Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

Objective:To evaluate the relationship between protein kinase C-delta (PKCδ) and pyroptosis during ventilator-induced lung injury (VILI) in rats.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), group VILI, and VILI plus specific PKCδ inhibitor KAI 9803 group (group K). Phosphate buffer solution 200 μl was injected through the tracheal tube after intubation in group VILI, and KAI 9803 200 μg/kg was given instead in group K. The patients were mechanically ventilated (tidal volume 40 ml/kg, respiratory rate 60 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%, positive end-expiratory pressure 0) for 4 h. Blood samples were taken from the femoral artery at the end of mechanical ventilation for blood gas analysis, and PaO 2 was recorded.Animals were sacrificed at the end of ventilation, lung tissues were removed, and bronchoalveolar lavage fluid (BALF) was prepared.The total protein concentrations in BALF were measured by coomassie blue staining, and concentrations of interleukin-18 (IL-18) and IL-1β in BALF by enzyme-linked immunosorbent assay.Lung tissues were obtained for microscopic examination of the pathological changes which were scored and for determination of wet/dry weight ratio (W/D ratio) and expression of PKCδ and gasdermin D N terminal fragment (GSDMD-N) protein and mRNA (by Western blot or by quantitative real-time polymerase chain reaction). Results:Compared with group C, the lung injury score, W/D ratio, and concentrations of total protein, IL-18 and IL-1β in BALF were significantly increased, PaO 2 was decreased, and the expression of PKCδ and GSDMD-N protein and mRNA was up-regulated in VILI and K groups ( P<0.01). Compared with group VILI, the lung injury score, W/D ratio, and concentrations of total protein, IL-18 and IL-1β in BALF were significantly decreased, PaO 2 was increased, and the expression of PKCδ and GSDMD-N protein and mRNA was down-regulated in group K ( P<0.05 or 0.01). Conclusion:PKCδ can mediates the pathophysiological process of VILI in which pyrolysis is involved in rats.

Objective:To evaluate the effect of rapamycin on the activity of NOD-like receptor C4 (NLRC4) inflammasomes in the rats with ventilator-induced lung injury (VILI).Methods:Thirty-six healthy clean-grade male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), VILI group and rapamycin group (group RAPA). In group RAPA, rapamycin 4 mg·kg -1·d -1 was intraperitoneally injected once a day for 3 consecutive days before establishing the model, while the equal volume of normal saline was given instead in group C and group VILI.The patients were mechanically ventilated for 4 h (tidal volume 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, fraction of inspired oxygen 21%) in VILI and RAPA groups.Blood samples were collected from the femoral artery after the end of ventilation for blood gas analysis and for determination of serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) concentrations (by enzyme-linked immunosorbent assay), and PaO 2 was recorded.The bronchoalveolar lavage fluid (BALF) was collected for determination of the neutrophil count and IL-1β and IL-18 concentrations by enzyme-linked immunosorbent assay.The lung tissues were obtained for examination of the pathological changes (under the light microscope) after HE staining which were scored and for determination of wet to dry weight (W/D) ratio, and expression of mammalian target of rapamycin (mTOR), NLRC4 and caspase-1 (by Western blot) and expression of NLRC4 mRNA (by real-time polymerase chain reaction). Results:Compared with group C, the W/D ratio, lung injury score, neutrophil counts in BALF, and concentrations of IL-1β and IL-18 in serum and BALF were significantly increased, PaO 2 was decreased, and the expression of mTOR, NLRC4, caspase-1 and NLRC4 mRNA was up-regulated in group VILI and group RAPA ( P<0.01). Compared with group VILI, the W/D ratio, lung injury score, neutrophil counts in BALF, and concentrations of IL-1β and IL-18 in serum and BALF were significantly decreased, PaO 2 was increased, and the expression of mTOR, NLRC4, caspase-1 and NLRC4 mRNA was down-regulated in group RAPA ( P<0.05). Conclusion:The mechanism by which rapamycin alleviates VILI may be related to inhibiting activation of mTOR signaling pathway and inhibiting the activity of NLRC4 inflammasomes in rats.

Objective To investigate the home-based rehabilitation of stroke patients in China, and to compare the curative effects under different factors, so as to discuss the strategies for home-based rehabilitation. Methods A total of 234 cases of stroke patients who has been discharged from the center of rehabilitation medicine of a Class Ⅲ Grade A hospital were selected by random cluster sampling method. Family rehabilitation status of patients and their caregivers was investigated by outpatient follow-up, home follow-up and telephone follow-up survey. In the survey, the general information questionnaire, the Barthel Index (BI), the Instrumental Activities of Daily Living (IADL), the Self-perceived Burden Scale (SPBS) and the Zarit Caregiver Burden Interview (ZBI) were applied. Results The results showed that the BI score was (61.77±22.83). The average score of IADL was (7.25±6.26). The SPB score was (29.26±7.07). 91.13% of the patients in the study group had a sense of burden. The ZBI score of the caregivers was (43.97±12.28), 59.40% of which had moderate or severe burden. The result of single factor analysis showed that the differences in the scores of BI, IADL, SPBS and ZBI of patients in different gender were statistically significant (P＜ 0.05). There were significant differences in BI and IADL scores among patients of different ages, main caregivers, family rehabilitation time and caregivers' gender (P＜ 0.05). The differences in the scores of IADL and SPBS of patients with different educational level were statistically significant (P＜0.05). The differences in BI and ZBI scores of patients with different disease types were statistically significant (P＜0.05). Conclusions The family rehabilitation of stroke patients is poor. Medical workers should pay attention to the rehabilitation of patients after discharge, especially to female stroke patients, caregivers and to strengthen the rehabilitation knowledge training for male caregivers. It is suggested that community rehabilitation, family doctor responsibility system and hospital-community-family Union should be vigorously developed so as to improve the family rehabilitation of stroke patients, reduce readmission rate, increase the utilization of social resources, and improve the health level of the whole people.

Objective To explore the effect of continuous quality improvement nursing on HAMA, HAMD score and pain in patients with cervical spine fracture.Methods A total of 120 cervical spine fracture patients in our hospital were randomly divided into control group (n=60) and experimental group(n=60).The patients of control group received routine nursing care interventions while the patients of experimental group received continuous quality improvement nursing intervention.The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) score, visual analogue scale and nursing quality score were compared between the two groups before and after the intervention.Results Compared with intervention before, the scores of HAMD and HAMA in the two groups were decreased after treatment (P<0.05).The scores of HAMD and HAMA in the experimental group were significantly lower (P<0.05).Compared with intervention before, the visual analogue scores of the two groups were decreased in different degrees after intervention, and was significantly lower in experimental group than that of the control group (P<0.05).The quality of nursing was significantly higher than that of the control group (P<0.05).Conclusion Compared with conventional care, continuous quality improvement in the treatment of patients with cervical fractures can not only effectively improve the patient''s pain, but also help to improve negative emotions, and improve the quality of care.So it''s worthy of clinical promotion.

Objective To explore the effect of continuous quality improvement nursing on HAMA, HAMD score and pain in patients with cervical spine fracture.Methods A total of 120 cervical spine fracture patients in our hospital were randomly divided into control group (n=60) and experimental group(n=60).The patients of control group received routine nursing care interventions while the patients of experimental group received continuous quality improvement nursing intervention.The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) score, visual analogue scale and nursing quality score were compared between the two groups before and after the intervention.Results Compared with intervention before, the scores of HAMD and HAMA in the two groups were decreased after treatment (P<0.05).The scores of HAMD and HAMA in the experimental group were significantly lower (P<0.05).Compared with intervention before, the visual analogue scores of the two groups were decreased in different degrees after intervention, and was significantly lower in experimental group than that of the control group (P<0.05).The quality of nursing was significantly higher than that of the control group (P<0.05).Conclusion Compared with conventional care, continuous quality improvement in the treatment of patients with cervical fractures can not only effectively improve the patient''s pain, but also help to improve negative emotions, and improve the quality of care.So it''s worthy of clinical promotion.

Objective To evaluate the role of mitochondrial fission in anoxia-reoxygenation injury to rat hippocampal neurons.Methods Neurons were enzymatically isolated from hippocampi of newborn Sprague-Dawley rats (less than 24 h old).The primary hippocampal neurons were cultured and seeded in 25 mm × 25 mm culture flasks at a density of 7 × 105/ml.The cultured neurons were randomly assigned into 3 groups (n =18 each) using a random number table:control group (C group),anoxia-reoxygenation group (I/R group),and mitochondrial fission inhibitor mdivi-1 group (M group).In group I/R,the vehicle dimethyl sulfoxide (DMSO,final concentration ＜ 0.1％) was added prior to anoxia and the cells were then incubated for 40 min.In group M,mdivi-1 (dissolved in DMSO,final concentration of DMSO ＜ 0.1％) was added prior to anoxia and the cells were then incubated for 40 min.The hippocampal neurons were subjected to oxygen-glucose deprivation (OGD) for 6 h followed by restoration of O2 supply for 20 h.After 20 h of reoxygenation,the level of reactive oxygen species (ROS) (by ELISA),cell apoptosis (using flow cytometry),and expression of mitochondrial fission protein Drp1,Bcl-2 and Bax (by Western blot) were measured.The apoptosis rate and the ratio of Bcl-2 to Bax were calculated.Results Compared with C group,ROS content and apoptosis rate were significantly increased,the expression of Drp1 and Bax was up-regulated,the expression of Bcl-2 was down-regulated,and the ratio of Bcl-2 to Bax was decreased in I/R group (P ＜ 0.05).Compared with I/R group,ROS content and apoptosis rate were significantly decreased,the expression of Drp1 and Bax was down-regulated,the expression of Bcl-2 was up-regulated,and the ratio of Bcl-2 to Bax was increased in M group (P ＜ 0.05).Conclusion Mitochondrial fission is involved in anoxia-reoxygenation injury to rat hippocampal neurons via mitochondria-mediated apoptotic pathway.

Objective To understand the incidence of common geriatric syndromes in hospitalized patients,and analyze the relationship between different kinds of geriatric syndromes.Methods A crosssectional study was conducted by five well-trained investigators-300 patients were chosen from geriatric department and medical department within 3 top three hospitals in Chengdu.Results 300 copies of questionnaires were distributed in total,and 300 questionnaires were returned (response rate 100％).Among those,277 questionnaires were considered valid (valid response rate 92.3％).Among those elderly which were above 65 years old,having risk of falling accounted for 91.3％,feeling pain accounted for 79.1％,chronic constipation accounted for 59.2％,having risk of malnutrition accounted for 49.1％,malnutrition accounted for 28.2％,having risk of pressure ulcers accounted for 32.5％,incontinence accounted for 25.3％,and dysphagia accounted for 17％.The correlation among these syndromes was signifcant.Conclusions The overall incidence of geriatric syndromes in hospitalized patients is higher than that in the community.These syndromes are correlated with each other.One can be a risk factor of other geriatric syndromes and also could affect each other.

Objective To investigate the correlation between plasma brain natriuretic peptide (BNP) ,central aortic systolic pres-sure with the degree of coronary artery lesion .Methods One hundred and fifty patients with coronary artery disease ,positive coro-nary angiographic results and without heart failure in the cardiological department of this hospital from March to June 2011 were selected and divided into the hypertension group (n=90) and the non-hypertension group(n=60) according to the blood pressure . The plasma BNP before angiography was detected by ELISA .The coronary lesion vessels and clinical scores were assessed after an-giography .The central aortic pressure before angiography was measured by the noninvasive measurement method and the diastolic blood pressure(DBP) ,systolic blood pressure(SBP) and pulse pressure(PP)were recorded .The correlation between PP and BNP was analyzed by Logistic regression .Results The plasma BNP concentration in the hypertension group was significantly higher than that in the non-hypertension group(P<0 .05) .The SBP level in 2 vessels ,3 vessels was significantly higher than that in the momal coronary group(P<0 .05) ,the PP in 3 vessels was significantly higher than that in the momal coronary group (P<0 .05) . The BNP level in 3 vessels ,2 vessels and single vessel of coronary artery lesion was significantly higher than that in the normal cor-onary artery group(P<0 .05) .The Logistic regression analysis on the PP influencing factors found that PP was closely related with the number of coronary artery lesion vessels ,lesion score ,LVEF and BNP ;the multiple correlation coefficient between PP with the number of coronary artery lesion vessels ,lesion score and BPN was 0 .91 ,its linear model was PP=0 .543 lesion vessels number +0 .656 lesion score + 0 .864 BNP .Conclusion PP of the central aortic pressure is a risk factor for the development and progress of coronary artery stenosis occurrence .BNP may be used as a plasma marker of the degree of coronary artery stenosis .

BACKGROUND:Autologous shed blood washing with the autologous transfusion system involving recovery, anticoagulation, centrifugation, concentrating and washing has been widely used in clinical practice.
OBJECTIVE:To clarify the characteristics of erythrocytes washing with autologous transfusion system, including recovery rate and hematocrit, the changes of shape, deformability, flow properties and in vivo half-life, oxygen carrying and delivering capacity and erythrocyte immunity and immunereceptor expression.
METHODS:The literatures published from January 1987 to January 2013 were retrieved by the first author in Wanfang and PubMed databases. Key words were“blood transfusion, autologus, blood preservation, erythrocytes”in English and Chinese. A total of 200 literatures relating to the erythrocyte characteristics in autologous blood transfusion were found by the computer, 60 of which were retained for further analysis after eliminating repetitive researches.
RESULTS AND CONCLUSION:Because of the mechanical force, such as negative pressure suction, centrifugal separation, and inflammatory mediators, enzymes, activated complements released by various damaged tissues and cells, the col ected erythrocytes were damaged to some extent. As a result, the total recovery rate of erythrocytes depended on the recovery rate, storage breakage rate and cleaning loss rate. The oxygen carrying capacity of erythrocytes was not influenced significantly by this procedure, so the recycled erythrocytes had the same oxygen carrying capacity with normal erythrocytes. To some extent, the number of surface receptors and immune function of recycled erythrocytes descended, but they were better than the erythrocytes preserved for 2 weeks. Studies suggested that blood recovery technology should be improved to reduce the functional decline in immune adherence of the recycled erythrocytes.