Modification of m6 A in human embryonic lung fibroblasts induced by neodymium oxide exposure and its mechanism / 环境与职业医学

Background Occupational and environmental particulate matter may cause fibrosis, accompanied by RNA m6A modification changes. Neodymium oxide (Nd2O3) can cause mouse lung fibrosis, which contains a large number of fibroblasts. Objective To investigate m6A modification of tumor necrosis factor receptor-associated protein 6/nuclear factor-κB (TRAF6/NF-κB) signaling pathway in fibrosis of human embryonic lung fibroblasts induced by Nd2O3, and identify the key m6A modification sites of TRAF6. Methods Designed concentrations of Nd2O3 (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100, and 200 mg∙L−1) were infected with HELF cells for 24 and 48 h, and cell viability was detected to determine exposure time and dose. Measurements included indicators of fibrosis [hydroxyproline (HYP) and transforming growth factor-β1 (TGF-β1)], m6A methylation level, methyltransferases (METTL3 and METTL14), demethylases (FTO and ALKBH5), reading proteins (YTHDC2 and YTHDF2), fibrosis-associated genes (collagen-І, vimentin, and α-SMA), and proteins related to signaling pathway (TRAF6, NFKB1, P65, and P-P65). The enrichment of m6A in TRAF6 mRNA was measured by methylated RNA immunoprecipitation-quantitative real-time PCR (MeRIP-qPCR). Results The results of cell viability indicated that 6.25, 12.5, 25 mg∙L−1 Nd2O3 and 48 h exposure time were used for subsequent experiments. After 48 h exposure, compared with the control group, the HYP level in the 25 mg∙L−1 Nd2O3 group was increased, and the levels of TGF-β1 in the 6.25, 12.5, and 25 mg∙L−1 Nd2O3 groups were increased (P<0.05); the overall m6A methylation levels of HELF cells in the 12.5 and 25 mg∙L−1 Nd2O3 groups were increased (P<0.05). At mRNA level, compared with the control group, the mRNA expression levels of methyltransferases METTL3 and METTL14 (6.25, 12.5, and 25 mg∙L−1 Nd2O3) were increased (P<0.05); the mRNA expression level of reading protein YTHDF2 (6.25, 12.5, and 25 mg∙L−1 Nd2O3) was increased (P<0.05), while the mRNA expression level of YTHDC2 (25 mg∙L−1 Nd2O3) was decreased (P<0.05); the mRNA expression levels of demethylases FTO (12.5 and 25 mg∙L−1 Nd2O3) and ALKBH5 (25 mg∙L−1 Nd2O3) were decreased (P<0.05); the mRNA expression levels of fibrosis-related genes vimentin, α-SMA, and collagen-Ⅰ (6.25, 12.5, and 25 mg∙L−1 Nd2O3) were increased (P<0.05); the mRNA expression levels of pathway-related genes TRAF6 (25 mg∙L−1 Nd2O3) and NFKB1 (12.5 and 25 mg∙L−1 Nd2O3) were increased (P<0.05). At protein level, compared with the control group, the expression levels of methyltransferases METTL3 (25 mg∙L−1 Nd2O3) and METTL14 (12.5 and 25 mg∙L−1 Nd2O3) were increased (P<0.05); the expression level of reading protein YTHDF2 (12.5 and 25 mg∙L−1 Nd2O3) was increased, while the expression level of YTHDC2 (25 mg∙L−1 Nd2O3) was decreased (P<0.05); the expression level of demethylase FTO (25 mg∙L−1 Nd2O3) was decreased (P<0.05); the expression level of fibrosis-associated protein vimentin was increased at 25 mg∙L−1 Nd2O3, and the expression levels of α-SMA and collagen-Ⅰ were increased at 12.5 and 25 mg∙L−1 Nd2O3 (P<0.05); the expression levels of TRAF6 and P-P65 were increased at 25 mg∙L−1 Nd2O3 (P<0.05). The MeRIP-qPCR results showed that compared with the control group, the concentrations of m6A in all Nd2O3 groups were significantly increased (P<0.05). Conclusions Upon exposure of HELF cells to Nd2O3, the alterations in fibrosis-related indexes increase the expression of some m6A methylases and decrease the expression of demethylases, thereby increasing the m6A methylase level, and may promote the progression of fibrosis by activating the TRAF6/NF-κB signaling pathway.

Research progress on relationship between N6-adenylate methylation modification and cell transformation and associated mechanism / 环境与职业医学

As a reversible and dynamic epigenetic marker, N6-adenylate methylation (m6A) modification is the most common mRNA modification in eukaryotes. This paper briefly described how m6A can influence RNA splicing, stability, and translation after transcription, and then participate in a variety of signaling pathways and biological and pathological processes, regulating cell proliferation, apoptosis, epithelial mesenchymal transformation (EMT) processes, and tumor invasion and metastasis. In addition, according to current studies, m6A methyltransferases (writers) are believed to promote EMT and tumor development, and readers and erasers both promote and inhibit EMT in different research objects. In this review, we summarized the mechanism of m6A modification and its role in cell transformation, and pointed out the direction of disease treatment.

Analysis of risk factors for deep vein thrombosis of lower extremity after thoracoscopic surgery for elderly lung cancer and establishment and validation of prediction model / 国际肿瘤学杂志

Objective:To analyze the risk factors of lower extremities deep vein thrombosis after thoracoscopic surgery in elderly patients with lung cancer, establish a nomogram prediction model and conduct internal verification.Methods:A total of 183 elderly patients with lung cancer who underwent thoracoscopic radical resection in Nanchong Central Hospital from February 2018 to February 2022 were selected as the study subjects. According to the presence or absence of deep venous thrombosis of the lower extremities within one month after operation, the patients were divided into lower extremities deep venous thrombosis group ( n=61) and non-deep lower extremities venous thrombosis group ( n=122) . Univariate and multivariate analyses of deep venous thrombosis of lower extremities after thoracoscopic surgery for lung cancer in the elderly were performed, and a nomogram prediction model was constructed according to the multivariate analysis results, and the model was verified. Results:There were statistically significant differences in smoking history ( χ2=13.40, P<0.001) , preoperative chemotherapy ( χ2=8.79, P=0.003) , surgical method ( χ2=7.97, P=0.005) , operation time ( t=7.23, P<0.001) , postoperative bed rest time ( t=10.40, P<0.001) , combined with diabetes ( χ2=6.37, P=0.012) , combined with hyperlipidemia ( χ2=9.58, P=0.002) , preoperative D-dimer ( t=13.08, P<0.001) , preoperative fibrinogen ( t=5.84, P<0.001) and preoperative platelet count ( t=7.01, P<0.001) between the lower extremity deep venous thrombosis group and the non-lower extremity deep venous thrombosis group. The results of multivariate logistic regression analysis showed that preoperative chemotherapy ( OR=2.45, 95% CI: 1.05-5.71, P=0.038) , surgical method ( OR=2.55, 95% CI: 1.14-5.73, P=0.023) , postoperative bed rest time ( OR=1.50, 95% CI: 1.24-1.81, P<0.001) , combined with diabetes ( OR=3.60, 95% CI: 1.05-12.33, P=0.042) , and preoperative D-dimer ( OR=1.01, 95% CI: 1.01-1.01, P<0.001) were all independent risk factors for lower extremity deep vein thrombosis in elderly patients with lung cancer after thoracoscopic surgery. The C-index of nomogram for predicting lower extremity deep vein thrombosis-related factors was 0.86 (95% CI: 0.81-0.93) . The calibration curve showed that the model had a good correlation in predicting lower extremities deep venous thrombosis. Conclusion:Preoperative chemotherapy, surgical method, postoperative bed rest time, combined with diabetes, and postoperative D-dimer level are influence factors for lower extremity deep vein thrombosis in elderly patients with lung cancer after thoracoscopic surgery. The nomogram prediction model established in this study has high accuracy and discrimination for the prediction of lower extremity deep vein thrombosis in elderly patients with lung cancer after thoracoscopic surgery.

Changes of m6A modification in arsenic-induced oxidative stress of human embryonic lung fibroblasts / 环境与职业医学

Background Arsenic can be toxic to human by triggering oxidative stress, which is companied by epigenetic modifications. Objective To investigate the modification of N6-methyladenosine (m6A) in human embryonic lung fibroblasts (HELF) during oxidative stress induced by sodium arsenite (NaAsO2). Methods HELF cells were treated by designed concentrations of NaAsO2 (0, 2.5, 5, 10, and 20 μmol·L−1) for 48 h. Cell viability was detected by 3-(4,5-dimethylthia zol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium (MTS) method; the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) as well as the content of malondialdehyde (MDA) were detected with corresponding kits; the level of m6A methylation in total RNA was detected by enzyme-linked immunosorbent assay; the mRNA expressions of m6A modified enzymes were detected by real-time fluorescence quantitative PCR, including methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), Wilms' tumor 1-associated protein (WTAP), fat mass and obesity-associated protein (FTO), alkB family of Fe(II)/α-ketoglutarate-dependent dioxygenases 5 (ALKBH5), YTH domain containing protein 2 (YTHDC2), YTH domain family protein 2 (YTHDF2), and YTH domain family protein 3 (YTHDF3); the protein expressions of METTL3, FTO, YTHDC2, YTHDF3, and nuclear factor erythroid 2-related factor 2 (NRF2) were detected by Western blotting. The enrichment of m6A in NRF2 mRNA was detected by RNA methylated immunoprecipitation combined with real-time fluorescence quantitative PCR (MeRIP-qPCR). Results After the 0, 2.5, 5, 10, and 20 μmol·L−1 NaAsO2 treatment, the MTS results showed that compared with the control group, the cell viability of the 20 μmol·L−1 group decreased to 84% (P<0.05). The colorimetry results showed that compared with the control group, the activities of T-SOD in the 10 and 20 μmol·L−1 groups decreased (P<0.05); the activities of GSH-Px in the 2.5 and 10 μmol·L−1 groups decreased (P<0.05); the contents of MDA in the 10 and 20 μmol·L−1 groups increased. The results of enzyme-linked immunosorbent assay showed that the overall m6A methylation levels in the 0, 2.5, 5, 10, and 20 μmol·L−1 groups were (0.193 ± 0.023)%, (0.247 ± 0.021)%, (0.253 ± 0.006)%, (0.233 ± 0.006)%, and (0.262 ± 0.010)%, respectively, and compared with the control group, the m6A methylation levels in all the NaAsO2 treated groups increased (P<0.05). The real-time fluorescence quantitative PCR results showed that compared with the control group, the mRNA relative expression level of METTL3 decreased in the 2.5, 10, and 20 μmol·L−1 groups (P<0.05); the mRNA relative expression level of FTO decreased in the 20 μmol·L−1 group; the mRNA relative expression level of YTHDC2 increased in the 10 and 20 μmol·L−1 groups (P<0.05); the mRNA relative expression level of YTHDF3 increased in the 2.5, 10, and 20 μmol·L−1 groups (P<0.05). The Western blotting results showed that compared with the control group, the relative protein expression of METTL3 decreased in the 10 and 20 μmol·L−1 groups; the relative protein expression of FTO decreased in the 5 and 20 μmol·L−1 groups; the relative protein expression of YTHDC2 decreased in the 20 μmol·L−1 group (P<0.05); the relative nuclear protein expression of NRF2 decreased in the 10 and 20 μmol·L−1 groups (P<0.05). The MeRIP-qPCR results showed that m6A enrichment was significantly increased in the 20 μmol·L−1 NaAsO2 exposure group compared with the control group (P<0.05). After over-expression of FTO, the mRNA and protein relative expression levels of FTO and the relative expression level of nuclear protein of NRF2 in the FTO group were higher than those in the control group (P<0.05); the mRNA and protein relative expression levels of FTO in the NaAsO2 + FTO group and the nuclear protein expression level of NRF2 were higher than those in the NaAsO2 group (P<0.05). Conclusion In the process of oxidative stress induced by NaAsO2, m6A methylation level, m6A modified enzymes, m6A modification of NRF2 mRNA, and NRF2 expression could change in HELF cells.

Preconditioning of endoplasmic reticulum stress protects against acrylonitrile-induced cytotoxicity in primary rat astrocytes: The role of autophagy.

This study explored the protective effects of endoplasmic reticulum (ER) stress preconditioning induced by 2-deoxy-d-glucose (2-DG) or oxidized dithiothreitol (DTTox) on acrylonitrile (AN)-induced cytotocity in primary rat astrocytes. Cells were pretreated with 2-DG or DTTox for different times at various concentration. Next, astrocytes were treated with 2.5mM AN for an additional 12h. Cell viability and cytotoxicity were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) leakage, respectively. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were determined. Expression of glucose-regulated protein 78 (GRP78), phosphorylated-eukaryotic translation initiation factor 2α (p-eIF2α), microtubule-associated protein light chain 3 (LC3), P62, and Beclin1 were used to assess autophagy. In addition, 3-methyadenine (3-MA), an autophagy-specific inhibitor, was used to assess the role of autophagy in ER stress preconditioning-induced protection against AN cytotoxicity. The results showed that AN alone significantly decreased astrocytic viability and enhanced cytotoxicity. Compared to the AN-alone group, preconditioning with 2-DG or DTTox significantly increased cell viability and reduced cytotoxicity to indistinguishable levels. Decreased ROS generation and increased ΔΨm were also inherent to ER stress preconditioning with these compounds. Furthermore, autophagy was activated by both 2-DG and DTTox. Blockage of autophagy attenuated the protection afforded by 2-DG or DTTox preconditioning in AN-treated astrocytes. These results establish that ER stress preconditioning affords cellular protection against AN, and that activation of autophagy mediates the cytoprotection. Modulation of ER stress and resultant activation of autophagy may be a novel target for to ameliorate AN toxicity.

Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes.

Autophagy is an evolutionarily conserved process in which cytoplasmic proteins and organelles are degraded and recycled for reuse. There are numerous reports on the role of autophagy in cell growth and death; however, the role of autophagy in methylmercury (MeHg)-induced neurotoxicity has yet to be identified. We studied the role of autophagy in MeHg-induced neurotoxicity in astrocytes. MeHg reduced astrocytic viability in a concentration- and time-dependent manner, and induced apoptosis. Pharmacological inhibition of autophagy with 3-methyladenine or chloroquine, as well as the silencing of the autophagy-related protein 5, increased MeHg-induced cytotoxicity and the ratio of apoptotic astrocytes. Conversely, rapamycin, an autophagy inducer, along with as N-acetyl-L-cysteine, a precursor of reduced glutathione, decreased MeHg-induced toxicity and the ratio of apoptotic astrocytes. These results indicated that MeHg-induced neurotoxicity was reduced, at least in part, through the activation of autophagy. Accordingly, modulation of autophagy may offer a new avenue for attenuating MeHg-induced neurotoxicity.

Analysis of the curative effect and safety of uterine artery embolization combined with hysteroscope in treating cesarean scar pregnancy / 中国内镜杂志

Objective To explore the curative effect and safety of uterine artery embolization combined with hysteroscope in treating cesarean scar pregnancy. Methods 36 cesarean scar pregnancy patients (CSP diameter under six cm by ultrasound) from June 2014 to June 2015 were selected and studied. All patients received the UAE and arterial injection of Methotrexate (MTX), and while the blood beta-HCG fell to around 1 000 u/L and the lesions thickness to serous membrane were over 0.2 cm by ultrasound, pregnancy lesions were resected by hysteroscopy surgery. Results The UAE and arterial injection of Methotrexate about (20.12 ± 3.85) min. Blood beta-HCG level and lesion diameter both fell or decreased, each with [(17 902.74±11 818.23) u/L vs (12 842.73 ± 8 525.73) u/L and (3.65 ± 1.02) cm vs (3.12 ± 0.97) cm] (t = 8.58, P < 0.01, t = 2.26, P < 0.05). Hysteroscopy surgery cost about (19.13 ± 2.67) min, the amount of bleeding were (17.43 ± 7.28) ml. Postoperative blood beta-HCG decreased to (113.45 ± 36.14) u/L within 2~4 days, the patients were discharged. Conclusion Hysteroscopy surgery with pretreatment of UAE combined with MTX injection could gain satisfactory outcome for patients with CSP. It has high success rate, low blood loss, fewer adverse reactions satisfactory outcome.

Discussion on the cultivation of new health inspection and quarantine professional talents under the background of internationalization / 中华医学教育探索杂志

On the background of internationalization for higher education,we have reformed the educational model for bachelor students majoring in public health laboratory science and quarantine.The exploration and pilot study are focused on educational principles,curriculum planning,teaching patterns,experiments and practice,and teachem training.The four teaching strategies have been firstly recommended as follows:laying the strongest foundation of chemistry,expanding quarantine-related curricula for increasing quarantine capability,making full use of strength of clinical laboratory medicine,emphasizing English application.The curricula structure is refined and more social supporting resources have been got to make globalization to cultivate more health inspection and quarantine talents with multidisciplinary knowledge,abilities and strong adaptability.

Turn-on Fluorescent Probe Based on Quantum Dots for Detection of Trace Amount Glutamate Dehydrogenase / 分析化学

We reported a simple and fast fluorescence system based on quantum dots ( QDs ) to detect glutamate dehydrogenase ( GLDH) , which inverted glutamate to α-ketogrutarate using NAD+ as a coenzyme. The fluorescence of CdTe QDs was quenched by nicotinamide adenine dimucleotide ( NAD+) through an electron transfer pathway, and the quencher NAD+ could be consumed by adding NAD+-dependent enzymes and corresponding substrates. Based on this principle we introduced GLDH to consume NAD+ in the QDs/NAD+ system, leading to the enhancement of the fluorescence intensity of QDs, which was in proportional to the amounts of GLDH added. Using this fluorescence system, we measured GLDH in a wide concentration range from 10 U/L to 1000 U/L, which was of significance in clinical diagnosis of different kinds of liver diseases.

Acrylonitrile has Distinct Hormetic Effects on Acetyl-Cholinesterase Activity in Mouse Brain and Blood that are Modulated by Ethanol.

Acrylonitrile(AN) is a neurotoxin both in animals and humans, but its effects on acetylcholinesterase (AChE) activity remain controversial. This study aimed to determine the dose-response effects of AN on AChE activity and the modulatory role of ethanol pre-treatment. A total of 144 Kunming mice were randomly divided into 18 groups: nine groups received 5% ethanol in their drinking water, and the remaining nine groups received regular tap water. One week later, both the ethanol and tap water only groups were given an intraperitoneal injection of AN at the following doses: 0 (control), 0.156, 0.3125, 0.625, 1.25, 2.5, 5, 10 or 20 mg AN/kg body weight. AChE activity was determined on whole blood and brain 24 h later. Blood AChE activity was higher in AN-injected mice than in controls at all doses. AChE activity in blood increased in a dose-dependent manner, peaking at 0.156 mg/kg, after which a gradual decrease ensued, displaying a ß-typed dose-response relationship. In contrast, brain AChE activity, following a single AN injection, was consistently lower than in control mice, and continued to fall up to a dose of 0.313 mg/kg, and thereafter increased gradually with higher doses. Mice receiving a 20 mg/kg dose of AN exhibited AChE brain activity indistinguishable from that of control mice, demonstrating a typical U-typed dose-response relationship. The activity of AChE in the blood and brain of the AN + ethanol-treated groups displayed a shift to the right, and the magnitude of the decrease in AChE activity induced by AN was attenuated relative to the AN-only group. These results suggest that AN affects AChE activity in both mouse blood and brain in a hormetic manner. Pretreatment with ethanol modifies the effect of AN on AChE, indicating that parent AN has a more prominent role than its metabolites in modulating enzyme activity.

Induction or inhibition of cytochrome P450 2E1 modifies the acute toxicity of acrylonitrile in rats: biochemical evidence.

The present study was designed to examine the effects of the inhibition or induction of CYP2E1 activity on acute acrylonitrile (AN) toxicity in rats. Increased or decreased hepatic CYP2E1 activity was achieved by pretreatment with acetone or trans-1,2-dichloroethylene (DCE), respectively. AN (50 mg/kg) was administered by intraperitoneal injection. Onset of convulsions and death were observed in rats with increased CYP2E1 activity, whereas convulsions and death did not appear in rats within 1 h after treatment with AN alone. Convulsions occurred in all AN-treated animals with increased CYP2E1 activity at approximately 18 min. The levels of cyanide (CN(-)), a terminal metabolite of AN, were significantly increased in the brains and livers of the AN-treated rats with increased CYP2E1 activity, compared with the levels in rats treated with AN alone, DCE + AN or acetone + DCE + AN. The cytochrome c oxidase (CcOx) activities in the brains and livers of the rats treated with AN or AN + acetone were significantly lower than those in the normal control rats and the rats treated with DCE, whereas the CcOx activities in the brains and livers of rats with decreased CYP2E1 activity were significantly higher than those in AN-treated rats. Brain lipid peroxidation was enhanced, and the antioxidant capacity was significantly compromised in rats with decreased CYP2E1 activity compared with rats with normal or increased CYP2E1 activity. Therefore, inhibition of CYP2E1 and simultaneous antioxidant therapy should be considered as supplementary therapeutic interventions in acute AN intoxication cases with higher CYP2E1 activity, thus a longer window of opportunity would be got to offer further emergency medication.

Curcumin pretreatment protects against acute acrylonitrile-induced oxidative damage in rats.

Acrylonitrile (AN) is widely used in the manufacturing of fibers, plastics and pharmaceuticals. Free radical-mediated lipid peroxidation is implicated in the toxicity of AN. The present study was designed to examine the ability of curcumin, a natural polyphenolic compound, to attenuate acute AN-induced lipid peroxidation in the brain and liver of rats. Male Sprague-Dawley rats were orally administered curcumin at doses of 0 (olive oil control), 50 or 100 mg/kg bodyweight daily for 7 consecutive days. Two hours after the last dose of curcumin, rats received an intraperitoneal injection of 50 mg AN/kg bodyweight. Acute exposure to AN significantly increased the generation of lipid peroxidation products, reflected by high levels of malondialdehyde (MDA) both in the brain and liver. These increases were accompanied by a significant decrease in reduced glutathione (GSH) content and a significant reduction in catalase (CAT) activity in the same tissues. No consistent changes in superoxide dismutase (SOD) activity were observed between the control and AN-treatment groups in both tissues. Pretreatment with curcumin reversed the AN-induced effects, reducing the levels of MDA and enhancing CAT activity and increasing reduced GSH content both in the brain and liver. Furthermore, curcumin effectively prevented AN-induced decrease in cytochrome c oxidase activity in both liver and brain. These results establish that curcumin pretreatment has a beneficial role in mitigating AN-induced oxidative stress both in the brains and livers of exposed rats and these effects are mediated independently of cytochrome P450 2E1 inhibition. Accordingly, curcumin should be considered as a potential safe and effective approach in attenuating the adverse effects produced by AN-related toxicants.

Lipid peroxidation and changes of trace elements in mice treated with paradichlorobenzene.

Paradichlorobenzene (pDCB) has been used as a space deodorant and moth repellant, as well as an intermediate in the chemical industry. Given its broad applications and high volatility, considerable concern exists regarding the adverse health effects of pDCB in the home and the workplace. In this study, changes in lipid peroxidation, antioxidants, and trace element levels in the liver and kidney of pDCB-treated mice were investigated to determine their roles in toxicity. Mice were orally gavaged once daily for seven consecutive days with pDCB (0 (corn oil control), 450, and 900 mg/kg). The level of malondialdehyde (MDA), an end product of lipid peroxidation, markedly increased in the high-dose pDCB group in both the liver and kidney compared with the control group. Changes in hepatic levels of reduced glutathione (GSH) in the pDCB groups were indistinguishable from the control group, while renal levels of reduced GSH in the high-dose pDCB group were significantly lowered in comparison to the control and the low-dose groups. Superoxide dismutase (SOD) activity in the liver of mice treated with pDCB showed a downward trend, whereas there was no consistent trend associated with changes in SOD activity in the kidney. Additionally, renal iron levels in the high-dose pDCB group were significantly decreased compared with the low-dose group and the controls, whereas hepatic iron content in the low-dose pDCB group was significantly lower compared with the controls. Selenium and zinc levels in the kidney were both significantly decreased in the high-dose pDCB group vs. the control and low-dose groups. There were no treatment-induced changes in copper levels in either the kidney or liver. However, a significant increase was found in the liver zinc/copper ratio in the high-dose pDCB group vs. the controls. In addition, blood zinc levels showed a downward trend with increased pDCB dosage. These results suggest that pDCB toxicity is mediated by oxidative damage and tissue-specific alterations in trace element levels both in the liver and the kidney of mice.

Effects of acrylonitrile on antioxidant status of different brain regions in rats.

While the adverse effects of acrylonitrile (AN) on the central nervous system (CNS) are known to be mediated, at least in part, by the generation of free radicals and oxidative stress, there is a paucity of data on region-specific alterations in biomarkers of oxidative stress in the brain of AN-exposed animals. The present study was designed to examine the effects of AN on biomarkers of oxidative stress in several brain regions of adult Sprague-Dawley rats. Daily intraperitoneal (i.p.) treatment of animals to 0 (control, normal saline solution), 25, 50 or 75mgAN/kg body weight for 7 days resulted in statistically significant (p<0.05) increases in the levels of lipid peroxidation product, malondialdehyde (MDA), in the cortex and cerebellum; a statistically significant (p<0.05) decrease MDA levels were noted in the striatum. Contents of reduced glutathione (GSH) were significantly (p<0.05) decreased in cortex, cerebellum and hippocampus. The activities of the antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were differentially affected by AN and these effects were brain region-specific and AN dose-dependent. Taken together, these data suggest brain region-specific effects of AN on lipid peroxidation, activities of antioxidant enzymes and non-enzymatic antioxidant levels. These effects may provide biochemical evidence for AN-induced neurobehavioral damage and disturbance of monoamine neurotransmitters.

Zinc, copper, iron, and selenium levels in brain and liver of mice exposed to acrylonitrile.

The mechanism of toxicity of acrylonitrile (AN) has not been fully defined. The research described herein was undertaken to investigate the possible effects of AN on the levels of metallic elements in liver and brain of mice. Thirty-two mice were randomly assigned to four separate groups and treated intraperitoneal (i.p.) once daily for 1 week. Mice in the control group received normal saline, and mice in the three exposure groups received 5, 10, or 20 mg AN/kg b.w. Samples of brain and liver were collected immediately after decapitation. Tissue levels of trace elements (zinc, copper, iron) were determined with flame atomic absorption spectrophotometer or double channel atomic fluorescence absorption spectrophotometer (selenium). Mean brain weights of AN-treated mice were increased as a function of dose compared to controls, but there was no significant change in the ratio of liver/body weight in the four groups. While mean brain zinc decreased as a function of AN dosage, mean liver zinc of the low-dose group significantly increased (p < 0.05); mean liver copper in the medium-dose AN group was significantly higher compared to controls (p < 0.05); however, mean brain copper was increased, but the difference did not attain statistical significance in the three AN groups when compared with the controls (p > 0.05). Mean brain iron levels were significantly decreased in the middle-dose AN group (p < 0.05), but there were no consistent changes in liver iron. Tissue levels of selenium in brain and liver were similar for the control and AN treatment groups. AN induces significant and differential changes in the levels of zinc, copper, and iron in brain and liver. These changes likely play a pivotal role in mediating AN toxicity, most likely via changes in cellular redox status.

Clinical Efficacy of Atorvastatin for Patients with Cerebral Infarction Complicating Carotid Atherosclerotic Plaque / 中国药房

OBJECTIVE:To study the therapeutic efficacy of atorvastatin for patients with carotid atherosclerotic plaques complicating cerebral infarction and the possible mechanism.METHODS:A total of 150 patients with cerebral infarction coexisting carotid atherosclerotic plaques were randomized to either control group (routine therapy against platelet aggregation) or trial group (routine therapy against platelet aggregation plus atorvastatin 20 mg?d-1).The scores of carotid atherosclerotic plaques,levels of blood lipid and C-reactive proteins (CRP) were compared between the two groups.RESULTS:At 6 and 12 months of follow-up,the scores of carotid atherosclerotic plaques in the trial group were significantly less than in the control group(P

Nosocomial Infection in Clinical Immunology Laboratory:Risk Factors and Control Strategies / 中华医院感染学杂志

OBJECTIVE To explore the risk factors and control strategies of nosocomial infection in clinical immunology laboratory.METHODS The positive detection rates of HBV marker and antibodies to HAV,HCV,HEV,HIV,TP,and TB in total of 91 877 samples in clinical immunology laboratory during Jul 2004 and Jul 2005 were retrospectively surveyed and statistically analyzed.RESULTS The number of positive specimens of HBV marker and antibodies to HAV,HCV,HEV,HIV,TP,and TB were respectively 8 376,7,26,24,107,3,522,and 52 and the positive detection rates of these items were respectively 16.68%,0.43%,0.20%,2.22%,6.49%,0.03%,4.75%,and 4.61%.CONCLUSIONS It is very important to understand the infection sources and risk factors in clinical immunology laboratory in order to strengthen management of hospital infection and protection of occupational exposure.

Clinical characteristics and prevention of myopia in children / 医学研究生学报

Objectives:To study the clinical characteristics of myopia in children and the measures to prevent it. Methods:748 patients with myopia were analyzed by refraction examination. Results:By the classification of the causes of myopia, the simple myopia constitutes the majority. By the degrees of the disease, the number of mild myopia was the first and moderate myopia was the second. By the patterns,the amount of compound myopic astigmatism was the majority. The correction of simple myopia or mild and moderate myopia was the most effective way. Of the patients(4～14 years), the age of 12 years had the highest myopia rate. Conclusions:To pay great attention to the prevention works of myopia in grade school years. Correcting refraction exactly and on time is an effective method to slow down the progression of myopia in children.

Preparation and identification of anti human myocardium troponin I monoclonal antibodies / 第二军医大学学报

Objective: To prepare monoclonal antibodies (McAb) with cardiac troponin I (cTnI) which was purified from fresh human cardiac muscle within 6 h. Methods: (1) Extraction and purification of human cTnI: cTnI was purified by high salt extraction, saltless precipitation, 65℃ treatment, ammonium sulfate fractionation and DEAE-cellulose chromatography, etc. (2) Preparation of anti human cTnI McAb: The purified cTnI was injected into the spleen of BALB/c mice. The cTnI-primed spleen cells were fused with Sp2/0 myoloma cell. The McAbs anti human cTnI were obtained by screening with indirect ELISA and 3 times clone. (3)The identification of anti cTnI McAb. Results: Five hybridoma cell lines, named 3A7，3A11，3D2，3F10 and 1H9 were developed, which could secret McAb stably. The 5 McAbs all were demonstrated to be IgG2a by double gel diffusion test. The number of hybridoma chromosomes was between 92 to 110 and the chromosomes were mainly telocentric. Five kinds of ascites had no cross-reaction to LDH，CK，CK-MB ，AST and cardiac troponin T(cTnT), and their titers were between 3.2×10-6 to 1.6×10-7. Conclusion: 3D2，3F10 and 3A7,3A11,1H9 react to different epitopes of cTnI.

Influence of Hyperthyroidism and Hypothyroidism on Serum Levels of Three Kinds of Cytokines / 中国医师杂志

0 05). The serum levels of both IL-8 and TNF (P