Exposure to occupational risk factors is associated with the severity and progression of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) results from a complex interaction between genes and the environment, and occupational exposures are an underappreciated risk factor. Until now, little research attention has been paid to the potential impact of occupational risk factor exposure on the COPD in China. The aim of this retrospective study was to analyze the role of occupational risk factor exposure on the severity and progression of COPD for exploring new prevention strategies for this disease. This study adopted a random cluster-sampling method. Five grade-A tertiary hospitals that met the inclusion criteria were selected as the survey sites, and patients with COPD hospitalized in these hospitals from January 1, 2019, to December 31, 2019, were selected as the research subjects. Data of the patients diagnosed with COPD met the Global Initiative for Chronic Obstructive Lung Disease (2019) criteria and were collected from the computerized medical record databases. Among 4082 investigated COPD patients, 1063 (26%) were found to have occupational risk factor exposure history. The top 3 industries with a large COPD case number and a history of occupational risk factor exposure ranked in the order of agriculture (including farming, forestry, animal husbandry, and fishery), manufacturing, and mining. Further multivariate logistic regression analysis indicated that when setting a low exposure level as a reference, medium and high exposure levels were correlated with the severity of COPD (odds ratio values were 2.837 and 6.201, respectively, P < .05). Linear regression analysis showed that cumulative exposure to occupational risk factors was negatively correlated with the forced expiratory volume in 1-second percentage of COPD patients, with a correlation coefficient of 0.68. Our results indicated that occupational risk factor exposure levels were related to the severity of COPD significantly. The incubation period of COPD in the exposure group was significantly shorter than that in the non-exposure group. To prevent worked-related COPD, special attention and control efforts should be taken to reduce the level of occupational risk factors such as organic dust, irritating chemicals, etc in the work environments, especially in the industries of agriculture, forestry, animal husbandry and fishery, manufacturing, and mining.

Genetic analysis of the LRP10 gene in Chinese patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by resting tremor, bradykinesia, muscle rigidity, and abnormal gait. The low-density lipoprotein receptor-related protein 10 (LRP10) was recently shown to be a causal gene for PD, and different ethnic cohorts have distinct frequencies and spectrum of LRP10 variants. METHODS: We sequenced the full coding regions and exon-intron boundaries of LRP10 in 129 patients with sporadic Chinese PD to further investigate the connection of LRP10 with PD in a sample of Chinese patients. RESULTS: In this study, we identified four potentially pathogenic mutations, including one novel mutation of p.Gly328Asp and three known mutations of p.Cys165Tyr, p.Arg230Trp, and p.Arg661His in four of the 129 Chinese patients with PD. CONCLUSION: According to our study, the LRP10 gene may attribute to PD pathogenesis.

Manganese exposure induces permeability in renal glomerular endothelial cells via the Smad2/3-Snail-VE-cadherin axis.

Manganese (Mn) is an essential micronutrient. However, it is well established that Mn overexposure causes nervous system diseases. In contrast, there are few reports on the effects of Mn exposure on glomerular endothelium. In the present study, the potential effects of Mn exposure on glomerular endothelium were evaluated. Sprague Dawley rats were used as a model of Mn overexposure by intraperitoneal injection of MnCl2·H2O at 25 mg/kg body weight. Mn exposure decreased expression of vascular endothelial-cadherin, a key component of adherens junctions, and increased exudate from glomeruli in Sprague Dawley rats. Human renal glomerular endothelial cells were cultured with different concentration of Mn. Exposure to 0.2 mM Mn increased permeability of human renal glomerular endothelial cell monolayers and decreased vascular endothelial-cadherin expression without inducing cytotoxicity. In addition, Mn exposure increased phosphorylation of mothers against decapentaplegic homolog 2/3 and upregulated expression of zinc finger protein SNAI1, a negative transcriptional regulator of vascular endothelial-cadherin. Our data suggest Mn exposure may contribute to development of glomerular diseases by inducing permeability of glomerular endothelium.

Chronic obstructive pulmonary disease caused by inhalation of dust: A meta-analysis.

BACKGROUND: A meta-analysis was performed to evaluate the relationship between chronic obstructive pulmonary disease (COPD) and occupational dust exposure, and to provide a scientific basis for the prevention and treatment of COPD caused by occupational factors. METHODS: PubMed and Embase databases were used to search for original epidemiological literature related to theme. Both random and fixed effects models were used to calculate pooled odds ratios and their corresponding 95% confidence intervals. Review Manager was used to perform data analysis. RESULTS: Nine studies were included in the meta-analysis in accordance with the inclusion criteria. There was a significantly obvious correlation between occupational dust exposure and COPD of the population-based studies assessed in this article. The risk of developing COPD for workers exposed to dust was 1.51 times higher than for controls (I = 40%, 95% confidence interval: 1.27-1.79). The presence of publication bias was not found. CONCLUSION: The study provided evidence supporting the association between occupational dust exposure and the risk of developing COPD.

Gene sequence screening for manganese poisoning-susceptible genes and analysis of gene interaction effects.

Manganese poisoning is a common occupational disease, studies have found that the susceptibility to manganese poisoning differs in individuals. We adopted genome-wide sequencing methods to screen for susceptibility genes involved in gene-mediated metabolic pathways from the perspective of manganese poisoning. We identified 18,439 genes in this study, including 14,272 known genes and 4398 new genes. We then selected 17 differential genes using p values, of which 7 genes were down-regulated and 10 genes were up-regulated. Possible interaction genes for each differential gene were selected according to the String database. Sgk1, HCRTr1, HspB1, Rem2, Oprd1, ATF5, and TRHr identified in this study may be involved in oxidative stress mechanisms, dopamine (DA) synthesis, and neuronal survival during apoptosis and may affect susceptibility to manganese poisoning.

Exploration of the establishment of manganese poisoning rat model and analysis of discriminant methods.

OBJECTIVE: We explored methods to establish an animal model of manganese poisoning and evaluate the feasibility of the determination method. METHODS: Twenty-four specific pathogen-free male rats were randomly divided into four groups: control, low-dose (15.0 mg/kg), middle-dose (25.0 mg/kg), and high-dose (50.0 mg/kg). Intraperitoneal injection of MnCl2·H2O was administered every 48 h for three months. Rats were tested for behavior, muscle tension, and with a balance beam experiment at the end of each month. Three months later, the rats were sacrificed and brain tyrosine hydroxylase (TH) expression levels were measured. RESULTS: Rats in each group exhibited changes in behavior, muscle tone, and balance after exposure to manganese, and the scores of each test for the high-dose and middle-dose groups were statistically different from the low-dose and control groups. Finally, a rat model of manganese poisoning was identified with the TH expression less than 30% of the normal value. We find that the modeling success rate of the middle-dose and high-dose groups were 66.67% and 100%, respectively. In addition, there were negative correlations between the three assessment methods such as behavioral tests and TH expression levels. CONCLUSIONS: Intraperitoneal injection of MnCl2·H2O (25 mg/kg) can successfully establish a manganese poisoning rat model with low mortality rate. Muscle tension, balance beam, and behavioral tests can be used as preliminary determination methods for modeling.

[Clinical analysis of hard metal lung disease].

OBJECTIVE: To analyze the clinical features and investigate the clinical diagnostic methods of hard metal lung disease (HMLD), then provide reference for the diagnostic criteria of occupational HMLD. METHODS: Retrieved the open published case reports associated with HMLD from January, 2000 to June, 2014. Regarding the ages, sex, types and years of work, clinical features and laboratory results for analyzing. RESULTS: Collected 21 clinical cases of HMLD belonged to 6 internal reports and 15 oversea reports. Among them 15 male and 6 female, ages were from 22 to 58, length of service between 1 year and 43 years. Clinical presentations included cough (20 cases), dyspnea on progressive (10 cases), and pulmonary function testing showed a restrictive abnormality. The imaging features presented as bilateral areas of ground-glass attenuation, diffuse small nodules, extensive reticular opacities and traction bronchiectasis. The finding of giant cell interstitial pneumonia (GIP) was almost pathognomonic for hard metal pneumoconiosis. The main pathological findings contained a different levels of lymphocyte, acidophilic cell infiltration, hyperplasia of fibrous tissue and numerous large multinucleated histiocytes which ingested inflammatory cells were admixed with macrophages. 16 cases of the 21 reports showed GIP. CONCLUSIONS: Clinical presentations include cough and dyspnea on progressive, and pulmonary function testing show a restrictive abnormality. The imaging features present as bilateral areas of ground-glass attenuation, areas of consolidation, diffuse small nodules, extensive reticular opacities and traction bronchiectasis. The prime pathological findings contain interstitial pneumonia with intra-alveolar macrophages and a large amount of multinucleated histiocytes.

[Analysis of the literature on acute aromatic amino or nitro-compounds poisoning].

OBJECTIVE: To review the clinical features of acute toxicity of aromatic amino and nitro compounds. METHODS: A total of 110 papers reporting 1240 cases of acute toxicity induced by aromatic amino and nitro compounds from 1979 to 2013 were collected from CNKI, VIP, and Wanfang database, and were analyzed in this study. RESULTS: Of all included cases, 939 were caused by occupational exposure, and 301 were caused by exposure in daily life. A total of 1044 cases were male, and 196 were female. Age ranged from 9 days to 75 years. There were 13 cases of contact reaction. The numbers of mild, moderate, and severe toxicities were 358, 348, and 139, respectively, and the other 382 cases were not graded for severity. The average incubation period was 4.50±5.71 h (M = 3 h). The average incubation period of aniline toxicity was significantly shorter than that of nitrobenzene toxicity. Methemoglobinemia was found in 1146 cases, while cases of poisonings with 5-nitro-o-toluidine, 2-methyl-4-nitroaniline, and 3-chloro-2-methyl aniline were not found to have methemoglobinemia. The detection rates of MHb and HzB were 83.73% (674/805) and 40.19% (129/321), respectively. Sixty-two (19.31%) out of 321 cases were complicated by intravascular hemolysis, 270 (30.93%) out of 873 cases suffered hepatic impairment, 50 (12.25%) out of 408 cases were accompanied by renal damage. Consciousness disorders were found in 66 cases, and chemical cystitis was found in 36 cases. Oral poisoning could immediately induce severe symptoms including cyanosis, unconsciousness, and hemolysis. In prognosis analysis, it was found that the cure rate was 98.71% (1224/1240), and 14 cases of death were caused by multiple organ dysfunction syndrome, renal failure, uncontrolled hemorrhagic shock, myocardial infarction, and sudden death. Two cases were left with neurological sequelae. CONCLUSION: The clinical manifestations of poisoning with aromatic amino and nitro compounds are methemoglobinemia, intravascular hemolysis, liver damage, and renal damage. Treatment with specific medicine methylene blue can produce ideal clinical prognosis, but severe poisoning may cause death from multiple organ failure.

[Relationship between mRNA expression of MnSOD and manganese neurotoxicity].

OBJECTIVE: To investigate the relationship between mRNA expression of manganese superoxide dismutase (MnSOD) and manganese neurotoxicity. METHODS: Thirty-one patients with occupational chronic manganese poisoning (case group), as well as 31 controls exposed to the same condition (control group), were included in the study. Whole blood RNA was extracted, and the mRNA expression of MnSOD was measured by RT-PCR; the two groups were compared in terms of the mRNA expression of MnSOD. PC12 cells were treated with 0, 100, 200, 400, 600, 800, and 1000 ümol/L MnCl2 for l, 2, 3, and 4 d; the cell viability was determined by MTT assay, and the mRNA expression of MnSOD was measured by RT-PCR. RESULTS: The case group had significantly lower mRNA expression of MnSOD than the control group (0.390 ± 0.080 vs 0.582 ± 0.219, P < 0.05). MnCl2 had a toxic effect on PC12 cells; the concentration of MnCl2 was positively correlated with the toxic effect but negatively correlated with the mRNA expression of MnSOD. CONCLUSION: MnSOD mRNA may be involved in the manganese-induced damage of nerve cells. It is hypothesized that high mRNA expression of MnSOD may play an inhibitory effect on manganese neurotoxicity.

[Experimental study on the therapeutic effect of C-phycocyanin against pulmonary fibrosis induced by paraquat in rats].

OBJECTIVE: To investigate the therapeutic effect of C-phycocyanin (C-PC) from Spirulina platensis on paraquat (PQ)-induced pulmonary fibrosis in rats. METHODS: A total of 90 healthy Wistar rats were randomly and equally divided into normal control group, model group (PQ group), and C-PC treatment group (C-PC group). Each rat in the PQ group and C-PC group were orally administered with a single dose of PQ (50 mg/kg) to establish a rat model of PQ poisoning. Then, the rats in the normal control group and PQ group were orally given saline solution (1 ml/100 g) every day, and the rats in the C-PC group were orally given C-PC (50 mg/kg) every day. Six rats were randomly selected from each group on days 1, 3, 7, 14, and 28. The inferior lobe of each rat's right lung was homogenized for the measurement of hydroxyproline (HYP) and maleic dialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Parts of each rat's left lung were subject to HE staining and Masson staining for pathological observation, and the expression of transforming growth factor-ß(1) (TGF-ß(1)), nuclear factor-kappa B p65 (NF-κB p65), and tumor necrosis factor-α (TNF-α) in lung tissue was measured by immunohistochemistry. RESULTS: The HYP levels on days 1, 3, 7, 14, and 28 and MDA levels on days 14 and 28 were significantly lower in the C-PC group than in the PQ group (P < 0.05, P < 0.01). The SOD activity was significantly higher in the C-PC group than in the PQ group on days 1, 7, 14, and 28 (P < 0.05, P < 0.01). The protein content of TGF-ß(1) and the activities of NF-κB p65 and TNF-α in the PQ group and C-PC group were significantly higher than those in the normal control group, while the indices in the C-PC group were significantly lower than those in the PQ group (P < 0.05, P < 0.01). The pathological observation showed that C-PC could alleviate pulmonary alveolitis and fibrosis in rats with PQ poisoning. CONCLUSION: C-PC can significantly inhibit PQ-induced pulmonary alveolitis and fibrosis in rats.

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats.

To investigate the potential protective effect of C-phycocyanin (PC) on paraquat (PQ)-induced acute lung injury, rats were divided into control, PQ-treated and PQ+PC-treated groups. Rats in PQ-treated group were orally administered with 50mg/kg PQ, and rats in PQ+PC-treated group were intraperitoneally injected with 50mg/kg PC after administration of PQ. At 8, 24, 48 and 72h after treatments, GSH-Px and SOD activities, MDA levels in plasma and BALF, HYP, NF-κB, IκB-α and TNF-α contents in lung tissues were measured. The pathological changes in lung were observed. After treatment with PC, the levels of MDA and the relative contents of NF-κB and TNF-α were significantly decreased, the activities of GSH-Px and SOD and the relative contents of IκB-α were significantly increased. The degree of rat lung damage was obviously reduced in PQ+PC-treated group. The results suggested that PC treatment significantly attenuated PQ-induced acute lung injury.

[Relationship between MnSOD polymorphisms and susceptibility of chronic poisoning exposed to manganism occupationally].

OBJECTIVE: To study the relationship between polymorphisms of MnSOD and the susceptibility of chronic poisoning exposed to manganism occupationally. METHODS: In a study of case-control, genotypes were determined by PCR-RFLP in 164 patients with chronic occupational mangamism poisoning and 328 controls with age- and sex-matched for MnSOD 9Ala-Val. RESULTS: There was a significant difference in the frequency of MnSOD 9Ala-Val at V locus mutant allele between cases and controls (χ(2) = 15.225, P < 0.01, 95%CI = 1.43 ∼ 3.00). Individuals with the genotype VV had a 1.30 of risk increase of occupational chronic manganism poisoning compared with the the genotype AV or AA (OR = 2.30, 95%CI = 1.52 ∼ 3.49, P < 0.05). CONCLUSION: The MnSOD polymorphisms may be related with the susceptibility to chronic occupational manganism poisoning, the risk of chronic occupational manganism poisoning increases in carriers with genotype VV at MnSOD 9Ala-Val locus.

[Clinical trial on standard treatment of acute organophosphorus poisoning].

OBJECTIVE: To explore the norms of treatment of acute organophosphorus pesticide poisoning (AOPP), and observe the curative effect. METHODS: On basis of the pre-research, the norms of treatment of AOPP were summarized, and a multi-center clinical trial was performed in 6 hospitals selected from high incidence of AOPP in Shandong Province. RESULTS: 422 patients of AOPP in 6 hospitals in observation period were treated and observed by the norms of treatment. Among them, the proportion of oral poisoning was 97.16%, middle and severe degree were 87.44%. Compared with themselves 2 years ago before standard treatment, the curative effect of the norms of treatment for AOPP was much better than before. The mortality rate of AOPP declined from 9.87% to 1.66% (Chi2 = 27.92, P < 0.01), that was much better than the average therapeutic effect level of all our province in the same period (the mortality rate: 8.92%) (Chi2 = 26.05, P < 0.01). The average amount of atropine [(37.54 +/- 17.76) mg], dropped greatly [(1280.70 +/- 69.22) mg] (U = 439.22, P < 0.01).The usage of atropine by continuous intravenous injection with venous pump was better than ordinary intravenous injection. The mean dosage of pralidoxime chloride increased twice than the previous (U = 19.48, P < 0.01). There was no drug poisoning. CONCLUSION: The standard treatment of AOPP is urgently needed in our country, especially in rural area. By this trial, the satisfactory effect of the norms of treatment for AOPP summarized is observed and it reduces the fatality rate remarkably.

Phenylmethylsulfonyl fluoride protects against the degradation of neurofilaments in tri-ortho-cresyl phosphate (TOCP) induced delayed neuropathy.

Tri-ortho-cresyl phosphate (TOCP) is an organophosphorus ester, which can cause a type of neurotoxicity known as organophosphate-induced delayed neuropathy (OPIDN). Our recent study has shown that the enhanced degradation of neurofilament (NF) in peripheral nerve of hens is an early event of TOCP-induced OPIDN (Song et al., 2009). The main objective of this investigation is to study the effect of TOCP administration on NF content and NF degradation when OPIDN is blocked by pretreatment with phenylmethylsulfonyl fluoride (PMSF). The hens were pretreated 24h earlier with PMSF and subsequently treated with a single dosage of 750 mg/kg TOCP, then sacrificed on the corresponding time points of 0, 1, 5, 10, and 21 days after dosing TOCP, respectively. The tibial nerves were dissected, homogenized, and centrifuged at 100,000 x g. The level of NF triplet protein in both pellet and supernatant fractions of tibial nerves was determined. Western blotting analysis showed a significant increase of three NF subunits in hens treated with PMSF and TOCP compared with the control. These changes were observed within 24h of PMSF administration and then followed by an obvious recovery. Furthermore, accompanied with the increase of NF content, a significant decline in NF-L degradation rate was observed in both fractions of tibial nerves. Taken together, these results demonstrated the pretreatment with PMSF could inhibit TOCP-induced NF degradation while it protected hens against the development of OPIDN, which suggested the inhibition of NF-associated protease in peripheral nerves might be an underlying protective mechanism of PMSF against OPIDN.

Neurofilaments degradation as an early molecular event in tri-ortho-cresyl phosphate (TOCP) induced delayed neuropathy.

Tri-ortho-cresyl phosphate (TOCP), an organophosphorus ester, is capable of producing organophosphorus ester-induced delayed neuropathy (OPIDN) in human being and sensitive animals. In the present study, adult hens were treated with TOCP by gavage at single dosage of 750 mg/kg, and sacrificed by decapitation on the corresponding time points of 1, 5, 10, and 21 day post-dosing, respectively. The tibial nerves were dissected, homogenized, and centrifuged at 100,000 xg. The level of neurofilaments protein in both pellet and supernatant fractions was determined. Western blot analysis showed a nearly depletion of NF-M and a dramatic decrease of NF-L in both fractions of tibial nerves. These changes were observed within 24h of TOCP administration and then followed by an obvious recovery. In contrast, a progressive reduction in NF-H was observed in tibial nerves of TCOP-treated hens throughout the period of experiment. With the reduction of NF-L level, the rate of NF-L degradation demonstrated a significant increase in both fractions of tibial nerves. Furthermore, the expression of mu-calpain in tibial nerves was increased following TOCP. Taken together, these results demonstrated that NFs changes occurred much earlier than the clinical appearance of ataxia in TOCP-induced delayed neuropathy, indicating that disruption of NF homeostasis in peripheral nerves might be an early molecular event in the development of OPIDN.

[Follow-up study on psychic and neuropathic delayed effects of acute organophosphorus pesticides poisoning].

OBJECTIVE: To study the delayed effect on neuropsychopathy and its related factors after acute organophosphorus pesticides poisoning (AOPP). METHODS: Two hundred and fifty-seven cases of AOPP in the observation period were chosen to follow-up 2 months later from the 4 county hospitals in Shandong Province where the incidence of organophosphorus pesticide poisoning is high. RESULTS: Nine cases of organophosphate induced delayed polyneuropathy (OPIDP) were found and the incidence rate was 3.5%. The occurrence of OPIDP were related to the need for emergent artificial respiration, and the degree of poisoning, and the kinds of organophosphorus pesticides (Ops). The positive rate of symptoms of peripheral nerves, central nerves and psychogeny except auditory and visual hallucination after poisoning was significantly higher than that before (P < 0.05). The patient's situation of health, economy and work became statistically worse (P < 0.05). CONCLUSION: We found some had delayed effects on neuropsychopathy after AOPP which could debase the patient's life quality. The control measure should be administered as early as possible.