Objective:To explore the characteristics of blood amino acid and acylcarnitine profiles in children with unexplained generalized developmental delay (GDD)/intellectual disability (ID), and provide useful exploration for their early clinical identification.Methods:A total of 1 087 children with unexplained GDD/ID and 100 children with normal development who visited the Department of Pediatrics at Xiangya Hospital, Central South University from October 2015 to January 2021 were included as the study subjects. High performance liquid chromatography tandem mass spectrometry was used to detect 107 amino acids, carnitine, and base carnitine in dry blood filter paper. Unsupervised principal component analysis (PCA) was used to observe differences in metabolic profiles among different groups. Orthogonal partial least squares discriminant analysis (OLPS-DA) was used to distinguish inter group differences between different groups. Candidate differential metabolites were screened using VIP>1.0 and P<0.05 as criteria. Results:The GDD group screened 28 differential metabolites of blood amino acids and acylcarnitine, while the ID group screened 27 differential metabolites of blood amino acids and acylcarnitine, mainly involving pathways such as arginine biosynthesis, histone metabolism, arginine and proline metabolism.Conclusions:Differential metabolites such as glutamine in whole blood are of great significance for early identification of GDD/ID.

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.
Child ; Epilepsy/genetics* ; Female ; Humans ; Intellectual Disability/genetics* ; Male ; Muscle Hypotonia/complications* ; Mutation ; Phenotype ; Seizures/genetics* ; Strabismus/complications*

Myasthenia gravis (MG) is an autoimmune disease with neuromuscular junction (NMJ) transmission disorder mediated by various antibodies, dependent on cellular immunity, and involved in complement and cytokines. MG is one of the common diseases in pediatric neurology, which is different from adult MG in diagnosis and treatment. However, there is still a lack of accurate and efficient diagnosis and treatment plan for pediatric MG. In recent years, with the development of pathogenesis, targeted diagnosis and treatment of NMJ transmission disorders caused by immune network disorders in immunopathology and pathogenic antibodies is the current main research direction. This article reviews the progress of auxiliary examination and treatment of MG in children.

Objective:To develop a framework for a national system of elderly health standards in response to population aging in China and to meet the need for health service standards for elderly care, thus providing a roadmap for the development of elderly health standards.Methods:Preliminary indicators for a framework of a Chinese elderly health standards system were established by literature review and expert consultations.Using the Delphi method, we invited 23 experts to form a consultation panel.After two rounds of expert consultations, the preliminary framework was updated and the weight of each indicator was calculated by using the analytic hierarchy process.Results:A framework of the Chinese elderly health standards system was established after two rounds of expert consultations.The expert authority coefficient was 0.847.The framework proposed four primary indicators, including basic health standards, medical service standards, public health standards and social support standards, for the elderly, with a weight of 0.204, 0.346, 0.260 and 0.189 for each indicator.There were 22 secondary indicators, including standardized terminologies, medical services, health education, geriatrics personnel training, etc., for elderly care.Conclusions:Our research has generated a preliminary framework of an elderly health standards system that incorporates China's specific issues, takes into consideration of the needs of various parties and covers many relevant aspects.It will provide the basis for decision-making in the elderly health standardization process in China and safeguard the implementation of the Healthy China strategy.

Objective:To investigate the expression of intestinal alkaline phosphatase (IAP) in intestinal mucosa with bile deficiency and the effect of bile on the expression of IAP in intestinal epithelial Caco-2 cell model.Methods:Thirty healthy male SD rats were randomly divided into control group (Ctrl, n=10), external drainage group (ED, n=10) and obstructive jaundice group (OJ, n=10). Ileum specimens were collected on the 7th day after modeling. Western blot and immunohistochemical staining were used to determine the expression of IAP in rat intestinal mucosa. Different concentrations of human bile were used to treat on Caco-2 cells, and Western blot was used to detect the changes in IAP expression in Caco-2 cells. Results:Rat models were successfully established. The expression level of IAP in the intestinal mucosa of ED group [(9.19±1.67)%] was significantly lower than that of the Ctrl group [(15.09±0.61)%, P<0.05]; the expression of IAP in the intestinal mucosa of OJ group [(6.86±1.07)%] was significantly lower than that of the Ctrl group ( P<0.05). Through in vitro cell experiments, expression of IAP in Caco-2 cells was increased in a time and dose-dependent manner when treated with human bile. Conclusions:Bile deficiency in the intestine can cause inhibition of IAP in the intestinal mucosa. Bile can promote the expression of IAP in intestinal mucosal epithelial cells.

Objective:To investigate the role of multimodal neuronavigation intraoperative and sodium fluorescein-guided techniques in microsurgery for intracranial malignant neoplasm.Methods:A retrospective analysis was conducted on 50 patients with intracranial malignant tumors treated by microsurgery from 2016 to 2019 in Inner Mongolia People′s Hospital. Preoperative imaging included computed tomography (CT), computed tomographic angiography (CTA), magnetic resonance imaging (MRI), MRI: MRA, MRV, DWI, PWI, DTI, DTI, MRS sequence scan, and before the operation, they were fused with the functional nervous system navigation workstation of Bo Yilai to make the navigation plan. During the operation, the functional navigation was combined with low dose fluorescein sodium (2 mg/kg) for operation. Intraoperative neuronavigation was used to determine the location of the tumor and its spatial relationship with the pyramidal tract of the main fiber conduction tract and the large blood vessels, and intraoperative yellow fluorescence mode of pentero900 Zeiss microscope showed the boundary between the tumor and normal brain tissue for tumor resection.Results:There were 38 cases of glioma, 10 cases of brain metastasis of lung cancer, 1 case of brain metastasis of renal clear cell carcinoma and 1 case of spindle cell tumor. The accuracy of preoperative neuronavigation was 95%. Compared with the preoperative lesions, MRI of the head was reexamined 3 days after operation to judge the degree of tumor resection. In this group, 38 cases (76%) were totally resected and 12 cases (24%) were subtotal resected. The 6-month survival rate was 85.9%, the 12-month survival rate was 53.1%, the 18-month survival rate was 24.5%, and the survival time was (15.0 ± 3.2) months.Conclusion:Multimodal functional neuronavigation combined with fluorescein sodium staining can locate and label tumors in real time, improve tumor resection rate, and improve the prognosis of brain cancer patients.

To summarize the clinical characteristics and chest CT findings of coronavirus disease 2019(COVID-19)patients in Peking Union Medical College Hospital(PUMCH). A total of 13 patients with COVID-19 confirmed at PUMCH from January 20 to February 6,2020 were selected as the research subjects.Their epidemiological histories,clinical characteristics,laboratory tests,and chest CT findings were analyzed retrospectively.The location,distribution,density,and other accompanying signs of abnormal lung CT lesions were recorded,and the clinical types of these patients were assessed. The clinical type was "common type" in all these 13 patients aged(46.8±14.7)years(range:27-68 years).Ten patients had a travel history to Wuhan or direct contact with patients from Wuhan,2 cases had recent travel histories,and 1 case had a travel history to Beijing suburb.The white blood cell(WBC)count was normal or decreased in 92.3% of the patients and the lymphocyte count decreased in 15.4% of the patients.Twelve patients(92.3%)had a fever,among whom 11 patients were admitted due to fever and 2 patients(15.4%)had low fever.Eight patients(61.5%)had dry cough.The CT findings in these 13 patients were all abnormal.The lesions were mainly distributed along the bronchi and under the pleura.The lesions were relatively limited in 8 patients(affecting 1-3 lobes,predominantly in the right or left lower lobe),and diffuse multiple lesions of bilateral lungs were seen in 5 patients.The CT findings mainly included ground glass opacities(GGOs)(=10,76.9%),focal consolidation within GGOs(=7,53.8%),thickened vascular bundle passing through the lesions(=10,76.9%),bronchial wall thickening(=12,92.3%),air bronchogram(=10,76.9%),vacuole signs in the lesions(=7,53.8%),fine reticulation and interlobular septal thickening(=3,23.1%),reversed halo-sign(=2,15.4%),crazy-paving pattern(=2,15.4%),and pleural effusion(=2,15.4%). Most of our patients diagnosed with COVID-19 at PUMCH had a travel history to Wuhan or direct contact with patients from Wuhan.The first symptoms of COVID-19 mainly include fever and dry cough,along with normal or reduced counts of WBC and lymphocytes.CT may reveal that the lesions distribute along the bronchi and under the pleura;they are typically localized GGOs in the early stage but can become multiple GGOs and infiltrative consolidation in both lungs in the advanced stage.Scattered vacuole signs may be visible inside the lesions in some patients.
Adult ; Aged ; Betacoronavirus ; Coronavirus Infections ; diagnostic imaging ; Humans ; Lung ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVE： To establish a method for simultaneous determination of matrine， oxymatrine， gallic acid， peoniflorin， costunolide and dehydrocostus lactone in Libiling tablets. METHODS： RP-HPLC method was adopted. The determination was performed on Agilent ZORBAX SB-C18 column with mobile phase consisted of methanol-0.1％ phosphoric acid （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelengths were 210 nm （matrine， oxymatrine） and 225 nm （gallic acid， peoniflorin， costunolide， dehydrocostus lactone）. The column temperature was set at 30 ℃， and sample size was 5 μL. RESULTS： The linear ranges of matrine， oxymatrine， gallic acid， peoniflorin， costunolide， dehydrocostus lactone were 0.053-5.28 mg/mL（r＝0.999 8）， 0.125-12.54 mg/mL（r＝0.999 9）， 0.013-1.33 mg/mL（r＝0.999 8）， 0.169-16.94   mg/mL（r＝0.999 9）， 0.048-4.77 mg/mL（r＝0.999 8）， 0.072-7.16 mg/mL （r＝0.999 9）. The limits of quantitation were 4.08×10－4， 4.48×10－4， 3.12×10－4， 2.10×10－4， 1.36×10－4， 1.84×10－4 mg/mL， respectively. The limits of detection were 1.24×10－4， 1.50×10－4， 1.02×10－4， 6.20×10－5， 4.20×10－5， 6.40×10－5 mg/mL， respectively. RSDs of precision， stability and reproducibility tests were all lower than 2％ （n＝6）. The recoveries were 98.03％-101.43％ （RSD＝1.25％， n＝6）， 97.73％-102.26％ （RSD＝1.96％， n＝6）， 97.18％-101.41％ （RSD＝1.98％，n＝6）， 97.45％-102.11％ （RSD＝1.88％，n＝6）， 96.85％-101.07％ （RSD＝1.75％， n＝6）， 97.12％-102.64％ （RSD＝1.82％，n＝6）， respectively. CONCLUSIONS： Established method is simple， stable and rapid， and can be used for simultaneous determination of 6 components in Libiling tablets.

Objective According to the clinical and gene mutation characteristics of ACADVL-related very long chain acyl-CoA dehydrogenase deficiency(VLCADD),the types that contribute to the gene mutation of ACADVL were summarized.Methods By analyzing clinical,laboratory and genetic data of 1 case with ACADVL-related very long chain acyl-CoA dehydrogenase deficiency diagnosed from Department of Pediatrics,the Affiliated Hospital of Inner Mongolia Medical University in August 2016,based on the agreement signed by both the litde patient's parents and the hospital,plus the high-throughput sequencing analysis and PCR sequencing test for the 2 generation genes,some presented mutation sites were analyzed and concluded,in addition to taking "ACADVL" as key words to search the databases from CNKI,Wanfang(updated in 2016) as well as PubMed and related documents from On-line Mendal Inheritant databases of Man (OMIM) and HGMD.Results Through physical examination,VLCADD was diagnosed.After being given Levocamitine and the diet likemedium-chain fatty acid food for a week,the metabolism returned to normal.Tracking him for 3 months,his hepatitis obviously rebounded,within the reach of 3 cm under the right rib and 1 cm under the xiphoid.The exome sequencing study (trios) was identified the novel heterozygous mutation according to the statistics below A CAD VL (N M_000018.3) Exon7:c.608 C ＞ T;p.(Pro203 Leu) (heterozygous) and A CAD VL (NM _000018.3) Exon18:c.1748C ＞ T;p.(Ser583Leu) (heterozygous) in ACADVL.Relevant literature reported suggest these two mutations from both the parents are pathogenic genes,which can account for the reason why the boy got ill.However,these two mutations had not been reported in ACADVL-related VLCADD so far.Up to now,73 types of mutations from documents index were related to the VLCADD,but the clinical case included 75 kinds of gene mutations.Conclusions The apparent symptoms of the boy with the gene mutation were reflected in abnormal heart rates,hepatomegaly and hypoglycemia.VLCADD was diagnosed through genetic testing,and systematic treatment can partly control the development of the disease.In conclusion,the findings (exon 7 and 18) show that according to the genetic tests,disease-causing genes from both parents are new mutations of ACADVL and they are pathogenic.

OBJECTIVETo confirm a new allele HLA-B*13:01:06 and analyze its nucleotide sequence.

METHODSGenomic DNA was extracted using a Qiagen DNA extraction kit. Nucleotide sequences of HLA-A, HLA-B, HLA-C and HLA-DRB1 were analyzed by polymerase chain reaction-sequence based typing (PCR-SBT). HLA high-resolution results were assigned, and the nucleotide sequences of HLA-B locus was compared with that of HLA-B*13:01:01.

RESULTSThe nucleotide sequence of the new allele shows a strong similarity to that of HLA-B*13:01:01. One nucleotide in exon 2 has changed from G to A at position 219 (codon 49 GCG>GCA), which however did not result in amino acid change.

CONCLUSIONThe novel allele verified by sequencing has been submitted to GenBank and officially named as HLA-B*13:01:06 by the World Health Organization HLA Nomenclature Committee.

Alleles ; Amino Acid Sequence ; Base Sequence ; Exons ; HLA-B Antigens ; genetics ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Sequence Analysis, DNA