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Objective To investigate the effect of Enterococcus faecalis (E. faecalis) lipoteichoic acid (LTA) on the expression of the macrophage immune checkpoint-programmed cell death protein ligand 1 (PD-L1) and explore the possible regulatory mechanisms. Methods In vitro model was established by stimulating mouse monocyte macrophage cell line (RAW264.7) with different concentrations of E. faecalis LTA. PD-L1 expression and nuclear factor kappa-B (NF-κB) p65 phosphorylation level were detected using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and cellular immunofluorescence. Macrophages were pretreated with the NF-κB signaling pathway inhibitor BAY 11-7082, then the expression of PD-L1 and p65 phosphorylation level were detected by the above methods. Results LTA induced PD-L1 expression in RAW264.7 cells, and p65 phosphorylation level increased (P

ObjectiveTo explore the effective prevention of wild mushroom poisoning， the years of life lost （YLLs） from wild mushroom poisoning in Yunnan Province from 2017 to 2021 was calculated .MethodsThe death data of wild mushroom poisoning in Yunnan Province were collated according to gender， age and year. The YLLs was calculated based on the World Health Organization excel calculation template， and the YLLs was compared among different age， gender and year groups. The indirect economic loss was estimated using human capital approach.ResultsThe YLLs due to wild mushroom poisoning was 2 760 person-years （5.70 person years per 100 000 population）. People aged from 30 to 59 years old were a risk group for wild mushroom poisoning with YLLs of 1 602 person-years. Children aged

To solve the deformation control problems caused by underpass construction of tunnel, the project of shield tunneling of Zhengzhou Metro Line 4, undercrossing closely the existing traffic pipe- jacking tunnels, is studied. Numerical simulation combined with field monitoring is used to reveal the deformation law of the existing jacking tunnels during shield tunnel construction. Based on numerical simulation results, settlement control standard of the pipe-jacking tunnel, the allowable joint opening value of pipe-jacking joints and the minimum allowable radius of curvature of the structural line are established. Then the correctness of the numerical calculation results and the feasibility of setting method of the settlement control standard are confirmed by on-site monitoring. The main conclusions are as follows:( 1 ) During the process of the two shield tunnels crossing the pipe-jacking tunnels at an intersection angle of 37°, the vertical settlement curves of the upper pipe-jacking tunnels present asymmetric characteristics, and the settlement curves of the tunnels show some translation and deflection. (2) Compared with the joint opening control standard, the settlement control requirements based on allowable additional curvature of pipe jacking tunnel deformation are relatively stricter. It is suggested that the maximum allowable settlement value of the jacking tunnel under construction disturbance should be 27mm. [ABSTRACT FROM AUTHOR]

In order to reduce the influences of the contact probes on the accuracy of the high-precision three-dimensional thread measuring machines, an optimization plan for the structure and size of the contact probes was designed, and the corresponding calibration method was proposed. The structural parameters of the probes were optimized through into element simulation and orthogonal experiments to determine the optimal structural parameters. The calibration model of the probes was established by the coordinate transformation theory and the principle of least square method and the calibration experiments were carried out. The optimized probes were tested through the screw plug gauge comparison experiments and the screw ting gauge and plug gauge comparison experiments under different preloads. The results show that the standard deviation of the parameters of the contact probe measuring thread plug gauge and ring gauge is about 1 µm, which meets the measurement accuracy requirements of the contact probes of the three-dimensional thread comprehensive measuring machines. The optimization scheme and calibration method provide important theoretical basis for the design of the probe structures. [ABSTRACT FROM AUTHOR]

Study on formation process of biological purification efficiency in raw watei delivery pipelines was beneficial to improve water quality in long distance raw water delivery pipes. Using simulated pipeline reactors to simulate water situation in raw water delivery pipelines, and water samples were prepared in laboratory. The influent and effluent water quality, the microorganisms in the biofilm is continuously monitored. Results show that the ammonia nitrogen (NH4+-N) and organic matter removal are stabilized after a gradual increase in first, and stable value decreases slightly compared to the maximum in the formation process of biological purification efficiency. Biofilm grow on polyethylene slides in simulated pipeline reactor and then harvest within 45 days, the removal rate of NH4+ - N remains stable at 75%. Nitrite nitrogen ( NO2- - N ) effluent concentration remains stable at 0.02 mg/L. Ammonia oxidizing bacteria (AOB) is dominant stiain compared to nitrite oxidizing bacteria (NOB) in raw water delivery pipes. Removal rate of UV254 and turbidity are about 30%, and orthophosphate (PO43-) removal rate ranges from 13. 64% to 38. 78%. [ABSTRACT FROM AUTHOR]

To investigate the main factor that influenced membrane fouling in ultrafiltration, a simulated process of powdered activated carbon and ultrafiltration (PAG/UF) was used to treat micro-polluted raw water and the sedimentation effluent. Membrane fouling characteristics of two samples, effect of particle size and dissolved organic matter on membrane fouling were investigated. The results indicated that PAG/UF process could mitigate the membrane fouling of the sedimentation effluent, but it could not alleviate the membrane fouling of raw water. Organics in the raw water were mostly hydrophilic organic-based small molecules, and it could not mitigate the membrane fouling of the raw water although the aromaticity and the dissolved microbiological products were reduced with the adsorption of PAG particles, which indicated that the adsorbed organic did not cause serious membrane fouling in the raw water. The particles in raw water, with a small particle size and high number, was thought to be the main factor that leading to the invalid fouling control function of PAG/UF process on raw water. Particle number and particle size distribution have a critical role in membrane fouling. [ABSTRACT FROM AUTHOR]

The combination of chlorine dioxide (ClO2) and chlorine (NaOCl) or monochloramine (NH2Cl) was used to degrade the formation of ClO2-, when ClO2 was used as an effective oxidant which could form undesirable oxidation by-products, i.e. ClO2-. In this article, Mill-Q water was used, and the impact of NaOCl or NH2Cl combined with ClO2 or ClO2 on the yield of ClO2 and ClO2 were investigated by monitoring the residual of NaOCl, NH2Cl, ClO2 and ClO2-. It was proved that when NaOCl or NH2Cl combined with ClO2, hypoehlorousacid (HOCl) formed by NaOCl or NH2Cl could react with ClO2-, which was the reason that ClO2 yield reduced and C102yield increased, and the increase in ClO2 yield exceeded the decrease in ClO2 yield. For the purpose of the highest reaction rate, the optimal ratio between NaOCl and ClO2 was 3:1, while it was 1:1 between NH2Cl and ClO2. The appropriate ratios of residual NaOCl/NH2Cl and ClO2 for ClO2 complete removal were found to be close to the value of 1 and 0.5 respectively. Furthermore, compared with NaOCl, equivalent yield of NH2Cl had much more ClO2 residual yield when reacted with ClO2, and had faster reaction rate in any ratio. It can be concluded that the generation of ClO2 is typically much lower and the residual of ClO2 is much higher with combination of ClO2 and NaOCl or NH2Cl when compared to the use of ClO2 alone. And the minimum ratio between NaOCl and ClO2, NH2Cl and CIO2 are 3:1 and 1:1 respectively when used in micro-polluted water. [ABSTRACT FROM AUTHOR]

To ensure the safety of water in the process of translation in long distance raw water diversion pipe, the damagemant and recovery of purification by added chlorine to Biofilms Annular Reactor (BAR) which simulated the pipe was investigated. The results showed that the prechlorination can damage the pipe bioflim, lower the removal rate of NH4+ - N, NO2- - N, CODMn, TP, and the effluent of concentration of CODMn, and TP was elevated in short term and NO2- - N concentration was rised in long term after prechlorination. The effluent concentration of NO2- - N can be reached 7 times of the influent. The recovery of removal of NH4+ - N was earlier 2 days than that of NO2- - N, and NH4+ - N and NO2- - N could be completely repaired on 8 days and 10 days, respectively. The removal of CODMn and TP can be completely repaired on 8 days. [ABSTRACT FROM AUTHOR]

Objective: To understand the status and related factors of overweight and obesity in children and adolescents aged 6-17 in Yunnan Province., Methods: From 2016 to 2017, 3463 children and adolescents aged 6-17 from 65 primary and secondary schools in 13 counties of Yunnan Province were selected by stratified cluster sampling method for face-to-face questionnaire survey, including 1716 boys and 1747 girls, 2098 elementary school students, 762 middle school students, 603 high school students, of which, 1368 students from urban area and 2095 students from rural area. The questionnaire included information including, weekly consumption of sugary drinks, sweets, puffed food, fruits, vegetables, breakfast, daily activities of moderate or high intensity, school sports, daily hours of playing video games and watching TV, daily sleep and outdoor activities. Height and weight were measured using standard method. SPSS20.0 was used for χ~(2 )test and multivariate Logistic regression analysis., Results: The prevalence of overweight and obesity among children and adolescents aged 6-17 were 8.43%(292/3463) and 6.01%(208/3463) respectively. The overweight rates of male students and female students were 8.45%(145/1716) and 8.41%(147/1747) respectively, and the statistic was significant differently(χ~(2 )=0.001, P>0.05). The overweight rates of urban and rural children and adolescents were 11.99%(164/1368) and 6.11%(128/2095) respectively, and the statistic was significant differently(χ~2=37.04, P<0.01). The overweight rates of primary school, middle school and high school were 7.53%(158/2098), 9.32%(71/762) and 10.45%(63/603) respectively, and the statistic was significant differently(χ~2=6.15, P<0.05). The obesity rates of male and female students were 7.11%(122/1716) and 4.92%(86/1747) respectively, and the statistic was significant differently(χ~2=7.33, P<0.01). The obesity rates of urban and rural children and adolescents were 9.50%(130/1368) and 3.72%(78/2095) respectively, and the statistic was significant differently(χ~2=48.97, P<0.01). The obesity rates of primary school, middle school and high school were 7.67%(161/2098), 3.15%(24/762) and 3.81%(23/603), respectively, and the statistic was significant differently(χ~2=26.48, P<0.01). Multivariate Logistic regression analysis showed that cities(OR=2.025, 95%CI 1.646-2.492) and non-residential schools(OR=1.808, 95%CI 1.470-2.223) were associated with overweight and obesity in children and adolescents, both of which were statistically significant(P<0.05)., Conclusion: The prevalence of overweight and obesity among children and adolescents aged 6-17 in Yunnan Province were high. Urban, non-residential school children and adolescents are more likely to be overweight and obesity.

Objective: To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c.609G>A homologous variant., Methods: A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164 patients of cblC type with MMACHC c.609G>A homologous variant was conducted. The patients were diagnosed by biochemical and genetic analysis from January 1998 to December 2020., Results: Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated from the age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance (P<0.05)., Conclusion: Most of the patients with MMACHC c.609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective This study is aimed to investigate the effect of paeonol on inflammation of BV2 microglia induced by lipopolysaccharide (LPS), and the underlying mechanism. Methods Mouse BV2 microglia was cultured in vitro. BV2 microglia was pretreated with paeonol of different concentration for 24 hours, then stimulated by LPS for 12 hours. Cell viability was detected by CCK-8 assay. Morphological changes of microglia were monitored by microscopy. The mRNA expression of TNF-α, IL-1β, IL-12 and IL-6 by BV2 microglia was measured by real time quantitative-PCR. The protein expression of NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) was determined by Western blot analysis. Results Paeonol treatment improved cell viability, and inhibited over-activation of BV2 microglia challenged by LPS. Paeonol treatment concentration-dependently suppressed LPS induced mRNA expression of inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-12 by BV2 microglia. Phosphorylation of NF-κB p65, but not protein level of NF-κB p65, was suppressed by paeonol treatment in a concentration-dependent manner. Conclusion Paeonol inhibits LPS induced phosphorylation of NF-κB p65 and transcription of downstream proinflammatory cytokines in BV2 microglia.

Objective: To analyzing the malnutrition status and influencing factors of children under 5 years in Yunnan Province., Methods: Multi-stage stratified sampling used in the national survey was performed. The subjects of the study were 2869 children under 5 years, selected from 13 counties(cities) in Yunnan Province from 2016 to 2017. The contents of the investigation included questionnaire survey and anthropometric measurement. Z-scores were calculated according to WHO growth standards by WHO Anthro V3.2.2 software. Non conditional Logistic regression model was used to analyze the multiple factors. SPSS 20.0 statistical software was used to calculate and analyze the malnutrition rate of children., Results: A total of 2869 children under 5 years old were investigated in Yunnan Province, including 1433 boys(49.95%) and 1436 girls(50.05%). The prevalence of stunting, underweight and wasting of children under 5 years old were 3.46%, 6.37% and 3.42%. Logistic multifactor regression analysis showed that low birth weight(OR=4.368, 95% CI 2.057-9.275), rural area(OR=1.931, 95% CI 1.076-3.462), household use of unsanitary toilets(OR=1.688, 95% CI 1.022-2.790), children without supplemental food(OR=2.000, 95% CI 1.130-3.542) were the most important factors making the child more likely to become malnutrition in 6-23 month age group. Asking children for advice on food selection or cooking(OR=3.570, 95%CI 1.249-10.204) was the most important factors making the child more likely to become malnutrition in 6-23 month age group., Conclusion: The nutritional status of children under 5 years old in Yunnan Province has been improved, but the prevalence of malnutrition is still high.

Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaricacidemia type II, is a relatively common disorder of fatty acid oxidation metabolism. The clinical manifestations are highly heterogeneous, symptoms can develop from newborn to adulthood. Neonatal onset type is more serious with high mortality. The symptoms of late onset patients include lipid deposition myopathy and vomiting, liver disease, and encephalopathy. Analysis of blood acyl carnitine spectrum by tandem mass spectrometry can be used for the screening. Late onset patients have relatively good prognosis with vitamin B 2 treatment. The purpose of this consensus is to standardize the diagnosis, treatment and management of MADD, so as to improve the prognosis of patients and reduce death and disability.

Glutaricacidemia type 1(GA1) is an autosomal recessive disease caused by reduced or missing glutaryl-CoA dehydrogenase activity which hamps metabolism of lysine, hydroxylysine and tryptophan. The catabolic products of glutarylcarnitine and glutaric acid are abnormally accumulated in the body, resulting in metabolic disorders which primarily lead to damage to the nervous system. Clinical manifestations of patients include macrocephaly, dystonia, dyskinesia, and developmental retardation. Acute encephalopathy may be induced in infants and young children due to infection, vaccination and surgery. For GA1 is a rare disease and its clinical manifestations are similar to other neurological diseases, it may be easily missed or misdiagnosed. To facilitate early diagnosis and treatment and improve the prognosis, this consensus was formulated by pediatric experts from the fields of endocrinology and genetic metabolism through full discussion and reference to the latest literature and guidelines home and abroad.

Objective: To test the performance of CHA 2 DS 2 -VASc score in predicting stroke recurrence in first-ever ischemic stroke survivors without atrial fibrillation (AF)., Methods: A total of 768 patients were included in this study, including 475 male (61.85%) and 293 female patients (38.15%) with a mean age of 61.52±12.59 years (17-90 years). The baseline information of the patients was collected by face-to-face questionnaire survey and electronic medical record review, and their follow-up information was collected by telephone follow-up once every 3 months. Chi-square test and Wilcoxon rank sum test were used to compare the baseline characteristics between the patients regularly followed up and those withdrawn from the study. The area under the ROC curve (AUC), sensitivity, specificity, positive likelihood ratio and other indicators of CHA 2 DS 2 -VASc score were determined, and C-index based on Cox proportional hazards model was used to evaluate the performance of CHA 2 DS 2 - VASc score in predicting the risk of stroke recurrence in patients at different time points during the follow-up., Results: The 1-year, 3-year, and 5-year recurrence rate of stroke was 10.59%, 20.45%, and 29.46% in these patients, respectively. The AUC value, Optimal Operating Point (OOP) and the corresponding positive likelihood ratios (LR+) for predicting stroke recurrence were 0.558 (95% CI : 0.492-0.624), 4.5, and 1.256 at 1 year; 0.574 (95% CI : 0.517-0.630), 4.5, and 1.397 at 3 years; and 0.604 (95% CI : 0.548-0.661), 4.5, and 1.655 at 5 years, respectively. Sensitivity analysis of congestive heart failure showed that the predictive effect of CHA 2 DS 2 -VASc score was basically unchanged., Conclusions: CHA 2 DS 2 -VASc score can be used to predict the 3-year and 5-year risk of stroke recurrence in first-ever ischemic stroke survivors without AF. The score has a better prediction ability for long-term stroke recurrence, but the prediction value remains low, suggesting the need to further improve the score or establish a new score for predicting stroke recurrence.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Objective: To understood the accuracy of oral fluid-based rapid HIV self-testing among men who have sex with men (MSM) and related factors., Methods: Survey was conducted among MSM selected through non-probability sampling to evaluate the quality of their rapid HIV self-testing, and related information was analyzed., Results: The most MSM were aged 21-30 years (57.0%). Among them, 45.7% had educational level of college or above, 78.5% were unmarried, 59.3% were casual laborers. The overall accuracy rate of oral fluid based self-testing was 95.0%, the handling of"inserting test paper into tube as indicated by arrow on it"had the highest accuracy rate (98.0%), and the handling of"gently upsetting tube for 3 times"had lowest accuracy rate (65.0%); Chi-square analysis showed that educational level, no touch with middle part of test paper, whether reading the instruction carefully, whether understanding the instruction and inserting test paper into tube as indicated by the arrow on it were associated with the accuracy of oral fluid-based rapid HIV self-testing, (P<0.05). Multivariate logistic regression analysis indicated that educational level, no touch with middle part of test paper and understanding instructions were associated with the accuracy of oral fluid-based rapid HIV self-testing., Conclusions: The accuracy of oral fluid-based rapid HIV self-testing was high among MSM, the accuracy varied with the educational level of the MSM. Touch with the middle part of test paper or not and understanding the instructions or not might influence the accuracy of the self-testing.

Objective: To analyze the characteristics of risky behaviors among different age groups of HIV positive female sex workers, and to explore the strengthening of their management., Methods: From January to June 2014, 22 814 female sex workers were investigated and tested HIV in 117 sentinel surveillance sites in Yunnan Province, and 181 were confirmed to be HIV antibody positive, who accepted questionnaire surveys. According to the age, the participants were divided into the < 35 years old age group and ≥ 35 years old age group. The demographic characteristics, knowledge about HIV/AIDS and related risk behaviors characteristics of the two groups were obtained via questionnaire surveys among 181 HIV positive female sex workers, and in-depth qualitative interviews were conducted from among 12 HIV positive sex workers., Results: HIV antibody positive rate was 0.8% (181), the age of the 181 subjects were (35.83 ± 9.17) years old, 76 cases (42.0%) were < 35 years old, and 105 cases (58.0%) were ≥ 35 years old. The differences of marital status, workplace class, the last work site among two groups were statistically significant (χ(2) = 20.80, 28.32, 7.83; P < 0.001, P < 0.001, P = 0.020, respectively). Among 181 HIV, the proportion of AIDS awareness was 95.6% (173); the proportion of drug use among ≥ 35 years old age group was 51.4% (54), which was higher than that in < 35 years old age group (34.2%, 26/76) (χ(2) = 5.30, P = 0.021). 96.7% (175) received condom promotion or HIV counseling and testing in the past year. The proportion of continuing to engage in sexual services over 5 years after HIV infection was 48.5% (51/105) and the proportion of receiving antiretroviral treatment was 69.5% (73/105) in ≥ 35 years old age group, which were higher than those in the < 35 age group (30.2% (23/76), 52.6% (40/76); χ(2) = 12.26, 5.36; P = 0.002, 0.021, respectively). In-depth interviews among 12 HIV positive female sex workers found that regular clients, not consistent use of condoms were the main cause of no condom use. Economic and livelihood factors are important reasons for continuing to engage in sexual services among HIV positive sex workers., Conclusion: HIV positive sex workers still have high risk behaviors including continuing to engage in commercial sexual service and no condom use after knowing their HIV infection status, and the proportion of using drugs in the ≥ 35 years old group was higher than that in < 35 years old group.

Objective: Argininemia is a rare disorder of urea cycle defect. The clinical manifestations of this disorder are similar to those of cerebral palsy so that the diagnosis is usually much delayed. This study aimed to investigate the phenotypes and genotypes of seven Chinese patients suffering from argininemia., Method: Three boys and four girls with spastic tetraplegia were diagnosed as argininemia by blood aminoacids analysis and ARG1 gene study. Patients were given a protein-restricted diet, citrulline, sodium benzoate, and other treatment intervention. The mother of Patient 5 and 6 accepted genetic counseling and underwent prenatal diagnosis by amniocentesis., Result: Seven patients presented with progressive spastic tetraplegia and poor physical growth from the age of 1 month to 4 years. Argininemia was found at the age of 1 year and 10 months to 12 years. Five patients had mental retardations. Three had seizures. Their blood arginine elevated (86.66 to 349.83 µmol/L, normal controls 5 to 25 µmol/L). Liver dysfunction was found in six patients. Five patients had elevated blood ammonia levels. In four patients, cerebral atrophy was observed by cranial magnetic resonance imaging. Nine mutations in the ARG1 gene were identified from 7 patients. Only two mutations, c.703G > A in exon 7 and c.32T > C in exon 1 had been reported. c.34G > T, c.53G > A, c.67delG, c.232dupG, c.374C > T, c.539G > C and c.646-649delCTCA, were novel mutations of ARG1. A homozygous mutation c.703G > A was found in the amniocytes of Patient 5's mother, indicating that the fetus was affected by argininemia. Induced abortion was performed. c.53G > A from Patient 6 was not found in the amniocytes of her mother, indicating that the fetus was not affected by hepatocyte arginase deficiency. The result was confirmed by postnatal mutation analysis of cord blood and the normal blood arginine of the newborn., Conclusion: Argininemia is one of the few treatable causes of pediatric spastic paralysis. In this study, seven Chinese patients with spastic tetraplegia were detected by blood aminoacids analysis and confirmed by molecular analysis. Seven novel mutations on ARG1 gene were identified. Prenatal diagnosis of the fetus of a family was performed by amniocytes ARG1 gene analysis.

Objective: To summarize clinical features and diagnosis of Chinese infantile patients with glycogen storage disease type II (GSD II)., Method: Six infant patients with GSD II diagnosed from January 2012 to June 2014 in the Department of Pediatrics, Peking University First Hospital were enrolled into this study. Clinical information of the 6 patients, including clinical manifestation, blood biochemistry, chest X-ray, echocardiogram, electrocardiogram, acid alpha-glucosidase (GAA) activity and GAA gene mutation analysis by direct sequencing of polymerase chain reaction (PCR) product were reviewed., Result: Of the 6 patients, five were female and one was male, five of whom were classic infantile type while the other one was atypical. The age of onset ranged from birth to 3-month-old. All patients had varying degrees of generalized muscle weakness, hypotonia and development retardation or retrogression. Other common findings were feeding difficulties in two patients, tongue weakness in two patients, respiratory distress in four patients, macroglossia in one patient, and hepatomegaly in two patients. Left ventricular hypertrophy and cardiomegaly were obvious in all the six patients. All six patients were found to have a enlarged heart in physical examination, and three patients who underwent a chest X-ray examination had an enlarged heart shadow. Four patients who had an echocardiography were found to have myocardial hypertrophy. The electrocardiogram in three patients showed short PR intervals and high voltage. The creatine kinase (CK) levels were three to seven times elevated. The mildest elevated CK was 441 IU/L, and the highest CK level was 1 238 U/L. Assay of GAA enzyme activity in whole blood showed significantly reduced activity (1.3 nmol/ (spot·d) to 2 nmol/(spot·d)) in the patients tested. Gene sequencing in 4 patients showed 8 pathogenic mutations, including 6 missense mutations, one nonsense mutation and one frameshift mutation. The missense mutations were c.998C > A (p.Thr333Lys), c.1280T > C (p.Met427Thr), c.1760T > C (p.Leu587Pro), c.1924G > T (p.Val642Phe), c.2012T > A (p.Met671Lys) and c.2105G > A (p.Arg702His). The nonsense mutation was c2662G > T (p.Glu888X), and the frameshift mutation was c2812&#95;2813delTG (p.Cys938fs). The 5 classic infantile patients died at the age of 7 to 22 months. The atypical infantile patient was 2 years and five months old according to our latest follow up., Conclusion: Infantile GSD II had similar motor manifestations and cardiac involvements, blood biochemical test, imaging findings, enzyme assays, though there were slight differences. The probability of GSD II should be taken into consideration if an infant has both muscular disease and cardiac involvement.

Mink plasmacytosis, caused by Aleutian Mink Disease Virus (AMDV), poses a threat to the development of the animal fur industry. Neutralizing antibodies against AMDV may result in a persistent infection rather than providing protection for minks. To date,no specific methods to prevent or cure this disease have been developed. In order to eliminate mink plasmacytosis, antibody detection technology has been used globally as a dominant approach to screen for AMDV-positive minks. This paper introduces the classical technology, counterimmunoelectrophoresis and emerging technology in terms of AMDV antibody detection,and provides a glimpse into the future development of these technologies.

Objective: We report the first case of acute encephalopathy induced by vaccination in an infant with methylmalonic aciduria cblA in China., Method: The clinical presentation, blood acylcarnitines analysis, urine organic acids analysis and gene studies of the patient were summarized., Result: The proband, a boy, was admitted at the age of 15 months because of recurrent vomiting, acidosis and development delay for 8 months. The previously healthy boy presented vomiting and coma just one hour after hepatitis B vaccination at the age of seven months. Moderate dehydration, electrolyte disturbance and metabolic acidosis had been found. Although his acute metabolic crisis had been corrected soon after intravenous transfusion, psychomotor retardation and recurrent vomiting had been observed. When he was 15 months old, vomiting and lethargy occurred again 3 hours after DTaP vaccination. He was weakened as the illness became worse and got coma with dyspnea 7 days later. He was hospitalized with the suspected diagnosis of viral encephalitis. Blood acylcarnitines analysis, urine organic acids analysis and gene study had been performed for the etiologic investigation.His blood propionylcarnitine (16.3 µmol/L vs. normal range 1.0-5.0 µmol/L) and propionylcarnitine/free carnitine ratio (0.27 vs. normal range 0.03 to 0.25) increased. Markedly elevated urinary methylmalonic acid (388.21 mmol/mol creatinine vs. normal range 0.2 to 3.6 mmol/mol creatinine) and normal plasma total homocysteine supported the diagnosis of isolated methylmalonic aciduria. Two mutations, c.650 T>A (p.L217X) and c.742 C>T (p.Q248X), were identified in his MMAA gene, confirmed the diagnosis of cblA. Each parent carried one of the two mutations. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 2 years and 7 months old with normal development and general condition., Conclusion: A boy with cblA was firstly detected after the acute encephalopathy induced by vaccination in China. It is important to pay more attention to the patients with metabolic crisis or organ damage after vaccination. Metabolic studies are keys to the diagnosis of potential diseases and improve the outcome.

Objective: To evaluate the feasibility of screening large cohorts of patients with developmental delay or intellectual disability (DD/ID) with multiplex ligation-dependent probe amplification (MLPA)., Methods: The peripheral blood samples were collected and DNA extracted from 276 patients with DD/ID from June 2012 to December 2013. MLPA was employed, including two distinct kits SALSA P036 and P070 for sub-telomere screening and SALSA P245 for 22 common microdeletion and microduplication syndromes., Results: MLPA analysis revealed 58 (21%) cases of chromosome aberrations. Among 32 cases of subtelomeric rearrangements on one chromosome, there were deletion (n = 25) and duplication (n = 7); subtelomeric deletions on p and q arms of one chromosome (n = 2); subtelomeric rearrangements on 2 chromosomes, one deletion and other duplication (n = 9); subtelomeric rearrangements on 3 chromosomes, 2 duplications and other deletion (n = 1). There were 1 case of subtelomeric rearrangements on chromosome X. A total of 11 syndromes were detected among 22 common microdeletion and microduplication syndromes and 6 located at subtelomeric regions., Conclusion: MLPA is an effective cytogenetic diagnostic tool for detecting chromosomal abnormalities, such as DD/ID.

Objective: To investigate the clinical, biochemical and genetic profiles of 28 Chinese patients with glutaric aciduria type 1., Method: Twenty-eight patients with glutaric aciduria type 1 seen in the Department of Pediatrics, Peking University First Hospital from July 2003 to October 2013 were studied. The data of clinical course, laboratory examinations, cranial MRI and GCDH gene mutations of the patients were analyzed., Result: (1) Three cases were detected by newborn screening, and the other patients were diagnosed at the age of 2 months to 17 years. (2) 22 patients (79%) were infant onset cases with psychomotor retardation, dystonia, seizures, athetosis, recurrent vomiting, drowsiness or feeding difficulty. Only two of the 22 patients with infant onset got normal intelligence and movement after treatment. Twenty of them were improved slowly with delayed development, dystonia and other neurological problems. Three patients (11%) had late onset. They had motor regression, headache and seizure at the age of 8, 9 and 17 years, respectively. Rapid improvement was observed after treatment. (3) Cranial MRI has been checked in 23 patients; 22 of them showed characteristic widening of the Sylvian fissure, abnormalities of the basal ganglia, leukoencephalopathy and brain atrophy. Thirty-five mutations in GCDH gene of the patients were identified; c.148T>C (p.W50R) was the most common mutation with the frequency of 7.7%; 6 mutations (c.628A>G, c.700C>T, c.731G>T, c.963G>C, c.1031C>T and c.1109T>C) were novel., Conclusion: Glutaric aciduria type 1 usually induced neurological deterioration resulting in severe psychomotor retardation and dystonia. Most of our patients were clinically diagnosed. Patients with early onset usually remained having neurological damage. Phenotype and genotype correlation has not been found in the patients. Neonatal screening for organic acidurias should be expanded in China.

Objective: To investigate the phenotype and genotype of a Chinese boy and his family affected by infantile Sandhoff disease., Methods: The proband, a boy, was the first child born to a non-consanguineous couple. He showed startle reaction after birth and progressive psychomotor regression from the age of 8 months. From the age of 16 months, he presented seizures. When he was admitted at 17 months old, severe mental retardation and weakness were observed. Fundus examination revealed bilateral cherry-red spots in the macula and optic atrophy. Cranial MRI revealed abnormal signals in the thalamus, basal ganglia and white matter. Enzymatic assay and genetic testing were performed for the diagnosis. His mother visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene diagnosis to the fetus was performed by direct sequencing., Results: Significant deficient total β-hexosaminidase (A and B) activity in peripheral leucocytes of the patient (0.0 nmol/h/mg compared with normal control, 41.9 to 135.1 nmol/h/mg) supported the diagnosis of Sandhoff disease. On his HEXB gene, two mutations were found. c.1645G-A (p.G549R) was novel. c.IVS7-48T was a reported mutation. Now, the patient was 2 years and 3 months old, with progressive general failure, severe epilepsy, blindness and hypermyotonia. Subsequently, the mother visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene analysis of the amniocytes was performed by direct sequencing. Both of the two mutations were not detected from cultured amniocytes. The result revealed that the fetus was not affected by Sandhoff disease. A healthy girl, the sibling of the proband, was born in term. Postnatal enzyme analysis and genetic analysis of the cord blood cells confirmed the prenatal diagnosis., Conclusion: One novel mutation on HEXB gene was identified. Prenatal diagnosis to the fetus of this family was performed by amniocytes gene analysis.

Objective: To investigate the MUT gene mutations in patients with methylmalonic acidemia (MMA), and analyze the genotype-phenotype correlation in patients with methylmalonyl-CoA mutase deficiency., Methods: The diagnosis of the disease mainly depends on the measurement of C3 (acylcarnitine), C3/C0 (free carnitine) and C3/C2 (acetylcarnitine) in the blood by tandem mass spectrometry, the detection of methylmalonic acid in the urine by gas-chromatography mass spectrometry, the determination of total homocysteine in the serum, and the loading test of vitamin B(12). The entire coding region of the MUT gene was screened by PCR combined with direct DNA sequencing in 21 isolated MMA patients. Novel mutations were identified by restriction fragment length polymorphism (RFLP) and sequence analysis in 100 controls., Results: Seventeen MUT gene mutations were detected in 14 of the 21 patients, among them 8 mutations were novel, and R108H, D244LfsX39 and G544X were more frequent, with the frequencies of 9.5%, 7.1% and 9.5%, respectively. Most mutations were missense mutations (64.7%), and majority of them were in exons 2 and 3 (55.6%). Ten out of the 14 patients with MUT gene mutations had early-onset disease, while one case had late-onset disease, and the remaining 3 cases were detected by newborn screening. In addition, 11 of these 14 patients did not respond to vitamin B(12)., Conclusion: This study revealed partial MUT gene mutation spectrum in Chinese patients with isolated MMA. The patients carrying MUT mutations often had early-onset disease, and most of them were VitB(12)- non-responsive.