Identification of DNA repair gene signature and potential molecular subtypes in hepatocellular carcinoma.

DNA repair is a critical factor in tumor progression as it impacts tumor mutational burden, genome stability, PD-L1 expression, immunotherapy response, and tumor-infiltrating lymphocytes (TILs). In this study, we present a prognostic model for hepatocellular carcinoma (HCC) that utilizes genes related to the DNA damage response (DDR). Patients were stratified based on their risk score, and groups with lower risk scores demonstrated better survival rates compared to those with higher risk scores. The prognostic model's accuracy in predicting 1-, 3-, and 5-year survival rates for HCC patients was analyzed using receiver operator curve analysis (ROC). Results showed good accuracy in predicting survival rates. Additionally, we evaluated the prognostic model's potential as an independent factor for HCC prognosis, along with tumor stage. Furthermore, nomogram was employed to determine the overall survival year of patients with HCC based on this independent factor. Gene set enrichment analysis (GSEA) revealed that in the high-risk group, apoptosis, cell cycle, MAPK, mTOR, and WNT cascades were highly enriched. We used training and validation datasets to identify potential molecular subtypes of HCC based on the expression of DDR genes. The two subtypes differed in terms of checkpoint receptors for immunity and immune cell filtration capacity.Collectively, our study identified potential biomarkers of HCC prognosis, providing novel insights into the molecular mechanisms underlying HCC.

IL-13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation.

Keloids are considered the manifestation of a fibroproliferative disease characterized by chronic inflammation that is induced following skin injury. Deciphering the underlying mechanism of keloid formation is essential for improving treatment outcomes. Here, we found that more macrophages were activated toward the M2 subtype in keloid dermis when compared with normal dermis. Western blotting revealed that the level of phosphorylated STAT6 (p-STAT6), a known inducer of M2 polarization, was higher in keloid fibroblasts as opposed to fibroblasts from normal dermis. Moreover, keloid fibrosis was shown to be positively correlated with the level of p-STAT6. Further, we identified downregulation of IL-13RA2, a decoy receptor for IL-13, in keloid fibroblasts compared with fibroblasts from normal dermis. Ectopic expression of IL-13RA2 in keloid fibroblasts resulted in inhibition of STAT6 phosphorylation, cell proliferation, migration, invasion, extracellular matrix secretion, and myofibroblast marker expression, as well as an increase in apoptosis. Consistently, knockdown of IL-13RA2 in normal fibroblasts induced a keloidal status. Furthermore, both in vitro application and intratumoral injection of p-STAT6 inhibitor AS1517499 in a patient-derived xenograft keloid-implantation mouse model resulted in proliferation inhibition and tissue necrosis, apoptosis, and myofibroblast marker reduction. Collectively, this study elucidates the key role of IL-13RA2 in keloid pathology and inspires further translational research of keloid treatment concerning JAK/STAT6 inhibition.

Early cannulation arteriovenous graft (Acuseal) versus standard arteriovenous graft in patients with end-stage renal disease.

INTRODUCTION: The use of Acuseal arteriovenous graft (AAVG) is spreading in end-stage renal disease (ESRD) patients for its advantages in early cannulation. However, comparison of clinical outcomes between AAVGs and standard arteriovenous grafts (SAVGs) is limited. In this study, we compared the performance of AAVGs and SAVGs. METHODS: Consecutive ESRD patients underwent prosthetic vascular access between October 2017 and May 2019 at a single center were identified. Patients were divided into AAVG group and SAVG group. Patients' demographics, perioperative characteristics, and clinical outcomes were collected. Primary, primary assisted, and secondary patency rates were compared using Kaplan-Meier analyses. Postsurgery complications were compared using chi-square test or the Fisher's exact test. FINDINGS: A total of 304 arteriovenous grafts (AVGs) were implanted in 145 males and 159 females (mean age, 60.1 years; range, 20-91 years), comprising 143 AAVGs and 161 SAVGs. Median time to first cannulation was 3 days (interquartile range [IQR], 1-15 days) in the AAVG group and 30 days (IQR, 20-52 days) in the SAVG group (P < 0.001). Adjusted primary, primary assisted, and secondary patency at 12 months were not significant different between AAVGs and SAVGs (P = 0.911, P = 0.945, and P = 0.640, respectively). There was no statistical significance in regards to thrombosis (AAVG, 34.3%; SAVG, 26.1%; P = 0.120) and infection (AAVG, 4.9%; SAVG, 2.5%; P = 0.261) between the groups. DISCUSSION: Acuseal grafts provide comparable patency, and complication rates to SAVGs, with less time to first cannulation from the graft implanted.

Variants and haplotypes in Flap endonuclease 1 and risk of gallbladder cancer and gallstones: a population-based study in China.

The role of FEN1 genetic variants on gallstone and gallbladder cancer susceptibility is unknown. FEN1 SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method in blood samples from 341 gallbladder cancer patients and 339 healthy controls. The distribution of FEN1-69G > A genotypes among controls (AA, 20.6%; GA, 47.2% and GG 32.2%) was significantly different from that among gallbladder cancer cases (AA, 11.1%; GA, 48.1% and GG, 40.8%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-69G > A GA (OR = 1.73, 95% CI = 1.01-2.63) and the FEN1-69G > A GG (OR = 2.29, 95% CI = 1.31-3.9). The distribution of FEN1 -4150T genotypes among controls (TT, 21.8%;GT, 49.3% and GG 28.9%) was significantly different from that among gallbladder cancer cases (TT, 12.9%; GT, 48.4% and GG 38.7%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-4150T GT(OR = 1.93, 95% CI = 1.04-2.91) and the FEN1-4150T GG(OR = 2.56, 95% CI = 1.37-5.39). A significant trend towards increased association with gallbladder cancer was observed with potentially higher-risk FEN1-69G > A genotypes (P < 0.001, χ2 trend test) and FEN14150G > T (P < 0.001, χ2 trend test) in gallstone presence but not in gallstone absence (P = 0.81, P = 0.89, respectively). In conclusion, this study revealed firstly that FEN1 polymorphisms and haplotypes are associated with gallbladder cancer risk.

Upregulated plasma and urinary levels of nucleosides as biological markers in the diagnosis of primary gallbladder cancer.

We first detected aberrant nucleoside levels in the plasma, urine, bile, and tissues from cases and controls to explore them as biomarkers in the diagnosis of gallbladder cancer. Reversed-phase high-performance liquid chromatography was used to assess the levels of ten nucleosides in these samples from gallbladder cancer patients, gallstone patients, and healthy controls. Plasma and urine samples were collected from patients with gallbladder cancer (n = 202), patients with gallstones (n = 203), and healthy controls (n = 205); bile and tissue samples were collected from 91 gallbladder cancer patients, 93 gallstone patients; and 90 were donated after cardiac death. Of the ten nucleosides analyzed, eight urinary nucleosides, five plasma nucleosides, three bile nucleosides, and one tissue nucleoside were significantly upregulated in the gallbladder cancer patients compared to control groups (p < 0.05). Among these upregulated nucleosides, the sensitivity, specificity, and accuracy of urinary nucleosides in the diagnosis of gallbladder cancer patients were 89.4, 97.1, and 95.7%, respectively, those of plasma nucleosides were 91.2, 95.6, and 94.2%, respectively, those of bile nucleosides were 95.3, 96.4, and 95.1%, respectively, and those of tissue nucleosides were 86.2, 93.8, and 92.6%, respectively. These results suggest that nucleosides may be as useful as biological markers for gallbladder cancer.

Laparoscopy and laparoscopic ultrasonography in judging the resectability of pancreatic head cancer.

OBJECTIVE: To explore the clinical value of laparoscopy and laparoscopic ultrasonography (LUS) in judging the resectability of pancreatic head cancer. METHODS: LUS was employed as a prospective diagnosis of tumor staging before exploratory laparotomy in 22 patients diagnosed with pancreatic head cancer to identify whether the liver and peritoneum had small metastases or local invasion to the portal vein, superior mesenteric vessel, aorta, inferior vena cava. RESULTS: In the 22 patients receiving laparoscopy and LUS, we found peritoneal or surface liver metastases (3 patients), hepatic parenchyma metastases (1), and pancreatitis proved by biopsy under ultrasound guidance (1). Laparotomy was avoided in these 5 patients. Of the remaining 17 patients, 8 patients, including 2 patients with portal vein emboli due to tumor metastases had hypertrophic lymph nodes or tumor invasion of local vessels in the peritoneal cavity, retroperitoneum, and omentum and the other 9 patients had resectable tumors shown by LUS. The 17 patients were subjected to exploratory laparotomy, and pancreaticoduodenectomy was successful in 8 patients. CONCLUSIONS: Laparoscopy and LUS can be used to precisely estimate the possibility of resection of pancreatic head cancer, and prevent unnecessary exploratory laparotomy and its complications. It can be used as a routine examination before exploratory laparotomy.