale-Chinese (GDS-C), the children in the experimental group demonstrated higher progress than those in the control group (P < 0.05). Furthermore, there was a significant decrease in the mean standard score of dysfunctional interaction, difficult children and the total level of parental stress in the term test for the experimental groups (P < 0.001 for all). Conclusions: PIEIP intervention can significantly improve the developmental outcome and prognosis of children with GDD, especially in the areas of locomotor, personal-social, and language.

The incidence and clinical characteristics of fragile X syndrome in China.

Introduction: Fragile X syndrome (FXS) is a X-linked neurodevelopmental disorder (NDD). This study aims to investigate the incidence of FXS in Chinese children and analyze the comprehensive clinical characteristics of these FXS children. Methods: Children diagnosed with idiopathic NDD were recruited between 2016 and 2021 from the department of Child Health Care, Children's Hospital of Fudan University. We combined tetraplet-primed PCR-capillary electrophoresis and whole exome sequencing (WES)/panel or array-based comparative genomic hybridization (array-CGH) to identify the size of the CGG repeats and the mutations or copy number variations (CNVs) in the genome and in FMR1. The clinical features of FXS children were analyzed according to pediatricians' recording, parental questionnaires, the results of examinations and follow-up. Results: The incidence of FXS in Chinese children with idiopathic NDD was 2.4% (42/1753) and in those with FXS, 2.38% had a deletion (1/42). Here, we present the clinical characteristics of 36 children with FXS. Overweight was observed in two boys. The average intelligence quotient (IQ)/development quotient (DQ) of all FXS patients was 48. The average ages of meaningful words and walking alone were 2 years and 10 months and 1 year and 7 months, respectively. The most frequent repetitive behavior was stimulated by hyperarousal to sensory stimulation. On social aspects, social withdrawal, social anxiety, and shyness accounted for 75%, 58%, and 56% of the total number of children, respectively. Approximately 60% of FXS children in this cohort were emotionally labile and prone to temper tantrums. Self-injury and aggression toward others could also be observed, at 19% and 28%, respectively. The most frequent behavioral problem was attention-deficit hyperactivity disorder (ADHD) seen in 64% and the most common facial features were a narrow and elongated face and large or prominent ears in 92% of patients. Discussion: Screening of FMR1 full mutation provides the possibility for patients' further medical supports and the clinical features of FXS children obtained in this study will increase the understanding and diagnosis of FXS.

Tailoring Hydrogen-Bonding Strategy for Sequence-Dependent and Thermo/pH Dual-Responsive Clusteroluminescence.

Rational design of monomer sequence for desired properties is challenging. This study investigates the effect of monomer distribution of double hydrophilic copolymers (DHCs) with electron-rich units on cluster triggered emission (CTE) capacity. By means of combining latent monomer strategy, reversible addition fragmentation chain transfer (RAFT) polymerization and selective hydrolysis technology, the random, pseudo di-block and the gradient DHCs consisting of pH-responsive polyacrylic acid (PAA) segments and thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) segments were successfully synthesized in a controlled manner. Moreover, the gradient DHCs showed a tremendously increased luminescent intensity due to the distinct hydrogen-bonding interaction compared to random and pseudo di-block DHCs. To the best of our knowledge, this is the first reported the direct correlation between luminescent intensity and sequence structure of non-conjugated polymer. Meanwhile, thermo and pH dual-responsive clusteroluminescence could be easily performed. This work demonstrates a novel and facile method to tailor the hydrogen-bonding for the stimuli-responsive light-emitting polymers.

Clinical characterization of Lamb-Shaffer syndrome: a case report and literature review.

BACKGROUND: Lamb-Shaffer syndrome (LAMSHF, MIM 616,803) is a rare neurodevelopmental disorder due to haploinsufficiency of SOX5. Furthermore, studies about the clinical features of LAMSHF patients with same allele of c.1477C > T (p. R493*) are very limited. CASE PRESENTATION: We analyzed the phenotypes of one of our cases and two previously reported cases with c.1477C > T (p. R493*), and reviewed the correlating literature. A de novo heterozygous variation c.1477C > T (p. R493*) in SOX5 was identified in a 4 years and 2 months old boy with global development delay by trio-based whole exome sequencing. We compared our case and previously 2 cases reported with recurrent variation, the overlapping clinical features are global developmental delay or intellectual disability, language delay and scoliosis, but their other clinical characteristics are different. CONCLUSIONS: This study suggests that the clinical features of LAMSHF patients with recurrent variations in the SOX5 gene are different. It is suggested that the LAMSHF-related SOX5 gene should be screened and included as one of the candidate genes for neurodevelopmental disorders of unknown etiology.

Triglyceride glucose index predicts all-cause mortality in oldest-old patients with acute coronary syndrome and diabetes mellitus.

BACKGROUND: Acute coronary syndrome (ACS) and diabetes mellitus (DM) are the leading health risks for the elderly. Triglyceride-glucose (TyG) index is a novel and reliable indicator of insulin resistance (IR). This study aims to explore the relationship between the TyG index and all-cause mortality in oldest-old patients with ACS and DM. METHODS: Seven hundred twenty hospitalized patients with ACS aged ≥ 80 years were enrolled, and 699 patients signed informed consent for the study. During the follow-up period, 37 were lost to follow-up, and the follow-up rate was 94.7%. 231 ACS patients with DM were selected for the study's analyses. Kaplan-Meier curve, Cox regression model and receiver operating characteristic (ROC) curve were used to analyze the association between the TyG index and all-cause mortality. RESULTS: The mean age of participants was 81.58 ± 1.93 years, and 32.47% were women. Compared to TyG tertile 1, the Hazard Ratio (HR) [95% confidence interval (CI)] of all-cause mortality was 2.04 (1.09, 3.81) for TyG tertile 3 in the fully adjusted model. For the TyG index per standard deviation (SD) increment, the HR (95% CI) of all-cause mortality was 1.44 (1.13, 1.83). Further, the association between the TyG index and all-cause mortality was dose-response (P for trend = 0.026). ROC curve analyses indicated that the TyG index outperformed FBG and TG in the prediction of mortality risk and improved the prognostic value of the Gensini score combined with LVEF. CONCLUSION: The TyG index predicts the risk of all-cause mortality in the oldest-old ACS patients with DM.

Patient-Reported Outcomes in Young Adults with Myeloproliferative Neoplasms.

INTRODUCTION: Genetic landscape, disease characteristics, and clinical outcomes of young adults with myeloproliferative neoplasms (MPNs) were reported. However, data on patient-reported outcomes (PROs) in young adults with MPNs were rare. METHODS: We conducted a multicenter, cross-sectional study to compare the PROs in respondents with thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) by age at survey, including the young group (18-40 years), middle-aged group (41-60 years), and elderly group (>60 years). RESULTS: Of the 1,664 respondents with MPNs, 349 (21.0%) were young including 244 (69.9%) with ET, 34 (9.7%) with PV, and 71 (20.3%) with MF. In multivariate analyses, the young groups with ET and MF were associated with the lowest MPN-10 scores among the 3 age groups; those with MF, highest proportion of reporting negative impact of disease and therapy on their daily life and work. The young groups with MPNs had the highest physical component summary scores but the lowest mental component summary scores in those with ET. The young groups with MPNs were most concerned about fertility; those with ET, treatment-related adverse events and long-term efficacy of treatment. CONCLUSIONS: We concluded that young adults with MPNs have different PROs compared with middle-aged and elderly patients.

A nomogram for predicting the readmission within 6 months after treatment in patients with acute coronary syndrome.

PURPOSE: To explore predictors for readmission within 6 months of ACS patients, and to build a prediction model, and generate a nomogram. METHODS: The retrospective cohort study included 498 patients with ACS in the Second Medical Center of the Chinese People's Liberation Army General Hospital between January 2016 and March 2019. Univariate and multivariate logistic regression with odds ratios (OR) and two-sided 95% confidence interval (CI) analysis were used to investigate predictors for readmission within 6 months. The cohort was randomly divided into training cohort to develop a prediction model, and the validation cohort to validate the model. The receiver operating characteristic curve (ROC) and the calibration curve was used to assess discriminative power and calibration. RESULTS: Eighty-three ACS patients were readmitted within six months, with a readmission rate of 16.67%. Predictors included ACS type, treatment, hypertension, SUA, length of stay, statins, and adverse events occurred during hospitalization were used to form a six-month readmission prediction model for readmission within 6 months in ACS patients. The area under the curve (AUC) of the model was 0.788 (95%CI: 0.735-0.878) and 0.775 (95%CI: 0.686-0.865) in the training cohort and the validation cohort, respectively. Calibration curves showed the good calibration of the prediction model. Decision-curve analyses and clinical impact curve also demonstrated that it was clinically valuable. CONCLUSION: We used seven readily available predictors to develop a prediction model for readmission within six months after treatment in ACS patients, which could be used to identify high-risk patients for ACS readmission.

Motor impairments in Chinese toddlers with autism spectrum disorder and its relationship with social communicative skills.

Objective: Motor impairments are prevalent in children with autism spectrum disorder (ASD) and persistent across age. Our current study was designed to investigate motor deficits in Chinese toddlers with ASD and to explore the relationships between motor deficits and social communication skills. Methods: For this cross-sectional study, we recruited a total of 210 Chinese toddlers with ASD aged between 18 and 36 months in the study during December 2017 to December 2020. Griffiths Developmental Scales-Chinese (GDS-C), Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Communication and Symbolic Behavior Scales Developmental Profile-Infant-Toddler Checklist (CSBS-DP-ITC) were administered in these toddlers to evaluate their development, social communicative skills, and autism severity. We compared the developmental and social communicational profiles of ASD toddlers in different gross and fine motor subgroups, and explored potential associated factors. The univariate generalized linear model tested the relationship of fine and gross motor skills and social communicative skills. Results: The prevalence of gross and fine motor deficits were 59.5 and 82.5%, respectively, which are almost equivalent in boys and girls. The motor impairments tended to be more severe with age in toddlers. After adjusting for age, sex, non-verbal development quotient (DQ) and restricted, repetitive behaviors, severer gross motor impairments were significantly related to higher comparison score of ADOS-2 and higher social composite score of CSBS-DP-ITC, without interactions with other variables. Meanwhile, lower fine motor skills were associated with more deficits of social communication and higher severity of ASD, also depending on non-verbal DQ. In the lower non-verbal DQ subgroup, both fine motor deficits and restricted repetitive behaviors (RRBs) might have effects on autism symptomology. Conclusion: Motor impairments are common in Chinese toddlers with ASD. Toddlers with weaker gross and fine motor skills have greater deficits in social communicative skills. Gross motor impairment might be an independent predictor of the severity of autism and social communication skills, while the effect of fine motor deficits might be affected by non-verbal DQ and RRBs of toddlers with ASD. We provide further justification for the inclusion of motor impairments in the early intervention for toddlers with ASD.

IntraCoronary Artery Retrograde Thrombolysis vs. Thrombus Aspiration in ST-Segment Elevation Myocardial Infarction: Study Protocol for a Randomized Controlled Trial.

Background: Type 2 diabetes (T2DM) is a major risk factor for myocardial infarction. Thrombus aspiration was considered a good way to deal with coronary thrombus in the treatment of acute myocardial infarction. However, recent studies have found that routine thrombus aspiration is not beneficial. This study is designed to investigate whether intracoronary artery retrograde thrombolysis (ICART) is more effective than thrombus aspiration or percutaneous transluminal coronary angioplasty (PTCA) in improving myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods/Design: IntraCoronary Artery Retrograde Thrombolysis (ICART) vs. thrombus aspiration or PTCA in STEMI trial is a single-center, prospective, randomized open-label trial with blinded evaluation of endpoints. A total of 286 patients with STEMI undergoing PPCI are randomly assigned to two groups: ICART and thrombus aspiration or PTCA. The primary endpoint is the incidence of >70% ST-segment elevation resolution. Secondary outcomes include distal embolization, myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, and in-hospital bleeding. Discussion: The ICART trial is the first randomized clinical trial (RCT) to date to verify the effect of ICART vs. thrombus aspiration or PTCA on myocardial perfusion in patients with STEMI undergoing PPCI. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR1900023849].

Brain structural alterations in young girls with Rett syndrome: A voxel-based morphometry and tract-based spatial statistics study.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function variants in the MECP2 gene, currently with no cure. Neuroimaging is an important tool for obtaining non-invasive structural and functional information about the in vivo brain. Multiple approaches to magnetic resonance imaging (MRI) scans have been utilized effectively in RTT patients to understand the possible pathological basis. This study combined developmental evaluations with clinical severity, T1-weighted imaging, and diffusion tensor imaging, aiming to explore the structural alterations in cohorts of young girls with RTT, idiopathic autism spectrum disorder (ASD), or typical development. Voxel-based morphometry (VBM) was used to determine the voxel-wised volumetric characteristics of gray matter, while tract-based spatial statistics (SPSS) was used to obtain voxel-wised properties of white matter. Finally, a correlation analysis between the brain structural alterations and the clinical evaluations was performed. In the RTT group, VBM revealed decreased gray matter volume in the insula, frontal cortex, calcarine, and limbic/paralimbic regions; TBSS demonstrated decreased fractional anisotropy (FA) and increased mean diffusivity (MD) mainly in the corpus callosum and other projection and association fibers such as superior longitudinal fasciculus and corona radiata. The social impairment quotient and clinical severity were associated with these morphometric alterations. This monogenic study with an early stage of RTT may provide some valuable guidance for understanding the disease pathogenesis. At the same time, the pediatric-adjusted analytic pipelines for VBM and TBSS were introduced for significant improvement over classical approaches for MRI scans in children.

Intracoronary artery retrograde thrombolysis combined with percutaneous coronary interventions for ST-segment elevation myocardial infarction complicated with diabetes mellitus: A case report and literature review.

Background: The management of a large thrombus burden in patients with acute myocardial infarction and diabetes is still a worldwide problem. Case presentation: A 74-year-old Chinese woman presented with ST-segment elevation myocardial infarction (STEMI) complicated with diabetes mellitus and hypertension. Angiography revealed massive thrombus formation in the mid-segment of the right coronary artery leading to vascular occlusion. The sheared balloon was placed far from the occlusion segment and urokinase (100,000 u) was administered for intracoronary artery retrograde thrombolysis, and thrombolysis in myocardial infarction (TIMI) grade 3 blood flow was restored within 7 min. At last, one stent was accurately implanted into the culprit's vessel. No-reflow, coronary slow flow, and reperfusion arrhythmia were not observed during this process. Conclusion: Intracoronary artery retrograde thrombolysis (ICART) can be effectively and safely used in patients with STEMI along with diabetes mellitus and hypertension, even if the myocardial infarction exceeds 12 h (REST or named ICART ClinicalTrials.gov number, ChiCTR1900023849).

Novel compound heterozygous mutation in STAMBP causes a neurodevelopmental disorder by disrupting cortical proliferation.

Background: Mutations in the STAMBP gene, which encodes a deubiquitinating isopeptidase called STAM-binding protein, are related to global developmental delay, microcephaly, and capillary malformation. Owing to the limited number of reported cases, the functional and phenotypic characteristics of STAMBP variants require further elucidation. Materials and methods: Whole exome sequencing was performed on a patient presenting with a neurodevelopmental disorder. Novel compound heterozygous mutations in STAMBP [c.843_844del (p.C282Wfs*11) and c.920G > A (p.G307E)] were identified and validated using Sanger sequencing. A 3D human cortical organoid model was used to investigate the function of STAMBP and the pathogenicity of the novel mutation (c.920G > A, p.G307E). Results: The patient was presented with global developmental delay, autism spectrum disorder, microcephaly, epilepsy, and dysmorphic facial features but without apparent capillary malformation on the skin and organs. Cortical organoids with STAMBP knockout (KO) showed significantly lower proliferation of neural stem cells (NSCs), leading to smaller organoids that are characteristic of microcephaly. Furthermore, STAMBP disruption did not affect apoptosis in early cortical organoids. After re-expressing wild-type STAMBP, STAMBP G307E , and STAMBP T313I (a known pathogenic mutation) within STAMBP KO organoids, only STAMBP WT rescued the impaired proliferation of STAMBP deficient organoids, but not STAMBP G307E and STAMBP T313I . Conclusion: Our findings demonstrate that the clinical phenotype of STAMBP mutations is highly variable, and patients with different STAMBP mutations show differences in the severity of symptoms. The STAMBP missense mutation identified here is a novel pathogenic mutation that impairs the proliferation of NSCs in human brain development.