To provide a theoretical basis for different drug decision-making scenarios by conducting a comprehensive clinical evaluation of nusinersen.

Objective To explore the automated identification and diameter measurement methods for inferior vena cava (IVC) based on clinical ultrasound images of IVC. Methods An automated identification and localization method based on topology and automatic tracking algorithm was proposed. Tracking algorithm was used for identifying and continuously locating to improve the efficiency and accuracy of measurement. Tests were conducted on 18 sets of ultrasound data collected from 18 patients in intensive care unit (ICU),with clinicians' measurements as the gold standard. Results The recognition accuracy of the automated method was 94.44％ (17/18),and the measurement error of IVC diameter was within the range of±1.96s (s was the standard deviation). The automated method could replace the manual method. Conclusion The proposed IVC automated identification and localization algorithm based on topology and automatic tracking algorithm has high recognition success rate and IVC diameter measurement accuracy. It can assist clinicians in identifying and locating IVC,so as to improve the accuracy of IVC measurement.

Objective:To explore the perceived stress and coping experience of spouses of elderly people with long-term disability and empty nest.Methods:Using phenomenological research methods, semi-structured interviews were conducted with 19 spouses of disabled elderly people in a community in Beijing from February to June 2023, and data analysis was conducted using Colaizzi's 7-step analysis method.Results:The perceived stress and coping experience of spouses of long-term disabled empty nest elderly people were summarized into three themes and ten sub-themes, namely, the dynamic and variable stress perception of spouses (stress changed synchronously with the state of disabled elderly people, stress changed in a "U" shape, and pressure increased in a progressive manner), the challenges for spouses in long-term care of disabled elderly people (difficult in unifying opinions and views, incomprehensible inner emotions, difficulty in ensuring their elderly care, and coexistence of multiple roles and identities) and positive coping experiences and strategies of spouses (actively seeking external support, respecting the subjective wishes of disabled elderly people, and improving dyadic coping abilities) .Conclusions:Community nursing staff should support and guide spouses who undertake care work based on changes in perceived stress characteristics of long-term disabled empty nest elderly people. At the same time, it is necessary to understand the various challenges they face in long-term care, draw on positive coping experiences of spouses, so as to provide a basis for building a friendly family support system for home-based elderly care.

Objective To analyze the stress distributions of two root canal preparation shapes of oval root canals with micro-crack.Methods Twenty single-canal mandibular premolars with oval canals were expanded to create micro-cracks.Roots were sectioned after staining.The generation and distribution of dentin micro-cracks were observed under microscope.Then a finite element(FE)model of sectioned enlarged oval canal roots with micro-cracks was established.The stress distribution of micro-crack and root were analyzed under lateral loading.Results Cracks always appeared in the buccolingual sides of oval canal roots and extended from the intracanal wall to the root surface.This was consistent with the stress concentration on the buccolingual side of the root canal wall shown by FE analysis.When micro-cracks occurred,stresses were transferred to the crack tip and the peak values increased sharply nearly 5 times.This made the cracks propagate easily along this direction,especially in the long axis direction of the tooth.Conclusions The presence of micro-cracks does not change the general stress concentration on root with two preparation morphologies of oval canals.However,the micro-crack causes an extreme stress concentration in the crack tip.This may be the mechanism of rapid propagation of microcracks into vertical root fracture,and dentists need to pay high attention.

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg^-1）， high-dose JTTP group （7.2 g·kg^-1）， and metformin group （0.2 g·kg^-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

OBJECTIVE: To explore the clinical and genetic characteristics of three children with KBG syndrome. METHODS: Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out. RESULTS: All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype. CONCLUSION The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.
Female ; Child ; Humans ; Abnormalities, Multiple/genetics* ; Intellectual Disability/genetics* ; Bone Diseases, Developmental/genetics* ; Tooth Abnormalities/genetics* ; Facies ; Repressor Proteins/genetics* ; Mothers ; Mutation

OBJECTIVE: To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. METHODS: Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. RESULTS: The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. CONCLUSION The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
Humans ; Intellectual Disability/genetics* ; Genetic Testing ; Phenotype ; Exome Sequencing ; Heterozygote ; Mutation ; Chromosomal Proteins, Non-Histone/genetics* ; Phosphoproteins/genetics*

Objective:To detect and analyze the gene variation types of 64 unrelated pedigrees affected with autosomal dominant polycystic kidney disease (ADPKD), and explore the detection efficiency of multiple gene analysis techniques and variation characteristics.Methods:It was a cross-sectional study. The clinical data of 64 pedigrees with ADPKD from Nephrology Department or Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from December 2017 to August 2020 were retrospectively analyzed. The blood samples of probands and other family members were collected. Genetic analysis was carried out by next generation sequencing, and suspected mutations were verified by multiplex ligation-dependent probe amplification, or long-range PCR combined with Sanger sequencing. Prenatal diagnosis for high-risk fetuses was performed by fetal villi or amniotic fluid cells after genotyping without maternal genomic DNA contamination.Results:Among detected 64 pedigrees, 57 pedigrees (89.06%) had genetic variants in PKD1/PKD2. A total of 49 pathogenic/likely pathogenic variants in PKD1/PKD2 were identified in 51 pedigrees (79.69%), including 14 nonsense variants (28.57%), 14 frameshift variants (28.57%), 11 missense variants (22.45%), 5 splicing variants (10.20%) and 5 deletion variants (10.20%). Of these variants, 87.76% (43/49) were in PKD1 and 12.24% (6/49) were in PKD2. Totally, 14 novel variants in PKD1/ PKD2 were identified, including 7 frameshift variants, 3 splicing variants, 2 nonsense variants, 1 deletion variant and 1 missense variant, of which 11 variants were in PKD1 and 3 variants were in PKD2. Twenty high-risk fetuses from 17 pedigrees received prenatal diagnosis, in whom 6 fetuses had PKD1 variation, and other 14 fetuses had no PKD1/ PKD2-genetic variation. Conclusions:The combination of next-generation sequencing, multiplex ligation-dependent probe amplification, and long-range PCR combined with Sanger sequencing can be helpful for rapid, efficient and accurate genetic diagnosis of ADPKD pedigrees. Point mutations are the most common types in PKD1/PKD2. Fourteen novel variants in PKD1/PKD2 extend its pathogenic variant spectrum and can provide basis for genetic counseling and prenatal diagnosis of ADPKD pedigrees.

OBJECTIVE: To explore the clinical features and genetic basis for a child with Bainbridge-Ropers syndrome (BRPS). METHODS: Clinical data of the child were retrospectively analyzed. Copy number variation sequencing (CNV-seq) and trio based whole exome sequencing (trio-WES) were carried out. Prenatal diagnosis was provided for a at risk fetus from the pedigree, and genotype phenotype correlation was summarized through a literature review. RESULTS: The proband, a 6-year-old boy, has presented with feeding difficulties, specific craniofacial features, global developmental delay and intellectual disability, which has not improved after rehabilitation treatment. CNV-seq analysis of the patient showed no obvious abnormalities. A de novo heterozygous truncating variation, c.1448dupT (p.T484Nfs*5), was identified in the ASXL3 gene by trio-WES, which was a previously reported pathogenic variant. So far 14 Chinese patients with BRPS and ASXL3 variants have been reported. All patients have shown specific craniofacial features and delayed motor and speech development, and harbored 12 loss of function ASXL3 variants, which were de novo in origin and have clustered in exons 11 and 12 of the ASXL3 gene. CONCLUSION The heterozygous frameshift c.1448dupT (p.T484Nfs*5) variant of the ASXL3 gene probably underlay the disorder in this patient. BRPS should be considered in infants with feeding difficulties, special craniofacial features, global developmental delay and hand anomalies, and WES can help to delineate the pathogenesis and establish the definite diagnosis.
Child ; Humans ; Female ; Pregnancy ; Developmental Disabilities/genetics* ; Phenotype ; Pedigree ; DNA Copy Number Variations ; Retrospective Studies ; Transcription Factors/genetics* ; Syndrome ; Intellectual Disability/genetics* ; Prenatal Diagnosis ; China

Objective:To evaluate the diagnostic and predictive value of ultrasonic cardiac output monitor (USCOM) in premature infants with hemodynamic significant patent ductus arteriosus (hsPDA).Methods:A total of 165 preterm infants with gestational age less than 34 weeks and within 72 hours after birth in the Neonatal Medical Center of Children′s Hospital of Nanjing Medical University from January 2018 to June 2020 were retrospectively analyzed.According to the echocardiograph (ECHO) results within 72 hours after birth, clinical manifestations and oral administration of Ibuprofen, premature infants were divided into non-patent ductus arteriosus (non-PDA group, 77 cases), non-hsPDA group (59 cases), and hsPDA group (29 cases). USCOM was performed within half of an hour after ECHO.During the course of oral medication of Ibuprofen in the hsPDA group, USCOM was repeatedly examined every 24 hours.ECHO and USCOM were re-examined within 24 hours after the course of oral medication of ibuprofen.Results:Compared with non-hsPDA group and non-PDA group, the gestational age [(31.51±1.62) weeks, (32.09±1.27) weeks vs.(30.82±1.61) weeks, F=8.425, P<0.001], birth weight [(1 154.49±192.55) g, (1 195.58±182.02) g vs.(1 094.66±153.69) g, F=3.366, P=0.037] and the mean blood pressure [(38.37±2.20) mmHg, (38.53±2.37) mmHg vs.(30.52±2.31) mmHg, 1 mmHg=0.133 kPa, F=142.860, P<0.001]were significantly lower in hsPDA group.On the contrary, the heart rate[(129.68±7.11) times/min, (130.34±7.27) times/min vs.(164.76±7.65) times/min, F=271.790, P<0.001], B-type natriuretic peptide[(203.76±108.68) ng/L, (152.43±54.24) ng/L vs.(3 385.31±856.26) ng/L, F=931.30, P<0.001] and left artrium/aorta (1.32±0.12, 1.29±0.09 vs.1.60±0.12, F=84.970, P<0.001)were significantly higher.Among the USCOM parameters, left ventricular cardiac output [(0.40±0.08) L/min, (0.40±0.08) L/min vs.(0.51±0.04) L/min, F=26.760, P<0.001], cardiac index (CI) [(3.76±0.48) L/(min·m 2), (3.54±0.30) L/(min·m 2) vs.(4.43±0.36) L/(min·m 2), F=56.060, P<0.001], stroke volume[(3.75±0.28) mL, (3.70±0.23) mL vs.(4.22±0.36)mL, F=40.170, P<0.001], stroke volume index [(34.42±2.66) mL/m 2, (34.47±3.29) mL/m 2vs.(38.45±3.32) mL/m 2, F=20.080, P<0.001], peak ejection velocity [(1.12±0.12) m/s, (1.11±0.10) m/s vs.(1.23±0.09) m/s, F=14.890, P<0.001] and corrected flow time [(379.02±22.69) ms, (376.51±27.95) ms vs.(403.69±39.04) ms, F=10.120, P<0.001]were significantly higher in hsPDA group, while systemic vascular resistance index (SVRI) [(1 109.49±115.67) ds·cm -5·m 2, (1 070.01±133.55) ds·cm -5·m 2vs.(861.31±115.22) ds cm -5m 2, F=41.130, P<0.001]was significantly lower than that of non-hsPDA and non-PDA group.The area under the receiver operating characteristic curve of CI and SVRI for predicting hsPDA were 0.916 and 0.905, respectively.The sensitivity and specificity of CI>4.05 L/(min·m 2) for predicting hsPDA was 0.828 and 0.860, respectively, which was 0.660 and 1.000 for SVRI<1 002.5 ds·cm -5·m 2.The sensitivity and specificity of combining CI and SVRI for predicting hsPDA was 0.966 and 0.949, respectively. Conclusions:USCOM has a good diagnostic and predictive value for hsPDA in premature infants.The combined application of CI and SVRI can improve the predictive value, and help formulate the early diagnostic and treatment strategy for PDA in premature infants