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 measure the predictive value of miR-424 on the risk of sepsis complicated with acute respiratory distress syndrome(ARDS), and to explore its correlation with the prognosis of ARDS children.Methods:A prospective study was conducted.The data of children with sepsis (some complicated with ARDS), who were treated in Henan Provincial People′s Hospital (People′s Hospital, Zhengzhou University) were collected from February 2020 to February 2021.The incidence of ARDS and the fatality rate of ARDS children were recorded.Children were divided into survival group and death group according to whether death or not.The expression of miR-424 in peripheral blood mononuclear cells was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Pearson correlation analysis was made to investigate the relationship between the expression level of miR-424 and Pediatric Critical Illness Score(PCIS), Sequential Organ Failure Assessment(SOFA) score, oxygenation index(P/F ratio), C-reactive protein(CRP), procalcitonin (PCT), interleukin 6 (IL-6) and interleukin 8 (IL-8). The factors affecting the prognosis of ARDS children were analyzed by multivariate Logistic regression.Receiver operating characteristic curve(ROC)was used to assess the accuracy of miR-424 in early diagnosis of sepsis complicated with ARDS, and to measure the predicative value of miR-424 on the risk of death in sepsis patients with ARDS. Results:A total of 121 sepsis patients were included in this study, and 36 cases of them were complicated with ARDS.The expression level of miR-424(0.56±0.17)in the blood of sepsis patients complicated with ARDS was significantly lower than that of sepsis patients without ARDS (0.98±0.26)( t=8.776, P<0.001). The expression of miR-424 was negatively co-rrelated with IL-6( r=-0.627, P<0.01), IL-8 ( r=-0.651, P<0.01) and CRP( r=-0.472, P<0.05)in sepsis patients with ARDS.The expression of miR-424 was positively correlated with PCIS score( r=0.330, P<0.05), P/F ratio ( r=0.592, P<0.001) and albumin ( r=0.496, P<0.05) in sepsis patients with ARDS.The ROC showed that miR-424 [area under curve(AUC)=0.908, 95% CI: 0.856-0.960] could differentiate sepsis patients with ARDS from those without ARDS.Compared with that of the survival group(0.63±0.15), miR-424 of the death group decreased significantly(0.42±0.14)( t=3.890, P<0.05). The decreased miR-424 (AUC=0.845, 95% CI: 0.696-0.995)indicated an increased risk of death in children with ARDS.Multivariate Logistic regression analysis showed that miR-424( OR=0.001, P=0.033)and albumin ( OR=0.553, P=0.040) were independent risk factors for death in ARDS children. Conclusions:miR-424 can help with early diagnosis of sepsis complicated with ARDS, and can be used as a predictor of the prognosis of sepsis children complicated with ARDS.

Regulatory B cells(Breg) are a subgroup of B lymphocytes and characterized by their immunosuppressive capacity. The regulation of immune response by Breg plays a critical role in the mouse and human immune systems. Previous studies on Breg mainly focus on autoimmune diseases and tumors, but in recent years, the role of Breg in chronic infectious diseases has attracted attention. This review summarized the phenotypes, modes of action and the role of Breg in the process of chronic infectious diseases aiming to provide a new sight for research on immunotherapy for chronic infectious diseases.

Through literature search in regular database and official websites of relevant countries, this paper combs and summarizes the main characteristics of disease prevention and control systems in five countries, the United States, Germany, South Korea, Australia and Japan, and the European Union at key levels including legal construction, organizational structure, financing, personnel construction and international cooperation, in order to provide decision support for the construction of disease prevention and control system in China in the future.

Through literature search in regular database and official websites of relevant countries, this paper combs and summarizes the main characteristics of disease prevention and control systems in five countries, the United States, Germany, South Korea, Australia and Japan, and the European Union at key levels including legal construction, organizational structure, financing, personnel construction and international cooperation, in order to provide decision support for the construction of disease prevention and control system in China in the future.

Objective: To investigate the implementation of disease prevention and control services at tertiary public general hospitals in Beijing for providing evidences to explore and build a scientific evaluation model of disease control service in medical institutions. Methods: June to September 2018, through a questionnaire survey of 50 tertiary public general hospitals in Beijing, a descriptive analysis was made on the department setting, personnel allocation and service provision status of disease prevention and control at tertiary public general hospitals in Beijing. Results: Among the 44 investigated public tertiary general hospitals, 26(59.1%) medical institutions have set up departments of disease prevention and control. The average staffing of 44 hospitals was 5.8 persons for the department. Professional composition of the staff was mostly nursing and clinical disciplines, and the academic and professional titles were mostly undergraduate and intermediate degrees respectively. Overall performance of disease prevention and control services in public tertiary general hospitals was satisfactory. The work was well carried out in communicable disease control and death-surveillance management, namely in immunoprophylaxis, chronic noncommunicable diseases and injury monitoring, which varies widely in mental health services, occupational health management, environmental and health monitoring and other functions. Conclusions Professional ability and management level of personnel still need to be improved. We should further clarify the joint prevention and control mechanism of the " Three-in-one" nature of disease control institutions, medical institutions and communities, promote the combination of medical treatment and prevention, and explore the classification and grading evaluation of disease control work based on the types and quantity requirements of disease prevention and control services undertaken by hospitals, so as to effectively improve the level of disease control services in hospitals.

Objective: To explore the establishment of an evaluation indicator system for disease prevention and control workload at public hospitals, based on the current situation of disease prevention and control work undertaken by public hospitals of and above secondary level in Beijing, and to provide evaluation assistance for them to do better in this regard. Methods: This research was based on our pervious study of the current situation description of disease prevention and control work undertaken by public hospitals in Beijing, by which the contents of routine disease prevention and control work at hospitals have been initially established. The unit strength of each work was consulted, and the disease prevention and control work was classified according to the results. Meanwhile the consistency test of the work intensity within the category was carried out. After integration, the classification and evaluation indicator of disease prevention and control work in public hospitals of and above secondary level in Beijing was finally established. Results: The workload evaluation indicator system was divided into eight parts: report work, report quality control work, monitoring work, training work, work of public health related clinical diagnosis and treatment, work of clinical examination and vaccination, work of sampling and testing and public health related consultation work. The work intensity of each category ranged from 4.78 to 7.34. Conclusions The evaluation indicator system of workload is suitable for the evaluation of basic works. The unified transformation of workload by using the value of work intensity is conducive to management evaluation, but the limitation of the indicators exists in time and region, making it necessary to adjust by the local specific situation at the promotion and application level.

Objective To define the effect of hypothyroidism on oxidative stress,p38 and c-Jun N-terminal kinases (JNK) mRNA expression in testicular mitochondria of male rats,and to explore the mechanism of hypothyroidism on reproduction.Methods According to body weight (240-270 g),30 male Wistar rats were divided into control group (C group,1 ml/kg normal saline by intragastric administration),low-dose group (L group,0.1 mg/kg propylthiouracil 1 ml/kg by intragastric administration) and high-dose group (H group,10.0 mg/kg propylthiouracil 1 ml/kg by intragastric administration),10 rats in each group,body mass was weighed once every 3 days.After 60 days,all rats were killed.The levels of thyroid hormones [total triiodothyronine (TT3),total thyroxine (TT4),and thyroid stimulating hormone (TSH)] were measured by radioimmunoassay.The activities of superoxide dismutase (SOD) and catalase (CAT) in the testicular mitochondria were determined with spectrophotometric assay.The mRNA expression levels of p38 and JNK in testicular mitochondria were detected by real-time quantitative PCR.Results The weights of H group in 30 and 60 days [(265.73 ± 5.10),(253.72 ± 5.09) g] were significantly decreased in comparison with those of C group [(344.62 ± 4.69),(395.33 ± 8.36) g] and L group [(333.66 ± 3.53),(386.08 ± 7.70) g,P ＜0.05].While,testis organ coefficient of H group [(1.20 ± 0.05) g/100 g] were significantly increased compared with those of L group [(0.93 ± 0.03) g/100 g] and C group [(0.88 ± 0.03) g/100 g,P ＜ 0.05].The serum levels of TT3 [(0.39 ± 0.01) nmol/L] and TT4 [(15.47 ± 1.21) nmol/L] in H group were found to be significantly decreased compared with those of C group [(0.86 ± 0.07),(45.56 ± 1.52) nmol/L] and L group [(0.79 ± 0.06),(39.02 ± 1.33) nmol/L,P ＜ 0.05];whereas the level of TSH [(0.65 ± 0.09) mU/L)] was increased in comparison with those of the C group [(0.18 ± 0.06) mU/L] and L group [(0.27 ± 0.05) mU/L,P ＜ 0.05].In addition,the level of SOD in H group [(60.37 ± 3.14) U/mg prot] was decreased compared with that of C group [(75.18 ± 6.13) U/mg prot,P ＜ 0.05];the level of CAT in H group [(1.46 ± 0.25) U/mg prot] and L group [(1.67 ± 0.39) U/mg prot] decreased significantly compared with that of C group [(3.79 ± 0.44) U/mg prot,P ＜ 0.05].And compared with C (1.000 0 ± 0.000 0) and L (1.114 2 ± 0.124 1) groups,p38 mRNA expression in H group (1.387 4 ± 0.122 0) was significantly increased (P ＜ 0.05).However,there was no significant change in JNK mRNA expression between groups (F =0.95,P ＞ 0.05).Conclusion Hypothyroidism may induce oxidative stress of testicular mitochondria leading to the change of p38 cell signal path and then damage the reproductive system in male rats.

Objective To evaluate the applicability of the Chinese version of SF-36 ( v. 2 ) scale for evaluating the quality of life of hospitalized patients with chronic heart failure. Methods From September 2013 to December 2014, 159 patients with chronic heart failure(NYHA I-IV), who were older than 18 years, clear mind and well self-expressed, were selected as participants. Questionnaire surveys included general survey and SF-36(v. 2) scale. Internal consistency reliability, binary reliability and construct validity were all analyzed as indicators to evaluate SF-36 ( v. 2 ) scale. Results A total of 159 questionnaires were issued and 159 valid questionnaires were recovered. The eight dimensions of SF-36(v. 2) scale including physical function (PF), role-physical (RP), bodily pain (BP), general health (GH), social function (SF), vitality (VT), role-emotion(RE), and mental health (MH) score conversion were (41.57 ±24.86), (48.35 ±21.64), (69.18 ± 25. 68), (31. 28 ± 16. 01), (48. 90 ± 19. 53), (45. 05 ± 22. 76), (59. 43 ± 24. 31), (57. 55 ± 19. 03); the floor effects were 2. 5%, 4. 4%, 3. 1%, 4. 4%, 3. 1%, 6. 3%, 0. 6%, 1. 3%; the ceiling effects were 0. 0%, 3. 8%, 21. 4%, 0. 0%, 0. 0%, 1. 9%, 3. 1%, 0. 0%. The item-convergent validity all achieved the standard (r≥0. 4), and the total scaling success rate of item-convergent was 100. 00%; the dimensions′success rates of item-discriminant validity of RP, BP, RE and SF were all 100%, the rest of four dimensions were PF 95. 71%, GH 85. 71%, VT 89. 29%, MH 94. 29%, and the total success rate was 94. 69%. Internal consistency reliability ranged from 0. 738 to 0. 919; the binary reliability ranged from 0. 808 to 0. 963. Within factors analysis, two common factors were confirmed, separately representing physical health and mental health, altogether making contribution of 61. 66% cumulative variance. Conclusions As the revision of SF-36(v. 1), SF-36(v. 2) scale seemed more friendly in layout for questions and answers, the floor and ceiling effects significantly reduced. Additionally, it also shows good reliability and validity in the evaluation of quality of life of hospitalized patients with chronic heart failure, and the SF-36(v. 2) scale can be used to evaluate the quality of life ( QOL) of patients with chronic heart failure.