Objective:To screen and identify the potential targets of carthamin against sepsis by studying the characteristics of carthamin.Methods:The pharmacological parameters and molecular characteristics of carthamin were analyzed with the aid of Traditional Chinese Medicine Systems Pharmacology (TCMSP). The targets of carthamin were screened by SwissTargetprediction (a website providing compound target prediction) and Drug Repositioning and Adverse drug Reaction via Chemical-Protein Interactome (DRAR-CPI). The anti-sepsis targets were selected from the three databases of Online Mendelian Inheritance in Man (OMIM), Comparative Toxicogenomics Database (CTD) and Therapeutic Targets Database (TTD). The targets of carthamin screened by the two websites and disease targets selected from the three databases were matched to screen the targets of carthamin against sepsis. The anti-sepsis potential targets of carthamin were identified by molecular docking software.Results:The oral bioavailability of carthamin was 41.15%, the drug-likeness was 0.24, and the rotational bond number was 1, which indicated that carthamin was well absorbed by oral administration and showed good drug formation. A total of 115 potential targets of carthamin were screened by SwissTargetprediction and DRAR-CPI; 149 disease targets were found from OMIM, CTD and TTD databases; 115 target proteins of carthamin screened by the two websites were matched with the disease targets , and 10 target proteins were found to be both molecular targets and disease targets. The 10 target proteins were coagulation factor Ⅸ (F9), adenosine A1 receptor (ADORA1), nitric oxide synthase 2 (NOS2), mitogen activity protein kinase 1 (MAPK1), cathepsin G (CTSG), neutrophil elastase (ELANE), protein C (PROC), lipocalin 2 (LCN2), glucose-6-phosphate dehydrogenase (G6PD) and prostaglandin endoperoxidase 2 (PTGS2). Molecular docking software analysis showed that carthamin had the ability to bind to the above 10 target proteins, which were potential targets of carthamin against sepsis. Carthamin could interact with the key amino acid residues of the targeted proteins, so as to play the corresponding efficacy.Conclusion:Carthamin combines with the targets could reduce the tissues and organs damage of sepsis by regulating CTSG, ELANE and LCN2, reduce inflammatory response of sepsis by regulating ADORA1, PTGS2, NOS2, MAPK1 and mediating PROC and F9 to inhibit clotting, and improve oxidative stress, reduce the incidence of sepsis by regulating G6PD, finally, prevented and treated sepsis.

Objective To Summarize experence of Dynamic Hip Screw for the treatment of femoral intertrochanteric fracture. Methods 54 cases with femoral intertrochanteric fracture were treated by DHS internal fixation. Results All patients were followed up for 4～36 months with an average of 7 months. Satisfactory effect was obtained. Conclusions The recovery of intact posterointernal cortex of femoral intertrochante, the standard postiton of fixation of DHS and an incarease in postoperative functional exercise are the key to obtain a satisfactory therapeutic effect.

24 patients suffering from tertian malaria were treated with 600 mg of artesunate tablet as a total dose in a 5-day course. The result showed that all patients were clinically cured with symptoms and signs subsided quickly. Defervescence and parasite clearance times were 19. 9?15.8 and 56. 8?17. 4 hours respectively. The recrudescent rate was 54.2％ within 28 days.

OBJECTIVETo study the possible mechanisms of chronic nonbacterial prostatitis (CNP) pain.

METHODSCNP models were established in male Wistar rats by the autoimmune method. Then the paw withdrawal threshold (PWT) was detected using the Von Frey filament, prostate pathological examination was conducted, the expressions of substance P (SP) and transient receptor potential vanilloid 1 (TRPV1) in the prostate tissue and L5-S2 spinal segments were determined by immunohistochemistry and their correlations were analyzed.

RESULTSCompared with the control group, the CNP model rats showed markedly decreased PWT (P < 0.05) and obvious inflammation in the prostate tissue, with significant differences in the scope of lesion and interstitial lymphocyte infiltration (P < 0.05). The expressions of SP and TRPV1 in the prostate and spinal cord dorsal horn L5-S2 were remarkably upregulated in the models as compared with the control rats (P < 0.05). However, the expression of SP in the prostate was not correlated with that in the spinal cord (r = 0.099, P = 0.338), nor was that of TRPV1 (r = 0.000, P = 0.5).

CONCLUSIONSP and TRPV1 were involved in the formation and persistence of pain in CNP rats through their upregulated expressions in the L5-S2 spinal segments.

Animals ; Lumbosacral Region ; Male ; Neuralgia ; metabolism ; physiopathology ; Pain ; metabolism ; physiopathology ; Prostate ; metabolism ; Prostatitis ; metabolism ; physiopathology ; Rats ; Rats, Wistar ; Spinal Cord ; metabolism ; Substance P ; metabolism ; TRPV Cation Channels ; metabolism

Cytochrome P450 (CYP450) is a key element in the Ganoderma triterpenoid biosynthetic pathway. The catalytic reaction process for CYP450 requires NADPH / NADH for electron transfer. After searching the genome dataset of Ganoderma lucidum, the unique sequence encoding CYP450 and NADPH were discovered, separately. The open reading frames of GLCYP450 and GLNADPH were cloned separately using RT-PCR strategy from G lucidum. The appropriate restriction enzyme cutting sites were introduced at the 5' and 3' ends of gene sequence. The genes of GLCYP450 and GLNADPH were recombined into the yeast expression vector pESC-URA, leading to the formation of the yeast expression plasmid pESC-GLNADPH-GLCYP450. This study provides a foundation for researching Ganoderma triterpene biosynthesis using the approach of synthetic biology.

ObjectiveTo evaluate the changes in the expression of purinergic P2X4 receptor (P2X4R) in spinal cord dorsal horn and dorsal root ganglion in a rat model of acute morphine tolerance or inflammatory pain.MethodsThirty male SD rats were randomly divided into 3 groups:normal saline group (group NS,n =5);acute morphine tolerance group (group M,n =5) and inflammatory pain group (group F,n =20).Inflammatory pain was induced by subcutaneous injection of 4％ formalin 50 μl into the plantar surface of left hindpaw in group F.The animals received intrathecal morphine 10 μg ( 10 μl) once every 2 h for 6 times (T1-6) in group M,while the equal volume of normal saline was given instead in group NS.The rats were then sacrificed 2 h after the last time administration.Paw withdrawal latency (PWL) to a thermal nociceptive stimulus was measured at T1-6 in groups M and NS,or on day 4,7,10 and 14 after establishing the model of inflammatory pain in group F,The rats were sacrificed after measurement of PWL and spinal cord dorsal horn and dorsal root ganglion were removed to detect the expression of P2X4 R by immuno-histochemisty.ResultsCompared with the baseline value,PWL was significantly decreased on day 4-14 after intlammatory pain in group F,and PWL was significantly increased at T1-5,while no significant change was found at T6 in group M ( P ＞ 0.05).Compared with group NS,the expression of P2X4 R was up-regulated in group M,and the expression of P2X4 R was up-regulated on day 4 after inflammatory pain,peaked on day 7 after inflammatory pain,and then was down-regulated gradually on day 10 and 14 after inflammatory pain in group F ( P ＜ 0.01).ConclusionThe expression of purinergic P2Y4 R is up-regulated in spinal cord dorsal horn and dorsal root ganglion in rats with acute morphine tolerance or inflammatory pain,and the change may be related to the development of acute morphine tolerance or inflammatory pain.

Objective To evaluate the right ventricular function in patients with congestive heart failure (CHF) after cardiac resynchronization therapy (CRT) by 2-dimensional speckle imaging (2D-STI).Methods 46 patients with CHF were divided into responders to CRT and non-responders to CRT according the standard of a decline in LV end-systolic volume ≥ 10％.All the patients received echocardiography examination 1-3 days before CRT and 6 month after CRT.Tissue Doppler imaging (TDI) indices included SD of time to peak velocity in systole (Ts-SD) among 12 segments.Right ventricular diameters included RV basal transverse diameter (D1),RV middle transverse diameter (D2) and RV longitudinal diameter (D3) in apical four views.2D-STI indices included systolic strain (S) and stain rate (SR) of basal or middle segment of RV free wall.Results Compared with before CRT,LVEDd,LVEDV,LVESV and Ts-SD significantly decreased,LVEF significantly increased in responders 6 months after CRT.Before CRT,compared with nonresponders,there was no significant difference of D1,D2 and D3 in responders,while S and SR in basal or middle segment of RV free wall were higher than non-responders.Compared with before CRT,D1,D2 and D3 in responders decreased significantly,S and SR in basal or middle segment of RV free wall increased significantly,while there was no difference in non-responders.There were significant negative correlation between S and SR in basal or middle segment of RV free wall and Ts-SD in responders.Conclusions The remodeling and systolic function of RV are improved after CRT.It may help for improving the efficacy of CRT when takes RV function data into account before CRT.

Objective To investigate the changes of follicular regulatory T cells ( Tfr cells) and follicular T helper cells ( Tfh cells) in peripheral blood of children with myasthenia gravis ( MG) . Methods We recruited 28 MG patients and 20 healthy subjects in this study. The percentages of Tfh and Tfr cells in peripheral blood samples were measured by flow cytometry. Real-time PCR was performed to detect the ex-pression of transcription factors and regulatory factors of Bcl-6, c-MAF, Blimp-1 and PD-1 at mRNA level. ELISA was used to detect the levels of IL-2, IL-6, IL-10 and IL-21 in plasma samples and the titers of Ach-Rab and PsMab. Results Compared with the healthy subjects, the MG patients showed higher percentages of Tfh cells and lower percentages of Tfr cells before receiving treatment. The expression of Bcl-6 and c-MAF on CD4+T lymphocytes cells at transcriptional level were significantly enhanced, while the expression of Blimp-1 on CD4+T cells and the expression of PD-1 on Treg cells at transcriptional level were inhibited in the MG patients in comparison with those in healthy subjects. Moreover, decreased levels of IL-2 and increased levels of IL-21 were found in plasma samples collected from the MG patients. Conclusion The decreased percentages of Tfr cells and increased percentages of Tfh cells in patients with MG resulted in abnormal ratios of Tfr/Tfh cells, which might be involved in the immunological pathogenesis of MG. Several changes in the patients with MG might be responsible for the imbalanced ratio of Tfr/Tfh cells, which included changes of IL-2 and IL-21 in microenvironment, enhanced expression of Bcl-6 and c-MAF at mRNA level and inhibited expression of Blimp-1 at mRNA level on CD4+T cells as well as over-expression of PD-1 at mRNA level on Treg cells.

Objective To measure left atrial appendage (LAA)in patients with atrial fibrillation using Flexi Slice imaging by real time 3D transesophageal echocardiography (TEE),and compare with common multiplane TEE.Methods Forty-six patients with atrial fibrillation were performed 2D and real time 3D TEE.Zero degree,45°,90° and 135° plane were acquired by 2D TEE and Flexi Slice remolding. Maximum and minimum values of ostium of left atrial appendage were acquired in the short axis view of LAA by Flexi Slice remolding.Results Compared with 2D TEE,values acquire by Flexi Slice in measurement of LAA ostium showed no significant difference(P >0.05).The depth measurement by Flexi Slicein 45° and 90° plane showed significant difference with 2D TEE (P-values were successively 0.045, 0.002),and in 0 and 135° plane showed no difference.All values measured by 2D TEE and Flexi Slices showed significant correlation.Bland-Altman plot showed that 94.29% of plots were among limits of agreement,which was (-2.5 mm,2.9 mm).The maximum values of LAA ostium values ranged from 30° to 160°,among which 87% (40/46 cases)distributed between 90° and 1 50°,and minimum values ranged from 0°to 160°,among which 85%(39/46 cases)distributed between 0°and 60°.Conclusions Measurement of LAA can be well achieved by Flexi Slice imaging,which showed significant advantage compared with 2D TEE.

Objective To investigate DNA double-strand breaks and radiosensitization in renal carcinoma 786-O cells induced by fludarabine (FA) combined with different ionizing radiations.Methods The 786-O cells were exposed to FA combined with X-ray or heavy ion beam irradiation.Flow cytometry was used to evaluate the percentage of γH2AX-positive cells and cell cycle.The neutral comet assay was used to detect DNA double-strand breaks.The colony-forming assay was used to evaluate the effects of different treatments on cell survival.Comparison between groups was made by one-way analysis of variance or Dunnet' s t test.Results Compared with FA alone or irradiation alone,FA combined with different ionizing radiations increased DNA double-strand breaks as shown by significantly increased levels of γH2AX (P=0.007,0.001);FA combined with heavy ion beam irradiation lead to a cell cycle block at the radiosensitive G2/M phase and significantly increased the expression of γH2AX in the G2/M phase (P=0.000,0.000);the neutral comet assay revealed that FA combined with irradiation significantly increased DNA sublethal damage (P=0.020,0.060);FA significantly reduced the colony-forming rate after irradiation (P=0.000,0.030;0.001,0.040).Conclusions FA enhances the effects induced by X-ray and heavy ion beam irradiation with different properties.Particularly,FA substantially enhances the cell death induced by heavy ion beam irradiation.