RÉSUMÉ
Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofission-associated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of pan-inhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.
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OBJECTIVE@#To assess the effect and safety of bloodletting puncture at hand twelve Jing-Well points (HTWPs) in acute stroke patients with conscious disturbance.@*METHODS@#In this multi-center and randomized controlled trial, 360 patients suffered from ischemic or hemorrhagic stroke with conscious disturbance within 48 h from the onset of symptom were divided into bloodletting (180 cases) and control (180 cases) groups using a block randomization. Patients in both groups received routine Western medicine, and patients in the bloodletting group received additional bloodletting puncture at HTWPs on admission immediately before conventional treatment. The primary outcome measure was Glasgow Coma Scale (GCS) score and the secondary outcomes included blood pressure, respiratory rate and pulse rate. All variables were evaluated at baseline (before bloodletting), 0 (after bloodletting immediately), 15, 30, 50 and 80 min post bloodletting.@*RESULTS@#At 80 min post bloodletting, the proportion of patients with improved consciousness in the bloodletting group was greater than the control group (P0.05).@*CONCLUSION@#The bloodletting puncture at HTWPs was safe and could improve conscious levels of ischemic stroke patients, highlighting a first-aid intervention for acute stroke. (Registration No. ChiCTR-INR-16009530).
RÉSUMÉ
Objective To explore the relationship between gene polymorphism of neuropeptide Y (NPY) promoter and cerebral stroke subtypes according to TOAST (Trail of ORG 10172 in Acute Stroke Treatment) criteria in Chinese Han population. Methods The gene polymorphisms at position of-399T/C, -883Tgins/del and -602G/T in NPY promoter were detected by PCR method and gene sequencing in 190 cases of large-artery atherosclerosis stroke (LAA), 260 cases of small-artery occlusion (SAO), 60 cases of cardioembolism stroke (CE), 29 cases of stroke of other demonstrated etiology (ODE),10 cases of stroke of other undemonstrated etiology (UE) and 423 healthy control subjects. The PCR products were directly sequenced. Multivariate logistic regression was performed to analyze the relationship between gene polymorphism of NPY promoter and cerebral stroke subtypes according to TOAST by removing the confounding variables. Results Significant differences in the frequency of genotype CC and allele C at position of-399T/C were noted between the patients with SAO and controls (P=0.046, P=0.010). Compared with the control group, patients with LAA and SAO were more likely having high level of uric acid, hypertension, diabetes mellitus and heard disease (P＜0.05). No statistic differences in the frequency of genotype DD and allele D at position of-883Tgins/del were noted between patients with SAO and controls (P=0.0605, P=0.155). Gene polymorphisms of-399T/C,-883Tgins/del and -602G/T did not associate with an increased risk of having LAA, CE, ODE and UE.Conclusions The gene polymorphisms of promoter in position of-399T/C gene maybe associate with the happening of SAO; allele C at the position of-399T/C may raise the risk of the disease. There is no relationship between the gene polymorphisms of promoter at position of-399T/C, -883Tgins/del, -602G/T and the patients with LAA, CE, ODE and UE. High level of uric acid, hypertension, diabetes mellitus and heard disease history are the risk factors of LAA and SAO.
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Moving cup of cupping therapy is studied in the present paper systematically. According to the experiences of clinical practice, duration, speed and intensity of moving cup has been quantified. Fifteen basic manipulations have been evolved, and 10 protocols for clinical application recommended. "Moving cup according to 3 factors of duration, speed and intensity" has been advanced on the basis of acupuncture therapy. And it has been concluded that the effects of warming needling, simple cupping, scraping, massage and medication can be achieved by moving cup with different techniques and clinical protocols.