Association of Combined Exposure to Ambient Air Pollutants, Genetic Risk, and Incident Rheumatoid Arthritis: A Prospective Cohort Study in the UK Biobank.

BACKGROUND: Evidence for a potential link between air pollution and rheumatoid arthritis (RA) is inconsistent, and the modified effect of genetic susceptibility on the relationship between air pollution and RA has not been well studied. OBJECTIVE: Using a general population cohort from the UK Biobank, this study aimed to investigate the associations between various air pollutants and the risk of incident RA and to further estimate the impact of combined exposure to ambient air pollutants on the risk of developing RA under the modification effect of genetic predisposition. METHODS: A total of 342,973 participants with completed genotyping data and who were free of RA at baseline were included in the study. An air pollution score was constructed by summing the concentrations of each pollutant weighted by the regression coefficients with RA from single-pollutant models to assess the combined effect of air pollutants, including particulate matter (PM) with diameters ≤2.5µm (PM2.5), between 2.5 and 10µm (PM2.5-10), and ≤10µm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). In addition, the polygenic risk score (PRS) of RA was calculated to characterize individual genetic risk. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of associations of single air pollutant, air pollution score, or PRS with incident RA. RESULTS: During a median follow-up time of 8.1 y, 2,034 incident events of RA were recorded. The HRs (95% CIs) of incident RA per interquartile range increment in PM2.5, PM2.5-10, PM10, NO2, and NOx were 1.07 (1.01, 1.13), 1.00 (0.96, 1.04), 1.01 (0.96, 1.07), 1.03 (0.98, 1.09), and 1.07 (1.02, 1.12), respectively. We also found a positive exposure-response relationship between air pollution score and RA risk (pTrend=0.000053). The HR (95% CI) of incident RA was 1.14 (1.00, 1.29) in the highest quartile group compared with the lowest quartile group of the air pollution score. Furthermore, the results of the combined effect of air pollution score and PRS on the RA risk showed that the risk of RA incidence in the highest genetic risk and air pollution score group was almost twice that of the lowest genetic risk and air pollution score group [incidence rate (IR) per 100,000 person-years: 98.46 vs. 51.19, and HR= 1.73 (95% CI: 1.39, 2.17) vs. 1 (reference)], although no statistically significant interaction between the air pollution and genetic risk for incident RA was found (pInteraction>0.05). DISCUSSION: The results revealed that long-term combined exposure to ambient air pollutants might increase the risk of RA, particularly in those with high genetic risk. https://doi.org/10.1289/EHP10710.

Short-term effect of ambient temperature and ambient temperature changes on the risk of warts outpatient visits in Hefei, China: a retrospective time-series study.

Concerns are growing about the adverse health effects of ambient temperature and ambient temperature changes. However, the association between ambient temperature and ambient temperature changes on the risk of warts outpatient visits is poorly understood. Our study used the distributed lag non-linear model (DLNM) aimed to evaluate the association between ambient temperature, ambient temperature changes (including temperature change between neighboring days (TCN) and diurnal temperature range (DTR)), and warts outpatient visits. We also performed subgroup analyses in order to find susceptible populations by gender and age groups. The maximum relative risk (RR) of low ambient temperature (0 °C) for warts outpatient visits was 1.117 (95% CI: 1.041-1.198, lag 04 days), and the maximum RR of high ambient temperature (32 °C) for warts outpatient visits was 1.318 (95% CI: 1.083-1.605, lag 07 days). The large temperature drop (TCN = - 3 °C) decreased the risk of warts visits, with the lowest RR value at the cumulative exposure of lag 7 days (RR = 0.888, 95% CI: 0.822-0.959), and the large temperature rise (TCN = 2 °C) increased the risk of warts visits, with the highest RR value at the cumulative exposure of lag 7 days (RR = 1.080, 95% CI: 1.022-1.142). Overall, both low and high ambient temperatures and large temperature rise can increase the risk of warts visits, while large temperature drop is a protective factor for warts visits. However, we did not find any association between DTR and warts visits. Furthermore, subgroup analyses showed that males and the young (0-17 years old) were more sensitive to low and high ambient temperatures, and the elderly (≥ 65 years old) were more susceptible to TCN. The results may provide valuable evidence for reducing the disease burden of warts in the future.

Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

PURPOSE: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. METHODS: OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. RESULTS: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. CONCLUSION: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.

A study involving antioxidizability and cytotoxicity of two kinds of phenol from Ajania Salicifolia and their mechanisms of apoptosis / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To extract two kinds of phenols 4-hydroxy-3, 5-dimethoxy-4-(2-oxopropyl) cyclohexa-2, 5-dien-l-one and 6-methoxy-5,7-dihydroxy coumarin (named as I and H compounds respectively) from Ajania salicifolia and to investigate their antioxidation and cytotoxicity to tumors and explore their pro-apoptosis mechanism.</p><p><b>METHODS</b>The antioxidant activities of two compounds were assessed by ABTS and DPPH radical-scavenging assays. Two compounds were evaluated for their cytotoxicity against human chronic myelogenous leukemia (K562) cells using the MIT assay. The expression of NF-kappaB P65 mRNA in K562 apoptotic cells was measured by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR. In addition, protein expression levels of the NF-ICB P65, p-Akt, Fas, P-catenina and E-cadherin were also measured by Western blot.</p><p><b>RESULTS</b>(1) We found that compound I displayed significant inoxidizability, while compound II had no obvious antioxidizability. (2) In cytotoxicity experiments, compound I didn't display cytotoxicity while compound H displayed obvious cytotoxicity. (3) Compared with the blank group, the expression of NF-kappaB P65 mRNA in K562 cell after treatment with compound II was obviously up-regulated. (4) Compared with the blank group, the expression levels of NF-kappaB P65, Fas, beta-catenina and E-cadherin were significantly increased in compound II treated groups and it appeared obvious dose-effect relationship between the expression of protein and drug concentration.</p><p><b>CONCLUSION</b>Two phenols have obvious antioxidizability and cytotoxicity respectively. On the one hand, the tumor-suppressing mechanism of compound II maybe act by up-regulation the expression of NF-kappaB P65 and Fas protein; thereby, affecting the classical Fas apoptosis signaling pathways. On the other hand, it can also up-regulate the expression of protein beta-catenin and E-cadherin, which participate in the adhesion between cells, and accordingly, playing an important role in preventing the proliferation and metastasis of cancer cells.</p>

Blood lead levels among children aged 0 to 6 years in 16 cities of China, 2004-2008 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The adverse health effects of lead for children under 6 years are well known. Studies to assess the lead exposure among children in China are small in sample size and lack of national representative data. The aim of this study therefore was to describe blood lead levels and identify risk factors for lead exposure among children aged 0 to 6 years living in 16 cities in China.</p><p><b>METHODS</b>We analyzed data from blood lead levels surveillance in China carried out in 16 large cities between 2004 and 2008. A stratified clustered random sampling strategy was used. A total of 69 968 children aged 0 to 6 years were included. We conducted multiple Logistic regression analyses to explore risk factors to high blood lead level.</p><p><b>RESULTS</b>The geometric mean blood lead level of the children was 4.50 µg/dl (median: 4.90 µg/dl; IQR: 3.20 - 7.00 µg/dl). Overall prevalence of blood lead level ≥ 10.00 µg/dl among 0- to 6-year-old children was 7.57%. But the proportion of blood lead level ≥ 5.00 but < 10.00 µg/dl was 42.12%. Blood lead levels were significantly higher in boys (4.63 µg/dl) than in girls (4.35 µg/dl) (P < 0.0001). The geometric mean blood lead levels and prevalence of blood lead level ≥ 10.00 µg/dl increased with age (P < 0.0001 for the two trends). After controlling for sociodemographic, dietary and behavior factors, multivariable analysis indicated that lower maternal education, male gender, younger age, often biting pencil or/and toys, walking or playing for long time on the street, not washing hands before eating are major risk factors for higher lead levels.</p><p><b>CONCLUSIONS</b>The blood lead levels among Chinese children in urban areas are lower than previous studies but close to those of developed countries. However, children with low lead exposure account for almost half and the sociodemographic factors (age, male sex, and low mother education level) continue to be associated with higher blood lead levels.</p>

Common underlying diseases do not contribute in determining the causes of sudden unexplained death / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Underlying diseases have a statistically significant positive correlation to sudden death. However, sudden unexplained death (SUD) is different from sudden death, as there is no clinical evidence to support the sudden death due to the original underlying disease, nor a lethal pathological basis to be found during autopsy. In addition, SUD are more common in young, previously healthy individuals, usually without any signs of disease, with no positive lesions found after autopsy. Therefore, a causal relationship between SUD and the underlying disease needs to be further explored. This study aimed to explore the role that common underlying diseases play in patients with SUD and to reveal the correlation between them.</p><p><b>METHODS</b>The medical records, history and case information of 208 patients with SUD were collected for the survey. All these SUD occurred in the emergency room of Peking University Third Hospital from January 2006 to December 2009. The patients were stratified by with and without common underlying diseases. To examine possible associations between the underlying diseases and the cause of unexplained sudden death, the chi-squared and Fisher's exact tests were used.</p><p><b>RESULTS</b>Among the 208 patients, 65 were diagnosed with common underlying diseases while 143 were not. Within these two groups, there were 45 patients for whom the clear cause of death was determined. However, there were no statistically significant differences or strong associations (χ(2) = 1.238, P > 0.05) between the 11 patients with (16.90%) and 34 without (23.78%) common underlying disease among these 45 patients. We also found that occurrence of the common underlying diseases, such as neurological system, cardiovascular and pulmonary system diseases, are not statistically significant (P > 0.05) in the diagnosis of the SUD.</p><p><b>CONCLUSION</b>Common underlying diseases make no obvious contributions to SUD and are not useful in diagnosing the underlying reasons for death.</p>

Analysis of the prodromal symptoms of unexplained sudden death in patients with or without underlying diseases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In recent years, the incidence of unexplained sudden death has risen significantly across the world. However, it occurred suddenly, often in young apparently healthy individuals and almost 50% of the patients did not have any warning signals or symptoms. Therefore, the prodromal symptoms before the incident are extremely important for early prediction of sudden death. In this article, we aimed to explore the value of prodromal symptoms for unexplained sudden death and whether the prodromal symptoms have a predictive function to unexplained sudden death (USD) without underlying diseases.</p><p><b>METHODS</b>A total of 208 sudden death cases were selected for the survey in the Emergency Department of Peking University Third Hospital from January 2006 to December 2009 and their medical records were reviewed. The patients were divided into two groups, 65 patients had underlying diseases while 143 had not underlying diseases. In the meantime, their prodromal symptoms were collected and compared, prodromal symptoms including chest distress, dyspnea, syncope, fever, headache, vomiting, etc.</p><p><b>RESULTS</b>Patients with underlying diseases were compared to those without underlying diseases associated with sudden death; there was no significant difference in gender and age distribution. Among the 208 cases, 39 cases (18.75%) had prodromal symptoms, patients with underlying diseases had prodromal symptoms in 12 cases (18.46%), while patients without underlying diseases had prodromal symptoms in 27 cases (18.88%). The difference between the two groups with prodromal symptoms was not statistically significant (P > 0.05).</p><p><b>CONCLUSIONS</b>Prodromal symptoms are extremely important warning signals in the occurrence of USD. It has equally important predictive value for patients both with and without underlying diseases, especially in predicting sudden death caused by cardiopulmonary and neurological diseases.</p>