Background: Epimedii Folium(EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI.Methods: Mouse were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo.Results: Icariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mice model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation.Conclusions: Our study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI.

Introduction: Anti-inflammatory medications, in particular aspirin, have chemopreventive and anticancer adjuvant effects on specific types of cancers, according to ongoing anti-tumor research. Additionally, efforts have been made to transform Poly(salicylic acid) (PSA) into delivery-related nanocarriers. to transport anticancer medications into nanocarriers. However, tumor cell targeting and tumor selectivity were lacking in the salicylic acid polymer-based nanocarriers, preventing them from performing to their full potential. Objective: The objective of this study is to prepare targeting and reduction-responsive poly pre-drug nanocarriers (HA-ss-PSA NPs) and to investigate the feasibility of delivering adriamycin (DOX) as nanocarriers. Method: The structures of the polymers were confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H-NMR) and infrared spectroscopy (IR); the encapsulation rate and drug loading of DOX-loaded nanoparticles were determined by HPLC; and the anti-tumor effects of the carriers were evaluated by MTT experiments and in vivo experiments. Results: The prepared nanocarriers had uniform particle size distribution. The drug release rate was up to 80% within 48 h in the tumor environment. DOX/HA-ss-PSA NPs showed significant cytostatic effects. In addition, HA-ss-PSA NPs showed significant targeting and inhibition of cell migration in cell uptake and scratch assays. In vivo experiments showed that the prepared carriers had high tumor inhibition rates, good targeting effects on the liver and tumor, and significantly reduced toxicity to other tissues. Conclusion: The prepared HA-ss-PSA NPs could effectively inhibit the growth of HepG2 cells and tumors in vivo, indicating that PSA could be used as a backbone component of a safe and reliable drug delivery system, providing a new strategy for the treatment of liver cancer.

Objective: To explore the audiological characteristics of infant auditory neuropathy (AN) patients with cochlear microphonic (CM) recorded but absent otoacoustic emission (OAE), clinically reducing the rate of missed diagnosis of AN. Methods:We retrospectively analyzed the audiological characteristics of infant AN patients in our medical center between 2003 and 2020. A total of 18 infant AN patients were OAE absent group, with CM present and distortion product otoacoustic emission (DPOAE) absent in both ears. A total of 44 infant AN patients were OAE present group, with CM and DPOAE present in both ears.Results: (1) The found age in OAE absent group was 0.9 (0.02) years old, which was younger than 1.11 (1.63) years old in OAE present group (p = .041). (2) The CM threshold of OAE absent group was 80 (10) dB nHL, which was significantly higher (p < .001) than OAE present group. CM amplitude were smaller (p < .05), and CM duration were shorter (p < .05) in OAE absent group. (3) The thresholds of auditory steady-state response (ASSR) at 0.5, 1, 2, and 4 kHz were 94 (10), 94 (10), 87 (20), and 81 (10) dB HL cg, respectively in OAE absent group, which were higher than those in OAE present group (p < .01).Conclusions: Infant AN patients with CM present and OAE absent showed earlier detection and different audiological performance, which was manifested in ASSR thresholds, audiometric configurations and CM performance. CM thresholds were increased, amplitude and duration were decreased, non-linearity of I/O function was reduced.

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Objective: To explore the audiological characteristics of infant auditory neuropathy (AN) patients with cochlear microphonic (CM) recorded but no otoacoustic emission (OAE) response and clinically reduce the rate of missed diagnosis of AN. Design: Retrospective clinical study of medical data from 2003 to 2020. Setting: Otolaryngology head and neck surgery clinical hearing center. Participants: Eighteen infant AN patients with CM present and distortion product otoacoustic emission (DPOAE) absent in both ears were OAE absent group. Forty-four infant AN patients with CM and DPOAE present in both ears were OAE present group. Main outcome measures: Audiological characteristics. Results: 1. The age of onset in OAE absent group was 0.9 (0.02) years old, which was less than 1.11 (1.63) years old in OAE present group (P=0.041). 2. The CM threshold of OAE absent group was 80 (10) dB nHL, which was significantly higher (P<0.001) than OAE present group. CM amplitude were smaller (P<0.05), and CM duration were shorter (P<0.05) in OAE absent group. 3. The thresholds of auditory steady-state response (ASSR) at 0.5, 1, 2 and 4 kHz were 94 (10), 94 (10), 87 (20) and 81 (10) dB HL cg respectively in OAE absent group, which were higher than those in OAE present group (P<0.01). Conclusions: Infant AN patients with CM present and OAE absent showed earlier onset, worse hearing level and worse CM performance. The influencing factors and value of CM in AN patients still need to be explored in the future.