Variable phenotypes and outcomes associated with the MMACHC c.482G > A mutation: follow-up in a large CblC disease cohort.

BACKGROUND: The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene (MMACHC) c.482G > A mutation in 195 Chinese cases with CblC disease. METHODS: We carried out a national, retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G > A variant either in a homozygous or compound heterozygous state. The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G > A mutation. Clinical features, including disease onset, symptoms, biochemical metabolites, gene mutation, and follow-up outcomes were reviewed and analyzed in detail. The median follow-up period spanned 3 years and 8 months, with a range of 1 year and 2 months to 12 years and 10 months. RESULTS: Among 195 patients carrying the c.482G > A variant, 125 (64.1%) cases were diagnosed by newborn screening (NBS), 60 (30.8%) cases were detected due to disease onset, and 10 (5.1%) cases were identified from sibling diagnoses. One hundred and seventeen (93.6%) individuals who were diagnosed by NBS, and nine patients who came from sibling diagnoses remained asymptomatic in this study. From 69 symptomatic patients of the c.482G > A group, more patients presented with later onset, and the top six common clinical symptoms at disease onset were developmental delay (59.4%), lower limb weakness and poor exercise tolerance (50.7%), cognitive decline (37.7%), gait instability and abnormal posture (36.2%), seizures (26.1%), and psychiatric and behavioral disturbances (24.6%). In the 159 symptomatic patients lacking c.482G > A variants, the most frequently observed clinical manifestations at disease onset included developmental delay (81.8%), lethargy and feeding difficulty (62.9%), lower limb weakness and poor exercise tolerance (54.7%), prolonged neonatal jaundice (51.6%), vomiting (47.2%), and seizures (32.7%). Before treatment, the levels of blood propionylcarnitine, propionylcarnitine/acetylcarnitine ratio, and homocysteine in the c.482G > A group were significantly lower (P < 0.05) than those in the non-c.482G > A group, while the concentration of urinary methylmalonic acid was slightly lower (P > 0.05). The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels (P < 0.05). In patients carrying the c.482G > A variant compared with the non-c.428G > A group, there were markedly lower rates of mortality (0.5% vs. 2.0%) and developmental delay (20.5% vs. 65.5%). When compared with individuals diagnosed due to disease onset, those identified through NBS in either group exhibited a reduced proportion of disease onset (6.7% vs. 100% in the c.482G > A group, 54.4% vs. 100% in the non-c.482G > A group), lower mortality (0.0% vs. 1.7% in the c.482G > A group, 0.0% vs. 3.6% in the non-c.482G > A group), and had a higher percentage of patients exhibiting normal psychomotor and language development (99.3% vs. 33.3% in the c.482G > A group, 58.9% vs. 10.9% in the non-c.482G > A group). CONCLUSIONS: The c.482G > A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease. Patients with this mutation tend to have a relatively better response to hydroxocobalamin, better metabolic control, and more favorable neurological outcomes. NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis, resulting in favorable clinical outcomes. Video Abstract (MP4 136794 kb).

Valorization of sewage sludge for facile and green wood bio-adhesives production.

A method is presented herein for the design of wood bio-adhesives using sewage sludge extracts (SSE). SSE was extracted from SS using deep eutectic solvents and processed with glycerol triglycidyl ether (GTE) to disrupt the secondary structure of proteins. An additive was also used to improve mechanical performance. The resulting bio-adhesive (SSE/GTE@TA) had a wet shear strength of 0.93 MPa, meeting the Chinese national standard GB/T 9846-2015 (≥0.7 MPa). However, the high polysaccharide content in SSE would weaken the mechanical properties of wood bio-adhesives. The key to improve bio-adhesive quality was the formation of a strong chemical bond via Maillard reaction as well as higher temperatures (140 °C) to reduce polysaccharide content via dehydration. This approach has lower environmental impact and higher economic efficiency compared to incineration and anaerobic digestion of sewage sludge. This work provides a new perspective on the high-value utilization of SS and offers a novel approach to developing bio-adhesives for the wood industry.

Meningioma preceding CASPR2 antibody limbic encephalitis with a stroke mimic: A case report.

RATIONALE: Todd paralysis (a stroke-like presentation in some patients with epilepsy) caused by limbic encephalitis (LE) is not easily distinguished from acute ischemic stroke by clinicians in the emergency room. PATIENT CONCERNS: We report a contactin-associated protein-like 2-antibody (CASPR2-Ab)-positive patient who presented with atypical LE. DIAGNOSES: CASPR2-Ab-positive LE was the presumed diagnosis. Re-evaluation of cerebrospinal fluid (CSF) samples revealed autoantibodies targeting CASPR2 at an immunoglobulin G titer of 1:1. The clinical presentation of subacute onset seizures, abnormal electroencephalography, hypermetabolism on positron emission tomography, good immunotherapy response, and the presence of specific antibodies in serum supports a diagnosis of autoimmune LE. INTERVENTION: The patient received glucocorticoids (1 g for 3 days and 500 mg for 3 days), immunoglobulin (25 g for 3 days), sodium valproate (1 g for 3 days), and clonazepam (1 mg for 3 days). OUTCOMES: Remission of temporal lobe epilepsy symptoms and cognitive dysfunction was observed. Follow-up analysis of CSF and serological examination were not approved by the patient. His Mini-Mental State Examination score improved to 21/30. Stable remission of symptoms was achieved throughout the follow-up period of 50 days. LESSONS: Autoimmune encephalitis (AE) should be considered in cases of late-onset epilepsy following meningioma peritumoral brain edema and resection. A diagnosis of AE should be considered in patients presenting with stroke-like symptoms if the magnetic resonance imaging abnormality does not match a known vascular territory. Early and correct diagnosis is crucial because immunotherapy is usually effective for this disease.

Bronchoscopy for diagnosis of COVID-19 with respiratory failure: A case report.

BACKGROUND: Although the imaging features of coronavirus disease 2019 (COVID-19) are starting to be well determined, what actually occurs within the bronchi is poorly known. Here, we report the processes and findings of bronchoscopy in a patient with COVID-19 accompanied by respiratory failure. CASE SUMMARY: A 65-year-old male patient was admitted to the Hainan General Hospital on February 3, 2020 for fever and shortness of breath for 13 d that worsened for the last 2 d. The severe acute respiratory syndrome coronavirus 2 nucleic acid test was positive. Routine blood examination on February 28 showed a white blood cell count of 11.02 × 109/L, 86.9% of neutrophils, 6.4% of lymphocytes, absolute lymphocyte count of 0.71 × 109/L, procalcitonin of 2.260 ng/mL, and C-reactive protein of 142.61 mg/L. Oxygen saturation was 46% at baseline and turned to 94% after ventilation. The patient underwent video bronchoscopy. The tracheal cartilage ring was clear, and no deformity was found in the lumen. The trachea and bilateral bronchi were patent, while the mucosa was with slight hyperemia; no neoplasm or ulcer was found. Moderate amounts of white gelatinous secretions were found in the dorsal segment of the left inferior lobe, and the bronchial lumen was patent after sputum aspiration. The right inferior lobe was found with hyperemia and mucosal erosion, with white gelatinous secretion attachment. The patient's condition did not improve after the application of therapeutic bronchoscopy. CONCLUSION: For patients with COVID-19 and respiratory failure, bronchoscopy can be performed under mechanical ventilation to clarify the airway conditions. Protection should be worn during the process. Considering the risk of infection, it is not necessary to perform bronchoscopy in the mild to moderate COVID-19 patients.

Ferroptosis is involved in alcohol-induced cell death in vivo and in vitro.

A critical pathogenic factor in the development of lethal liver failure is cell death induced by the accumulation of lipid reactive oxygen species. In this study, we discovered and illuminated a new mechanism that led to alcoholic liver disease via ferroptosis, an iron-dependent regulated cell death. Study in vitro showed that both necroptosis inhibitor and ferroptosis inhibitors performed significantly protective effect on alcohol-induced cell death, while apoptosis inhibitor and autophagy inhibitor had no such effect. Our data also indicated that alcohol caused the accumulation of lipid peroxides and the mRNA expression of prostaglandin-endoperoxide synthase 2, reduced the protein expression of the specific light-chain subunit of the cystine/glutamate antiporter and glutathione peroxidase 4. Importantly, ferrostatin-1 significantly ameliorated liver injury that was induced by overdosed alcohol both in vitro and in vivo. These findings highlight that targeting ferroptosis serves as a hepatoprotective strategy for alcoholic liver disease treatment.

A novel missense COL10A1 mutation: c.2020G>A; p. Gly674Arg linked with the bowed legs stature in the Schmid metaphyseal chondrodysplasia-affected Chinese lineage.

To evaluate the clinical-phenotypic characteristics of Schmid metaphyseal chondrodysplasia (SMCD) inflicted by a novel missense mutation of COL10A1 gene: c.2020G > A; p.Gly674Arg. A female child aged about 3 yrs. and 8 months was subjected to Radiograph test to validate the symptoms of SMCD. The polymorphism analysis by the next-generation sequencing (NGS) was performed using the peripheral blood DNA samples of the patient and other family inmates, including, the younger male sibling. The effect of the mutation on the non-collagenous carboxyl-terminal (NC1) domain of collagen X was studied using the SWISS-MODEL online server for trimer modelling; PROSA and PROCHECK-Ramachandran plot for structural validation; Mean Square Plot (RMSF) for structural rigidity. Radiograph examination of lower limbs confirmed the bowed legs in both the patient and her younger brother (study groups). The inheritance of the novel missense mutation of COL10A1: c.2020G > A; p.Gly674Arg (at chromosome-6q22.1) was confirmed in the study groups from the SMCD-affected mother. The extended interactions of the mutant-Arg674 with the Ser552 and Phe589 (ß strand B) in the NC1 domain of α1(X) chain monomer is more likely to intervene its trimer formation by weakening the structural rigidity of the crucial strand H compared to its wild type. This plausibly deters the collagen X synthesis inflicting the bowed legs with the altered distal ulna bone morphology in the study groups. The inheritance of COL10A1 mutation: c.2020G > A; p.Gly674Arg has inflicted the SMCD with the characteristic bowed legs in the study groups. Radiograph and NGS could be a valid diagnostic module to initiate the treatment of SMCD.

[Correlation between serum microRNA-122 and insulin resistance in obese children].

OBJECTIVE: To study the relationship between serum microRNA-122 (miR-122) and insulin resistance in obese children. METHODS: Forty-seven children with severely obesity aged 7-14 years and 45 age- and gender matched healthy children with normal weight (control group) were enrolled. The levels of height, weight, waistline, hip circumference, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), interleukin-6 (IL-6) and miR-122 in the two groups were measured. Body mass index (BMI), waist-hip ratio (WHR) and insulin resistance index (HOMA-IR) were calculated. RESULTS: Compared with the control group, the height, weight, BMI, WHR, FINS, HOMA-IR, TG, FFA, IL-6, and miR-122 levels in the obese group were significantly increased (P<0.05). MiR-122 levels in the obese group were positively correlated with FINS, HOMA-IR and IL-6 levels (r=0.408, 0.442, and 0.464 respectively, P<0.05). The changes of miR-122 have a linear regression relationship with IL-6 (b'=0.318, P<0.05). CONCLUSIONS: The elevated serum miR-122 levels may be correlated with insulin resistance in obese children. The mechanism needs to be further studied.

[Protective effect of vitamin A on residual pancreatic ß cell function in children with type 1 diabetes mellitus].

OBJECTIVE: To study the protective effect of vitamin A on residual pancreatic ß cell function in children with type 1 diabetes mellitus (T1DM) and its mechanism. METHODS: A total of 46 children with T1DM (with a course of disease of 0.5-1 year) were randomly divided into an intervention group and a non-intervention group (n=23 each). The children in both groups were given insulin treatment, and those in the intervention group were also given vitamin A at a daily dose of 1 500-2 000 IU. A total of 25 healthy children were enrolled as the control group. The daily dose of insulin was calculated for the children with T1DM, and the serum levels of glycosylated hemoglobin (HbA1C), stimulated C-peptide, vitamin A, and interleukin-17 (IL-17) were measured before intervention and 3 months after intervention. RESULTS: Before vitamin A intervention, the intervention group and the non-intervention group had a significantly lower serum level of vitamin A and a significantly higher level of IL-17 than the control group (P<0.01). After 3 months of intervention, the intervention group had significantly lower serum IL-17 level and insulin dose and a significantly higher level of stimulated C-peptide than the non-intervention group (P<0.05). CONCLUSIONS: Vitamin A may protect residual pancreatic ß cell function, possibly by improving the abnormal secretion of IL-17 in children with T1DM.

Association of COL1A1 polymorphism with high myopia: a Meta-analysis.

AIM: To investigate the association between collagen type I alpha 1 (COL1A1) gene and high myopia. METHODS: In this Meta-analysis, we examined 5 published case-control studies that involved 1942 high myopia cases and 2929 healthy controls to assess the association between the COL1A1 rs2075555 polymorphism and high myopia risk. We calculated the pooled odds ratios (ORs) of COL1A1 rs2075555 polymorphism in high myopia cases vs healthy controls to evaluate the strength of the association. RESULTS: Overall, there was no significant difference both in the genotype and allele distributions of COL1A1 rs2075555 polymorphism between high myopia cases and healthy controls: CC vs AA OR=1.10, 95% confidence interval (CI)=0.76-1.58; AC vs AA OR=0.98, 95%CI 0.80-1.20; CC/AC vs AA/OR=1.01, 95%CI 0.84-1.22; CC vs AC/AA OR=1.06, 95%CI=0.93-1.20; C vs A OR=1.06, 95%CI 0.91-1.23). In addition, in the stratified analyses by ethnicity, no significant associations were found in any genetic model both in European and Asia cohorts. CONCLUSION: Our results indicate that the COL1A1 rs2075555 polymorphism may not affect susceptibility to high myopia.

Dynamic evolution of resistance gene analogs in the orthologous genomic regions of powdery mildew resistance gene MlIW170 in Triticum dicoccoides and Aegilops tauschii.

KEY MESSAGE: Rapid evolution of powdery mildew resistance gene MlIW170 orthologous genomic regions in wheat subgenomes. Wheat is one of the most important staple grain crops in the world and also an excellent model for plant ploidy evolution research with different ploidy levels from diploid to hexaploid. Powdery mildew disease caused by Blumeria graminis f.sp. tritici can result in significant loss in both grain yield and quality in wheat. In this study, the wheat powdery mildew resistance gene MlIW170 locus located at the Triticum dicoccoides chromosome 2B short arm was further characterized by constructing and sequencing a BAC-based physical map contig covering a 0.3 cM genetic distance region (880 kb) and developing additional markers to delineate the resistance gene within a 0.16 cM genetic interval (372 kb). Comparative analyses of the T. dicoccoides 2BS region with the orthologous Aegilops tauschii 2DS region showed great gene colinearity, including the structure organization of both types of RGA1/2-like and RPS2-like resistance genes. Comparative analyses with the orthologous regions from Brachypodium and rice genomes revealed considerable dynamic evolutionary changes that have re-shaped this MlIW170 region in the wheat genome, resulting in a high number of non-syntenic genes including resistance-related genes. This result might reflect the rapid evolution in R-gene regions. Phylogenetic analysis on these resistance-related gene sequences indicated the duplication of these genes in the MlIW170 region, occurred before the separation of the wheat B and D genomes.

High-density genetic linkage map construction and QTL mapping of grain shape and size in the wheat population Yanda1817 × Beinong6.

High-density genetic linkage maps are necessary for precisely mapping quantitative trait loci (QTLs) controlling grain shape and size in wheat. By applying the Infinium iSelect 9K SNP assay, we have constructed a high-density genetic linkage map with 269 F 8 recombinant inbred lines (RILs) developed between a Chinese cornerstone wheat breeding parental line Yanda1817 and a high-yielding line Beinong6. The map contains 2431 SNPs and 128 SSR & EST-SSR markers in a total coverage of 3213.2 cM with an average interval of 1.26 cM per marker. Eighty-eight QTLs for thousand-grain weight (TGW), grain length (GL), grain width (GW) and grain thickness (GT) were detected in nine ecological environments (Beijing, Shijiazhuang and Kaifeng) during five years between 2010-2014 by inclusive composite interval mapping (ICIM) (LOD ≥ 2.5). Among which, 17 QTLs for TGW were mapped on chromosomes 1A, 1B, 2A, 2B, 3A, 3B, 3D, 4A, 4D, 5A, 5B and 6B with phenotypic variations ranging from 2.62% to 12.08%. Four stable QTLs for TGW could be detected in five and seven environments, respectively. Thirty-two QTLs for GL were mapped on chromosomes 1B, 1D, 2A, 2B, 2D, 3B, 3D, 4A, 4B, 4D, 5A, 5B, 6B, 7A and 7B, with phenotypic variations ranging from 2.62% to 44.39%. QGl.cau-2A.2 can be detected in all the environments with the largest phenotypic variations, indicating that it is a major and stable QTL. For GW, 12 QTLs were identified with phenotypic variations range from 3.69% to 12.30%. We found 27 QTLs for GT with phenotypic variations ranged from 2.55% to 36.42%. In particular, QTL QGt.cau-5A.1 with phenotypic variations of 6.82-23.59% was detected in all the nine environments. Moreover, pleiotropic effects were detected for several QTL loci responsible for grain shape and size that could serve as target regions for fine mapping and marker assisted selection in wheat breeding programs.

[Status of penis and testicular development and effects of overweight/obesity on them in boys in the Zhengzhou area].

OBJECTIVE: To evaluate the current status of penis and testicular development in boys and the effects of overweight/obesity on their development in the Zhengzhou area of Henan Province. METHODS: Height, weight, waist circumference, hip circumference, penis length and testicular volume were measured in 3 546 4 to 12-year-old boys. The penis length and testicular volume were compared between the overweight/obesity and normal weight groups. RESULTS: Before 9 years of age, the testicular volume was progressively smaller, and after 9 years old, it gradually increased. By the age of 11, it increased rapidly. The penis length increased gradually between 4 and 11 years of age, and after the age of 11 it increased rapidly. Phimosis was found in 144 cases (4.01%) and cryptorchidism was found in 18 cases (0.51%). A total of 639 (18.02%) boys were overweight or obese among 3 546 boys. At the ages of 6 and 7 years, the testicular volume in the overweight/obesity group was greater than in the normal control group (P<0.05). The penis length in the overweight/obesity group was significantly shorter than in the normal control group (P<0.05) by the age of 11 years. The correlation analysis showed that the testicular volume at the ages of 4 and 5 years was positively correlated with height, weight, BMI, waist circumference and hip circumference in overweight/obese boys. The penis length at the ages of 7 and 8 years was negatively correlated with weight, waist circumference and hip circumference. By the age of 12 years, the penis length was positively correlated with the height. CONCLUSIONS: The development of penis and testicles in boys in the Zhengzhou area is in line with the level of sex development of Chinese boys. Overweight/obesity adversely affects the development of penis and testicles.

Fine physical and genetic mapping of powdery mildew resistance gene MlIW172 originating from wild emmer (Triticum dicoccoides).

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most important wheat diseases in the world. In this study, a single dominant powdery mildew resistance gene MlIW172 was identified in the IW172 wild emmer accession and mapped to the distal region of chromosome arm 7AL (bin7AL-16-0.86-0.90) via molecular marker analysis. MlIW172 was closely linked with the RFLP probe Xpsr680-derived STS marker Xmag2185 and the EST markers BE405531 and BE637476. This suggested that MlIW172 might be allelic to the Pm1 locus or a new locus closely linked to Pm1. By screening genomic BAC library of durum wheat cv. Langdon and 7AL-specific BAC library of hexaploid wheat cv. Chinese Spring, and after analyzing genome scaffolds of Triticum urartu containing the marker sequences, additional markers were developed to construct a fine genetic linkage map on the MlIW172 locus region and to delineate the resistance gene within a 0.48 cM interval. Comparative genetics analyses using ESTs and RFLP probe sequences flanking the MlIW172 region against other grass species revealed a general co-linearity in this region with the orthologous genomic regions of rice chromosome 6, Brachypodium chromosome 1, and sorghum chromosome 10. However, orthologous resistance gene-like RGA sequences were only present in wheat and Brachypodium. The BAC contigs and sequence scaffolds that we have developed provide a framework for the physical mapping and map-based cloning of MlIW172.

Low-dose levodopa protects nerve cells from oxidative stress and up-regulates expression of pCREB and CD39.

OBJECTIVE: This study aimed to investigate the influence of low-dose levodopa (L-DOPA) on neuronal cell death under oxidative stress. METHODS: PC12 cells were treated with L-DOPA at different concentrations. We detected the L-DOPA induced reactive oxygen species (ROS). Meanwhile, MTT and LDH assay were performed to determine the proliferation and growth of PC12 cells with or without ROS scavenger. In addition, after pretreatment with L-DOPA at different concentrations alone or in combination with CD39 inhibitor, PC12 cells were incubated with hydrogen peroxide (H2O2) and the cell viability was evaluated by MTT and LDH assay. In addition, the expression of pCREB and CD39 was detected by immunofluorescence staining and Western blot assay in both cells and rat's brain after L-DOPA treatment. RESULTS: After treatment with L-DOPA for 3 days, the cell proliferation and growth were promoted when the L-DOPA concentration was <30 µM, while cell proliferation was comparable to that in control group when the L-DOPA concentration was >30 µM. Low dose L-DOPA could protect the PC12 cells from H2O2 induced oxidative stress, which was compromised by CD39 inhibitor. In addition, the expression of CD39 and pCREB increased in both PC12 cells and rats' brain after L-DOPA treatment. CONCLUSIONS: L-DOPA at different concentrations has distinct influence on proliferation and growth of PC12 cells, and low dose (<30 µM) L-DOPA protects PC12 cells against oxidative stress which might be related to the up-regulation of CD39 and pCREB expression.

[NH3, N2O, CH4 and CO2 emissions from growing process of caged broilers].

To obtain Ammonia and greenhouse gas (GHG) emission factors of caged broilers, ammonia (NH3), methane (CH4), nitrous oxide (N2O) and carbon dioxide (CO2) emissions of broilers aged 0 d to 42 days were monitored in caged broilers production systems located in Shandong province. Gas concentrations of incoming and exhaust air streams were measured by using INNOVA 1312 multi-gas monitor with multi-channel samplers. Building ventilation rates were determined by on site FANS (Fan Assessment Numeration System) measurement systems. The NH3 emission factors showed a trend of increase at the beginning and then decreased with the broiler ages. The NH3 emission rates were 8.5 to 342.1 mg x (d x bird)(-1) and the average daily emission rate was 137.9 mg x (d x bird)(-1) [48.6 g x (d x AU)(-1)] over the 42-d period. The GHGs emission rates were 19.5-351.9 mg x (d x bird)(-1) with an average of 154.5 mg x (d x bird)(-1) [54.4 g x (d x AU)(-1)] for CH4, and 2.2- 152.9 g x (d x bird)(-10 with an average of 65.9 g x (d x bird)(-1) [23.2 kg x (d x AU)(-1)] for CO2. No emission of N2O was observed. The CH4 and CO2 emission rates increased with the increase of broilers ages. The total NH3 emission over the 42 d growing period averaged (5.65 +/- 1.02) g x (bird x life cycle)(-1). The NH3 emission contribution in different growth phase to the total emission were 33.6% in growth phase 1 (0-17 day, GP1), 36.4% in GP2 (18-27 days), and 29.9% in GP3 (28-42 days), respectively. The NH3 emission in GP2 was significantly higher than emission in GP1 and GP3. CH4 and CO2 cumulative emission rates were (6.30 +/- 0.16) g x (bird(-1) x life cycle)(-1) and (2.68 +/- 0.18) kg x (bird x life cycle)(-1), respectively. The cumulative emission rates of CH4 and CO2 in GP3 were significantly higher than emission rates in GP2 and in GP1, accounting for 50% of total emissions. The results of this study could provide the data support for mitigation of gas emission from broilers production.

[Association of cytotoxic T lymphocyte-associated antigen-4+49A/G polymorphism with childhood type 1 diabetes mellitus: a meta-analysis].

OBJECTIVE: To evaluate the association of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) + 49A/G polymorphism with type 1 diabetes mellitus (T1DM) in children. METHODS: Papers about the association of CTLA4+49A/G polymorphism with T1DM in children were collected by searching PubMed, EBSCO, CBM, CNKI, and Wanfang Data. A meta-analysis was performed to examine differences in the genotypes (AG, GG, and GG+AG) and G allele at position 49 of the CTLA-4 gene between a childhood T1DM group and a control group. RESULTS: A total of 10 papers involving 1084 T1DM children and 1338 healthy children were included. The Meta-analysis was performed to evaluate the association of the genotypes (AG, GG, and GG+AG) and the G allele at position 49 of the CTLA-4 gene with T1DM using a fixed effect model according to the heterogeneity test results of all studies. The pooled OR values (95% CI) were 1.13 (0.97-1.33), 1.42 (1.16-1.75), 1.20 (1.03-1.40), and 1.21 (1.09-1.33), suggesting a significant difference in genotypes (AG, GG, and GG+AG) and the G allele at position 49 of the CTLA-4 gene between the two groups. CONCLUSIONS: CTLA-4 +49A/G polymorphism is associated with T1DM in children.

[Effects of Astragalus membranaceus on cytokine secretion of peripheral dendritic cells in children with Henoch-Schonlein purpura in the acute phase].

OBJECTIVE: To explore the effects of Astragalus membranaceus (AM) on the cytokines secretion of peripheral dendritic cells (DC), including interleukin-10, -12, and -18 (IL-10, IL-12 and IL-18), in children with Henoch-Schonlein purpura (HSP) in the acute phase; and to study the immunological regulation mechanism of AM. METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 28 children with acute HSP by density gradient centrifugation, and each sample was divided into two parts, one untreated and one treated with AM. All cells were developed to mature DC through treating with recombinant human granulocyte macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha). Expression of CD83 in the surface of mature DC was detected by flow cytometry, and levels of IL-10, IL-12 and IL-18 in the supernatant were measured by ELISA. RESULTS: The supernatant level of IL-12 was higher [(141.58 +/- 100.19) ng/L vs (96.18 +/- 76.65) ng/L, t = 3.90, P<0.01], while levels of IL-10 and IL-18 were lower (t = 2.70, P<0.05; t = 4.07, P<0.01) in AM treated PBMCs than those in the untreated ones. CONCLUSION: AM can correct the immunologic dysfunction of HSP children through increasing the IL-12, and decreasing the IL-10 and IL-18 secretions of PBMCs.