The effects of beta-cypermethrin (consisting of alpha-cypermethrin and theta-cypermethrin) on the transient outward potassium current (I(A)) and delayed rectifier potassium current (I(K)) in freshly dissociated hippocampal CA3 neurons of rats were studied using whole-cell patch-clamp technique. The results indicated that alpha-cypermethrin increased the value of I(A) and theta-cypermethrin decreased the value of I(A), though both of them shifted steady activation curve of I(A) towards negative potential. theta-cypermethrin contributed to the inactivation of I(A). The results also showed that alpha-cypermethrin and theta-cypermethrin decreased the value of I(K), and shifted the steady state activation curve of I(K) towards negative potential. Both alpha-cypermethrin and theta-cypermethrin had no obvious effects on the inactivation of I(K). theta-cypermethrin prolonged recovery process of I(K). These results imply that both transient outward potassium channels and delayed rectified potassium channels are the targets of beta-cypermethrin, which may explain the mechanism of toxical effects of beta-cypermethrin on mammalian neurons.
Animals ; CA3 Region, Hippocampal ; cytology ; physiology ; Cells, Cultured ; Female ; Insecticides ; toxicity ; Male ; Neurons ; cytology ; drug effects ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Voltage-Gated ; drug effects ; physiology ; Pyrethrins ; toxicity ; Rats ; Rats, Wistar

OBJECTIVETo investigate the relationship between genetic polymorphism in exon 12 C1236T, exon 21 G2677T/A and exon 26 C3435T of the multidrug resistance 1 (MDR1) gene and the risk of childhood acute lymphocytic leukemia (ALL).

METHODA total of 176 patients with ALL and a cohort of 170 matched healthy subjects were included. SNaPshot SNP typing was used to determine the genotypes of MDR1 C1236T, G2677T/A, C3435T. Based on the clinical data, the relationship between genetic polymorphism of MDR1 and the risk of childhood ALL was analyzed.

RESULTThere was significant difference in the distribution of genotype of MDR1 C3435T between the group of controls and cases. The mutant homozygous TT genotype was found to be associated with occurrence of ALL (P = 0.000; OR = 4.504). The data show evidence of pairwise linkage disequilibrium between the three common SNPs (C1236T-G2677T/A-C3435T). The haplotypes of TTT, TGC, CGC and CAC were predominant. The haplotype CGT distributed significantly differently between the groups of controls and cases (P = 0.034). The frequency of the haplotype TTT/TTT in the high risk group was higher than the other groups (P = 0.037).

CONCLUSIONThe present findings suggest that 3435C→T polymorphism in MDR1 gene may be a genetic susceptibility factor for ALL. The haplotype of MDR1 (C1236T-G2677T/A-C3435T) could be the clinical parameter at diagnosis.

ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Acute Disease ; Asian Continental Ancestry Group ; genetics ; Child, Preschool ; China ; ethnology ; Exons ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Infant ; Linkage Disequilibrium ; Male ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Risk Factors

AIM:To investigate the role of microRNA (miR)-199a-5p in myocardial fibrosis and the potential target of miR-199a-5p.METHODS:C57BL/6 mouse cardiac fibroblasts were isolated and cultured for cellular experimen-tal study.Dual-luciferase reporter assay was performed to confirm the interaction between miR-199a-5p and the 3'-untrans-lated region (3'-UTR) of silent information regulator 1 (SIRT1).The expression of SIRT1 and fibrosis markers collagen (Col) 1a1, Col3a1 and α-smooth muscle actin (α-SMA) at mRNA and protein levels was determined by RT-qPCR and Western blot, respectively.RESULTS:The expression levels of miR-199a-5p, Col1a1, Col3a1 andα-SMA were marked-ly increased in cardiac fibroblasts after treatment with angiotensin Ⅱ(AngⅡ).The over-expression of miR-199a-5p signif-icantly increased the expression of Col1a1, Col3a1 andα-SMA in cardiac fibroblasts.Moreover, the results of dual-lucifer-ase reporter assay revealed that miR-199a-5p interacted with the 3'-UTR of SIRT1.miR-199a-5p inhibited SIRT1 expres-sion at post-transcriptional level.Meanwhile, miR-199a-5p mimic, in parallel to SIRT1 siRNA, inhibited SIRT1 expres-sion, increased the expression of Col1a1, Col3a1 and α-SMA in cardiac fibroblasts.Inactivation of NF-κB signaling con-tributed to the decrease in miR-199a-5p in Ang II-treated cardiac fibroblasts .CONCLUSION:SIRT1 is a target gene of miR-199a-5p, which mediates the pro-fibrotic effect of miR-199a-5p on cardiac fibroblasts .

OBJECTIVETo examine the effect of the zedoary essential component-eluting stent (ZES) on a porcine coronary neointimal formation.

METHODSZES, sirolimus-eluting stents (SES), and bare metal stents (BMS) were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperplasia effects.

RESULTSZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES (P<0.05). Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69 ± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups (both were 3.00 ± 0.00 at either 30 or 90 days, P<0.05). Well developed endothelium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group.

CONCLUSIONThe ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.

Animals ; Coated Materials, Biocompatible ; pharmacology ; Coronary Stenosis ; pathology ; Coronary Vessels ; drug effects ; pathology ; Curcuma ; chemistry ; Endothelium, Vascular ; drug effects ; pathology ; Inflammation ; pathology ; Microscopy, Electron, Scanning ; Neointima ; pathology ; Prosthesis Implantation ; Stents ; Sus scrofa ; Time Factors

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Apoptosis ; Cell Differentiation ; Cell Line, Tumor ; Humans ; Leukemia, Promyelocytic, Acute ; RNA, Long Noncoding ; Tretinoin

OBJECTIVETo evaluate the prognosis effect of Chinese herbal medicines (CHMs) for benefiting qi and activating blood circulation adjunctive to conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).

METHODSA total of 702 patients with ACS who underwent PCI were enrolled and randomly assigned to receive conventional treatment plus CHMs for benefiting qi and activating blood circulation (treatment group, 351 cases) or conventional treatment alone (control group, 351 cases) for 6 months. Six months later, all patients received conventional treatment alone. Follow-ups were scheduled at 6th, 12th, 18th, 24th month after enrollment in April 2008, and the final follow-up visit was during September 2011 and November 2011. The primary endpoint was the composite of cardiac death, nonfatal myocardial infarction or revascularization (PCI or coronary artery bypass grafting); and the secondary endpoint was the composite of re-admission for ACS, congestive heart failure, nonfatal stroke or other thrombus events.

RESULTSA total of 621 (88.59%) patients completed 35.4±3.8 months follow-up, while 80 (11.41%) patients withdrew from the trial (41 in the treatment group and 39 in the control group). The incidence of primary endpoint was 5.7% (20 patients) in the treatment group versus 10.86% (38 patients) in the control group [relative risk (RR): 0.53; 95% confidence interval (CI): 0.30, 0.88; P=0.013; absolute risk reduction (ARR):-0.052, 95% CI: -0.06, 0.01]. The incidence of secondary endpoint was 5.98% (21 patients) in the treatment group versus 10.28% (36 patients) in control group (RR: 0.58, 95% CI: 0.33, 0.97, P=0.037; ARR: -0.043, 95% CI: 0.06, 0.01). Most of the primary and secondary endpoints were occurred in 18 months (84.50% in the treatment group versus 78.10% in the control group).

CONCLUSIONCHMs for benefiting qi and activating blood circulation adjunctive to conventional treatment improved clinical outcomes for patients with ACS after PCI in long-term follow-up.

OBJECTIVE: To analyze the clinical effects of CCLG-AML-2015 protocol on newly diagnosed children with acute myeloid leukemia (AML). METHODS: The clinical data of 60 newly diagnosed AML children in the Department of Hematology and Oncology, Wuhan Children's Hospital from August 2015 to September 2019 were summarized, the effect of chemotherapy using the CCLG-AML-2015 regimen (hereinafter referred to as the 2015 regimen) were retrospectively analyzed. 42 children with AML treated by the AML-2006 regimen (hereinafter referred to as the 2006 regimen) from February 2010 to July 2015 were used as control group. RESULTS: There were no statistical differences between the 2015 regimen group and the 2006 regimen group in sex, age at first diagnosis, and risk stratification (P>0.05). The complete remission rate of bone marrow cytology after induction of 1 course of chemotherapy (84.7% vs 73.1%, P=0.155), and minimal residual disease detection (MRD) negative (42.3% vs 41.4%, P=0.928) in the 2015 regimen group were not statistically different than those in the 2006 regimen group. The bone marrow cytology CR (98.1% vs 80.6%, P=0.004) and MRD negative (83.3% vs 52.8%, P=0.002) in the 2015 regimen group after 2 courses of induction were higher than those in the 2006 regimen group. The 5-year overall survival (OS) rate in the 2015 regimen group (62.3%±6.4% vs 20.6%±6.4%, P=0.001), the 5-year disease-free survival (EFS) rate (61.0%±6.4% vs 21.0% ±6.4% , P=0.001) were better than those in the 2006 regimen group. The 5-year OS and EFS of high-risk transplant patients in the 2015 regimen group were significantly better than those of high-risk non-transplant patients (OS: 86.6%±9.0% vs 26.7%±11.4%, P=0.000; EFS: 86.6%±9% vs 26.7%±11.4%, P=0.000). CONCLUSION The 2015 regimen can increase the CR rate after 2 courses of induction compared with the 2006 regimen. High-risk children receiving hematopoietic stem cell transplantation can significantly improve the prognosis.
Child ; Disease-Free Survival ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Prognosis ; Remission Induction ; Retrospective Studies