AIM:The effect of salvianolic acid B on myocardial ischemia-reperfusion injury(MIRI)and its possible mechanism of action.METHODS:In this experiment,human induced pluripotent stem cell-derived cardiomyo-cytes(hiPSC-CMs)were used to establish a myocardial injury model by hypoxia for 6 hours and reoxygenation for 24 hours.Salvianolic acid B(7.5,15,30,60,120 μg/mL)was selected Study the effects of 5 dose groups on the imped-ance and field potential of hiPSC-CMs and hiPSC-CMs myocardial injury models.Subsequently,animal experiments were conducted and divided into sham surgery group,myocardial ischemia-reperfusion model group,salvianolic acid B low(15 mg/kg),medium(30 mg/kg),high(60 mg/kg)dose group,and positive control propranolol(2.5 mg/kg)group.After 4 days of gastric administration,left anterior descending coronary artery ligation surgery(ischemia for 30 minutes,reperfu-sion for 24 hours)was performed to establish a rat MIRI model,and the ischemic area of the rat heart was observed using TTC staining method.HE staining method was used to observe the pathological morphology of rat myocardial structure.Ex-ploring the protective effect of salvianolic acid B on MIRI by measuring serum central muscle enzyme activity using a fully automated biochemical analyzer.Use a reagent kit to detect the possible antioxidant mechanisms involved in the protection of MIRI by salvianolic acid B.RESULTS:Salvianolic acid B has the effect of enhancing the contractility of hiPSC CMs,reducing myocardial injury,and improving field potential function.And it can effectively reduce the myocardial ischemic area of the rat MIRI model,improve myocardial structural damage,reduce myocardial enzyme activity,and protect the heart.In addition,it can also reduce the content of malondialdehyde(MDA)in the serum of MIRI rats,enhance the activ-ity of superoxide dismutase(SOD)and reduced glutathione(GSH),and play an antioxidant role in improving myocardial injury.CONCLUSION:Salvianolic acid B can effectively reduce MIRI and play a role in improving the physiological function of myocardial cells and protecting the heart.Its mechanism of action may be related to reducing MDA levels,in-creasing SOD activity,and enhancing GSH activity of the serum.

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Objective: This study was designed to investigate the protective effects of didymin (Did) on doxorubicin (DOX)-induced cardiotoxicity. Methods: After pretreatment with Did (2, 4, 8 mg/kg intraperitoneal i.p.) for 7 d, the male C57 mice were injected with single dose of DOX (20 mg/kg i.p.). The cardioprotective effect of Did was observed on the 7th day after DOX treatment. Results: DOX delayed body growth and caused cardiac tissue injury, oxidative stress, and mitochondrial dysfunction. Similar experiments in H9C2 cardiomyocytes showed that DOX reduced cell viability, increased generation of reactive oxygen species (ROS) and fragmentation of DNA, decreased mitochondrial membrane potential, and induced cardiomyocyte apoptosis. However, all of these adverse effects were suppressed by Did pretreatment. Did increased protein expression of glutamate-L-cysteine ligase catalytic subunit (GCL), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Besides, Did also induced activation of PI3K/AKT. Conclusion: These findings indicated Did prevented DOX-induced cardiac injury and apoptosis via activating PI3K/AKT/Nrf2 signaling pathway.

Realtime xCELLigence analysis (RTCA) is a new cell detection technology to continuously monitor, record and analyze a variety of information generated by cell activity. In drug research, it plays an important role in assessing myocardial toxicity and cell biological activity. Here, we first introduce the underlying mechanisms and characteristics of RTCA. Then we review the applications of RTCA in the research of myocardial toxicity and cell biological activity, to provides the fundamental baseline for understanding and exploiting RTCA. With the real-time, unlabeled, non-invasive, high throughput, and high accuracy features, RTCA not only promotes drug research and development, but also has a broad and good application prospect in other fields.
Pharmaceutical Preparations

Objective:To examine the early outcome of valve sparing aortic root replacement with reimplantation technique (David procedure) with partial upper sternotomy.Methods:From April 2016 to April 2020, 31 patients underwent valve sparing aortic root replacement under partial upper sternotomy at Vascular Surgery Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. There were 28 males and 3 females, aging (44±13) years (range: 11 to 65 years). Preoperative aortic regurgitation was found greater than moderate in 15 patients, moderate in 6 patients and less than moderate in 10 patients. The diameter of aortic annulus was (26±3) mm (range: 21 to 34 mm), the diameter of aortic sinus was (51±6) mm (range: 41 to 68 mm), the diameter of ascending aorta was (43±8) mm (range: 26 to 62 mm). The preoperative ejection fraction was (65±4) % (range: 59% to 72%) and left ventricular end-diastolic diameter was (55±6) mm (range: 42 to 68 mm). All cases were treated with David Ⅰ procedure, including simple David procedure in 26 patients, David+ascending aorta and partial aortic arch replacement in 3 patients, David+thoracic endovascular aortic repair in 1 patient, David+stent elephant trunk implantation in 1 patient.Results:The operation time, cardiopulmonary bypass time and aortic cross-clamping time were (330±58) minutes (range: 214 to 481 minutes), (138±23) minutes (range: 106 to 192 minutes) and (108±17) minutes (range: 82 to 154 minutes), respectively. There were no death and serious complications (stroke, myocardial infarction, renal insufficiency, severe infection, etc.). The postoperative drainage volume within 24 hours was (314±145) ml (range: 130 to 830 ml). The intubation time was (14±3) hours (range: 8 to 21 hours), and the ICU time was ( M( Q R)) 2.1(1.5) days (range: 1.0 to 5.0 days). Eight patients had no blood transfusion, the proportion of red blood cell use was 9.7% (3/31), plasma use was 22.6% (7/31), and platelet use was 71.0% (22/31). The postoperative left ventricular ejection fraction was (62±4)% (range: 54% to 69%), and left ventricular end-diastolic diameter was (48±4) mm (range: 39 to 56 mm). After operation, aortic regurgitation was significantly improved, with no more than moderate regurgitation, small to moderate regurgitation in 3 patients, minor regurgitation in 3 patients, micro regurgitation in 12 patients and no regurgitation in 13 patients. The follow-up period was 3.5(6.1) months (range: 2.0 to 39.0 months). Echocardiographic follow-up data were obtained in 26 cases, including moderate regurgitation in 1 patient, small to moderate regurgitation in 9 patients, minor regurgitation in 5 patients, micro regurgitation in 6 patients and no regurgitation in 5 patients. There were no major adverse cardiovascular events and aortic events during the follow-up period. No patient was reoperated for aortic regurgitation. Conclusion:Valve sparing aortic root replacement under partial upper sternotomy is safe and feasible, and the early result is satisfactory.

Objective:To examine the early outcome of valve sparing aortic root replacement with reimplantation technique (David procedure) with partial upper sternotomy.Methods:From April 2016 to April 2020, 31 patients underwent valve sparing aortic root replacement under partial upper sternotomy at Vascular Surgery Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. There were 28 males and 3 females, aging (44±13) years (range: 11 to 65 years). Preoperative aortic regurgitation was found greater than moderate in 15 patients, moderate in 6 patients and less than moderate in 10 patients. The diameter of aortic annulus was (26±3) mm (range: 21 to 34 mm), the diameter of aortic sinus was (51±6) mm (range: 41 to 68 mm), the diameter of ascending aorta was (43±8) mm (range: 26 to 62 mm). The preoperative ejection fraction was (65±4) % (range: 59% to 72%) and left ventricular end-diastolic diameter was (55±6) mm (range: 42 to 68 mm). All cases were treated with David Ⅰ procedure, including simple David procedure in 26 patients, David+ascending aorta and partial aortic arch replacement in 3 patients, David+thoracic endovascular aortic repair in 1 patient, David+stent elephant trunk implantation in 1 patient.Results:The operation time, cardiopulmonary bypass time and aortic cross-clamping time were (330±58) minutes (range: 214 to 481 minutes), (138±23) minutes (range: 106 to 192 minutes) and (108±17) minutes (range: 82 to 154 minutes), respectively. There were no death and serious complications (stroke, myocardial infarction, renal insufficiency, severe infection, etc.). The postoperative drainage volume within 24 hours was (314±145) ml (range: 130 to 830 ml). The intubation time was (14±3) hours (range: 8 to 21 hours), and the ICU time was ( M( Q R)) 2.1(1.5) days (range: 1.0 to 5.0 days). Eight patients had no blood transfusion, the proportion of red blood cell use was 9.7% (3/31), plasma use was 22.6% (7/31), and platelet use was 71.0% (22/31). The postoperative left ventricular ejection fraction was (62±4)% (range: 54% to 69%), and left ventricular end-diastolic diameter was (48±4) mm (range: 39 to 56 mm). After operation, aortic regurgitation was significantly improved, with no more than moderate regurgitation, small to moderate regurgitation in 3 patients, minor regurgitation in 3 patients, micro regurgitation in 12 patients and no regurgitation in 13 patients. The follow-up period was 3.5(6.1) months (range: 2.0 to 39.0 months). Echocardiographic follow-up data were obtained in 26 cases, including moderate regurgitation in 1 patient, small to moderate regurgitation in 9 patients, minor regurgitation in 5 patients, micro regurgitation in 6 patients and no regurgitation in 5 patients. There were no major adverse cardiovascular events and aortic events during the follow-up period. No patient was reoperated for aortic regurgitation. Conclusion:Valve sparing aortic root replacement under partial upper sternotomy is safe and feasible, and the early result is satisfactory.

OBJECTIVE:To study the effect and its possible mechanism of Xuezhiping capsule on blood lipid levels of high blood lipid model golden hamsters. METHODS:Golden hamsters were randomly divided into normal control group,model group, atorvastatin group (3 mg/kg),combination group (Xuezhiping capsule 1.3 g/kg+atorvastatin 1.5 mg/kg),Xuezhiping capsule low-dose,medium-dose,high-dose groups(Xuezhiping capsule 1.3,2.6,5.2 g/kg),10 in each group. Hamsters in normal control group received normal diet,the other groups were given high-fat diet to establish high blood lipid model. Then relevant drugs were intragastrically given 2 weeks later. Normal control group and model group were intragastrically given equal volume of distilled wa-ter,once a day,for 4 weeks. After last administration,blood lipid indexes(TG,TC,HDL-C,LDL-C,FFA),mRNA and protein expressions of lipid metabolism related genes (PPAR-α,CYP7A1,ACOX,SREBP-1c,ACC1) were detected. RESULTS:Com-pared with normal control group,serum contents of TC,TG,LDL-C,FFA in model group increased,HDL-C content decreased;PPAR-α,CYP7A1,ACOX mRNA and protein expressions were weakened,SREBP-1c,ACC1 mRNA and protein expressions were enhanced(P<0.05). Compared with model group,above-mentioned indexes were obviously improved in Xuezhiping capsule high-dose group,atorvastatin group and combination group (except for HDL-C in Xuezhiping capsule high-dose group)(P<0.05);TC,TG,FFA contents,and PPAR-α,CYP7A1,ACOX,ACC1 mRNA,and CYP7A1,SREBP-1c,ACC1 protein were obviously improved in Xuezhiping capsule medium-dose group(P<0.05);TC,TG contents,and PPAR-α mRNA,and CYP7A1, SREBP-1c protein were obviously improved in Xuezhiping capsule low-dose group (P<0.05). CONCLUSIONS:Xuezhiping cap-sule has a promising effect of lowering blood lipid,the mechanism may be related to activating PPAR-α and inhibiting SREBP-lc signaling pathway.

Notch signaling, a highly conserved pathway, is wide-ly found in invertebrates and vertebrates. By mediating cell com-munication, it can regulate many physiological and pathological processes in various kinds of cells, including cell proliferation, differentiation and apoptosis in multi-cellular organism. Accu-mulating evidence shows that abnormality in Notch signaling is highly related to diabetes mellitus and its complications. Accord-ingly, this paper reviews the molecular basis of Notch signaling and the relations between its abnormal expression and diabetes mellitus, and focuses on the impact of key elements in the Notch signaling pathway on diabetic complications as well as correlative mechanisms.

Aim To investigate the protective effect of Panax Notoginseng Saponins ( PNS ) on Aβ25-35-in-duced apoptosis in PC12 cells and molecular mecha-nism. Methods The cell viability of PC12 cells was detected by MTT assay. The levels of LDH leakage, ROS,MDA,Caspase-3 activity and antioxidant enzyme activities of SOD, CAT, and GSH-Px activity were de-termined by respective kits. The apoptosis of cells was decteced by Western blot. Results PNS could signifi-cantly inhibit the decrease of cell viability and LDH leakage, reduce the production of MDA and ROS( P<0. 01), increase the activity of SOD,CAT and GSH-Px ( P <0. 01 ) , and the mitochondrial membrane poten-tial, inhibit the activation of caspase-3 ( P <0. 01 ) in PC12 cells which were induced by Aβ25-35 . PNS could incrase nuclear Nrf2 and up-regulate HO-1 . The neu-roprotective of PNS could be inhibited by HO-1 inhibi-tor ZnPP. Conclusion PNS may inhibit Aβ25-35-in-duced oxidative stress and apoptosis in PC12 cells by activating Nrf2/HO-1 signaling pathway.

Arsenic trioxide has a significantly positive effect on the treatment of acute promyelocyte leukemia( APL) , and it also has been proved that arsenic trioxide can protect against some other kinds of malignant tumors in recent years. However, with the further research about arsenic trioxide, the reports about car-diac toxicity of arsenic trioxide are increasing. Currently, the possible mechanisms of As2 O3-induced cardiotoxicity are mainly considered to be associated with changes in cardiac ion chan-nels, oxidative stress injury and apoptosis. Research advances on cardiac toxicity of arsenic trioxide and some ways of preven-tion are summarized.