Evaluation of diagnostic potential of CD38 in rickets.

BACKGROUND: Rickets occurs in infants and children (aged 2 months to 3 years), compromising their skeletal development and damaging nervous, hematopoietic, immune, and other system functions. This study aimed to explore the significance of CD38 in rickets. METHODS: The microarray dataset GSE22523 was analyzed to obtain differentially expressed genes in rickets patients. A total of 36 rickets patients and healthy controls were recruited for the study, and their blood samples were collected, followed by detecting mRNA levels of CD38 using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the significance of CD38 in rickets patients was analyzed by receiver operating characteristic (ROC) analysis, while the correlation between CD38 and 25-hydroxy-vitamin D (25OHD)/parathyroid hormone (PTH) was analyzed with Pearson's correlation. RESULTS: Results showed that CD38 mRNA levels and PTH contents were significantly increased in the rickets patients while 25OHD contents were decreased. Correlation analysis indicated that CD38 was positively correlated with PTH and negatively correlated with 25OHD in both serum and plasma samples of rickets patients. Moreover, ROC analysis showed that serum CD38 was 0.9005 (95 % CI: 0.8313-0.9696), and the AUCs of plasma CD38 was 0.7215 (95 % CI: 0.6031-0.8398) in differentiating rickets patients from healthy persons, advocating serum CD38 had better diagnostic value. CONCLUSION: CD38 mRNA levels were upregulated in rickets patients and closely correlated with PTH and 25OHD contents, indicating CD38 might be a diagnostic marker of rickets patients. Further research on the diagnostic utility of CD38 is necessary for the diagnosis and treatment of ricketsin rickets in the future.

Diagnosis and treatment of "medial to lateral diagonal injury of the elbow" in children: Concomitant medial epicondylar and radial neck fractures.

Purpose: The simultaneous and ipsilateral occurrence of medial epicondylar and radial neck fractures is rare. This study evaluated the clinical and radiological outcomes of medial to lateral diagonal injury of the elbow (MELAINE). Methods: Six males and 6 females were diagnosed with MELAINE (left: 10, 83.3%; right: 2, 16.7%). Medial epicondylar and radial neck fractures were classified according to Papavasiliou's classification (seven type II, two type III, three type IV) and Judet's classification (three type I, four type II and five type III), respectively. All patients underwent surgery. The carrying angle, range of motion, and Kim et al. Elbow Performance Score were used to evaluate clinical and functional outcomes; related complications were recorded. Results: Mean age at injury and mean follow-up were 11.1 ± 2.5 (range, 6-14) and 40 ± 25.6 months (range, 13-90), respectively. All fractures consolidated in 6.3 ± 1.2 weeks on average (4-9). Outcomes were good (n = 1; 8.3%) to excellent (n = 11; 91.7%). The carrying angle of the injured and uninjured side was 15.5°± 2.6° and 14.7°± 2°, respectively (p = 0.218). The range of motion of elbow flexion-extension and forearm pronation-supination of the injured side was 144.2°± 10.4°, 4.6°± 5.4°, 76.7°± 9.1°, 80.4°± 9.2°, respectively, with no significant differences from the healthy side (p > 0.05). The Elbow Performance Score of the injured and uninjured side was 96.3 ± 5.3 and 98.8 ± 2.3, respectively (p = 0.139). No cases of infection, cubitus valgus, stiffness, or instability were recorded. Conclusion: Although uncommon, MELAINE should not be neglected. Surgery aims to stabilize the elbow and avoid valgus deformity. If diagnosed and treated, clinical and radiological results are excellent in most cases.

Good outcomes of elbow arthroscopy-assisted absorbable screw fixation for capitellum fracture of the humerus in children: a case series.

Background: Capitellum fractures are rare coronal fractures of the distal humerus which accounts for 6% of all distal humeral fractures and only 1% of all elbow fractures. The purpose of this study was to investigate the efficacy and complications of arthroscopically assisted reduction and fixation with absorbable screws for capitellar fracture of the humerus in children. Methods: This was a retrospective case series study, which considered four patients (4 elbows), ranging from 10 to 15 years old, who were treated by arthroscopic-assisted percutaneous absorbable screw between 2018 and 2020. The elbow flexion-extension and forearm supination-pronation ranges of motion (ROM) were measured at the preoperative examination and last follow-up examination. Finally, the clinical and radiological results were assessed. Results: The result of operations is satisfactory. The mean follow-up was 3.0 years (range 2-3.8 years). Average range of motion significantly improved from pre- to postoperation, with forearm supination from 60°(50°-60°) to 90°(90°) and pronation improved from 75°(70°-80°) to 90°(90°). The postoperative elbow flexion-extension range of motion was significantly higher compared with range of motion before surgery (P < 0.001; r = 0.949). At the final follow-up examination, the Mayo Elbow Performance Score was excellent. Satisfactory clinical results were achieved in all patients, and no postoperative complications were observed. Conclusions: It is an effective and safe surgical option to use arthroscopic-assisted percutaneous absorbable screw fixation for treating capitellum fracture of the humerus without any complications in children. Level of evidence: Level IV; case series.

The function of Piezo1 in hepatoblastoma metastasis and its potential transduction mechanism.

Background: Hepatoblastoma (HB) is the most common primary malignant liver tumor in children. The prognosis of HB metastasis is poor, despite the increasing diversity of treatment. Piezo, a ubiquitously expressed membrane mechano-transduction protein, is involved in the process of tumor cell migration. Under the gene expression profiling interactive analysis (GEPIA) database, Piezo1 was highly expressed in HB and negatively correlated with the overall survival time. Methods: Firstly, the expression of Piezo1 in both paracancerous and HB tissues (n = 7) was detected, and the prognostic value of Piezo1 was assessed in HB (n = 160) patients. Secondly, the inhibition and overexpression of Piezo1were executed in two HB cell lines, HepG2 and Huh 6. Methyl thiazolyl tetrazolium (MTT), wound healing and trans-well assays were performed to identify the effect of Piezo1 on the proliferation and metastasis of HB cells, respectively. In addition, a co-immunoprecipitation assay was performed to determine whether Piezo1 has an interaction with HIF-1α. Finally, the expressions level of Piezo1, HIF-1α, and VEGF by overexpression/inhibition each other were detected by RT-qPCR and western blots to find a possible signaling channel in HB metastasis. Results: We found that Piezo1 was highly expressed in HB tissues and associated with poor prognosis of patients. Piezo1 was related to cell proliferation in HepG2 and Huh 6 cells. We also found that Piezo1 stimulated HIF-1α expression. Meanwhile, overexpression of Piezo1 promoted the migration and invasion of HB cells, while the promotion was not detected when HIF-1α was suppressed. Additionally, the silencing of HIF-1α inhibited the expression of VEGF, but showed no effect on Piezo1 expression. Conclusion: In this study, we identified that Piezo1 was involved in HB metastasis, and the Piezo1-HIF-1α-VEGF axis could be a possible signaling pathway in HB metastasis.

Comparison of arthroscopic internal drainage and open excision for the treatment of popliteal cysts.

BACKGROUND: The purpose of this study was to introduce the arthroscopic internal drainage with anterior-anteromedial approach for the treatment of popliteal cysts in children. To compare its clinical efficacy with open surgery. METHODS: This was a retrospective case-control study of 102 patients diagnosed with popliteal cysts from January 2018 to February 2020 who received surgery. The study included 27 cases with minimally invasive group (MI group) and 75 cases with open surgery group (OS group). The MI group included 21 males and 6 females, age 6.71 ± 2.16 years who received arthroscopic internal drainage of the cysts to adequately widen the valve opening between the cyst and the articular cavity, excised the fibrous diaphragm without complete excision of the cyst wall. The OS group included 57 males and 18 females, age 6.21 ± 1.67 years who received open excision. The clinical parameters regarding the preoperative characteristics and surgical results were compared. Ultrasound or MRI was used to identify the recurrence of the popliteal cysts. Rauschning-Lindgren grade was recorded to evaluate the clinical outcome. RESULTS: All patients were followed up for at least 24 months. There were no significant differences between the two groups in age, gender, left and right sides, disease time, cyst size, length of hospitalization, preoperative Rauschning-Lindgren grade (p > 0.05). At the last follow-up, the preoperative and postoperative Rauschning-Lindgren grade was improved in both groups. Compared with the OS group, operation time was significantly shortened in the MI group (28.89 ± 4.51 min vs 52.96 ± 29.72 min, p < 0.05). The MI group was superior to the OS group in terms of blood loss and plaster fixation, with statistical significance (p < 0.05). There was obvious difference in recurrence rate between the two groups (0% vs 17.33%, p = 0.018). No postoperative complications occurred during the follow-up period. CONCLUSIONS: Compared with open excision, the treatment of popliteal cyst in children by arthroscopic internal drainage to expand the articular cavity and eliminate the "one-way valve" mechanism between the cyst and the articular cavity exhibits better clinical outcomes and significantly reduces the recurrence rate, which is worthy of further clinical promotion.

Effects of prophylactic antibiotic administration and antibiotic timing on culture results and clinical outcomes of paediatric musculoskeletal infection: a protocol for a randomised controlled clinical trial.

INTRODUCTION: Musculoskeletal infection (MSI) is a common cause of morbidity among the paediatric population. Some clinicians recommend withholding prophylactic antibiotics until culture collection with an aim to improve the culture sensitivity. However, a recent retrospective study reported that prophylactic antibiotic administration did not affect culture sensitivities in either disseminated or local MSI in paediatric population, which is surprising. The aim of the present study is to investigate the effects of prophylactic antibiotic administration and the timing of antibiotic administration on culture sensitivity and clinical outcomes of paediatric MSI. METHODS AND ANALYSIS: A randomised controlled clinical trial will be carried out. Individuals aged 0-18 years with a diagnosis of MSI will be screened and evaluated at the Shenzhen Children's Hospital. The participants will be randomly allocated into four groups, and they will receive the antibiotic treatment at different time points, that is, 1 week, 3 days, 1 day prior to tissue culture collection and 1 day after tissue culture collection, respectively. The primary outcome will be culture sensitivity. In addition, the disease-related markers including white blood cell count, C reactive protein, erythrocyte sedimentation rate, vital signs as well as the length of hospital stay will be measured or recorded accordingly. Using χ2 tests, the rates of positive cultures will be compared between different groups. Statistical comparisons between the different patient groups regarding the confounding and outcome variables will be conducted using independent t-tests, Mann-Whitney U tests, χ2 tests and Fisher's exact tests as appropriate with the significance level set to 5% (p<0.05). ETHICS AND DISSEMINATION: This study has received ethical approval. The findings will be disseminated both in scientific conferences and peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100041631.

Personal ozone exposure and stress hormones in the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes.

BACKGROUND: The effect of ozone exposure on neuroendocrine responses in humans has not been fully studied. METHODS: We conducted a longitudinal panel study with four rounds of visits among 43 college students in Shanghai, China, from May to October 2016. For each visit, we monitored personal real-time ozone exposure for consecutive 3 days (from 8:00 a.m. to 6:00p.m. each day), followed by blood sample collection. We measured serum levels of three hormones in the hypothalamus-pituitaryadrenal (HPA) axis, including corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol, and three catacholamines indicating sympathetic-adrenal-medullary (SAM) axis activation, including adrenaline, noradrenaline, and dopamine. We applied linear mixed-effect models to evaluate the associations between ozone exposure and these neurohormones and further compared models using personal and fixed-site ozone measurements. MAIN RESULTS: At lag 0-8 h, personal ozone exposure ranged from 4.5 ppb to 104.3 ppb with an average of 21.0 ± 14.7 ppb, which was approximately half of the ambient ozone concentration. Per 10-ppb increase in personal ozone exposure (lag 0-8 h) was associated with increases of 5.60% [95% confidence interval (CI): 2.30%, 9.01%] in CRH, 5.91% (95% CI: 0.55%, 11.56%) in cortisol, and 10.13% (95% CI: 2.75%, 18.05%) in noradrenaline, whereas associated with a 12.15% (95% CI: 1.23%, 21.87%) decrease in dopamine. Overall, models using personal ozone measurements yielded larger effect estimates and better model fits than models using fixed-site measurements. CONCLUSIONS: Short-term exposure to low levels of ozone may lead to activation of the HPA and SAM axes.

Comparison of different treatments for children with radial neck fracture and analysis of prognostic factors.

INTRODUCTION: The aim of this was to analyze the effect of different treatment options on radial neck fractures in children and to explore the factors affecting the prognosis of fractures. METHODS: The clinical data of 131 children with radial neck fractures admitted to our hospital from 2010 to 2018 were retrospectively analyzed, and the patients were divided into 6 groups according to treatment methods [manual reduction with Kirschner wires (K-wires) for internal fixation (group A); manual reduction with elastic stable intramedullary nails (ESINs) for internal fixation (group B); leverage reduction with K-wires for internal fixation (group C); leverage reduction with ESINs for internal fixation (group D); manual and leverage reduction with K-wires/ESINs for internal fixation (group E); and open reduction with K-wires/ESINs for internal fixation (group F)]. Postoperative elbow function and complications were analyzed. RESULTS: Among the 131 patients with fractures, the median age was 8 years, the median preoperative angulation was 52°, the follow-up rate was 86.3% (113/131), the average follow-up time was 58.3 months, and the postoperative complication rate was 17.7% (20/113). The comparison among the different treatment groups showed that group B had the best recovery of elbow function, postoperatively, and the lowest postoperative complication rate. Age, duration of hospitalization, and preoperative angulation were independent factors affecting postoperative complications. Older age, longer duration of hospitalization, and higher angulation increase the postoperative complications. CONCLUSION: Different treatment options have different efficacies for radial neck fractures in children, of which manipulative reduction with internal fixation using ESINs can achieve good efficacy and a low postoperative complication rate. Age, duration of hospitalization, and preoperative angulation are independent factors for postoperative complications.

Acute Effects of Personal Ozone Exposure on Biomarkers of Inflammation, Oxidative Stress, and Mitochondrial Oxidative Damage - Shanghai Municipality, China, May-October 2016.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: It remains inconclusive whether short-term ozone exposure can cause an inflammatory response and oxidative damage in the circulatory system, particularly at low concentrations. WHAT IS ADDED BY THIS REPORT?: This study made an accurate exposure assessment by conducting personal ozone monitoring, thus minimizing the exposure misclassification commonly found in previous environmental epidemiological studies. Our study found that even short-term exposure to low concentrations of ozone was associated with inflammation, lipid peroxidation, and mitochondrial oxidative damage. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Short-term exposure to low concentrations of ozone can still lead to subclinical cardiovascular effects, suggesting the current air quality standards for ozone need to be further tightened in China.

The acute effects of fine particulate matter constituents on circulating inflammatory biomarkers in healthy adults.

BACKGROUND: Systemic inflammation is considered one of the key mechanisms in the development of cardiovascular diseases induced by fine particulate matter (PM2.5) air pollution. However, evidence concerning the effects of various PM2.5 constituents on circulating inflammatory biomarkers were limited and inconsistent. OBJECTIVES: To evaluate the associations of short-term exposure to a variety of PM2.5 constituents with circulating inflammatory biomarkers. METHODS: We conducted a panel study from May to October 2016 among 40 healthy adults in Shanghai, China. We monitored the concentrations of 27 constituents of PM2.5. We applied linear mixed-effect models to analyze the associations of PM2.5 and its constituents with 7 inflammatory biomarkers, and further assessed the robustness of the associations by fitting models adjusting for PM2.5 mass and/or their collinearity. Benjamini-Hochberg false discovery rate was used to correct for multiple comparisons. RESULTS: The associations of PM2.5 were strongest at lag 0 d with tumor necrosis factor-α (TNF-α), at lag 1 d with interleukin-6, interleukin-8, and interleukin-17A, at lag 02 d with monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1). After correcting for multiple comparisons in all models, Cl-, K+, Si, K, As, and Pb were significantly associated with interleukin-8; SO42- and Se were marginally significantly associated with interleukin-8; SO42-, As, and Se were marginally significantly associated with TNF-α; and Si, K, Zn, As, Se, and Pb were marginally significantly associated with MCP-1. CONCLUSIONS: Our results suggested that some constituents (SO42-, Cl-, K+, and some elements) might be mainly responsible for systemic inflammation triggered by short-term PM2.5 exposure.

Alleviated systemic oxidative stress effects of combined atmospheric oxidant capacity by fish oil supplementation: A randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Combined atmospheric oxidant capacity (Ox), represented by the sum of nitrogen dioxide (NO2) and ozone (O3), is an important hazardous property of outdoor air pollution mixture. It remains unknown whether its adverse effects can be ameliorated by dietary fish-oil supplementation. OBJECTIVE: To assess the effects of fish-oil supplementation against oxidative stress induced by acute Ox exposure. METHODS: We conducted a randomized, double-blinded and placebo-controlled study among 65 young adults in Shanghai, China between September 2017 and January 2018. We randomly assigned participants to receive either 2.5 g/day of fish oil or placebo, and conducted four repeated physical examinations during the last two months of treatments. Ox concentrations were calculated as the sum of hourly measurements of NO2 and O3. We measured six biomarkers on systemic oxidative stress and antioxidant activity. Linear mixed-effect models were used to assess the short-term effects of Ox on biomarkers in each group. RESULTS: During our study period, the 72-h average Ox concentration was 93.6 µg/m3. Short-term exposure to Ox led to weaker changes in all biomarkers in the fish oil group than in the placebo group. Compared with the placebo group, for a 10-µg/m3 increase in Ox, there were smaller decrements in myeloperoxidase (MPO, difference = 5.92%, lag = 0-2 d, p = 0.03) and malondialdehyde (MDA, difference = 5.00%, lag = 1 d, p = 0.04) in the fish-oil group; there were also larger increments in total antioxidant capacity (TAC, difference = 16.33%, lag = 2 d, p = 0.02) and in glutathione peroxidase (GSH-Px, difference = 8.89%, lag = 0-2 d, p = 0.03) in the fish-oil group. The estimated differences for MPO were robust to adjustment for all co-pollutants and the differences for other biomarkers remained for some co-pollutants. CONCLUSIONS: This trial provides first-hand evidence that dietary fish-oil supplementation may alleviate the systemic oxidative stress induced by Ox.

Effects of filtered fresh air ventilation on classroom indoor air and biomarkers in saliva and nasal samples: A randomized crossover intervention study in preschool children.

To evaluate the short-term effects of filtered fresh air ventilation system on classroom indoor air and biomarkers in saliva and nasal samples in preschool children, a randomized crossover study was conducted in a kindergarten in Shanghai, China in 2016. Two classrooms at the same grade (n = 43) were selected and fresh air ventilation systems (FAVS) with high efficiency particulate air filter (HEPA) were installed. In the first week, FAVS-HEPA was run in one classroom for 2 continuous school days and the other classroom was remained as usual with no use of FAVS-HEPA. After one week of wash-out, the ventilation modes exchanged between two classrooms and another 2 days of intervention were repeated. Real-time indoor and outdoor air pollution and climate factors (PM2.5, Temp and relative humidity (R.H.)) were measured. Saliva and nasal internal mucosa samples were collected immediately at the end of each intervention scenario. Linear mixed-effect regression model was applied to evaluate the effects of intervention on children's health indicators controlling for age, gender, height, BMI and temperature. The results showed, with FAVS-HEPA, the classroom indoor fine particulate matter (PM2.5)(29.1 ±â€¯17.9 µg/m3) was on average significantly lower than that without FAVS-HEPA (85.7 ±â€¯43.2 µg/m3). By regression analysis, each 10 µg/m3 decrease of indoor PM2.5 during the 8 school hours in the first intervention day was associated with an average of 1.76% (95% confidence interval (CI) 0.43-3.08%) increase in saliva lysozyme. This percentage increased to 2.41% (95%CI 0.52-4.26%) if related to the PM2.5 level in 16 school hours over 2 days of intervention. A total of 19 nasal bacterial taxa were lower in subjects exposed to FAVS-HEPA, compared to that with no use of FAVS-HEPA, despite the general bacteria diversity levels in nasal samples were not statistically different. Among others, Providencia species showed significant effects in mediating the associations between higher PM2.5 and lower lysozyme. In conclusion, using FAVS-HEPA was effective in decreasing the classroom indoor PM2.5. Saliva lysozyme, as a non-specific immune biomarker, was significantly inversely associated with indoor PM2.5. Certain nasal bacteria might play key roles in mediating PM2.5 exposure and children's lysozyme levels.

Effects of personal nitrogen dioxide exposure on airway inflammation and lung function.

BACKGROUND: Few epidemiological studies have evaluated the respiratory effects of personal exposure to nitrogen dioxide (NO2), a major traffic-related air pollutant. The biological pathway for these effects remains unknown. OBJECTIVES: To evaluate the short-term effects of personal NO2 exposure on lung function, fractional exhaled nitric oxide (FeNO) and DNA methylation of genes involved. METHODS: We conducted a longitudinal panel study among 40 college students with four repeated measurements in Shanghai from May to October in 2016. We measured DNA methylation of the key encoding genes of inducible nitric oxide synthase (NOS2A) and arginase (ARG2). We applied linear mixed-effect models to assess the effects of NO2 on respiratory outcomes. RESULTS: Personal exposure to NO2 was 27.39 ±â€¯23.20 ppb on average. In response to a 10-ppb increase in NO2 exposure, NOS2A methylation (%5 mC) decreased 0.19 at lag 0 d, ARG2 methylation (%5 mC) increased 0.21 and FeNO levels increased 2.82% at lag 1 d; and at lag 2 d the percentage of forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow in predicted values decreased 0.12, 0.37 and 0.67, respectively. The model performance was better compared with those estimated using fixed-site measurements. These effects were robust to the adjustment for co-pollutants and weather conditions. CONCLUSIONS: Our study suggests that short-term personal exposure to NO2 is associated with NOS2A hypomethylation, ARG2 hypermethylation, respiratory inflammation and lung function impairment. The use of personal measurements may better predict the respiratory effects of NO2.

The effects of fine particulate matter constituents on exhaled nitric oxide and DNA methylation in the arginase-nitric oxide synthase pathway.

BACKGROUND: Fine particulate matter (PM2.5) has been widely associated with airway inflammation represented by increased fractional concentration of exhaled nitric oxide (FeNO). However, it remains unclear whether various PM2.5 constituents have different impacts on FeNO and its production process from the arginase (ARG)-nitric oxide synthase (NOS) pathway. OBJECTIVES: To investigate the acute effects of PM2.5 constituents on FeNO and DNA methylation of genes involved. METHODS: We conducted a longitudinal panel study among 43 young adults in Shanghai, China from May to October in 2016. We monitored the concentrations of 25 constituents of PM2.5. We applied the linear mixed-effect model to evaluate the associations of PM2.5 constituents with FeNO and DNA methylation of the ARG2 and NOS2A genes. RESULTS: Following PM2.5 exposure, NOS2A methylation decreased and ARG2 methylation increased only on the concurrent day, whereas FeNO increased most prominently on the second day. Nine constituents (OC, EC, K, Fe, Zn, Ba, Cr, Se, and Pb) showed consistent associations with elevated FeNO and decreased NOS2A methylation or increased ARG2 methylation in single-constituent models and models adjusting for PM2.5 total mass and collinearity. An interquartile range increase of these constituents was associated with respective decrements of 0.27-1.20 in NOS2A methylation (%5mC); increments of 0.48-1.56 in ARG2 methylation (%5mC); and increments of 7.12%-17.54% in FeNO. CONCLUSIONS: Our results suggested that OC, EC, and some metallic elements may be mainly responsible for the development and epigenetic regulation of airway inflammatory response induced by short-term PM2.5 exposure.

Cardiovascular Benefits of Fish-Oil Supplementation Against Fine Particulate Air Pollution in China.

BACKGROUND: Few studies have evaluated the health benefits of omega-3 fatty acid supplementation against fine particulate matter (aerodynamic diameter <2.5 µm [PM2.5]) exposure in highly polluted areas. OBJECTIVES: The authors sought to evaluate whether dietary fish-oil supplementation protects cardiovascular health against PM2.5 exposure in China. METHODS: This is a randomized, double-blinded, and placebo-controlled trial among 65 healthy college students in Shanghai, China. Participants were randomly assigned to either the placebo group or the intervention group with dietary fish-oil supplementation of 2.5 g/day from September 2017 to January 2018, and received 4 rounds of health examinations in the last 2 months of treatments. Fixed-site PM2.5 concentrations on campus were measured in real time. The authors measured blood pressure and 18 biomarkers of systematic inflammation, coagulation, endothelial function, oxidative stress, antioxidant activity, cardiometabolism, and neuroendocrine stress response. Acute effects of PM2.5 on these outcomes were evaluated within each group using linear mixed-effect models. RESULTS: The average PM2.5 level was 38 µg/m3 during the study period. Compared with the placebo group, the fish-oil group showed relatively stable levels of most biomarkers in response to changes in PM2.5 exposure. Between-group differences associated with PM2.5 exposure varied by biomarkers and by lags of exposure. The authors observed beneficial effects of fish-oil supplementation on 5 biomarkers of blood inflammation, coagulation, endothelial function, oxidative stress, and neuroendocrine stress response in the fish-oil group at a false discovery rate of <0.05. CONCLUSIONS: This trial shows that omega-3 fatty acid supplementation is associated with short-term subclinical cardiovascular benefits against PM2.5 exposure among healthy young adults in China. (Effect of Dietary Supplemental Fish Oil in Alleviating Health Hazards Associated With Air Pollution; NCT03255187).

Protein-solvent interfaces in human Y145Stop prion protein amyloid fibrils probed by paramagnetic solid-state NMR spectroscopy.

The C-terminally truncated Y145Stop variant of prion protein (PrP23-144), which is associated with heritable PrP cerebral amyloid angiopathy in humans and also capable of triggering a transmissible prion disease in mice, serves as a useful in vitro model for investigating the molecular and structural basis of amyloid strains and cross-seeding specificities. Here, we determine the protein-solvent interfaces in human PrP23-144 amyloid fibrils generated from recombinant 13C,15N-enriched protein and incubated in aqueous solution containing paramagnetic Cu(II)-EDTA, by measuring residue-specific 15N longitudinal paramagnetic relaxation enhancements using two-dimensional magic-angle spinning solid-state NMR spectroscopy. To further probe the interactions of the amyloid core residues with solvent molecules we perform complementary measurements of amide hydrogen/deuterium exchange detected by solid-state NMR and solution NMR methods. The solvent accessibility data are evaluated in the context of the structural model for human PrP23-144 amyloid.

Structural Studies of Amyloid Fibrils by Paramagnetic Solid-State Nuclear Magnetic Resonance Spectroscopy.

Application of paramagnetic solid-state NMR to amyloids is demonstrated, using Y145Stop human prion protein modified with nitroxide spin-label or EDTA-Cu2+ tags as a model. By using sample preparation protocols based on seeding with preformed fibrils, we show that paramagnetic protein analogs can be induced into adopting the wild-type amyloid structure. Measurements of residue-specific intramolecular and intermolecular paramagnetic relaxation enhancements enable determination of protein fold within the fibril core and protofilament assembly. These methods are expected to be widely applicable to other amyloids and protein assemblies.

Effects of Personal Short-Term Exposure to Ambient Ozone on Blood Pressure and Vascular Endothelial Function: A Mechanistic Study Based on DNA Methylation and Metabolomics.

Short-term exposure to ambient ozone is associated with adverse cardiovascular effects, with inconsistent evidence on the molecular mechanisms. We conducted a longitudinal panel study among 43 college students in Shanghai to explore the effects of personal ozone exposure on blood pressure (BP), vascular endothelial function, and the potential molecular mechanisms. We measured real-time personal ozone exposure levels, serum angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1), and locus-specific DNA methylation of ACE and EDN1 (coding ET-1). We used an untargeted metabolomic approach to explore potentially important metabolites. We applied linear mixed-effect models to examine the effects of ozone on the above biomarkers. An increase in 2 h-average ozone exposure was significantly associated with elevated levels of BP, ACE, and ET-1. ACE and EDN1 methylation decreased with ozone exposure, but the magnitude differed by genomic loci. Metabolomics analysis showed significant changes in serum lipid metabolites following ozone exposure that are involved in maintaining vascular endothelial function. Our findings suggested that acute exposure to ambient ozone can elevate serum levels of ACE and ET-1, decrease their DNA methylation, and alter the lipid metabolism, which may be partly responsible for the effects of ozone on BP and vascular endothelial function.

Personal Ozone Exposure and Respiratory Inflammatory Response: The Role of DNA Methylation in the Arginase-Nitric Oxide Synthase Pathway.

Little is known regarding the molecular mechanisms behind respiratory inflammatory response induced by ozone. We performed a longitudinal panel study with four repeated measurements among 43 young adults in Shanghai, China from May to October in 2016. We collected buccal samples and measured the fractional exhaled nitric oxide (FeNO) after 3-day personal ozone monitoring. In buccal samples, we measured concentrations of inducible nitric oxide synthase (iNOS) and arginase (ARG), and DNA methylation of NOS2A and ARG2. We used linear mixed-effect models to analyze the effects of ozone on FeNO, two enzymes and their DNA methylation. A 10 ppb increase in ozone (lag 0-8 h) was significantly associated with a 3.89% increase in FeNO, a 36.33% increase in iNOS, and a decrease of 0.36 in the average methylation (%5mC) of NOS2A. Ozone was associated with decreased ARG and elevated ARG2 methylation, but the associations were not significant. These effects were more pronounced among allergic subjects than healthy subjects. The effects were much stronger when using personal exposure monitoring than fixed-site measurements. Our study demonstrated that personal short-term exposure to ozone may result in acute respiratory inflammation, which may be mainly modulated by NOS2A hypomethylation in the arginase-nitric oxide synthase pathway.

Fine particulate matter constituents and stress hormones in the hypothalamus-pituitary-adrenal axis.

Fine particulate matter (PM2.5) has recently been associated with the activation of the hypothalamus-pituitary-adrenal (HPA) axis, increasing cardiometabolic risks. However, it is unknown which constituents of PM2.5 were mainly responsible for these associations. In a longitudinal panel study with 4 repeated measurements among 43 college students in Shanghai, China, we measured serum levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol, as indicators of HPA axis activation. Then, we evaluated the associations of 22 constituents of PM2.5 with these stress hormones using linear mixed-effect models. During the study period, the average daily concentration of PM2.5 was 41.1 µg/m3. We found that short-term exposure to PM2.5 was associated with elevated levels of the 3 stress hormones. We observed that water-soluble inorganic ions, especially nitrate (NO3-) and ammonium, had stronger influences on 3 hormones. Six metallic elements, including Zn, Mn, Cu, Fe, Br, and Cr, had positive but generally instable associations with 3 hormones. The effects of organic carbon and elemental carbon on hormones were generally weak. When correcting for multiple comparisons using false discovery rate, NO3- was still significantly associated with CRH, but other important associations turned to be insignificant. An interquartile range increase in NO3- on the previous day were associated with 12.13% increase (95% confidence interval: 4.45%, 20.37%) in CRH. Our findings suggested that water-soluble inorganic constituents of PM2.5 (especially, NO3-) might have stronger influences on the activation of HPA axis than carbonaceous and elemental components.