Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective To investigate the effect of Pericarpium Citri Reticulatae on changes of the intestinal absorption of ginsenoside components in Yi Gong San based on the rat model of spleen deficiency and whether its effect is related to the exocytosis of P-gp protein.Methods The group design included the P-gp protein agonist rifampicin and the inhibitor verapamil,and 36 SD rats were randomly divided into a blank control group(6 rats)and a model group(30 rats),and then subcutaneously injected with rifampicin to establish a model of splenic deficiency,and then the model group was divided into the Yigong San fullparty(Y)group,the lack of Pericarpium Citri Reticulatae(Y-C)group,the YiGong San combined with rifampin(Y+R)group,the lack of Pericarpium Citri Reticulatae combined with verapamil(Y-C+V)group and the lack of Pericarpium Citri Reticulatae combined with rifampin(Y-C+R)group,Ginsenoside Rb1,ginsenoside Re and ginsenoside Rg1 were used as the index components in an in situ unidirectional intestinal perfusion test,and HPLC-MS was used to determine the content of the index components and to calculate the kinetic parameters of intestinal absorption,the effective permeability coefficient(Peff)and the absorption rate constant(Ka).Results Compared with group Y,Peff of ginsenoside Rb1 and Re were significantly lower in Y-C at multiple perfusion sessions,and Peff and Ka of ginsenoside Rb1,ginsenoside Re,and ginsenoside Rg1 were lower in Y+R at multiple perfusion sessions,suggesting that Pericarpium Citri Reticulatae promotes the intestinal absorption of ginsenoside Rb1 and ginsenoside Re and that this effect is related to the activity of the P-gp protein,but failed to change the intestinal absorption of ginsenoside Rg1.The P-gp protein inhibitor verapamil significantly increased the Peff of ginsenoside Rb1 and Re in the Y-C+V compared with the Y-C,while the P-gp protein agonist rifampicin significantly decreased the Peff and Ka of ginsenoside Rb1,ginsenoside Re,and ginsenoside Rg1 in the Y-C+R in multiple perfusion sessions.The significant decrease in Peff and Ka at multiple perfusion times suggests that ginsenoside Rb1,ginsenoside Re,and ginsenoside Rg1 may be substrates for P-gp proteins in the absence of Pericarpium Citri Reticulatae intervention.Conclusion Pericarpium Citri Reticulatae promotes the intestinal absorption of ginsenoside Rb1 and ginsenoside Re by exerting a verapamil-like effect that inhibits the activity of P-gp proteins in Yi Gong San.

Objective:To analyze the epidemiological characteristics of etiology from patients with hand, foot and mouth disease(HFMD) in ji’an of Jiangxi from 2013 to 2020, and provide effective prevention and control measures for the diagnosis and treatment of HFMD in the region.Methods:We collected 5089 stool and other clinical specimens from patients with HFMD. Fluorescence quantitative PCR was used for enterovirus detection and typing, SAS statistical software was used to analyze the epidemiological characteristics of pathogens from the types of specimens, time, age, gender, and regional distribution.Results:A total of 3 062 positive samples for enterovirus (EV) were detected out of 5 089 samples, with a total positive rate of 60.17%. The proportions of EV71, CoxA16 and other enteroviruses were 15.15%, 16.36% and 68.49%, and other enterovirus infections were the main ones; the positive rate of enterovirus showed a downward trend from 2013 to 2020; the difference in the positive rate of enterovirus in different years was statistically significant ( χ2=118.47, P<0.05). In the past 8 years, the EV71 type of HFMD in Ji’an showed a downward trend year by year. The number of positive cases was mainly concentrated in April-November, with the peak around May and September. There was no significant difference in the positive detection rate between male and female ( χ2=3.44, P>0.05). The positive rate of stool, anal swab and herpes fluid was higher than that of throat swab, and the difference was significant ( χ2=78.76, P<0.01). Conclusions:In recent years, the surveillance result showed that the pathogenic spectrum of enterovirus had changed in Ji’an, relevant surveillance should be carried out according to the actual situation of HFMD etiology in this region, which is conducive to the prevention and control of HFMD in this region.

{L-End}Objective To understand the prevalence of work-related musculoskeletal disorders (WMSDs) and sickness absence due to WMSDs among key industry workers in Shenzhen City. {L-End}Methods A total of 14 949 workers exposed to dust, noise, chemical and radiation (hereinafter referred to as "traditional occupational groups") in some key industries in Shenzhen City, as well as bus drivers, teachers, medical staff, policemen, courier, sanitation workers and video operators were selected as the research subjects using stratified cluster sampling. The Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of WMSDs and sickness absence due to WMSDs in the past year. {L-End}Results The overall prevalence of WMSDs among the study subjects was 56.3% (8 423/14 949). The prevalence of WMSDs in different body parts from high to low was neck, waist, shoulder, back, knee, wrist, ankle, hip, and elbow, which was 37.6%, 35.7%, 31.7%, 25.2%, 18.3%, 15.4%, 14.9%, 12.4%, and 11.6%, respectively (P<0.01). The overall prevalence of WMSDs among different occupational groups from high to low was teachers, video operators, bus drivers, couriers, medical staff, policemen, traditional occupational groups, and sanitation workers, which was 82.2%, 75.7%, 74.9%, 73.9%, 67.9%, 64.3%, 43.3%, and 31.9%, respectively (P<0.01). The overall rate of sickness absence due to WMSDs was 18.3% (2 736/14 949). The overall rate of sickness absence among different occupational groups from high to low was bus drivers, couriers, teachers, traditional occupational groups, policemen, video operators, medical staff, and sanitation workers, which was 31.6%, 24.5%, 20.9%, 20.2%, 15.2%, 12.4%, 9.3%, and 6.7%, respectively (P<0.01). Among different parts of the body, the highest correlation coefficient of WMSDs was found between neck and shoulder ［correlatioon cofficient (r)=0.648, P<0.01］, while the lowest was between neck and ankle (r=0.303, P<0.01). {L-End}Conclusion The prevalence of WMSDs and sickness absence due to WMSDs among key industry workers in Shenzhen City is relatively high. Comprehensive prevention and control measures should be taken according to the characteristics of occupational population to reduce the impact of WMSDs on the health of occupational population.

Objective:To investigate the prevalence, gene variation and prognosis of very long chain acyl CoA dehydrogenase deficiency (VLCADD) in newborns in Henan Province.Methods:From January 2013 to December 2019, 867 103 newborns were investigated for VLCADD by tandem mass spectrometry.Children who diagnosed as VLCADD and their families were subjected to next-generation sequencing and Sanger sequencing.Clinical data, biochemical changes and gene variation characteristics of the confirmed cases of VLCADD were analyzed.Dietary guidance was given, and their growth and development were followed up.Results:Six neonates were diagnosed as VLCADD, and the prevalence of VLCADD in the Henan Province was 1/144 517.A total of 11 mutations in the ACADVL gene were found, including 5 new variants c. 692-2_692-1delAG, c.753-23_753-22del, c.960delG, c.1361A>G, and c. 1955C>T.The newborns were given a high-carbohydrate, low-fat diet, and followed up for 8-56 months.Except for two deaths, all patients had a good outcome. Conclusions:The prevalence of neonatal VLCADD in Henan Province is 1/144 517.This results has enriched the ACADVL gene mutation spectrum and provided an important basis for the screening and diagnosis of VLCADD.

Along with the develoipment of high-throughput sequencing technologies, both sample size and SNP number are increasing rapidly in genome-wide association studies (GWAS), and the associated computation is more challenging than ever. Here, we present a memory-efficient, visualization-enhanced, and parallel-accelerated R package called"rMVP"to address the need for improved GWAS computation. rMVP can 1) effectively process large GWAS data, 2) rapidly evaluate population structure, 3) efficiently estimate variance components by Efficient Mixed-Model Association eX-pedited (EMMAX), Factored Spectrally Transformed Linear Mixed Models (FaST-LMM), and Haseman-Elston (HE) regression algorithms, 4) implement parallel-accelerated association tests of markers using general linear model (GLM), mixed linear model (MLM), and fixed and random model circulating probability unification (FarmCPU) methods, 5) compute fast with a globally efficient design in the GWAS processes, and 6) generate various visualizations of GWAS-related information. Accelerated by block matrix multiplication strategy and multiple threads, the association test methods embedded in rMVP are significantly faster than PLINK, GEMMA, and FarmCPU_pkg. rMVP is freely available at https://github.com/xiaolei-lab/rMVP.

Objective: To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD). Methods: From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up. Results: In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c. 1484T>C, c. 394-1G>T, c. 431T>C and c. 265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c. 1400C>G (42.3%), c. 760C>T (11.5%) and c. 51C>G (7.7%). During the 8 ~ 42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment. Conclusion The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c. 1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.

Objective To investigate the predictive value of pregnancy-associated plasmaprotein-A (PAPP-A) and GRACE risk score for death and nonfatal myocardial infarction (combined endpoint) in AMI patients.Methods All AMI patients hospitalized in our department during July 2011 to July 2015 were included consecutively in this prospective study.Plasma PAPP-A were measured at admission.GRACE risk score was acquired with the application of GRACE risk score calculator.Patients were followed up for at least 1 year for any nonfatal myocardial infarction or MACE.Kaplan Meier survival study was analysed according to PAPP-A and GRACE score risk stratification respectively.A cutoff value of 3.0 ng/ml of PAPP-A was chosen from pilot work in this cohort.Results A total of 220 patients were enrolled in the study.The death and nonfatal myocardial infarction during follow-up were significantly higher in patients with PAPP-A≥3.0 ng/ml compared to patients with PAPP-A<3.0 ng/ml (15.7% vs.6.0%, log-rank χ2=5.684, P=0.017).The area under ROC curve of PAPP-A was 0.796(95%CI 0.696-0.896, P<0.01) and the ROC curve of PAPP-A GRACE risk stratification was 0.715 (95%CI 0.567-0.863,P<0.01).Subgroup analysis showed that death and nonfatal myocardial infarction during follow-up was significantly higher in patients with PAPP-A≥3.0 ng/ml compared to patients with PAPP-A<3.0 ng/ml in intermediate and low risk group by GRACE risk stratifcation (log-rank χ2=14.63,P<0.001).Conclusions PAPP-A could predict mortality and nonfatal myocardial infarction in patients with AMI.PAPP-A combined with GRACE risk score can better predict outcome than GRACE risk score alone in intermediate and low risk patients by GRACE risk stratifcation.

Cognitive dysfunction,as a common symptom among patients with chronic fatigue syndrome (CFS) and patients with fibromyalgia(FM),impacts on life quality,occupation and study of these patients.However,the neural correlates to the cognitive impairment are unknown.Event related potentials,which reflect the information processing objectively and constantly,provide possibility for taking a insight into and estimating the dysfunction.By summarizing and analyzing studies in event related potentials about chronic fatigue syndrome,fibromyalgia,we found that CFS patients were characterized with prolonged latency of N200 and P300 accompanied by decreased P300 amplitude when they performed on Oddball paradigm,fibromyalgia patients were characterized with lower P300 amplitude when they concentrated on Oddball task,meanwhile,fibromyalgia patients also showed decreased P100/N100,P200,P300,LPC in emotional word decision task and somatic pictures decision task.It's suggests that the cognitive dysfunction in CFS is mainly caused by slowed speed of information identification and classification,whereas in FM it's dysregulation in attention control system results in the cognitive dysfunction.Limitations in current studies and prospects on researches about cognitive dysfunction in CFS for future were also discussed.

Objective: To explore the relationship between occupational stress and physiological and biochemical indexes, to research the health effect of the occupational stress in aircrew. Methods: 450 aircrews were conducted with the OSI-R questionnaire survey, examine the level of blood pressure, blood routine, ALT and UA. Results: The concentration of HB was positively related with task conflict and entertainment and leisure (β=0.262 and 0.106, both P<0.05) , while heavy task, task discomfort and psychological stress reactions were negatively related with HB (β=-0.163, -0.102, and -0.137, all P<0.05) ; task conflict and self-care were positively related with RBC (β=0.221 and 0.159, both P<0.01) , heavy task, psychological stress reactions and social support were negatively related with RBC (β=-0.157, -0.119, and -0.113, all P<0.05) ; task ambiguity and self-care had a positive relationship with ALT (β=0.144 and 0.159, both P<0.01) while heavy task, psychological stress reactions and social support had a negative relationship with ALT (β=-0.176, -0.096, and -0.102, all P<0.05) ; self-care was positively related with SBP (β=0.170, P<0.01) , task discomfort, interpersonal stress reactions and social support were negatively related with SBP (β=-0.093, -0.103, and -0.111, all P<0.05) ; while self-care was positively related with DBP (β=0.139, P<0.01) , social support was negatively related with DBP (β=-0.114, P<0.05) . Conclusion Occupational stress of the aircrew is significantly related with blood pressure, RBC, ALT and UA, occupational stress can make effects on the health of aircrew.