T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.

Objective:To compare the prognosis of patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV)-associated ICC after radical resection.Methods:The clinicopathological and survival data of 69 patients with ICC undergoing radical resection in the Department of Hepatobiliary and Pancreatic Surgery, Lihuili Hospital Affiliated to Ningbo University from January 2012 to February 2024 were retrospectively analyzed, including 40 males and 29 females, aged (62.9±10.2) years. Patients were divided into the stone group ( n=40, with hepatolithiasis) and HBV group ( n=29, with HBV). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison. Cox proportional hazard regression model was used for multivariate analysis to analyze the effect of hepatolithiasis and HBV on the prognosis. Results:The median overall survival of ICC patients in the stone group was 16 months, and that in the HBV group was 27 months. The 1-, 3-, and 5-year cumulative survivals of the stone group were 56.6%, 23.2%, and 10.3%, respectively, which were lower than those of the HBV group (72.0%, 50.7%, and 43.4%, respectively, χ2=5.95, P=0.015). The median recurrence-free survivals (RFS) of the stone group and the HBV group were 12 months and 23 months, respectively. The 1-year and 3-year RFS of the stone group were 49.2% and 18.1%, which were lower than those of the HBV group (65.0% and 39.8%, respectively, χ2=3.94, P=0.047). Univariate analysis showed that hepatolithiasis was assciated with prognosis ( χ2=5.95, P=0.015). Multivariate Cox regression analysis showed that hepatolithiasis and hepatitis B virus infection had no effect on the prognosis of ICC patients after surgery (all P>0.05). Conclusion:Compared to HBV infection, ICC patients with hepatolithiasis have a worse prognosis. Hepatolithiasis and HBV infection have no effect on the prognosis of ICC after radical resection.

Objective To study the effects of Danggui-Chuanxiong herb pair medicine on vasoactive substances,adhesion factors,inflammatory factors,and VEGF-PI3K-AKT/NF-κB signaling pathways,in order to elucidate the mechanism of Danggui-Chuanxiong herb pair on the treatment of ischemic stroke(IS).Methods The oxygen glucose deprivation/reoxygenation(OGD/R)model of human umbilical vein endothelial cells(HUVEC)was constructed,and the cell viability was detected by cell proliferation kit(CCK-8 method)to explore the optimal modeling time of seven components;The release of lactate dehydrogenase(LDH)was detected by cytotoxicity kit;The expression of related cytokines was detected by enzyme-linked immunosorbent assay(ELISA);The mRNA expression of key proteins in the signaling pathway was detected by reverse transcription-polymerase chain reaction(RT-PCR).Results Reoxygenation after 6 h of oxygen-glucose deprivation of HUVEC is the best modeling time.High-dose chlorogenic acid group,ferulic acid group,senkyunolide H,low-dose and medium-dose butylidenephthalide group,medium-dose and high-dose senkyunolide A and ligustilide groups significantly decreased LDH leakage rate(P<0.05,P<0.01);The expression of IL-6 in the cells of the partial dose group of chlorogenic acid,caffeic acid,butenylphthalide,senkyunolide H and senkyunolide A was significantly increased,the expression of IL-1 in the cells of the partial dose group of chlorogenic acid,ferulic acid and senkyunolide A was significantly decreased,the expression of VEGF,ICAM-1 and VCAM-1 in the cells of the partial dose group of chlorogenic acid,ferulic acid and senkyunolide H was significantly decreased,the expression of NF-κB in the cells of the partial dose group of chlorogenic acid,ferulic acid,senkyunolide H and ligustilide was significantly decreased,the expression of PAI-1 in the cells of ferulic acid and senkyunolide H partial dose group decreased significantly(P<0.05,P<0.01);The mRNA relative expression levels of ERK,VEGF,NF-κB,VEGFR2 and MMP9 were significantly down-regulated in the cells of chlorogenic acid,ferulic acid,caffeic acid,butylidenephthalide and senkyunolide A partial dose group,while the mRNA relative expression levels of AKT were significantly up-regulated in the cells of senkyunolide H and senkyunolide A partial dose groups(P<0.05,P<0.01).Conclusion The medicinal components of Danggui-Chuanxiong herb pair may play a role in IS by inhibiting the mRNA expression of adhesion factor,inflammatory factor and key protein of VEGF-PI3K-AKT/NF-κB signaling pathway in HUVEC.

Objective:To investigate the factors influencing recipient liver regeneration after full-size split liver transplantation (fSLT).Methods:The clinical data of patients undergoing split liver transplantation in the Affiliated Li Huili Hospital of Ningbo University from May 2019 to Sep 2023 were retrospectively collected. Graft volume (GV) and initial graft volume (IGV) at (30±7) days after operation were measured, and postoperative liver regeneration rate (LRR) was calculated. The patients undergoing fSLT were divided into high regeneration group and low regeneration group with LRR=30% as boundary. The differences of donor and recipient data and perioperative data between the two groups were compared.Results:A total of 52 patients were included. The low fSLT regeneration group (16 cases) was compared with the high fSLT regeneration group (36 cases), and in high fSLT regeneration group donor age was lower, the donor liver steatosis was less, GRWR was lower, the incidence of hepatitis B virus-related liver disease was lower, the postoperative diagnosis of malignant liver disease was lower, the intraoperative blood loss was less, and the postoperative platelet count was higher. The levels of liver enzyme and total bilirubin (TBiL) were higher than those in high regeneration group ( P<0.05). Conclusions:Donor age, donor liver steatosis, GRWR, hepatitis B virus associated liver disease, and recipient pathogenesis are important factors affecting liver regeneration after fSLT. Postoperative platelet and liver enzyme levels are important indicators for monitoring liver regeneration after fSLT.

Objective:To evaluate the short-term efficacy of split liver transplantation (SLT) in patients with acute-on-chronic liver failure (ACLF).Methods:The clinical data of 9 ACLF patients receiving SLT in our center from Mar 2021 to May 2022 were retrospectively analyzed to evaluate its safety and efficacy.Results:The preoperative APASL ACLF Research consortium (AARC) score of the 9 ACLF patients was 8 points in 1 case, 9 points in 3 cases, 10 points in 3 cases, 11 points in 1 case and 12 points in 1 case, 7 cases were in AARC-ACLF grade 2, and 2 cases in grade 3.In-situ liver splitting was performed in 9 deceased donors, including 4 classical split cases, 5 full size split cases. Among these 9 ACLF patients, 2 received left half liver transplantation, 3 received right half liver transplantation, and 4 received extended right lobe liver transplantation. After transplantation, all 9 recipients were discharged fully recovered, 1 case developed Clavien grade Ⅳa complication and 2 cases developed Clavien grade Ⅲb complication.After SLT treatment the median postoperative hospital stay was 27 days, the 1-year survival rate was 100%, and the organ survival rate was 88.9%.Conclusion:Split liver transplantation is a safe and feasible treatment method for ACLF patients.

Peribiliary glands (PBG) is a kind of microscopic structure around the intra-hepatic bile ducts and extrahepatic bile ducts. PBG not only participates in maintaining the normal physiological function of biliary epithelial tissue, but also plays an important role in its damage and repair process. Biliary tree stem/progenitor cells in PBG are important cell sources of biliary epithelial regeneration and repair. PBG and the surrounding peribiliary vascular plexus are key influencing factors for the occurrence of ischemic-type biliary lesions (ITBL) after liver transplantation. Based on relevant literatures and clinical practice, the authors summarize the function of PBG as well as its relationship with ITBL.

Objective:To analyze the correlation between the histological classification of hepatocellular carcinoma (HCC), especially macrotrabecular-massive (MTM), tumor invasiveness, and prognosis.Methods:The clinical and follow-up data of 246 consecutive HCC cases who met the inclusion criteria from 2015 to 2018 were retrospectively analyzed. They were divided into trabecular/pseudoglandular, trabecular/patchy, and MTM types according to the histological classification. The relationship between each type and related clinicopathological features was analyzed. The Kaplan-Meier method was used to plot tumor-free survival (DFS) and overall survival (OS) curves. Log rank tests, COX univariate, and multivariate regression analyses were conducted to analyze the relationship between clinical features, including histological classification, DFS, and OS.Results:Trabecular/pseudoglandular, trabecular/nodular, and MTM type proportions were 44.7% (110 cases), 32.9% (81 cases), and 22.4% (55 cases), respectively. The results of the clinicopathological features showed that MTM-type HCC was significantly more invasive than the other two types, with alpha-fetoprotein (AFP) ≥400 ng/ml, tumor diameter≥8 cm, no tumor capsule, poor differentiation, and MVI positivity proportions, and the differences were statistically significant (P < 0.05).The proportion of MTM-type HCC patients with American Joint Committee on Cancer TNM Stage III to IV and Chinese Liver Cancer Staging (CNLC) II to II was significantly higher than that of the first two types, and the differences were statistically significant (P < 0.05). In addition, the proportion of MTM subtypes undergoing transcatheter arterial chemoembolization was also raised (P < 0.05). The DFS and OS were significantly lower for MTM-type HCC compared to trabecular/pseudoductal-type HCC at 1-, 3-, and 5-years, and the differences were statistically significant (P < 0.05). Univariate analysis indicated that strongly invasive clinical pathological features such as alpha fetoprotein (AFP) ≥400 ng/ml, tumor diameter ≥ 8 cm, no tumor capsule, poor differentiation, positive microvascular invasion, tumor stage, and MTM staging were all risk factors affecting DFS and OS (P < 0.05). Multivariate COX analysis showed that MTM histological staging, AFP ≥ 400 ng/ml, tumor non-encapsulation, satellite nodules, CNLC stages II~III, and TNM stages III~IV were independent risk factors for DFS (P < 0.05), while AFP ≥ 400 ng/ml, tumor non-encapsulation, and CNLC stage II~III were independent risk factors for OS ( P < 0.05).Conclusion:Histological classification is highly correlated with tumor invasiveness and HCC prognosis. Trabecular/pseudoglandular types have lower malignancy and a better prognosis, while MTM types exhibit strong invasive features and a poor prognosis.

Objective:To analyze the risk factors of newly developed non-alcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) based on a propensity score matching (PSM) analysis.Methods:The clinicopathological data of 219 patients with pancreatic or periampullary tumors undergoing PD in the Ningbo Medical Center Lihuili Hospital from December 2015 to December 2021 were retrospectively analyzed, including 129 males and 90 females, aged (63.68±11.07) years old. The patients were divided into two groups according to the newly occurrence of NAFLD within one year after PD: the NAFLD group ( n=57) and non-NAFLD group ( n=162). A caliper value of 0.1 was employed for 1∶1 matching, resulting in a well-balanced PSM between the groups. Results:A total of 144 patients were successfully matched by PSM. Univariate analysis indicated that gender, body mass index, preoperative serum triglyceride and operative time were risk factors for newly developed NAFLD after PD. Multivariate analysis showed that female ( OR=6.493, 95% CI=2.631-16.129, P<0.001), preoperative serum triglycerides ≥1.5 mmol/L ( OR=3.055, 95% CI=1.220-7.654, P=0.017) and operative time ≥300 min ( OR=5.092, 95% CI=1.374-18.865, P=0.015) were the independent risk factors for newly developed NAFLD after PD. Conclusion:Based on PSM analysis, female, preoperative triglyceride ≥1.5 mmol/L and operative time ≥300 min were independent risk factors for newly developed NAFLD after PD.