OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

Objective:To investigate the risk factors for the occurrence and poor in-hospital prognosis in patients with peripartum cardiomyopathy (PPCM).Methods:The clinical data of 35 patients with PPCM and 35 healthy pregnant women in Xuanwu Hospital, Capital Medical University and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2003 to January 2022 were retrospectively analyzed. The personal histories, laboratory examination, imaging examination, cardiac function outcome, etc were collected. According to the left ventricular ejection fraction (LVEF) at discharge, the patients with PPCM were divided into in-hospital recovery group (LVEF≥50%, 18 cases) and prolonged disease group (LVEF<50%, 17 cases). Multivariate Logistic regression analysis was used to analyze independent risk factors of poor in-hospital prognosis in patients with PPCM.Results:Among 35 patients with PPCM, the age was (29.81 ± 5.37) years old, 17 cases (48.57%) complicated with gestational hypertension, 6 cases (17.14%) complicated with gestational diabetes mellitus, 24 cases (68.57%) of New York Heart Association (NYHA) cardiac function classification was Ⅲ to Ⅳ class, and 4 cases died (11.43%). The gestational age in patients with PPCM was significantly shorter than that in healthy pregnant women: (36.26 ± 4.27) weeks vs. (38.54 ± 4.59) weeks, the rates of multiple pregnancy and gestational hypertension were significantly higher than those in healthy pregnant women: 17.14% (6/35) vs. 2.86% (1/35) and 48.57% (17/35) vs. 11.43% (4/35), and there were statistical differences ( P<0.05 or <0.01). Compared with hospital recovery group, the patients in protracted disease group had shorter gestational age, larger left ventricular end-diastolic diameter, higher serum creatinine, C-reactive protein and amino-terminal pro-brain natriuretic peptide (NT-proBNP), worse NYHA cardiac function classification, and there were statistical differences ( P<0.05 or <0.01); but there were no statistical difference in LVEF at the first diagnosis and troponin I between two groups ( P>0.05). Multivariate Logistic regression analysis result showed that elevated creatinine was an independent risk factor for poor in-hospital prognosis in patients with PPCM ( OR = 4.554, 95% CI 1.536 to 13.684, P = 0.018). Conclusions:The gestational hypertension may be a risk factor for PPCM. The gestational hypertension, earlier onset time, enlarged left ventricular end-diastolic diameter, high NT-proBNP, high C-reactive protein, high creatinine and high cardiac function NYHA classification may be risk factors for poor in-hospital prognosis in patients with PPCM; and elevated creatinine is an independent risk factor for poor in-hospital prognosis in patients with PPCM.

Objective:To compare the influence of single and staged percutaneous coronary intervention (PCI) on long-term prognosis in patients with multi-vessel coronary artery disease.Methods:Using prospective research methods, 1 832 patients with multi-vessel coronary artery disease from January to December 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences were selected. According to the time of PCI, the patients were divided into single PCI group (1 218 cases) and staged PCI group (614 cases). The patients were followed up for 2 years, the primary endpoint was major cardiovascular and cerebrovascular event (MACCE), including target vessel-related myocardial infarction (TV-MI), target vessel-related revascularization (TVR), cardiogenic death and stroke, and the secondary endpoint was stent thrombosis. The propensity score matching (PSM) was applied to balance the discrepancies between 2 groups, and the baseline and follow-up data were compared. The Kaplan-Meier survival curves were drawn to evaluate the survival rates events; multifactor Cox proportional risk regression was used to analyze whether staged PCI was an independent risk factor for the endpoint events.Results:The in-hospital stay, duration of procedure and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score in single PCI group were significantly lower than those in staged PCI group: (5.54±3.09) d vs. (9.50±4.06) d, (43.12±28.55) min vs. (79.54±44.35) min, (14.04±7.63) scores vs. (18.51±7.79) scores, and there were statistical differences ( P<0.01); there were no statistical difference in complete revascularization rate and SYNTAX score after PCI between 2 groups ( P>0.05). Based on 2-year follow-up, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.5% (6/1 218) and 2.0% (12/614) vs. 0.4% (5/1 218), and there were statistical differences ( P<0.01). Kaplan-Meier survival curves analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were better than those in staged PCI group (99.5% vs. 97.9% and 99.6% vs. 98.0%, P<0.01). Multifactor Cox proportional risk regression analysis results showed that staged PCI was an independent risk factor for stent thrombosis ( HR = 3.91, 95% CI 1.25 to 12.18, P = 0.019). After PSM, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.7% (4/614) and 2.0% (12/614) vs. 0.5% (3/614), and there were statistical differences ( P<0.05); Kaplan-Meier survival curve analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were significantly higher than those in staged PCI group: (99.3% vs. 97.9% and 99.5% vs. 98.0%, P<0.05); multifactor Cox proportional risk regression analysis results showed that staged PCI was not an independent risk factor of stent thrombosis ( HR = 2.29, 95% CI 0.58 to 9.00, P = 0.234). Both before and after PSM, there were no evidences for interaction between the type of angina pectoris and staged PCI ( P>0.05). Conclusions:Although a seemingly increase exists in the incidence of TV-MI and stent thrombosis in the staged PCI group, staged PCI is an independent risk factor neither for MACCE and its components, nor for stent thrombosis. In addition single PCI reduces the in-hospital days and duration of PCI procedure, which may be a relatively reasonable approach to clinical practice.

Objective To explore the predictive value of CT image texture analysis for early enlargement of hypertensive intracerebral hemorrhage.Methods One hundred and eight patients with hypertensive intracerebral hemorrhage were divided into enlarged hematoma group (positive group)and non-enlarged hematoma group (negative group),according to whether the volume of hematoma on 24 h follow up CT scan was more than 30% or 6 mL of the baseline CT.Phillis Radiomics Tool V93 software was used to segment the hematoma on CT plain scan images of two groups,four features of first-order and three of gray-level co-occurrence matrix (GLCM),thirteen of gray-level size zone matricx (GLSZM)and eleven of gray-level run-length matricx (GLRLM)were obtained.The differences of thirty-one texture features between the two groups were compared.The ROC curves of the features with statistical differences were analyzed.The independent predictors of early enlargement of intracerebral hemorrhage were screened by Logistic multivariate regression model.Results Among the one hundred and eight patients,twenty-eight were positive group and eighty were negative group.Skewness and long run low gray-level emphasis (LRLGE)in positive group were significantly higher than those in negative group (P＜0.05).There was no significant difference in the remaining twenty-nine features between the two groups (P＞0.05).ROC curve analysis showed that the AUC of Skewness,LRLGE and their combined diagnosis were 0.634,0.814 and 0.828,respectively.The independent variables were screened by stepwise regression analysis.The LRLGE (OR＝1.238,95%CI＝1.009－1.51 9,P＜0.05)was selected as the regression model, suggesting that LRLGE was an independent predictor of the early enlargement of intracerebral hemorrhage.Conclusion Texture analysis of CT images is helpful to predict the early enlargement of hypertensive intracerebral hemorrhage,and LRLGE based on GLRLM algorithm can be used as an independent predictor.

Objective: To evaluate the relationship between platelet distribution width(PDW) and the extent of coronary artery disease and 2-year outcome in patients received percutaneous coronary artery intervention(PCI) because of stable coronary artery disease(SCAD). Methods: We consecutively enrolled 4 293 patients who received PCI because of SCAD in Fuwai Hospital from Jan 2013 to Dec 2013, patients were followed up for 2 years. Patients were divided into three groups according to tertiles values of PDW as follows: PDW≤11.4%(1 402 patients), 11.4%12.9% (1 450 patients). Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as the occurrence of death, myocardial infarction, target vessel revascularization, intra stent thrombosis and stroke during follow-up. Multivariable logistic regression was used to evaluate the relationship between PDW and the extent of CAD. Multivariable Cox regression was used to evaluate the relationship between PDW and prognosis of SCAD patients. Results: PDW was associated with diabetes mellitus, body mass index, red cell distribution width, mean platelet volume (MPV), platelet counts and glycosylated haemoglobin (P<0.05), but not associated with age, sex, estimated glomerular filtration rate (P>0.05). PDW was not correlated with the extent of CAD(P=0.990), SYNTAX score(P=0.721), no-reflow phenomenon after PCI(P=0.978). Multivariable logistic regression also showed no relationship between PDW and extent of CAD (OR=0.994, 95%CI 0.961-1.029, P=0.73). PDW was found to be an independent risk factor of 2-year cardiac death (HR=1.242, 95%CI 1.031-1.497, P=0.022), but was not an independent risk factor of all-cause death and MACCE. Conclusions PDW is not related with the extent of coronary artery disease. PDW is an independent risk factor of 2-year cardiac death, but is not an independent risk factor of all-cause death and MACCE in this patient cohort.

Objective: To observe the impact and clinical outcome of intra-aortic balloon pump(IABP) use in patients underwent percutaneous coronary intervention (PCI). Methods: From January 2013 to December 2013, 10 724 consecutive patients undergoing PCI were enrolled.After 2 years′ follow-up, the incidence of major adverse cardiovascular and cerebrovascular events such as death, myocardial infarction, stent thrombosis, revascularization, recurrent stroke were recorded, propensity score was used to match baseline data, and the clinical outcomes in patients with IABP and non-IABP were compared. Results: The overall use of IABP was 1.3%(143/10 724), clinical and angiographic risks were significantly higher in IABP group than non-IABP group.The rate of cardiac shock was significantly higher (9.8%(14/143) vs. 0.2%(16/10 581), P<0.01) and left ventricular ejection fraction was significantly lower (54.3%±11.0% vs. 62.9%±7.2%, P<0.01) in the IABP group than in the non-IABP group.Patients in IABP group had a significantly higher rate of left main or triple-vessel disease (P<0.01), and their SYNTAX score, target lesion number, stent number were also significantly higher compared with non-IABP patients (all P<0.01). During the 2-year follow-up, all-cause mortality was significantly higher in IABP group than in non-IABP group (10.5%(15/142) vs. 1.1%(116/10 581), P<0.001). Multivariable analyses indicated that IABP was associated with increased mortality (HR=3.51, 95%CI 1.71-7.17, P=0.001). However, after propensity score matched analyses (137 pairs), IABP use was no longer an independent predictor of all-cause mortality (HR=2.09, 95%CI 0.72-6.13, P=0.177). Conclusions In this single large center of coronary heart disease in China, the IABP usage was about 1.3%.Propensity score matched analyses showed that during the 2 years′ follow-up, adverse effect including similar long-term mortality is similar between PCI patients with or without IABP after adjusting for confounders.

Objective: To explore aspirin resistance (AR) phenomenon in patients with coronary artery disease (CAD) for secondary prevention and to study the relationships between AR and COX1, COX2, TBXA2R gene polymorphisms. Methods: A total of 2881 CAD patients taken aspirin (100 mg/day) in 7 consecutive days were enrolled. Among them, 2 groups were established as AR group, n=166 and Control group, n=200 aspirin sensitive patients. Platelet aggregation function was induced by arachidonic acid (AA), COX1, COX2 and TBXA2R gene polymorphisms were examined by polymerase chain reaction-restricted fragment length polymorphisms (PCR-RFLP) method. Results: The occurrence rate of AR was 5.76% (166/2881). There were 8 tagSNPs locus in 3 genes as in COX1:(rs3842788), (rs4273915), (rs7866582); in: COX2 (rs3218625); in TBXA2R: (rs2238630), (rs2238631), (rs2238633), (rs3786989). The frequencies of wild type, heterozygous genotype and homozygous genotype were similar between 2 groups. Conclusion: The incidence rate of AR is not high in CHD patients with regular aspirin medication; single nucleotide gene polymorphisms of COX1, COX2 and TBXA2R have no obvious correlation to AR.

Objective To investigate the value of fast track surgery (FTS) principles in the perioperative management of liver cancer patients after hepatectomy.Methods Forty patients with primary liver cancer who were admitted to the First People's Hospital of Qinzhou from September 2011 to July 2013 were enrolled in this prospective study.All the patients were randomly divided into the FTS group (20 patients) and the control group (20 patients) according to the random number table.The perioperative management of patients in the FTS group was guided by the FTS principles,patients in the control group were managed with traditional methods.The intraoperative condition,time for portal occlusion,operation time,volume of intraoperative blood loss and blood transfusion,time to drainage tube removal,time to flatus and defecation,duration of postoperative hospital stay,expenses,changes of C-reactive protein on postoperative day 1,3,6,recovery of hepatic function and incidence of postoperative complications.All patients were followed up via phone call and out-patient examination till September 2013.All data were analyzed using the t test or chi-square test.The non-normal distribution paramenters were analyzed using the rank sum test.Results All patients were cured with no perioperative death.The time for postoperative drainage tube removal,time to flatus and defecation,duration of postoperative hospital stay and expenses were (2.3 ± 1.0)days,(2.5 ±0.5)days,(3.1 ±0.7)days,(7.0 ±0.8)days and (3.6 ±0.3) × 104 yuan in the FTS group,and (4.6 ± 0.7) days,(4.3 ± 0.7) days,(4.8 ± 0.4) days,(8.5 ± 0.9) days and (4.1 ± 0.3) ×104 yuan,with significant differences between the 2 groups (t =0.74,0.34,1.70,0.23,0.57,P ＜ 0.05).The levels of C-reactive proteins at postoperative day 1,3,6 were (56 ±7)mg/L,(122 ±7)mg/L and (35 ±7)mg/L in the FTS group,and (198 ± 24) mg/L,(137 ± 5) mg/L and (49 ± 8) mg/L,with significant differences between the 2 groups (F =64.91,P ＜0.05).The levels of prealbumin at postoperative day 1,3,6 were (196 ± 14) mg/L,(243 ± 17) mg/L,(260 ± 10) mg/L in the FTS group,and (198 ± 24) mg/L,(199 ± 16) mg/L and (245 ± 7) mg/L in the control group,with significant differences between the 2 groups (F =22.69,P ＜ 0.05).The levels of alanine transaminase at postoperative day 1,3,6 were (379 ±34)U/L,(166 ± 12)U/L,(49 ± 14)U/L in the FTS group,and (367 ±75)U/L,(210 ±28)U/L,(197 ±22)U/L in the control group,with significant differences between the 2 groups (F =4.51,P ＜ 0.05).One patient was complicated with peritoneal effusion and 1 with thoracic effusion in the FTS group; 4 patients was complicated with peritoneal effusion,3 with thoracic effusion,4 with pulmonary infection and 2 with incisional infection in the control group,with no significant difference in the complication between the 2 groups (x2 =0.78,1.11,4.44,2.11,P ＞ 0.05).All the patients were followed up for 2-24 months,no patients received reoperation or re-admitted to the hospital due to complications.Conclusion The application of FTS principle in the perioperative management of liver cancer patients after hepatectomy is safe and effective,it could alleviate the post-operative stress reaction and accelerate the recovery of liver function and patients' condition.