Visual effect of air pollution on the need for arousal and variety-seeking behavior.

Research on air pollution, one of the most common environmental factors, has primarily focused on its effects on physical, mental, and cognitive health. However, air pollution-induced achromatic color of an environment, which is a prominent feature of air pollution, has received little attention. This study explored the visual effects of air pollution on the variety-seeking purchase behavior of consumers through two scenario-based experiments and primed manipulation (Study 1 and Study 2) and one natural experiment using data from a local fruit chain store (Study 3). Study 1 tested the main effect of air pollution on the variety-seeking behavior and found that primed air pollution increased variety-seeking when consumers purchased beverages. Study 2 broadened the category and tested the mechanism, and the results indicated that primed air pollution increased the variety of purchased chocolates and demonstrated the mediating effect of the need for arousal. Study 3 tested the boundary condition and extended the external validity with actual purchases. The results revealed that severe air pollution increased the purchased SKUs by 22.9% and visibility reduced the moderation effect. This research extended the literature on the visual effect of air pollution by providing evidence of the effects of air pollution on variety-seeking behavior through the need for arousal. And, product managers could leverage the results by offering a greater variety of goods on days with air pollution to increase sales.

Protective effect of zinc gluconate on intestinal mucosal barrier injury in antibiotics and LPS-induced mice.

Objective: The aim of the study is to investigate the function and mechanism of Zinc Gluconate (ZG) on intestinal mucosal barrier damage in antibiotics and Lipopolysaccharide (LPS)-induced mice. Methods: We established a composite mouse model by inducing intestinal mucosal barrier damage using antibiotics and LPS. The animals were divided into five groups: Control (normal and model) and experimental (low, medium, and high-dose ZG treatments). We evaluated the intestinal mucosal barrier using various methods, including monitoring body weight and fecal changes, assessing pathological damage and ultrastructure of the mouse ileum, analyzing expression levels of tight junction (TJ)-related proteins and genes, confirming the TLR4/NF-κB signaling pathway, and examining the structure of the intestinal flora. Results: In mice, the dual induction of antibiotics and LPS led to weight loss, fecal abnormalities, disruption of ileocecal mucosal structure, increased intestinal barrier permeability, and disorganization of the microbiota structure. ZG restored body weight, alleviated diarrheal symptoms and pathological damage, and maintained the structural integrity of intestinal epithelial cells (IECs). Additionally, ZG reduced intestinal mucosal permeability by upregulating TJ-associated proteins (ZO-1, Occludin, Claudin-1, and JAM-A) and downregulating MLCK, thereby repairing intestinal mucosal barrier damage induced by dual induction of antibiotics and LPS. Moreover, ZG suppressed the TLR4/NF-κB signaling pathway, demonstrating anti-inflammatory properties and preserving barrier integrity. Furthermore, ZG restored gut microbiota diversity and richness, evidenced by increased Shannon and Observed features indices, and decreased Simpson's index. ZG also modulated the relative abundance of beneficial human gut bacteria (Bacteroidetes, Firmicutes, Verrucomicrobia, Parabacteroides, Lactobacillus, and Akkermansia) and harmful bacteria (Proteobacteria and Enterobacter), repairing the damage induced by dual administration of antibiotics and LPS. Conclusion: ZG attenuates the dual induction of antibiotics and LPS-induced intestinal barrier damage and also protects the intestinal barrier function in mice.

Resolving sulfation PTMs on a plant peptide hormone using nanopore sequencing.

Peptide phytohormones are decorated with post-translational modifications (PTMs) that are crucial for receptor recognition. Tyrosine sulfation on these hormones is essential for plant growth and development1. Measuring the occurrence and position of sulfotyrosine is, however, compromised by major technical challenges during isolation and detection2. We recently introduced a nanopore peptide sequencing method that sensitively detects PTMs at the single-molecule level3. By translocating PTM variants of the plant pentapeptide hormone phytosulfokine (PSK) through a nanopore, we here demonstrate accurate identification of sulfation and phosphorylation on the two tyrosine residues of PSK. Sulfation can be clearly detected and distinguished (>90%) from phosphorylation on the same residue. Moreover, the presence or absence of PTMs on the two close-by tyrosine residues can be accurately determined (>96% accuracy). Our findings demonstrate the extraordinary sensitivity of nanopore protein measurements, providing a new tool for identifying sulfation on peptide phytohormones and promising wider applications to identify protein PTMs.

Cumulative Exposure to Oxidized Low-density Lipoprotein is a Potential Predictor for Prognosis in Acute Ischemic Stroke: A Cohort Study.

BACKGROUND: Oxidized Low-Density Lipoprotein (ox-LDL) is crucial in the recrudescence and prognosis of acute ischemic stroke (AIS). We aimed to probe into the influence of cumulative ox-LDL exposure on the 90-day prognosis of AIS. METHODS: Patients with AIS were recruited in this research. AIS severity at admission was estimated with infarct volumes and National Institute of Health Stroke Scale (NIHSS) scores. AIS prognosis was assessed using Modified Rankin Scale (mRS) scores at 90 days and the change in NIHSS scores from admission to discharge. Cumulative ox-LDL exposure was defined as ox-LDL level (pg/mL) multiplied by age(y). Multivariate logistic regression analysis was employed to reveal the correlation between exposure factors and the prognosis of AIS. The prognostic prediction ability of cumulative ox-LDL exposure was compared with cumulative LDL exposure by the receiver operating characteristic curve (ROC). RESULTS: Higher cumulative ox-LDL exposure was related to worse prognosis, including neurological worsening at discharge (NIHSS increasing more than 2 points) (OR = 3.02, 95% CI, 1.30-6.98, P = 0.01) and poor functional prognosis at 90 days (mRS ≥ 3) (OR = 21.21, 95% CI, 4.72-95.36, P < 0.001). As multivariate regression analysis showed, significantly increased cumulative ox-LDL exposure was relevant to poor functional prognosis at 90 days (OR = 9.92, 95% CI, 1.23-79.76, P = 0.031), but not with neurological worsening at discharge (P = 0.414). ROC curve revealed that cumulative ox-LDL exposure had a higher predictive value (AUC = 0.843, P < 0.001) for functional prognosis of AIS than cumulative LDL exposure (AUC = 0.629, P = 0.023). CONCLUSION: Cumulative ox-LDL exposure has a positive correlation with poor prognosis at 90 days of AIS, and has a more accurate predictive ability than cumulative LDL exposure.

Taurine Regulates the Expression of Interleukin -17/10 and Intestinal Flora and Protects the Liver and Intestinal Mucosa in a Nonalcoholic Fatty Liver Disease Rat Model.

Purpose: To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU). Methods: Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method. Results: The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05). Conclusion: TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.

Determination of the median lethal dose of zinc gluconate in mice and safety evaluation.

BACKGROUND: Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. METHODS: A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. RESULTS: The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. CONCLUSION: The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.

DNase I targeted degradation of neutrophil extracellular traps to reduce the damage on IgAV rat.

BACKGROUND: In the past two years, studies have found a significant increase in neutrophil extracellular traps (NETs) in patients with IgA vasculitis (IgAV), which is correlated with the severity of the disease. NETs have been reported as an intervention target in inflammatory and autoimmune diseases. This study aimed to investigate the effect of targeted degradation of NETs using DNase I in IgAV rat model. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into three groups: the IgAV model group, the DNase I intervention group and the normal control group, with an average of 8 rats in each group. The model group was established by using Indian ink, ovalbumin, and Freund's complete adjuvant. In the intervention group, DNase I was injected through tail vein 3 days before the end of established model. The circulating cell free-DNA (cf-DNA) and myeloperoxidase-DNA (MPO-DNA) were analyzed. The presence of NETs in the kidney, gastric antrum and descending duodenum were detected using multiple fluorescences immunohistochemistry and Western blots. Morphological changes of the tissues were observed. RESULTS: After the intervention of DNase I, there was a significant reduction in cf-DNA and MPO-DNA levels in the intervention group compared to the IgAV model group (all P<0.001). The presence of NETs in renal, gastric, and duodenal tissues of the intervention group exhibited a significant decrease compared to the IgAV model group (P < 0.01). Moreover, the intervention group demonstrated significantly lower levels of renal MPO and citrullinated histone H3 (citH3) protein expression when compared to the IgAV model group (all P < 0.05). The HE staining results of intervention group demonstrated a significant reduction in congestion within glomerular and interstitial capillaries. Moreover, there was a notable improvement in gastric and intestinal mucosa necrosis, congestion and bleeding. Additionally, there was a substantial decrease in inflammatory cells infiltration. CONCLUSION: The degradation of NETs can be targeted by DNase I to mitigate tissue damage in IgAV rat models. Targeted regulation of NETs holds potential as a therapeutic approach for IgAV.

AP profiling resolves co-translational folding pathway and chaperone interactions in vivo.

Natural proteins have evolved to fold robustly along specific pathways. Folding begins during synthesis, guided by interactions of the nascent protein with the ribosome and molecular chaperones. However, the timing and progression of co-translational folding remain largely elusive, in part because the process is difficult to measure in the natural environment of the cytosol. We developed a high-throughput method to quantify co-translational folding in live cells that we term Arrest Peptide profiling (AP profiling). We employed AP profiling to delineate co-translational folding for a set of GTPase domains with very similar structures, defining how topology shapes folding pathways. Genetic ablation of major nascent chain-binding chaperones resulted in localized folding changes that suggest how functional redundancies among chaperones are achieved by distinct interactions with the nascent protein. Collectively, our studies provide a window into cellular folding pathways of complex proteins and pave the way for systematic studies on nascent protein folding at unprecedented resolution and throughput.

Neutrophil extracellular traps involved in the pathogenesis of IgA vasculitis: Confirmed in two IgAV rat models.

BACKGROUND: Neutrophil extracellular traps (NETs) have been found to play a role in the development of autoimmune diseases. In the past two years, studies have demonstrated a significantly increase of NETs in skin tissues during the early stages of IgAV, indicating their involvement in disease activity among children with IgAV. However, the presence of NETs in IgAV animal models has not yet been reported. The objective of this study is to investigate whether NETs are involved in the pathogenesis of IgA vasculitis (IgAV) rats. METHODS: Twenty-four SD rats were randomly divided into three groups: the ovalbumin group, the gliadin group, and the control group. The IgAV rat models were established administering Indian ink with ovalbumin (ovalbumin group) or gliadin (gliadin group) with Freund's complete adjuvant. The cell-free DNA (cf-DNA) was quantified by using dsDNA quantification kit, while the levels of Immunoglobulins, complement C3 and myeloperoxidase-DNA (MPO-DNA) in serum were tested using enzyme linked immunosorbent assay (ELISA). The IgA, complement C3 and NETs in tissues were detected through multiple immunofluorescences. RESULTS: Both the ovalbumin group and gliadin group showed IgA and C3 deposition in various tissues, including the glomerular mesangial region, skin, and digestive tract, while the control group showed no such deposition. The levels of circulatory cf-DNA and MPO-DNA, which are components of NETs, were significantly elevated in both ovalbumin and gliadin groups compared with the control group. Furthermore, the presence of NETs were found in gastrointestinal and renal tissues of the ovalbumin and gliadin groups, but not in the control group. CONCLUSIONS: IgAV model rat can be established through the combination of ovalbumin and gliadin with Indian ink and Freund's complete adjuvant. This study provides the first confirmation that NETs are involved in the pathogenesis of IgAV rat.

Hypobaric Hypoxia Aggravates Renal Injury by Inducing the Formation of Neutrophil Extracellular Traps through the NF-κB Signaling Pathway.

OBJECTIVE: The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. METHODS: A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining. RESULTS: After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated. CONCLUSION: HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.

Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA.

Acute kidney injury (AKI) is a serious and frequently observed disease associated with high morbidity and mortality. Weighted gene co-expression network analysis (WGCNA) is a research method that converts the relationship between tens of thousands of genes and phenotypes into the association between several gene sets and phenotypes. We screened potential target genes related to AKI through WGCNA to provide a reference for the diagnosis and treatment of AKI. Key biomolecules of AKI were investigated based on transcriptome analysis. RNA sequencing data from 39 kidney biopsy specimens of AKI patients and 9 normal subjects were downloaded from the GEO database. By WGCNA, the top 20% of mRNAs with the largest variance in the data matrix were used to construct a gene co-expression network with a p-value < 0.01 as a screening condition, showing that the blue module was most closely associated with AKI. Thirty-two candidate biomarker genes were screened according to the threshold values of |MM|≥0.86 and |GS|≥0.4, and PPI and enrichment analyses were performed. The top three genes with the most connected nodes, alanine-glyoxylate aminotransferase 2(AGXT2), serine hydroxymethyltransferase 1(SHMT1) and aconitase 2(ACO2), were selected as the central genes based on the PPI network. A rat AKI model was constructed, and the mRNA and protein expression levels of the central genes in the model and control groups were verified by PCR and immunohistochemistry experiments. The results showed that the relative mRNA expression and protein levels of AGXT2, SHMT1 and ACO2 showed a decrease in the model group. In conclusion, we inferred that there is a close association between AGXT2, SHMT1 and ACO2 genes and the development of AKI, and the down-regulation of their expression levels may induce AKI.

Deep medullary veins: a promising neuroimaging marker for mild cognitive impairment in outpatients.

BACKGROUND AND PURPOSE: Mild cognitive impairment is an age-dependent pre-dementia state caused by varied reasons. Early detection of MCI helps handle dementia. Vascular factors are vital for the occurrence of MCI. This study investigates the correlation between deep medullary veins and multi-dimensional cognitive outcomes. MATERIALS AND METHODS: A total of 73 participants with MCI and 32 controls were enrolled. Minimum Mental State Examination and Montreal Cognitive Assessment were used to examine the global cognitive function, and different cognitive domains were measured by specific neuropsychological tests. MRI was used to assess the visibility of the DMV and other neuroimage markers. RESULTS: DMV score was statistically significantly higher in the MCI group compared with the control group (P = 0.009) and independently related to MCI (P = 0.007). Linear regression analysis verified that DMV score was linearly related to global cognition, memory, attention, and executive function after adjusting for cerebrovascular risk factors. CONCLUSION: DMV score was independently related to the onset of MCI, and correlates with overall cognition, memory, attention, and executive function in outpatients.

Rosiglitazone attenuates hypoxia-induced renal cell apoptosis by inhibiting NF-κB signaling pathway in a PPARγ-dependent manner.

BACKGROUND: In recent years, peroxisome proliferator-activated receptor γ (PPARγ) has been found to be closely associated with hypoxia renal disease. The aim of this study was to investigate the relationship between rosiglitazone and mitochondrial apoptosis in renal tissue and its associated mechanisms. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups (n = 8 in each): normal control group, hypoxia injury group (equal volume of 0.9% saline), and PPARγ agonist group (Rosiglitazone, 10 mg/kg · d, intraperitoneally). The hypoxia injury group and PPARγ agonist group were placed in a hypoxia chamber and the simulated altitude was set at 7,000 m for 7 days. Blood and kidney samples were collected after 7 days. The quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of PPARγ, nuclear factor kappa-B (NF-κB), B-cell lymphoma-2 (Bcl-2), and Bax. RESULTS: The results showed that compared with the normal control group, the renal tissue of rats after hypoxia was severely damaged, as shown by massive renal tubular epithelial cell degeneration and detachment, and renal tubular dilation. The NF-κB protein expression significantly increased, the Bcl-2 protein and mRNA expression significantly decreased, and Bax protein and mRNA expression significantly increased (p < .05 for all). Renal injury was much less severe in the PPARγ agonist group compared to the hypoxia injury group. CONCLUSIONS: Rosiglitazone can alleviate hypoxia renal injury, with the possible mechanism involving attenuation of apoptosis by inhibiting the activation of the NF-κB signaling pathway in a PPARγ-dependent manner and increasing Bcl-2 and decreasing Bax expression.

Screening for Wilson's disease in acute liver failure: A new scoring system in children.

Background: Wilson's disease (WD) is a rare cause of acute liver failure (ALF) and has a high fatality rate. Rapid and accurate diagnosis is important for ALF because of WD (ALF-WD). Our objective was to establish a simple, rapid, and accurate diagnostic test to distinguish ALF-WD from non-WD ALF (NWDALF) in children. Materials and methods: The data from all cases with pediatric ALF were retrospectively collected and analyzed. We performed receiver operator characteristics curve (ROC) analysis and confirmed the optimum cut-off points. Results: Fifty-eight patients with pediatric ALF (12 with WD, 46 with other etiologies) were included. Older age was observed in ALF-WD compared to NWDALF (11.16 ± 2.51 years vs. 3.34 ± 3.81 years, p < 0.001). An analysis based on routine biochemical testings revealed that total bilirubin (TBil), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST:ALT ratio, alkaline phosphatase (ALP), ALP:TBil ratio, serum albumin, gamma-glutamyl transferase, cholinesterase, hemoglobin, and platelet were statistically significant between the ALF-WD and NWDALF groups. The optimum cut-off points were obtained through ROC analysis. A scoring system was formed by assigning a score of 1 or 0 to patients who met the 13 cut-off points. Using ROC analysis, we determined a cut-off point of ≥ 6.5 for ALF-WD with 91.7% sensitivity and 97.8% specificity (p < 0.0001). In addition, a best cut-off point of ≥ 1.5 based on only five variables (ALT, AST, AST:ALT ratio, ALP, and ALP:TBil ratio), had 100% sensitivity and 91.3% specificity for ALF-WD (p < 0.0001). Based on this, when age was calculated as the sixth indicator, the best cut-off value of ≥ 2.5 had 100% sensitivity and 97.8% specificity (p < 00.0001). Conclusion: Our study developed a new scoring system that consists of simple laboratory tests with good sensitivity and specificity and can be used by clinicians to quickly distinguish ALF-WD from NWDALF in children.

An Emerging Role for Neutrophil Extracellular Traps in IgA Vasculitis: A Mini-Review.

Immunoglobulin A vasculitis (IgAV) is the most common systemic small vessel vasculitis in childhood. Its clinical manifestations are non-thrombocytopenic purpura, accompanied by gastrointestinal tract, joint, kidney and other organ system involvement. The pathogenesis of IgAV has not been fully elucidated. It may be related to many factors including genetics, infection, environmental factors, and drugs. The most commonly accepted view is that galactose-deficient IgA1 and the deposition of IgA and complement C3 in small blood vessel walls are key contributors to the IgAV pathogenesis. Extensive neutrophil extracellular traps (NETs) in the peripheral circulation and skin, kidney, and gastrointestinal tissue of patients with IgAV has been identified in the past two years and is associated with disease activity. This mini-review provides a possible mechanism for NETs involvement in the pathogenesis of IgAV.

Congenital disorder of glycosylation caused by mutation of ATP6AP1 gene (c.1036G>A) in a Chinese infant: A case report.

BACKGROUND: The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases (V-ATPase) is located on chromosome Xq28. Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation (CDG). CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs. Therefore, the clinical presentation of patients with ATP6AP1-CDG varies widely. In this report, we present a case of ATP6AP1-CDG in a Chinese infant, with clinical features and genotype. CASE SUMMARY: An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital. A post-admission examination at our hospital revealed abnormalities in the infant's liver, brain, and immune system. Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A (p.E346K) in exon 9 of the ATP6AP1 gene. This variant of the ATP6AP1 gene has not been reported in East Asian countries until now. CONCLUSION: Based on the infant's clinical manifestations and the results of genetic detection, he was clearly diagnosed with ATP6AP1-CDG. The clinical manifestations of children with CDG vary widely. Genetic testing analysis helps in the clinical diagnosis of children with CDG.

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis.

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children. Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed. Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples. Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.

Colony-Stimulating Factors on Mobilizing CD34+ Cells and Improving Neurological Functions in Patients With Stroke: A Meta-Analysis and a Systematic Review.

Background and Purpose: CSF therapy is considered a promising therapeutic approach for stroke. We performed a meta-analysis to explore the safety and efficacy of CSF in published clinical stroke studies. Methods: We searched articles online and manually. Two reviewers selected studies independently, selecting data based on study quality, characteristics of intervention (administration time, observation time, type, dose, and injection approach of CSF), and the baseline characteristics of patients (age, sex, hypertension, diabetes, smoker, and lipids) were extracted. Main prognosis outcomes were measured as all-cause death in severe adverse events (SAE) and recurrent stroke in SAE. Secondary outcomes were measured as CD34+ cell counts in periphery blood at day 5, National Institutes of Health Stroke Scale (NIHSS), and Barthel index (BI), Side effects of CSF were taken as the indicator of safety. STATA13 software was used to perform the meta-analysis.Keywords: Stroke, Colony-stimulating factor, Meta-analysis, therapy, Neurological Diseases Results: This meta-analysis involved 485 patients from eight studies. Among them, 475 patients from seven studies were gauged SAE (all-cause death), 393 patients from six studies were checked SAE (recurrent stroke); 137 patients from three studies underwent CD34+ measurement, 389 patients from six studies were tested NIHSS and 307 patients from five studies accessed BI. Compared with the control group, both all-causes death (RR= 1.73, 95%CI= (0.61, 4.92), P=0.735, I2=0.0%) and recurrent stroke (RR= 0.43, 95%CI= (0.14, 1.32), P=0.214, I2=33.1%) present no statistical differences, indicating that the application of CSF does not statistically alter the prognosis of patients with stroke. The application of CSF effectively enhanced CD34+ cell counts in periphery blood at day 5 (SMD= 1.23, 95%CI= (0.54, 1.92), P=0.04, I2=69.0%) but did not statistically impact NIHSS (SMD= -0.40, 95%CI= (-0.93, 0.13), P ≤ 0.001, I2=79.7%) or BI (SMD= 0.04, 95%CI= (-0.38, 0.46), P=0.068, I2=54.3%). Conclusion: Our study consolidates the security of CSF administration for its exerting no effect on detrimental outcomes. It has proven to be effective in elevating CD34+ cell counts in periphery blood at day 5, indicating CSF may participate in stroke recovery, but its efficacy in stroke recovery remains detected.

Clinical value of NT-proBNP measurements in assessing patients in the pediatric intensive care unit.

BACKGROUND: N-terminal brain natriuretic peptide precursor (NT-proBNP) and brain natriuretic peptide (BNP) are mainly produced and secreted in the heart. In 2008, the European Heart Association recommended that serum BNP/NT-proBNP levels should be included in one of the diagnostic criteria of heart failure. Serum NT-proBNP is more stable than BNP, and the detection results are less affected by objective factors, so it is widely used. At present, NT-proBNP has long been beyond the scope of heart failure markers, and has a wide range of clinical value in the evaluation and prediction of some serious diseases. This study prospectively studied the predictive value of serum NT-proBNP in pediatric intensive care unit (PICU). METHODS: This was a prospective study involving 375 children in the PICU. The patients were divided into three groups: non-risk, low-risk, and high-risk groups. Serum NT-proBNP levels and the 28-day mortality rate were analyzed. RESULTS: The serum NT-proBNP levels and the mortality of the high-risk group was significantly higher than those of the low- and non-risk groups (P<0.01 in both cases). Receiver operating characteristic curve (ROC curve) analysis showed that the area under the curve was 0.705 (P<0.001, sensitivity =0.643, specificity =0.692). Death multivariate binary logistic regression analysis indicated that NT-proBNP was not an independent factor for 28-day mortality. CONCLUSIONS: Serum NT-proBNP was significantly correlated with the severity of illness for critically ill patients in PICU. Although high levels of NT-proBNP indicated greater severity, this was not an independent risk factor affecting the prognosis of patients.