Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration

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.

Laparoscopic liver tumor resection of clinical experience in 126 patients / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the clinical application technology of completely laparoscopy hepodectomy (LH).</p><p><b>METHODS</b>From June 2006 to December 2011, the 126 cases of LH were performed, the data including operating time, blood loss and postoperative complications, etc, were analyzed retrospectively. The patients included 87 males and 39 female and they were 28-83 years old with an average age of 44.5 years old. The parenchyma was transected using laparoscopic ultrasonic scalpel and ligasure, accomplished with endoscopic linear stapler. Of all the patients, the diseases performed LH including primary liver carcinoma (45 cases), liver hemoangioma (58 cases), colon carcinoma with livermetastasis (23 cases), liver focar (5 cases), liver granuloma (1 case), liver adenoma (4 cases). The operations included left hemihepatectomy (n = 17), left lateral lobectomy (n = 34), right hemihepatectomy (n = 15), segmentectomy (n = 22), local resection (n = 59).</p><p><b>RESULTS</b>Of all the patients, mean blood loss was 180 ml (10-1250 ml), mean surgical time was 142 minutes (43-220 minutes), mean postoperative hospital day was 2.2 days (3-12 days). Postoperative complications including eight cases of bile leakage, recovered after 1-3 weeks by appropriately draining. The patients with malignant tumor were followed up for 18 months (12-46 months), recurrence happened in 12 cases and four cases was died of recurrence and metastasis.</p><p><b>CONCLUSIONS</b>LH is a safe, feasible and effective procedure for the treatment of benign liver disease and malignant liver neoplasm as long as the patient is properly selected, it should be recommended for radical resection of hepatocellular carcinoma.</p>

Clinicopathologic features, diagnosis and treatment with solid-pseudopapillary tumor of the pancreas: a report of 33 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic and immunohistochemical features, biological behavior, diagnosis and treatment of solid pseudopapillary tumor of the pancreas (SPTP).</p><p><b>METHODS</b>A retrospective clinical and clinicopathologic analysis was made on 33 cases of SPTP admitted from May 2001 to 2010 July. There were 7 male and 26 female patients, aging from 13 to 66 years with a mean of 34.3 years.</p><p><b>RESULTS</b>The tumor was located in pancreatic head of 10 patients, in pancreatic neck of 5 patients, in pancreatic body and tail of 18 patients. Of the 33 patients treated with surgery, 8 underwent simple resection of pancreatic tumor, 6 underwent pancreaticoduodenectomy, 3 underwent tumor resection plus pancreaticojejunostomy, 1 underwent tumor resection plus pancreaticogastrostomy, 11 underwent distal pancreatectomy, 4 underwent distal pancreatectomy plus spleen resection (1 underwent mesohepatectomy for hepatic metastasis). Sixteen of the 33 operations were completed by laparoscopy. Histologically, tumors were composed of papillary and microcystic solid structures, with uniformed population of cells. The pancreas and blood vessels invasion were identified in 3 cases, one of them was combined with liver metastasis, and they are male. Immunohistologically, the tumors were positive for α1-antitrypsin, α1-antichymotrypsin, β-catenin, CD10, CD56 and vimentin (all cases), neuron-specific enolase (3 cases), synaptophysin (6 cases), chromogranin A (4 cases), progesterone receptor (28 cases), estrogen receptor (3 cases), S-100 (6 cases). Totally 33 cases were followed up with a median period of 49 months without tumor recurrence.</p><p><b>CONCLUSIONS</b>SPTP is of low graded malignancy. It primarily affects young women. It may be located in any part of pancreas. Immunohistochemistry is very important for the diagnosis and differential diagnosis of SPTP. Surgical resection is recommended as the treatment of choice. Laparoscopic distal pancreatectomy or tumor resection is feasible and safe for some selected patients, and the prognosis is good.</p>