ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

ObjectiveTo establish a model of inflammasome activation induced by psoralidin based on bone marrow-derived macrophages （BMDM） in mice， and to explore the immunomodulatory effects of psoralidin combined with echinatin. MethodLipopolysaccharide （LPS） and psoralidin were used to activate inflammasomes， and after 4 h LPS stimulation， echinatin （40 μmol·L^-1） was administered for pre-protection for 1 h， followed by stimulation with psoralidin （10， 20， 40 μmol·L^-1） for 4 h. The protein expression of Caspase-1 p20 in cell supernatant and precursor （pro）-Caspase-1 and pro-interleukin（IL）-1β in cell lysate were simultaneously detected by Western blot. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the content of IL-β and TNF-α in the supernatant of BMDM. ResultWestern blot revealed that compared with the conditions in the control group， the maturation of psoralidin-induced pro-Caspase-1 and the secretion of IL-1β was inhibited by echinatin （P<0.05，P<0.01）. ELISA showed that the production of IL-1β and TNF-α was enhanced by psoralidin of different concentrations （P<0.05，P<0.01） compared with the condition in the control group. In addition， compared with the psoralidin group， the psoralidin combined with echinatin group reduced the secretion of IL-1β and TNF-α （P<0.01）. ConclusionEchinatin could significantly inhibited the excessive immune-inflammatory response mediated by psoralidin， and thus achieve the effect of toxicity reduction. The present study explored the toxicity-reducing effect of psoralidin combined with echiantin， providing a basis for safe clinical application.

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Adenosine Triphosphate ; Animals ; Chemical and Drug Induced Liver Injury/etiology* ; Flavonoids ; Humans ; Inflammasomes ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nigericin

[This corrects the article DOI: 10.1016/j.apsb.2019.02.003.].

Discordance, such as overlap, repetition and inconsistent, of standards is one of the major problems in current standardization affair in China. Therefore, improving the unity and authority of standards through reduction of overlap, repetition and inconsistency has become the main goal of deepening standardization reform in China. This paper summarizes the discordance in public health standards in China, analyzes the major reasons and provides specific strategic suggestions through case analysis of public health standards in the ways of comparisons of same kind standards of other deparments and standards in administration documents and guidelines or technical specifications of academic associations or societies.

Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb , has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-B-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1 production induced by LPS , which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV), limited research has been done with this drug. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-(IFN-) in a dose-dependent manner in CD4T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

Aim To explore the protective effects and underlying mechanisms of Liu weiwuling Tablets (LW-WL)in concanavalin A (ConA)induced acute immu-nological liver injury in mice.Methods Mice were randomly divided into control,model,Bicyclol,LW-WL low dose (8 g·kg-1 )and LWWL high dose (16 g ·kg-1 )group.The medicattion was performed once daily for seven consecutive days,then the model of im-munological liver injury was prepared by intravenous injection of ConA (15mg·kg-1)in the tail of mice in each group except for the control group one hour after the last treatment.The pathological changes of liver tissues of mice were evaluated by HE staining with, and the levels of alanine amino transferase (ALT),as-partate aminotransferase (AST),and total bilirubin (TBIL)in serum were analyzed by colorimetric meth-od;the level of interleukin 12 (IL-12 ),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleu-kin 4 (IL-4)and interleukin 10 (IL-10)in liver was measured by real-time quantitative polymerase chain reaction (RT-qPCR);the changes of Th1 (IFN-γ) and Th2 (IL-4)cells were observed by flow cytometric (FCM)analysis;the expression of Th1/Th2 transcrip-tion factor T-bet/GATA-3 in liver tissue was detected by Western blot.Results Compared with normal con-trol group,the serum ALT,AST and TBIL were signif-icantly increased in model group, the pathological damage of the liver tissue was severe,and the necrosis and apoptosis of hepatic cells were large, which showed that the model was successful .Compared with model group,both low and high dose of LWWL could significantly reduce ALT,AST,TBIL levels in serum induced by ConA;Th1 cells in the spleen decreased, while Th2 cells increased;the expressions of IL-12, IFN-γand TNF-αmRNA were significantly inhibited with IL-4 and IL-10 mRNA expression elevated in mouse liver tissue;the expression of GATA-3 protein was up-regulated,T-bet protein expression showing no significant changes.Conclusion LWWL could regu-late Th1/Th2 balance,thus inhibiting the acute immu-nity hepatic injury induced by ConA.

A method was developed for determination of thirteen amines including seven aliphatic amines, two heterocyclic amines and four aromatic amines in atmospheric particulate matter (PM) by gas chromatography-mass spectrometry (GC-MS). Samples were ultrasonically extracted with ultra-pure water and derivatized with benzenesulfonyl chloride (BSC) under alkaline conditions. The derivatives were extracted with dichloromethane and then detected by GC-MS using DB-5MS chromatographic column. The method detection limit (S/N=3) and quantitation limit (S/N=10) were 0.00008-0.017 μg/mL and 0.00026-0.0565 μg/mL respectively, and the correlation coefficients were 0.9903-0.9996, which indicated that the standard curve had good linear correlation. In addition, the relative standard deviation was less than 30％ and the average recovery was 54.4％-159.7％ except for methylamine and benzylamine at spiked level of 1.0 μg/mL, showing high precision and accuracy. 9 kinds of amines were detected in the PM2.5 samples collected in Guangzhou city by this method, among which dimethylamine and butylamine accounted for 90％ of the total nine amines, which indicated that they were primary amines in PM2.5; while propylamine exhibited the lowest level in PM2.5 with the concentration less than 1.0 ng/m3.