Brain-derived neurotrophic factor protects against acrylamide-induced neuronal and synaptic injury via the TrkB-MAPK-Erk1/2 pathway.

Acrylamide has been shown to be neurotoxic. Brain-derived neurotrophic factor (BDNF) can alleviate acrylamide-induced synaptic injury; however, the underlying mechanism remains unclear. In this study, dibutyryl-cyclic adenosine monophosphate-induced mature human neuroblastoma (NB-1) cells were exposed with 0-100 µg/mL acrylamide for 24-72 hours. Acrylamide decreased cell viability and destroyed synapses. Exposure of co-cultured NB-1 cells and Schwann cells to 0-100 µg/mL acrylamide for 48 hours resulted in upregulated expression of synapsin I and BDNF, suggesting that Schwann cells can activate self-protection of neurons. Under co-culture conditions, activation of the downstream TrkB-MAPK-Erk1/2 pathway strengthened the protective effect. Exogenous BDNF can increase expression of TrkB, Erk1/2, and synapsin I, while exogenous BDNF or the TrkB inhibitor K252a could inhibit these changes. Taken together, Schwann cells may act through the BDNF-TrkB-MAPK-Erk1/2 signaling pathway, indicating that BDNF plays an important role in this process. Therefore, exogenous BDNF may be an effective treatment strategy for acrylamide-induced nerve injury. This study was approved by the Laboratory Animal Welfare and Ethics Committee of the National Institute of Occupational Health and Poison Control, a division of the Chinese Center for Disease Control and Prevention (approval No. EAWE-2017-008) on May 29, 2017.

Long-term exposure to diesel engine exhaust induced lung function decline in a cross sectional study.

To clarify the effects of lung function following exposure to diesel engine exhaust (DEE), we recruited 137 diesel engine testing workers exposed to DEE and 127 non-DEE-exposed workers as study subjects. We performed lung function tests and measured cytokinesis-block micronucleus (CBMN) cytome index and levels of urinary polycyclic aromatic hydrocarbons (PAHs) metabolites. There was a significant decrease of forced expiratory volume in 1 second (FEV1), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/ FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF50%), and forced expiratory flow at 75% of FVC (FEF75%) in the DEE-exposed workers than non-DEE-exposed workers (all p<0.05). Among all study subjects, the decreases of FEF75% were associated with the increasing levels of PAHs meta-bolites (p<0.05), and there were negative correlations between FEV1, FEV1/FVC, MMF, FEF50%, and FEF75% with CBMN cytome index (all p<0.05). Our results show that long-term exposure to DEE can induce lung function decline which shows mainly obstructive changes and influence of small airways function. The decreased lung function is associated with internal dosage of DEE exposure, and accompany with the increasing CBMN cytome index.

[Safety and Tolerance of Healthy People to Injection of Astragalosides-a New Drug for Coronary Heart Disease].

OBJECTIVES: To assess the safety and tolerance of healthy volunteers to as tragalosides injection (AGI), and to determine a safe dose range for phase II clinical trial. METHODS: A total of 62 healthy volunteers participated in this study, with 26 being given a single AGI of 100 mL, 200 mL, 300 mL, 400 mL, 500 mL, or 600 mL and 36 subjects being given 500 mL, 400 mL, 200 mL or 300 mL of AGI once a day for 7 d. Discomfortsymptoms, vital signs and safety problems were recorded 3 d and 7 d after the administration of AGI. The results were analyzed. RESULTS: Of the 62 participants, 40 adverse events (AEs) were reported by 31 participants, which included 23 mild adverse reactions (ADRs) and 4 moderate ADRs. Nine AEs were reported by 9 participants with single AGI, including 7 ADRs. Fourteen AEs were reported by 10 participants with 500 mL and 400 mL multiple AGI, including 12 ADRs occurred in 9 participants.Seventeen AEs were reported by 12 participants with 300 mL and 300 mL multiple AGI, including 3 mild ADRs. The main ADRs included abnormal liver function [slightly elevated glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST),and serum total bilirubin (TBil)], low blood potassium, increased urine red blood cell count, rash, and phlebitis. CONCLUSIONS: The maximum tolerance is 600 mL for single-dose treatment, and 400 mL for multiple-dose (7 d). The dose guidance given in this study should be examined its effects and safety in patients with coronary heart disease in phase II clinical trial.

[Changes of Serum IgE and Tryptase in Anaphylactic Shock Rats].

OJECTIVE: To explore the changes of serum IgE and tryptase caused by anaphylactic shock rats and discuss the relation to PMI and preservative environment of corpse and specimen. METHODS: Rats were used for establishing anaphylactic shock models and randomly divided into room temperature group, refrigeration group, frozen group, manual hemolysis group, specimen preservation group. And the control group was also established. The blood samples were collected after rats were sacrificed. The degree of hemolysis was graded according to the color of the upper layer of the serum. The mass concentration of IgE and tryptase in each group was detected by ELISA. RESULTS: The levels of serum IgE and tryptase in anaphylactic shock dead rats were higher than that of the control group. Room temperature and frozen made obviously differences on the levels of serum IgE and tryptase with various PMI. The levels of serum IgE and tryptase in refrigeration group showed relatively stable. The levels of serum tryptase and IgE were elevated with differently increasing hemolysis. The levels of serum IgE and tryptase showed no obvious changes during the specimen kept under different temperature conditions for 25 days. CONCLUSION: Serum IgE and tryptase obviously increased in anaphylactic shock rats. However, the levels were influenced by PMI and environmental temperature, especially under the conditions of room temperature and frozen.

Health implications of engineered nanoparticles in infants and children.

BACKGROUND: The nanotechnology boom and the ability to manufacture novel nanomaterials have led to increased production and use of engineered nanoparticles (ENPs). However, the increased use of various ENPs inevitably results in their release in or the contamination of the environment, which poses significant threats to human health. In recent years, extraordinary economic and societal benefits of nanoproducts as well as their potential risks have been observed and widely debated. To estimate whether ENPs are safe from the onset of their manufacturing to their disposal, evaluation of the toxicological effects of ENPs on human exposure, especially on more sensitive and vulnerable sectors of the population (infants and children) is essential. DATA SOURCES: Papers were obtained from PubMed, Web of Science, and Google Scholar. Literature search words included: "nanoparticles", "infants", "children", "exposure", "toxicity", and all relevant cross-references. RESULTS: A brief overview was conducted to 1) characterize potential exposure routes of ENPs for infants and children; 2) describe the vulnerability and particular needs of infants and children about ENPs exposure; 3) investigate the current knowledge about the potential health hazards of ENPs; and 4) provide suggestions for future research and regulations in ENP applications. CONCLUSIONS: As the manufacturing and use of ENPs become more widespread, directed and focused studies are necessary to measure actual exposure levels and to determine adverse health consequences in infants and children.

Gene-gene interaction of GJB2, SOD2, and CAT on occupational noise-induced hearing loss in Chinese Han population.

The effects of genetic factors on the noise-induced hearing loss (NIHL) are still unclear. In the present study, eight single-nucleotide polymorphisms (SNPs) included rs1227049 and rs3802711 (CDH23), rs1695 (GSTP1), rs137852540 (GJB2), rs2289274 (PMCA2), rs4880 (SOD2), rs7943316, and rs769214 within CAT that might associated with NIHL were further validated in Chinese workers. The results showed that the carriers of the T allele (AT+TT) of rs7943316 and A allele (GA+AA) of rs769214, were significantly associated with an increased risk of NIHL compared to those with AA genotype (P<0.05) and GG genotype (P<0.05). Moreover, a significant three-locus model (P=0.0107) involving rs2016520, rs9794, and rs1805192 were observed that might associated with NIHL, with 53.95% of testing accuracy. Thus, our present study provided the evidence that GJB2, SOD2, and CAT genes might account for the NIHL development in independently and/or in an interactive manner.

Association of miR-193b down-regulation and miR-196a up-regulation with clinicopathological features and prognosis in gastric cancer.

Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRT- PCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR- 196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.

Effects of Ginkgo biloba extract on periodontal pathogens and its clinical efficacy as adjuvant treatment.

OBJECTIVE: To determine the effects of Ginkgo biloba extract (EGB) on major periodontal pathogens in subgingival plaque. METHODS: Sixty patients with moderate to severe periodontitis were selected and randomly assigned to 3 groups: EGB group, a positive (periocline) and a negative control groups. Subgingival plaque samples were collected before treatment and 1 week, 2 months and 4 months after treatment. The detection rates of 4 major periodontal pathogens-Treponema denticola (Td), Tannerella forsythus (Tf), Prevotella intermedia (Pi), and Porphyromonas gingivalis (Pg)-were detected by polymerase chain reaction (PCR). Clinical indicators were examined before treatment, 3 and 6 months after treatment. RESULTS: EGB significantly decreased the detection rate of all the 4 pathogens 1 week after treatment, and then gradually increased at 2 and 4 months. EGB's inhibition effect was better than or comparable to periocline, except for Pg in short-term. The difference of plaque index (PLI) and bleeding index (BI) was not statistically significant among the groups, while for probing depth (PD) and attachment loss (AL), the difference was statistically significant between the EGB group and negative control group at 3 and 6 months after treatment. CONCLUSION: EGB significantly inhibited major periodontal pathogens and can be used as an adjuvant for periodontitis treatment.

[Biochemical indicators of anaphylactic shock and the application in forensic medicine].

Fatal anaphylactic shock is common in forensic practice. However, it is difficult to diagnose for lacking specific pathological and morphologic changes in forensic autopsy. The application of some biochemical indicators is of great significance. This paper reviews the biological characteristics of some biochemical indicators and detection methods. The forensic application, problems and prospects of these indicators are also introduced in details. The stable biochemical indicators, IgE, tryptase and chymase, show great potential and advantages in the identification of fatal anaphylactic shock in forensic medicine.

Effects of clasp retention forces and abrasion on different cast crowns.

STATEMENT OF PROBLEM: Dental alloys have different mechanical properties compared with enamel. However, few studies have been conducted to determine the effects of the retention forces of clasps when applied on different cast crowns. PURPOSE: The purpose of this study was to evaluate the retention forces of cast circumferential clasps made of cobalt-chromium alloy on complete cast crowns made of cobalt-chromium (CC group) and gold-silver-palladium (AC group) alloys, and to observe their abrasion patterns. MATERIAL AND METHODS: Two groups of specimens were fabricated (n=5) and subjected to repeated insertion-removal tests (100 to 15,000 cycles). The mean values of removal forces at 100, 400, 800, 1500, 4500, 7500, 10,000, and 15,000 cycles, and their corresponding change rates compared with the initial 100 cycles' retention were determined. The differences between the 2 groups were analyzed by 2-way repeated measures analysis of variance at 100, 7500, and 15,000 cycles. The surfaces of specimens were observed with scanning electron microscopy. RESULTS: There were significant differences between the CC and AC groups in retention forces (P<.05). Clasp retention showed a descending trend for cobalt-chromium alloy crowns from the initial value, which decreased by 29.9% after 15,000 insertion-removal cycles. A sharp increase in retention could be observed in the AC group, which rose by 99.7% ultimately. The worn surfaces of the gold-silver-palladium crowns showed different wear patterns compared with the cobalt-chromium alloy crowns. CONCLUSIONS: The results indicate that cobalt-chromium alloy crowns and gold-silver-palladium alloy crowns perform differently when cobalt-chromium alloy clasps are designed as retainers for partial removable dental prostheses. Crown designs should be changed, depending on the retainer and clasp materials for partial removable dental prostheses abutment teeth.

[Repeatability of three-dimensional measurements based on cone-beam CT images].

OBJECTIVE: To investigate the repeatability of three-dimensional (3-D) cephalometric measurements for the clinical application of 3-D cephalometry. METHODS: Forty-nine measurements that widely used in traditional cephalometric analyses were defined in 3-D cone-beam CT (CBCT) images. Three examiners identified landmarks on CBCT images of 17 subjects with normal occlusion, respectively, and 3-D measurements were exported automatically by software SimPlant. Inter-examiner reliability correlation coefficients (ICC) were obtained for all measurements. RESULTS: Repeatability of 36 measurements was high (ICC value greater than 0.9), including SNA, SNB. Repeatability of 11 measurements was moderate (ICC value between 0.8 and 0.9), including CoL-GoL, CoL-MSP. Repeatability of 2 measurements was low (ICC value lower than 0.8), including Gn-MSP and MPR-MSP. CONCLUSIONS: Most 3-D cephalometric measurements based on CBCT had high repeatability. However, some 3-D cephalometric measurements had limited repeatability.

[Expression of BNP in rat myocardial tissue after acute cardiac dysfunction].

OBJECTIVE: To investigate the expression of brain natriuretic peptide (BNP) in rat myocardial tissue after acute cardiac dysfunction and to explore the role of BNP in diagnosis of cardiac dysfunction in forensic practice. METHODS: Rat models of acute cardiac dysfunction were established. The expression of BNP protein and BNP mRNA in myocardial tissue after cardiac dysfunction were detected by immunohistochemistry, Western blotting and real-time RT-PCR. RESULTS: The extent of positive staining of BNP increased over the time course during cardiac dysfunction. The expression of BNP showed mild positive in cardiomyocytes from 1 h to 2 h. From 4 h to 6 h, the expression was moderate positive. From 10 h to 12 h, the BNP showed a strongest positive expression. The expression of BNP presented a significant raise with the increasing time of cardiac dysfunction by Western blotting and real-time RT-PCR. The expression of BNP mRNA increased significantly 1 h after cardiac dysfunction. CONCLUSION: Investigating the expression of BNP protein and BNP mRNA in myocardial tissue may provide a new approach to evaluate the cardiac function for forensic pathologists.

[Early expression of hypoxia-inducible factor-1 alpha after acute myocardial ischemia in rats].

OBJECTIVE: To observe the changes of hypoxia-inducible factor-1 alpha (HIF-1alpha), the expression in the early stage (within 6 h) of acute myocardial ischemia and to explore the potential forensic application. METHODS: SD rats were randomly divided into one control group, one sham operation group and five myocardial ischemia groups which received ligation of the left anterior descending (LAD) coronary artery. The five experiment groups divided into 15min, 30min, 1 h, 3 h and 6h after LAD ligation. The expression of HIF-1alpha was detected by immunohistochemistry, immunofluorescence and Western blotting, respectively. RESULTS: Both the control group and sham operation group showed no expression of HIF-1alpha, whereas the expression of HIF-1alpha could be weakly detected beneath the endocardium at 15 min after LAD ligation. With the increase of myocardial ischemia process, the positive staining gradually extended from endocardium to epicardium, reached the peak at 3 h, and began to decrease gradually at 6h after LAD ligation but still maintained at a relatively high level. In addition, the expression of HIF-1alpha without a time-dependent way was also detected in full thickness of the right ventricle in occurrence of ventricular arrhythmia after LAD ligation. CONCLUSION: HIF-1alpha may be regarded as a sensitive marker for sudden cardiac death induced by early acute myocardial ischemia, and may also be helpful for the diagnosis of fatal arrhythmia.

[Time-dependent expression of vascular endothelial growth factor after acute myocardial ischemia in rats].

OBJECTIVE: To investigate the immunohistochemical distributions and expressions of vascular endothelial growth factor (VEGF) in the model of rat myocardial ischemia. METHODS: The model of myocardial ischemia was established by ligating the left anterior descending (LAD) coronary artery of rats. The changes of VEGF expression were detected by immunohistochemistry and Western blot at time points after myocardial ischemia. The electrocardiographic changes were evaluated uninterruptedly. RESULTS: The expression of VEGF was not be found in control group. Fifteen minutes after LAD ligation, weak positive expression of VEGF were found in the ischemic myocardium. The expression of VEGF reached the peak at 3 hours after ligation. The VEGF distribution was mainly localized in the ischemic and peri-ischemic regions. Six hours after LAD ligation, the expression of VEGF decreased comparing with 3 hours and showed a relatively higher level. Fatal arrhythmia was found in nine rats by the electrocardiograph. CONCLUSION: The immunohistochemical staining of VEGF could be helpful for investigating the location and severity of acute myocardial ischemia. Fatal arrhythmia may be secondary to myocardial ischemia.

[Mechanism of methamphetamine intoxication and its medical identification].

Methamphetamine (MA) is a representative drug of amphetamine-type stimulants for central nervous system and has become one of the most dangerous drugs in the world recently. The present article reviews the pharmacological effects, distribution, metabolism, intoxication mechanism, the effects of MA on cardiovascular and central nervous systems of MA, and the current situation of forensic investigation on MA.

[Effect of orthodontic force on periodontal healing after autotransplantation: an experimental study].

OBJECTIVE: To investigate the effect of the continuous light force to the donor teeth on the periodontal healing after transplantation. METHODS: Thirty-two maxillary and mandibular incisors in four 10-month-old male Beagle dogs were autotransplanted. The pulps were removed in all teeth. The teeth were divided into four groups, one control and three experimental groups. In control group (group 1), the teeth were unloaded. In the other three experimental groups, continuous force (0.49 N) was applied in the 1st (group 2), 2nd (group 3) and 4th (group 4) week, respectively. The dogs were sacrificed in the 8th week. The tissue blocks were demineralized and sectioned perpendicular to the long axis of the teeth. The histological analysis was made. RESULTS: Histomophometric analysis revealed a significantly lower occurrence of replacement root resorption in the group 3 (2.1%) than in the control group (12.5%, P < 0.05). The significant lower incidence of replacement root resorption, and a higher surface and inflammatory root resorption were found in group 2 (6.3% and 68.8%) than in the control group (12.5% and 41.7%, P < 0.05). No significant difference was found between group 4 and control group (P > 0.05). CONCLUSIONS: The orthodontic force promoted the regeneration of the periodontal ligament and prevented dentoalveolar ankylosis, whereas excessive initial force might cause root and bone resorption.

[Three-dimensional analysis of craniofacial growth in adolescents with normal occlusion in Beijing].

OBJECTIVE: To analyze craniofacial growth three-dimensionally for adolescents with normal occlusion in Beijing. METHODS: One hundred and twenty-six adolescents with normal occlusion were selected according to the criteria. The sample was divided into four age groups (53 within 4 years, 30 within 7 years, 27 within 10 years and 16 within 13 years). Information of growth was collected. Three-dimensional cephalometric system based on cone-bean CT was established. RESULTS: From 4 to 13 years Co-A increased (14.55 ± 1.15) mm on average on the left and (13.66 ± 1.14) mm on the right, and Co-Gn increased (22.89 ± 1.40) mm on the left and (22.82 ± 1.38) mm on the right; and U1-NA increased (2.20 ± 0.44) mm on the left and (1.60 ± 0.46) mm on the right; and CoL-CoR and GoL-GoR increased (13.31 ± 1.21) mm and (18.59 ± 1.40) mm, and N-Me increased (18.03 ± 1.32) mm.SN-PP and SN-MPL basically remained unchanged. CONCLUSIONS: Adolescents with normal occlusion in Beijing grew obviously in three-dimensions and developed harmoniously.

[Twenty autopsy cases of anaphylactic shock induced by cephalosporins].

OBJECTIVE: To explore the characteristics of autopsy cases of anaphylactic shock induced by cephalosporins and provide the evidences in forensic medicine. METHODS: Twenty cases of anaphylactic shock induced by cephalosporins were collected from April 2005 to August 2009 in judicial expertise center of China Medical University, and the characteristics of the cases were analyzed retrospectively. RESULTS: The age of decedents ranged from 40 to 60 years. Ninety percent of cases were from local medical centers and private clinics. The symptoms of the shock appeared 30 s-150 min after the administration of the drug, and death occurred 10 min-210 min after the appearance of the shock symptoms. In all cases, various degrees of eosinophil infiltration were observed in trachea and the lungs. Serum IgE detected by ELISA method was normal value in 14 cases. CONCLUSION: In fatal anaphylactic cases, little specific findings are detected during postmortem and microscope examination. For this reason, the determination of cause of death in these cases requires comprehensive analysis combined with clinic information and excludes other diseases leading to the sudden death.

[Application of brain natriuretic peptide in evaluation of cardiac function in forensic medicine].

Brain natriuretic peptide (BNP) is a major marker for evaluating cardiac function and has been widely used in clinical practice. Recent researches show that BNP is also useful for identification of sudden cardiac death in forensic pathology. This article reviews the molecular structure and biological characteristics of the BNP and its application as a functional indicate in forensic medicine. It shows that the expression of BNP in cardiac muscles, together with the expression of BNP in blood and pericardium liquid can be used to evaluate the pathological physiology changes and dysfunction degrees of the heart during the cardiac sudden death.