Previous studies showed that three methods for regulating and invigorating lung and kidney (lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, and Qi supplementing and kidney nourishing) could regulate inflammatory signaling pathways of chronic obstructive pulmonary disease (COPD) in rats, so as to alleviate inflammation. In the present study, R-value comprehensive evaluation method was used to evaluate the comprehensive effect of three methods for regulating and invigorating lung and kidney on inflammatory signaling pathways. Rats were randomly divided into control, model, lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing and aminophylline groups. The COPD rat models were established by cigarette smoking combined with bacterial infection, and orally administered with drugs between the 9th and 20th week. Afterwards, efforts were made to observe the long-term effects between the drug withdrawal and the 32rd week and detect indicators in two batches in the 20th week and 32th week. Specifically, (1) Linking JAK/STAT signaling pathway: JAK2 mRNA, and protein expressions of STAT-1, STAT-3, STAT-5, JAK-2; (2) NF-kappaB signaling pathway: Smad2 mRNA and protein expressions of I-kappaB, NF-kappaB, TGF-beta1; (3) PPARgamma and antioxidant signaling pathway: SOD, PGE mRNA, PPARgamma protein. According to the results, 5 indicators in JAK/STAT pathway, 4 indicators in NF-kappaB pathway, and 3 indicators in PPARgamma pathway were significantly rectified by three methods for regulating and invigorating lung and kidney in between the 20th week and 32nd week. Between the 20th and 32nd week, the recipes for rectifying JAK/STAT pathway with intensity from high to low were recipes for lung invigorating and spleen strengthening, Qi supplementing and kidney nourishing, lung invigorating and kidney tonifying, aminophylline, particularly those for lung invigorating and spleen strengthening; The recipes for rectifying NF-kappaB pathway with intensity from high to low were recipes for lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing and aminophylline, particularly the first three types of drugs. The recipes for rectifying PPARgamma and antioxidant signaling pathway with intensity from high to low were recipes for lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing, lung invigorating and spleen strengthening and aminophylline. Therefore, three methods for regulating and invigorating lung and kidney showed better long-term effects in regulating COPD lung inflammation signaling pathways. Specifically, recipe for lung invigorating and spleen strengthening showed a better effect in JAK/STAT and NF-kappaB pathways, while recipe for lung invigorating and kidney tonifying and Qi supplementing and kidney nourishing showed better effects in PPARgamma and antioxidant signaling pathways. In conclusion, R-value comprehensive evaluation method can evaluate the comprehensive effect of medicines and define the ranking of multiple drugs and their main targets.
Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; physiopathology ; Lung ; drug effects ; immunology ; metabolism ; physiopathology ; NF-kappa B ; immunology ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; immunology ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Smad2 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo project the future impacts of climate change on heat-related mortality in shanghai.

METHODSThe statistical downscaling techniques were applied to simulate the daily mean temperatures of Shanghai in the middle and farther future under the changing climate. Based on the published exposure-reaction relationship of temperature and mortality in Shanghai, we projected the heat-related mortality in the middle and farther future under the circumstance of high speed increase of carbon e mission (A2) and low speed increase of carbon emission (B2). The data of 1961 to 1990 was used to establish the model, and the data of 1991 - 2001 was used to testify the model, and then the daily mean temperature from 2030 to 2059 and from 2070 to 2099 were simulated and the heat-related mortality was projected. The data resources were from U.S. National Climatic Data Center (NCDC), U.S. National Centers for Environmental Prediction Reanalysis Data in SDSM Website and UK Hadley Centre Coupled Model Data in SDSM Website.

RESULTSThe explained variance and the standard error of the established model was separately 98.1% and 1.24°C. The R(2) value of the simulated trend line equaled to 0.978 in Shanghai, as testified by the model. Therefore, the temperature prediction model simulated daily mean temperatures well. Under A2 scenario, the daily mean temperature in 2030 - 2059 and 2070 - 2099 were projected to be 17.9°C and 20.4°C, respectively, increasing by 1.1°C and 3.6°C when compared to baseline period (16.8°C). Under B2 scenario, the daily mean temperature in 2030 - 2059 and 2070 - 2099 were projected to be 17.8°C and 19.1°C, respectively, increasing by 1.0°C and 2.3°C when compared to baseline period (16.8°C). Under A2 scenario, annual average heat-related mortality were projected to be 516 cases and 1191 cases in 2030 - 2059 and 2070 - 2099, respectively, increasing 53.6% and 254.5% when compared with baseline period (336 cases). Under B2 scenario, annual average heat-related mortality were projected to be 498 cases and 832 cases in 2030 - 2059 and 2070 - 2099, respectively, increasing 48.2% and 147.6% when compared with baseline period (336 cases).

CONCLUSIONUnder the changing climate, heat-related mortality is projected to increase in the future;and the increase will be more obvious in year 2070 - 2099 than in year 2030 - 2059.

China ; Climate Change ; Greenhouse Effect ; Humans ; Models, Theoretical ; Mortality ; Risk Assessment

OBJECTIVETo investigate the relationship between plasma levels of fibrinogen, the-beta455 G/A fibrinogen gene polymorphism and the severity of periodontal inflammation and to explore the possible role of fibrinogen in the association of periodontitis with coronary heart disease (CHD).

METHODSA total of 121 patients with moderate to severe periodontitis and periodontally healthy and gingivitis controls were enrolled in the study. Peripheral blood samples were collected and the plasma fibrinogen levels were determined by the clotting method of Clauss. Polymerase chain reaction and restriction fragment length polymorphism analysis with Hae III were used to examine the -beta455 G/A fibrinogen gene polymorphism.

RESULTSFibrinogen levels were significantly higher in moderately or severely chronic periodontitis patients [(3.45 +/- 0.68) g/L] than periodontally healthy and gingivitis controls [(2.47 +/- 0.42) g/L, P < 0.001]. The carrier status of the A allele at position -455 in the beta fibrinogen gene was associated with elevated fibrinogen levels and the frequency of the-A455 allele in the beta fibrinogen gene in the patient group was significantly higher than in the control group (P = 0.032). Carriers of the -A455 allele were about 3-fold more likely to have moderate or severe periodontitis as compare to individuals without the -A455 allele( OR = 3. =135, P= 0.008).

CONCLUSIONSFg-beta455 G/A polymorphism may contribute to the elevated plasma fibrinogen levels and put individuals at higher risk of having severe periodontitis. As the independent risk factor of CHD, fibrinogen levels and Fg-beta455 G/A polymorphism may play a role in the pathogenesis of periodontitis.

Adult ; Alleles ; Case-Control Studies ; Chronic Periodontitis ; genetics ; Coronary Disease ; genetics ; Female ; Fibrinogen ; analysis ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo investigate the correlation between moderately and severely chronic periodontitis and coronary heart disease, as well as the role of fibrinogen in the mechanisms responsible for the correlation between periodontitis and coronary heart disease.

METHODS95 subjects who were systemic health or patients of coronary heart disease with or without periodontitis were enrolled. All the subjects were placed into 4 groups based on their periodontal status and cardiovascular health. The 4 groups were healthy control group (HC), moderately and severely chronic periodontitis group (MSP), coronary heart disease group(CHD), and MSP coexisted with CHD group (MSP+CHD). Clinical periodontal index were examined, at the same time, plasma fibrinogen levels and serological changes used in diagnosing of cardiovascular disease routinely were determined. ANOVA and ANCOVA were used in the statistical analysis.

RESULTSFibrinogen levels of HC, MSP, CHD, and MSP+CHD group were (2.36+/-0.37), (3.63+/-0.73), (4.08+/-0.84), and (4.14+/-0.96) g/L, respectively. Fibrinogen levels of MSP and MSP+CHD group were significantly higher than that of healthy controls (P<0.01). The patients with moderately to severely chronic periodontitis were more likely to have coronary heart disease as compared to periodontally healthy controls (OR=2.527, P=0.047) after adjusted for blood pressure and body mass index.

CONCLUSIONModerately and severely chronic periodontitis maybe a risk factor of coronary heart disease and fibrinogen could be one of the biological basis which links periodontitis with coronary heart disease.

Chronic Periodontitis ; Coronary Disease ; Female ; Humans ; Male ; Middle Aged ; Periodontal Index ; Periodontitis ; Risk Factors

OBJECTIVETo compare the effect of the extracts from Decoction for resuscitation (DRE) and its component herbs on prostacyclin (PGI2), thromboxane A2 (TXA2) and nitric oxide (NO) release from rat vascular endothelial cells under hypoxia.

METHODAfter treatment with the extracts from DRE and its component herbs, the contents of 6-keto-prostaglandin F1alpha(6-keto-PGF1alpha), thromboxane B2 (TXB2) as well as nitrite (NO), which were degradation products of PGI2, TXA2 and NO respectively, in culture medium of rat vascular endothelial cells under hypoxia were measured with radioimmunoassay and Griess Reaction.

RESULTCompared with the control group, the results indicated that DRE, prepared licorice root extract (LE), dried ginger extract (GE), aconite root extract (AE), extracts of aconite root and prepared licorice root (ALE), extracts of aconite root and dried ginger (AGE) increased significantly the content of 6-keto-PGF1alpha and the ratio of 6-keto-PGF1alpha/TXB2, but had no effect on the content of TXB2 in culture medium of rat vascular endothelial cells under hypoxia. The content of 6-keto-PGF1alpha in the DRE group was higher than that in the groups of LE, GE, AE, ALE, AGE. The ratio of 6-keto-PGF1alpha/TXB2 in the DRE group was higher than that of the groups of GE, AE, ALE. Compared with the control group, DRE, LE, GE, AE, ALE, AGE increased significantly the content of NO2- in culture medium of rat vascular endothelial cells under hypoxia. Moreover, the content of NO2- in the DRE group was higher than that of the groups of GE, AE, ALE.

CONCLUSIONThe results suggested that DRE increased significantly the content of PGI2 and the ratio of PGI2/TXA2 as well as the content of NO. The effect of DRE on the parameters in culture medium of rat vascular endothelial cells under hypoxia was better than that of the extracts from its component herbs.

6-Ketoprostaglandin F1 alpha ; metabolism ; Aconitum ; chemistry ; Animals ; Aorta, Abdominal ; cytology ; Cell Hypoxia ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelial Cells ; metabolism ; Ginger ; chemistry ; Glycyrrhiza uralensis ; chemistry ; Nitric Oxide ; metabolism ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Thromboxane B2 ; metabolism

OBJECTIVETo study the role of fibrinogen molecule in the pathogenesis of periodontal diseases.

METHODSAn in vitro cell culture model was used. Methyl-(3)H Thymidine radiolabeled Porphyromonas gingivalis (Pg) ATCC 33277 were examined for their ability to adhere to and invade the confluent monolayers of human oral epithelial KB cells with or without exogenous human fibrinogens by scintillation spectrometry.

RESULTSThe addition of exogenous fibrinogens made more amount of and higher ratios of adhesive and invasive Pg, in contrast to the group without exogenous fibrinogen (P < 0.001). At different concentrations of exogenous fibrinogen, the amount and ratios of adhesive and invasive Pg varied significantly (P < or = 0.007). The higher concentrations of exogenous fibrinogen was added, the greater amount and ratios of adhesive and invasive Pg were found.

CONCLUSIONSFibrinogen promotes the adherence of Pg to human oral epithelial cells and may play an important role in the pathogenesis of periodontal diseases.

Bacterial Adhesion ; drug effects ; Fibrinogen ; administration & dosage ; pharmacology ; Humans ; KB Cells ; Mouth Mucosa ; drug effects ; microbiology ; Periodontitis ; etiology ; Porphyromonas gingivalis ; pathogenicity

OBJECTIVETo investigate the effect of one of the acute-phase proteins, fibrinogen, on the release of IL-1beta and -8 by human peripheral polymorphonuclear leukocytes (PMN) and the possible role of fibrinogen during the destruction of periodontium.

METHODSPeripheral PMN were isolated by discontinuous density gradient centrifuging technique. The freshly isolated PMN were suspended in Hank's balanced saline solution (1 x 10(9)/L) supplemented with 0.5% BSA and 0.1% glucose. The levels of IL-1beta and -8 in the supernatants produced by cultured cells upon the addition of human fibrinogen at different concentrations were measured by ELISA technique.

RESULTSIncubated with human fibrinogen at 2 g/L or 10 g/L for different time periods, human peripheral PMN released significantly greater amount of IL-1beta [(10.41 +/- 0.37) - (35.86 +/- 0.30) ng/L or (22.81 +/- 0.45) - (57.77 +/- 2.08) ng/L] and IL-8 [(93.90 +/- 13.95) - (2045.66 +/- 53.03) ng/L or (115.02 +/- 10.61) - (3858.69 +/- 25.65) ng/L] than PMN without the stimulation of fibrinogen (IL-1beta, P < 0.001, and IL-8, P < or = 0.016). The higher concentration of fibrinogen or the longer treatment time, the higher levels of IL-1beta and -8 were released by PMN (P < 0.001).

CONCLUSIONSFibrinogen induced the secretion of pro-inflammatory cytokines IL-1beta and -8 by PMN and may be involved in magnification of the inflammatory response of periodontium and bone resorption.

Cells, Cultured ; Fibrinogen ; pharmacology ; Humans ; Interleukin-1beta ; metabolism ; Interleukin-8 ; metabolism ; Middle Aged ; Neutrophils ; drug effects ; secretion

OBJECTIVETo summarize the clinical characteristic and radiotherapeutic effect of germinomas arising in basal ganglia and thalamus.

METHODSThe clinical data of 13 cases were reviewed retrospectively. All cases were pathologic diagnosis through stereotactic biopsy. Gamma-knife or ordinary irradiation were 2 cases respectively and the combined therapy with interstitial brachytherapy as foundation were 9 cases.

RESULTAll cases were male, median age of 16.1 years. Hemiparesis and ataxia were major symptoms, some cases were accompanied with precocious puberty. Imaging manifested intratumoral cystic components represented 76.9% of all lesions, calcification represented 30.8%, ipsilateral cerebral and brain stem hemiatrophy represented 46.2%, cerebral white matter invasion through internal capsule or corpus callosum represented 30.8%. One case died because of late complication and 12 cases had achieved satisfied therapeutic effect (the mean followed-up period was 40.6 months). Tumor-control were effective.

CONCLUSIONSThe clinical manifestation and imaging characteristics are helpful to diagnosis. Stereotactic biopsy make the affirmatory diagnosis. Operative total-removal is impossible because of deep location, neighbour of vital structure and invasion. The combined therapy with interstitial brachytherapy was effective.

Adolescent ; Adult ; Basal Ganglia ; Brain Neoplasms ; diagnosis ; radiotherapy ; surgery ; Child ; Follow-Up Studies ; Germinoma ; diagnosis ; radiotherapy ; surgery ; Humans ; Male ; Retrospective Studies ; Thalamus ; Treatment Outcome

Aim To investigate the effect of curcumin ( CUR) combined with cytarabine( Ara-C) on the pro-liferation and apoptosis of human acute myeloid leuke-mia cell line KG1a and its relationship with autophagy. Methods The optimal combination concentration of curcumin and cytarabine was screened by MTT method and the combined effects were detected. The effects of CUR and Ara-C on the proliferation, autophagy, apop-tosis and cycle of KG1a cells were analyzed. Results Both CUR and Ara-C significantly inhibited the prolif-eration of KG1a cells ( P<0.05) , and showed a dose-and time-dependent manner. The inhibition rate of cells treated with 40 μmol·L-1CUR and 0.5 μmol· L-1 Ara-C was significantly higher than that of the other doses alone. The survival rate of cells pretreated with 3-MA was significantly decreased ( P <0.05 ) . Auto-phagic vacuoles was observed in cells with Acridine or-ange staining methods, the expression rate of the com-bination group was higher than the single group, and can be inhibited by 3-MA. The apoptosis rate of the combined group was higher than that of the single group. The apoptosis rate of the 3-MA pretreatment group was higher than that of the single group ( P <0.05). Cell numbers of the G0/G1 phase were signifi-cantly more than the S phase. The expression of caspase-3, LC3 and Beclin-1 were up-regulated while the Bcl-2 was down-regulated(P<0.05). The protein level of caspase-3 and Beclin-1 of the combination group was significantly higher than that of the single group ( P <0.05 ) , and the ratio of LC3-Ⅱ/LC3-Ⅰwas increased. The Beclin-1 expression and caspase-3 expression in 3-MA pretreatment group decreased ( P<0.05) . Conclusion Curcumin can induce autoph-agy and apoptosis of KG1a cells and increase the sensi-tivity of leukemic cells to cytarabine. Autophagy inhib-itor 3-MA can not only inhibit the autophagy but also promote apoptosis.

AIMTo observe the expressional alterations of colony stimulating factor-1 receptor (CSF-1R) after ischemic injury of cerebral cortex, and study the function of colony stimulating factor-1 (CSF-1)/CSF-1R signal during the process of ischemic injury and repair of central nervous system (CNS).

METHODSWe examined the distribution and expression of CSF-1R in normal brain tissues and ischemic brain tissues by immunohistology and Western blot analysis.

RESULTSThe expression of CSF-1R in neurons could be up-regulated by ischemic injury in CNS.

CONCLUSIONCSF-1/CSF-1R might take part in the process of ischemic injury and repair.

Animals ; Brain Ischemia ; pathology ; physiopathology ; Cerebral Cortex ; blood supply ; Female ; Macrophage Colony-Stimulating Factor ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Neurons ; metabolism ; Random Allocation ; Receptor, Macrophage Colony-Stimulating Factor ; genetics ; metabolism ; physiology ; Reperfusion Injury ; metabolism ; physiopathology