OBJECTIVE: To block the transmission of Cranio-facial-nasal syndrome (CFNS) caused by a large deletion of the EFNB1 gene through preimplantation genetic testing for monogenic disorders (PGT-M). METHODS: A patient with craniofacial deformities and his parents who had visited Shiyan People's Hospital in June 2020 were selected as the study subjects. The child underwent whole exome sequencing (WES) and qPCR validation. After genetic counseling, PGT-M was chosen for the reproductive blockage. This study was approved by the Ethics Committee of the Hospital (Ethics No.: sysrmyy-087). RESULTS: The child was diagnosed with CFNS due to a heterozygous deletion of exons 1-5 of the EFNB1 gene through WES and qPCR, which showed a X-linked dominant inheritance. The mother underwent ovarian stimulation with a modified PPOS protocol, which has yielded 11 oocytes. After ICSI fertilization, 4 blastocysts were formed, and MALBAC whole genome amplification was performed on the trophoblast biopsy cells, and SNP haplotypes of the family members and embryos were analyzed to indirectly determine the presence of maternal pathogenic haplotypes. Chromosomal copy number variation analysis was conducted through next-generation sequencing to screen for euploid embryos, resulting in the identification of two euploid embryos that did not carry the mutation of the EFNB1 gene. The first transfer was unsuccessful, but after adjusting the transfer timing through endometrial receptivity assessment (ERA), clinical pregnancy was achieved. Prenatal diagnosis at 19 weeks excluded the EFNB1 gene exons 1-5 deletion in the fetus. A healthy girl was delivered by Cesarean section at 38⁺⁶ weeks, and Q-PCR confirmed she has no aforementioned EFNB1 gene deletion. CONCLUSION This study has successfully blocked the transmission of CFNS caused by a large deletion of the EFNB1 gene (exons 1-5) using a PGT-M strategy, which may provide reference for the intervention of similar genomic variations that cannot be directly detected.
Humans ; Female ; Male ; Craniofacial Abnormalities/diagnosis* ; Ephrin-B1/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Pedigree ; Asian People/genetics* ; Craniosynostoses/genetics* ; Pregnancy ; Gene Deletion ; Sequence Deletion ; Genetic Testing/methods* ; Adult ; East Asian People

【Objective】 To examine the association between psychological behavioral problems and sleep problems in disabled children in Beijing, in order to provide reference for reducing the sleep problems of disabled children. 【Methods】 From September 2017 to February 2018, children with disabilities aged 6 to 17 years were selected by random sampling, and were investigated by a self-designed questionnaire to get their demographic characteristics.Pediatric Symptom Checklist-17 (PSC-17) was used to assess psychological and behavioral problems.The relationship between psychological behavior and sleep problems was analyzed by binary Logistic regression. 【Result】 Totally 650 children with disabilities were included in the study.The detection rates of sleep problems was significantly different in children with different genders, different school styles, different types of disabilities and different grades of disabilities (χ²=3.984, 4.437, 12.925, 18.104, P<0.001). There was statistically significant difference in the detection rate of sleep problems between children with and without psychological and behavioral problems (χ²=30.722, P<0.001).Psychological and behavioral problems were the main risk factors for sleep problems of disabled children (OR=2.540, 95%CI:1.740 - 3.709).The risk of sleep problems in day students with disabilities was 1.577 times as high as that of boarders with disabilities. 【Conclusions】 Psychological and behavioral problems of disabled children are related to sleep problems.Improving psychological and behavioral status can effectively prevent their sleep problems.

Chiral drugs are closely related to the safety and effectiveness of drug use.Most dihydropyridine drugs have chiral carbon atoms,which are used as racemes and produce stereoselective disposal characteristics after entering the body,and may affect the safety and effectiveness of drugs.Therefore,based on the chiral resolution and pharmacokinetic characteristics of this class of drugs,the selection rules of chiral HPLC and CE methods and in vivo analysis applications of this class of drugs in recent years were reviewed.The stereoselective pharmacokinetics of this class of drugs were listed and compared.It was found that some of these drugs had obvious differences in stereoselective pharmacokinetics,and the pharmacokinetics and toxicity in vivo were also different.

Objective To investigate the protective and treatment role of ulinastatin(UTI)on con-trast-induced acute kidney injury(CIAKI)in the elderly with coronary heart disease(CHD)and chronic kidney diseases(CKD).Methods A total of 321 elderly CHD inpatients complicated with CKD undergoing coronary angiography admitted in the First Medical Center of Chinese PLA Gen-eral Hospital from November 2021 to November 2022 were enrolled consecutively and then divid-ed into UTI group(n=161)and hydration group(n=160).Their cardiac and renal function pa-rameters were collected and analyzed before and 2 d after intervention.The changes in above pa-rameters and incidence of CIAK were observed and compared between the two groups.Results In 2 d after intervention,the UTI group had significantly lower Scr,urea,CysC,homocysteine and NT-proBNP,but higher eGFR than the hydration group(P＜0.01).There were 62 patients(62/321,19.3％)developing CIAKI,including 17 from the UTI group and 45 from the hydration group,and statistical difference was observed in the incidence(10.6％vs 28.1％,P＜0.01).For the patients with comorbidities of hypertension,diabetes,hyperlipidemia and hyperuricemia,the incidence of CIAKI was obviously lower in the UTI group than the hydration group(P＜0.01).Multivariate logistic regression analysis showed that UTI was an independent protective factor for occurrence of CIAKI(OR=0.348,95％CI:0.180-0.673,P=0.001).Conclusion UTI can im-prove renal function and reduce the risk of CIAKI in elderly CHD patients with CKD.

Objective To explore the possibility of rhabdomyolysis and related organ damage in new recruits training in high temperature and high humidity environment by comparing the effects of different training environments on the laboratory indicators and electrocardiogram.Methods A total of 250 new recruits from a unit in Beijing and another 250 ones from a unit in Hainan were recruited and assigned into conventional environment group and high temperature and high humidity environment group,respectively.All of them were male,with an average age of 21.36±2.59 years.Before and in 4 weeks after training in the same subjects,their general information,blood and urine indicators,and electrocardiogram were collected.All data were statistically analyzed.Results The incidences of inflammatory reaction,myocardial injury,muscle injury,liver injury,and kidney injury were 45.76％,3.39％,12.71％,25.42％,and 12.71％,respectively,in the high temperature and high humidity environment group,which were all significantly higher than those in the conventional environment group(P＜0.05).The former group had an incidence rate of 6.78％,5.93％,8.47％,6.78％,and 2.54％,respectively,in sinus bradycardia,atrial premature beats,unspecific ST-T changes,left ventricular hypertension and short PR interval,and all of the rates were higher than those of the conventional environment group(P＜0.05).Conclusion The incidences of inflammatory reaction,myocardial injury,muscle injury,liver injury,kidney injury,and ECG abnormalities are more common in new recruits after military training in high temperature and high humidity environment.

This study explores the effects of enhancing the definitive hematopoiesis(DH)signals during the differentiation of human embryonic stem cells(hESCs)into hematopoietic stem/progenitor cells on the generation efficiency and effector function of natural killer(NK)cells generated from hESCs(also known as hESC-NK cells).The hESC(H1)were transformed into embryoid bodies(Ebs)by centrifugation,and during the induction of K562,were used to analyze the efficiency of hematopoietic differentiation,the efficiency of NK cell generation from hESC,the in vitro effector functions,and the expression of effector function related surface receptors.Compared to the control group,the DH group had a significant increase in the number of arterial hematopoietic endothelial cells(CD34+DLL4+)and a significant decrease in primitive hematopoietic related cells(CD34-CD43+)on day 8 of hematopoietic differentiation(P<0.05).On day 28 of NK cell differentiation,the DH group demonstrated a significant increase in the number of NK cells(CD45+CD56+),while a slight increase in the expression of effector function-related molecules such as IFN-γ,Granzyme B,Perforin and CD107a without statistical significance.Furthermore,the activation receptors CD16a and CD69 were significantly increased,NKP46 was significantly decreased,the inhibitory receptor NKG2A was significantly increased,while CD96 was significantly decreased on hESC-NK cells of DH groups(P<0.05).Conclusively,enhancing the signals for definitive hematopoiesis during hESC differentiation into hematopoietic stem/progenitor cells significantly improves the yield of NK cells and the expression of CD16a without affecting their in vitro effector functions.Our study provides a new approach to improving the efficiency of hESC-NK cell or iPSC-NK cell generation.

Objective:To develope and analyze and optimize the performance of some kinds of environmentally friendly flexible X-ray protective materials in attempt to tackle the various environmental and high energy consumption problems in the development of traditional medical X-ray protective clothing.Methods:The Monte Carlo program was used to establish a simplified model of medical X-ray tube. The aim was to carry out numerical simulation and prediction of the shielding materials′ performance against X-ray, prepare the flexible X-ray shielding materials through experiments and test and verify the their shielding performances The development and optimization path was also obtained by comparing the result between simulation and experiment.Results:Bi was the preferred alternative to toxic Pb elements, while W was able to compensate for weak X-ray absorption zone of Bi. The shielding efficiency of the composite material doped with 25% Bi+ 25% W was able to reach 77.8% and 66.3% at 80 and 120 kV p tube voltages, respectively. Conclusions:With both the selection of elements and the optimization of functional particles, the combination of W and Bi is an economical, environmentally friendly, and efficient shielding way within the energy range of medical diagnostic X-rays. The numerical simulation helps reduce experimental costs, shorten the research period, and improve the design efficiency of X-ray shielding materials.

Targeted protein degradation(TPD)has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell's endogenous protein degrada-tion machinery.However,the susceptibility of proteins for targeting by TPD approaches,termed"degradability",is largely unknown.Here,we developed a machine learning model,model-free anal-ysis of protein degradability(MAPD),to predict degradability from features intrinsic to protein tar-gets.MAPD shows accurate performance in predicting kinases that are degradable by TPD compounds[with an area under the precision-recall curve(AUPRC)of 0.759 and an area under the receiver operating characteristic curve(AUROC)of 0.775]and is likely generalizable to inde-pendent non-kinase proteins.We found five features with statistical significance to achieve optimal prediction,with ubiquitination potential being the most predictive.By structural modeling,we found that E2-accessible ubiquitination sites,but not lysine residues in general,are particularly associated with kinase degradability.Finally,we extended MAPD predictions to the entire proteome to find 964 disease-causing proteins(including proteins encoded by 278 cancer genes)that may be tractable to TPD drug development.

The interventional treatment of congenital heart diseases has been developed for more than 50 years since Rashkind et al.performed balloon atrial septostomy in 1966.From the initial catheter examination and palliative operation to the current radical occlusion, stent implantation, valve replacement, etc, interventional catheterization has become one of main means of treating congenital heart disease.The interventional therapy of congenital heart disease in China has made great progress, but there is still a certain gap with developed countries.This article summarizes the progress of interventional treatments in septal defect diseases, aortic artery to pulmonary artery shunt diseases, valvular diseases, and hybrid therapy, in order to provide reference for the interventional treatment of congenital heart disease in China.

Objective?To analyze the literature about the research situation and developmental trend of swallowing dysfunction nursing in China and to provide reference for further swallowing dysfunction nursing practice. Methods?Using blibiometric method and NoteExpress 2.0 soft-ware, we searched China National Knowledge Infrastructure (CNKI) database and Wan Fang database for swallowing dysfunction nursing related publications in China (from January 2000 to December 2016). Results?A total of 1 330 publications published have been searched out. The number of articles increased every year, and 814 (61.20%) articles were published in recent 5 years. The articles were mainly clinical trial research literature, accounting for 50.83%, followed by experience introduction and case report literature, accounting for 44.28%. These articles mainly focused on rehabilitation nursing and rehabilitation training. 96 articles were cited over 10 times, accounting for 7.22%, and the highest was cited for 135 times. 35 articles (2.63%) were funded by grants. Conclusions?Swallowing dysfunction nursing related articles have been increasing yearly, however, the contents and the objects needs to be expended. There is great space for the improvement in research depth, breadth and quality.