Sirt1-ROS-TRAF6 Signaling-Induced Pyroptosis Contributes to Early Injury in Ischemic Mice / 神经科学通报·英文版

Stroke is an acute cerebro-vascular disease with high incidence and poor prognosis, most commonly ischemic in nature. In recent years, increasing attention has been paid to inflammatory reactions as symptoms of a stroke. However, the role of inflammation in stroke and its underlying mechanisms require exploration. In this study, we evaluated the inflammatory reactions induced by acute ischemia and found that pyroptosis occurred after acute ischemia both in vivo and in vitro, as determined by interleukin-1β, apoptosis-associated speck-like protein, and caspase-1. The early inflammation resulted in irreversible ischemic injury, indicating that it deserves thorough investigation. Meanwhile, acute ischemia decreased the Sirtuin 1 (Sirt1) protein levels, and increased the TRAF6 (TNF receptor associated factor 6) protein and reactive oxygen species (ROS) levels. In further exploration, both Sirt1 suppression and TRAF6 activation were found to contribute to this pyroptosis. Reduced Sirt1 levels were responsible for the production of ROS and increased TRAF6 protein levels after ischemic exposure. Moreover, N-acetyl-L-cysteine, an ROS scavenger, suppressed the TRAF6 accumulation induced by oxygen-glucose deprivation via suppression of ROS bursts. These phenomena indicate that Sirt1 is upstream of ROS, and ROS bursts result in increased TRAF6 levels. Further, the activation of Sirt1 during the period of ischemia reduced ischemia-induced injury after 72 h of reperfusion in mice with middle cerebral artery occlusion. In sum, these results indicate that pyroptosis-dependent machinery contributes to the neural injury during acute ischemia via the Sirt1-ROS-TRAF6 signaling pathway. We propose that inflammatory reactions occur soon after oxidative stress and are detrimental to neuronal survival; this provides a promising therapeutic target against ischemic injuries such as a stroke.

Effects of not monitoring gastric residual volume on the risk of ventilator-associated pneumonia: a meta-analysis / 中国实用护理杂志

Objective:To assess the effects of not monitoring gastric residual volume compared to the routine monitoring gastric residual volume on the risk of ventilator-associated pneumonia.Methods:A systematic literature search of PubMed, EMBASE, Cochrane Library, CNKI, CBM and WanFang Database was conducted from inception up to January 2019.Two independent reviewers screened potentially eligible articles, selected eligible studies and abstracted pertinent data. Relative risk ( RR), weighted mean difference ( MD), and 95% confidence interval (95% CI) were calculated and heterogeneity was assessed with the I2test. Results:Four studies with a total of 785 patients were included in this meta-analysis. No monitoring gastric residual volume did not significantly increase the incidence of ventilator-associated pneumonia ( RR=1.30, 95% CI 0.78-2.16, P=0.32), compared with monitoring gastric residual volume. However, the incidence of vomiting in the no monitoring gastric residual volume group is higher ( RR=1.52, 95% CI 1.20-1.91, P=0.000 4). Not monitoring gastric residual volume decreased the rate of feeding intolerance in critically ill patients ( RR=0.61, 95% CI 0.51-0.72, P<0.01).There were no differences in the duration of mechanical ventilation ( MD=0.39, 95% CI -0.70-1.47, P=0.49) and ICU length of stay ( MD=-0.19, 95% CI -1.55--1.16, P=0.78). Conclusion:The absence of monitoring gastric residual volume did not increase the risk of ventilator-associated pneumonia in critically patient with mechanical ventilation. Gastric residual volume monitoring can not be used as a maker to prevent aspiration and to assess feeding intolerance. We still need to conduct large-scale,well-desighed clinical trials to verify whether gastric residual volume monitoring can be eliminated.

Dose and timing of normal saline resuscitation on endothelial glycocalyx in early septic shock / 中华危重病急救医学

Objective@#To observe the effect of different doses and timing of normal saline (NS) resuscitation combined with norepinephrine (NE) on endothelial glycocalyx in rabbits with early septic shock.@*Methods@#Thirty New Zealand male rabbits were randomly divided into sham group, model group, 30 mL and 60 mL timely resuscitation groups (30 mL and 60 mL timely group), and 30 mL delayed resuscitation group (30 mL delayed group) with 6 rabbits in each group. The rabbit model of septic shock was reproduced by cecal ligation and puncture (CLP). The rabbits in sham group were only received abdominal cavity open without cecal and ligation. The rabbits in 30 mL and 60 mL timely groups and 30 mL delayed group were intravenous infused with 30 mL/kg or 60 mL/kg NS immediately or 1 hour after model reproduction for 1 hour, and the mean arterial pressure (MAP) was maintained over 75 mmHg (1 mmHg = 0.133 kPa) compared with intravenous pumping of 0.02-0.05 μg·kg-1·min-1 NE followed by 5 mL/h NS infusion till the end of the experiment. The rabbits in sham and model groups were only given 5 mL/h NS. The changes in arterial blood gas before and immediately after resuscitation were observed in three fluid resuscitation groups. The internal jugular vein blood was collected at 0, 3, 6 hours after model reproduction. The levels of syndecan-1 (polysaccharide envelope marker) in plasma were determined by enzyme linked immunosorbent assay (ELISA). The rabbits were sacrificed at 6 hours after model reproduction, and the lung tissue was harvested. Western Blot was used to determine the protein expressions of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase 2 (MMP-2) and syndecan-1. The positive expression of syndecan-1 in lung tissue was observed by immunohistochemical method.@*Results@#① Blood gas analysis: compared with the results before resuscitation, the levels of lactic acid (Lac) after resuscitation in three fluid resuscitation groups were significantly decreased, especially in 30 mL timely group; the central venous blood oxygen saturation (ScvO2) was significantly increased, especially in 30 mL delayed group. Oxygenation index (PaO2/FiO2) was improved in 30 mL timely and 30 mL delayed resuscitation groups, which was decreased in 60 mL delayed group. ② Plasma marker: compared with sham group, plasma syndecan-1 level in model group was significantly increased with a time-dependent manner. Plasma syndecan-1 levels at 3 hours in 30 mL timely and 30 mL delayed groups were significantly decreased as compared with those of model group (ng/L: 138.0±2.4, 139.7±15.7 vs. 161.5±4.1, both P < 0.05), but it was significantly increased at 6 hours in 30 mL delayed group (ng/L: 213.1±19.4 vs. 206.4±15.5, P < 0.05). The plasma syndecan-1 levels at 3 hours and 6 hours in 60 mL timely group were significantly higher than those in model group (ng/L: 233.0±28.9 vs. 161.5±4.1, 252.3±27.2 vs. 206.4±15.5, both P < 0.05). ③ Protein expression in lung tissue: compared with sham group, the protein expressions of ICAM-1 and MMP-2 in lung tissue of model group were significantly increased, and syndecan-1 protein expression was significantly decreased. After 30 mL timely or 30 mL delayed resuscitation, the protein expressions of ICAM-1 and MMP-2 in lung tissue were significantly decreased, and syndecan-1 protein expression was significantly increased, especially in 30 mL timely group, which showed statistical differences as compared with those of model group (ICAM-1 protein: 0.56±0.09 vs. 1.04±0.05, MMP-2 protein: 0.83±0.15 vs. 1.06±0.06, syndecan-1 protein: 2.09±0.08 vs. 0.99±0.03, all P < 0.05). The change tendency of protein expressions in 60 mL timely group was opposite to the other two resuscitation groups. ④ Immunohistochemistry: the positive expression of syndecan-1 in lung tissues was significant in the sham group, and it was lowered in model group. The positive expression of syndecan-1 was increased after 30 mL timely or 30 mL delayed resuscitation, but further weakened in 60 mL timely group.@*Conclusions@#The dose and timing of resuscitation with NS in septic shock can affect pulmonary vascular endothelial glycocalyx function. The timely resuscitation with 30 mL NS in combination with NE plays a protective effect on endothelial cell and glycocalyx. However, NS resuscitation which was not timely or excessive infusion can make the glycocalyx degradation more obvious, resulting in increased endothelial permeability, microcirculation damaged, thus aggravate lung injury.

Dose and timing of normal saline resuscitation on endothelial glycocalyx in early septic shock / 中华危重病急救医学

OBJECTIVE@#To observe the effect of different doses and timing of normal saline (NS) resuscitation combined with norepinephrine (NE) on endothelial glycocalyx in rabbits with early septic shock.@*METHODS@#Thirty New Zealand male rabbits were randomly divided into sham group, model group, 30 mL and 60 mL timely resuscitation groups (30 mL and 60 mL timely group), and 30 mL delayed resuscitation group (30 mL delayed group) with 6 rabbits in each group. The rabbit model of septic shock was reproduced by cecal ligation and puncture (CLP). The rabbits in sham group were only received abdominal cavity open without cecal and ligation. The rabbits in 30 mL and 60 mL timely groups and 30 mL delayed group were intravenous infused with 30 mL/kg or 60 mL/kg NS immediately or 1 hour after model reproduction for 1 hour, and the mean arterial pressure (MAP) was maintained over 75 mmHg (1 mmHg = 0.133 kPa) compared with intravenous pumping of 0.02-0.05 μg×kg-1×min-1 NE followed by 5 mL/h NS infusion till the end of the experiment. The rabbits in sham and model groups were only given 5 mL/h NS. The changes in arterial blood gas before and immediately after resuscitation were observed in three fluid resuscitation groups. The internal jugular vein blood was collected at 0, 3, 6 hours after model reproduction. The levels of syndecan-1 (polysaccharide envelope marker) in plasma were determined by enzyme linked immunosorbent assay (ELISA). The rabbits were sacrificed at 6 hours after model reproduction, and the lung tissue was harvested. Western Blot was used to determine the protein expressions of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase 2 (MMP-2) and syndecan-1. The positive expression of syndecan-1 in lung tissue was observed by immunohistochemical method.@*RESULTS@#(1) Blood gas analysis: compared with the results before resuscitation, the levels of lactic acid (Lac) after resuscitation in three fluid resuscitation groups were significantly decreased, especially in 30 mL timely group; the central venous blood oxygen saturation (ScvO2) was significantly increased, especially in 30 mL delayed group. Oxygenation index (PaO2/FiO2) was improved in 30 mL timely and 30 mL delayed resuscitation groups, which was decreased in 60 mL delayed group. (2) Plasma marker: compared with sham group, plasma syndecan-1 level in model group was significantly increased with a time-dependent manner. Plasma syndecan-1 levels at 3 hours in 30 mL timely and 30 mL delayed groups were significantly decreased as compared with those of model group (ng/L: 138.0±2.4, 139.7±15.7 vs. 161.5±4.1, both P < 0.05), but it was significantly increased at 6 hours in 30 mL delayed group (ng/L: 213.1±19.4 vs. 206.4±15.5, P < 0.05). The plasma syndecan-1 levels at 3 hours and 6 hours in 60 mL timely group were significantly higher than those in model group (ng/L: 233.0±28.9 vs. 161.5±4.1, 252.3±27.2 vs. 206.4±15.5, both P < 0.05). (3) Protein expression in lung tissue: compared with sham group, the protein expressions of ICAM-1 and MMP-2 in lung tissue of model group were significantly increased, and syndecan-1 protein expression was significantly decreased. After 30 mL timely or 30 mL delayed resuscitation, the protein expressions of ICAM-1 and MMP-2 in lung tissue were significantly decreased, and syndecan-1 protein expression was significantly increased, especially in 30 mL timely group, which showed statistical differences as compared with those of model group (ICAM-1 protein: 0.56±0.09 vs. 1.04±0.05, MMP-2 protein: 0.83±0.15 vs. 1.06±0.06, syndecan-1 protein: 2.09±0.08 vs. 0.99±0.03, all P < 0.05). The change tendency of protein expressions in 60 mL timely group was opposite to the other two resuscitation groups. (4) Immunohistochemistry: the positive expression of syndecan-1 in lung tissues was significant in the sham group, and it was lowered in model group. The positive expression of syndecan-1 was increased after 30 mL timely or 30 mL delayed resuscitation, but further weakened in 60 mL timely group.@*CONCLUSIONS@#The dose and timing of resuscitation with NS in septic shock can affect pulmonary vascular endothelial glycocalyx function. The timely resuscitation with 30 mL NS in combination with NE plays a protective effect on endothelial cell and glycocalyx. However, NS resuscitation which was not timely or excessive infusion can make the glycocalyx degradation more obvious, resulting in increased endothelial permeability, microcirculation damaged, thus aggravate lung injury.

The effects of 4 different clinical factors on endotracheal cuff pressure / 中华护理杂志

Objective To investigate the effects of endotracheal suctioning,turning over,oral caring and swallowingon cuff pressure,so as to provide evidence for the management of the endotracheal cuff.Methods During continuous monitoring of cuff pressure with pressure sensor,the changes of cuff pressure were recorded in the process of endotracheal suctioning,turning over,and oral caring.The data of cuff pressure were recorded including before activity,during activity,after activity for 5 min,15 min and 30 min.In addition,the data of cuff pressure were recorded including before swallowing,during swallowing,after swallowing for 1 min,5 min and 10 min.Results The cuff pressure during endotracheal suctioning and after endotracheal suctioning for 5 min was higher than that before endotracheal suctioning,the difference was statistically significant (P＜0.05);the cuff pressure during turning over and after turning over for 5 min was higher than that before turning over,the difference was statistically significant (P＜0.05);the cuff pressure during the oral caring was higher than that before oral caring,the difference was statistically significant(P＜0.05);the cuff pressure during swallowing was higher than that before swallowing,the difference was statistically significant(P＜0.05).Conclusion These clinical factors would lead to transient increase of cuff pressure including suctioning,turning over,oral caring,and swallowing.The instantaneous cuff pressure will mislead the staff to judge the safey of endotracheal cuff.The cuff pressure should not be blindly adjusted,so as to avoid the risks of leakage and aspiration.

The effect of AN69 ST membrane on filter lifetime in continuous renal replacement therapy without anticoagulation in patients with high risk of bleeding / 中华危重病急救医学

ObjectiveTo evaluate whether AN69 ST membrane would prolong filter lifetime in continuous renal replacement therapy (CRRT) without anticoagulation in patients with high risk of bleeding.Methods A single-center, prospective, randomized, double-blind control trial with crossover design was conducted. From March 1st to December 31st in 2013, patients who were admitted to Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University meeting CRRT treatment indications, but could not receive systemic anticoagulation because of high risk of bleeding were studied. The selected patients were randomly divided into two groups according to a random number table, and four filters consisting of two AN69 ST100 membrane filters (A) and two traditional AN69 M100 membrane filters (B) were used for them. GroupⅠ with the filter order of A-B-A-B, and groupⅡ with the order of B-A-B-A. The clinical data of patients was recorded in detail, and conventional AN69 ST and AN69 membrane filter lifetime, their influence on coagulability, and the incidence of bleeding complications were compared.Results Seventeen patients were enrolled, with 10 in groupⅠ, and 7 in groupⅡ. The basic medical characteristics including gender, age, acute physiology and chronic health evaluationⅡ (APAECHⅡ) score, sequential organ failure score (SOFA), Acute Renal Injury Network (AKIN) stage, activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), platelet count (PLT), and use of mechanical ventilation were not significantly different between two groups. But the use of vasoactive drug was more frequent in groupⅡcompared with that of groupⅠ[100.0% (7/7) vs. 30.0% (3/10),χ2 = 8.330,P = 0.010]. AN69 ST filter lifetime (n =34) was (15.92±2.10) hours, there was no statistically significant difference compared with that of AN69 membrane (t = 0.088,P = 0.942), filter lifetime of which (n = 34) was (16.12±1.38) hours. It was also found by Kaplan-Meier survival analysis that there was no significant difference between the two membrane filter lifetime (χ2=1.589,P =0.208). Logistic regression analysis showed that the life of the first filter was not correlated with coagulation indicators, including APTT, PT, INR, and PLT [APTT: odds ratio (OR) = 0.977, 95% confidence interval (95%CI) = 0.892-1.071, P = 0.623; PT:OR = 1.001, 95%CI = 0.901-1.109,P = 0.988; INR:OR = 1.078, 95%CI = 0.348-3.340,P = 0.896;PLT:OR = 0.996, 95%CI = 0.974-1.019,P = 0.735]. The application rate of vasoactive drugs, which was different between two groups for basic medical indications showed no effect on filter life time (OR = 2.541, 95%CI = 0.239-26.955,P = 0.439). Reasons of clotting in filters were also analyzed, and it was found that blood coagulation in the filter ranked the top (88.2%), and the other reasons were catheter-related problems, death, and unscheduled transport. No difference in blood coagulation function was found in both groups after treatment for 12 hours, and there was no bleeding complication.ConclusionDuring the CRRT without systemic anticoagulant, both surface-treatment with polyethyleneimine AN69 and AN69 ST membrane cannot prolong filter lifetime.

Behavioral study of affective arousal by pictures on female tonic pain / 中华行为医学与脑科学杂志

Objective To investigate the modulation of affective pictures on experimental tonic cold and heat pain in a behavioral study. Methods Fifteen healthy female subjects went through the tonic cold and tonic heat stimulation when watching the affective pictures in a counter-balanced order after the pictures were grouped into the pleasant, the unpleasant and the neutral picture sets. The pain tolerance time ( PTT ) was recorded.Results The tolerance time was prolonged when watching the pleasant and unpleasant pictures contrast to thatwhen watching the neutral ( Unpleasant ( 146.20 ± 13.68 ) s, Neutral ( 86. 73 ± 12.93 ) s, Pleasant ( 145.27 ±15.99 ) s, F(2,42) = 5.718, P ＜ 0.01 ) ). However, no significant difference was observed in the heat pain test under the different experimental conditions ( Unpleasant ( 74.73 ± 15.78 ) s, Neutral ( 68.80 ± 15.85 ) s, Pleasant ( 78.80± 14.81 )s, F(2.42) =0. 109, P＞0.05) ). A correlation between the residual difference of arousal in pleasant and neutral picture sets and the residual difference of heat PTT in pleasant and neutral picture sets was investigated (r = 0.546, P = 0.035 ). Conclusion Besides the emotional valence,the arousal may be one of the key elements that modulate the tonic pain.

The effect of space and color on judging speeds of traffic lights / 中华行为医学与脑科学杂志

Objective To investigate the effect of mental processing speeds of judging traffic lights varying in location and color meaning. Methods 20 healthy adult male (age: 18 ～30 years) were enrolled in this study. By simulation of traffic lights as picture stimuli, all subjects performed a Go/NoGo task separately under normal condition, location-reversed condition, color meaning-reversed condition and both location and color meaning-reversed condition randomly. The accuracy rate and reaction time of the behavior task were quantified. Results The average accuracy rate of the four conditions was 99. 13% , no differences were found in different traffic light colors and different conditions. In the normal condition,the subjects' reaction time(ms) of traffic lights were as fallowings: red light 491.59 ±71.74; green light 487.55 ±58. 11, no difference was found between the two traffic light colors (P=0.522). In the location-reversed condition, subjects' average reaction time(ms) was respectively for red light 606.29 ± 107.59, and green light 593.13 ± 102.45. In the color meaning-reversed condition, it was respectively for red light 572.08 ±78.75, and green light 592.43 ±87.58. Compared with the normal condition, subjects' reaction time was prolonged in the location-reversed condition (F(1,19)=59.77, P<0.01), and also in the color meaning-reversed condition (F(1,19) =52.55, P<0.01). When in the both location and color meaning-reversed condition, the subjects' reaction time (ms) of traffic lights was respectively 502.92 ± 65.27 for red light, and 508.97 ±63.40 for green light,the result came close to statistical significance(P= 0.065)compared with the normal condition. Conclusion A likely "conceptual constancy" is demonstrated on the basis of prolonging the brains' information processing when location and color information changes.

Teaching of chapter "Language and Attention" in Neurobiology / 中华医学教育探索杂志

Neurobiology is a cross subject,in which"Language and Attention"is an impor-tant chapter as a hotspot involved with physiology,psychology,anatomy and biology.Inorder to im-prove the teaching efficiency,it is necessary to apply the techniques such as arranging the content logically,giving prominence to the emphases and breaking through the difficulty,using interactive teaching method and collocating the assistant method rationally. Through this way,it is easier for the students to get interested in this chapter and grasped the content.

Exploration on how to interest medical students in extracurricular activities / 中华医学教育探索杂志

Extracurricular activities are necessary to curricular study and significant in quality and practical ability education for medical students.Research and practice on how to improve the interest in extracurricular activities for medical students were carried out,and good results were achieved in the aspect of the development of teaching efficiency.

The relationship between catecholamines levels in mother and fetus, and pathogenesis of pregnancy-induced hypertension / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To study the relationship between pregnancy-induced hypertension (PIH) and catecholamine levels.</p><p><b>METHODS</b>Catecholamines levels in maternal and fetal blood were determined in 116 patients with PIH and 40 normal control subjects using high performance liquid chromatography. The normal control subjects and PIH cases were selected from patients at term pregnancy receiving elective cesarean section.</p><p><b>RESULTS</b>Plasma norepinephrine (NE) levels were significantly higher in patients with severe PIH than those in control subjects (P < 0.05). Both patients and control subjects had higher NE levels in the umbilical artery blood than in the umbilical vein blood (P < 0.05). NE levels in the umbilical artery blood were five times higher than those in the maternal blood.</p><p><b>CONCLUSION</b>The pathogenesis of PIH may relate to catecholamine concentrations in fetus.</p>

The relationship between glutathione S-transferase M1 genotypes and lipid peroxidation in asbestos workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the relationship between glutathione S-transferase M1 (GSTM1) genotypes and lipid peroxidation of asbestos workers.</p><p><b>METHODS</b>94 asbestos workers and 51 controls were selected as subjects. The general information, occupational history and individual habits were collected by questionnaires in all participants. The venous blood was sampled and the plasma was separated for the detection of malondialdehyde (MDA) level and lymphocytes for DNA isolation and GSTM1 genotyping.</p><p><b>RESULTS</b>MDA level was significantly higher in asbestos workers [(0.283 +/- 0.054) nmol/L] than that in controls [(0.163 +/- 0.053) nmol/L, P < 0.01], however, neither duration of exposure nor accumulated asbestos exposure dose was related to MDA levels; MDA levels in control workers with GSTM1 +/- genotype [(0.190 +/- 0.034) nmol/L] were significantly higher than that in control workers with GSTM1 +/+ genotype [(0.138 +/- 0.055) nmol/L, P < 0.01]. Among asbestos workers, the same trend could be found, but the differences was not significant(P > 0.05). When the workers were stratified by duration of exposure or accumulated asbestos exposure dose, MDA levels in individuals with GSTM1 -/- genotype were also higher than those with GSTM1 +/+ genotype, but the differences were also not significant(P > 0.05).</p><p><b>CONCLUSION</b>Both exposure to asbestos and deficiency of GSTM1 genotype were related to lipid peroxidation in workers, but the role of the former may be more important than that of the latter.</p>

Effects of exposure to asbestos on plasma activity of glutathione S-transferases / 中华预防医学杂志

<p><b>OBJECTIVE</b>To understand the effects of exposure to asbestos and GSTM1 genotypes on plasma activity of glutathione S-transferases (GSTs).</p><p><b>METHODS</b>Ninety-four workers exposed to asbestos and 51 controls were selected, and their general information, occupational history and personal behavior were collected by questionnaire. Venous blood specimen was collected from each of them and plasma was separated for detection of GSTs activity and lymphocytes for DNA extraction and GSTM1 genotyping.</p><p><b>RESULTS</b>Plasma activity of GSTs in the asbestos-exposed workers (23.0 +/- 6.9) U/L was significantly lower than that in the controls (32.6 +/- 11.8) U/L, which declined with the length of employment in asbestos industry and the increase of cumulated dose of asbestos. Stratification of workers by GSTM1 genotypes showed that plasma activity of GSTs in asbestos-exposed workers with GSTM1+/+ or GSTM1-/- were (24.0 +/- 6.1) and (22.5 +/- 7.3) U/L, respectively, lower than those in the controls with the same genotypes (38.1 +/- 13.2) and (26.8 +/- 6.6) U/L. Plasma activity of GSTs in the control workers with GSTM-/- was significantly lower than in those with GSTM+/+, and, so did in asbestos-exposed workers, but without statistically significant difference.</p><p><b>CONCLUSION</b>Exposure to asbestos could significantly decrease plasma activity of GSTs, and GSTM1 genotypes could affect on the activity of GSTs in the control workers, which was not so obvious in asbestos-exposed workers.</p>