Abstract Despite substantial breakthroughs in the treatment of hepatocellular carcinoma (HCC) in recent years, many patients are diagnosed in the middle or late stages, denying them the option for surgical excision. Therefore, it is of great importance to find effective therapeutic targets of HCC. In this study, it is found that Gap junction protein beta‐2 (GJB2) is highly enriched in malignant cells based on single‐cell RNA sequencing and higher expression of GJB2 indicates a worse prognosis. The localization of GJB2 in HCC cancer cells is changed compared with normal liver tissue. In cancer cells, GJB2 tends to be located in the cytoplasm and nucleus, while in normal tissues, GJB2 is mainly located on the cell membrane. GJB2 is related to glycolysis, promoting NF‐κB pathway via inducing the ubiquitination degradation of IκBa, and activating HIF‐1α/GLUT‐1/PD‐L1 pathway. In addition, GJB2 knockdown reshapes tumor immune microenvironment and Salvianolic acid B inhibits the activity of GJB2. In conclusion, GJB2 promotes HCC progression by activating glycolysis through cytoplasmic translocation and generating a suppressive tumor microenvironment. Salvianolic acid B inhibits the expression of GJB2 and enhances the sensitivity of anti‐PD1 therapy, which may provide insights into the development of novel combination therapeutic strategies for HCC.
This paper presents a non-contact electrocardiogram (ECG) measurement platform that compensates for motion-induced impedance changes via interdigitated electrode channels in concert with software reconstruction algorithms. Specifically, the impedance of the non-contact electrode is non-invasively acquired in real-time by exploiting a custom electrode designed with two independent channels featuring independent transfer functions that are used to reconstruct motion-compensated ECG waveforms. The developed platform is validated on human subjects, illustrating up to a 76.3% improvement over conventional approaches, paving the path towards comfortable, convenient, and robust non-contact electrophysiological sensing.
Objective
To investigate the correlations between the systemic immune inflammatory index (SII) and prognosis of patients with gallbladder cancer.
Methods
From April 2005 to January 2019, patients with gallbladder cancer underwent surgical treatment in the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Zhengzhou University were followed up and their SII values were analyzed. The receiver operating characteristic curve (ROC) was used to determine the best clinical boundary value of SII. According to the boundary value, patients were divided into two groups: low SII and high SII. Survival curves were drawn by Kaplan-Meier method. The overall survival time of the two groups was analyzed, and univariate analysis of postoperative survival was performed using log-rank test. Cox regression proportional hazard model was used for multivariate analysis of clinical prognosis.
Results
A total of 312 patients were included, including 120 males and 192 females, aged 30.0 to 86.0 (61.5±9.9) years. The best clinical cut off value of preoperative SII was determined by ROC curve to be 510.42. A total of 312 patients with gallbladder cancer were divided into low SII group (SII≤510.42) and high SII group (SII>510.42). Kaplan-Meier survival curve was used to analyze the 1, 3 and 5-year survival rates of gallbladder cancer patients in low SII group and high SII group after operation. The survival rates were 65.7%, 39.6% and 30.2%, and 27.9%, 12.0% and 9.6% respectively. The median survival time was 25 months (95% CI: 16.9-33.1) and 9 months (95% CI: 8.1-9.9), respectively. The survival rate of gallbladder cancer patients in low SII group was better. There were significant differences of the overall survival rate between the two groups (P 510.42 (HR=0.086, 95% CI: 0.032-0.289) was a risk factor for overall survival of gallbladder cancer patients. Cox multivariate analysis confirmed that preoperative SII (HR=2.649, 95% CI: 1.981-3.543) was an independent risk factor for overall survival of gallbladder cancer patients.
Conclusions
SII can be used as an independent prognostic factor to predict the prognosis of patients with gallbladder cancer. The higher the preoperative SII, the worse the prognosis of patients with gallbladder cancer.
Key words:
Gallbladder neoplasms; Systemic immune-inflammation index; Prognostic facts
Tumor immune evasion relies on the crosstalk between tumor cells and adaptive/innate immune cells. Immune checkpoints play critical roles in the crosstalk, and immune checkpoint inhibitors have achieved promising clinical effects. The long non-coding RNA taurine-upregulated gene 1 (TUG1) is upregulated in hepatocellular carcinoma (HCC). However, how TUG1 is upregulated and the effects on tumor immune evasion are incompletely understood. Here, METTL3-mediated m
Enolase-phosphatase 1 (ENOPH1), a newly identified enzyme involved in l-methionine biosynthesis, is associated with anxiety and depression. In this study, ENOPH1 was found to play a crucial role in promoting the proliferation and migration of glioma cells. Among high-grade glioma patients, the overall survival of the group showing high ENOPH1 expression was shorter than that of the group showing low ENOPH1 expression. ENOPH1 knockdown inhibited glioma cell proliferation and migration. In parallel, ENOPH1 knockdown suppressed tumor growth capacity and prolonged survival in an orthotopic glioma model. Mechanistically, we found that ENOPH1 activates the PI3K/AKT/mTOR signaling pathway by regulating THEM4. In conclusion, ENOPH1 is an important mediator that promotes glioma cell proliferation and migration.
Human varicose veins are commonly claimed to be responsible for lower limb symptoms. Mutation in KRAS gene has been implicated in various diseases, including cancers and vascular diseases. While little known about the novel mutation in KRAS gene and its contribution to the development of varicose veins. Here, we have generated human induced pluripotent stem cell (iPSC) line, which harboured a novel mutation in KRAS (c.209A>T) gene. This cell line provided a novel tool for understanding the mechanism of KRAS mutation in the pathogenesis of varicose veins.
Neurofibromatosis type 1 (NF-1) is commonly associated with a variety of rare tumors. However, no case of multiple gastric gastrointestinal stromal tumors (GISTs) or duodenal ampulla neuroendocrine tumors (NETs) with multiple liver metastases in a patient with NF-1 has yet been reported. Here, we describe a case of a 55-year-old female patient with NF-1 whose serum Pro-Gastrin-Releasing Peptide (pro-GRP) levels were elevated. Gastrointestinal endoscopy and biopsy showed duodenal papilla space-occupying mass, and the pathological diagnosis turned out to be neuroendocrine tumors (NETs). During surgical exploration, multiple tumors were found on the serosal surface of the stomach and numerous miliary metastases in the liver. Following histopathological examination, it was determined that the liver metastases were NF-1 and the tumors in the gastric wall were GISTs. The patient benefited from targeted therapy and had an uneventful hospital stay. In this case, we emphasize treating patients with neurofibromatosis type 1 who exhibit abdominal symptoms with a high degree of clinical suspicion and performing thorough evaluations to rule out multiple tumors.
Abstracts Glycine decarboxylase (GLDC) belongs to the glycine cleavage system and is involved in one-carbon metabolism. We previously reported that GLDC downregulation enhances hepatocellular carcinoma (HCC) progression and intrahepatic metastasis through decreasing ROS-mediated ubiquitination of cofilin. The role of autophagy in cancer metastasis is still controversial. Redox-dependent autophagy largely relies on the magnitude and the rate of ROS generation. Thus, we aimed to explore the role of GLDC in cellular autophagy during HCC progression. We showed that a high GLDC expression level is associated with better overall survival and is an independent factor for the favorable prognosis of HCC patients. GLDC overexpression significantly induced cell autophagy, whereas GLDC downregulation reduced cell autophagy. Of note, GLDC is the post-transcriptional target of miR-30d-5p. GLDC overexpression could rescue miR-30d-5p-mediated cell metastasis and increase autophagy. Furthermore, upregulation of GLDC could significantly decrease p62 expression and impair intrahepatic metastasis in vivo. Taken together, our results suggest that GLDC may play an important role to increasing miR-30d-5p-reduced autophagy to suppress HCC progress.
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