Postnatal heart maturation is the basis of normal cardiac function and provides critical insights into heart repair and regenerative medicine. While static snapshots of the maturing heart have provided much insight into its molecular signatures, few key events during postnatal cardiomyocyte maturation have been uncovered. Here, we report that cardiomyocytes (CMs) experience epigenetic and transcriptional decline of cardiac gene expression immediately after birth, leading to a transition state of CMs at postnatal day 7 (P7) that was essential for CM subtype specification during heart maturation. Large-scale single-cell analysis and genetic lineage tracing confirm the presence of transition state CMs at P7 bridging immature state and mature states. Silencing of key transcription factor JUN in P1-hearts significantly repressed CM transition, resulting in perturbed CM subtype proportions and reduced cardiac function in mature hearts. In addition, transplantation of P7-CMs into infarcted hearts exhibited cardiac repair potential superior to P1-CMs. Collectively, our data uncover CM state transition as a key event in postnatal heart maturation, which not only provides insights into molecular foundations of heart maturation, but also opens an avenue for manipulation of cardiomyocyte fate in disease and regenerative medicine.
Gene Expression Regulation ; Heart ; Myocytes, Cardiac/metabolism* ; Single-Cell Analysis ; Transcription Factors/metabolism*

OBJECTIVES: This study evaluated the prognostic power of serum uric acid (UA) in predicting adverse events in elderly acute coronary syndrome (ACS) patients with diabetes mellitus (DM). METHODS: The analysis involved 718 ACS patients ‍>80 years old whose general clinical data and baseline blood biochemical indicators were collected prospectively from January 2006 to December 2012. These patients were classified into two groups based on DM status, and then followed up after discharge. The Kaplan-Meier method was used for major adverse cardiac event (MACE) rates and all-cause mortality. Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis. Receiver operating characteristic (ROC) curves were analyzed to predict the cutoff value of UA in elderly ACS patients with DM. There were 242 and 476 patients in the DM and non-DM (NDM) groups, respectively, and the follow-up time after discharge was 40‒120 months (median, 63 months; interquartile range, 51‒74 months). RESULTS: The all-cause mortality, cardiac mortality, and MACE rates in both DM and NDM patients were higher than those in the control group ( CONCLUSIONS Serum UA level is a strong independent predictor of long-term all-cause death and MACE in elderly ACS patients with DM.

To construct overexpression lentivirus vector for human regulatory factor X1 (RFX1) gene, and to explore its effect on proliferation of F98 cell line.
 Methods: Huamn RFX1 gene was amplified by polymerase reaction. Gene amplification products were inserted into lentivirus vector pITA, and the lentivirus vector pITA-RFX1 was constructed. The constructed vector was verified by agarose gel electrophoresis and DNA sequencing. Lentivirus vector pITA-RFX1 and virus packaging plasmids were cotransfected into 293T cells, and then transfected into F98 cells. RFX1 protein expression were detected by Western blot and laser confocal before and after transfection. Flow cytometry and cell counting kit-8 were used to detect cellular proliferation.
 Results: Agarose gel electrophoresis and DNA sequencing showed that recombinant lentivirus plasmids pITA-RFX1 were constructed successfully. After transfection of pITA-RFX1, the RFX1 protein were over-expressed, which significantly inhibited the proliferation of F98 cells.
 Conclusion: The overexpression lentivirus vector for RFX1 was constrcted successfully, and the up-regulation of RFX1 can prevent the proliferation of glioblastoma cells.
Animals ; Cell Line, Tumor ; Cell Proliferation ; genetics ; Genetic Vectors ; Glioblastoma ; genetics ; physiopathology ; HEK293 Cells ; Humans ; Lentivirus ; genetics ; Plasmids ; Rats ; Regulatory Factor X1 ; genetics ; physiology ; Transfection ; Up-Regulation

AIM: To analyze and compare the changes of pressure phase plane(PPP) derived τ and K on isolated rat heart during ischemia/reperfusion, and to explore the value of PPP derived τ and K for evaluation of left ventricular diastolic dysfunction. METHODS: LVEDP, -d(p/dt)_(max), τ and K were measured and calculated during ischemia/reperfusion in Sprague-Dawley rat hearts. Meanwhile, the level of lactate dehydrogenase (LDH) in the coronary effluent was measured, and the ultrastructure changes in myocardium were observed under electron microscope. RESULTS: Compared with control group, τ increased and K reduced significantly in each ischemic group in a time dependent manner (P<0.05). With prolonged ischemia, τ was even higher and K was even lower (P<0.05). Compared with control group, except ischemia 15 min, LDH in other groups increased significantly at 10 min and 20 min after reperfusion (P<0.05). Compared with ischemia 30 min, LDH of ischemia 45 min and ischemia 60 min were even higher at 10 min and 20 min after reperfusion (P<0.05). With prolonged ischemia, the abnormal changes of the myocardial ultrastructure were observed. CONCLUSION: PPP derived τ and K may be promising indexes for quantitative assessment of left ventricular diastolic function on isolated) rat heart during ischemia/reperfusion, and indication of the severity of ischemia/reperfusion injury.

Objective To compare the immune protective effects of three antigens of Trichinella spiralis encapsulated larvae on mice.Methods The mice were immunized with Trichinella spiralis encapsulated larvae somatic antigen,encapsulated larva excretory-secretory antigen and encapsulated larva surface antigen,3 times with a 7-day interval,and the adjuvant control and normal control group were set up.Seven days after the final immunization,each mouse was orally challenged with 200 Trichinella spirais larvae.The intestinal adult worms and muscle larvae of Trichinella spiralis of each group were recoveried and examined on Day 7 and Day 30 post-challenge,respectively.The level of 8eruln IgG to antigens of Trichinella muscle muscle larvae wa8 detected by ELISA.Results The intestinal adult worms were reduced by 84.89%.89.73%,85.65%.2.57% in the encapsulated larva somatic,excretory-secretory and surface antigen groups,respectively.The muscle lalwae were reduced by 71.71%,80.98%,73.66%,5.60%, respectively.Adtlltwornl reduction rates(P<0.05) and musclelarva reduction rates(P<0.01) of the encapsulated larva excretory-secretory antigen group and surface antigen group were higher than those of encapsulated larva somatic antigen group.The antibody titers in all the immunized groups increased significantly.and the GMRT values of the encapsulated larva somatic,excretory-secretory and surface antigen groups were 32 798.89,3 474.51,2 984.83,respectively,and were 6.09,7.56,6.50 times higher than those of the normal control group(459.32).Conclusions Trichinella spiralis encapsulated larva antigens can induce strong resistance of host to a subsequent challenge infection.Among these antigens,excretory-secretory antigen is more immunogenic.

The methods for evaluating left ventricular diastolic function completely and simply are lacking in our country at present. To solve this problem, we presents in this paper a novel method, which is developed according to certain algorithms and mathematic models and is carried out by a MATLAB program. This method mainly obtains dP/dt loops, and calculates four important indices, including left ventricular end-diastolic pressure (LVEDP), Maximal decrease in velocity of left ventricular pressure (--(dP/dt)max), Time constant of ventricular isovolumic relaxation (tau) and Chamber stiffness (Kd), according to the changes of left ventricular pressure. The results obtained from the experiment of isolated rat hearts during ischemia/reperfusion have demonstrated the usefulness and validity of this method. Therefore, with the use of tau and Kd as indicators, this is a sensitive and effective method for evaluating the left ventricular diastolic function, and it can be applied to early detection of left ventricular diastolic dysfunction.
Algorithms ; Animals ; Blood Pressure ; Diastole ; Humans ; In Vitro Techniques ; Male ; Models, Cardiovascular ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; Ventricular Dysfunction, Left ; diagnosis ; physiopathology ; Ventricular Function, Left ; physiology

Aim To investigate the influence of intranasal delivery of calcitonin gene-related peptide(CGRP)on cerebral blood supply and expression of vascular endothelial growth factor(VEGF)following experimental subarachnoid hemorrhage(SAH).Methods Wistar rats were divided into normal control group,SAH group,intranasal normal saline(NS)+SAH group and intranasal CGRP+SAH group.SAH models were produced by double injection of autologous arterial blood into cisterna magna.CGRP and NS were given by intranasal perfusion.Dynamic observations of regional cerebral blood flow(rCBF)of cerebral cortex were made using a laser Doppler flowmeter probe.On the third day after the second cisternal injection,the expression of VEGF protein in cerebral cortex was observed by immunofluorescence method combined with laser confocal microscopic observation.Results Anatomic observation revealed that SAH models were successfully manufactured.In SAH and intranasal NS+SAH groups,a drastic and persistent drop in rCBF was noted during the observed periods.The decrease of rCBF in intranasal CGRP+SAH group was slighter as compared with that in SAH and intranasal NS+SAH groups.In SAH and intranasal NS+SAH groups,increased expression of VEGF protein in cerebral cortex was observed on the third day after second cisternal injection as compared with that in normal control group.The expression of VEGF in intranasal CGRP+SAH group was more obvious than that in intranasal NS+SAH group.Conclusion Intranasal delivery of CGRP improves cerebral blood supply and promotes angiogenesis by enhancing the expression of VEGF after SAH.

To evaluate the effectiveness of traditional Chinese medicine (TCM) combined with western medicine on breast cancer after surgical resection.

AIM　To study the glucose and lipids metabolis m and insulin sensitivity of MSG rats during their growing period, and to evalua te the effects of insulin sensitizer pioglitazone on the model rats. MET HODS　Body weights were measured regularly, and glucose and insulin tole rance tests were taken. In their 3 and 10 months old, rats were given insulin se nsitizer pioglitazone orally, then the effects on serum glucose, triglyceride, c holesteral, free fatty acid and insulin concentrations were determined. RESULTS　Compared with normal rats, a slight but significant increase of glucose in MSG rats was revealed. The serum triglyceride, cholesteral, free fat ty acid and insulin concentrations were significantly higher in model rats. More over, gluconeogenesis increased significantly, and insulin tolerance showed abno rmal. However, glucose tolerance was nearlly normal. Pioglitazone could ameliora te all these metabolic disorders. CONCLUSION　Obesity and insuli n resistance were induced by injecting monosodium glutamate (MSG) to neonatal Wi star rats. Pioglitazone can significantly improve the insulin sensitivity of MSG rats. These results suggested that MSG obese rats can be used as an easily acce ssible and inexpensive insulin resistance animal model for evaluating the effica cy and mechanisms of antidiabetic agents.

Purpose:To determine the impact of serum tissue polypeptide specific antigen (TPS) in the treatment for advanced cancer patients. Methods:Serum TPS was examined in 60 advanced cancer cases. 42 of the patients received hepatic arterial chemoembolization or chemotherapy. For those with tumors derived from digestive system, TPS monitoring was performed in serial during the therapeutic courses. Results:No significant differentiation was observed in terms of age, gender, disease or tumor stage. Patients with initial TPS lower than 300 U/L had the most favorable response rate to treatment (PR,CR or MR) of 52.94%, while those with initial TPS higher than 1000 U/L showed no evidence of remission after therapy. 55.56% of the latter developed into PD ( P