Itch is an unpleasant sensation that urges people and animals to scratch. Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions, including the insular lobe. However, the role and functional specificity of the insular cortex (IC) and its subdivisions in itch mediation remains unclear. Here, we demonstrated by immunohistochemistry and fiber photometry tests, that neurons in both the anterior insular cortex (AIC) and the posterior insular cortex (PIC) are activated during acute itch processes. Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons, or selective inhibition of the activity of glutaminergic neurons in the AIC, reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine (5-HT), but not those induced by compound 48/80. However, both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80. In addition, pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior, and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching. These findings provide preliminary evidence that the AIC is involved, at least partially via aversive emotion mediation, in the regulation of 5-HT-, but not compound 48/80-induced itch.
Humans ; Animals ; Serotonin ; Insular Cortex ; Pruritus/chemically induced* ; Cerebral Cortex/physiology* ; Neurons

Humans ; Melphalan/therapeutic use* ; Multiple Myeloma/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Transplantation Conditioning

PURPOSE: Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. MATERIALS AND METHODS: Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg.kg-1.d-1) and high-dose darapladib (50 mg.kg-1.d-1) interventions were then administered over the course of 2 weeks. RESULTS: The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p<0.05 vs. sham group), whereas nitric oxide (NO) production was reduced. Levels of TC, LDL-C, CRP, Lp-PLA2, and Rho kinase activity were respectively reduced in darapladib groups, whereas NO production was enhanced. When compared to the low-dose darapladib group, the reduction of the levels of TC, LDL-C, CRP, and Lp-PLA2 was more prominent in the high-dose darapladib group (p<0.05), and the increase of NO production was more prominent (p<0.05). Cardiomyocyte apoptosis of the high-dose darapladib group was also significantly reduced compared to the low-dose darapladib group (p<0.05). However, there was no significant difference in Rho kinase activity between the low-dose darapladib group and the high-dose darapladib group (p>0.05). CONCLUSION: Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.
1-Alkyl-2-acetylglycerophosphocholine Esterase/*antagonists & inhibitors/blood/drug effects ; Animals ; Atherosclerosis/blood/*drug therapy/*enzymology ; *Benzaldehydes ; C-Reactive Protein/metabolism ; Cholesterol/blood ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Dose-Response Relationship, Drug ; Male ; *Oximes ; Phospholipase A2 Inhibitors/*administration & dosage/adverse effects ; Rats ; Rats, Sprague-Dawley ; Triglycerides/blood ; rho-Associated Kinases/*metabolism

OBJECTIVETo investigate whether sodium valproate (VPA) directly regulates the activity of Ankyrin G(AnkG) promoter in vitro.

METHODSThe mouse AnkG promoter sequence was identified by comparing both human and mouse AnkG promoter sequences. The promoter was amplified from C57BL/6 mouse genome DNA and cloned into pGL3 Luciferase reporter vector. The Luciferase activity was detected in N2a and 293T cells and then treated with 0,0.5, and 1 mmol/L VPA for 12 h. The transcription activity of AnkG promoter in cells and the activity of VPA-treated Luciferase reporter vector in cells were detected using dual Luciferase reporter assay.

RESULTSThe AnkG promoter clone and its expression vector were successfully established, as confirmed by enzyme digestion and sequencing. The AnkG promoter showed high transcription activity in both N2a and 293T cells. The Luciferase activity was significantly induced following 0.5 mmol/L VPA treatment in both N2a and 293T cells. CONCLUSIONS VPA can up-regulate the AnkG expression via directly increasing its transcription activity. Thus, the in vivo AnkG expression may be directly regulated by the VPA at transcriptional level.

Animals ; Ankyrins ; Cell Line ; Genetic Vectors ; Humans ; Luciferases ; Mice ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; Up-Regulation ; Valproic Acid

BACKGROUNDCurrently available evidence suggests that outcomes are less favorable when left main (LM) bifurcation lesions are treated with 2-stent techniques compared with a single-stent technique. We aimed to evaluate the long-term outcomes of the 2-stent techniques for treating unprotected LM bifurcation lesions in Chinese patients.

METHODSWe enrolled 301 consecutive patients treated with drug-eluting stents (DES) implantation using 2-stent techniques for unprotected LM bifurcation lesions (MEDINA 1, 1, 1, 70.5%). The 2-stent techniques included crush technique, V stenting, T stenting, and Culottes stenting. After stenting, both vessels were redilated at a high pressure before final kissing balloon (FKB). Clinical and angiographic data were analyzed. The primary endpoints were major adverse cardiac events (MACE), which included death, myocardial infarction, and target lesion revascularization.

RESULTSImmediate procedural success was obtained in all cases with a FKB success rate of 95.3%. Follow-up data were available for all patients. The overall incidence of angiographic in-stent restenosis (ISR) rate was 20.3% and most ISRs were of the focal type. During long-term follow-up (mean duration, (54 ± 22) months), the cumulative incidence of MACE was 11.0%, with 8 (2.7%) deaths, 7 (2.3%) myocardial infarctions, and 18 (6.0%) repeated lesion revascularization. MACEs in high SYNTAX score terciles were significantly higher compared with those in low and intermediate SYNTAX score terciles (P = 0.001).

CONCLUSIONSAlthough percutaneous coronary intervention (PCI) with 2-stent technique for unprotected LM bifurcation lesions was accompanied with a slightly high incidence of ISR, the long-term clinical follow-up is acceptable. Technical modifications and stent innovations may further improve both the angiographic and clinical outcomes for patients with LM bifurcation disease treated by PCI.

Adult ; Aged ; Aged, 80 and over ; Coronary Artery Disease ; mortality ; therapy ; Coronary Restenosis ; epidemiology ; Drug-Eluting Stents ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; adverse effects ; methods ; Time Factors ; Treatment Outcome

This study was aimed to evaluate the prognostic value of serum IL-6 (sIL-6) in patients with multiple myeloma (MM). The sIL-6 level in 288 patients with MM was retrospectively analyzed, and the clinical characteristics and prognosis in patients with different IL-6 level were compared. The newly diagnosed patients with MM were divided into two groups: the low sIL-6 group (sIL-6 < 100 pg/ml) and the high sIL-6 group (sIL-6 ≥ 100 pg/ml). The results showed that high sIL-6 level was more common in patients with ECOG score>3, myeloma bone disease (MBD) between grade 2 to 4, and high creatinine level. There was no significant differences in age, abnormal karyotype percentage, chromosome 13q14 abnormality percentage, CD138(+)/CD38(+) cells percentage and the level of calcium, phosphorus, albumin, C-reactive protein, β2-MG, lactate dehydrogenase, hemoglobin, platelet between the two groups at diagnosis, and also no significant difference in response to initial induction chemotherapy among the two groups. The overall survival was significantly different between the low and high IL-6 groups (P = 0.04, 35 m vs 29 m), but no difference in time to progress between the two groups (P = 1.93, 23 m vs 14 m). It is concluded that the sIL-6 level correlates with the clinical characteristics and prognosis. Radioimmunoassay is an appropriate measurement for human IL-6 in serum, and suitable for clinical application.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Multiple Myeloma ; blood ; diagnosis ; Prognosis ; Retrospective Studies

Objective To provide insights into the evaluation index and evaluation methods of clinical thinking of nursing staff.Methods 14 nursing experts in Heilongjiang province were interviewed by a halfstructured in-depth outline with 8 questions.Themes were obtained by phenomenological data analysis method,including coding,classification,explanation of phenomena and significance,refining essence and elements.Results Two themes of evaluation approach of clinical thinking of nursing staff was obtained:evaluation index and evaluation method.Basic theoretical knowledge,basic practical skills,strain capacity,communication ability,originality of thinking and critical thinking are subthemes of the evaluation index.The best way of evaluating methods is combining multiple evaluations.Conclusions Cultivation of clinical thinking of nursing staff requires efforts from schools and hospitals to establish a scientific,rigorous evaluation approach.

OBJECTIVETo evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study.

METHODSA total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance.

RESULTSAmong the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h.

CONCLUSIONSAs2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Carcinoma, Hepatocellular ; blood ; drug therapy ; pathology ; Disease Progression ; Female ; Follow-Up Studies ; Half-Life ; Humans ; Injections ; Leukopenia ; chemically induced ; Liver Neoplasms ; blood ; drug therapy ; pathology ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Oxides ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Quality of Life ; Remission Induction ; Survival Rate ; Vomiting ; chemically induced

Objective To construct the nursing undergraduate training model based on TPN, and to apply it in teaching through theoretical teaching, practical teaching, and the second class. Methods The model was constructed on the basis of fundamental theory of undergraduate training in higher education system, with experience from home and abroad, and combined with the actual situation in our college. Results Construction of nursing undergraduate training model of TPN and its application made the students' quality improved, 100% employment rate maintained and fair praises by employers raised steadily. Conclusions TPN training model,consistent with the actual situation in our college, has a good practicality, and provides a proper model for cultivating nursing talents.

Objective To analyze the application of objective structured clinical examination (OSCE) in graduation examination of nursing undergraduate students to promote exam reform. Methods Multistation OSCE was carried out among 110 nursing undergraduate students of Grade 2006 in our school at the end of graduation practice, and the results were analyzed. Results Fine reliability and validity was found of OSCE. Authentic performance of the students was reflected. Conclusions OSCE is a scientific and effective evaluation of clinical nursing ability among nursing undergraduate students.