Background: Olfactory dysfunction, ranging from mild impairment to complete loss, is a prevalent and bothersome symptom in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Objective: This study aimed to identify risk factors associated with the severity of olfactory dysfunction in the CRSwNP population, which have been largely overlooked. Methods: A total of 282 patients with CRSwNP were enrolled and categorized into normosmia, hyposmia, and anosmia groups according to their olfactory levels examined by the smell identification test specifically for the Chinese population (CSIT). Patients' demographic characteristics, history of asthma, computed tomography (CT)-based imaging scores, blood cytology, immunoglobulin E, and serum lipid profiles were recorded for all participants. Ordinal logistic regression analysis was used to identify risk factors of gradual olfactory dysfunction, and receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of those factors for discriminating different degrees of olfactory dysfunction from normosmia. Results: Significant differences were observed in age, prevalence of comorbid asthma, blood eosinophils, serum lipid profiles, and CT-based imaging scores of CRSwNP among the 3 groups stratified by olfactory outcomes ( P < 0.05, respectively). Multivariate ordinal logistic regression analysis identified Lund-Mackay scores, ethmoidal-to-maxillary (E/M) sinus ratio, age, and total cholesterol as independent risk factors for gradual olfactory dysfunction in CRSwNP ( P < 0.01, respectively). Correlation analysis indicated that the 4 identified risk factors were all significantly inversely correlated with the olfactory score measured by CSIT ( P < 0.001, respectively). ROC analysis demonstrated that the combined model based on the 4 risk factors showed strong power to discriminate between anosmic and normosmia (area under the curve [AUC]: 0.893, 95% confidence interval [CI]: 0.848–0.939), and moderate accuracy in classifying hyposmia and normosmia (AUC: 0.716, 95% CI: 0.640–0.792). When compared the AUC between different models, the combined model shows a better prediction ability than E/M ratio, age, and total cholesterol alone ( P < 0.05, respectively). Conclusion: Lund-Mackay score, E/M ratio, age, and serum total cholesterol are independent risk factors for gradual olfactory dysfunction in patients with CRSwNP, which can be used to develop a predictive model for olfactory outcomes.

BACKGROUND:Trace element and metal exposure is closely related to the occurrence of chronic diseases, particularly affecting blood pressure and blood glucose. Current studies suggest that heavy metal exposure is a risk factor for hypertension and diabetes. Aluminum can enter the human body through daily life and occupational exposure from food, environment, drugs, and other sources, affecting the cardiovascular, endocrine, and other systems. Therefore, it is significant to observe the effect of aluminum on blood pressure and blood glucose in workers with high concentration. OBJECTIVE:In this study, electrolytic workers naturally exposed to high concentrations of aluminum were selected. The aim of the 5-year cohort study was to investigate the effects of continuous occupational aluminum exposure on blood pressure and blood glucose in workers and to assess the risk of potential cardiovascular and metabolic diseases due to heavy metal exposure. METHODS:In 2014, 183 participants from an electrolysis workshop at an aluminum plant in Shanxi were enrolled. Inductively coupled plasma mass spectrometry (ICP-MS) was performed to determine the plasma aluminum (P-Al) concentration of the workers and measured their blood pressure and glucose levels. At the 2019 follow-up, all parameters were measured again in the same workers. The relationship of the P-Al concentration with blood pressure and glucose levels was assessed using generalized linear regression, and risks of developing hypertension and hyperglycemia (diabetes or pre-diabetes) due to Al exposure were assessed using binary logistic regression. Dose-response relationships between average annual rates of change in P-Al and average annual rates of change in blood pressure and blood glucose were analyzed using RCS. The relative risk (RR) and attributable risk (AR) were also calculated. RESULTS:Generalized linear regression showed that the average annual rate of change in P-Al concentration was positively correlated with the annual rates of change in SBP, DBP, and blood glucose levels, with each e-fold increase in P-Al concentration increasing the annual rates of change in SBP and DBP by 3.55 % (P < 0.01) and 3.43 % (P = 0.03), respectively. Binary logistic regression showed that as the average annual rate of change in P-Al concentration (categorical variable) increased, the risk of developing hypertension increased (Ptrend < 0.05). The RCS results showed that the relationship between the average annual rate of change in P-Al and the average annual rate of change in SBP was a showed a dose-response relationship (P for overall association<0.05). RR and AR increased with increasing P-Al concentration in both hypertensive and diabetic patients. CONCLUSION:Persistent occupational aluminum exposure is associated with elevated blood pressure levels in workers and increases the risk of developing hypertensive disorders.

Epithelial cell‐derived thymic stromal lymphopoietin (TSLP) plays a crucial role in mediating type 2 immune responses, which is one of the key underlying pathophysiological mechanisms of allergic rhinitis (AR) and most presentations of chronic rhinosinusitis with nasal polyps (CRSwNP). Researches show that inhibiting TSLP signaling has significant therapeutic potential in alleviating type 2 inflammation. Biologics targeting TSLP have been developed and introduced into clinical practice, yielding promising therapeutic outcomes, especially in asthma. Several anti‐TSLP antibodies are undergoing clinical trials to investigate the efficacy and safety in treating CRSwNP and AR. This review aims to delve into the latest progress regarding the functional role of TSLP, the clinical outcomes associated with anti‐TSLP therapies, and the therapeutic potential of anti‐TSLP antibodies in treating nasal type 2 inflammation.

AbstractBackgroundMolecular signatures of chronic rhinosinusitis with nasal polyps (CRSwNP) related to macrophages remain unclear. This study aimed to develop a macrophage‐associated diagnostic signature for CRSwNP.MethodsTranscriptome data from 54 patients with CRSwNP and 37 healthy controls across GSE136825, GSE36830, and GSE72713 were used to identify differentially expressed genes (DEGs) between two groups. Gene Set Enrichment Analysis and Weighted Gene Co‐Expression Network Analysis pinpointed crucial pathways and gene clusters. A diagnostic model was created from these analyses and receiver operating characteristic curve (ROC), and further validated in our transcriptome data from 29 samples. Immune cell infiltration analysis was performed and linked those diagnostic genes to macrophages and verified by single‐cell RNA sequencing data. Immunofluorescence co‐staining of CD163 and HMOX1 was performed in nasal tissues. Mouse bone marrow‐derived macrophage (BMDMs) cultures were used in functional experiments. Correlations between the expression of HMOX1 and eotaxin genes were investigated.ResultsDEGs of CRSwNP versus control group were enriched in the INTERLEUKIN_4_AND_13_SIGNALING pathways. A four‐gene diagnostic model (HMOX1, ALOX5, F13A1 and ITGB2) was developed and demonstrated high diagnostic precision with an area under ROC curve of 0.980 for training dataset and 0.895 for test dataset. M2 macrophage presence and HMOX1 expression significantly correlated with CRSwNP (p < 0.001). Single‐cell RNA sequencing data underscored the altered cellular composition in CRSwNP, with HMOX1 notably expressed in M2 macrophages. Immunofluorescence staining highlighted the increased infiltration of CD163+ M2 macrophages in nasal mucosa samples of eosinophilic CRSwNP, which correlated with HMOX1 protein levels (p < 0.05). The HMOX1 inhibitor zinc protoporphyrin reduced the ratio of CD163 + HMOX1 + M2 macrophages in mouse BMDM cultures (p < 0.05). HMOX1 expression showed a strong positive correlation with the expression of eotaxin genes (CCL11, CCL24, and CCL26; p < 0.05 respectively).ConclusionM2 macrophage‐derived HMOX1 can be used as an innovative diagnostic signature for CRSwNP, which might be a potential regulator of eosinophilic inflammation.

OBJECTIVE:To investigate the interaction between plasma polymetallic exposure and lifestyle factors on cognitive function abnormalities in occupational aluminum workers. The aim is to develop a new occupational health management model that integrates lifestyle behaviors with occupational activities to comprehensively protect the health of these workers. METHOD:476 Participants were recruited from an aluminum factory in Shanxi, China. Cognitive functioning was assessed using the Montreal Cognitive Assessment Scale (MoCA). Plasma polymetallic levels were measured using ICP-MS. Logistic regression analyzed the relationship between nine plasma metals, lifestyle factors, and cognitive abnormalities. A 3D model validated the interaction between metals and analyzed the combined effects of plasma metals and lifestyle on MoCA scores. The Chi-squared Automatic Interaction Detector (CHAID) decision tree was used to identify factors influencing cognitive dysfunction. RESULTS:High blood aluminum concentration (>47.85 μg/L), high blood lithium concentration(>3.15 μg/L), as well as sleep time(≤7 h and > 8 h), smoking, alcohol consumption, and length of mobile phone use(≥2 h) were risk factors for abnormal cognitive functioning. In addition aluminum and lithium have a multiplicative interaction on cognitive function(OR=1.86,95 %CI:1.14,3.050). There was an interaction between high plasma levels of aluminum and lithium and smoking on cognitive function in workers, and an interaction between high plasma levels of aluminum and lithium and sleep duration ≤7 or >8 h on cognitive function in workers. CONCLUSION:The levels of blood metal elements aluminum and lithium, as well as sleep time, smoking, drinking, and length of mobile phone use, are risk factors for cognitive dysfunction in occupational aluminum workers. There are the synergetic effect to increase the risk of cognitive dysfunction between blood aluminum concentration ≥50.59μg/L and blood lithium concentration ≥3.44μg/L, sleep duration ≤7h& >8 h, smoking, drinking, mobile phone use ≥2 h.

Background. Serine proteinase inhibitors, clade B, member 3 (SerpinB3) and B4 are highly similar in amino acid sequences and associated with inflammation regulation. We investigated SerpinB3 and B4 expression and their roles in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods. The expression of SerpinB3 and B4 in nasal mucosa tissues, brush cells, and secretions from CRSwNP patients was measured, and their regulation by inflammatory cytokines were investigated. Their functions were also analyzed using air–liquid interface (ALI)-cultured primary human nasal epithelial cells (HNECs) and transcriptomic analysis. Results. Both SerpinB3 and B4 expression was higher in nasal mucosa, brush cells, and secretions from eosinophilic (E) CRSwNP and nonECRSwNP patients than in healthy controls. Immunofluorescence staining indicated that SerpinB3 and B4 were primarily expressed in epithelial cells and their expression was higher in CRSwNP patients. SerpinB3 and B4 expression was upregulated by interleukin-4 (IL-4), IL-5, IL-6, and IL-17a. Transcriptomic analysis identified differentially expressed genes (DEGs) in response to recombinant SerpinB3 and B4 stimulation. Both the DEGs of SerpinB3 and B4 were associated with disease genes of nasal polyps and inflammation in DisGeNET database. Pathway enrichment indicated that downregulated DEGs of SerpinB3 and B4 were both enriched in cytokine–cytokine receptor interactions, with CXCL8 as the hub gene in the protein–protein interaction networks. Furthermore, CXCL8/IL-8 expression was downregulated by recombinant SerpinB3 and B4 protein in ALI-cultured HNECs, and upregulated when knockdown of SerpinB3/B4. Conclusion. SerpinB3/B4 expression is upregulated in nasal mucosa of CRSwNP patients. SerpinB3/B4 may play an anti-inflammatory role in CRSwNP by inhibiting the expression of epithelial cell-derived CXCL8/IL-8.

Objective To assess the diagnostic utility of lncRNA 51A in detecting cognitive decline among aluminum-exposed workers occupationally. Methods 921 male workers from an aluminum manufacturing facility underwent cognitive assessments, measurement of plasma aluminum levels and quantification of lncRNA 51A levels. Receiver Operating Characteristic (ROC) curves were constructed to assess the diagnostic potential of lncRNA 51A. Bayesian network model was utilized to predict the likelihood of cognitive decline among the study population. Results Significant differences in lncRNA 51A levels, plasma aluminum concentration and MMSE scores were observed between cognitive normal and decline groups. The lncRNA 51A expression was negatively correlated with MMSE scores. The area under the curve (AUC) was 0.894, with 89.3% sensitivity and 73.9% specificity. The Bayesian network model indicated varying probabilities of cognitive decline based on lncRNA 51A expression levels. Conclusion Plasma lncRNA 51A shows potential as an excellent biomarker for cognitive decline diagnosis in aluminum-exposed workers.

Aluminum (Al) is a neurotoxic substance associated with cognitive dysfunction and neurodegenerative diseases, such as Alzheimer's disease, but the mechanisms for aluminum neurotoxicity remain to be identified. In this work, we try to investigate a novel potential biomarker of cognitive dysfunction following aluminum exposure and the mechanism involved. Recently, miR-134-3p was reported as a novel regulator of cognitive function. To address this, we investigate the expression level of miR-134-3p in plasma from 280 aluminum factory workers and analyzed the correlation between miRNA-134-3p, blood Al concentration, and Montreal Cognitive Assessment Scale (MoCA scale) score. The results implied that occupational aluminum exposure elevated miR-134-3p expression in the plasma of workers accompanied by cognitive impairment. Our experiment studies using both animal models and PC12 cells validated the upregulation of miR-134-3p caused by aluminum. In addition, we identified that palmitoylation enzyme zDHHC3 was the target of miR-134-3p, and the decreasing AMPAR receptor (AMPAR) trafficking was related to the learning and memory impairment induced by aluminum. More importantly, using transfection and interference approaches in PC12 cells, inhibition of miR-134-3p resulted in a recovery of zDHHC3-AMPARs axis to a certain extent in response to aluminum. In summary, miR-134-3p was found to be involved in aluminum neurotoxicity by targeting zDHHC3-AMPARs axis and could serve as a potential biomarker or helpful target.

BackgroundPrevious studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet.ObjectiveTo evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers.MethodsA total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q1-Q4) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models.ResultsThe workers' medians (P25, P75) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q1 group, blood aluminum in the Q2, Q3, or Q4 group had an impact on related plasma miR-134-3p expression level and total MoCA score (P<0.05). With increasing blood aluminum concentration, the expression level of miR-134-3p in workers' plasma gradually increased, showing a positive correlation (b>0, Ptrend<0.001), while the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). As the expression level of miR-134-3p in plasma increased, the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). There was a linear relationship between peripheral blood aluminum concentration and plasma relative expression level of miR-134-3p of the workers in the middle school and below group and the high school group (Ptrend<0.05), b (95%CI)=1.796 (1.248, 2.344) and 1.192 (0.874, 1.510), and no correlation was found in the workers in the college and above group (Ptrend>0.05).ConclusionOccupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.

Objectives: To evaluate the risk of cognitive impairment in workers with plasma aluminum concentrations and lifestyles using a Bayesian network (BN). Methods: In 2019, 476 male workers in the Shanxi Aluminum factory were investigated. We measured plasma aluminum concentrations in workers by inductive coupled plasma mass spectrometry (ICP-MS) and tested workers' cognitive function by the MoCA scale. We collected the data of lifestyle by the occupational Workers' Health questionnaire and express the influence of lifestyle on cognition by the OR value (95 %CI) of logistic regression. A Bayesian network model was used to predict the risk of cognitive dysfunction. Results: The subjects were divided into a cognitively normal group and cognitively impaired group according to MoCA scores. There were statistically significant differences in age, education level, alcohol consumption, physical exercise, reading, aluminum length of service and blood aluminum concentration between the two groups (P < 0.05). The plasma aluminum concentration in the cognitive impairment group was 1.68 times higher than that in the cognitive normal group. Four groups were established according to the quartile of blood aluminum concentration of the subjects, namely, Group Q1 (<14.95 mu g/L), Q2 group (14.95-32.96 mu g/L), Q3 group (32.96-56.62 mu g/L), and Q4 group (>56.62 mu g/L). Binary logistic regression analysis showed that in the adjustment variable Model2, drinking, short sleep, long sleep, and mobile phone use increased the risk of cognitive impairment by 1.505(0.99,2.289), 1.269(0.702,2.295), 1.125(0.711,1.781) and 1.19(0.779,1.82), respectively, compared with their reference values. The risk of cognitive impairment from reading and exercise was 0.7(0.398,1.232) and 0.787(0.51,1.217), respectively, compared with those of no reading and no exercise. The risk of cognitive impairment of blood aluminum concentration in the Q2, Q3, and Q4 groups was 2.103 (1.092,4.051), 1.866(0.955,3.644) and 3.679(1.928,7.020), respectively, compared with that in the Q1 group. Compared with age <40 , the risk of cognitive impairment of age >= 40 was 2.515(1.508,4.193) (P < 0.05). Bayesian network model results showed that if all participants had plasma aluminum concentrations higher than Q4, the prevalence of cognitive impairment was 54.5 %. The prevalence of cognitive impairment was 75.0 % if all participants had plasma aluminum levels above Q4, were older than 40, smoked, drank alcohol, used a cell phone for more than 2 h, slept for more than 8 h, did not exercise, and did not read. Conclusions: Our findings suggest that both poor lifestyle and occupational aluminum exposure may affect cognitive function. Workers must maintain a reasonable lifestyle and reduce aluminum exposure, which can control the occurrence of cognitive impairment.

Précis: The proportion, clinical characteristics, and risk factors of zonulopathy in primary angle closure disease (PACD) were analyzed. Zonulopathy is an underrecognized common finding in PACD, especially in patients with acute angle closure (AAC). Purpose: To examine the proportion and risk factors associated with intraoperative zonulopathy in PACD. Patients and Methods: This is a retrospective analysis of 88 consecutive patients with PACD who underwent bilateral cataract extraction at Beijing Tongren Hospital from August 1, 2020 to August 1, 2022. Zonulopathy was diagnosed based on intraoperative findings including the presence of a lens equator, radial folds of the anterior capsule while making capsulorhexis, and other signs of the unstable capsular bag. The subjects were grouped based on their PACD subtype diagnoses: AAC, primary angle closure glaucoma (PACG), primary angle closure (PAC), or primary angle closure suspect (PACS). Multivariate logistic regression was performed to identify risk factors associated with zonulopathy. The proportion and the risk factors of zonulopathy were estimated in patients with PACD and in PACD subtypes. Results: Of 88 patients with PACD (67.3 ± 6.9 y old, 19 males and 69 females), the overall proportion of zonulopathy was 45.5% of patients (40/88) and 30.1% of eyes (53/176). Among the PACD subtypes, the proportion of zonulopathy was highest (69.0%) in AAC, followed by 39.1% in PACG, and 15.3% in PAC and PACS combined. AAC was an independent risk factor associated with zonulopathy ( P = 0.015, AAC vs PACG, PAC, and PACS combined; odds ratio: 0.340, CI: 0.142–0.814). Shallower anterior chamber depth ( P = 0.031) and greater lens thickness ( P = 0.036), but not laser iridotomy, were associated with an increased proportion of zonulopathy. Conclusions: Zonulopathy is common in PACD, especially in patients with AAC. Shallow anterior chamber depth and thick lens thickness were associated with an increased proportion of zonulopathy.

Introduction Olfactory dysfunction (OD) is a typical symptom of chronic rhinosinusitis (CRS), which adversely affects the patient's quality of life and results in mood depression. Studies investigating the impairment of olfactory epithelium (OE) have indicated that inflammation-induced cell damage and dysfunction in OE plays a vital role in the development of OD. Consequently, glucocorticoids and biologics are beneficial in the management of OD in CRS patients. However, the mechanisms underlying OE impairment in CRS patients have not been fully elucidated.Areas covered This review focuses on mechanisms underlying inflammation-induced cell impairment in OE of CRS patients. Additionally, the methods used for detection of olfaction and both currently available and potentially new clinical treatments for OD are reviewed.Expert opinion Chronic inflammation in OE impairs not only olfactory sensory neurons but also non-neuronal cells that are responsible for regeneration and support for neurons. The current treatment for OD in CRS is mainly aimed at attenuating and preventing inflammation. Strategies for use of combinations of these therapies may achieve greater efficacy in restoration of the damaged OE and consequently better management of OD.

This study investigates the effects of lithium and caffeine on psychomotor activities, defecation, and gastric lesions induced by restraint stress. Rats exposed to restraint stress typically exhibited a biphasic response consisting of an initial hypermotility (such as tail-flipping, body-rolling, jaw movement, and vocalization) accompanied by defecation, and followed by hypomotility (decrease in motility) accompanied by gastric ulceration. Lithium chloride (150 micrograms, ICV; 50 and 100 mg/kg, IP) significantly attenuated these responses while N6-cyclohexyl adenosine (CHA; 1.5 micrograms, ICV; 0.3 mg/kg, IP), a potent adenosine A1 receptor agonist, attenuated the behavioral effects but potentiated the gastric ulceration. Caffeine (3 micrograms, ICV; 1.0 mg/kg, IP), an adenosine receptor antagonist, inhibited the effects of CHA in animals exposed to 3 h of stress, but aggravated the effects in animals exposed to 6-12 h of stress. These results suggest that caffeine consumption may produce supersensitivity of adenosine receptors, which potentiate the actions of adenosine or CHA. Lithium may modulate the effects of stress by indirectly inhibiting central adenosine receptor activity.

目的 探讨"以器官系统为中心"的护理教学查房模式的应用效果,为护理教学临床推广提供依据.方法 将2019年1—12月实习的护理专科生,分为对照组41名运用传统护理教学查房模式,观察组42名运用"以器官系统为中心"临床护理教学查房模式;两组分别于入科时及教学查房后接受评判性思维能力测量表调查,比较五个维度:求知欲、寻求真理、分析能力、系统化能力、开放思想得分差异.结果 教学查房后,观察组的得分五个维度分别均高于对照组,差异有统计学意义(P<0.01).结论 通过"以器官系统为中心"的临床护理教学查房模式,强化护生发现问题、解决问题的能力以及系统化能力和求知欲,最终提高学习效果及综合能力.

BackgroundOccupational aluminum exposure is closely related to cognitive impairment, and alcohol consumption is also closely related to cognitive dysfunction.ObjectiveTo explore the effects of types of alcohol consumption on cognitive function of occupational aluminum exposed workers.MethodsA total of 181 workers aged from 23 to 56 years were selected by cluster sampling method in an electrolytic aluminum workshop of an aluminum plant in a region and in a maintenance workshop of another plant in the same region from July to August, 2019. Venous blood was collected, and plasma aluminum concentration was determined by inductively coupled plasma mass spectrometry. The study subjects were divided into low and high exposure groups based on the median blood aluminum level and type of work. Their basic information was collected by occupational health examination. Workers' cognitive function was assessed using the Montreal Cognitive Assessment Scale-Beijing Edition. Logistic regression was used to analyze the association between plasma aluminum concentration and cognitive impairment, and between the types of alcohol consumption (including Baijiu, red wine, and beer) and cognitive impairment, Unconditional logistic regression was used to fit multiplicative interaction model as well as additive interaction model of plasma aluminum concentration and the types of alcohol consumption, and to calculate the relative excess relative risk due to interaction (RERI) and attributable proportion due to interaction (AP).ResultsThe M (P25, P75) concentrations of plasma aluminum were 40.01 (25.05, 60.56) µg·L−1 in the total study subjects, 25.16 (17.13, 34.78) µg·L−1 in the low exposure group and 60.56 (47.40, 68.53) µg·L−1 in the high exposure group. After adjusting the type of alcohol consumption, drinking, age, duration of exposure to aluminum, education, marital status, and smoking, the odds ratios for impairments of attention, language expression, and overall cognitive function in the high exposure group were 4.295 (95%CI: 1.912-9.648), 5.687 (95%CI: 1.355-23.867), and 2.720 (95%CI: 1.225-6.040) times of the low exposure group respectively. Besides, after adjusting blood aluminum concentration, total alcohol consumption, age, duration of exposure to aluminum, education, marital status, and smoking, the risk of attention impairment of the Baijiu drinkers was 2.613 (95%CI: 1.054 to 6.837) times of the non-Baijiu drinkers; the risks of impairment of visuospatial abilities and execution functions, language expression, delayed recall, and overall cognitive function of the beer drinkers were 3.165 (95%CI: 1.285-7.797), 17.898 (95%CI: 1.590-201.480), 3.118 (95%CI: 1.215-8.003), and 3.824 (95%CI: 1.736-8.423) times of the non-beer drinkers. There were both additive [RERI (95%CI): 1.745 (1.394-2.097), AP (95%CI): 0.415 (0.201-0.630)] and multiplicative (OR=3.591, 95%CI: 1.393-9.255) interactions between Baijiu intake and plasma aluminum concentration levels on the attention domain. The cognitive impairment attributed to the interactive effects of drinking Baijiu and plasma aluminum concentration in individuals with attention impairment accounted for 41.5%. There were both additive [RERI (95%CI): 5.955 (0.562-11.328), AP (95%CI): 0.829 (0.577-1.081)] and multiplicative (OR=42.174, 95%CI: 5.469-325.252) interactions between beer drinking and plasma aluminum concentration on the overall cognitive function. Among the individuals with overall cognitive impairment, the cognitive impairment caused by the interaction of beer drinking and plasma aluminum concentration accounted for 82.9%.ConclusionOccupation aluminum exposed workers' attention, language expression, and overall cognitive function are closely related to their plasma aluminum concentration. Plasma aluminum concentrations have interactions with Baijiu and beer consumption on cognitive impairment of workers.

Purpose MicroRNA-21 (miR-21) is a well-known oncomiR and plays key roles in regulating various biological processes related to pulmonary diseases, especially lung carcinoma. The regulatory roles and downstream targets of miR-21 remain far from well understood. We aimed to identify miR-21-gene regulatory network in lung tissue. Methods Transcriptome and proteome analyses were performed on lung tissues from miR-21 knockout (KO) mice and their wildtype (WT) littermates. Differentially expressed genes (DEGs) and proteins (DEPs) between miR-21KO and WT were analyzed, and correlation analysis was performed between transcriptional and translational level. DEPs were used for prediction of miR-21 target genes and construction of co-expression network. Results Comparing with WT mice, 820 DEGs and 623 DEPs were identified in lung tissues of miR-21KO mice. Upregulated DEGs and DEPs were both significantly enriched in pathways of metabolism of xenobiotics by cytochrome P450, drug metabolism, and chemical carcinogenesis. Of the 31 molecules commonly identified in DEGs and DEPs, 9 upregulated genes were tumor suppressor genes while 8 downregulated genes were oncogenes, and 12 genes showed closely positive correlation between mRNA and protein expression. Real-time PCR validation results were consistent with the omics data. Among the upregulated DEPs in miR-21KO mice, 21 genes were predicted as miR-21 targets. The miR-21 regulatory network was constructed by target genes and their highly co-expressed proteins, which identified the miR-21 target Itih4 as a hub gene. Conclusion MiR-21-gene regulatory network was constructed in mouse lung tissue. MiR-21KO resulted in extensive upregulation of tumor suppressor genes and downregulation of oncogenes.

BackgroundChemical modification of RNA is a recent hotspot in the field of epigenetics, but the specific mechanism of chemical modification of RNA in aluminum neurotoxicity has not been fully reported.ObjectiveTo investigate the alterations of fat mass and obesity-associated protein (FTO), that demethylates N6-methyladenosine (m6A), and brain-derived neurotrophic factor (BDNF) in different brain regions of rats and rat adrenal pheochromocytoma differentiated cells (PC12 cells) following aluminum exposure.MethodsAnimal experiment: Twenty-four healthy male SD rats were randomly divided into a control group (normal saline) and 10, 20, and 40 μmol·kg−1 exposure groups according to body weight, with 6 rats in each group. Maltol aluminum [Al(mal)3] was injected intraperitoneally every other day for 3 months. Cell experiment: PC12 cells were divided into a control group and 100, 200, and 400 μmol·L−1 exposure groups exposed to Al(mal)3 for 24 h. After exposure, the learning and memory ability of rats was measured by water maze experiment, and the protein expression levels of FTO and BDNF in rat cortex (n=6) and hippocampus (n=6) samples as well as in PC12 cells (n=5) were determined by Western blotting.ResultsThe results of water maze test showed that the escape latency of the 40 μmol·kg−1Al(mal)3 group was higher than those of the control group, the 10 μmol·kg−1Al(mal)3 group, and the 20 μmol·kg−1Al(mal)3 group on day 3, 4, and 5 of training (P<0.05). The retention time of the target quadrant of the 40 μmol·kg−1Al(mal)3 group was also reduced compared with that of the control group (P<0.05), indicating that aluminum exposure damaged the learning and memory ability of the rats. The Western blotting results showed that in the cortex, compared with the control group, the protein expression levels of FTO and BDNF in the aluminum treated groups were decreased (P<0.05). In the hippocampus, compared with the control group, the protein expression levels of FTO and BDNF in the 20 μmol·kg−1 and the 40 μmol·kg−1Al(mal)3 groups were decreased (P<0.05). In PC12 cells, compared with the control group, the protein expression levels of FTO and BDNF in the aluminum treated groups were decreased (P<0.05).ConclusionAluminum-induced learning and memory impairment is related to a simultaneous reduction of FTO and BDNF protein expressions, suggesting that m6A methylation may be involved.

Objective To evaluate the risk factors of occupational aluminum exposure on workers’ executive function.Methods A total of 172 aluminum-exposed workers were selected by convenient sampling method. According to the blood aluminum concentration, the subjects were divided into low-, medium-, and high-level groups. The trail making test（TMT） was used to evaluate the executive function and its risk factors of the subjects. Results The median and 25th and 75th percentiles [M(P 25 , P 75 )] of blood aluminum was 23.71（13.14, 38.27） μg/L. The M(P 25 , P 75 ) of blood aluminum levels in low-, medium-and high-level groups were 9.84（2.60, 13.18）, 23.18（19.45, 28.23） and 45.02（38.23, 62.52） μg/L, respectively.The total time and abnormality rate of TMT-A, TMT-B and TMT in this study increased with the increasing blood aluminum levels（all P＜0.05）. The results of binary logistic regression analysis showed that the abnormal risks of total time on TMT-B and TMT in the medium-level group were 2.59 and 2.98 times respectively（both P＜0.05）, and the abnormal risks of total time on TMT-A, TMT-B and TMT in the high-level group were 7.77, 11.04 and 9.74 times respectively compared with the low-level group（all P＜0.05）. The longer the length of service, the higher the abnormal risk of total time on TMT-B and TMT（both P＜0.05）. The higher the education level, the lower the risk of abnormal risk of total time on TMT-A and TMT（both P＜0.05）.Conclusion Occupational aluminum exposure may impair the executive function of workers with a dose-effect relationship.Blood aluminum level and length of employment are risk factors and education level is a protective factor for the executive function of workers.

目的 探讨铝暴露对作业工人延迟回忆的影响.方法 采用蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)北京版和听觉词语学习测验(Auditory Verbal Learning Test,AVLT)对山西省某铝厂435名作业工人进行延迟回忆评估.根据血铝浓度的P33.3,P66.7将研究对象分为低、中、高暴露组(分别以T1、T2、T3组表示).采用多元logistic回归分析模型分析铝暴露工人轻度认知功能障碍(mild cognitive impairment,MCI)影响因素.结果 三组工人均为男性.在年龄、婚姻状况、家庭人均月收入、吸烟、饮酒等方面差异无统计学意义(均有P＞0.05).在工龄、文化程度上比较,差异均有统计学意义(均有P＜0.05).三组在MoCA和AVLT中,延迟回忆指标均有统计学意义(均有P＜0.05).多元logistic回归分析模型显示听觉词语学习测验延迟回忆(Auditory Verbal Learning Test-long Recall,AVLT-LR)评分≥6(OR=0.860,95％CI:0.769～0.960)时,发生MCI的风险降低;当文化程度越低(OR=3.556,95％CI:1.589～7.957),插入词语个数(OR=1.415,95％CI:1.070～1.871)和重复词语个数(OR=1.419,95％CI:1.043～1.931)越多、没有采用记忆策略(OR=2.124,95％CI:1.119～4.032)发生MCI的风险增加.结论 铝暴露可以影响作业工人延迟回忆功能.MoCA和AVLT量表的评估可以判断延迟记忆受影响情况,两个量表相结合更好找出可能有MCI倾向的工人.