[Accumulation Pathway of Cd, Pb, and Zn in Chinese Cabbage under the Condition of Exogenous Pollution Superposition in High Geological Background Area].

Northwest Guizhou is a karst area with a high geological background. Affected by historical soil zinc smelting, the heavy metal content of atmospheric dust in the region is high, and soil pollution is severe. In order to explore the accumulation pathway of heavy metals in leafy vegetables, Chinese cabbage was used as the test crop, and the geological high background soil and zinc smelting-contaminated soil with the same contents of Cd, Pb, and Zn were selected. A pot experiment was carried out in the polluted area of zinc smelting and the non-polluting control area. The heavy metal content, enrichment coefficient (BCF), and transport coefficient (TF) of Chinese cabbage were studied under open-air, plastic mulching film, and greenhouse cultivation conditions. The results showed that the contents of Cd, Pb, and Zn in Chinese cabbage in the polluted area and the control area were 0.10-1.01 and 0.10-0.91 mg·kg-1, 0.31-0.62 and 0.23-0.37 mg·kg-1, and 7.50-32.74 and 4.88-21.79 mg·kg-1, respectively. Overall, the contents of heavy metals in the polluted area were relatively high. The contents of Cd and Pb in Chinese cabbage planted in soil with a high geological background met the requirements of the national food safety standard limits. Affected by atmospheric deposition, the contents of Pb and Zn in Chinese cabbage in the polluted area were significantly higher than that in the control area, and the difference in Cd was insignificant. The proportions of weak acid-soluble Cd, Pb, and Zn in the contaminated soil were 48%, 3.0%, and 16%, respectively, which were 3.15, 1.01, and 1.57 times higher than those in the control soil with a high geological background. Affected by the activity of heavy metals, the contents of Cd and Zn in Chinese cabbage planted in the contaminated soil exceeded the national standard and were significantly higher than those in the control soil. The root-soil BCF of Cd, Pb, and Zn in polluted soil was significantly higher than that in the control soil, and the BCF of Cd and Zn was higher than that of Pb. The TF aboveground root Cd and Zn in Chinese cabbage was significantly higher than in the control soil, whereas the TF aboveground root Pb in the polluted area was significantly higher than that in the control area. The Pb content of Chinese cabbage in the two study areas showed open field>plastic mulching film>greenhouse cultivation. In conclusion, the content of Cd and Zn in Chinese cabbage was greatly affected by the activity of heavy metals in soil, and the main accumulation pathway was root absorption and transportation. In addition to root absorption, atmospheric deposition was an important accumulation pathway of Pb. Therefore, in areas with high geological backgrounds, attention should be paid to controlling the exposure risk of Cd and Zn in leafy vegetables planted on exogenously polluted soils. Additionally, greenhouse cultivation could effectively reduce the accumulation of Pb.

A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Serum levels of degraded monosaccharides in children with Henoch-Schönlein purpura. / è¿‡æ•æ€§ç´«ç™œæ‚£å„¿è¡€æ¸ é™è§£å•ç³–æ°´å¹³çš„å˜åŒ–åŠæ„ä¹‰.

OBJECTIVES: To examine the serum levels of degraded monosaccharides in children with Henoch-Schönlein purpura (HSP) and to study the clinical significance of degraded monosaccharides in HSP. METHODS: A prospective analysis was performed on 132 children who were diagnosed with HSP from September 2019 to January 2022, and 132 healthy children were enrolled as the control group. High-performance liquid chromatography was used to determine the content of degraded monosaccharides in serum in both groups. The receiver operating characteristic (ROC) curve was used to evaluate the efficiency of degraded monosaccharides for the diagnosis of HSP. RESULTS: Compared with the control group, the HSP group had significantly higher serum levels of mannose, glucosamine, aminogalactose, and galactose (P<0.001). The four degraded monosaccharides had an area under the ROC curve of 0.919, 0.913, 0.832, and 0.932 respectively for the diagnosis of HSP (P<0.05). CONCLUSIONS: Children with HSP have higher serum levels of mannose, glucosamine, aminogalactose, and galactose than the healthy population. The levels of degraded monosaccharides may have an important value for the diagnosis of HSP.

[Role of hypomethylation of suppressor of cytokine signaling in T helper 17 cell/regulatory T cell imbalance in children with Henoch-Schönlein purpura].

OBJECTIVE: To investigate the association between suppressor of cytokine signaling (SOCS) hypomethylation and T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance in children with Henoch-Schönlein purpura (HSP) and the immune pathogenesis of HSP. METHODS: A total of 32 children in the acute stage of HSP who were hospitalized from May 2014 to January 2015 were enrolled as subjects, and 28 children who underwent physical examination were enrolled as normal control group. ELISA was used to measure the plasma level of interleukin-6 (IL-6). Flow cytometry was used to measure the percentages of CD4+ IL-17A+ T cells (Th17 cells) and CD4+CD25+ Treg cells (Treg cells) in peripheral blood and mean fluorescence intensity (MFI) for phosphorylated-STAT3 (pSTAT3) protein in CD4+ T cells. Quantitative real-time PCR was used to measure the mRNA expression of suppressor of cytokine signaling-1 (SOCS1) and suppressor of cytokine signaling-3 (SOCS3) in CD4+ T cells. High-resolution melting (HRM) was used to evaluate the methylation level of the CpG islands in SOCS1 exon 2 and the CpG islands of the potential bind sites for STAT3 in the 5'-untranslated region (5'-UTR) of SOCS3 in peripheral blood mononucleated cells. RESULTS: Compared with the normal control group, the HSP group had significant increases in plasma IL-6 concentration and MFI for pSTAT3 in CD4+ T cells, as well as a significant increase in the percentage of Th17 cells and a significant reduction in the percentage of Treg cells (P<0.05). The HSP group had significantly higher mRNA expression of SOCS1 and SOCS3 in peripheral blood mononucleated cells than the normal control group (P<0.05). In the HSP group, the mRNA expression of SOCS1 and SOCS3 was negatively correlated with Th17/Treg ratio (P<0.05). The HSP group had hypomethylation of the CpG islands in SOCS1 exon 2 and the potential binding site for STAT3 in SOCS3 5'-UTR, while the normal control group had complete demethylation. CONCLUSIONS: Low relative expression of SOCS1 and SOCS3 caused by hypomethylation may be a factor for Th17/Treg imbalance in children with HSP.

Correlation of TLR2 and TLR4 expressions in peripheral blood mononuclear cells to Th1- and Th2-type immune responses in children with henoch-schönlein purpura.

We discussed the correlation of TLR2 (Toll-like receptor) and TLR4 expressions in peripheral blood mononuclear cells (PBMCs) to Th1- and Th2-type immune responses in children with Henoch-Schönlein Purpura (HSP). The role of TLR2 and TLR4 in the pathogenesis of HSP was analyzed. Sixty-four HSP children treated at our hospital from October 2011 to November 2012 were enrolled and divided into NHSPN group (complicated by renal impairment, 36 cases) and HSPN group (not complicated by renal impairment, 28 cases). In the meantime, 30 normal children receiving physical examination at our hospital were recruited as controls. Peripheral blood T cell subgroups and TLR2 and TLR4 expressions in PBMCs were detected by using flow cytometry; relative expression levels of TLR2 and TLR4 mRNA in PBMCs by real-time quantitative fluorescence PCR, and plasma levels of IFN-γ, IL-4 and IL-6 by ELISA method. Relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in children with HSP were significantly higher than those of the controls (P<0.01). The relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in HSPN group were obviously higher than those in NHSPN group (P<0.05; P<0.01; P<0.01; P<0.01); CD3(+) T cells and CD3(+)CD4(+) T cells in HSP group were significantly decreased, while CD3(+)CD8(+) T cells and CD3(+)HLADR(+) T activated cells were considerably increased (P<0.01); The plasma levels of IL-4 and IL-6 in HSP group were significantly higher than those of the normal controls (P<0.01, P<0.01); IFN-γ level in the former was much lower than in the control group (P<0.05); IFN-γ/IL-4 ratio in the former was also lower than that in the control (P<0.01); TLR2 and TLR4 expressions in HSP group showed significantly positive correlation with the plasma levels of IL-4 and IL-6 (P<0.01, P<0.05; P<0.01, P<0.01) and significantly negative correlation with IFN-γ/IL-4 ratio (P<0.01; P<0.01). TLR2 and TLR4 activation may be involved in the pathogenesis of HSP. TLR2 and TLR4 overactivation may induce HSP-related renal impairment; Children with HSP showed T-cell disorders and Th1/Th2 imbalance. Activated TLR2 and TLR4 possibly mediate the pathogenesis of HSP by upregulating Th2-type immune responses.

Clinical significance of TLR3 and TLR4 in peripheral blood mononuclear cells from children with Henoch-Schönlein purpura nephritis.

The aim of the present study was to investigate the expression levels and clinical significance of Toll-like receptor (TLR) 3 and 4 in peripheral blood mononuclear cells (PBMCs) collected from children with Henoch-Schönlein purpura (HSP) nephritis. The randomized controlled trial was conducted between August 2011 and March 2013, and 105 children with a clinical diagnosis of HSP were enrolled in the study. According to the 24-h urinary protein measurements and the presence of renal damage, the 105 cases were divided into groups A, B and C as follows: Group A, children with HSP but without renal damage; group B, children with HSP nephritis but without proteinuria; group C, children with HSP nephritis and proteinuria. A total of 30 healthy children were enrolled in the normal control group (group N). The primary endpoints were the detection of TLR3 and 4 mRNA and protein expression levels in PBMCs by flow cytometry and quantitative polymerase chain reaction. The mRNA and protein expression levels of TLR4 in the PBMCs were significantly higher in groups A, B and C when compared with group N. In addition, the mRNA and protein expression levels of TLR4 in group C were much higher when compared with groups A and B. A positive correlation was identified between TLR4 protein expression and 24-h urinary protein levels in group C. The expression levels of TLR3 did not significantly differ among the groups. Protein and mRNA expression levels of TLR4 in PBMCs significantly increased and exhibited a positive correlation with urinary protein excretion. These results indicate that aberrant activation of TLR4 may be relevant to the development of HSP nephritis.

[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.

[Levels of IL-12 produced by dendritic cells and changes of TH1/TH2 balance in children with Henoch-Schonlein purpura].

OBJECTIVE: To study the changes of IL-12 produced by dendritic cells in peripheral blood in children with Henoch-Schonlein purpura (HSP), and to explore its influence on TH1/TH2 balance in order to elucidate its significance in the pathogenesis of HSP. METHODS: The levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and interleukin-12 (IL-12) in plasma were determined by ELISA in 60 HSP children (HSP group) and 21 healthy children (Control group). Peripheral blood mononuclear cells (PBMC) of 22 HSP patients and 21 healthy children were cultured in vitro and then were transformed into dendritic cells. The levels of IL-12 in the supernatant were detected by ELISA and the positive expression rate of CD1a(+) was detected by indirect immunofluorescence procedure. RESULTS: 1) The levels of IFN-gamma and the ratio of IFN-gamma/IL-4 in plasma of the HSP group were lower than those of the Control group (IFN-gamma 30.59 +/- 11.27 pg/mL vs 43.38 +/- 19.19 pg/mL; IFN-gamma/IL-4 ratio 0.70 +/- 0.28 vs 1.33 +/- 0.57) (P < 0.01). The levels of IL-12 in the HSP group were also lower than those of the Control group (153.95 +/- 91.88 pg/mL vs 323.06 +/- 162.34 pg/mL; P < 0.01). In contrast, the levels of IL-4 were higher than those of the Control group (45.08 +/- 9.19 pg/mL vs 32.95 +/- 7.10 pg/mL; P < 0.01). The plasma levels of IL-12 positively correlated with the IFN-gamma levels (r=0.52, P < 0.01) and the ratio of IFN-gamma/IL-4 (r=0.43, P < 0.01) in the HSP group. 2) The IL-12 levels in the supernatant of the HSP group were lower than those of the Control group (357.06 +/- 153.56 pg/mL vs 489.80 +/- 213.45 pg/mL; P < 0.05), and had a positive correlation with the plasma IL-12 levels (r=0.74, P < 0.01). 3) The positive expression rate of CD1a(+) of the HSP group was lower than that of the Control group [(27.42 +/- 10.75)% vs (35.68 +/- 12.18)%; P < 0.05], and positively correlated with the IL-12 levels in the supernatants (r=0.57, P < 0.01) and in plasma (r=0.68, P < 0.01). CONCLUSIONS: There was an imbalance of TH1/TH2 in HSP children. The decrease of TH1 function had a positive correlation with the low levels of IL-12 in plasma, while the latter correlated closely with decreased number and / or function of dendritic cells, suggesting that the decreased number and / or function of dendritic cells in peripheral blood resulted in the imbalance of TH1/TH2 indirectly.