Objective:To summarize the clinical characteristics of children with dystonia 28 (DYT28) caused by KMT2B gene variations so as to improve clinicians′ understanding of the disease. Methods:The clinical manifestations, treatment and gene variation data of 11 children with DYT28 caused by KMT2B gene variations were retrospectively collected and analyzed.The subjects were recruited from the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from March 2018 to January 2021.The patients were followed up. Results:There were 8 males and 3 females.The age at onset was ranging from 1 month to 6 years without inducement.Eight cases were gene-ralized dystonia and 3 cases were multifocal dystonia.The initial symptoms of 7 cases were unilateral or bilateral lower limbs tiptoeing.Four cases presented dysarthria, retching or swallowing difficulties at onset.As the disease progressed, all the cases had laryngeal dystonia, 10 cases had lower limbs dystonia, and 8 cases had upper limbs dystonia.Six cases were complicated with other dyskinesia symptoms.Ten cases had varying degrees of short stature, microcephalus, micrognathia, musculoskeletal abnormalities, intellectual disability, endocrinopathies and sleep difficulties.The brain magnetic resonance imaging showed abnormal in only 1 case.Eleven KMT2B gene pathogenic variants were found, including 8 frameshift variants, 1 in-frame variant and 2 missense variants.Four variants were novel.Eleven cases were followed up at the age of 1 year and 7 months to 17 years and 9 months.One case wasn′t given therapy.The dystonia in 3 cases was mildly improved after medication.Dysfunction of urination and defecation was disappeared in 1 case after medication.The symptom of 6 cases had no improvement after drug therapy.Among the above 6 cases, 5 drug refractory cases had deep brain stimulation, and their dystonia symptoms are all obviously improved; 2 cases had normal control of urination and defecation after deep brain stimulation.The motor scores in the Burke-Fahn-Marsden dystonia rating scale were improved by 55.8%-90.7%, and the disability scores were improved by 14.8%-69.6%. Conclusions:DYT28 caused by KMT2B gene variations is one of the most common and early-onset genetic dystonia in children.The dystonia symptom progresses from local parts to the whole body, prominently involving laryngeal muscles and lower limbs.Control of urination and defecation requires attention.Patients with mild dystonia symptoms can be effectively treated by drugs.However, patients with severe dystonia symptoms were drug refractory, and their dystonia symptoms can be effectively improved by deep brain stimulation.

Objective:To explore the current status of mental workload and its relationship with work engagement and fatigue, as well as the impact path among the three.Methods:Clinical nurses from six tertiary hospitals including Shanghai Traditional Chinese Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, etc. were selected to conduct a cross-sectional survey using convenience sampling method from February to March 2020. They were investigated by general information questionnaire, NASA Task Load Index (NASA-TLX), Utrecht Work Engagement Scale (UWES), and Fatigue Scale-14 (FS-14).Results:The total mental workload score of 776 clinical nurses was 76.50(69.00, 84.00). Single factor analysis showed that clinical nurses of different ages, marriage and childbirth status, education level, professional title and working years had different mental workload ( Z = -2.61, H values were 10.22-22.41, all P<0.01). Bivariate analysis revealed that the mental workload of clinical nurses was positively correlated with work engagement ( r = 0.27, P<0.01) and fatigue ( r = 0.23, P<0.01), and work engagement and fatigue were negatively correlated ( r = -0.23, P<0.01). Mediation effect analysis demonstrated that mental workload had a positive predictive effect on fatigue ( β = 0.39, P<0.01) and work engagement ( β = 0.35, P<0.01); the suppressing effect of work engagement between mental workload and fatigue, the absolute value of the ratio of the suppressing effect to the direct effect was |-0.17/0.39|. Conclusions:The mental workload of clinical nurses is at relatively high level. Hospital administrators can partially improve the fatigue state of clinical nurses with high mental load through the adjustment effect of work engagement.

Objective:To investigate the clinical effects of anterior cage inserting for old thoracolumbar fractures with kyphosis through facet joint approach.Methods:A retrospective analysis was conducted on 32 patients with old thoracolumbar fractures complicated with kyphosis admitted from January 2018 to December 2019, including 14 males and 18 females. The average age was 47.3±13.1 years (range, 26-70 years). Thoracolumbar injury classification (TLICS) scores of patients with initial injury were 3-5 points, with an average of 4.0 points. After 6.3±2.9 months (range, 3-16 months) conservative treatment, intractable thorax and lumbar or back pain still existed. Anterior cage inserting via articular protrusion was performed in 15 cases and posterior screw placement and bone grafting fusion of injured vertebrae was performed in 17 cases. Preoperative sagittal Cobb angle was 27.0°±3.9° and 26.8°±4.6° in the anterior cage inserting group and fixation on fractured vertebrae group ( t=0.07, P=0.946), respectively. Sagittal vertical axis (SVA) was 4.2±1.8 cm and 4.1±2.1 cm ( t=0.14, P=0.887), respectively. The number of patients with ASIA impairment scale (AIS) of the anterior cage inserting group before surgery was 1 in grade C, 4 in grade D and 10 in grade E. However, the number of that in fixation on fractured vertebrae group was 2 in grade C, 2 in grade D and 13 in grade E. There was no significant difference between the two groups (χ 2=1.34, P=0.520). Results:All 32 patients were followed up for 12.2±3.1 months in the anterior cage inserting group and 12.0±3.3 months in fixation on fractured vertebrae group. The operative duration of the anterior cage inserting group and fixation on fractured vertebrae was 128±24.5 min and 123±40.6 min ( t=0.42, P=0.681). The intraoperative blood loss was 485±12.6 ml and 478±16.3 ml ( t=0.13, P=0.894), respectively. At the last follow-up, the improvement rate of VAS score of the anterior cage inserting group was higher than that of fixation on fractured vertebrae group (90%±10% vs. 75%±20%, t=3.17, P=0.004). The height of anterior margin of injured vertebra in the two groups was increased by 1.02±0.10 cm and 0.29±0.14 cm, the change rate of anterior cage inserting group was higher than that of fixation on fractured vertebrae group (67.1%±31.5% vs. 19.0%±14.9%, t=16.29, P<0.001). The sagittal Cobb angle of the anterior cage inserting group was significantly lower than that of fixation on fractured vertebrae group (7.4°±1.5° vs. 11.6°±2.5°, t=-5.85, P<0.001). The SVA of anterior cage inserting group was lower than that of fixation on fractured vertebrae group (1.1±0.6 cm vs. 1.6±0.6 cm, t=2.35, P=0.025). There were 15 patients in AIS grade E in the anterior cage inserting group, while 1 patient in grade D and 16 patients in grade E in fixation on fractured vertebrae group without significant difference between the two groups (χ 2=0.83, P=0.706). Conclusion:The treatment of old thoracolumbar fractures with kyphosis through facet joint approach and anterior fixation could achieve satisfied effects and could relieve pain symptoms of thoracolumbar and back, compared with posterior fusion for injured vertebra with nail and bone grafting.

Objective:To explore the effect of pre-rehabilitation on postoperative recovery of patients undergoing elective cardiac surgery through Meta-analysis.Methods:Randomized controlled trials of pre-rehabilitation in patients undergoing elective cardiac surgery were retrieved by computer in PubMed, Web of Science, Cochrane Library, Embase, Medline, China National Knowledge Infrastructure (CNKI) , Wanfang Data, VIP and China Biomedical Literature Database. The retrieval time limit was from the establishment of the database to January 1, 2021. Two reviewers independently conducted literature screening, data extraction and literature quality evaluation according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4.Results:A total of 13 articles were included, including 1 542 subjects. Meta-analysis results showed that preoperative rehabilitation had positive effects on reducing postoperative complications in patients undergoing elective cardiac surgery [ Z=4.79, RR=0.57, 95% CI (0.45, 0.72) , P<0.01], and increasing the distance of 6-minute walking test [ Z=5.21, SMD=0.51, 95% CI (0.32, 0.70) , P<0.01] and maximum inspiratory pressure [ Z=4.16, SMD=0.76, 95% CI (0.40, 1.12) , P<0.01]. Conclusions:Pre-rehabilitation can effectively reduce the incidence of postoperative complications in patients undergoing elective cardiac surgery, and increase the postoperative 6-minute walking test distance and maximum inspiratory pressure.

Objective:To summarize the clinical characteristics and genetic features of tyrosine hydroxylase deficiency(THD) caused by TH gene variants for the improvement of the understanding of the disease. Methods:The clinical and genetic data of 33 children with THD caused by TH gene variants were diagnosed in the Department of Neurology of Beijing Children′s Hospital, Capital Medical University from May 2011 to January 2020 and their data were retrospectively collected and analyzed. Results:There were 19 females and 14 males.The age at onset was ranged from 0 to 6.3 years.13 patients developed diseases, accompanied with fever after infection, and 1 patient suffered from hypoxia, 19 patients suffered from no predisposing factors.There were 7 mild TH-deficient dopa-responsive dystonia cases, 16 severe TH-deficient infantile parkinsonism with motor delay cases and 10 very severe TH-deficient progressive infantile encephalopathy cases.Clinical symptoms were fluctuating, including 26 cases of diurnal fluctuation, 22 cases of infection aggravation, and 30 cases of fatigue aggravation.The initial symptoms included tiptoeing and numbness in the limbs(7 cases), motor development retardation or degression (26 cases), fremitus (8 cases), ptosis (2 cases), and status dystonicus (3 cases). Other clinical features had hypermyotonia (23 cases), hypomyotonia (27 cases), decreased movement (27 cases), decreased facial expression (24 cases), fremitus (18 cases), tiptoeing (20 cases), talipes equinovarus (7 cases), ptosis (8 cases), oculogyric crisis (10 cases), salivation (21 cases), dysphagia (12 cases), dysarthria (16 cases), dyspnea (3 cases), increased sleep (10 cases), decreased sleep (5 cases), irritable mood (15 cases), apathetic mood (2 cases), profuse sweating (8 cases), and status dystonicus (6 cases). A total of 6 patients′ right limbs were more severe, and 14 patients′ lower limbs were more severe.Eight patients had family history, and Levodopa treatment was effective for all patients.Ten patients suffered side effects, including dyskinesia and irritability.Four patients were lost follow-up, and 29 patients were followed up between 0.8 and 13.2 years old until Ja-nuary 2020.Totally, 22 patients almost had no such symptoms.Twenty-five TH gene pathogenic variants were discovered in 33 patients.There were 13 novel variants (c.1160T>C, c.1303T>C, c.887G>A, c.1084G>A, c.1097A>T, c.734G>T, c.907C>G, c.588G>T, c.992T>G, c.755G>A, c.184-6C>T, c.1510C>T, c.910G>A) and 2 patients had c. 910G>A variant.Meanwhile, there were 5 hot variants [c.698G>A(13 cases), c.457C>T(9 cases), c.739G>A(6 cases), c.1481C>T(4 cases), c.694C>T(3 cases)]. c.910G>A(2 cases) may be the foun-der variant of Chinese population. Conclusions:THD caused by TH gene variant mostly onsets from infant, with complex clinical features.Most of these patients were severe, and only a few were very severe and mild.Very severe and mild symptoms were easily misdiagnosed.Levodopa treatment was obviously effective.A possible founder variant of Chinese population (c.910G>A) was found.c.698G>A and c. 457C>T mutations mainly appeared in patients with severe and extremely severe THD, while c. 739G>A mainly appeared in patients with mild THD.

Objective:In the teaching practice based on "Internet+", there are relatively few studies on the transformation of learners' learning styles. This paper focuses on the practical factors that may affect the change of students' learning style in the teaching process of blended learning.Methods:Taking students from Batch 2017 of Inner Mongolia Medical University as the teaching objects who taught by blended learning, by means of questionnaire survey, interview, course performance analysis and other methods, this paper discusses the influence of students' learning style on learning effect and possible influencing factors in the process of blended learning.Results:In the process of teaching, students' learning styles have a profound impact on the learning effect to some extent. Therefore, the subjective and objective factors that affect students' learning style should be paid attention to.Conclusion:With the popularization of "Internet + education", the ways and environment of traditional education have undergone great changes. In the process of blended learning reform, teachers should pay more attention to learning styles of students, so as to better improve the teaching effect.

Objective To investigate the clinical characteristics of paraneoplastic syndrome with prominent osteoarticular involvement. Methods The clinical materials of 20 patients with paraneoplastic syndrome with prominent osteoarticular involvement were collected. The characteristics of clinical manifest-ations, laboratory tests and imagines were analyzed. Results Among the 20 patients, 16 were male and 4 were female, with a mean age of 44.5 years and a median course of 6 months. Ten cases were associated with hematological tumor and 10 cases were associated with solid tumor. Eleven cases presented as peripheral arthritis (7 cases of polyarthritis, 4 cases of oligoarthritis/monoarthritis), 5 cases presented with hypertrophic osteoarthropathy (HOA) and 4 cases presented with tumor-induced osteomalacia (TIO). Three cases were acute lymphocytic leukemia, 2 cases were multiple myeloma, 1 case was lymphoma, and 1 case was bone tumor in polyarthritis. Four oligoarthritis cases were all associated with acute lymphocytic leukemia. All 5 cases of HOA were associated with lung cancer. All 4 cases of TIO were associated with tumor of mesenchymal tissue. Extra-articular manifestations presented in 14 cases and inflammatory markers increased in 15 cases. anti-cyclic cirullinated peptide (anti-CCP) antibodies was low titer positive in only 1 case and other parameters including rheumatoid factor (RF), anti-CCP antibodies, antinuclear antibodies spectrum (ANAs) and human leukocyte antigen (HLA)-B27 were negative. Multiple bone imaging abnormalities appeared in 15 cases. Conclusion Osteoarticular manifestations may be the first symptom of malignancy and difficult to diagnose. It is necessary to be highly aware of potential malignancy.

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.

Objective: To investigate the clinical features and diagnostic bases of childhood leukoencephalopathy with cerebral calcifications and cysts (LCC). Methods: The clinical data involving manifestations and laboratory examinations of 4 children with LCC admitted to Beijing Children's Hospital Affiliated to Capital Medical University from 2012 to 2017 were retrospectively summarized. Each patient had a follow-up visit ranging from 4 months to 5 years and 9 months after initial examination. Results: Patients consisted of 2 males and 2 females, whose age of onset was respectively 2 years and 9 months, 6 years and 2 months, 7 years and 10 months, and 5 years and 1 month. The main clinical symptoms of these cases included headache, dizziness, partial seizure and claudication, and two of these cases had insidious onset. Cerebral calcifications and cysts with leukoencephalopathy were detected by neuroimaging in all patients. In addition, multifocal microhemorrhages and calcifications were observed by magnetic susceptibility-weighted imaging (SWI) series in 3 patients. Brain biopsy performed on 1 case disclosed a neuronal reduction in the cerebral cortex, loosening of focal white matter, multifocal lymphocyte infiltration, fresh hemorrhages, and gliosis, as well as angiomatous changes of blood vessels with hyalinized thicken-wall, stenotic or occlusive lumina and calcification deposits. The compound heterozygous mutations of n.*10G>A and n.82A>G in SNORD118 were identified in 1 case by target-capture next-generation sequencing. Sanger sequencing verified that the variant n.*10G>A was a novel mutation and it was of paternal-origin, while the variant n.82A>G was of maternal-origin, which had already been reported to be pathogenic to LCC. Follow-up study had shown continued partial seizure in 1 case and remissive claudication in another, while the remaining 2 cases had a relatively favorable outcome without obvious neurological symptoms at present time. Conclusions The clinical manifestations of LCC are nonspecific, and the onset of the disease tends to be insidious. The triad neuroimaging findings of cerebral calcifications, cysts and leukoencephalopathy are essential to the diagnosis of the disease, and the signals of microhemorrhages revealed by SWI series provide another eloquent reference for the diagnosis. As biopsy is invasive and usually unavailable in the early stage, gene assessment, instead of pathological data, should be the gold standard in the diagnosis of LCC.

Objective: To summarize the detailed clinical characteristics and genetic features of benign infantile epilepsy with PRRT2 mutation, in order to improve the understanding of the disease. Methods: The clinical data and genetic results of 40 benign infantile epilepsy patients with PRRT2 mutation who were diagnosed and treated in the neurology department of National Center for Children's Health (Beijing) , Beijing Children's Hospital affiliated to Capital Medical University from January 2002 to October 2017 and their affected family members were analyzed. Results: Forty benign infantile epilepsy patients were recruited for this study, with 18 males and 22 females. The age at onset ranged from 3 to 15 months (median: 4.6 months). All patients presented focal seizures with or without secondary generalization. Decreased responsiveness, eyes stare and cyanosis were commonly observed. A cluster of seizures was observed in 20 patients at the beginning of the disease, but interictal clinical conditions were normal. Interictal electroencephalograms were normal in 32 cases but 8 cases showed small amount scattered spike and spike wave. Two patients developed paroxysmal kinesigenic dyskinesia in 30 months and 12 years respectively after the cessation of the seizure. Thirty-four affected pedigree members had a history of paroxysmal episodes in 24 families, including 19 individuals of infantile afebrile convulsion, 6 individuals of paroxysmal kinesigenic dyskinesia during childhood or adulthood, 8 individuals of infantile convulsion and paroxysmal kinesigenic dyskinesia during adulthood, one individual of infantile febrile convulsion. The follow-up time ranged from 6 months to 15 years. Thirty-six patients were treated with antiepileptic drugs and their seizures were easy to control. Four patients stayed seizure free without medication (all <2 years). Seizure stopped in 24 patients within 1 year of age, in 10 patients stopped during 12-24 months and in 2 patients stopped during 24-36 months. All cases had PRRT2 mutations, 7 cases of a complete PRRT2 deletion, 33 cases of PRRT2 heterozygous mutations consisted of 28 frameshift mutations and 5 missense mutations. Of these heterozygous mutations, 30 cases were hereditary mutations while 3 were de novo mutations. Nine family members harbored the same PRRT2 mutations without any symptom. Conclusions Benign infantile epilepsy with PRRT2 mutation is characterized by early onset of seizure mostly before 6 months, focal seizures with or without secondary generalization, a high incidence of a cluster of seizures, rapid resolution of seizure by antiepileptic drugs and cessation of seizure mostly before 2 years of age. Partial patients may develop paroxysmal kinesigenic dyskinesia increasing with age. Most PRRT2 gene mutations are heterozygous mutations, and a few are the overall deletion of PRRT2 gene.