OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.
Humans ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/genetics* ; Macrophages/metabolism* ; Cytokines/metabolism* ; Lipopolysaccharides/pharmacology* ; NF-kappa B

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

OBJECTIVETo explore the relation between serum vitamin D (25(OH)D) concentrations and liver cirrhosis.

METHODSA nested case control study was designed based on the Nutrition Intervention Trial (NIT) cohort, from which non-degraded serum samples and complete baseline and follow-up data were available for 282 individuals diagnosed with liver cirrhosis and 564 healthy controls. The serum samples were tested by enzyme-linked immunosorbent assay to detect and quantify 25(OH)D, as well as hepatitis B virus surface antigen and core antibody and hepatitis C virus antibody. The study participants were divided into four groups according to quartile range of 25(OH)D concentration and logistic regression modeling was used to evaluate the relation with liver cirrhosis risk by estimating odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTSThe liver cirrhosis group had a significantly lower concentration of 25(OH)D than the control group (median and quartile range in nmol/L, cases: 15.3 and 13.8; controls: 20.2 and 16.6; t = 5.169, P = 0.002). When the first interval was set as the reference level, the ORs(95% CIs) of the second, third, and fourth intervals were: 0.495(0.333 - 0.736), 0.452(0.303 - 0.675), and 0.349(0.231- 0.527). After adjusting the analysis for the presence of pathogenic-related confounding factors, the ORs(95% CIs) of the second, third, and fourth intervals were: 0.499(0.328 - 0.759), 0.427(0.278 - 0.654), and 0.344(0.222-0.532). The 25(OH)D level was inversely correlated with risk of liver cirrhosis (Chi2 = 25.200, P < 0.001).

CONCLUSIONRisk of liver cirrhosis increases as 25(OH)D serum concentration decreases. Vitamin D might function as a protective factor against development of cirrhosis.

Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Liver Cirrhosis ; blood ; epidemiology ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Vitamin D ; blood

OBJECTIVETo analyze the periodicity of pandemic influenza A (H1N1) in Changsha in year 2009 and its correlation with sensitive climatic factors.

METHODSThe information of 5439 cases of influenza A (H1N1) and synchronous meteorological data during the period between May 22th and December 31st in year 2009 (223 days in total) in Changsha city were collected. The classification and regression tree (CART) was employed to screen the sensitive climatic factors on influenza A (H1N1); meanwhile, cross wavelet transform and wavelet coherence analysis were applied to assess and compare the periodicity of the pandemic disease and its association with the time-lag phase features of the sensitive climatic factors.

RESULTSThe results of CART indicated that the daily minimum temperature and daily absolute humidity were the sensitive climatic factors for the popularity of influenza A (H1N1) in Changsha. The peak of the incidence of influenza A (H1N1) was in the period between October and December (Median (M) = 44.00 cases per day), simultaneously the daily minimum temperature (M = 13°C) and daily absolute humidity (M = 6.69 g/m(3)) were relatively low. The results of wavelet analysis demonstrated that a period of 16 days was found in the epidemic threshold in Changsha, while the daily minimum temperature and daily absolute humidity were the relatively sensitive climatic factors. The number of daily reported patients was statistically relevant to the daily minimum temperature and daily absolute humidity. The frequency domain was mostly in the period of (16 ± 2) days. In the initial stage of the disease (from August 9th and September 8th), a 6-day lag was found between the incidence and the daily minimum temperature. In the peak period of the disease, the daily minimum temperature and daily absolute humidity were negatively relevant to the incidence of the disease.

CONCLUSIONIn the pandemic period, the incidence of influenza A (H1N1) showed periodic features; and the sensitive climatic factors did have a "driving effect" on the incidence of influenza A (H1N1).

China ; epidemiology ; Climate ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; epidemiology ; virology ; Regression Analysis ; Risk Factors ; Seasons ; Temperature

OBJECTIVETo explore the influence of landscape elements on the transmission of hemorrhagic fever with renal syndrome (HFRS) in Changsha.

METHODSA total of 327 cases of HFRS diagnosed between year 2005 - 2009 were recruited in the study. Based on the demographic data, meteorological data and the data of second national land survey during the same period, a GIS landscape elements database of HFRS at the township scale of Changsha was established. Spatial-temporal cluster analysis methods were adopted to explore the influence of landscape elements on the spatial-temporal distribution of HFRS in Changsha during the year of 2005 - 2009.

RESULTSThe annual incidences of HFRS in Changsha between year 2005 - 2009 were 1.16/100 000 (70 cases), 0.95/100 000 (58 cases), 1.40/100 000(87 cases), 0.75/100 000(47 cases) and 1.02/100 000(65 cases) respectively. The results of poisson regression model analysis of principal component showed that the incidence of HFRS was positively correlated with farmland area (M = 29.00 km2) and urban and rural area (M = 6.12 km2; incidence rate ratios (IRR) = 1.34, 95% CI: 1.27 - 1.41); but negatively correlated with forestland area (M = 39.00 km2; IRR = 0.67, 95% CI: 0.55 - 0.81) and garden plot area (M = 0.99 km2; IRR = 0.74, 95% CI: 0.63 - 0.86). A significant cluster of the spatial-temporal distribution of HFRS cases was found in the study. The primary cluster (28.9 N, 113.37 E, radius at 22.22 km, RR = 5.23, log likelihood ratio (LLR) = 51.61, P <0.01, 67 cases of HFRS and incidence at 4.4/100 000) was found between year 2006 and 2007; and the secondary cluster (28.2 N, 113.6 E, RR = 10.77, LLR = 16.01, P < 0.01, 11 cases of HFRS and the incidence at 10.6/100 000) was found between year 2008 and 2009.

CONCLUSIONThe landscape elements were found to be closely related to the prevalence and transmission of HFRS.

China ; epidemiology ; Climate ; Geographic Information Systems ; Hemorrhagic Fever with Renal Syndrome ; epidemiology ; transmission ; Humans ; Regression Analysis ; Space-Time Clustering

OBJECTIVETo investigate the association between concentration levels of fasting serum glucose and liver cirrhosis.

METHODSA nested case-control study was carried out based on the sample cohort from the Nutrition Intervention Trials previously conducted in one country in Henan province. Using an automatic biochemical analysis system and enzyme-linked immunoassay, baseline serum samples from 310 liver cirrhosis patients and 620 healthy controls were tested for fasting glucose concentration, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis C virus antibody (anti-HCV). Baseline demographic information was collected by questionnaire. The serum glucose values were divided into quintiles and applied to a logistic regression model to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).

RESULTSThe mean fasting blood glucose level was significantly higher in cases (4.5+/-1.8 mmol/L) than in controls (4.2+/-2.1 mmol/L) (t=-2.414, P=0.016). The individuals in the highest quintile had a significantly higher risk of disease than those in the lowest quintile [OR=1.672 (1.080, 2.588)]. Moreover, increase in glucose level was accompanied by increased risk, and the relation showed statistically significant linearity (P=0.002). The statistical significance of risk remained after adjustment for potential confounders, including sex, age, HBsAg, anti-HBc, and residence running water status [OR=1.96 (1.216, 3.157), P=0.001].

CONCLUSIONElevated serum fasting glucose concentration was an independent risk factor of cirrhosis.

Adult ; Blood Glucose ; metabolism ; Case-Control Studies ; China ; epidemiology ; Female ; Humans ; Liver Cirrhosis ; blood ; epidemiology ; Male ; Middle Aged ; Prospective Studies ; Risk Factors

OBJECTIVETo explore the feasibility of surgical design for mandibular retrusion using three-dimensional software.

METHODSThree-dimensional reconstruction was performed by Mimics software based on the preoperative CT data. The model of the maxillofacial region was imported into Rapidform software for measuring the associated parameters and Geomagic software for simulation of osteotomy. The reliability of the virtual operation was validated during the surgery.

RESULTSThe model of mandibular retrusion was reconstructed and successfully used to simulate the surgery. The simulation result was applied in subsequent actual surgery and good surgical outcomes were achieved.

CONCLUSIONThe three-dimensional software can be used to simulate the surgery for mandibular retrusion and improve the predictability and accuracy of the surgery.

Computer Simulation ; Feasibility Studies ; Humans ; Image Processing, Computer-Assisted ; methods ; Imaging, Three-Dimensional ; methods ; Male ; Malocclusion, Angle Class II ; surgery ; therapy ; Mandible ; abnormalities ; diagnostic imaging ; surgery ; Maxilla ; diagnostic imaging ; Models, Anatomic ; Retrognathia ; diagnostic imaging ; surgery ; Software ; Surgery, Computer-Assisted ; methods ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo summarize the clinical characteristics of secondary coagulation disorders caused by exposure to poison (raticide) in children and to investigate the diagnosis and corresponding treatment.

METHODThe process of diagnosis, clinical characteristics, response to treatment and the prognosis were analyzed.

RESULTSThe main clinical manifestation was mucosal bleeding (66.6%), including epistaxis, gingival bleeding, hematomas and so on. All these children were previously well and had no history of bleeding. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged, factor II was undetectable and the levels of factors VII, IX, and X were lower. The fibrinogen was normal. A raticide was detected in blood and urine of 13 children although 12 of the patients had no definite history of raticide ingestion. Prothrombin complex, fresh frozen plasma and vitamin K(1) were effective in these cases. However, 2 - 3 weeks later, 6 patients presented with recurrent bleeding.

CONCLUSIONFor children with secondary coagulation disorders of unknown cause, intoxication of raticide should be considered. The administration of blood coagulation factors and vitamin K(1) are effective in early treatment, and the treatment period should be more than 2 months. The PT and APTT should be followed up. Vitamin K(1) should be stopped when PT and APTT are normal.

Blood Coagulation Disorders ; chemically induced ; diagnosis ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Rodenticides ; poisoning ; Vitamin K 1 ; administration & dosage ; therapeutic use

Objective To determine the urinary iodine level of people in Yunyang and Bishan County of Chongqing and explore into its influencing factors. Methods Using multistage cluster stratified simple random sample method, Yunyang and Bishan County were chosen as research spots, then thirty children aged 8-10 in each 3 primary school of the 2 counties were selected using stratified randomization sampling method to inspected their urine and household salt for iodine and the iodine content in drinking water. Results Five hundred and seventy-one urine samples were inspected and the urinary iodine median was 261.47 μg/L. 5.78% (33/571) and 37.48%(214/571) of samples had an urinary iodine median less than 100 μg/L and more than 300 μg/L. The urinary iodine median of Yunyang County was higher than that of Bishan (H = 7.42, P < 0.01). The iodine salt coverage rate, the qualified rate and edible qualified iodine salt rate respectively were 99.64%(554/556), 94.22% (522/554) and 93.88% (522/556) in 556 samples of family table salt. Eighty-seven samples of drinking water were inspected, resulting an averaged iodine content of 8.81 and 2.97 μg/L, respectively in the 2 counties. Conclusions The 2 counties are all the area of iodine deficiency. The urinary iodine level, although meeting the demand of eliminating iodine deficiency diseases, is a little bit higher given that iodized salt of present doage has been taken for a long time. The content of iodized salt should be adjusted accordingly.

Objective To investigate the antibacterial molecular mechanism of Traditional Chinese Medicine Coptis rhizome against Yersinia pestis(Y.pestis).Methods The method based on whole genome DNA micrnarray of Y.pestis was used.The minimal inhibition concentration(MIC)of berberine to Y.pestis was determined with liquid dilution method.Then gene expression profile of Y.pestis was performed after exposed to berberine at the concentration of 10×MIC for 30 minutes.Total RNA extracted and purified from Y.pestis and reverse-transcribed to cDNA,then labeled by Cy-dye.Finally,the labeled probes were hybridized to the microarray and the results were obtained by a laser scanner and analyzed by the SAM software.Results The gene expression profile data revealed that the response of Y.pestis to berberine was a global phenomenon.A total of 360 genes changed significantly.Among them,333 genes were up-regulated,27 down-regulated.These differentially expressed genes were further classified into 24 different functional categories based on the genomie annotation of Y.pestis CO92,in which the number of mainly related genes were 83,75 and 48,including cell envelop,unkown,transport/binding proteins functions.The 40 genes related to the metabolism were upregulated,which was a remarkable change.Conclusion Our results have revealed the general gene expression changes of Y.pestis in response to berberine and demonstrated the antibacterial molecular mechanism of the Coptis rhizome.The major mechanism of Y.pestis in response to berberine is the upregulation of genes related to the metabolism.