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*

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

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.

Digestive endoscopy is an important approach for the diagnosis and treatment of digestive tract diseases. With the expansion of gastrointestinal tumor screening projects, more and more patients and asymptomatic healthy people will receive digestive endoscopy, and digestive endoscopy training has become particularly important. The traditional patient-based training mode will be replaced by more standardized training mode. Due to the objectivity, safety and economic advantages, virtual reality (VR) simulation will be helpful for promoting and perfecting the standardized training mode of digestive endoscopists in China. This article reviewed the application, research progress, advantages, current limitations, and potential prospects of VR technique in the digestive endoscopy training.

Objective:To evaluate the efficacy of holographic image technology in robot-assisted laparoscopic radical prostatectomy (RARP).Methods:The clinical data of 34 patients with prostate cancer who underwent RARP in our hospital during October 2020 and December 2020 was analyzed retrospectively. The average age of the patients was 67.8 (52-78) years. The mean BMI was 25.8 (18.0-32.3) kg/m 2. The median level of PSA before surgery was 13.4 (2-149) ng/ml. Median prostate volume was 31.7 (9.5-159.1) ml. EAU risk groups for biochemical recurrence of localised and locally advanced prostate cancer were list as below: 5 cases of low-risk, 7 cases of medium-risk, 22 cases of high-risk. There were 9, 16, 9 cases with the ASA score of 1, 2, 3 point, respectively. Preoperative Gleason score of 34 patients were list as below: 9 cases in score ≤6 group, 15 cases in score=7 group, 10 cases in score ≥8 group. For clinical stage before the surgery, 13 cases ≤T 2a stage, 1 case in T 2b stage, 20 cases ≥T 2c stage. The engineers established holographic images of 34 patients based on multiparametric magnetic resonance imaging (mpMRI) and the reports before the operation. Surgeons can obtain the size and location of tumors, surrounding neurovascular bundles visually by revolving, assembling, disassembling and concealing images, which was helpful for pre-surgery planning. By manipulating the holographic images extracorporeally, surgeons can discriminate Internal sphincter of urinary bladder and vesicoprostatic muscle, neurovascular bundles, membranous part, seminal vesicle easily, which improves the operation accuracy. Results:All 34 cases underwent operation successfully without transferring to open surgery. The median operative time was 157.5 (95-276) min with an estimated blood loss of 50 (20-300) ml. The median drainage removal time was 2 d and median hospitalization time was 3.5 d, respectively. The catheters were removed within an average time of 20.5 d. For postoperative Gleason score, there were 2 cases in score ≤6 group, 16 cases in score =7 group, 8 cases in score ≥8 group and 8 cases can’t make a score. For clinical stage after the surgery, 10 cases were ≤T 2a stage, 1 case was T 2b stage, 23 cases were ≥cT 2c stage. 22 cases underwent pelvic lymph node dissection, including a patient with right iliac fossa lymph node metastasis. There were 2 cases with positive surgical margin and 3 cases with Clavien-DindoⅠcomplications. The rate of 1-month and 3-month urinary continence were 47.1% and79.4%, respectively, 8 cases recovered erectile function after 3 month. Conclusions:Holographic image technology can promote cancer dissection completely, achieve urinary continence early and reduce perioperative complications tremendously. The technology is the "intraoperative security" for the accurate surgical treatment of prostate cancer.

Objective:To investigate the characteristics of 18F-DCFPyL PET/CT imaging in castration-resistant prostate cancer (CRPC) patients with different PSA levels. Methods:The imaging and clinical data of 50 patients with CRPC who underwent 18F-DCFPyL PET/CT examination in Chinese PLA General Hospital from January 2018 to December 2020 were analyzed retrospectively. The average age was 72 (54-95) years old. Serum total PSA was 92.28(0.36-2000.00) ng/ml. According to the total PSA level, the patients were divided into low PSA group(total PSA ≤ 1 ng/ml, n=9), medium PSA group (1 ng/ml10ng/ml, n=23). According to the standardized evaluation standard of molecular imaging, the suspicious tumor lesions on 18F-DCFPyL PET/CT imaging were scored by molecular imaging PSMA(miPSMA), and the miPSMA score ≥2 was defined as positive lesions. According to the number of lesions displayed by 18F-DCFPyL PET/CT, patients were divided into oligofocal group (the number of lesions ≤3) and multiple lesions group (the number of lesions >3). The imaging characteristics of patients in different groups were summarized. Results:The 18F-DCFPyL PET/CT imaging results of 50 cases in this study were all positive, including oligofocal group (n=27) and multiple lesions group (n=23). Of the 30 patients with unresected prostate, 18 had local recurrence of the prostate, while the other 12 patients with unresected prostate and 20 patients with resected prostate had no signs of local recurrence. The oligofocal group showed local recurrence, regional lymph node metastasis or bone metastasis. Patients with multiple lesions showed multiple lymph nodes and/or bone metastasis with or without local recurrence. There were 9, 18 and 4 patients with oligofoci in low, middle and high PSA groups, respectively.There were 27 patients in the oligonucleogenous group, and 21 of the 22 patients receiving local treatment were effective. All 3 patients treated with systemic treatments were effective. PSA progressed in 2 untreated patients. In the multi-foci group of 23 patients, 6 of 9 patients treated with abiraterone were effective. Two patients treated with enzalumide were ineffective. One of the 4 patients with chemotherapy was effective. One of the two patients treated with 177 Lu-PSMA nuclide was effective. One case did not respond to treatment with 89SrCl 2. Radiotherapy failed in 2 cases. PSA progressed in 3 untreated patients. Conclusions:18F-DCFPyLPET/CT imaging has a high detection rate of lesions in patients with CRPC and has potential guiding significance for follow-up treatment. The number of lesions in CRPC patients with different PSA levels was different, and the patients with low PSA levels were mainly oligofoci.

Sixty general practitioners of in-service training undertaking rotation in gastroenterology department of Qingdao Municipal Hospital from July 2017 to July 2019 were randomized assigned in trial group ( n=30) and control group ( n=30). The problem-oriented mode was applied in trial group and conventional mode was applied in control group for teaching of two typical digestive diseases (upper gastrointestinal bleeding and acute pancreatitis). The formative evaluation and questionnaire survey were used to compare the teaching effects and the results of evaluation were compared with χ 2 test by SPSS 17.0 between two groups. The excellent and good rates of evaluation for the clinical psychological quality, clinical reasoning ability, doctor-patient communication ability and practice-based learning and improvement ability in trial group were significantly higher than those in the control group(χ2=7.38, P=0.03; χ2=12.96, P<0.01; χ2=23.33, P<0.01; χ2=16.14, P<0.01). Questionnaire survey showed more satisfaction towards teaching method in trial group was higher than that in control group(χ2=12.86, P<0.01); and the clinical reasoning ability, learning initiative and self-confidence in trial group were improved more markedly than those in control group(χ2=8.26, P=0.02; χ2=19.48, P<0.01; χ2=21.46, P<0.01). The problem-oriented clinical thinking teaching model demonstrates good effects on clinical comprehensive ability for general practitioners of in-service training during gastroenterology rotation, which is worth further promotion.

In this paper, the current situation and existing problems of spinal surgery practice are analyzed and summarized. Combined with the review of the structure and function of spinal region, we have expounded the application and advantages of Essential Anatomy software in the clinical practice teaching of spinal surgery. This software has a friendly interface, simple operation, real content, intuitive and visual model, and it can provide videos and slice function, which makes the original complex and abstract spinal anatomy practice content become novel and vivid, and greatly deepens doctors' understanding of the structure, function, movement and the disease pathogenesis of spinal region. At the same time, it also greatly mobilizes the learning interest and initiative of the clinical practice doctors, and improves the effect of clinical practice.

Background: Artificial intelligence (AI) is a research hotspot in various fields of medicine at present. Its powerful image recognition and processing ability make it having a strong advantage in the field of digestive endoscopy. Aims: To construct a gastroscopy image recognition system based on AI, and to explore its value in the diagnosis of chronic atrophic gastritis (CAG). Methods: A total of 3 813 gastroscopy images were collected from patients who underwent gastroscopy and biopsy for pathological examination from April 2018 to August 2020 at Qingdao Municipal Hospital, including 1 927 images of CAG and 1 886 images of chronic non-atrophic gastritis (CNAG). Among them, 3 055 images were selected as training set (CAG/CNAG, 1 541/1 514) and 379 images (CAG/CNAG, 193/186) as the adjustment set, the remaining images as the test set. Deeping learning model was trained and verified. The receiver operating characteristic curve (ROC curve) and P-R curve were calculated. The sensitivity, specificity and accuracy of deep learning model and that of 3 less experienced endoscopists, 3 experienced endoscopists for diagnosis of CAG were compared. Results: The area under ROC curve of deep learning model for CAG was 0.916 8, the area under P-R curve was 0.931 6, and sensitivity was 89.1%, specificity was 74.2%, accuracy was 81.8%. The sensitivity, specificity and accuracy of deep learning model were superior to the three less experienced endoscopists, and even superior to some of the experienced endoscopists. Conclusions: The CAG diagnostic model based on deep learning technology has high sensitivity, specificity and accuracy, and can effectively identify CAG and assist the clinical endoscopists to diagnose CAG in gastroscopy.

Objective To investigate the significance of "merge" model versus "traditional" model in rotation training for professional clinical postgraduate students in department of gastroenterology. Methods The professional clinical postgraduate students who underwent rotation training in Qingdao Municipal Hospital from July 2012 to July 2016 were enrolled as subjects and were trained with the"merge" model and the "traditional" model, respectively. The two groups of subjects were compared in terms of clinical knowledge , skills , and core competencies . Results The postgraduates trained by the"merge" model had a significantly higher total score of clinical examinations than those trained by the"traditional" model [(92.60±2.52) vs. (83.80±3.14), t=10.93, P<0.01], while there were no significant differences in professional quality and doctor-patient communication between the two groups. Compared with those trained with the"traditional"model, the postgraduates trained by the"merge"model had significantly better understanding of clinical knowledge and clinical thinking ability, diagnosis and treatment skills, and psychological quality (χ2=27.00, 10.23, and 12.21, all P<0.01);however, there was no significant difference in clinical research ability between the two groups (χ2=1.39, P=0.24). Conclusion The model of professional clinical postgraduate training combined with standardized training of residents is superior to the traditional training model, and compared with the "traditional" model, the "merge" model is more beneficial to the training of comprehensive clinical practice abilities and thus holds promise for further application.