In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.

Aim To design and synthesize new phenyloxyisobutyric acid analogues as antidiabetic compounds. Methods Eight new target compounds were synthesized by combination of lipophilic moieties and acidic moiety with nucleophilic replacement or Mitsunobu condensation. The eight compounds were confirmed by 1H NMR, 13C NMR, IR and MS. Results In vitro insulin-sensitizing activity (3T3-L1adipocyte) demonstrated, that the cultured glucose concentration of up-clear solution detected with GODpioglitazone, compounds A and B were added to the insulin-resistant system. Conclusion In vitro insulin-sensitizing activity of target compound A is in between that of rosiglitazone and pioglitazone, and activity of target compound B is slightly less than that of pioglitazone.

Objective To evaluate the effect of TGF-β1 and IL-1β expression in serum on acute radiation-induced heart disease (RIHD) in patients with thoracic tumors.Methods Three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiotherapy (IMRT) was delivered at 1.8-2.0 Gy,5 times per week to a total dose of 50-66 Gy to 44 patients with lung cancer and 10 patients with esophagus cancer.The target and organs at risk dose distribution were analyzed by 3-dimensiond treatment planning system.The expressions of TGF-β1 and IL-1β in serum were detected by enzyme linked immunosorbent assay before and at the end of the irradiation.The cardiac injury was evaluated by detecting the cmyocardium creatase,cardiac troponin I (cTnI),electrocardiogram and cardiac function before and at the end of the irradiation within 90 d.The acute RIHD was evaluated by the Common Terminology Criteria V 3.0 (NCI-CTCAE 3.0).The expressions of TGF-β1 and IL-1β in the serum of RIHD patients with thoracic tumors were analyzed.Results The expression of TGF-β1 in serum was (888.4 ± 41.1) μg/L before the irradiation and approached to (926.1 ± 23.1) μg/L at the end of the radiotherapy.The expression level of TGF-β1 in the serum of acute RIDH group was (900.6 ± 34.5) μg/L,higher than that of normal group [(865.7 ±47.0) μg/L,t =-2.646,P ＜0.05)].The acute RIDH was correlated with the expression level of TGF-β1 before irradiation and the difference before and at the end of irradiation (r =0.378,0.311,P ＜0.05).The IL-1β expression had no significant difference before and after irradiation.The expression of TGF-β1 in serum before and at the end of irradiation had positive correlation with the expression of IL-1β at the end of the irradiation (r =0.416,0.389,P ＜ 0.05).Conclusions The expression of TGF-β1 in the serum of patients with thoracic tumor increases after irradiation and correlated with the acute RIHD,but the expression of IL-1β in serum has no relationship with RIHD.TGF-β1 could induce the expression of IL-1β at the end of the irradiation.

Objective To examine the expression of MMP-2 gene and Survivin gene in subclinical microscopic tumor and its peripheral normal esophageal tissues,and study the radiation target in molecular level. Methods Esophageal squamous cancer and its peripheral tissue samples of 34 patients were cut into sequential sections.The expression of MMP-2 gene and Survivin gene then examined.The length of the peripheral esophageal tissue,positively expressing the two genes,was measured,and the relation among the experimental date,tumor stage and vertical length of tumor were analyzed. Results For tumor tissue,subclinical microscopic tumor and the peripheral differentiated normal tissue,the positive expression rate of MMP-2 was 85%,83%and 79%,respectively.The positive expression rate of Survivin was 76%,85%and 85%,respectively.The positive expression level of both MMP-2 and Survivin genes in subclinical microscopic tumor was significantly higher than that in the peripheral differentiated normal tissue(χ2=6.46,P=0.028 and χ2=16.15,P=0.001).The length was 17.2-70.4 mm and 15.0-82.4 mm of cancerous peripheral tissue with positive expression of MMP-2 gene upside and downside of the tumor.The length was＜70 mm in 97% of the samples.For Survivin gene.the length was 3.7-76.4 mm and 16.1-56.3 mm.and was＜70 mm in 96%of the samples.The length of cancerous peripheral esophageal tissue expressing the two genes increased significantly along with tumor stage or tumor length,and there was statistical correlation between the length of tumor and the positive expression ranges of Survivin gene. Conclusions Both MMP-2 gene and Survivin gene are positively expressed in esophageal cancerous peripheral tissue.The range positively expressing the two genes is＜70 mm in more than 96%of the samples,and the length is correlated with the tumor stage.More attention should be paid to the peripheral differentiated normal tissue with positive expression of MMP-2 gene and Survivin gene in esophageal squamous carcinoma.

Objective To assess the clinical effect of lumboperitoneal shunting (LPS) on communicating hydrocephalus.Methods An retrospectively study was conducted on communicating hydrocephalus patients who were hospitalized from Sep.2009 and Dec.2013 at the No.174th Hospital of Chinese People's Liberation Army.All patients were underwent the LPS.All patients were with difference degrees of coma,and lumbar punctured for continued cerebrospinal fluid extended drainage before LPS.The change of disturbance of consciousness and the complications of LPS were assessed.Results There were 12 patients with communicating hydrocephalus.Of them,7 cases were underwent routine lumboperitoneal shunts,and 5 cases were experienced adjustment valve.After the LPS operation,3 patients were awakened from the coma,and 8 patients were improved in terms of consciousness and the decompression pressure of skull window as well as decreased enlarged lateral ventricles in pre-operation by CT.As for another 1 patient,the lumboperitoneal catheter had been slipped into the peritoneal cavity after 2 months of operation.There were no complications of infection,intracranial hemorrhages,obstruction of catheter and epilepsy.Conclusion The LPS should be the first selection of those patients who suffered from communicating hydrocephalus without trouble in spine and abdomen.A positive response to pre-operative continuing cerebrospinal fluid extend drainage is good prediction factor for surgical results of LPS.

Objective To explore the value of afterdischarges monitoring for intraoperative electrical stimulation for brain mapping. Methods 34 patients received cerebral cortex electrical stimulation for brain mapping during operation of brain function area , afterdischarges were monitored simultaneously to determine the upper limit of stimulus intensity. Results 34 cases underwent electrical stimulation successfully , and received surgery without neurologic decline except 2 cases of hypokinesia. Conclusion After discharges monitoring improve the accuracy, reduce the risk of intraoperative cerebral cortex electrical stimulation.

Objective To validate and compare the pyramidal tracts traced by functional magnetic resonance mo?tion activated area as the region of interest method (fMRI guided DTI-FT) and by the anatomy of primary motor cortex as region of interest method(traditional DTI-FT)using subcortical electrical stimulation (DsCS). Methods A prospective study was conducted in 12 cases of patients with central lesions involving the motor area. The pyramidal tracts were traced by fMRI guided DTI-FT method and traditional DTI-FT method. The lesions were resected with the assistance of neuronavigation. The distances between same stimulation positive point and pyramidal tracts traced by the fMRI DTI-FT or traditional DTI-FT were recorded. The coincidence rates between pyramidal tract imaging and DsCS were analyzed in order to verify the accuracy and reliability of these two methods. Results Two cases were excluded:one due to the failure of the fMRI activation caused by movement dysfunction and one case due to negative electrical stimulation.,The pyrami?dal tracts were successfully reconstructed in the rest 10 patients using these two methods which were further applied to assist surgery. The coincidence rates between DsCS and pyramidal tracts were 77%in fMRI DTI-FT and 70%in tradition?al DTI-FT. The shortest distances were 4.3mm±2.8mm and 5.5mm±3.4mm in fMRI DTI-FT and in traditional DTI-FT in 16 DsCS positive sites and the difference was statistically significant (P<0.05). Five cases had temporary postoperative pa?ralysis. Among them, four cases had upper limb paralysis and one case had hemiplegia. The motor function was improved in four cases and remained unchanged in two cases two weeks after the operation. The motor function in the rest six cases did not have any change before and after operation. Conclusion The fMRI guided DTI-FT can be helpful to deal with le?sions and effectively protect the brain function area in patients with the central area lesions involved motor area.

Objective To investigate the clinical effect of induction chemotherapy plus concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer (NSCLC) through a meta-analysis.Methods CBM, CNKI, Cochrane Library, PubMed, and EMbase were searched for the articles on comparison between induction chemotherapy plus concurrent radiochemotherapy and concurrent radiochemotherapy for patients with locally advanced NSCLC.According to the inclusion and exclusion criteria, the data on short-term outcome and survival were collected.A Meta-analysis was performed to evaluate the clinical effect of induction chemotherapy followed by concurrent radiochemotherapy.Results A total of 5 articles were included, which involved 845 patients.The results showed that the short-term outcome and the 2-and 3-year survival rates were similar between patients receiving induction chemotherapy plus concurrent radiochemotherapy and those receiving concurrent radiochemotherapy ( OR=0.875, 95% CI 0.507-1.510, P=0.631;HR=0.770, 95% CI 0.515-1.151, P=0.203;HR=0.809, 95% CI 0.559-1.172, P=0.262), but the patients receiving induction chemotherapy plus concurrent radiochemotherapy showed a significantly higher incidence rate of grade ≥ 3 leukopenia than those receiving concurrent radiochemotherapy alone ( OR=0.637, 95% CI 0.435-0.931, P=0.020).Conclusions Induction chemotherapy plus concurrent radiochemotherapy shows no significant advantages over concurrent radiochemotherapy alone in the short-term outcome and 2-and 3-year survival rates, but it significantly increases myelosuppression.Since there are few studies involving a limited number of cases included in this analysis, more multicenter randomized trials are needed to provide more detailed data and further clarify the clinical value of induction chemotherapy plus concurrent radiochemotherapy.

OBJECTIVETo investigate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in the salvage therapy for the grade IV neutropenia induced by concurrent chemoradiotherapy, and to provide evidence for its clinical rational application.

METHODS114 malignant tumor patients suffered with grade IV neutropenia induced by concurrent chemoradiotherapy were treated in the following groups. In the P-50 group, 42 patients received a single subcutaneous injection of 50 µg/kg PEG-rhG-CSF. In the P-100 group, 30 patients received a single subcutaneous injection of 100 µg/kg PEG-rhG-CSF. In the P+R group, 22 patients received a single subcutaneous injection of 50 µg/kg PEG-rhG-CSF and multiple subcutaneous injections of 5 µg×kg(-1)×d(-1) rhG-CSF, until the absolute neutrophil count (ANC) ≥ 2.0×10(9)/L. In the R group, 20 patients received multiple subcutaneous injections of 5 µg×kg(-1)×d(-1) rhG-CSF, until ANC ≥ 2.0×10(9)/L. The P-50, P-100 and P+R groups were experimental groups, and the R group was defined as control group. In each group, the neutrophil proliferation rate and the neutrophil counts at different time points, the period of neutropenia symptom relief, and the rate of adverse reactions induced by above drugs were analyzed.

RESULTSBoth neutrophil proliferation rates and neutrophil counts in the patients of experimental groups at different time points were significantly higher than those in the control group. In the experimental groups the period of the clinical effect began in 12-24 hours, and the conditions of neutropenia were improved in 36 hours. In the experimental groups, the period of the symptom relief such as fever and skeletal muscle pain was (30.00 ± 7.48) hours and (30.00 ± 5.10) hours, respectively, significantly shorter than (72.00 ± 17.89) hours and (59.00 ± 11.46) hours in the control group (P < 0.05). The adverse drug reaction rate was 26.1% in the experimental groups and 25.0% in the control group (P > 0.05).

CONCLUSIONSFor the treatment of grade IV neutropenia induced by concurrent chemoradiotherapy, PEG-rhG-CSF is effective and safe. The recommend dose of this drug for the salvage therapy for those patients is a single hypodermal injection of 50 µg/kg. Usually it becomes effective in 12-24 hours.

Chemoradiotherapy ; Granulocyte Colony-Stimulating Factor ; genetics ; metabolism ; Humans ; Injections, Subcutaneous ; Leukocyte Count ; Neutropenia ; chemically induced ; Neutrophils ; Recombinant Proteins ; Salvage Therapy ; methods

BACKGROUNDThe molecular and cellular origins of migraine headache are among the most complex problems in contemporary neurology. Up to now the pathogenesis of migraine still remains unclearly defined. The objective of this study was to explore new factors that may be related to the mechanism of migraine.

METHODSThe present study performed a comprehensive analysis of gene expression in the trigeminal nucleus caudalis induced by electrical stimulation of dura mater surrounding the superior sagittal sinus in conscious rats using microarray analysis followed by quantitative real-time reverse-transcribed polymerase chain reaction (qRT-PCR) verification. Student's two sample t-test was employed when two groups were compared. A P value <0.05 was considered to be statistically significant.

RESULTSComparing the placebo and the electrical stimulation groups, 40 genes were determined to be significantly differentially expressed. These significantly differentially expressed genes were involved in many pathways, including transporter activity, tryptophan metabolism, G protein signaling, kinase activity, actin binding, signal transducer activity, anion transport, protein folding, enzyme inhibitor activity, coenzyme metabolism, binding, ion transport, cell adhesion, metal ion transport, oxidoreductase activity, mitochondrion function, and others. Most of the genes were involved in more than 2 pathways. Of particular interest is the up-regulation of Phactr3 and Akap5 and the down-regulation of Kdr.

CONCLUSIONThese findings may provide important clues for a better understanding of the molecular mechanism of migraine.

Animals ; Dura Mater ; physiology ; Electric Stimulation ; Gene Expression ; physiology ; Male ; Microarray Analysis ; Migraine Disorders ; genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Superior Sagittal Sinus ; physiology