Protective effect of chrysin regulates AMPK-NLRP3 signaling mediated pyroptosis to alleviate hepatic fibrosis / 药学学报

This study investigated the protective effect of chrysin on hepatic fibrosis by regulating AMP-activated kinase (AMPK)-NOD-like receptor protein 3 (NLRP3) mediated pyroptosis pathway. The hepatic fibrosis model of mice was established by thioacetamide (TAA) in vivo. Except the control and chrysin alone groups, the mice were injected intraperitoneally with TAA at 100 mg·kg-1, three times per week for the first week. From the 2nd to 5th week, mice were injected intraperitoneally with TAA at 200 mg·kg-1, three times per week for the next 4 weeks. Chrysin groups were intragastrically administrated once per day to 5th week. The histopathological changes were detected by HE and Masson staining. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed by the kits. All animal experiments were approved by the Medical Ethics Committee of Affiliated Zhongshan Hospital of Dalian University (DWLL2019060). LX-2 cells were stimulated by (transforming growth factor-β, TGF-β) in vitro. The protein expressions of AMPKα, p-AMPKα, NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD) were detected by Western blot, and the mRNA levels of collagen-Ι, α-smooth muscle actin (α-SMA), interleukin-1β (IL-1β), IL-18, caspase-1, GSDMD were analysis by reverse transcription-polymerase chain reaction (RT-PCR). Chrysin attenuated the increases in serum AST and ALT levels in the TAA group, while significantly improved the changes of liver morphology, reduced liver tissue inflammatory cell infiltration and inhibited collagens deposition. Compared with TAA group, chrysin effectively activated AMPKα phosphorylation and inhibited hepatic NLRP3 inflammasome activation. Additionally, the protein expressions and mRNA levels of IL-1β, IL-18, caspase-1 and GSDMD in chrysin groups were decreased. Chrysin inhibited the expressions of collagen-Ι and α-SMA, enhanced the phosphorylation of AMPKα, and decreased the expressions of NLRP3 and GSDMD. Therefore, chrysin may inhibit inflammatory injury and pyroptosis possibly by activating AMPK and inhibiting NLRP3 inflammasome to alleviate hepatic fibrosis.

Clinical Study of Acute Vasoreactivity Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls.</p><p><b>METHODS</b>We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test.</p><p><b>RESULTS</b>The rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381).</p><p><b>CONCLUSIONS</b>The rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.</p>

Mid-term outcome of endoscopic greater saphenous vein harvesting in coronary artery bypass grafting / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the mid-term clinical outcome of endoscopic greater saphenous vein harvesting (EVH) in coronary artery bypass grafting (CABG). Method A total of 205 patients receiving off-pump CABG between July, 2012 and April, 2013 at our department were enrolled in this study, including 66 patients (35 male and 31 female patients with a mean age of 60.3±7.92 years) undergoing EVH and 139 patients (109 male and 30 female patients with a mean age of 59.20±8.37 years) undergoing open greater saphenous vein harvesting (OVH).</p><p><b>RESULTS</b>The surgical procedures were completed smoothly in all the cases. The perioperative mortality rates was 3.03% (2/66) in EVH group, as compared with 3.60% (5/139) in OVH group (P=1.00). Acute myocardial infarction (AMI) occurred during the perioperative period in 3 (2.16%) patients in OVH group and in 1 (1.52%) patient in EVH group. Perioperative low cardiac output syndrome was diagnosed in 4 (2.88%) patients in OVH group and in 2 (3.03%) in EVH group (P>0.05). During the follow-up, 8 (8.80%) patients in OVH group and 5 (8.06%) in EVH group had recurrent angina (P=0.93). No patients experienced AMI during the follow-up. The 2-year patency rate of the venous grafts was 83.59% in OVH group and 82.22% in EVH group (P=0.73).</p><p><b>CONCLUSION</b>EVH has significant advantage in reducing the complications of the incision in the lower limbs. The mid-term patency rates of venous grafts are similar between OVH and EVH, but the long-term patency rate needs further evaluation.</p>

Study on the differential expression of lipid metabolism-related genes in young LDLR knockout mice liver / 中华病理学杂志

<p><b>OBJECTIVE</b>To clarify the differential expression of the genes related to the lipid metabolism in the early stage of atherosclerosis in the young LDLR-/- mice of different ages.</p><p><b>METHODS</b>A RT-PCR assay was used to analyse the gene expression patterns in the livers of LDLR-/- mice and wild type (WT) mice from 14 to 90 days. The characteristics of early lipid deposition in intima were evaluated using biochemical and pathological techniques.</p><p><b>RESULTS</b>In LDLR-/- mice, when compared to WT mice, the mRNA level of the apolipoprotein A IV (apoA IV), fatty acid translocase (Fat/CD36) and carnitine palmitoyl transferase I (CPT I) changed prominently at the age of 14-days (P < 0.05). At 30 days, the mRNA level of apolipoprotein A I (apoA I) was up regulated, but apolipoprotein F (apoF), CD36 and CPT I were down regulated (P < 0.05). At 60 days, the mRNA levels of apoA I, CPT I and liver X receptor alpha (LXRalpha) were up regulated, but apoA IV was down regulated (P < 0.05). At 90 days, the level of the apoA I was higher, but the expression of the apoA IV, apoF and acyl-coenzymeA oxidase 1 (ACOX1) were down regulated (P < 0.05), whereas the expression of apolipoprotein A V (apoA V), apolipoprotein E (apoE), peroxidase proliferator-activated receptor alpha (PPARalpha) and angiopoietin-like protein 3 (angptl 3) had no significant changes (P > 0.05). The serum levels of TC (P < 0.05), TG (P < 0.05) and LDLC (P < 0.05) in LDLR-/- mice were significantly higher than those in wild type mice with the same age.</p><p><b>CONCLUSIONS</b>The mRNA levels of the apoA I, apoA IV, apoF, FAT/CD36, CPT I, ACOX1 and LXRalpha of the LDLR-/- mice were significantly changed compared to the WT mice. The genes may be of some relevance to the complicated lipid metabolism network, and have effect in the early stage of atherogenesis.</p>

Expression profiles of lipid metabolism-related genes in liver of apoE(-/-)/LDLR(-/-) mice / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the expression characteristics of lipid metabolism-related genes in the liver and early atherosclerotic lesions in apolipoprotein E and low density lipoprotein receptor gene double knockout (apoE(-/-)/LDLR(-/-)) mice.</p><p><b>METHODS</b>RT-PCR was used to detect the differential expression of lipid metabolism-related genes in the liver of apoE(-/-)/LDLR(-/-) and wild type (WT) mice. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) level as well as aortic morphology were also analyzed.</p><p><b>RESULTS</b>Among the 11 lipid metabolism-related genes, apolipoprotein B100 (apoB100) mRNA levels were significantly higher in apoE(-/-)/LDLR(-/-)mice compared with WT mice. At 14 days, 1, 2 and 3 months of age, the level of mRNA expression were 1.55, 1.47, 1.50 and 2.42 folds of those of the age matched WT mice respectively. The fatty acid transporter (FAT/CD36) mRNA expression levels were higher in 14-day and 3-month old mice at 1.30 and 1.35 folds of those of the age matched WT mice, respectively. Apolipoprotein A IV (apoA IV) and Apolipoprotein AV (apoAV) mRNA levels were significantly down-regulated (0.89 fold decrease in 14-day, and 0.90 folds decrease in 3-month, respectively). The mRNA expression levels of apolipoprotein AI (apo AI), apolipoprotein F (apo F), peroxidase proliferator-activated receptor alpha (PPAR-alpha), liver X receptor alpha (LXRalpha), angiopoietin-like protein 3 (ANGPTL3), acyl-coenzymeA oxidase 1 (ACOX1) and carnitine palmitoyl transferase 1 (CPT1) had no significant changes. Serum TC, TG and LDL-C were higher than those of age matched WT mice at 7, 2 and 30 folds, respectively. Furthermore, apoE(-/-)/LDLR(-/-) mice demonstrated typical early atherosclerotic lesions at sinus and root regions of aorta in an age dependent manner.</p><p><b>CONCLUSION</b>Alterations of the expression of lipid metabolism-related genes in liver play important roles in the development of AS in the apoE(-/-)/LDLR(-/-) mice at early ages.</p>

Effect of extract of leave Ginkgo biloba(EGb_(50))on sciatic nerve regeneration in rats and its doseeffect relationship / 中华显微外科杂志

Objective To provide the promoting effect of extract of leave Ginkgo biloba(EGb_(50))on nerve regeneration and the dose-effect relationship.Methods Sciatic nerve injury model was set up in 96 male Spraque-Daweiy rats and then randomly divided into four groups:normal saline (NS) group,the low dose EGb_(50) group (50mg?kg~(-1)?d~(-1)),the moderate dose EGb_(50) group (100 mg?kg~(-1)?d~(-1)) ,the high dose EGb_(50) group (200 mg?kg~(-1)?d~(-1)).Electrophysiological,histological examinations and functional eval- uation were used to assess nerve regeneration and the functional recovery in 2,4,6,8 weeks of operative inter- vals respectively.Results The recovery rate of sciatic functional index(SFI),tetanic tension,motor nerve conduction velocity,muscle cell cross-section area of triceps surae and the passing rate of myelinated nerve were significantly higher in EGb_(50) group in all the time point than in control(P＜0.01).Except the recovery rate of sciatic functional index (SFI),there was significant difference between high dose group and moderate, low dose group.(P＜0.01,P＜0.05).Conclusion EGb_(50) has the effect of promoting regeneration of in- juried peripheral nerve and the high dose can get the best result.