ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.

Anatomical liver resection by trans-Glisson sheath methylene blue staining for treatment of hepatolithiasis of right posterior lobe / 中华普通外科杂志

Objective To investigate the effectiveness and technical points of anatomical liver resection by trans-Glisson Sheath methylene blue staining in treatment of hepatolithiasis of right posterior lobe.Methods The clinical data of 12 cases of hepatolithiasis of right posterior lobe treated with anatomical liver resection by Glisson sheath methylene blue staining were retrospectively analyzed.Result 6 of 12 patients had undergone more than 2 previous biliary surgeries.All patients underwent contrast-enhanced CT scan and portography,hepatolithiasis of segment Ⅵ in 4 cases,right posterior lobe in 8 cases,accompanied by left lateral lobe bile duct stones in 2 cases,the right caudate lobe bile duct stones in 1 case.Methylene blue was injected into the portal vein,the methylene blue interface of segment Ⅵ or right posterior lobe displays well.Methylene blue interface was larger than the ischemia interface,which is in accordance with the anatomy.Along the methylene blue interface,hepatic resection was performed including right posterior lobe resection (n =9),segment Ⅵ resection (n =3),and combined with left lateral lobe resection (n =2) and the right caudate lobe resection (n =1).There was no postoperative mortality.Incision infection occurred in 5 cases,4 had right pleural effusion and 2 had a biliary fistula that were treated conservatively.With a mean follow-up period of 3.2 years,all patients are symptoms free and stone free.Conclusions Anatomical liver resection by methylene blue staining is a safe and effective treatment for hepatolithiasis of right posterior lobe.

Inhibition of allogeneic T-cell responses by Kupffer cells expressing indoleamine 2,3-dioxygenase in vitro / 中华肝胆外科杂志

Objective To investigate kupffer cells (KCs) expressing indoleamine 2,3-dioxygenase(IDO)in the inhibition of allogeneic T-cell proliferation in vitro. Methods Real-time PCR was used to investigate the expression of IDO mRNA and FasL mRNA in KCs pretreated with or without IFNγ. High performance liquid chromatography was used to analyze the catabolism of tryptophan by IDO from KCs. Allogeneic T-cell response was used to confirm the inhibition of KCs in vitro. The proliferation of lymphocytes was detected using [3 H] thymidine incorporation. Cell cycle and lymphocyte apoptosis were evaluated by flow cytometric assay. Results Real-time PCR revealed IDO mRNA and FasL mRNA expression in KCs pretreated with IFN-γ. IDO catabolic effect was confirmed by a decrease in tryptophan and increase in kynurenine concentration. KCs expressing IDO and FasL from BABL/c mice acquire the ability to suppress the proliferation of T-cells from C57BL/6, which could be blocked by the addition of 1-methyl-tryptophan and anti-FasL antibody. The co-cultured T-cells with KCs expressing IDO and FasL could induce allogeneic T-cell apoptosis and exhibited cell-cycle arrest in G1. Conclusion In addition to the Fas/FasL pathway, IDO may also play an important role in KCs to inhibit allogeneic T-cell proliferation in vitro.

The analysis of portal vein thrombosis following orthotopic liver transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate and summarize the experience in clinical presentation, diagnosis and treatment of portal vein thrombosis after orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>The clinical data of 402 patients who underwent OLT from January 2003 to February 2007 were reviewed. A retrospective study was performed on etiology, prognosis and treatment in 9 cases of portal vein thrombosis after OLT.</p><p><b>RESULTS</b>All of the 9 cases received anticoagulant and antiaggregation therapy, within whom one underwent percutaneous transluminal angioplasty and stent placement, one underwent retransplantation after failure of thrombolysis therapy, and one received surgical embolectomy. Six patients died of multiple organ failure on 9th, 30th, 34th, 40th, 48th, 6 2nd days, respectively, while 3 patients survived.</p><p><b>CONCLUSIONS</b>The major risk factors of portal vein thrombosis after OLT were pathological changes in portal vein, abnormal blood stream dynamics, hypercoagulable status and improper surgical technique. Prophylactic intervention to patients with high risk factors, early diagnosis and aggressive comprehensive therapy on portal vein thrombosis patients are essential to improve prognosis.</p>