{L-End}Objective To investigate the influencing factors of work-related musculoskeletal disorders (WMSDs) that affect neck-shoulder-back among manufacturing workers. {L-End}Methods A total of 8 250 front-line workers from 27 manufacturing enterprises in Henan Province and Hubei Province were selected as the research subjects using cluster sampling method. The Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of neck-shoulder-back (include neck, shoulder, upper back, and lower back) WMSDs in the past year. The log-binomial model, principal component analysis (PCA) and multivariate logistic regression analysis were used to analyze the influencing factors of WMSDs in the neck-shoulder-back. {L-End}Results The prevalence of WMSDs was 77.2%. The prevalence of neck-shoulder-back WMSDs was 50.9%. The prevalence ratios of WMSDs were relatively higher among the neck, shoulder, and upper back (all P<0.05). The results of PCA improved logistic regression analysis showed that the influencing factors of neck-shoulder-back WMSDs were individual factors, biomechanical factors, psychosocial factors and environmental factors. In terms of individual factors, the risk of neck-shoulder-back WMSDs was higher in females than in males (P<0.05). With the increase of age, length of service, and education level, the risk of neck-shoulder-back WMSDs increased among manufacturing workers (all P<0.05). The risk of neck-shoulder-back WMSDs of workers in textile, clothing, shoes and hats manufacturing industry was relatively lower than that in the other nine industries (all P<0.05). In terms of the biomechanical factors, spending a lot of effort to operate tools/machines, sitting for a long time at work,bending greatly bending and turning at the same time, neck leaning forward or maintaining this posture for a long time, neck twisting or maintaining this posture for a long time and uncomfortable position resulting in difficulty exerting exertion were all risk factors of neck-shoulder-back WMSDs among manufacturing workers (all P<0.05) Bending slightly for a long time was a protective factor for neck-shoulder-back WMSDs among manufacturing workers (P<0.05). In terms of the psychosocial factors, doing the same work every day, self-determination in resting time between works staff shortage, and frequent overtime work were risk factors for neck-shoulder-back WMSDs among manufacturing workers (all P<0.05). Adequate resting time was a protective factor for neck-shoulder-back WMSDs among manufacturing workers (P<0.01). In terms of environmental factors, working under cold or fluctuating temperature, having nothings to lean on, and soles slipping or falling at work were all risk factors for neck-shoulder-back WMSDs among manufacturing workers (all P<0.05). {L-End}Conclusion Manufacturing workers are prone to suffer from neck-shoulder-back WMSDs. The influencing factors include individual factors, biomechanical factors (force load and static load), psychosocial factors and environmental factors.

Background Work-related musculoskeletal diseases (WMSDs) occur in a variety of occupational populations. Because of their various discomfort and serious disease burden, they have become an important issue worthy of attention in the field of occupational health. The prevention and control of WMSDs is one of the public health problems to be solved. Objective To evaluate the intervention effect on WMSDs among assembly workers in a railway vehicle manufacturing enterprise, so as to provide scientific basis for the prevention and control of WMSDs. Methods A total of 250 assembly workers in a railway vehicle manufacturing enterprise were selected using convenience sampling from August to December 2017. The Chinese Musculoskeletal Questionnaire was used for epidemiological investigation, and the Ergonomic Checkpoints was used for ergonomic inspection and worker interview. According to the above survey results, a six-month intervention plan including stepladder improvement and ergonomics training were implemented in the assembly workshop from September 2018 to February 2019. The intervention effects including the awareness of WMSDs, the exposure level of ergonomic load, and the occurrence of WMSDs symptoms were evaluated with relevant cross-sectional survey results before and after the intervention. The scores of WMSDs symptom intensity, symptom duration, and symptom frequency from low to high were 0-10, 1-4, and 1-5, respectively. Results After the intervention, the awareness rates of assembly workers on WMSDs types, affected body sites, influencing factors, preventive measures, and symptoms all increased from 52.3%, 51.9%, 25.5%, 19.1%, and 51.5% to 68.5%, 61.3%, 48.1%, 40.9%, and 61.3%, respectively (P<0.05). After the intervention, the proportion of assembly workers who "often" bend their head backwards frequently decreased from 34.6% to 21.8%, the proportion who "often" keep their trunk backward for a long time decreased from 26.6% to 15.0%, and the proportion who "never" raise their arms frequently increased from 3.4% to 9.0% (P<0.05). After the intervention, the scores of WMSDs symptom intensity in neck, shoulders, upper back, low back, elbows, hands/wrists, hips/thighs, knees, and ankles/feet all decreased, and the medians were mostly decreased from 6 to 3 (P<0.05); the scores of WMSDs symptom duration only decreased in neck (P<0.05) and there was no significant difference in the other body sites before and after the intervention; the median scores of WMSDs symptom frequency in low back, hands/wrists, and hips/thighs decreased from 3 to 2 (P<0.05). Conclusion The six-month intervention of stepladder improvement and ergonomics training among assembly workers in a railway vehicle manufacturing enterprise can improve workers' awareness of WMSDs, and reduce the exposure frequency of awkward postures and the intensity, duration, and frequency of WMSDs symptoms.

Objective: To summarize the clinical features of leukoencephalopathy with vanishing white matter disease (VWM) in children. Methods: A retrospective cohort study was performed on 54 genetically diagnosed VWM patients in Peking University First Hospital from January 2007 to March 2019. Paper registration form and electronic medical record system were used to collect the data,and the children were divided into five groups according to the age of disease onset:<1 year, 1-<2 years, 2-<4 years, 4-<8 years and 8-<18 years respectively. The progression of motor function, episodic aggravation, epileptic seizures, survival time, brain magnetic resonance imaging (MRI) and genotype features were analyzed and compared. Non-parametric test, χ² test or Fisher′s exact test were used for comparison among groups; Kaplan-Meier survival curve was adopted to delineate the survival status of the children. Results: Fifty-four VWM patients were included in the study, including 34 males and 20 females.The age of disease onset was 2 years and 8 months (ranged from 6 months to 9 years and 7 months). Onset age was less than 1 year in 5 cases; onset age was 1-<2 years in 12 cases; onset age was 2-<4 years in 25 cases; onset age was 4-<8 years, in 10 cases; onset age was 8-<18 years in 2 cases; 94% (51/54) of patients had complaint of motor regression at the first visit; 87% (47/54) of patients suffered from episodic aggravation. Episodic seizures occurred in 43% (23/54) patients. In survivors with disease durations of 1-3 years, in 38% (9/24) patients the disease was classified as grades Ⅳ-Ⅴ by gross motor function classification system (GMFCS). For the onset age 1-<2 years group, 1 patient was classified as GMFCS Ⅳ among 3 survivors with disease durations of 1-3 years. As for the 2-<4 years group, 6 patients were classified as GMFCS Ⅳ-Ⅴ among 15 patients with disease durations of 1-3 years, whereas 1 patient was classified as GMFCS Ⅳ-Ⅴ among 4 patients with disease durations of 1-3 years in the 4-<8 years group. Lesions, liquefaction and diffusion restriction in brain MRI were compared among different groups, and it was revealed that the earlier the age of disease onset was, the more likely the subcortical white matter (frontal lobe P<0.01,temporal and parieto-occipital lobe both P=0.002), internal capsule (anterior limb P<0.01, posterior limb P=0.00) and brain stem (midbrain P=0.001, pons P<0.01) were to be involved. In addition, internal capsule (anterior limb P=0.002, posterior limb P=0.005) and brain stem (midbrain P=0.001, pons P=0.003) showed more diffuse restricted diffusion. Moreover, the subcortical white matter (frontal and parieto-occipital lobe both P<0.01, temporal lobe P=0.005) showed earlier rarefaction. The 1-year and 2-year survival rates of the overall patients were 81% and 75% respectively, while the 15-year survival rate was 45%. EIF2B5 gene variation was the most common, which accounts for 43% (23/54), followed by EIF2B3 (22%, 12/54). Conclusions The majority of VWM patients complained of motor regression at the first visit, episodic aggravation and epileptic seizures are common in the course. Earlier age at onset is associated with more rapid clinical progression, shorter survival time as well as more extensive lesions, liquefaction and diffusion restriction in brain MRI. The most common variant gene is EIF2B5, followed by EIF2B3.

To summarize the clinical features of leukoencephalopathy with vanishing white matter disease (VWM) in children. Methods A retrospective cohort study was performed on 54 genetically diagnosed VWM patients in Peking University First Hospital from January 2007 to March 2019. Paper registration form and electronic medical record system were used to collect the data,and the children were divided into five groups according to the age of disease onset:<1 year, 1-<2 years, 2-<4 years, 4-<8 years and 8-<18 years respectively. The progression of motor function, episodic aggravation, epileptic seizures, survival time, brain magnetic resonance imaging (MRI) and genotype features were analyzed and compared. Non?parametric test, χ2 test or Fisher's exact test were used for comparison among groups;Kaplan?Meier survival curve was adopted to delineate the survival status of the children. Results Fifty?four VWM patients were included in the study, including 34 males and 20 females.The age of disease onset was 2 years and 8 months (ranged from 6 months to 9 years and 7 months). Onset age was less than 1 year in 5 cases; onset age was 1-<2 years in 12 cases; onset age was 2-<4 years in 25 cases; onset age was 4-<8 years, in 10 cases; onset age was 8-<18 years in 2 cases; 94% (51/54) of patients had complaint of motor regression at the first visit; 87% (47/54) of patients suffered from episodic aggravation. Episodic seizures occurred in 43% (23/54) patients. In survivors with disease durations of 1-3 years, in 38% (9/24) patients the disease was classified as grades Ⅳ?Ⅴ by gross motor function classification system (GMFCS). For the onset age 1-<2 years group, 1 patient was classified as GMFCSⅣamong 3 survivors with disease durations of 1-3 years. As for the 2-<4 years group, 6 patients were classified as GMFCS Ⅳ-Ⅴamong 15 patients with disease durations of 1-3 years, whereas 1 patient was classified as GMFCS Ⅳ-Ⅴ among 4 patients with disease durations of 1-3 years in the 4-<8 years group. Lesions, liquefaction and diffusion restriction in brain MRI were compared among different groups, and it was revealed that the earlier the age of disease onset was, the more likely the subcortical white matter (frontal lobe P<0.01,temporal and parieto?occipital lobe both P=0.002), internal capsule (anterior limb P<0.01, posterior limb P=0.00) and brain stem (midbrain P=0.001, pons P<0.01) were to be involved. In addition, internal capsule (anterior limb P=0.002, posterior limb P=0.005) and brain stem (midbrain P=0.001, pons P=0.003) showed more diffuse restricted diffusion. Moreover, the subcortical white matter (frontal and parieto?occipital lobe both P<0.01, temporal lobe P=0.005) showed earlier rarefaction. The 1?year and 2?year survival rates of the overall patients were 81% and 75% respectively, while the 15?year survival rate was 45%. EIF2B5 gene variation was the most common, which accounts for 43% (23/54), followed by EIF2B3 (22%, 12/54). Conclusions The majority of VWM patients complained of motor regression at the first visit, episodic aggravation and epileptic seizures are common in the course. Earlier age at onset is associated with more rapid clinical progression, shorter survival time as well as more extensive lesions, liquefaction and diffusion restriction in brain MRI. The most common variant gene is EIF2B5, followed by EIF2B3.

Objective To analyze the clinical and imaging features of hypomyelination with brain stem and spinal cord involvement and leg spasticity (HBSL) due to mutations in DARS,and to identify DARS mutations responsible for HBSL.Methods Data on 2 HBSL patients who were admitted to the pediatric department of Peking University First Hospital from January 2009 through December 2016 were reviewed and the 2 patients were followed up.Targeted next generation sequencing,whole exome sequencing and Sanger sequencing were employed to identify potential genetic variations of the children and their parents.The clinical manifestations,MRI features and genotypic characteristics of two patients were reviewed,and the literature was reviewed.HBSL reported cases were searched with"leukoencephalopathies,DARS" on databases of PubMed,Wanfang,China National Knowledge Infrastructure and VIP from 1975 to 2017.The clinical manifestations and molecular features were analyzed.Results Both patients showed delayed motor development,but had normal cognitive development.At the age of 8 years,case 1 reached the most significant motor development milestone of only standing with help during the last follow-up.At the age of 9,case 2 could walk independently during the last follow-up.On physical examination,both showed leg spastcity,active tendon reflex,positive Babinski sign.Both patients had brain MRI findings of high T2WI signal in bilateral deep cerebral white matter,slightly lower T1WI,and no abnormal DWI signal.Lesions of case 1 were relatively extensive and involved subcortical white matter,corpus callosum and internal capsule.Spinal MRI scans for both patients showed no abnormal signals.Novel mutations in DARS gene-namely,c.1498_1499insTCA (p.500_501insIle) and c.1210A＞G (p.Met404Val),c.1432A＞G (p.Met478Val) and c.1210A＞G (p.Met404Val)were identified in case 1 and case 2 respectively.On the database,2 reports involving 13 foreign patients were retrieved.The age of disease onset was from 4 months to 18 years,and their initial symptoms were development delay or regression.Most of them presented with progressive lower extremity spasm,and the brain magnetic resonance imaging was characterized by hypomyelination in white matter.Clinical phenotypes of different age groups were significantly different.Conclusion We have reported two patients with HBSL in China,and 3 novel mutations in DARS,which is helpful for the diagnosis and genetic counseling of HBSL.

Objective To analyze the clinical characteristics of 3 unrelated boys with paroxysmal nonkinesigenic dyskinesia and developmental delay caused by de novo mutation in KCNMA1,and to expand the knowledge of clinical phenotype of KCNMA1 mutation.Methods Clinical data of patients were collected,including gender,age,condition of the perinatal period,personal history,and family history.And the features of genotype data were collected including features of attack,developmental milestones,physical examinations,treatments,and responses to treatment.The data including blood biochemical results,results of metabolic screening and genetic testing and the pedigree validation were collected,while the relationship between phenotype and genotype was analyzed.Results (1)Phenotypic features:3 unrelated boys were diagnosed.The ages of disease onset were 20 days,7 months and 13 months,respectively.All the patients manifested paroxysmal nonkinesigenic dyskinesia and were characterized by the episodes that occurred during wakefulness,presented with sudden onset of asymmetric limb dystonic posture,sometimes with nystagmus and strabismus,or sudden decrease of voluntary movement of limbs with hypotonia and occasional esotropia and yawning.There was no loss of awareness during attack.No precipitating factors were observed before attacks.The developmental milestones were delayed.Three children had no response to anti-epilepsy drug before diagnosis.After diagnosis,2 cases used Clonazepam and 1 case showed less attack.There was not any epileptic seizure until the last follow-up at the ages of 3 years and 6 months old,7 years old,and 5 years and 8 months old,respectively.The frequency of attacks was decreased.The episodes were recorded during video-electroencephalogram(EEG) monitoring,which showed normal ictal and interictal EEG.(2)Genotypic features:all 3 children were detected to have KCNMA1 genetic heterozygous missense mutation,while c.2650G>A (p.Glu884Lys) mutation was identified in 1 patient,and c.3158A>G(p.Asn1053Ser)mutation in the other 2 patients,but no such mutation was found in their parents.Conclusion This finding expands the phenotype of KCNMA1mutation.KCNMA1 should be considered as one of the candidate genes for screening in patients with early onset of paroxysmal nonkinesigenic dyskinesia without triggers,or early-onset of developmental delay,with or without epilepsy.

Objective: To identify the clinical and genetic characteristics in 43 Chinese children diagnosed with type Ⅰ Alexander disease (AxD). Method: Forty-three type Ⅰ AxD cases identified by glial fibrillary acidic protein (GFAP) gene mutations in Peking University First Hospital from 2005 to 2016 were followed up. The data of medical history, physical examination and magnetic resonance imaging (MRI) were collected. All these patients were followed up in December 2010, Febury 2012, June 2014 and January 2016, respectively. Result: Forty-three patients were genetically confirmed as type I AxD and the median age at the last visit was 11.71 years (10.27, 13.15). The characteristic clinical manifestations of these type Ⅰ AxD patients were developmental delay (79%, 34/43), seizures (86%, 37/43), macrocephaly (the median percentile of head circumference is 90%), and paroxysmal deterioration (27%, 13/43). All the 43 patients′ brain MRI satisfied typical MRI features proposed by van der Knaap. According to the analysis of the long-term follow-up, patients with type Ⅰ AxD began to have obvious regression in motor function after 7 years of age, and the social life ability was milally impaired 8(6, 10)scores at the last follow-up. Seventeen heterozygous missense mutations of GFAP were identified in 43 genetically confirmed patients, and 4 mutations were novel. The mutations in 41 patients (95%, 41/43) were de novo. Three hot spots of mutation in Chinese patients were found: p. Arg239(35%, 15/34), p. Arg79 (26%, 11/43) and p. R88 (16%, 7/43). Conclusion The characteristic clinical manifestations of type Ⅰ AxD patients are developmental delay, seizures, macrocephaly and paroxysmal deterioration. Moreover, a few patients may present with brain stem symptoms, mental abnormalities, scoliosis or kyphosis. Patients with type Ⅰ AxD may show significant regression in motor function after 7 years of age.

Objective: To explore the phenotypic and genotypic characteristics in Chinese children with classic pantothenate kinase-associated neurodegeneration (PKAN). Method: The clinical, radiographic and genetic data of all PKAN patients diagnosed at pediatric department of Peking University First Hospital from November 2006 to December 2016 were retrospectively collected and analyzed. Result: Twenty patients with classic PKAN were included in the study. The median age at onset was 3.5 years (ranging from 1.0 to 10.0 years), and the most common initial symptom was gait disturbance (16 cases). At the last evaluation, the clinical features were limbs dystonia (20 cases), dysarthria (16 cases), dysphagia (11 cases), pyramidal sign (7 cases), mental regression (3 cases) and pigmentary retinopathy (5 cases). For those classic PKAN patients, the median time from onset of disease to loss of independent ambulation was 6.9 years (ranging from 2.0 to 12.0 years). Imaging data showed, except "eye of tiger" in MRI (19 cases), globus pallidus calcification in CT was also found in four patients. In gene testing, 26 different mutations in PANK2 gene were identified, and 16 of 26 were novel mutations. Moreover, c. 1502T>C (p.Ile501Asn) was the most common mutation (4 cases). Conclusion Dystonia is the major neurologic feature of classic PKAN. Disease progression is rapid, with loss of independent ambulation within 10 years after onset. Except "eye of tiger" in MRI, globus pallidus calcification in CT may be another imaging feature of PKAN.Sixteen novel mutations of PANK2 gene were identified in the study.

Objective To analyze the clinical and MRI features of patients with type Ⅱ Alexander disease (AxD) in order to better understand and diagnose it earlier.Methods Four type Ⅱ AxD patients identified by glial fibrillary acidic protein gene mutations from Peking University First Hospital and 128 type Ⅱ AxD cases from published literatures were collected,and the clinical and MRI features were summarized.Results (1) In 4 type Ⅱ AxD patients,2 adult patients showed abnormal MRI features without clinical manifestation.The other 2 children patients both manifested motor dysfunction of lower limbs,pyramidal signs,paroxysmal deterioration,and seizures during the course of disease,while 1 of them had bulbar paralysis.The MRI of all the cases was abnormal,but only 1 case MRI corresponded with typical MRI features of type Ⅱ AxD.In the other 3 cases MRI showed thc atrophy in the medulla and upper spinal cord,or the brainstem lesions and abnormal signal in the periventricular white matter,and abnormal basal ganglia region.(2) In 128 reported type Ⅱ AxD cases,the age of onset was (32±19) years old.The initial syndromes mainly contained bulbar and/or pseudobulbar paralysis (32.48％,38/117 cases),motor dysfunction of the lower limbs (31.62％,37/117 cases) and autonomic nerve dysfunction (13.67％,16/117 cases).During the course of the disease,the clinical manifestation showed bulbar and/or pseudobulbar paralysis (73.50％,86/117 cases),pyramidal signs (60.68％,71/117 cases) and ataxia (51.28％,60/117 cases).The MRI of all cases was characterized by atrophy or abnormal signals in the brainstem,especially in medulla oblongata,and spinal cord.And abnormal signals in the cerebellar dentate nuclei,white matter,basal ganglia and thalamus were also commonly shown in the MRI.Conclusions The patients with type Ⅱ AxD are late-onsct.The clinical manifestation mainly contains bulbar and/or pseudobulbar paralysis,motor dysfunction of the lower limbs and pyramidal signs.The MRI is characterized by atrophy or abnormal signals in the brainstem (especially in medulla oblongata) and spinal cord.

Objective To summarize the phenotypic features of an unrecognized leukoencephalopathy in infants sharing same clinical features,and to better understand the disease and provide new evidence for identification of new leukoencephalopathy. Methods Clinical and follow-up data of 13 patients with unrecognized infantile leukoen-cephalopathy were collected from Peking University First Hospital from January, 2006 to December, 2014. Results (1) There were 7 male and 6 female. The average age of onset was 11 months (4-25 months). Thirty-eight percent (5/13 cases) of patients had incentives before the onset;all of the cases had acute onset and rapid motor function regression. Fifteen percent (2/13 cases) of the patients suffered from seizures in the course of the disease. Patients′condition became stable,and cognition and motor function improved gradually 1 month after onset. No patient died till the last follow-up. (2) Imaging features:magnetic resonance imaging (MRI) of the patients was characterized by im-plicating deep white matter,presenting T1 hypointense,T2 and fluid attenuated inversion recovery ( FLAIR) hyperin-tense in the periventricular area. All of MRI showed massive and symmetric lesions with heterogeneous signal and cystic degeneration. DWI showed patch or massive hyperintense in some of the lesions. The follow-up MRI showed the original lesions decreased in 88% ( 8/9 cases ) of patients, and white matters atrophied in 55% ( 5/9 cases ) of patients;the cystic degeneration still existed and even expanded;DWI showed regional linear or spot hyperintense in 88% (8/9 cases) of patients,which was smaller than before,and distributed around the original lesions. Conclusions The patients with leukoencephalopathy caused by unknown pathogenic gene were much likely to be mitochondrial leukoencephalopathy. This study provided evidence for further exploration of new pathogenic genes causing leu-koence-phalopathy.