Publications by authors named "Wei-Min Gao"

36 Publications

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

Neural Regen Res 2021 Jan;16(1):150-157

Department of Toxicology, Key Lab of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.

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.
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http://dx.doi.org/10.4103/1673-5374.286976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818888PMC
January 2021

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

Sichuan Da Xue Xue Bao Yi Xue Ban 2016 Sep;47(5):805-809

Affiliated Hospital of Nanjing University of TCM, Jiangsu Provincial Hospital of TCM, Nanjing 210029,China.

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.
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September 2016

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

Ind Health 2017 Feb 23;55(1):13-26. Epub 2016 Jun 23.

Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, China.

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 (FEV), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV/ FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF), and forced expiratory flow at 75% of FVC (FEF) in the DEE-exposed workers than non-DEE-exposed workers (all p<0.05). Among all study subjects, the decreases of FEF were associated with the increasing levels of PAHs meta-bolites (p<0.05), and there were negative correlations between FEV, FEV/FVC, MMF, FEF, and FEF 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.
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http://dx.doi.org/10.2486/indhealth.2016-0031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5285310PMC
February 2017

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

Fa Yi Xue Za Zhi 2015 Jun;31(3):181-4

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.
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June 2015

Health implications of engineered nanoparticles in infants and children.

World J Pediatr 2015 Aug 8;11(3):197-206. Epub 2015 Aug 8.

The Institute of Environmental and Human Health, Texas Tech University, Lubbock, Texas, 79416, USA.

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.
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http://dx.doi.org/10.1007/s12519-015-0028-0DOI Listing
August 2015

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

Biomed Environ Sci 2014 Dec;27(12):965-8

Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.

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.
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http://dx.doi.org/10.3967/bes2014.131DOI Listing
December 2014

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

Asian Pac J Cancer Prev 2014 ;15(20):8893-900

Department of Clinical Laboratory Center, The Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China E-mail :

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.
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http://dx.doi.org/10.7314/apjcp.2014.15.20.8893DOI Listing
July 2015

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

Chin J Integr Med 2014 Oct 6;20(10):729-36. Epub 2014 Aug 6.

Department of Stomatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

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.
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http://dx.doi.org/10.1007/s11655-014-1824-4DOI Listing
October 2014

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

Fa Yi Xue Za Zhi 2014 Apr;30(2):117-21

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.
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April 2014

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

J Prosthet Dent 2014 Jun 11;111(6):493-8. Epub 2014 Jan 11.

Professor, Department of Prosthetic Dentistry, School of Stomatology, Capital Medical University, Beijing, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.prosdent.2013.07.025DOI Listing
June 2014

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

Zhonghua Kou Qiang Yi Xue Za Zhi 2013 Apr;48(4):248-52

Department of Orthodontics, Capital Medical University School of Stomatology, Beijing 100050, China.

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.
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April 2013

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

Fa Yi Xue Za Zhi 2013 Apr;29(2):86-90

School of Forensic Medicine, China Medical University, Shenyang 110001, China.

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.
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April 2013

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

Zhonghua Kou Qiang Yi Xue Za Zhi 2012 Dec;47(12):735-8

Department of Orthodontics, Capital Medical University School of Stomatology, Beijing 100050, China.

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.
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http://dx.doi.org/10.3760/cma.j.issn.1002-0098.2012.12.010DOI Listing
December 2012

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

Zhonghua Kou Qiang Yi Xue Za Zhi 2012 Oct;47(10):618-21

Department of Orthodontics, Capital Medical University School of Stomatology, Beijing 100050, China.

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.
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http://dx.doi.org/10.3760/cma.j.issn.1002-0098.2012.10.010DOI Listing
October 2012

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

Fa Yi Xue Za Zhi 2012 Oct;28(5):327-32

School of Forensic Medicine, China Medical University, Shenyang 110001, China.

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.
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October 2012

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

Fa Yi Xue Za Zhi 2012 Jun;28(3):179-84

School of Forensic Medicine, China Medical University, Shenyang 110001, China.

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.
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June 2012

[Mechanism of methamphetamine intoxication and its medical identification].

Fa Yi Xue Za Zhi 2012 Apr;28(2):126-9

School of Forensic Medicine, China Medical University, Shenyang 110001, China.

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.
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April 2012

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

Fa Yi Xue Za Zhi 2011 Oct;27(5):369-71, 375

School of Forensic Medicine, China Medical University, Shenyang 110001, China.

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.
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October 2011

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

Fa Yi Xue Za Zhi 2011 Apr;27(2):125-8

School of Forensic Medicine, China Medical University, Shenyang 110001, China.

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.
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April 2011

[Maximum resistance strength of the bone-bonding screw orthodontic anchorage].

Zhonghua Kou Qiang Yi Xue Za Zhi 2009 Sep;44(9):535-7

Department of Orthodontics, Capital Medical University School of Stomatology, Beijing 100050, China.

Objective: To investigate the maximum resistance strength of a new orthodontic anchorage system named bone-bonding screw.

Methods: Thirty-six self-designed two-section bone-bonding screws were bonded to the surface of tibia in 12 rabbits with N-2-butyl cyanoacrylate. The maximum resistance strength of the screws was tested immediately, 2 weeks, 4 weeks and 8 weeks after bonding, respectively.

Results: The average maximum resistance strengths of the bone-bonding screws immediately, 2 weeks, 4 weeks and 8 weeks after bonding were 11.55 (8.96, 12.73), 6.04 (1.88, 10.57), 2.30 (0, 3.24), and 49.85 (20.70, 66.01) N, respectively. The difference between each group was statistically significant (P < 0.05). The failure rate of the bone-bonding screws was 17% (6/36).

Conclusions: The maximum resistance strength of the bone-bonding screw could suffice for orthodontics.
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September 2009

Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients.

World J Gastroenterol 2008 May;14(19):3074-80

Department of Medical Oncology, Jinling Hospital, Nanjing 210002, Jiangsu Province, China.

Aim: To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma.

Methods: Methylation-specific polymerase chain reaction (MSPCR) was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease (30 with benign gastric disease and 30 with benign colorectal disease), and 30 healthy donor controls. A paired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postoperative serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy.

Results: The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric (34.0%) and colorectal (28.9%) adenocarcinoma patients were significantly higher than those in patients with benign gastric (3.3%) or colorectal (6.7%) disease or in healthy donors (0%) (P < 0.01). The methylation status of RASSF1A promoter in serum samples was consistent with that in paired primary tumors, and the MSPCR results for RASSF1A promoter methylation status in paired preoperative samples were consistent with those in postoperative serum samples. The serum RASSF1A promoter hypermethylation did not correlate with patient sex, age, tumor differentiation grade, surgical therapy, or serum carcinoembryonic antigen level. Although the serum RASSF1A promoter hypermethylation frequency tended to be higher in patients with distant metastases, there was no correlation between methylation status and metastasis.

Conclusion: Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712178PMC
http://dx.doi.org/10.3748/wjg.14.3074DOI Listing
May 2008

[Fluid shear stress increases the Ca2+ concentration in bone-marrow derived osteoclast-like cells].

Hua Xi Kou Qiang Yi Xue Za Zhi 2007 Aug;25(4):412-4

Dept. of Prosthodontics, Beijing Stomatologicul Hospital, Capital Medical University, Beijing 100050, China.

Objective: To study the change of Ca2+ density in cultured osteoclast-like cells in response to fluid shear stress.

Methods: Laser scanning confocal microscope and fluorescent probe were used to detect the free Ca2+ in osteoclast-like cells before and after undergoing fluid shear stress. The images were analyzed and compared with image software.

Results: At 37 degrees C the free Ca2+ in osteoclast-like cells could be labelled effectively with 10 micromol/L Fluo-3/AM. Compared with contol group, the average intensity of Ca2+ fluorescent signal in osteoclast-like cells undergoing fluid shear stress increased significantly.

Conclusion: The Cal2+ concentration in bone-marrow derived osteoclast-like cells is sensitive to fluid shear stress, which suggests osteoclast-like cells modulate their function in response to fluid shear stress through the change of free Ca2+ concentration.
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August 2007

A gel-based proteomic comparison of human cerebrospinal fluid between inflicted and non-inflicted pediatric traumatic brain injury.

J Neurotrauma 2007 Jan;24(1):43-53

Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.

Traumatic brain injury (TBI) is the most common cause of traumatic death in infancy, and inflicted TBI (iTBI) is the predominant cause. Like other central nervous system pathologies, TBI changes the composition of cerebrospinal fluid (CSF), which may represent a unique clinical window on brain pathophysiology. Proteomic analysis, including two-dimensional (2-D) difference in gel electrophoresis (DIGE) combined with mass spectrometry (MS), was used to compare the CSF protein profile of two pooled samples from pediatric iTBI (n = 13) and non-inflicted TBI (nTBI; n = 13) patients with severe injury. CSF proteins from iTBI and nTBI were fluorescently labeled in triplicate using different fluorescent Cy dyes and separated by 2-D gel electrophoresis. Approximately 250 protein spots were found in CSF, with 90% between-gel reproducibility of the 2-D gel. Following in-gel digestion, the tryptic peptides were analyzed by MS for protein identification. The acute phase reactant, haptoglobin (HP) isoforms, showed an approximate fourfold increase in nTBI versus iTBI. In contrast, the levels of prostaglandin D(2) synthase (PGDS) and cystatin C (CC) were 12-fold and sevenfold higher in iTBI versus nTBI, respectively. The changes of HP, PGDS, and CC were confirmed by Western blot. These initial results with conventional gel-based proteomics show new protein changes that may ultimately help to understand pathophysiological differences between iTBI and nTBI.
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http://dx.doi.org/10.1089/neu.2006.0061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721471PMC
January 2007

Gel-based hippocampal proteomic analysis 2 weeks following traumatic brain injury to immature rats using controlled cortical impact.

Dev Neurosci 2006 ;28(4-5):410-9

Neurological Surgery, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Traumatic brain injury (TBI) to postnatal day 17 rats has been shown to produce acute changes in hippocampal global protein levels and spatial learning and memory deficits. The purpose of the present study was to analyze global hippocampal protein changes 2 weeks after a moderate ipsilateral controlled cortical impact in postnatal day 17 rats using 2-dimensional difference gel electrophoresis and mass spectrometry. Paired sham and ipsilateral injured hippocampal lysates were independently labeled with different fluorescent cyanine dyes and coseparated within the same immobilized pH gradient strips and slab gel based on isoelectric point and molecular mass. Significant changes in key proteins involved in glial and neuronal stress, oxidative metabolism, calcium uptake and neurotransmitter function were found 2 weeks after injury, and their potential roles in hippocampal plasticity and cognitive dysfunction were discussed.
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http://dx.doi.org/10.1159/000094167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721469PMC
November 2006

Polymorphisms in DNA repair genes XPD and XRCC1 and p53 mutations in lung carcinomas of never-smokers.

Mol Carcinog 2006 Nov;45(11):828-32

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.

The etiology of lung cancer in population with little or no tobacco exposure is not well understood. Individual genetic susceptibility factors have been suggested to contribute to lung cancer risk in this population. Mutations in the p53 tumor suppressor gene are implicated in the development of lung cancer as they are frequently found in lung tumors from both smokers and never-smokers. In order to determine whether genetic polymorphisms affecting DNA repair capacity modulate p53 mutations in lung tumors from never-smokers, we compared p53 mutations with genotypes of XPD 312, XPD 751, and XRCC1 399 in lung tumors from 43 lifetime never-smokers. p53 mutations were identified in 10 (23%) cases and consisted mostly of G/C to A/T transitions. No statistically significant association was found between p53 mutations and genotypes of XPD 312 or XPD 751. However, patients with the XRCC1 399 Gln allele, that results in a lower base excision repair capacity, were more likely to have p53 mutations, compared with patients the wild-type Arg allele (P = 0.03). In addition, the p53 mutation frequency increased with an increasing number of combined genotypes associated with a lower DNA repair capacity of XPD 312, XPD 751, and XRCC1 399 (P = 0.02). These results suggest that individuals who never smoked and had XRCC1 399 Gln allele may be at a greater risk of p53 mutations, especially if combined with the genotypes of XPD 312 and XPD 751 that may result in a lower DNA repair capacity.
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http://dx.doi.org/10.1002/mc.20208DOI Listing
November 2006

Immunohistochemical analysis of histone H3 acetylation and methylation--evidence for altered epigenetic signaling following traumatic brain injury in immature rats.

Brain Res 2006 Jan 9;1070(1):31-4. Epub 2006 Jan 9.

Neurological Surgery, U. Pittsburgh, Pittsburgh, PA 15260, USA.

Posttranslational modifications (PTMs) of histone proteins may result in altered epigenetic signaling after pediatric traumatic brain injury (TBI). Hippocampal histone H3 acetylation and methylation in immature rats after moderate TBI were measured and decreased only in CA3 at 6 h and 24 h with persistent methylation decreases up to 72 h after injury. Decreased histone H3 acetylation and methylation suggest altered hippocampal CA3 epigenetic signaling during the first hours to days after TBI.
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http://dx.doi.org/10.1016/j.brainres.2005.11.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721467PMC
January 2006

Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis.

BMC Cancer 2005 Aug 23;5:110. Epub 2005 Aug 23.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

Background: Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response.

Methods: Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance.

Results: Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and alpha-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified.

Conclusion: Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer.
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http://dx.doi.org/10.1186/1471-2407-5-110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1198221PMC
August 2005

Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan Wei County, China.

Carcinogenesis 2005 Feb 25;26(2):303-8. Epub 2004 Nov 25.

Department of Environmental and Occupational Health and Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Lung cancer mortality rates in the Xuan Wei County population are among the highest in China and are associated with exposure to indoor emissions from the burning of smoky coal. Previous studies of lung tumors from both non-smoking women and smoking men in this region showed high frequencies of mutations, consisting mostly of G-->T transversions in the p53 tumor suppressor gene and K-ras oncogene, suggesting that these mutations were caused primarily by polycyclic aromatic hydrocarbons. In this study sputum samples from 92 individuals with no evidence of lung cancer from Xuan Wei County were screened for p53 and K-ras mutations. Sputum cells were collected on glass slides by sputum cytocentrifugation, stained and cytopathologically analyzed. Cytologically non-malignant epithelial cells were taken from each sputum sample using a laser capture microdissection microscope and molecularly analyzed. Cells taken from the sputum of 15 (16.3%) individuals were mutation positive, including 13 (14.1%) individuals each with a p53 mutation, 1 (1.1%) individual with a K-ras mutation and 1 (1.1%) individual with a p53 and a K-ras mutation. p53 mutations were found in both the sputum of individuals with evidence of chronic bronchitis (3 of 46 or 6.5%) and those without evidence of this disease (11 of 46 or 23.9%). Therefore, mutations in the p53 gene and, to a lesser extent, the K-ras gene were frequent in non-malignant epithelial cells taken from the sputum of individuals without evidence of lung cancer who were exposed to smoky coal emissions in Xuan Wei County and were at a high risk for developing the disease.
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http://dx.doi.org/10.1093/carcin/bgh328DOI Listing
February 2005

Analysis of p53 mutations in cells taken from paraffin-embedded tissue sections of ductal carcinoma in situ and atypical ductal hyperplasia of the breast.

Cancer Lett 2004 Aug;212(1):121-30

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15260, USA.

Mutations in the p53 tumor suppressor gene are frequent in breast tumors but the implication of p53 mutations in breast cancer development remains poorly understood. In this study, we applied laser capture microdissection (LCM) microscope to histologically review and sample cells from paraffin-embedded breast tissue sections obtained from six cases of ductal carcinoma in situ (DCIS) and ten cases of atypical ductal hyperplasia (ADH). p53 mutations were detected, using single stranded conformational polymorphism (SSCP) and sequencing, in cell samples of three cases with DCIS and five cases with ADH. p53 mutations are therefore present in DCIS and ADH of the breast, considered as pre-malignant precursors to breast cancer, and some of them may represent early events in breast cancer development.
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http://dx.doi.org/10.1016/j.canlet.2004.03.010DOI Listing
August 2004

No association between the XPD 312, 751, or XRCC1 399 polymorphisms and K-ras gene mutation in smoking non-small-cell lung cancer.

Cancer Epidemiol Biomarkers Prev 2004 Apr;13(4):673-5

Department of Environmental and Occupational Health, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15260, USA.

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April 2004
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