bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early onset of pathological polyploidization and cellular senescence in hepatocytes lacking RAD51 creates a pro-fibrotic and pro-tumorigenic inflammatory microenvironment
Authors: Bu Wenqing , Sun Xue , Xue Xiaotong , Geng Shengmiao , Yang Tingting , Zhang Jia , Li Yanan , Feng Chao , Liu Qiao , Zhang Xiyu , Li Peishan , Liu Zhaojian , Shi Yufang , Shao Changshun 
Published: March 2024

Background and Aims:
RAD51 recombinase (RAD51) is a highly conserved DNA repair protein and is indispensable for embryonic viability. As a result, the role of RAD51 in liver development and function is unknown. Our aim was to characterize the function of RAD51 in postnatal liver development.

Approach and Results:
RAD51 is highly expressed during liver development and during regeneration following hepatectomy and hepatic injury, and is also elevated in chronic liver diseases. We generated a hepatocyte-specific Rad51 deletion mouse model using Alb-Cre (Rad51-conditional knockout (CKO)) and Adeno-associated virus 8-thyroxine-binding globulin-cyclization recombination enzyme to evaluate the function of RAD51 in liver development and regeneration. The phenotype in Rad51-CKO mice is dependent on CRE dosage, with Rad51
fl/fl; Alb-Cre+/+ manifesting a more severe phenotype than the Rad51
fl/fl; Alb-Cre+/− mice. RAD51 deletion in postnatal hepatocytes results in aborted mitosis and early onset of pathological polyploidization that is associated with oxidative stress and cellular senescence. Remarkable liver fibrosis occurs spontaneously as early as in 3-month-old Rad51
fl/fl; Alb-Cre+/+ mice. While liver regeneration is compromised in Rad51-CKO mice, they are more tolerant of carbon tetrachloride–induced hepatic injury and resistant to diethylnitrosamine/carbon tetrachloride–induced HCC. A chronic inflammatory microenvironment created by the senescent hepatocytes appears to activate ductular reaction the transdifferentiation of cholangiocytes to hepatocytes. The newly derived RAD51 functional immature hepatocytes proliferate vigorously, acquire increased malignancy, and eventually give rise to HCC.

Conclusions:
Our results demonstrate a novel function of RAD51 in liver development, homeostasis, and tumorigenesis. The Rad51-CKO mice represent a unique genetic model for premature liver senescence, fibrosis, and hepatocellular carcinogenesis.
Risk factors and Nomogram Prediction for Splanchnic Venous Thrombosis in Moderate and Severe Acute Pancreatitis
Authors: Li Hai-Chao , He Huan , Huang Bo-Han , Yang Lei , Ding Yi-Xuan , Cao Feng , Li Fei 
Published: March 2024

BACKGROUND:
Acute pancreatitis is one of the most common gastrointestinal diseases with significant morbidity and mortality, especially in the moderate to severe types. Splanchnic vein thrombosis(SVT) is related to acute pancreatitis but the pathogenesis of SVT in patients with AP is incompletely understood.

AIM
To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated by splanchnic venous thrombosis.

METHODS
The clinical data of 290 patients with MSAP and SAP admitted to Xuanwu Hospital of Capital Medical University between December 2015 and December 2020 were retrospectively analyzed. Patients were divided into two groups: 1) with thrombosis and 2) without thrombosis. Sex, age, etiology, severity of acute pancreatitis, platelet (PLT), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), prothrombin time (PT), activated partial thrombin time (APTT), D-dimer (D-D) levels, type of pancreatic necrosis, proportion and location of pancreatic parenchymal necrosis (PPN), location of local complications, computed tomography severity index (CTSI) and modified CTSI(mCTSI) were recorded. Univariate, logistic multivariate regression analyses and nomogram were used to determine the risk factors for splanchnic venous thrombosis complicated by acute pancreatitis (AP). A receiver operating characteristic (ROC) curve, decision curve and calibration curve were drawn.

RESULTS
Among 290 patients with AP, 71 (24.5%) had SAP, and 219 (75.5%) had MSAP. The median age of all the patients was 49 years; 172 patients (59.3%) had biliary disease, 91 patients (31.4%) had hypertriglyceridemia, 13 patients (4.5%) had alcohol disease, and 14 patients (4.8%) had other diseases. Of the 290 patients, SVT was detected in 35 (12.1%). Univariate analysis showed that the severity of acute pancreatitis, PLT, CRP, PCT, IL-6, PT, D-D, proportion of pancreatic parenchyma necrosis (PPN), necrosis of body-tail, and necrosis involving perihepatic and right subphrenic space, CTSI and mCTSI in the thrombus group were all statistically significant (P < 0.05). The results of multivariate analysis showed that PLT≧422 × 109/L, necrosis of body-tail, and necrosis involving perihepatic and right subphrenic space were independent risk factors for AP complicated with splanchnic venous thrombosis. The nomogram incorporating these factors demonstrated good discrimination, calibration and clinical utility. The area under the curve was as high as 0.845.

CONCLUSION
PLT≧422 × 109/L, necrosis of body-tail, and necrosis involving perihepatic and right subphrenic space are independent risk factors for splanchnic vein thrombosis. A simple nomogram tool helps in the early, accurate prediction of AP. Early and relevant clinical intervention should be provided.