Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.

Objective:To evaluate the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in striatum in paclitaxel-induced neuropathic pain and the relationship with GABA B receptors in rats. Methods:Healthy clean-grade male Sprague-Dawley rats, aged 6-9 weeks, weighing 180-220 g, were used in this study.The neuropathic pain model was established by intraperitoneal injection of paclitaxel 2 mg/kg once every 2 days for 7 consecutive days in anesthetized rats, and then intrathecal catheterization was performed.Fifty rats in which intrathecal catheters were successfully implanted were divided into 5 groups ( n=10 each) using a random number table method: paclitaxel group (P group), paclitaxel plus normal saline group(N group), paclitaxel plus lentivirus empty vector group (BV group), paclitaxel plus HCN4 channel lentivirus group (H group), and paclitaxel plus HCN channel inhibitor ZD7288 group (I group). Ten rats of the same age were selected as the blank control group (C group). At 15 days after intraperitoneal injection of paclitaxel, normal saline 20 μl was intrathecally injected in group N, group BV received intrathecal injection of HCN4 channel lentivirus empty vector 1×10 8 TU/ml, 20 μl, group H received intrathecal injection of HCN4 channel lentivirus 1×10 8 TU/ml, 20 μl, and group I received intrathecal injection of ZD728830 μg, 20 μl.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before paclitaxel injection and 14 and 21 days after injection.The cerebral striatum tissues were obtained at T 2, and the expression of HCN4 channel and GABA B receptors was determined by immunohistochemistry and Western blot. Results:Compared with group C, the MWT was significantly decreased, HCN4 channel expression was up-regulated, and GABA B receptor expression was down-regulated in group P ( P<0.05). Compared with group P, the MWT was significantly increased, HCN4 channel expression was down-regulated, and GABA B receptor expression was up-regulated in group H and group I ( P<0.05), and no significant change was found in the parameters mentioned above in group N and group BV ( P>0.05). Conclusion:Up-regulation of expression of HCN4 channels in striatum can induce down-regulation of GABA B receptor expression, which is involved in the pathophysiological mechanism of paclitaxel-induced neuropathic pain in rats.

Objective To compare right anterolateral minithoracotomy and traditional median sternotomy in the treatment of left atrial myxoma. Methods Forty-one patients with left atrial myxoma treated in our hospital from January 2009 to January 2018 were divided into two groups according to the operation method: a right anterolateral minithoracotomy group including 15 patients, with 7 males and 8 females, aged 45.1±15.4 years; a median sternotomy group including 26 patients, with 10 males and 16 females, aged 49.4±11.9 years. The clinical data of the two groups were compared. Results There was no significant difference in preoperative clinical data between the two groups. All patients completed the operation without perioperative death. There was no significant difference in the operation time, cardiopulmonary bypass time, aortic clamp time or the incidence of postoperative complications between the two groups. However, compared with the median sternotomy group, the right anterolateral minithoracotomy group had shorter duration of mechanical ventilation, ICU stay and postoperative hospital stay, and less volume of drainage and blood transfusion 24 hours after surgery (all P<0.05). After 3–106 months follow-up, no recurrence was observed in both groups. Conclusion Compared with traditional median sternotomy for left atrial myxoma resection, right anterolateral minithoracotomy is safe, effective and less traumatic. It can be used as a routine treatment for left atrial myxoma.

Objective    To analyze the effect of loop-in-loop technique and annuloplasty ring for the treatment of mitral valve prolapse (MVP) under total thoracoscopy. Methods    Between May 2012 and May 2017, 21 patients with MVP underwent mitral valve repair in our hospital. There were 12 males and 9 females with a mean age of 50.90±9.66 years and the mean weight of 64.81±11.56 kg. Loop-in-loop artificial chordae tendonae reconstruction and mitral annuloplasty were performed through the right atrial-atrial septal incision under total thoracoscopy. The water test and transesophageal echocardiography were performed during the operation to evaluate the effect of mitral annuloplasty. Data of echocardiography and chest radiography were collected postoperatively one week, before discharge and after discharge. Results    All the operations were successful without re-valvupoplasty or valve replacement, conversion to median thoracotomy, malignant arrhythmia, perioperative death or wound infection. Among them, 10 patients underwent tricuspid valvuloplasty, 1 patient underwent tricuspid valvuloplasty plus radiofrequency ablation simultaneously. The mean cardiopulmonary bypass time was 255.57±37.24 minutes, aortic occlusion time was 162.24±19.61 minutes, the number of loop was 2–5 (3.29±0.78), the size of ring was 28–34 (31.11±1.88) mm, ventilator assistance time was 19.43±14.68 hours, ICU time was 58.45±24.60 hours and postoperative hospital stay was 12.28±3.61 days. Transthoracic echocardiography was re-examined postoperatively. Mild-mitral regurgitation was found in 3 patients. Warfarin anticoagulant therapy was given orally for 6 months postoperatively. The patients were followed up regularly for 2–51 months at 1, 3, 6 and 12 months postoperatively. Left ventricular end-diastolic diameter (LVEDD) was 45.06±2.96 mm, left ventricular end-diastolic volume 108.11±17.09 mL, left atrial diameter (LAD) 35.56±6.93 mm and cardiothoracic ratio 0.53±0.13 at discharge which were significantly smaller than those at admission (P<0.05). Pulmonary artery pressure was 19.22±6.38 mm Hg which was significantly lower than that at admission (P<0.05), but left ventricular ejection fraction (62.33%±4.00%) had no significant change (P>0.05). The LAD and LVEDD were significantly smaller than those before operation, and the cardiac function improved to some extent during the follow-up. No new mitral valve prolapse, increased regurgitation, infective endocarditis, thromboembolism or anticoagulation-related complications were found during the follow-up. Conclusion    Loop-in-loop artificial chordae tendon implantation combined with mitral annuloplasty is a safe and effective method for MVP under total thoracoscopy with minimal trauma, satisfactory cosmetic effect, and good early- and medium-term results. It is worth of popularizing. However, the operation time needs to be further shortened, and its long-term clinical effect needs further follow-up and other researches to confirm.

Objective    To analyze the near-term clinical efficacy of two different surgical procedures (Sun's procedure and Debranching combined endovascular stent-graft procedure) to cure Stanford type A aortic dissection, and summarize the clinical experience to help better master the indications of the two surgical procedures. Methods     We retrospectively analyzed the clinical data of 46 patients with Stanford A aortic dissection in our hospital between September 2014 and September 2017. There were 39 males and 7 females at age of 20–74 (48.67±11.80) years. According to different surgical methods, the patients were divided into a Sun's procedure group (26 patients) and a debranching combined endovascular stent-graft procedure group (20 patients). The clinical effect of the two groups was compared. Results     The debranching combined endovascular stent-graft procedure group was significantly superior to the Sun's group in cardiopulmonary bypass (CPB) time, aortic cross clamp(ACC) time, intraoperative urine output, postoperative mechanical ventilation time, postoperative 24 h volumes of drain, CICU time, renal function recovery of postoperative 72 h and total hospital stay(P<0.05). The incidence of transient neurological damage after operation in the debranching combined endovascular stent-graft procedure group was significantly lower than that of the Sun's procedure group(P<0.05). The follow-up time ranged from 3 to 36 months. And the follow-up rate was 90.5%. One patient in the Sun's procedure group died of serious pulmonary infection postoperative 30 days. One patient in the debranching combined endovascular stent-graft group was found to have internal leakage in the early postoperative examination and   disappeared after 6 months. Sun's procedure group did not find endoleak. All patients during the follow-up time did not appear brain, coagulation disorders, stroke, paraplegia, upper limb ischemia and other complications. Conclusion     For Stanford type A aortic dissection, debranching combined surgery may have the risk of postoperative endoleak, but the overall effect is superior to Sun's operation. Therefore, debranching combined surgery should be preferred for the treatment of this type of dissection.

Objective To evaluate the safety aod efficacy of device closure of ventricular septal defect (VSD) through parasternal approach,and to compare the advantages and disadvantages of three approaches.Methods Between Jan 2012 and Jul 2015,209 cases(Group A) underwent per-ventricular device closure of VSD through a left parasternal approach,and 36 cases(Group B) underwent per-atrial device closure of VSD through a fight parasternal approach,and 49 cases(Group C) underwent per-ventricular device closure of VSD through a median sternotomy approach.In group A,a 1.0 to 2.0 cm left parasternal iucision was made in the fourth or third intercostal space.Press the right ventricular(RV) free wall to select the puncture point.After securing double purse-string suture around the optimal puncture site,the occluder was introduced via a sheath inserted directly into the RV and navigation and positioning of the device guided by transesophageal echocardiography(TEE).In group B,a 1.0 to 2.0 cm right parasternal incision was made in the fourth or third intercostal space.After securing double purse-string suture at the right atrium near the atrioventricular groove,a specially designed hollow probe was inserted into the right atrium and was passed through the tricuspid valve into the right ventricle.The tip of the probe was manipulated to aim at or cross VSD,and a spring guide-wire was inserted into the left veotricle(LV) through the channel of the probe under TEE guidance.Then the delivery sheath was positioned into LV passing over the wire,and the device was pushed into the sheath and was deployed to finish closure.In group C,after a 1.5 to 3.0 cm median sternal incision was made,the closure of VSD was finished as the same procedure as in group A.Results There was no significant differences at the age and weight between 3 groups,as well as the size of VSD and devices.But the position of VSD varied between 3 groups.The rate of successful closure in group A (98.1％,205/209) and B (97.2％,35/36) was similar to group C (97.9％,48/49).The mean intracardiac manipulating time was shorter in group A(10 ± 6) min and group C (7 ± 5) min than in group B(19 ± 11) min.The mean time of skin cut to suture was shorter in group A(40 ± 15) min and group B(43 ± 17) min than in group C(55 ±21) min.And the average hospitalization time in group A (5.9 ± 2.2) days and group B (5.5 ± 2.7) days was shorter than in group C (8.3 ± 3.6) days.During the follow-up period of 1 to 40 months,no obvious residual leakage,arrhythmia or valvular inadequacy were found in all cases,and no device dropped out.Conclusion Minimally invasive technique of device closure of VSD through parasternal approach appears to be safe and effective,further reducing trauma and recovering faster than median sternal approach.Accurate and all-round TEE evaluation is very important to case selection of VSD.Individually procedure approach should be performed according to the size,position,and path and flow direction of VSD.

Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.

BACKGROUND:It has been demonstrated to be effective for the improvement of heart function after acute myocardial infarction with intravenous or intramyocardial administration of bone marrow mesenchymal stromal cels. However, little is known regarding the effect of the combination of intravenous and intramyocardial administration of mesenchymal stromal cels on the heart function of a chronic myocardial infarction model. OBJECTIVE:To study the effect of intravenous and intramyocardial administration of bone marrow mesenchymal stromal cels on the heart function of a rat chronic myocardial infarction model and the relevant mechanism. METHODS:Bone marrow mesenchymal stromal cels isolated from Lewis rats were expandedex vivo. BrdU-labeled bone marrow mesenchymal stromal cels (3×106) were administeredvia the femoral vein and the myocardial surface respectively into rat models of chronic myocardial infarction in cel transplantation group. The equal volume of PBS was injected into the same place in control group. Four weeks after injection, echocardiography was performed to evaluate the heart function, and then the heart tissues were harvested for immunohistochemistry examination. The total blood vessel density in the scar area was evaluated. RESULTS AND CONCLUSION:At 4 weeks after cel implantation, the left ventricular function was not improved in the two groups. The immunohistochemistry staining showed that (1) the mesenchymal stromal cels in the myocardium did not differentiate to myocardial cels; (2) there was no significant difference in the total blood vessel density in the scar area between the cel transplantation and control groups. Taken together, the combined intravenous and intramyocardial administration of bone marrow mesenchymal stromal cels cannot improve heart function in a rat chronic myocardial infarction model.

Aim To investigate whether EGCG treat-ment ameliorates cognitive deficits in APP/PS1 trans-genic mice and, whether it has the ameliorating effect of p75 NTR signaling to neuronal apoptosis in the hippo-campus of APP/PS1 mice. Methods Morris water maze test and locomotivity test were used to predict be-havioral changes; further TUNEL staining and Fluoro-Jade B staining were applied to confirm the neuronal apoptosis and neuronal degeneration;Western blot was employed to detect protein expression levels of p75 NTR signaling in the hippocampus of APP/PS1 mice. Re-sults EGCG treatment dramatically ameliorated the cognitive impairments, and inhibited the neuronal ap-optosis in the APP/PS1 mice. Moreover, EGCG treat-ment dramatically inhibited the p75 NTR signaling by de-creasing the p75ICD expression, JNK2 phosphorylation, and cleaved-caspase 3 expression. Conclusion EGCG treatment dramatically ameliorates the cognitive impairments, and inhibits the neuronal apoptosis by in-hibiting the p75NTR signaling.