Abstract OBJECTIVE To investigate the effect of isodon ternifolia-containing serum(ITS) on the activation of rat primary hepatic Kupffer cell(KC) induced by lipopolysaccharide(LPS) through TLR4/NF-κB/NLRP3 signal pathway. METHODS The primary KC of rats were isolated and cultured, and the primary KC induced by LPS were divided into blank control group, model control group, blank serum group, positive control group(colchicine containing serum group), ITS group, TLR4 blocker group and TLR4 blocker+ITS group. MTT assay was used to detect the effect of different concentrations of ITS on the proliferation activity of KC. The content of interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in KC supernatant were detected by ELISA. Fluorescence quantitative polymerase chain reaction(PCR), Western blotting and immunofluorescence were used to detect the expression of TLR4, nuclear factor κB inhibitor protein α(IκBα), cysteine protease-1(Caspase-1), NLRP3 mRNA and TLR4, IκBα, phosphorylated IκBα(p-IκBα), Caspase-1, NLRP3 and NF-κBp65 in KC. RESULTS Compared with the model control group, the contents of IL-1β, IL-18, TNF-α and IL-6 in the supernatant of KC and the expression of TLR4, IκB α, Caspase-1, NLRP3 mRNA and TLR4, IκBα, p-IκBα, Caspase-1, NLRP3, NF-κBp65 protein in the supernatant of KC in all drug groups were down-regulated or decreased(P<0.05 or P<0.01). Compared with TLR4 blocker group, the improvement of most of the above indexes in TLR4 blocker+ITS group was more obvious. CONCLUSION Isodon ternifolia may inhibit the activation of KC and reduce the expression and release of inflammatory factors by down-regulating TLR4/NF-κB/NLRP3 signal pathway, thus alleviating the inflammatory injury of liver.

OBJECTIVE To investigate the effects of Isodon ternifolius extract on Toll -like receptor 4（TLR4）/nuclear factor - κB（NF-κB）/NOD-like receptor protein 3（NLRP3）pathway in hepatic stellate cells and hepatocytes . METHODS Using primary hepatic stellate cells and primary hepatocytes of rats as subjects ，inflammatory injury model was induced by lipopolysaccharide （LPS，100 ng/mL）. Using colchicine （1 μmol/L）as positive control and TLR 4 inhibitor（TAK-242，1 μmol/L）as reference ，the contents of transforming growth factor -β1（TGF-β1），α-smooth muscle actin （α-SMA），type Ⅰ collagen（COL-Ⅰ），COL-Ⅲ in the supernatant of hepatic stellate cells ，and the contents of alanine aminotransferase （ALT），aspartate aminotransferase （AST），interleukin-1β （IL-1β） and IL -18 in the supernatant of hepatocytes were detected after intervention with I. ternifolius extract（1 mg/mL）. The mRNA expressions of TLR 4，inhibitor α of NF -κB（IκBα），NF-κB p 65，NLRP3，Gasdermin D （GSDMD），apoptosis-associated speck -like protein containing CARD （ASC） and protein expressions of TLR 4， phosphorylated I κBα（p-IκBα），NF-κB p 65，NLRP3，GSDMD，ASC in the above cells were determined . RESULTS Compared with LPS model group ，the contents of TGF -β1，α-SMA， COL-Ⅰ and COL -Ⅲ in the supernatant of hepatic stellate cells and the contents of ALT ，AST，IL-1β and IL -18 in the supernatant of hepatocytes were significantly decreased ；the mRNA expressions of TLR 4，NF-κB p 65，NLRP3，GSDMD，ASC and the protein expressions of TLR 4，p-IκBα，NF-κB p 65，NLRP3，GSDMD，ASC in the two kinds of cells were significantly down - regulated，and the mRNA expression of I κBα was significantly up -regulated in all administration groups （P＜0.05）. Compared with TLR 4 inhibitor group ，the improvement of most of above indexes was more significant in the TLR 4 inhibitor+I. ternifolius extract group （P＜0.05）. CONCLUTIONS I. ternifolius extract could inhibit the activation of TLR 4/NF-κB/NLRP3 pathway， reduce the release of fibrosis factors and inflammatory factors ，alleviate the inflammatory injury of liver cells ，and inhibit the activation of hepatic stellate cells ，so as to protect liver cells and resist liver fibrosis .

Objective: Fufang Biejia Ruangan Tablet (FBRT) is widely used for the treatment of liver fibrosis. However, Hominis Placenta (HP), as an important adjuvant of FBRT, has been restricted for medicinal using due to the limited availability, ethical controversy and safety issues. The present study aimed to investigate the therapeutic effects of novel FBRT (N-FBRT) with sheep placenta (SP) as substitute for HP on liver fibrosis and explore its possible mechanisms. Different dosages of SP in N-FBRT were also evaluated. Methods: Rats were subcutaneously injected with CCl

Type A aortic dissection (AD) is a critical and severe disease with high mortality. The Sun's operation is a standard surgical method for this kind of disease at present. For the procedure, an elephant trunk stent is inserted into the true lumen of the descending aorta and the aortic arch is replaced. A patient was admitted to the First Hospital of Lanzhou University due to sudden chest and back pain for 6 days. Computed tomography angiography (CTA) showed type A AD. Ascending aorta replacement, Sun's operation, and ascending aorta to right femoral artery bypass grafting were performed. After surgery, the patient's condition was worsened. The digital subtraction angiography (DSA) showed the elephant trunk stent was inserted into the false lumen of AD, leading to the occlusion of the large blood vessel at the distal part of the abdominal aorta and below. Although we performed intima puncture and endovascular aortic repair, the patient was still dead.
Aneurysm, Dissecting/surgery* ; Aorta, Abdominal ; Aorta, Thoracic/surgery* ; Blood Vessel Prosthesis Implantation/adverse effects* ; Humans ; Stents/adverse effects* ; Treatment Outcome

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.].

Objective:To evaluate the efficacy and safety of statin combined with ezetimibe for elderly patients with coronary heart disease (CHD) and dyslipiclemia.Methods:Clinical data of 293 patients with CHD and dyslipidemia treated with statins and ezetimibe in the outpatient clinic of Beijing Hospital from November 2009 to June 2019 were retrospectively analyzed. There were 153 patients aged ≥65 years (elderly group) and 140 patients aged<60 year (control group). The low density lipid cholesterol reduction (ΔLDL-C), LDL-C compliance rate and safety were compared between the two groups.Results:The longest follow-up time was 9 months, the average follow-up time was 5.3 months in the elderly group, and 5.2 months in the control group. After treatment the TC, LDL-C, and TG levels were lower than those before treatment in both groups ( P<0.05), and there was no significant changed in HDL-C levels. After treatment there were no significant differences in TC [3.50(3.15,4.01) vs.3.49(3.14,4.00) mmol/L], LDL-C [1.85(1.56,2.23) vs.1.85(1.56,2.40) mmol/L], and TG [1.23(0.94,1.57) vs.1.32(0.84,1.70)mmol/L] between two groups (all P>0.05). There were also no significant differences in ΔLDL-C [-0.85(1.14,-0.55) vs.-0.81 (-1.34, -0.50) mmol/L], LDL-C decline rate (29.3% vs. 28.5%), and LDL-C compliance rate [44.4%(68/153) vs.45.0%(63/140)] between two group (all P>0.05). After combined treatment, AST and ALT increased in both groups, but they were still in the normal range. The difference of AST and ALT before and after treatment in the two groups was not statistically significant. There were no significant changes in CK in both groups ( P>0.05). Conclusion:The combined administration of ezetimibe and statin can significantly reduce LDL-C level and increase LDL-C compliance rate in treatment of elderly patients with coronary heart disease and dyslipidemia safety.

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.

Objective To explore the improvement of cognitive impairment in patients with mild and moderate vascular cognitive impairment( VCI) treated with cerebralcare granule ( CG) and basic treat-ment.Methods From October in 2014 to December in 2016 year,143 cases of VCI patients were admitted from six hospitals in some areas of Hebei Province as the research objects,and divided into CG treatment group (experimental group,n=98) and conventional treatment group (control group,n=66).Three months and six months after treatment,the score of mental state examination ( MMSE) ,the Montreal cognitive assess-ment scale ( MoCA) and the daily living capacity scale( ADL) of the two groups were compared after 3 and 6 moths of treatment.Results ①The total score of MMSE in the experimental group was higher than that of the control group for six months after treatment, and the difference was statistically significant ( ( 23. 76 ± 4.02) vs (21.52±5.13),P<0.05).②Six months after treatment,the total score of MoCA ((21.06±4.66) vs (18.32±5.20)) and visual spatial/executive function((3.05±1.37) vs (2.42±1.66)),calculation force ((2.24±0.84) vs (1.83±1.05)) and orientation ability((5.20±1.12) vs (4.06±1.35)) scores in the ex-perimental group were significantly higher than those in the control group (P<0.05) .③Six months after treat-ment,the ADL score in the experimental group was lower than that before treatment,and the difference was statistically significant((24.96±8.74) vs (29.20±11.55),P<0.05);while there was no significant difference in the ADL score between the experimental group and the control group after 6 months (P>0.05).Conclusion CG can improve cognitive function in mild to moderate VCI patients,mainly in visual space/execution func-tion,calculation ability and orientation ability,and with the extension of treatment time,the curative effect is more obvious.

Objective To investigate the biliary complications and recovery of liver function after liver transplantation from citizen's deceased donors (DCD) versus standard criteria donors (SCD).Method The clinical data of 269 patients who underwent orthotopic liver transplantation from January 2009 to December 2016 at the Fuzhou General Hospital were collected.197 livers were from SCD and 72 from DCD.Propensity score matching (PSM) was used to compare the biliary complications and recovery of liver function after liver transplantation in the two groups.Results PSM matched 61 pairs of patients.There were 10 (16.4％) and 8 (13.1％) biliary complications in the DCD and the SCD groups,respectively,with no significant difference between them (P ＞ 0.05).The recovery of liver function was significantly delayed in the DCD group when compared with the SCD group.The levels of ALT,AST,GGT and AKP in the DCD group were significant different on the postoperative first,third,fifth,seventh and fourteenth day (P ＜ 0.05).At 30 days after surgery,there was no significant difference in liver function between the two groups.Conclusions Liver grafts from DCD had a significant impact on the recovery of liver function.When compared with the SCD group,the DCD group recovered significantly slower in liver function.There was no significant increase in the incidence of biliary complications.