Objective To explore the inhibitory effects of Zibu Piyin Recipe(ZBPYR)serum on neuron apoptosis induced by tunieamyein(Tm,5 μg/ml)and its mechamsm in vitro by using sero-pharmacological method.Method Totally 12 healthy adult male SD rats(220～250 g)(SPF)were divided randomly into control group and ZBPYR group,6 in each group,then the blank and ZBPYR serum were prepared.The mouse.neuroblastoma cell line Neum2a cells were treated with Tunicamycin(Tin,an inhibitor of N-glycoslytion)to establish the endoplasmic reticulum(ER)stress model.The cells treated by ZBPYR aerum of different concentrations were interventional groups,and the cells treated by blank serum were control group.The viability of Neuro2a cells was meusurcdd by MTT assay.Flow cytometry wus applied to observe the apoptosis of Neuro2a cells.Western blotting was utilized to detect the protein expressions of two molecules,ER molecular chaperone-ucose regulated protein 78(CRP78)and transcriptional factor CCAAT/enhancer-binding protein-homologous protein(CHOP).The results were analyzed by sNK-q test.Results Compared to Tm group(cell viability 0.1673±0.0213,apoptotic rate 62.7050±1.4056),The cell viability of interventional groups(5%0.5295±0.0373,10%0.5843±0.0428,15%0.6274±0.0324)increased significantly(P<0.05);and the apoptotic rate(5%47.8733±2.8166,10%46.3366±1.2748,15%39.8833±1.0524)reduced significantly(P<0.05).The protein expressions of GRP 78(5%2.1228±0.2251,10%1.3293±0.9443,15%;15%0.0931±0.1168)and CHOP(5%1.1776±0.2927,10%0.7290±0.1708,15%0.6577±0.1883)of interventional groups reduced significantly compared with Tm group(GRP78 2.9149±0.5355;CHOP 1.6611±0.2913)P<0.05.Condusions ZBPYR serurn could increase the cell viability of Neuro2a cells treated with Tm and inhibit cell apoptosis.Thereby it may have neuroprotective effects,and the mechanism may be associated with the inhibition of ER stress and apoptosis pathway.

Objective:To screen radiosensitive lipid metabolites in rat small intestine and analyze their metabolic pathways, in order to provide scientific basis for radiation enteropathy biomarkers.Methods:The total body irradiation of 60Co γ rays was performed to rats with different doses of 0, 1, 2, 3, 5 and 8 Gy. The changes of lipids in small intestine were studied by targeted lipidomics method based on liquid chromatography coupled mass spectrometry (LC-MS). Results:Fifteen lipids in small intestine were screened as radiosensitive metabolites at 3 d after irradiation, including 4 up-regulated lipids and 11 down-regulated lipids( t=-6.395, 5.998, 5.836, -5.503, -5.449, -5.422, 4.841, 4.802, 4.621, 4.457, 4.426, 4.373, 4.110, 3.945, 3.902, P< 0.05 and FDR < 0.05). The metabolic pathways of sphingolipid, glycerophosphoplipid were significantly enriched. Four phosphatidyl serines (PS)increased while 1 phosphatidic acid(PA), 2 sphingomyelins(SM) and 4 fatty acids(FA)decreased in a good dose-response manner( R2> 0.80, P< 0.05), which were more potential radiation enteropathy biomarkers. Conclusions:Lipid metabolites in rat small intestine were significantly changed after the rat was total body irradiated with 60Co γ-rays.Eleven lipids with good dose-response relationship were more potential to be radiation enteropathy biomarkers.

Pseudomonas aeruginosa (PA) pneumonia is a refractory,even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process.We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells,i.e.,Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10).Seventy-two BALB/c mice were divided into four groups randomly:control (A),PA pneumonia (B),immunosuppression (C) and immunosuppression with PA pneumonia (D).Mice were sacrificed at 4,8 and 24 h after establishing experimental models.The pathological changes of lung tissue were graded,and the FOXP3 mRNA and serum IL-10 levels were detected.Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C,but significantly pathological changes were found in groups B and D,especially in group D at 8 h (P＜0.05).The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points,which were significantly lower than those in groups B and D (P＜0.05).FOXP3 mRNA levels were lowest at 4 h,and there was significant difference between groups B and D (P＜0.05).The serum levels of IL-10 in groups A and C were almost normal at the three time points,but decreased significantly in groups B and D (P＜0.05).The serum levels ofIL-10 decreased to the lowest at 8 h,especially in group D (P＜0.05).The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly,which may be associated with Treg cells function disturbance.And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

OBJECTIVE Using bioinformatics methods, to establish Xiao-Xu-Ming decoction (XX-MD)"compound-vasoconstriction G Protein-Coupled Receptors(GPCR)targets"network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD. METHODS Ac-cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da-ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1AR,5-HT1BR),AT1R,β2-AR,hUTR and ETB were retrieved from Bank Pro-tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col-lected and analyzed. The collected data were further used to construct and analyze the network. RE-SULTS 859 single compound structures information in XXMD were generalized following the screen-ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors. Most of the chemical composition effects were associated with different vasoconstric-tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi-ple targets,but also from the interaction between some effective component and multiple targets.

OBJECTIVETo evaluate the hemodynamic response to passive leg raising (PLR) indicates fluid responsiveness in patients with septic shock.

METHODSTwenty patients with septic shock, considered for fluid challenge (FC), were enrolled in the study from June 2009 to May 2010. Hemodynamic changes were determined by pulse-contour derived cardiac index at baseline, before and after PLR, return to baseline for 10 min, before and after fluid challenge (250 ml saline for 10 min). An increase of SV after fluid challenge (FC-ΔSV) ≥ 10% were defined responders.

RESULTSTwenty patients with septic shock were included in the study. PLR and fluid challenge were performed 46 instances, among which 15 instances were defined as response group. SV and pulse pressure induced by PLR (PLR-ΔSV and PLR-ΔPP) were increased significantly in response group [(76 ± 19) ml vs. (65 ± 18) ml, (73 ± 20) mmHg vs. (62 ± 20) mmHg (1 mmHg = 0.133 kPa), P < 0.05], while in nonresponse group there were no significant change. PLR-ΔSV and PLR-ΔPP were correlated with FC-ΔSV (r = 0.51, P = 0.001; r = 0.45, P = 0.006), central venous pressure (CVP) were unrelated with FC-ΔSV. Area under curve (AUC) for PLR-ΔSV, PLR-ΔPP and stroke volume variation (SVV) were 0.846, 0.791 and 0.708. PLR-ΔSV ≥ 12.5% predicted fluid responsiveness with sensitivity of 80% and specificity of 93.5%. PLR-ΔPP ≥ 9.5% predicted fluid responsiveness with sensitivity of 73.3% and specificity of 83.9%.

CONCLUSIONSPLR-ΔSV and PLR-ΔPP can predict fluid responsiveness in patients with septic shock. PLR-ΔSV and PLR-ΔPP have a greater ability in predicting volume responsiveness than CVP and SVV.

Adult ; Aged ; Aged, 80 and over ; Female ; Hemodynamics ; physiology ; Humans ; Leg ; Male ; Middle Aged ; Posture ; Sensitivity and Specificity ; Shock, Septic ; physiopathology

BACKGROUND/AIMS: To reveal possible factors predicting the effect of adefovir dipivoxil (ADV) treatment on chronic hepatitis B (CHB) and optimize the utilization of ADV. METHODS: In total, 168 treatment-naive CHB patients were enrolled, including 117 hepatitis B e antigen (HBeAg)-positive patients and 51 HBeAg-negative patients who met the inclusion criteria. All patients were treated with ADV 10 mg per day for 48 weeks. Multiple logistic regression analyses were used to investigate baseline factors, and responses at weeks 12 and 24 were analyzed as predictive values. RESULTS: Multiple regression analyses showed that baseline HBeAg status and HBV DNA levels significantly affected the virological response (VR) (p<0.05), baseline ALT levels were an independent predictor of serological response (SR) (p<0.05) and the body mass index (BMI) may affect the biochemical response (BR) (p<0.05). There was a statistically significant difference in the VR and SR between patients with a primary nonresponse (PNR) at week 12 and those with a VR at week 12 (p<0.01). Additionally, the VR was significantly different between patients with HBV DNA lower than 103 copies/mL at week 24 and those with greater than 103 copies/mL (p<0.01). CONCLUSIONS: Patients with negative HBeAg, lower HBV DNA levels and higher ALT values at baseline are more suitable for ADV treatment, whereas patients with lower BMIs may be more amenable to ALT normalization. Adjustments for treatment strategy should be considered if PNR at week 12 or HBV DNA > or =10(3) copies/mL at week 24 is observed.
Adenine ; Body Mass Index ; DNA ; Hepatitis B ; Hepatitis B e Antigens ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Logistic Models ; Organophosphonates

Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant α-GalCer. As results, TgCPC1 DNA vaccine with or without adjuvant α-GalCer showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and IFN-γ in the spleen compared to controls (PBS, pEGFP-C1, and α-Galcer). Upon challenge infection with tachyzoites of T. gondii (RH), pCPC1/α-Galcer immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and α-Galcer). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.
Animals ; B-Lymphocytes ; Cathepsin C* ; Cathepsins* ; DNA* ; Epitopes, T-Lymphocyte ; Immunoglobulin G ; Interleukin-2 ; Mice* ; Peptide Hydrolases ; Spleen ; Toxoplasma* ; Toxoplasmosis* ; Vaccines, DNA*

OBJECTIVETo observe the changes of sex hormones and sexual function in male patients with Graves' disease (GD) after Radioiodine-131 (I-131) therapy.

METHODSThirty-four male GD patients, aged 21 -40 (32.3 +/- 6.7) years, were treated with I-131 at the dose of 111 - 407 (237.8 +/- 51.8) MBq. The levels of serum sex hormones were measured, and the patients'scores on erectile function (IIEF-5) were obtained before and 3 and 6 months after the treatment. Another 20 healthy men aged 25 - 37 (31 +/- 3.1) years were enlisted as controls.

RESULTSThe baseline levels of estrogen (E2), testosterone (T) and luteinizing hormone (LH) were (132.5 +/- 40.4) pmol/L, (21.6 +/- 4.6) nmol/L and (10.1 +/- 4.4) IU/L in the GD patients, significantly higher than (80.4 +/- 31.2) pmol/L, (14.5 +/- 4.2) nmol/L and (6.2 +/- 1.9) IU/L in the healthy controls (P < 0.05). The E2, T and LH levels showed a significant decrease in the GD patients after 3 months of treatment ([110.2 +/- 20.6] pmol/L, [17.7 +/- 5.5] nmol/L and (9.4 +/- 3.9) IU/L, P < 0.05), but exhibited no statistically significant differences from the healthy controls at 6 months ([82.6 +/- 30.1] pmol/L, [13.8 +/- 3.4 ] nmol/L and [6.6 +/- 1.5] IU/L, P > 0.05). The IIEF-5 score of the GD patients was 5 - 25 (15.5 +/- 3.5) before I-131 treatment, significantly lower than that of the controls (19 - 25, 24 +/- 0.5) (P < 0.05), and it was 8 - 25 (19.5 +/- 1.0) at 3 months and 10 - 25 (23.5 +/- 1.5) at 6 months, significantly higher in the latter than in the former (P < 0.05), and with no significant difference between the 6-month treated patients and the healthy controls (P > 0.05).

CONCLUSIONThe E2, T and LH levels are increased while the IIEF-5 score decreased markedly in male GD patients. Six-month treatment with I-131 can not only restore the E2, T and LH levels to normal but also significantly improve the patient's sexual function.

Adult ; Case-Control Studies ; Estrogens ; blood ; Follicle Stimulating Hormone ; blood ; Graves Disease ; blood ; therapy ; Humans ; Iodine Radioisotopes ; therapeutic use ; Luteinizing Hormone ; blood ; Male ; Testosterone ; blood ; Young Adult

OBJECTIVETo identify the candidate auto-antigen of rheumatic heart disease as a molecular marker for this disease.

METHODSThe total RNA of the heart tissue of patients with rheumatic heart disease was extracted and reverse-transcribed into long cDNA to construct the phage expression library. The library was screened using the serum from patients with active rheumatic fever, and the positive clone was identified and analyzed by bioinformatics and expressed in vitro. The expressed products were evaluated with Western blotting and its cross-reactivity was assessed.

RESULTSThe phage expression library of the heart tissue of patients with rheumatic heart disease was constructed, with the titer of the primary library of 3.3×10(6) pfu/ml, recombinant rate of 99%, and 81% of the inserted segments were larger than 1 kb. An auto-antigen RHDAG1 was identified by screening, which was homologous to keratin 18. RHDAG1 was detected in the serum of patients with active rheumatic fever and of those with rheumatic heart disease, but not in the serum of healthy subjects.

CONCLUSIONPhage display library can be an effective strategy to screen the auto-antigens of rheumatic heart disease. The auto-antigen RHDAG1 can be a candidate molecular biomarker of rheumatic heart disease and/or rheumatic fever.

Autoantibodies ; blood ; immunology ; Autoantigens ; immunology ; isolation & purification ; Autoimmune Diseases ; blood ; immunology ; Humans ; Peptide Library ; Rheumatic Heart Disease ; immunology