Exploring molecular mechanisms of anti-platelet adhesion of Chinese medicine for promoting blood circulation and removing blood stasis by activity screen and network analysis / 药学学报

Platelet adhesion is a key process in thrombosis. Anti-platelet adhesion effect of some Chinese medicines for promoting blood circulation and removing blood stasis (PBCRBS) has been reported, but their relative efficacies as a whole and specific targets remained unclear. This paper combined activity screening, drug compatibility analysis, pathway clustering, target prediction, and molecular docking to explore the mechanism of anti-platelet adhesion by PBCRBS Chinese medicine. Screening the activity of anti-platelet adhesion of 58 commercially available PBCRBS Chinese patent medicines showed that about 50.0% significantly inhibit ADP-induced platelet adhesion in vitro, and about 96.6% significantly inhibit thrombin-induced platelet adhesion in vitro. The animal experiment involved was approved by the Animal Ethics Committee of Tianjin International Biomedical Research Institute. Combined with the auxiliary platform for TCM (V2.0) inheritance showed that the compatibility of Danshen-Chuanxiong was used most frequently among the top 20 active proprietary Chinese patent medicines. IPA network analysis revealed that IL-1, APP and CCL2 might be the key targets for anti-platelet adhesion function of Danshen-Chuanxiong against atherosclerosis, neuroinflammation and chemokine signaling pathways as the main mechanisms. Molecular docking analysis confirmed the interaction between one of the active compounds shared by Danshen and Chuanxiong, i.e. chlorogenic acid, with its target CCL2. This study provides TCM theory guidance and experimental support for targeting platelet adhesion in anti-thrombosis therapy by Chinese medicine for promoting blood circulation and removing blood stasis.

Endocrine Disruption Activity of 30-day Dietary Exposure to Decabromodiphenyl Ethane in Balb/C Mouse / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study aimed to evaluate the hepatotoxicity, metabolic disturbance activity and endocrine disrupting activity of mice treated by Decabromodiphenyl ethane (DBDPE).</p><p><b>METHODS</b>In this study, Balb/C mice were treated orally by gavage with various doses of DBDPE. After 30 days of treatment, mice were sacrificed; blood, livers and thyroid glands were obtained, and hepatic microsomes were isolated. Biochemical parameters including 8 clinical chemistry parameters, blood glucose and hormone levels including insulin and thyroid hormone were assayed. The effects of DBDPE on hepatic cytochrome P450 (CYP) levels and activities and uridinediphosphate-glucuronosyltransferase (UDPGT) activities were investigated. Liver and thyroid glands were observed.</p><p><b>RESULTS</b>There were no obvious signs of toxicity and no significant treatment effect on body weight, or liver-to-body weight ratios between treatment groups. The levels of ALT and AST of higher dose treatment groups were markedly increased. Blood glucose levels of treatment groups were higher than those of control group. There was also an induction in TSH, T3, and fT3. UDPGT, PROD, and EROD activities were found to have been increased significantly in the high dose group. Histopathologic liver changes were characterized by hepatocyte hypertrophy and cytoplasmic vacuolization. Our findings suggest that DBDPE can cause a certain degree of mouse liver damage and insufficiency.</p><p><b>CONCLUSION</b>DBDPE has the activity of endocrine disruptors in Bal/C mice, which may induce drug-metabolizing enzymes including CYPs and UDPGT, and interfere with thyroid hormone levels mediated by AhR and CAR signaling pathways. Endocrine disrupting activity of DBDPE could also affect the glucose metabolism homeostasis.</p>

Biomechanical analysis of the correlation between sacral tilt displacement and L₅S₁ disc degeneration / 中国骨伤

<p><b>OBJECTIVE</b>To biomechanical analysis of the correlation between sacral tilt displacement and L₅-S₁ disc degeneration.</p><p><b>METHODS</b>From July 2011 to July 2013, 81 patients with lumbar disc herniation and sacroiliac joint disorder including 45 males and 36 females with an average age of (45.39±1.30) years ranging from 18 to 65 years old were selected. The course of the disease ranged from 1 to 144 months with an average of (12.64±2.19) months. All patients were taken lumbar spine lateral X-ray films, the lumbar curvature angle, L₄-L₅ or L₅-S₁ intervertebral gap distance between points, and the lumbosacral angle was measured and correlated analyzed.</p><p><b>RESULTS</b>The lumbar curvature of female patients with L₅S₁DH were significantly larger than male patients [(22.18±8.62)° vs (16.17±4.97)°,<0.05]. Lumbar curvature and lumbosacral angle showed a positive correlation in LDH (=0.48,<0.01,y=7.25+0.38x,<0.01); Male patients with L₄-₅DH were more obvious (=0.55,<0.05, y=5.80+0.43x,<0.01); Female patients with L₅S₁DH were particularly evident(=0.74,<0.01,y=0.91x-5.30,<0.01). The lumbosacral angle and L₄-₅ intervertebral gap was a positive correlation in L₄-₅DH(=0.27,<0.05); While L₅-S₁ intervertebral gap and lumbosacral angle were not correlated(>0.05) in L₅S₁DH.</p><p><b>CONCLUSIONS</b>The sacral tilt displacement and L₅-S₁ disc degeneration were closely related to provide a new understanding philosophy and therapeutic approach for clinical treatment of intractable lumbar L₅S₁DH.</p>

Biomechanical analysis on the correlation between iliac rotation displacement and L(4,5) disc degeneration / 中国骨伤

<p><b>OBJECTIVE</b>To study the biomechanical relationship between iliac rotation displacement and L(4,5) disc degeneration, and to provide clinical evidences for the prevention and treatment of L(4,5) disc degeneration and herniation.</p><p><b>METHODS</b>From March 2012 to February 2014,68 patients with lumbar disc herniation combined with sacroiliac joint disorders were selected. Among them, 42 patients with L(4,5) disc herniation combined with sacroiliac joint disorders included 22 males and 20 females, ranging in age from 19 to 63 years old, with an average of (51.78 +/- 20.18) years old, and the duration of the disease ranged from 1 to 126 months with an average of (11.18 +/- 9.23) months. Twenty-six patients with L5S1 disc herniation combined with sacroiliac joint disorders included 11 males and 15 females, ranging in age from18 to 65 years old with an average of (45.53 +/- 27.23) years old, and the duration of the disease ranged from 0.5 to 103 months with an average of (11.99 +/- 12.56) months. Sixty-eight anteroposterior lumbar radiographs, 68 lateral lumbar radiographs,and 68 pelvic plain films were taken. The degree of lumbar scoliosis, pelvic tilt,and disc thickness were measured. The correlation between pelvic tilt and lumbar scoliosis ,lumbar scoliosis and disc thickness were studied by using linear and regression methods. The hiomechanical analysis was performed.</p><p><b>RESULTS</b>There was a positive correlation between pelvic tilt and lumbar scoliosis in patients with L(4,5) disk herniation (R=0.49, P=0.00). There was a causal relationship and good linear proportional relationship (Y=3.05+1.07X, P=0.00) in the two variables. There was a negative correlation between lumbar scoliosis and intervertebral space in male patients with L (4,5) disk herniation (R = -0.50, P=0.01). There was a causal relationship and good linear proportional relationship in the two variables (Y=13.09-0.27X, P=0.02). But there was a positive correlation between lumbar scoliosis and intervertebral space in male patients with L5S1 disk herniation (R=0.46, P=0.04).</p><p><b>CONCLUSION</b>Iliac rotational displacement are closely related with L(4,5) disc degeneration and herniation in biomechanics. A new concepts and therapeutic approach is provided for clinical treatment of chronic and refractory herniation of L(4,5) disc in patients</p>

Exposure Assessment of Sb2O3 in PET Food Contact Materials / 生物医学与环境科学（英文）

This study was conducted to do exposure assessment of the possible migration of antimony trioxide (Sb2O3) from Polyethylene terephthalate (PET) food contact materials (FCM). Consumption Factor (CF) and Food-type Distribution Factor (fT) were calculated from survey data with reference to the US FDA method. The most conservative migration conditions were obtained by testing Sb migration from PET FCM based on the Chinese national standard of GB/T 5009.101-2003[1]. Migration levels of Sb from PET FCM were tested and migration levels of Sb2O3 were obtained through molecular weight conversion between Sb and Sb2O3. Exposure assessment of Sb2O3 was undertaken. The Chinese Estimated Daily Intake (EDI) of Sb2O3 resulted from PET FCM was 90.7 ng p-1d-1.

Influence of Iron Supplementation on DMT1 (IRE)-induced Transport of Lead by Brain Barrier Systems in vivo / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the potential involvement of DMT1 (IRE) protein in the brain vascular system in vivo during Pb exposure.</p><p><b>METHODS</b>Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the mRNA.</p><p><b>RESULTS</b>Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1 (IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1 (IRE) mRNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1 (IRE).</p><p><b>CONCLUSION</b>These results suggest that Pb is transported into the brain through DMT1 (IRE), and the ERK MAPK pathway is involved in DMT1 (IRE)-mediated transport regulation in brain vascular system in vivo.</p>

Subacute effect of decabromodiphenyl ethane on hepatotoxicity and hepatic enzyme activity in rats / 生物医学与环境科学（英文）

Information regarding decabromodiphenyl ethane (DBDPE) effects on hepatotoxicity and metabolism is limited. In the present study, Wistar rats were given oral DBDPE at different doses. DBDPE induced oxidative stress, elevated blood glucose levels, increased CYP2B2 mRNA, CYP2B1/2 protein, 7-pentoxyresorufin O-depentylase (PROD) activity, and induced CYP3A2 mRNA, CYP3A2 protein, and luciferin benzylether debenzylase (LBD) activity. UDPGT activity increased with its increasing exposure levels, suggesting that oral DBDPE exposure induces drug-metabolizing enzymes in rats via the CAR/PXR signaling pathway. The induction of CYPs and co-regulated enzymes of phase II biotransformation may affect the homeostasis of endogenous substrates, including thyroid hormones, which may, in turn, alter glucose metabolism.

Epidemiology investigation and biomechanics analyses for the correlation between sacroiliac joint disorder and lumbar intervertebral disc degeneration / 中国骨伤

<p><b>OBJECTIVE</b>To study the correlation between lumber disc degeneration and sacroiliac joint disorder, in order to provides a new understanding concepts and therapeutic approach for the prevention and treatment of chronic intractable low back pain.</p><p><b>METHODS</b>From August 2009 to October 2010,129 cases with lumbar disc herniation were studied with epidemiological methods. Among them, 61 patients with L4, disc herniation included 37 males and 24 females, ranging in aged from 20 to 75 years old, duration of the disease ranged from 1 to 144 months; The other 68 patients with L5S1 disc herniation included 32 males and 36 females,ranging in aged froml8 to 76 years old,duration of the disease ranged from 0.5 to 240 months. The clinical data, symptoms and signs,X-ray characteristics of lumbar spine and pelvis of the patients were investigated by epidemiological. The risk of lumbar disc herniation was calculated with case-control study; independent variables were screened with single factor analysis; the risk factors for lumbar disc herniation were determined with logistic regression analysis, and biomechanics analyses were taken.</p><p><b>RESULTS</b>Among 129 patients with lumbar disc herniation, 88 cases associated with sacroiliac joint disorders, sacroiliac joint disorder was a risk factor of lumbar disc herniation (OR = 4.61, P = 0.00); 47 cases associated with sacroiliac joint disorders in 61 patients with L4,5 disc herniation, iliac crest uneven caused by iliac rotational displacement was a high risk factor of L4,5 disc herniation (OR = 11.27, P = 0.00); 41 cases associated with sacroiliac joint disorders in 68 patients with L5S1 disc herniation, lumbar sacral angle abnormalities caused by sacral tilt shift was a high risk factor L5S1 disc herniation (OR = 2.31, P = 0.03).</p><p><b>CONCLUSION</b>Lumbar disc herniation and sacroiliac joint disorder are two of fallot, the two factors affect each other and there is a causal relationship. They are common exists in low back pain.</p>

Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes.</p><p><b>METHODS</b>A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C.</p><p><b>RESULTS</b>Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers.</p><p><b>CONCLUSIONS</b>Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.</p>

X-ray characteristics of sacroiliac joint disorders and its clinical significance / 中国骨伤

<p><b>OBJECTIVE</b>To study the X-ray characteristics of sacroiliac joint disorders and its clinical significance,so as to provide clinical diagnosis basis for Tuina treatment of sacroiliac joint disorder.</p><p><b>METHODS</b>From July 2009 to March 2011,104 patients with sacroiliac joint disorder were reviewed,including 64 males and 40 females,ranging in age from 18 to 81 years, with an average of (45.39 +/- 1.30) years. The duration of the disease ranged from 1 to 144 months,with an average of (12.64 +/- 2.19) months. One hundred and four pelvic plain films and 97 lumbar spine lateral films of the patients with sacroiliac joint disorder were taken. On the lateral X-ray of lumbar,the sacral horizontal angles (lumbosacral angle) were measured; and on the X-ray of pelvis,the vertical distance of two side iliac crest (iliac crest difference), the distance from lateral border to medial margin of two hips (hip width),the clip angle between sacral spin connection and vertical axis were measured,and then the data were analyzed.</p><p><b>RESULTS</b>The mean difference of iliac crest was (10.34+/-0.73) mm; the mean width difference of hip'was (6.73+/-1.01) mm; and the mean difference of the iliac crest was larger than that of mean difference of hip (P<0.01). The occurrence rate of inequal width of hip was higher(P<0.01). The mean abnormal lumbosacral angle was (7.29 +/- 1.86) degrees,and the mean angle of sacral crest tilting to left or right was (3.18 +/- 0.47) degrees; the mean abnormal lumbosacral angle was larger than that of angle of sacral crest tilting to left or right (P<0.01), and the occurrence rate of sacral crest tilting to left or right was higher</p>

Improved approach to atrial septum puncture: experience in 539 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The transseptal puncture technique has been widely used in therapeutic left atrium catheterization. But this technique may lead to some life-threatening complications. It can not be used widely because it is restricted by economy and deferring the transseptal puncture procedure. The aim of this study was to introduce a simple and safe transseptal puncture procedure.</p><p><b>METHODS</b>The distal of coronary sinus (CS) electrode was positioned close to the lateral margin of heart, which was about at 3 o'clock at left anterior oblique (LAO) 30° referred to whole cardiac profile. It was then used as the marker for the level of fossa ovalis at posterior-anterior projection to guide the pull of transseptal needle. The midpoint between the distal CS and the posterior margin of heart at right anterior oblique (RAO) 45° view was considered as the location of fossa ovalis. Once the puncture was succeeded, the guidewire was introduced to the left superior pulmonary vein via puncture sheath after the needle was retrieved. The end of outer sheath was introduced into left atrium with the protection of guidewire. It was applied in 539 patients (316 male, 223 female; (53 ± 16) years old) who underwent catheter ablation of atrial fibrillation or left-sided atrioventricular accessory pathway.</p><p><b>RESULTS</b>This transseptal approach reached 100.0% success and was succeeded in 98.9% with the first attempt. The first attempt puncture was aborted due to greater resistance to needle advancement or smaller needle curve in six patients. However, the second attempts were all succeeded after the needle curve was reshaped. There was no tamponade and embolism occurred.</p><p><b>CONCLUSION</b>The atrial septum puncture approach using the location of distal CS electrode as important marker and the guidewire for protection when sending outer sheath into left atrium is reliable and safe.</p>

Cytotoxicity and apoptosis induction in human HepG2 hepatoma cells by decabromodiphenyl ethane / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the toxic effects of decabromodiphenyl ethane (DBDPE), used as an alternative to decabromodiphenyl ether in vitro.</p><p><b>METHODS</b>HepG2 cells were cultured in the presence of DBDPE at various concentrations (3.125-100.0 mg/L) for 24, 48, and 72 h respectively and the toxic effect of DBDPE was studied.</p><p><b>RESULTS</b>As evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays and nuclear morphological changes, DBDPE inhibited HepG2 viability in a time- and dose-dependent manner within a range of 12.5 mg/L to 100 mg/L and for 48 h and 72 h. Induction of apoptosis was detected at 12.5-100 mg/L at 48 h and 72 h by propidium iodide staining, accompanied with overproduction of reactive oxygen species (ROS). Furthermore, N-acetyl-L-cysteine, a widely used ROS scavenger, significantly reduced DBDPE-induced ROS levels and increased HepG2 cells viability.</p><p><b>CONCLUSION</b>DBDPE has cytotoxic and anti-proliferation effect and can induce apoptosis in which ROS plays an important role.</p>

Oxidative damage to lung tissue and peripheral blood in endotracheal PM2.5-treated rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats.</p><p><b>METHODS</b>PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase (GSH-Px) and concentration of malondialdehyde (MDA) were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length (microm) and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method.</p><p><b>RESULTS</b>The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length (microm) and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood.</p><p><b>CONCLUSION</b>PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length (microm) and rate of tail are simple and valuable biomarkers of PM2.5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.</p>

Empirical Study on the Effect of Osmotic Opening of Blood Brain Barrier on the Facilitation of Nerve Growth Factor Passing / 实用儿科临床杂志

Objective To explore the change of nerve growth factors(NGF) through the blood brain barrier(BBB) after distal intravenous injection of mannitol into the experimental rats and the effect of exogenous NGF on the expression of growth associated protein-43 in hypoxic-ischemic brain.Methods One hundred cases of 7 days rats were divided into 2 units.One unit was divided into 3 groups:treatment group,control group and sham operated group,20 rats in each group.The other unit was divided into 4 groups:mannitol and NGF treated group,NGF treated group,control group,and sham operated group,there were 10 rats in each group.The model rats with perinatal hypoxic-ischemic brain damage(HIBD) rats were prepared by ligation of left common carotid artery with a temporary systemic hypoxia(inhaling 80 mL/L O2 and 920 mL/L N2).The sections of brains were processed by immunochemistry with antibodies against GAP-43,and the study and memory ability of rats were tested by maze test.The effect of osmotic opening of BBB on the facilitation of NGF′s passage was tested by ELISA.Results The expression of GAP-43 increased after NGF treatment,and the differences were remarkable(P