Adolescent ; Catheter Ablation ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Tachycardia, Supraventricular ; surgery

This study is to investigate the effects of indirubin on ATP-induced immune responses of macrophages. For this, neutral red dye uptake method was used to test phagocytosis, MTT assay was used for measuring cell death, and reactive oxygen species (ROS) was tested with fluorescent probe DHE. The data showed that extracellular ATP attenuated phagocytosis, induced cell death and increased ROS production, and these effects were restored by pre-treating with indirubin. This result suggested that indirubin blockade the effects of ATP on macrophages, because extracellular ATP-induced effects are dependent on P2 receptors, in particular P2X7 receptors. Furthermore, the effects of indirubin on the activation of P2 receptors were tested, in particular P2X7 receptors. The data showed that indirubin significantly decreased ATP-induced, P2 receptors mediated intracellular Ca2+ concentration ([Ca2+]i) rise and inhibited P2X7 receptor-based ethidium bromide (EB) dye uptake. These results suggested the inhibitory effects of indirubin on the activation of P2X7 receptors, which may underlying the effects on ATP induced ROS production, phagocytosis attenuation and cell death of macrophages.

OBJECTIVETo analyze PD-1 expression in CD8 + T cell of Peripheral blood with HBV-associated acute-on-chronic liver failure and effect on CD8+ T cell.

METHODSWe selected 60 patients with HBV-ACLF and collected their peripheral blood. We analyzed the expressions of PD-1, CD95, perforin, granzyme A, granzyme B, CD107a on CD8+ T lymphocytes and the expression of PD-L1 on monocytes peripheral blood by using flow cytometry. 15 liver cirrhosis patients( LC) and 15 healthy individuals( HC) are control groups.

RESULTPD-1 expression was (1) The PD-1 expression in HBV-ACLF patients was significantly elevated compared with those in HC and lower in improved group than that in invalid group and death group (P < 0.05) and increased from prophase, metaphase to advanced stage (P < 0.05). Moreover, (2) PD-L1 expression on monocytes was positively correlated with disease progression. (P < 0.05). (3) Both PD-1 and CD95 expressions were higher in dead group than those in improved and non-improved groups. Perforin, granzymes and CD107a expressions on CD8+ T cells significantly increased in dead group compared with those in improved and non-improved groups (P < 0.05). However, PD-1 expressions on these cells were lower, compared with normal persons.

CONCLUSIONSThe expression of PD-1 and PD-L1 in HBV-ACLF patients was positively correlated with disease progression. The elevated PD-1 expression promoted apoptosis of CD8+ T cells. For HBV-ACLF patients, the PD-1 expression on effector CD8+ T cells was lower than those in other CD8+ T cells, which maybe accounted for the failure to controlling immune injury in liver.

Antigens, CD ; metabolism ; Apoptosis Regulatory Proteins ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Female ; Flow Cytometry ; Hepatitis B virus ; pathogenicity ; Humans ; Liver Failure, Acute ; immunology ; metabolism ; virology ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor

Using the latency of paw withdrawal (PWL) from a noxious thermal stimulus as a measure of hyperalgesia, the effects of i.p. injection of meptazinol and its isomers, 112824 and 112825, on carrageenan-induced thermal hyperalgesia were studied in awaked carrageenan-inflamed rats. Peripheral inflammation was induced by intraplantar (i.pl.) injection of carrageenan (2 mg/100 microl) into one hindpaw in rats. Carrageenan produced marked inflammation (edema and erythema) and thermal hyperalgesia in the injected paws, which peaked at 3 h after injection and showed little change in magnitude for another 3 h. Injection of 0.1 mg/kg meptazinol (i.p.) at 3 h after carrageenan had no effect on the PWLs of either inflamed or non-inflamed hindpaw during the next 100 min (P>0.05, n=8). At the dosage of 1 and 10 mg/kg, meptazinol produced marked anti-nociception and anti-hyperalgesia in non-inflamed and inflamed hindpaw, respectively (P<0.05, n=8-11). The prolonging effect of meptazinol on PWL in inflamed hindpaw was more potent than that in non-inflamed hindpaw. Pre-administration of 1.5 mg/kg naloxone significantly antagonized meptazinol-induced anti-nociception and anti-hyperalgesia. Intraperitoneal injection of an isomer of meptazinol, 112825 (1.5 mg/kg), but not 112824 (1 mg/kg), markedly increased the PWL of the non-inflamed hindpaw. Nevertheless, both the isomers produced similar anti-hyperalgesic effect to that of meptazinol (P<0.05, n=8), which was completely reversed by naloxone (1.5 mg/mg). The results suggest that meptazinol and its isomers have anti-nociceptive and anti-hyperalgesic properties with the former more potent. The effects are mainly mediated by mu opioid receptors. This study provides an important clue for extending clinical utilization of meptazinol and its isomers.
Analgesics, Opioid ; pharmacology ; Animals ; Carrageenan ; Hyperalgesia ; chemically induced ; physiopathology ; Inflammation ; chemically induced ; Isomerism ; Male ; Meptazinol ; pharmacology ; Nociceptors ; drug effects ; Pain ; physiopathology ; Pain Measurement ; methods ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the role of glutamine in LPS and D-Gal induced acute hepatic injury.

METHODSA total of 61 Wistar rats were randomly divided into three groups: control group, model group and GLN pretreated group. The animal model was established by LPS and D-Gal intraperitoneal injection. GLN at dose of 1 g/kg was intragastrically administrated for 7 d before intraperitoneal injection. To evaluate the hepatic injury, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBiL) were detected by automatic biochemistry analysator. The liver and bowel tissue was observed by lightmicroscope and transmission electron microscope (TEM). The apoptosis of hepatocyte was detected by TUNEL. HPLC-PED was used in the study of intestinal permeability.

RESULTSNo significant differences were noted between ALT, AST, TBIL level, death rate and intestinal permeability (L/M) between model group and GLN pretreated group; In microscope, the confused structure of hepatic injury and inflammatory infiltration were similar between model group and GLN pretreated group. The injury of bowel was not obviously. Compared with the model group, there was better trend in liver and bowel in GLN pretreated group by transmission electron microscope (TEM). The apoptosis index in GLN pretreated group were lower than those in model group.

CONCLUSIONLPS can induce acute liver injury in D-Gal-sensitized rats.Glutamine has't the trend of protecting liver function and intestinal barrier function,decreasing death rates.

Animals ; Apoptosis ; drug effects ; Female ; Glutamine ; administration & dosage ; Injections, Intraperitoneal ; Intestinal Mucosa ; drug effects ; enzymology ; physiology ; Liver ; drug effects ; injuries ; Random Allocation ; Rats ; Rats, Wistar

BACKGROUNDThe risk of clinical deterioration still exists in the acute phase despite the fact that patients with minor stroke may display less severe symptoms. The impact of this clinical deterioration on long-term outcomes is unknown. We characterized the clinical features of neurological deterioration (ND) in the acute phase of minor ischemic stroke (MIS) and investigated its impact on mid- and long-term outcomes.

METHODSThis was a multi-centered, prospective clinical study involving patients with MIS (the National Institutes of Health Stroke Scale, NIHSS ≤3) recruited from the China National Stroke Registry. Patients were included who had been hospitalized within 24 hours of stroke onset. Baseline characteristics, complication rates during hospitalization, etiology of stroke, as well as 3-, 6-, and 12-month post-stroke outcomes were compared between patients with and without ND during the acute phase.

RESULTSA number of 368 (15.2%) out of 2424 patients included in the study exhibited ND in the acute phase. Compared to patients without ND, patients with ND had longer hospital stay, increased rate of baseline diabetes, and multiple complications. Multivariate Logistic regression indicated that ND in acute phase was an independent factor predictive of increased dependence (adjusted odds ratio = 5.20, 95% CI, 3.51-7.70, P < 0.001) at 12-month post-stroke.

CONCLUSIONSThe risk of ND in the acute phase is high in patients with MIS. ND in the acute phase is an independent predictor for poor outcomes at 12 months post-stroke onset.

Aged ; China ; Female ; Humans ; Male ; Middle Aged ; Nervous System Diseases ; etiology ; physiopathology ; Prognosis ; Prospective Studies ; Risk Factors ; Stroke ; complications ; pathology

OBJECTIVESThe effect of vascular active peptides on the development of pulmonary remodeling and pulmonary hypertension due to left to right shunt congenital heart diseases is the focus of today's studies. The present study was conducted to investigate the roles of adrenomedullin (ADM) and adrenotensin (ADT) in pulmonary remodeling due to left to right shunt in rat lungs.

METHODSTwenty-one male Wistar rats were divided into two groups randomly. A right common carotid artery to external jugular vein shunt operation was performed on experimental rats (n = 9) to establish a left to right shunt animal model. Meanwhile, the common carotid artery and external jugular vein of the control group rats (n = 12) were just isolated without connection. Twelve weeks later, the mean pulmonary artery pressure (mPAP), the right ventricle to left ventricle plus septum ratio [weight, RV/(LV + SP)], the percentage of media wall thickness (MT%) were calculated. The distributions and relative protein contents of ADM and ADT in lungs were measured by immunohistochemical staining and Western blotting analysis. The relative gene expression for ADM, ADT, p46-p54 stress-actived protein kinase (SAPK) and p44 extracellular signal-regulated protein kinase 1 (ERK(1)) were investigated by RT-PCR.

RESULTSThe muscular and the tunica intimae layer of pulmonary artery were thicker in experiment group rats than those of control group, and the mPAP increased significantly in shunt group [(27.10 +/- 6.67) mm Hg (1 mm Hg = 0.133 kPa)] compared with that in control group [(14.32 +/- 3.14) mm Hg] (t = 5.5507, P < 0.001). The ratios of RV/(LV + SP) and MT% increased significantly in experimental group in contrast to the control group (P < 0.001). ADM and ADT positive granules distributed mainly over vascular smooth muscle cells, and Western blotting and integrated optical density analysis showed that the content of ADM increased in shunt group rats (P < 0.001), however, ADT content decreased (P < 0.001). The mRNA expression of ADM, SAPK and ERK(1) up-regulated in experiment group compared with the control group (P < 0.01, and P < 0.001 respectively), however, the ADT mRNA expression decreased in experimental rats in contrast to the control group (P < 0.001).

CONCLUSIONSThe phenomenon of intramolecular regulation of ADM and ADT, which both derived from proadrenomedullin, existed in the development of pulmonary remodeling and pulmonary hypertension due to left to right shunt. The mitogen-activated protein kinases (MAPKs) signal transduction pathway has been activated in the formation of left to right shunt pulmonary remodeling and pulmonary hypertension, and ADM may slow down the occurrence of pulmonary hypertension through cutting off MAPKs signaling pathway.

Adrenomedullin ; biosynthesis ; Airway Remodeling ; Animals ; Hypertension, Pulmonary ; metabolism ; Lung ; metabolism ; physiopathology ; Male ; Mitogen-Activated Protein Kinases ; metabolism ; Peptide Fragments ; biosynthesis ; Pulmonary Artery ; metabolism ; Pulmonary Circulation ; Rats ; Rats, Wistar ; Signal Transduction

We reconstructed the erythromycin macrocyclic lactone (6-deoxyerythronolide B, 6dEB) synthesis pathway in Escherichia coli. We first cloned all the genes needed to synthesize the 6dEB into multi-gene co-expressed vectors. Then using the recognition sequences of isoschizomers Xba I/Spe I of vectors, we assembled the related genes into a series multiple-genes recombinant plasmids pBJ144, pBJ130. The recombinant plasmids pBJ144, pBJ130 were cotransformed into BAP1 to get the recombinant BAP1(pBJ144/pBJ130). SDS-PAGE analysis showed that individual genes were expressed correctly. After inducing at low temperature, adding propionate as substrate, we validated the crude product by mass spectrometry and the 6dEB yield was about 10 mg/L. These results indicated that the synthetic pathway of 6dEB was successfully assembled and reconstructed in Escherichia coli, which will greatly facilitate the reconstruction of whole erythromycin synthesis pathway and finally help to establish a stable research platform for developing of new derivatives of erythromycin and combinatorial biosynthesis of polyketide-type antibiotics.
Anti-Bacterial Agents ; biosynthesis ; Cloning, Molecular ; Electrophoresis, Polyacrylamide Gel ; Erythromycin ; analogs & derivatives ; biosynthesis ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; genetics

OBJECTIVETo study the protective effect of Shenxiong injection on the cerebral ischemia-reperfusion injury of senile rats.

METHODTotally 108 Sprague-Dawley (SD) rats were randomly divided into the sham operation group, the model group, the Ni-modipine group and Shenxiong injection groups (low, middle, and high doses). The rat brain ischemia-reperfusion model was established by the middle cerebral artery occlusion (MCAO) method in rats, in order to observe the effect of Shenxiong injection on neurological score and brain infarct volume of rats with cerebral ischemia-reperfusion injury, and determine the contents of NOS, NO, SOD, MDA and LDH in brain tissues. The contents of TNF-alpha and IL-1beta levels in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA) method.

RESULTShenxiong injection could significantly decrease neurological score, injury degree of brain tissues and brain infarct volume of rats with cerebral ischemia-reperfusion injury, increase the vigor of SOD, decrease the levels of MDA, NO, NOS and LDH, and inhibit IL-1beta and TNF-alpha expressions.

CONCLUSIONShenxiong injection has the obvious protective effect on the brain ischemia-reperfusion injury in rats. Its mechanism may be related to the improvement of neurological function, the reduction of free radical injury, and the inhibition of inflammation factor expression.

Animals ; Brain ; blood supply ; drug effects ; metabolism ; Brain Ischemia ; complications ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Injections ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; drug therapy ; enzymology ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo estimate the effectiveness of inactivated influenza vaccine in elderly population.

METHODSAn quasi-experimental study was used. 590 elderly people who volunteered to receive the influenza vaccine were served as vaccine group, while 602 persons who did not want to receive the inoculation but could match the vaccine group were served as controls. One baseline and three follow-up surveys were carried out.

RESULTSThe protective rates of influenza like ill (ILI) as 52.38%, 36.84% and 37.89% with the decreasing rates of visits to ILI clinic as 45.16%, 50.54% and 50.54% were found after 1 month, 3 month and 6 month of inoculation of influenza vaccine; The protective rates of common cold, other respiratory tract or chronic disease were 49.54%, 64.54%, and 38.82%, respectively. The benefit-cost ratio was 4.98:1 in elderly population.

CONCLUSIONInfluenza vaccination could decrease ILI incidence and recurrence rates of related chronic diseases on elderly population to provide better economic benefits for the elderly.

Aged ; China ; epidemiology ; Cost-Benefit Analysis ; Female ; Humans ; Influenza Vaccines ; economics ; immunology ; Influenza, Human ; epidemiology ; prevention & control ; Male ; Middle Aged ; Vaccination