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 safety and efficacy of endovascular thrombectomy (EVT) in acute anterior circulation large vessel occlusive stroke (ALVOS) and explore the related influencing factors for prognoses in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECT).Methods:Patients with acute ALVOS who underwent EVT in Yijishan Hospital of Wannan Medical College from January 2019 to June 2022 were sequentially enrolled. (1) Patients were divided into a low ASPECT group (0-5) and a non-low ASPECT group (6-10), and the differences between the two groups were compared with respect to incidence of perioperative complications and good prognosis rate [modified Rankin scale (mRS) score≤2] 90 days after onset. (2) According to the prognoses 90 days after onset, the low ASPECT group was divided into the good prognosis (mRS score≤2) and poor prognosis (mRS score>2) subgroup. Univariate analysis and multivariate logistic regression analysis were used to investigate the independent risk factors for prognoses of the low ASPECT patients after EVT.Results:A total of 582 patients [age 26-94(69±11) years, 345 male patients (59.3%)] were enrolled for analysis. The baseline ASPECT score was 8 (7, 10), and the baseline NIHSS score was 14 (11, 18). Among them, 102 (17.5%) patients were in the low ASPECT score group and 480 (82.5%) patients were in the non-low ASPECT score group. In the total cohort, patients in the low ASPECT score group had a higher incidence of symptomatic intracranial hemorrhage, lower 90-day good prognosis rate, and higher 90-day mortality rate. Further, propensity score matching statistical analysis showed that patients in the low ASPECT score group had a significantly higher incidence of malignant brain edema after EVT treatment (40.0% vs. 17.6%, χ2=9.13, P=0.003), and a significantly lower 90-day good prognosis rate (24.7% vs. 41.6%, χ2=4.96, P=0.026), but there was no significant difference in the incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups (40.3% vs. 26.0%, χ2=3.55, P=0.060). Among 102 patients with low ASPECT score, 22 (21.6%) patients had good prognosis and 80 (78.4%) had poor prognosis. Multivariate logistic regression analysis showed that history of atrial fibrillation ( OR=4.478, 95% CI 1.186-16.913, P=0.027) was an independent risk factor for poor prognosis of EVT in patients with low ASPECT score, while good collateral circulation (grade 2 vs. grade 0: OR=0.206, 95% CI 0.051-0.842, P=0.028) was a protective factor for good prognosis of EVT in patients with low ASPECT score. Conclusions:Although the 90-day good prognosis rate of EVT treatment for patients with low ASPECT score was lower than that of the non-low ASPECT group, 21.6% patients still benefitted from EVT treatment, especially patients with non-atrial fibrillation and good collateral circulation. Future studies involving more patients are needed to validate our observations.

Objective:To evaluate the benefits and risks of advanced age patients with acute anterior circulation large vessel occlusive stroke (ALVOS) accepted mechanical thrombectomy (MT), and explore the related influencing factors for prognoses in these patients.Methods:Six hundred and eighty patients with acute anterior circulation ALVOS accepted MT in 3 comprehensive stroke centers from January 2014 to December 2020 were sequentially collected. (1) Patients were divided into advanced age group (≥80 years old) and non-advanced age group (<80 years old) according to age, and the differences between the two groups were compared in successful postoperative vascular recanalization rate, incidence of perioperative complications, and good prognosis rate (modified Rankin scale [mRS] scores≤2) and mortality 90 d after onset. (2) Patients were divided into good prognosis group (mRS scores≤2) and poor prognosis group (mRS scores>2) according to the prognoses 90 d after onset; univariate analysis and multivariate Logistic regression analysis were used to investigate the independent factors for prognoses of the patients after MT. (3) According to the prognoses 90 d after onset, the advanced age patients were divided into good prognosis subgroup (mRS scores≤2) and poor prognosis subgroup (mRS scores>2). Univariate analysis and multivariate Logistic regression analysis were used to investigate the independent factors for prognoses of the elderly patients after MT.Results:(1) In these 680 patients, 92 patients (13.5%) were into the advanced age group and 588 patients (86.5%) were in the non-advanced age group; patients in the advanced age group had significantly lower successful recanalization rate (67.4% vs. 77.9%), significantly lower good prognosis rate 90 d after onset (20.7% vs. 50.2%), and statically higher mortality 90 d after onset (40.2% vs. 21.1%) as compared with the non-advanced age group ( P<0.05); however, there was no significant difference between the two groups in the incidences of symptomatic intracranial hemorrhage (sICH, 15.6% vs. 10.6%) and malignant cerebral edema (MCE, 12.2% vs. 17.6%, P>0.05). The baseline data of the advanced age and non-advanced age patients were further matched with propensity score matching analysis (1:1) and statistically analyzed: the 91 elderly patients had significantly lower good prognosis rate 90 d after onset (20.9% vs. 36.3%) and MCE incidence (12.4% vs. 33.3%) than the 91 non-elderly patients ( P<0.05); there was no significant differences in successful vascular recanalization rate (67.0% vs. 71.4%), sICH incidence (15.7% vs. 17.6%) or mortality 90 d after onset (39.6% vs. 37.4%) between the two groups ( P>0.05). (2) Among the 680 patients, 314 (46.2%) had good prognosis and 366 (53.8%) had poor prognosis. As compared with the good prognosis group, the poor prognosis group had significantly higher proportion of patients at advanced age, significantly lower proportion of male patients, significantly higher proportion of patients with hypertension, diabetes or atrial fibrillation, significantly lower baseline Alberta Stroke early CT (ASPECT) scores, significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) scores, statistically higher proportion of patients with cardiogenic embolism, significantly lower incidence of tandem lesions, significantly shorter time from onset to sheathing, statistically higher proportion of internal carotid artery occlusion, significantly lower proportion of patients with grading 2 collateral circulation, and significantly lower proportion of successful vascular recanalization ( P<0.05). Advanced age ( OR=3.144, 95%CI: 1.675-5.900, P<0.001) was an independent factor for prognoses 90 d after MT, in addition to baseline ASPECT scores, baseline NIHSS scores, diabetes mellitus, successful recanalization, and collateral circulation grading. (3) In the advanced age group, there were 19 patients (20.7%) with good prognosis and 73 patients (79.3%) with poor prognosis. As compared with the good prognosis subgroup, the poor prognosis subgroup had significantly lower proportion of male patients, significantly lower proportion of patients with grading 2 collateral circulation or complete recanalization, and significantly higher baseline NIHSS scores ( P<0.05). Baseline NIHSS score ( OR=1.482, 95%CI: 1.187-1.850, P=0.001) was an independent factor for prognoses 90 d after MT in advanced age patients. Conclusion:Although advanced age is an independent risk factor for prognoses of patients with acute anterior circulation ALVOS accepted MT, there are still some advanced age patients benefiting from MT without increased complications, especially for those with low baseline NIHSS scores.

Objective To investigate the expression level of serum miR-486-5p in patients with pancreatic cancer and the value of serum miR-486-5p combined with carbohydrate antigen 19-9 (CA19-9) in predicting the resectability of pancreatic cancer. Methods A total of 60 patients who were diagnosed with pancreatic cancer in Qingdao Municipal Hospital from September 2018 to December 2020 were enrolled, among whom 32 patients had resectable or borderline resectable pancreatic cancer (operable group) and 28 had unresectable pancreatic cancer (non-operable group), and a benign pancreatic disease group with 30 patients and a healthy control group with 44 individuals were also established. Quantitative real-time PCR was used to measure the serum level of miR-486-5p in each group, and the relative expression level of miR-486-5p was calculated to analyze its association with the clinical features of pancreatic cancer, including age, sex, tumor location, tumor size, TNM stage, lymphatic metastasis, and distant metastasis. The Mann-Whitney U test was used for comparison of non-normally distributed continuous variables between two groups, and the chi-square test was used for comparison of categorical variables. The receiver operating characteristic (ROC) curve was plotted, and a binary logistic regression analysis was used to calculate the combined predictive value and then investigate the value of serum miR-486-5p combined with CA19-9 in predicting the resectability of pancreatic cancer. Results The relative expression level of serum miR-486-5p in the operable group [2.16 (1.38~3.30)] and the non-operable group [4.65 (2.80~9.90)] was significantly higher than that in the benign pancreatic disease group [1.01 (0.52~1.53)] and the healthy control group [0.99 (0.24~1.01)] (all P < 0.001). There were significant differences in the number of patients with low or high expression of miR-486-5p between the patients with different TNM stages, presence or absence of lymphatic metastasis, and presence or absence of distant metastasis ( χ 2 =13.765, 5.157, and 6.638, all P < 0.05). Compared with CA19-9 alone, miR-486-5p+CA19-9 had a significantly better value in distinguishing the operable group from the benign pancreatic disease group (area under the ROC curve [AUC]=0.87, 95% confidence interval [ CI ]: 0.760-0.942; with a sensitivity of 81.3% and a specificity of 83.3%), distinguishing the operable group from the healthy control group (AUC=0.92, 95% CI : 0.836-0.970; with a sensitivity of 90.6% and a specificity of 86.4%), and distinguishing the operable group from the non-operable group (AUC=0.94, 95% CI : 0.884-0.998; with a sensitivity of 85.7% and a specificity of 93.7%) ( Z =2.841, 2.510, and 2.387, all P < 0.05), and the optimal cut-off values were 3.12, 3.21, and 6.63, respectively. Conclusion MiR-486-5p can be used as a serum biomarker for the diagnosis of pancreatic cancer, and miR-486-5p combined with CA19-9 has a better clinical value than CA19-9 alone in predicting the resectability of pancreatic cancer in the patients with benign pancreatic diseases and the healthy population.

Objective: To identify the independent risk factors of esophageal varices (EV) in cirrhosis by endoscopic ultrasonography (EUS), and further to establish a risk assessment model for predicting EV occurrence and evaluate the clinical predictive value of the model. Methods: A retrospective cohort study was used in this study. Data of patients with cirrhosis without varicosity, who were hospitalized in Tianjin Second People's Hospital from September 2014 to March 2017 were collected. The location, diameter, and number of esophageal collateral circulation were measured by EUS. The non-selective beta blocker (NSBB) medication history and antiviral therapy were recorded. The time of the first EUS examination was taken as the starting point and the follow-up period was set up as 18 months. The end point was the occurrence of EV or the end of follow-up. The independent risk factors of EV occurrence were determined by univariate and multivariate logistic regression analysis, and the risk assessment model of EV occurrence was constructed. The predictive value of evaluation model for disease was studied by ROC analysis. Hosmer-Lemeshow goodness of fit was used to test the fitting efficiency of the evaluation model. Results: A total of 638 subjects were recruited initially, 13 of them were lost in the course of the study. Finally, 625 cases were included in the study. Among them, 369 cases did not develop EV (the non-progress group) and 256 cases developed EV (the progress group). (1) Multivariate logistic regression analysis showed that 7 independent risk factors were selected into the risk assessment model of EV occurrence, and were assigned corresponding scores: no NSBB (3 points), no antiviral treatment (2 points), Child-Pugh stage B (1 point), the diameter of peri-ECV>2 mm (1 point), the number of peri-ECV≥5 (3 points), the diameter of para-ECV≥5 mm (4 points), and the number of para-ECV≥5 (4 points). (2) In the risk assessment model, the risk factor scores ranged from 1 to 4 with a total score of 0-18. The predicted incidence of EV increased from 0.003 to 1.000 with the increase of the score. (3) In the risk assessment model, the total risk score ≤2 was assigned into low-risk group, 3-5 into medium-risk group, and ≥6 into high-risk group. The actual EV incidence of each risk stratification was 2.78% in the low-risk group, 36.36% in the medium-risk group and 93.91% in the high-risk group, respectively. (4) The ROC analysis showed that area under curve (AUC) was 0.947 (P<0.05), suggesting that the risk assessment model had a good effect on predicting disease progression. Hosmer-Lemeshow test showed that P was 0.450, suggesting that the model fitted well. Conclusion The risk assessment model based on EUS can accurately predict the occurrence of EV, and is simple and easy to use. The model can provide scientific basis for the prevention and rational treatment of EV in liver cirrhosis.

Objective To assess the clinical value of endoscopic ultrasonography ( EUS ) for predicting esophageal varices ( EV ) progression in patients with hepatitis B virus ( HBV )-related hepatocirrhosis. Methods A retrospective cohort study was performed on 299 HBV-related hepatocirrhosis patients with light EV in Tianjin Second People′s Hospital admitted from September 2014 to September 2015. The diameter and number of peri-esophageal collateral veins ( ECV ) and para-ECV were measured and described by EUS. The first EUS examination time was the starting point, and the follow-up of 24 months or EV progression was the end. Risk factors of EV progression were evaluated by multivariate Cox regression model, and the predictive value of EUS for EV progression was analyzed by receiver operating characteristic ( ROC) curve. Results The cumulative incidence of EV progression was 2. 3％ ( 7/299 ) , 14. 8％( 44/297) , 33. 7％ ( 96/285) and 40. 0％ ( 120/273) at 6 months, 12 months, 18 months and 24 months of follow-up, respectively. The results of multivariate Cox regression analysis showed that the diameter of peri-ECV ( P=0. 0112, HR=1. 3232, 95％CI: 1. 0656-1. 6429 ) , the number of peri-ECV ( P=0. 0001, HR=1. 3666, 95％CI:1. 1634-1. 6052) and para-ECV diameter ( P=0. 0002, HR=1. 3641, 95％CI:1. 1558-1. 6100) were risk factors for EV progression. The use of nucleoside analogues treating HBV (P=0. 0020, HR=0. 4969, 95％CI: 0. 3186-0. 7751) and non-selective β-blockers descending portal venous pressure ( P=0. 0765, HR=0. 5732, 95％CI:0. 3097-1. 0611) were the protective factors for EV progression. The results of ROC curve analysis showed that the diameter of peri-ECV[ P<0. 001, area under the curve (AUC)= 0. 850, 95％CI: 0. 804-0. 895], the number of peri-ECV (P<0. 001, AUC=0. 831, 95％CI: 0. 784-0. 878), the diameter of para-ECV (P<0. 001, AUC=0. 924, 95％CI: 0. 895-0. 954) , and the number of para-ECV ( P<0. 001, AUC=0. 761, 95％CI: 0. 704-0. 817 ) had higher predictive value for EV progression;and the optimum cut-off values of each index were 1. 85 mm, 3. 5, 3. 35 mm, and 4. 5, respectively. The accuracies of prediction for EV progression were 76. 60％, 75. 19％, 84. 48％ and 70. 29％, respectively. Conclusion EUS can be used to predict EV progression in HBV-related hepatocirrhosis patients. Peri-ECV diameter>1. 85 mm, number>3. 5, and para-ECV diameter>3. 35 mm, number>4. 5 suggest a high risk of EV progression. For patients with HBV-related hepatocirrhosis complicated with mild EV, nucleoside analogues to anti-HBV and non-selective β-blockers to reduce portal hypertension can prevent EV progression.

Objective To investigate reflectance confocal microscopy (RCM) characteristics of childhood hypopigmented lichen striatus.Methods RCM was performed to image skin lesions and perilesional normal skin in 11 children with hypopigmented lichen striatus.Then,confocal microscopic findings of the skin lesions were compared with pathological findings.Results Histopathological examination of the skin lesions showed mild intercellular and intracellular edema,thickening of prickle cell layer to different extent,local liquefaction degeneration of basal cells,and perivascular infiltration of plenty of lymphocytes and a few melanophages in the superficial dermis.RCM horizontal images showed multifocal liquefaction degeneration of basal cells,which caused indistinct dermo-epidermal junction,incomplete or unclear dermal papillary rings,infiltration of many highly refractive melanophages and slightly to moderately refractive inflammatory cells in papillary and superficial dermis.Conclusion RCM characteristics can serve as strong evidences for the diagnosis and differential diagnosis of childhood hypopigmented lichen striatus.

Objective To analyze and compare reflectance confocal microscopy (RCM) features between Paget's disease and eczema on the scrotum.Methods RCM was performed to image scrotal lesions of 5 male patients with suspected Paget's disease and 5 male patients with eczema.Then,the scrotal lesions were resected and subjected to histopathological examination,and a comparison was conducted between the confocal microscopic and pathological findings.Results RCM imaging for the 5 cases of Paget's disease showed disorganized epidermal structure,absence of normal honeycomb structures,single or clustered pagetoid cells in the prickle cell layer.RCM imaging for the 5 cases of eczema showed intercellular edema in the prickle cell layer,reticular degeneration of blisters in all the cases,and pustule formation in some cases.Conclusion RCM features are obviously different between Paget's disease of the scrotum and scrotal eczema,so RCM imaging can facilitate the early diagnosis of Paget's disease.

Objective To evaluate CT findings and dynamic changes of post-traumatic intrapulmonary hematoma.Methods CT data of 43 patients with traumatic intrapulmonary hematomas were analyzed retrospectively.Results A total of 52 lesions were found in 43 patients with intrapulmonary hematomas.The majority of hematomas were located in the peripheral lung fields close to the pleura,single or multiple in number.CT showed nodular,mass,fusiform,ribbon and irregular shadows with uniform and high density in lung.There are two types of evolution: (1) The hematomas gradually reduced in size and finally disappeared;(2)The hematomas evolved into gas-liquid cyst cavity or gas cyst cavity, and then was absorbed gradually.Conclusion CT examination is helpful in the early diagnosis of post-traumatic intrapulmonary hematomas, and can monitor the morphology changes over time.

Objective To assess the predictive value of endoscopic ultrasonography(EUS)for esophageal varices(EV)bleeding by studying the relationship between esophageal collateral veins(ECV), portal vein(PV)trunk with its main branches and EV bleeding. Methods A retrospective cohort study of 114 cases of moderate and severe EV was conducted. The ECV level was determined through EUS. At the same time,diameters of PV,azygos vein(AIV)and spleen vein(SV)were measured through EUS. The predictive value of ECV level and diameters of PV, AIV, SV for EV bleeding were assessed during the 1-year follow-up, which started from the first EUS examination to EV bleeding or the end of follow-up. Results Single factor Cox regression analysis showed severe peri-ECV varices had higher risk than mild in EV bleeding(HR=4.081,95%CI:1.833-9.086,P=0.001); severe para-ECV varices had higher risk than mild in EV bleeding(HR= 4.042, 95%CI:1.814-9.005,P= 0.001). Multivariable Cox retrospective analysis showed ECV level was an effective predictor for EV bleeding, when the peri-ECV and para-ECV were severe varices, EV bleeding risk increased to 3.831 3(P=0.004 3)and 3.493 3(P=0.003 1) times compared with mild respectively. Diameters of PV,AIV and SV could predict EV bleeding(PV AUC=0.959,P<0.001;AIV AUC=0.958,P<0.001;SV AUC=0.830,P<0.001).In addition, when diameter of PV>13.65 mm(sensitivity=0.94, specificity=0.84), AIV>8.65 mm(sensitivity=0.94, specificity=0.89),SV>9.45 mm(sensitivity=0.90, specificity=0.67), EV bleeding risk increased significantly. Conclusion EUS is helpful to predict the risk of moderate and severe EV bleeding, and severe varices of ECV,PV,AIV,and SV can be used as indicators to predict risk of EV bleeding.