Recent studies have shown that oxidative phosphorylation (OXPHOS) is a target for the effective attenuation of cancer drug resistance. OXPHOS inhibitors can improve treatment responses to anticancer therapy in certain cancers, such as melanomas, lymphomas, colon cancers, leukemias and pancreatic ductal adenocarcinoma (PDAC). However, the effect of OXPHOS on cancer drug resistance is complex and associated with cell types in the tumor microenvironment (TME). Cancer cells universally promote OXPHOS activity through the activation of various signaling pathways, and this activity is required for resistance to cancer therapy. Resistant cancer cells are prevalent among cancer stem cells (CSCs), for which the main metabolic phenotype is increased OXPHOS. CSCs depend on OXPHOS to survive targeting by anticancer drugs and can be selectively eradicated by OXPHOS inhibitors. In contrast to that in cancer cells, mitochondrial OXPHOS is significantly downregulated in tumor-infiltrating T cells, impairing antitumor immunity. In this review, we summarize novel research showing the effect of OXPHOS on cancer drug resistance, thereby explaining how this metabolic process plays a dual role in cancer progression. We highlight the underlying mechanisms of metabolic reprogramming in cancer cells, as it is vital for discovering new drug targets.

Gamma-glutamyltransferase (GGT) is one of the most important laboratory tests for the evaluation of liver damage. Through a long-term clinical observation of patients with secondary asymptomatic choledocholithiasis, we found that most patients had abnormal GGT serum levels. To investigate the combination of serum GGT and alkaline phosphatase (ALP) in predicting the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis. In this retrospective cohort study, the clinical data of 829 patients with cholecystolithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from August 2014 to August 2017 were collected. Among these patients, 151 patients had secondary asymptomatic choledocholithiasis and served as the observation group, and the remaining 678 cholecystolithiasis patients served as the control group. Serum liver function indexes were detected in both groups, and the receiver operating characteristic (commonly known as ROC) curves were constructed for markers showing statistical significances. The cutoff value, sensitivity, and specificity of each marker were calculated according to the ROC curves. The overall incidence of asymptomatic choledocholithiasis secondary to cholecystolithiasis was 18.2%. The results of liver function indexes including serum aspartate aminotransferase, alanine aminotransferase, direct bilirubin and total bilirubin levels showed no significant differences between the two groups (P > 0.05). However, the serum GGT and ALP levels were significantly higher in the observation group than in the control group (P < 0.05). The ROC curve analysis showed that the area under the curve was 0.881 (95% CI: 0.830-0.932), 0.647 (95% CI: 0.583-0.711) and 0.923 (0.892-0.953) for GGT, ALP, and GGT + ALP, respectively. The corresponding cut-off values of GGT and ALP were 95.5 U/L and 151.5 U/L, sensitivity were 90.8% and 65.1%, and specificity were 83.6% and 59.8%, respectively. The sensitivity and specificity of GGT + ALP were 93.5% and 85.1%, respectively. An abnormally elevated serum GGT level has an important value in the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis. The combination of serum GGT and ALP has better diagnostic performance. As a convenient, rapid and inexpensive test, it should be applied in secondary asymptomatic choledocholithiasis routine screening.

Hemolymphangioma is a malformation of both lymphatic vessels and blood vessels. Splenic hemolymphangioma is extremely rare. Herein, we present a case of 62-year-old woman with ambiguous upper quadrant abdominal pain for two months who was found to have an occupying lesion in the spleen on computed tomography. She was eventually diagnosed with hemolymphangioma of the spleen. The patient underwent total splenectomy. Neither symptoms nor recurrence was found during the one-year follow-up period.

AIM To investigate the diagnostic value of abnormal serum carbohydrate antigen 199 (CA199) level in acute cholan-gitis secondary to choledocholithiasis. METHODS In this retrospective cohort study, the clinical data of 727 patients with choledocholithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from June 2011 to June 2017 were collected. Among these patients, 258 patients had secondary acute cholangitis and served as observation group, and the remaining 569 choledocholithiasis patients served as the control group. Serum liver function indexes and tumor markers were detected in both groups, and the receiver operating characteristic (ROC) curves were constructed for markers showing statistical significances. The cutoff value, sensitivity, and specificity of each marker were calculated according to the ROC curves. RESULTS The results of liver function tests showed no significant differences between the two groups (P > 0.05). Tumor markers including serum CA125, CA153, carcinoembryonic antigen, and alpha fetoprotein levels were also not significantly different (P > 0.05); however, the serum CA199 level was significantly higher in the observation group than in the control group (P < 0.05). The ROC curve analysis showed that the area under the curve was 0.885 (95% CI: 0.841- 0.929) for CA199, and the cutoff value of 52.5 kU/L had the highest diagnostic accuracy, with a sensitivity of 86.8% and a specificity of 81.6%. CONCLUSION Abnormally elevated serum CA199 level has an important value in the diagnosis of acute cholangitis secondary to choledocholithiasis. It may be a specific inflammatory marker for acute cholangitis.

Background: Colorectal cancer (CRC) is one of the most aggressive malignancies of the digestive tract, characterized by aberrant post-transcriptional RNA modifications, including pseudouridine (Ψ). TruB pseudouridine synthase family member 1 (TRUB1) is a key pseudouridine synthase but its role in CRC progression remains unclear. Methods: Public databases and CRC cell lines were analysed to assess TRUB1 expression in CRC. Receiver-operating characteristic (ROC) curve analysis and survival analysis were performed to evaluate the diagnostic and prognostic significance of TRUB1. The impact of TRUB1 on tumor proliferation and Ψ modification was examined in TRUB1-knock-down HCT116 cell lines. Mechanistically, RNA sequencing of control and TRUB1-knock-down HCT116 cells was conducted to identify potential pathways, which were validated by using real-time polymerase chain reaction (PCR), Western blot, and immunofluorescence assays. Results: TRUB1 was significantly upregulated in CRC tumor tissues and cell lines. ROC analysis showed that TRUB1 had strong diagnostic potential and its overexpression was associated with poorer overall survival in CRC patients. In TRUB1-knock-down HCT116 cells, apoptosis increased and tumor growth slowed in nude mice, with a corresponding increase in apoptosis-related proteins and decreased Ψ modification. Mechanistically, RNA sequencing indicated that tumor necrosis factor α signaling via the nuclear factor kappa B (NFκB) pathway was activated in TRUB1-knock-down HCT116 cells. Further analysis identified Baculoviral inhibitor of apoptosis proteins repeat-containing 3 (BIRC3) as a potential downstream target gene that was regulated by TRUB1 in the NFκB pathway. Conclusions: TRUB1 serves as a potential biomarker for CRC diagnosis and prognosis, and it can inhibit apoptosis in CRC cells via BIRC3-mediated NFκB signaling.

Pancreatic lymphoepithelial cyst is a rare pancreatic lesion of undetermined pathogenesis, which is a true pancreatic cyst. Castleman’s disease is a rare lymphoproliferative disorder, and a mesenteric location is unusual. The simultaneous occurrence of the two diseases are rarer than metachronous ones and has not been reported to date. We present a case report of a patient with simultaneous occurrence of pancreatic lymphoepithelial cyst and duodenal mesenteric Castleman’s disease.