Sirtuin 6 Deacetylates Apoptosis-Associated Speck-Like Protein (ASC) to Inhibit Endothelial Cell Pyroptosis in Atherosclerosis.

Endothelial cell dysfunction is the main pathology of atherosclerosis (AS). Sirtuin 6 (SIRT6), a deacetylase, is involved in AS progression. This study aimed to investigate the impacts of SIRT6 on the pyroptosis of endothelial cells and its underlying mechanisms. ApoE-/- mice were fed a high-fat diet (HFD) to establish the AS mouse model, atherosclerotic lesions were evaluated using oil red O staining, and blood lipids and inflammatory factors were measured using corresponding kits. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish the cell model, and pyroptosis was evaluated by flow cytometry, ELISA, and western blot. Immunoprecipitation (IP), co-IP, western blot, and immunofluorescence were used to detect the molecular mechanisms. The results showed that SIRT6 expression was downregulated in the blood of HFD-induced mice and ox-LDL-induced HUVECs. Overexpression of SIRT6 reduced atherosclerotic lesions, blood lipids, and inflammation in vivo and suppressed pyroptosis of HUVECs in vitro. Moreover, SIRT6 interacted with ASC to inhibit the acetylation of ASC, thus, reducing the interaction between ASC and NLRP3. Moreover, SIRT6 inhibits endothelial cell pyroptosis in the aortic roots of mice by deacetylating ASC. In conclusion, SIRT6 deacetylated ASC to inhibit its interaction with NLRP3 and then suppressed pyroptosis of endothelial cells, thus, decelerating the progression of AS. The findings provide new insights into the function of SIRT6 in AS.

Immune checkpoint inhibitor­associated diabetes mellitus in patients with HCC: Report of three cases and literature review.

Treatment with immune checkpoint inhibitors (ICIs) is steadily becoming the standard of care for hepatocellular carcinoma (HCC), with an increasing number of immune-related adverse events (irAEs). However, only a small number of reports on the occurrence of diabetes mellitus (DM) in patients with HCC treated with ICIs have been published. In the present study, the clinical manifestations, laboratory findings, treatment and prognosis of three patients with advanced HCC were reported, who suffered immune-related DM when receiving treatment with ICIs. Furthermore, the relevant literature was reviewed in order to summarize clinical manifestations, possible mechanisms, diagnosis, prognosis of rechallenge and recommended management options, as well as clinical treatment suggestions. ICI-induced diabetes is rare but irAEs are potentially fatal, as diabetic ketoacidosis (DKA) is often the first manifestation. The incidence of immune-related DM is 0.86% and among those cases, the incidence of DKA is 59%. The combination of two ICIs markedly increases the risk. The human leukocyte antigen genotype, islet autoantibodies and autoreactive T cell-mediated ß-cell destruction may be linked to the occurrence of immune-related DM. Patient education and clinicians' awareness of ICI-related DM are good management options. Adequate clinical judgment, close monitoring and early detection are also needed to decide whether to continue immunotherapy or to rechallenge it, so as to achieve the maximum benefit of clinical treatment.

Integrinß-1 in disorders and cancers: molecular mechanisms and therapeutic targets.

Integrinß-1 (ITGB1) is a crucial member of the transmembrane glycoprotein signaling receptor family and is also central to the integrin family. It forms heterodimers with other ligands, participates in intracellular signaling and controls a variety of cellular processes, such as angiogenesis and the growth of neurons; because of its role in bidirectional signaling regulation both inside and outside the membrane, ITGB1 must interact with a multitude of substances, so a variety of interfering factors can affect ITGB1 and lead to changes in its function. Over the past 20 years, many studies have confirmed a clear causal relationship between ITGB1 dysregulation and cancer development and progression in a wide range of benign diseases and solid tumor types, which may imply that ITGB1 is a prognostic biomarker and a therapeutic target for cancer treatment that warrants further investigation. This review summarizes the biological roles of ITGB1 in benign diseases and cancers, and compiles the current status of ITGB1 function and therapy in various aspects of tumorigenesis and progression. Finally, future research directions and application prospects of ITGB1 are suggested. Video Abstract.

MYC-activated LINC00607 promotes hepatocellular carcinoma progression by regulating the miR-584-3p/ROCK1 axis.

BACKGROUND: There have been many reports of long non-coding RNAs (lncRNAs) in tumors, and abnormally expressed lncRNA is closely related to hepatocellular carcinoma (HCC). The mechanism of LINC00607 in HCC has not been reported. METHODS: We utilized qPCR to evaluate the RNA expression level. The mechanism of MYC binding to the LINC00607 promoter was revealed through chromatin immunoprecipitation assay and dual luciferase reporter assay. The proliferation and invasive ability were evaluated by CCK-8 and transwell assays. The relation between LINC00607 and miR-584-3p was assessed by RNA immunoprecipitation assay and dual luciferase reporter assay. The level of ROCK1 was evaluated by qPCR and western blot. RESULTS: In this research, we found that the expression of LINC00607 was higher in HCC tissues when compared with that in the adjacent non-tumor tissues. Meanwhile, MYC was observed to interact with the LINC00607 promoter, leading to the upregulation of LINC00607 in HCC. We further revealed that LINC00607 functioned as a sponge for miR-584-3p. Cell proliferation and migration assays showed that miR-584-3p may inhibit the HCC progression. Moreover, we found that the miR-584-3p inhibitor could reverse the effects of LINC00607 downregulation in HCC through rescue experiments. Through verification, miR-584-3p bound to the 3' UTR of ROCK1 to downregulate its expression. CONCLUSION: LINC00607 regulated by MYC can promote the proliferation, migration and invasion of HCC cells through the miR-584-3p/ROCK1 axis.

One filter may be enough for duplicate inferior vena cava filter implantation in patients with deep venous thrombosis: Two cases report.

BACKGROUND: Duplicate inferior vena cava (IVC) is an uncommon congenital malformation, but should be treated carefully under the circumstances of deep venous thrombosis (DVT). However, there is a paucity of clinical guidance on this situation. METHODS: Duplicate IVC was diagnosed based on the imaging examination that revealed the dual IVC. Deep venous thrombosis was diagnosed by Compression Doppler ultrasonography of both lower extremities with the high-elevated D-dimer. Retrievable IVC filters were implanted to prevent massive and fatal pulmonary embolism. Appropriate anticoagulation therapy was also performed. RESULTS: Two retrievable filters were successfully implanted and retrieved in two patients with deep venous thrombosis and duplicate inferior vena cava, respectively. During further follow-up, no adverse event was reported. CONCLUSION: Comprehensive imaging examination might contribute to the diagnosis of duplicate IVC, especially when individual conditions were limited. The position above the confluence of bilateral IVCs might be an appropriate suprarenal retrievable filter insertion location. To deal with different types of dual IVC anatomy, different strategies should be taken into consideration.

Hazardous Situation During Conversion of a Long-term Indwelling VenaTech Convertible Inferior Vena Cava Filter.

BACKGROUND: A lack of high-quality research and data has restricted the comprehensive understanding of the conversion procedure of convertible inferior vena cava filters. The aim of this study was to present an unusual situation with a high risk of causing complication, during conversion of VenaTech convertible inferior vena cava filter and our management procedure. METHODS: Lower extremity deep venous thrombi were detected in a 62-year-old woman before major orthopedic surgery. A VenaTech convertible inferior vena cava filter was placed to prevent possible pulmonary embolism and 106 days later, the filter was converted without any complications. RESULTS: At the 6-month follow-up, no adverse events were reported. CONCLUSIONS: The long-term indwelling of a filter might increase the complexity and uncertainty of the conversion procedure. This report presented a rare but hazardous situation during conversion and our management procedure.

A novel approach for monitoring TGF-ß signaling in vivo in colon cancer.

The TGF-ß receptor kinase inhibitors (TRKI) have been reported to inhibit tumorigenicity in colon cancer. However, there is no direct evidence showing that these inhibitors function through inhibiting the TGF-ß- mediated tumor-promoting effects in vivo. We established a TGF-ß inducible reporter system by inserting a luciferase reporter gene to the vector downstream of TGF-ß-inducible promoter elements, and transfected it into colon cancer cell lines. TRKIs SB431542 and LY2109761 were used to treat TGF-ß inducible cells in vitro and in vivo. The luciferase activity was induced 5.24-fold by TGF-ß in CT26 inducible cells, while it was marginally changed in MC38 inducible cells lacking Smad4 expression. Temporary treatment of mice with SB431542 inhibited the TGF-ß pathway and TGF-ß induced bioluminescence activity in vivo. Long-term treatment with LY2109761 inhibited tumorigenicity and liver metastasis in vivo in concomitant with reduced luciferase activity in the tumor. In this study, we established a model to monitor the TGF-ß pathway in vivo and to compare the antitumor effects of TRKIs. Based on this novel experimental tool, we provided direct evidences that LY2109761 inhibits tumorigenicity and liver metastasis by blocking the pro-oncogenic functions of TGF-ß in vivo.

Small hepatocellular carcinoma suppressed by chemotherapy for synchronous gastric carcinoma after laparoscopy-assisted radical distal gastrectomy: A case report and literature review.

RATIONALE: Synchronous gastric carcinoma and hepatocellular carcinoma (HCC) is rare. It is hard to distinguish synchronous HCC from metastatic liver cancer in this condition. The treatment and prognosis is quite different for synchronous HCC of gastric carcinoma and liver metastasis of gastric carcinoma. PATIENT CONCERNS: A 68-year-old man with a chief complaint of epigastric pain for 1 year, accompanied by reflux and belching. The patient was diagnosed with gastric carcinoma (cT4NxM0) and laparoscopy-assisted radical distal gastrectomy was performed. This was followed by chemotherapy of FOLFOX regimen. However, a liver nodule growth was observed after postoperative systemic treatment. DIAGNOSIS: The initial diagnosis was liver metastasis of gastric carcinoma. However after hepatectomy of segment VI and VII as well as thrombectomy of right hepatic vein, histology revealed intermediate to poor differentiated HCC. Hence this case was diagnosed as synchronous gastric carcinoma and HCC. INTERVENTIONS: A preventive transcatheter arterial chemoembolization (TACE) was conducted at 4 weeks after hepatectomy. Another FOLFOX regimen was suggested, but was refused by the patient. OUTCOMES: The patient survived without tumor recurrence for 9 months after the second surgery. LESSONS: Synchronous HCC should be routinely distinguished from gastric carcinoma liver metastasis, especially for patients with hepatitis B virus (HBV) infection. The FOLFOX4 regimen for treating gastric carcinoma liver metastasis may have inhibited the progression of primary HCC in this case. This patient with HCC benefited from liver resection, inspite of hepatic vein tumor thrombosis.

Effect of surgical liver resection on circulating tumor cells in patients with hepatocellular carcinoma.

BACKGROUND: This study explored the effect of liver resection on perioperative circulating tumor cells (CTCs) and found that the prognostic significance of surgery was associated with changes in CTC counts in patients with hepatocellular carcinoma (HCC). METHODS: One hundred thirty-nine patients with HCC were consecutively enrolled. The time-points for collecting blood were one day before operation and three days after operation. CTCs in the peripheral blood were detected by the CellSearch™ System. RESULTS: Both CTC detection incidence and mean CTC counts showed greater increases postoperatively (54%, mean 1.54 cells) than preoperatively (43%, mean 1.13 cells). The postoperative CTC counts increased in 41.7% of patients, decreased in 25.2% of patients and did not change in 33.1% of patients. The increase in postoperative CTC counts was significantly associated with the macroscopic tumor thrombus status. Patients with increased postoperative CTC counts (from preoperative CTC < 2 to postoperative CTC ≥ 2) had significantly shorter disease-free survival (DFS) and overall survival (OS) than did patients with persistent CTC < 2. Patients with persistent CTC levels of ≥2 had the worst prognoses. CONCLUSIONS: Surgical liver resection is associated with an increase in CTC counts, and increased postoperative CTC numbers are associated with a worse prognosis in patients with HCC.

Aneurysm of the Anomalous Splenic Artery Arising from Superior Mesenteric Artery Treated by Coil Embolization: A Report of Two Cases and Literature Review.

BACKGROUND: Aneurysm of splenic artery (SA) which arises from the superior mesenteric artery (SMA) is a very rare condition. The aim of this study was to present our experience with 2 such patients treated by coil embolization. METHODS: A 33-year-old man and a 61-year-old woman were incidentally identified with aneurysms of the SA which arose from the SMA. Endovascular therapy of coil embolization was chosen to treat the aneurysm. RESULTS: Follow-up computed tomography showed no change in the location of the coils and occlusion of majority of the aneurysm sac. The 2 patients have been doing well during a 26-month and 10-month follow-up period, respectively. CONCLUSIONS: Combined with the experience of the previous literature, we think coil embolization can be cost-effective and minimally invasive in selected cases, depending on the morphology and site of the lesion.

A propensity score analysis of two methods of hepatic vascular occlusion in hepatectomy.

BACKGROUND: The key points in hepatectomy are reducing blood loss and preservation of hepatic function. The aim of this study was to compare the perioperative outcomes of partial hepatectomy using two techniques of hepatic vascular inflow occlusion. MATERIALS AND METHODS: A total of 1817 patients were selected from our multi-institutional hepatectomy database in China and classified into two groups: the hemihepatic inflow occlusion (HIO) group (n = 1693) and the ipsilateral portal vein branch occlusion (IPVBO) group (n = 124). Propensity score matching of patients in a ratio of 1:1 was conducted. The primary outcome was intraoperative blood loss. Secondary outcomes were postoperative liver function, postoperative morbidity and mortality, and duration of hospital stay after surgery. RESULTS: After propensity score matching, there were 124 patients in the IPVBO group and the HIO group, respectively. There were no significant differences between the two groups regarding intraoperative blood loss, blood transfusion requirement, operating time, postoperative morbidity and mortality, and duration of hospital stay after surgery (P > 0.05). However, The IPVBO group was associated with significantly lower peak in postoperative ALT level than the HIO group (P < 0.05). CONCLUSIONS: The results indicated that IPVBO did not lead to more intraoperative blood loss compared with HIO, and it decreased the peak of postoperative ALT level. In terms of postoperative morbidity and mortality, duration of hospital stay after surgery, IPVBO was also equal to HIO. Thus, IPVBO could be an alternative method of hepatic inflow occlusion.

Primary hepatic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type: A case report and literature review.

RATIONALE: Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare disease. To the best of our knowledge, only 67 cases had been reported in 39 English literatures to date. The aim of this study was to add a new case of this disease to the literature and to review the current literature. PATIENT CONCERNS: A 50-year-old man was incidentally identified with a solitary mass of 5 cm in diameter in the left lobe of the liver. DIAGNOSES: Based on the results of imaging studies, intrahepatic cholangiocellular carcinoma was suspected, and then surgery was performed. Microscopic findings showed that the tumor was a hepatic MALT lymphoma, and immunohistochemical analysis revealed that the lymphoma cells were CD20+, CD79a+, BCL-2+, CD3-, and CD5-. INTERVENTIONS: The patient received rituximab after surgery. OUTCOMES: He was free of disease for 13 months at the time of this report. LESSONS: Since previously published case reports and our case described nonspecific clinical features of this rare disease, it was usually misdiagnosed before histological confirmation and surgery resection may be a good choice for both diagnosis and local therapy.

Hepatocellular Carcinoma With Tumor Thrombus Occupying the Right Atrium and Portal Vein: A Case Report and Literature Review.

Hepatocellular carcinoma (HCC) patients with tumor thrombus extended through the major hepatic veins and inferior vena cava into the right atrium (RA) are rare, and most cases are considered as the advanced stage with a poor prognosis.We report a case of HCC with a tumor thrombus extending into the RA and a tumor thrombus in the portal vein. A literature search for case reports was performed on PubMed.Compared with the published literature, our case is one of the youngest patients, but with the most advanced HCC that invades both the hepatic inflow and outflow vasculature. For this patient, we resected the tumor thrombus in the RA with the use of cardiopulmonary bypass, and then removed the tumor thrombus in the portal vein and ligated the left branch of portal vein. Because of insufficient remnant liver volume, microwave ablation and transcatheter arterial chemoembolization were performed to control the growth of HCC. The patient survived 6 months after surgery.This case suggests that for patients with extension of HCC into the RA and portal vein, surgery is a useful therapeutic modality, even in case that liver tumor cannot be resected.