ABSTRACT
Objective To explore the effect of exposure to noise of 3.0T magnetic resonance imaging(MRI)on children's cochlear function.Methods We prospectively recruited 72 children who underwent cranial MRI examination at our hospital from May to November 2018;3M earplugs and sponge mats were used for hearing protection during MRI scanning.Noise level(dBA)of each MRI sequence was detected with a nonmagnetic microphone and a sound level meter.Distortion product otoacoustic emissions(DPOAE)test at 2-7 kHz was performed 24 hours before and 30 minutes after the MRI examination.Paired t-test or Wilcoxon signed-rank test was used to analyze differences in DPOAE amplitude before and after the MRI examination.Results The average noise level of MRI measured in the study was(107.7±3.92)dBA.Compared with that before the MRI examination,the DPOAE amplitude(dB)changed little after the MRI examination;the range of amplitude differences in each age group was as follows:left ear(-0.24-1.10)and right ear(-0.24-0.74)in the 0-1 year-old group;left ear(-0.07-0.59)and right ear(-0.57-0.75)in the 2-5 year-old group;left ear(-0.36-0.44)and right ear(-0.30-0.57)in the 6-12 year-old group.No statistically significant difference was found(correction P＞0.05).Conclusion No potential impact of 3.0T MRI noise on children's cochlear function was observed under routine hearing protection.
ABSTRACT
ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg-1） and total alkaloids of C. saxicola group（210 mg·kg-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（tmax） and half-life（t1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC0-∞） of tetrahydropalmatine was the highest and the t1/2 was the shortest， and the AUC0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.
ABSTRACT
Immunotherapy is a new anti-tumor method. The application of immune checkpoint inhibitor greatly improves the survival benefit for patients, but the drug resistance of immunotherapy affects the efficacy. Therefore, it is very important to explore the mechanism of drug resistance and solve the problem of drug resis-tance in tumor immunotherapy. Hypoxia in tumor microenvironment is the key factor of immune drug resistance. Hypoxia can inhibit the immune cells function and lead to immune escape through various mechanisms. It can be the breakthrough for overcoming the immunotherapy drug resistance that blocking pathway of hypoxia to promote immune resistance. By reviewing the mechanism of immunotherapy drug resistance induced by hypoxia, it is helpful to explore the development prospect of hypoxia-inducible factor-1α (HIF-1α) related targeted drugs in clinical application for immunotherapy.