Objective:To explore the effect of post-pyloric feeding by spiral nasoenteric tubes on the prognosis of critically ill patients with acute gastrointestinal injury (AGI) grade Ⅱ.Methods:A retrospective study was performed to analyze the clinical data of critically ill adult patients with AGI grade Ⅱ, who were enrolled in three randomized controlled trials conducted by Guangdong Provincial People's Hospital for post-pyloric tube placement between April 2012 and May 2019. Data including demographic characteristics, serological indicators of nutrition, the tube tip position confirmed by abdominal X-ray 24 h after tube insertion, and intensive care unit (ICU), 28-day and hospital mortality were collected. Patients were divided into the post-pyloric feeding group and gastric feeding group according to the tube tip position. Propensity score matching method was used to perform 1:1 matching, and the differences of each index between the two groups were compared after matching. Then the influencing factors of P<0.1 were included in multivariate logistic regression analysis to investigate the potential ICU mortality risk factors of critically ill patients with AGI gradeⅡ. Factors with 0.1 level of significance from the univariate analysis were considered in the multivariate analysis. Results:There were 90 patients in post-pyloric feeding group and 90 patients in the gastric feeding group. Demographics and clinical characteristics of study population were well balanced between the two groups after matching. ICU, 28-day and hospital mortality in the post-pyloric feeding group were significantly lower than those in the gastric feeding group (4.4% vs 15.6%, 14.4% vs 27.8%, 6.7% vs 17.8%, all P < 0.05). Multivariate logistic regression analysis indicated that post-pyloric feeding was an independent protective factor [odds ratio ( OR)=0.295, 95% confidence internal (95% CI): 0.091-0.959, P=0.042] and APACHEⅡ score was an independent risk factor ( OR=1.111, 95% CI: 1.025-1.203, P=0.010) for ICU mortality of critically ill patients with AGI gradeⅡ. Conclusions:Post-pyloric feeding for critically ill patients with AGI grade Ⅱ could decrease ICU mortality and is an independent protective factor against mortality.

Characterized by impaired neuromuscular transmission, congenital myasthenic syndromes (CMS) are a group of genetic disorders.The main manifestations include fatigue and weakness of skeletal muscle, with most onset in infant or early childhood.The common cause of death is respiratory failure, with high disability rate.With the improvement of gene sequencing technology and the in-depth study on the structure and function of pathogenic proteins, the pathogenesis of the disease has been deeply understood in the past 20 years.Early diagnosis and treatment can significantly improve the symptoms in patients.In this manuscript, the etiology, clinical characteristics, diagnosis and treatment of CMS are reviewed.

Objective:To explore the phenotypes and genotypes of molybdenum cofactor deficiency type B (MoCD-B) manifested as Leigh-like syndrome.Methods:The clinical data, laboratory tests, neuroimaging and gene results of one patient diagnosed as MoCD-B at Beijing Children′s Hospital and Hebei Children′s Hospital in December 2018 were collected. Related literature was searched and reviewed at Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed (up to September 2020) by using terms "MOCS2" "molybdenum cofactor deficiency" "Leigh-like syndrome,MOCS2" "molybdenum cofactor deficiency, Leigh-like syndrome". The phenotypes and genotypes of MoCD-B were summarized.Results:A 7 months and 14 days old boy with the chief complaint of "cough for 6 days, abnormal posture for 4 days and fever for 2 days" was admitted to Hebei Children′ Hospital on December 2018. His abnormal posture presented as opisthotonos accompanied with dysphagia, without seizures. His previous psychomotor development was described as normal. He was born at term after an uneventful pregnancy to non-consanguineous parents. Blood test showed a slightly increased lactic acid and a significantly decreased uric acid. Urine metabolism test showed an obviously increased xanthine and hypoxanthine. Brain magnetic resonance imaging showed hyperintense signal on T2 weighted image and fluid attenuated inversion recovery in bilateral globus pallidus and pedunculus cerebri. The patient was diagnosed with Leigh-like syndrome. No obvious improvement was achieved after cocktail therapy and symptomatic treatment. The whole exome sequencing showed that the patient carried a homozygous variant of MOCS2 gene, c.19G>T(p.Val7Phe), which was a previously reported pathogenic site in the literature and could cause MoCD-B. His parents carried a heterozygous variant respectively. A total of 41 MoCD-B cases with MOCS2 gene variants were collected through literature review and our study, among which 30 cases had full medical records. The onset ages of 23 (77%) cases were in neonate, manifesting with severe encephalopathy, including neonatal-onset intractable seizures, developmental delay, laboratory abnormalities included very low levels of serum and urinary uric acid, increased urinary levels of xanthine and hypoxanthine. Cranial imaging showed cerebral atrophy, cystic encephalomalacia, etc. The onset ages of 7 patients varied from 5 months to 23 years. Four cases had normal psychomotor development before disease onset. Neurological disorders appeared acutely or exacerbated after external triggers and all of them had basal ganglia involvement. Among the 30 cases, 3 cases had a relatively milder phenotype with the ability of brief communication and walking without or with support.Conclusions:Molybdenum cofactor deficiency is a rare disease. Most cases had severe phenotypes and poor outcomes, but some cases may have mild phenotype. MoCD-B caused by MOCS2 gene variants may manifest as Leigh-like syndrome with a normal psychomotor development before the trigger of infection strike. Hypouricemia, xanthinuria and hypoxanthinuria can be indicators of the disease. The presence of MOCS2 gene variants would confirm a final diagnosis.

Objective: To investigate the clinical significance of different samples (the peripheral blood, urine and skeletal muscle) that could be detected the large-scale single deletions directly by using next-generation sequencing in the diagnosis of Kearns-Sayre syndrome (KSS) by concluding the clinical and genetic features of KSS, in order to explore a non-invasive method for diagnosis. Methods: The clinical data, skeletal muscle′s pathology and enzymology and genetic results of individuals with KSS, who were hospitalized from October 2016 to October 2017 in Department of Neurology, Beijing Children′s Hospital, Capital Medical University, were collected.The gene tests were performed by using next generation sequencing technology and long-PCR technology of mitochondrial DNA(mtDNA) and the whole exon in the peripheral blood, urine and skeletal muscle. Results: Four patients were all consistent with the diagnosis criteria of KSS, among whom the age of onset was 8.2 years old on average, and the initial symptoms were statue, ptosis, headache and vomiting, and visual impairment.The common symptoms of the 4 cases were ophthalmoplegia, exercise intolerance, development delay, loss of appetite, hypotonia, muscle weakness, with cerebrospinal fluid protein concentration over 1 000 mg/L, the cerebral magnetic resonance imaging showed that abnormal signals in the brainstem, in addition, white matter, thalamus, basal ganglia, cerebrum and cerebellum atrophy could be found.Moreover, 3 cases had cardiac conduction block.Two cases had maternal family history.Molecular analysis of the 4 cases revealed the large-scale single deletions of mtDNA from the peripheral blood, the urine, the skeletal muscle through the next-generation sequencing, which were m. 6460-15590(9 131 bp del), m.8482-13446(4 964 bp del), m.6831-14981(8 151 bp del), m.7983-15495(7 513 bp del), respectively.Among 3 cases who did pedigree analysis, only the mother of case 4 was detected with the same variation of the proband. Conclusions KSS is a rare mitochondrial disease, which could be detected with the single large scale mtDNA deletions in the peripheral blood, urine and skeletal muscle.With the development of the methodology, the diagnosis of KSS maybe no longer than depends on the muscle biopsy with the next-generation sequencing.And the possibility to get the positive results in the peripheral blood and urine by the non-invasive method could improve the molecular diagnosis of KSS.

Objective: To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods: Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children′s Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ² test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results: Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic-clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged-red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex Ⅰ deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m.3243A>G variants, 6 cases had m.8344A>G variants, and 3 cases had m.8993T>G/C variants, m.3271T>C, m.3481G>A, m.3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complex Ⅰ were in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty-three patients were followed up, and the follow-up time was 20 (3-84) months. According to the follow-up results, the anti-epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group (t=1.662, 0.860; P=0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non-first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ²=2.794, 0.164, 3.380; P=0.095, 0.686, 0.066). Conclusions The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic-clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.

Objective To explore the phenotype and genotype of mitochondrial DNA depletion syndromes (MDS) in Chinese children.Methods The clinical and genetic data of 12 MDS patients (8 were boys and 4 were girls) diagnosed in the Department of Neurology in Beijing Children's Hospital,Capital Medical University from October 2010 to April 2018 were retrospectively collected and analyzed.Results The developmental milestones were normal or mildly retardated before disease onset.The age of onset ranged from 0 to 2.9-year-old.Most cases developed postnatal or after infection.The most common initial symptoms were feeding difficulty,seizure,muscle weakness,psychomotor regression and hepatic dysfunction.At the last evaluation,all the patients had developmental retardation,failure to thrive,muscle weakness,and dysphagia.Other clinical features were weight loss (9 cases),hearing impairment (7 cases),ptosis (6 cases),seizure (5 cases),dyspnea (4 cases),visual impairment (1 case),hirsutism (1 case),lactic acidosis (7 cases),elevated hepatic enzymes (4 cases) and creatine kinase (2 cases),elevated protein in cerebrospinal fluid (3 cases),abnormalities on screening for inborn error of metabolism (10 cases) and brain magnetic resonance imaging (MRI) (10 cases),abnormal electromyogram (including neurogenic or myogenic injury) (5 cases).Five patients died of infection or multiple organ failure.A total of 18 novel mutations presented below were detected in these patients.Among the 6 cases of encephalomyopathy,there were 3 with SUCLG1 mutation (c.916G＞T,c.619T＞C,c.980dupT were novel),2 with SUCLA2 mutation (c.851G＞A,c.971G＞A were novel),and one with RRM2B mutation (c.456-2A＞G,c.212T＞C were novel).All the cases of hepatic encephalopathy all had POLG mutations (c.3151G＞A,c.2294C＞T,c.2858G＞C,c.680G＞A and c.150_158delGCAGCAGCA were novel).Two cases of infantile-onset spinocerebellar ataxia had TWNK mutations (c.1163C＞T,c.1319T＞C,c.1388G＞A and e.257_258delAG were novel).One case of myopathy had TK2 mutations (c.557C＞G and c.341A＞T were novel).Conclusions The clinical and genetic features of MDS were heterogeneous.Eighteen novel mutations in six MDS related genes were reported,which expanded the genetic spectrum of MDS in Chinese children.

To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children's Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ2 test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic?clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke?like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged?red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex Ⅰ deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m. 3243A>G variants, 6 cases had m. 8344A>G variants, and 3 cases had m. 8993T>G/C variants, m. 3271T>C, m. 3481G>A, m. 3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complexⅠwere in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty?three patients were followed up, and the follow?up time was 20 (3-84) months. According to the follow?up results, the anti?epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group (t=1.662, 0.860; P=0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non?first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ2 =2.794, 0.164, 3.380; P=0.095, 0.686, 0.066). Conclusions The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic?clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.

Objective To explore the effect of social relationship quality intervention on blood pressure and mental state of patients after hypertensive hemorrhage. Methods From November 2014 to March 2016,48 patients with hypertensive intracerebral hemorrhage were assigned as control group and another 48 patients with the same disease in our hospitalfrom April 2016 to August 2017 as observation group:The former received routine nursing care and the latter was treated with social relationship quality intervention plus the routine nursing care.The blood pressure and mental states before intervention were compared with those 1 month after intervention. Result After intervention,the systolic and diastolic blood pressures in the observation group were significantly lower than those in the control group,and the scores on resilience,optimism and strength were all significantly higher than those in the control group (P<0.01, P<0.001). Conclusions The social relationship quality intervention is effective in the care to patients with hypertensive cerebral hemorrhage. It can effectively improve the clinical efficacy, reduce blood pressure and improve mental state, worthy of clinical application and promotion.

Objective To investigate the clinical and genetic features of congenital myasthenia syndrome with episodic apnea (CMS-EA) caused by gene mutation of choline acetyltransferase (CHAT)Methods The clinical data of 2 patients with congenital myasthenia syndrome were collected,and both were diagnosed from 2013 to 2015 in Beijing Children's Hospital,Capital Medical University.The clinical features and gene mutation characteristics were analyzed,and the patients were followed-up for therapeutic efficacy.Results The two patients (case 1 and case 2) had the onset soon after birth and at 3 months after birth respectively.The two patients were admitted to the PICU due to dyspnea,cyanotic episodes that required intubation.The patients had repeated apnea and became ventilator dependent.Case 1 died due to refusal of any treatment.Case 2 had a tracheotomy,and gradually weaned from ventilator after using pyridostigmine.The hospitalization of case 2 lasted 162 days.Case 2 was followed up to the age of 3 years and 4 months,and was extubated and was maintained on oral neostigmine but still had fluctuating ptosis and minor physical and mental retardation.Both cases were negative for anti-AChR,anti-acetylcholinesterase,anti-MuSK antibodies.Neostigmine test was negative in case 1 and suspiciously positive in case 2.Low-frequency repetitive nerve stimulation testing of case 2 was negative.Cranial MRI scans of both cases showed brain atrophy-like change.Genetic testing showed compound heterozygous deletions (exon 4,5,6) and pathogenic variant c.914T＞C (p.I305T) in CHAT in case 1,compound heterozygous variants c.1007T＞C (p.I336T) and c.64C＞T (p.Q22X) in CHAT in case 2.To our knowledge,compound heterozygous deletions (exon 4,5,6) and p.Q22X were novel,previously unreported variants.Conclusion CMS-EA usually presents at birth or in the neonatal period with hypotonia,ptosis,dysphagia due to severe bulbar weakness,and respiratory insufficiency with cyanosis and apnea.Early treatment with pyridostigmine is helpful to the improvement of clinical symptoms and prognosis.

Objective: To investigate the clinically and genetic characteristics of children with Leigh syndrome. Method: Patients with clinically diagnosed Leigh syndrome(LS)in the department of Neurology, Beijing Children′s Hospital from January 2013 to February 2016 underwent the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) detecting with next generation sequencing (NGS) technology. The clinical data of gene confirmed cases were retrospectively collected and analyzed. The differences in the onset age, clinical manifestations, lactic acid level and MRI results between the mtDNA variation and nDNA variation were compared and analyzed.t test, Chi-square test and Fisher′s exact test were used for statistical analysis. Result: Thirty-five cases were diagnosed by gene detection, including 20 males and 15 females. The median onset age was 1 year (ranging from the neonatal period to 4.4 years old). The age of onset within 2 years accounted for 74%(26 cases). The onset age of initial symptoms, including developmental delay, developmental regression, and seizures, were 6 (4, 12) months, 12 (8, 14) months, and 6 (1, 23) months respectively. The onset age of ptosis, extrapyramidal symptoms and ataxia were 26 (18, 44) months, 28 (23, 40) months and 28 (19, 35) months, respectively. There were significant differences in the onset age between the three groups (H=21.919, P=0.01). Within the 35 cases, 29 were manifested with developmental delay (83%), 26 with dystonia (74%), 18 with growth retardation, 15 with myasthenia, 13 with developmental regression, 11 with dysphagia, 10 with feeding difficulties, 4 with skeletal dysplasia, and 2 with digestive tract symptoms; nystagmus and respiratory abnormalities were observed in 9 cases respectively; extrapyramidal symptoms, peripheral nerve injury, ptosis, seizures were observed in 8 cases respectively; and ataxia, ophthalmoplegia and hypertrichiasis were found in 5 cases respectively.The blood lactic acid was measured in 32 LS patients, within which 23 cases (72%) had increased results; 8 out of 11 cases who underwent were cerebrospinal fluid lactic acid test had increased results. The results of neuroimaging revealed that all the patients were involved in the brainstem and (or) basal ganglia, of whom 27 (77%) had brainstem involvement, 24 (69%) had basal ganglia involvement. Thirteen out of 14 patients who had medulla oblongata involvement had nDNA variation; while 7 out of 8 patients with cerebellar involvement had nDNA variation. Genetic etiology was confirmed in all patients, among whom there were 17 cases (49%) with mtDNA mutation, including 8993T>C/G (n=5), 14487T>C (n=4), 13513G>A (n=2), 9176T>C, 10158T>C, 3697G>A, 10191T>C, 14459A>G and 11777C>A (n=1) respectively. Remaining 18 cases(51%) had nDNA mutation, including SURF1 gene(n=10), PDHA1 gene(n=3) and one case each of NDUFV1, NDUFAF6, NDUFAF5, NDUFS1 and COQ7 genes. In this study, 27 types of mutations were founded, 15 of which had not been previously reported. Respiratory chain gene mutations have been found in 31 cases(89%); 3 cases had PDHc gene mutations, and 1 case had other mutation. Conclusion LS usually occurs in infants. The most common primary symptoms are age-dependent abnormal movements, ocular symptoms, and seizures. Respiratory chain defects is the most common causes of LS.SURF1 is the most common variation, followed by 8993T>C/G, 14487 T>C and 13513G>A mutation.