A signature of seven hypoxia-related lncRNAs is a potential biomarker for predicting the prognosis of melanoma.

Melanoma is the most aggressive type of skin cancer and has a high mortality rate once metastasis occurs. Hypoxia is a universal characteristic of the microenvironment of cancer and a driver of melanoma progression. In recent years, long noncoding RNAs (lncRNAs) have attracted widespread attention in oncology research. In this study, screening was performed and revealed seven hypoxia-related lncRNAs AC008687.3, AC009495.1, AC245128.3, AL512363.1, LINC00518, LINC02416 and MCCC1-AS1 as predictive biomarkers. A predictive risk model was constructed via univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Patients were grouped according to the model risk score, and Kaplan-Meier analysis was performed to compare survival between groups. Functional and pathway enrichment analyses were performed to compare gene set enrichment between groups. Moreover, a nomogram was constructed with the risk score as a variable. In both the training and validation sets, patients in the low-risk group had better overall survival than did those in the high-risk group (P<0.001). The 3-, 5- and 10-year area under the curve (AUC) values for the nomogram model were 0.821, 0.795 and 0.820, respectively. Analyses of immune checkpoints, immunotherapy response, drug sensitivity, and mutation landscape were also performed. The results suggested that the low-risk group had a better response to immunotherapeutic. In addition, the nomogram can effectively predict the prognosis and immunotherapy response of melanoma patients. The signature of seven hypoxia-related lncRNAs showed great potential value as an immunotherapy response biomarker, and these lncRNAs might be treatment targets for melanoma patients.

Establishment and validation of a ferroptosis-related prognostic signature for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with high heterogeneity. The prognosis of HCC is quite poor and the prognostic prediction also has challenges. Ferroptosis is recently recognized as a kind of iron-dependent cell death, which is involved in tumor progression. However, further study is needed to validate the influence of drivers of ferroptosis (DOFs) on the prognosis of HCC. Methods: The FerrDb database and the Cancer Genome Atlas (TCGA) database were applied to retrieve DOFs and information of HCC patients respectively. HCC patients were randomly divided into training and testing cohorts with a 7:3 ratio. Univariate Cox regression, LASSO and multivariate Cox regression analyses were carried out to identify the optimal prognosis model and calculate the risk score. Then, univariate and multivariate Cox regression analyses were performed to assess the independence of the signature. At last, gene functional, tumor mutation and immune-related analyses were conducted to explore the underlying mechanism. Internal and external databases were used to confirm the results. Finally, the tumor tissue and normal tissue from HCC patients were applied to validate the gene expression in the model. Results: Five genes were identified to develop as a prognostic signature in the training cohort relying on the comprehensive analysis. Univariate and multivariate Cox regression analyses confirmed that the risk score was able to be an independent factor for the prognosis of HCC patients. Low-risk patients showed better overall survival than high-risk patients. Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Furthermore, internal and external cohorts were consistent with our results. There was a higher proportion of nTreg cell, Th1 cell, macrophage, exhausted cell and CD8+T cell in the high-risk group. The Tumor Immune Dysfunction and Exclusion (TIDE) score suggested that high-risk patients could respond better to immunotherapy. Besides, the experimental results showed that some genes were differentially expressed between tumor and normal tissues. Conclusion: In summary, the five ferroptosis gene signature showed potential in prognosis of patients with HCC and could also be regarded as a value biomarker for immunotherapy response in these patients.

Application of 5G technology to conduct tele-surgical robot-assisted laparoscopic radical cystectomy.

BACKGROUND: The aim of this study was to test the effectiveness, safety and stability of the 5G communication technology in clinical laparoscopic telesurgery. METHODS: An ultra-remote radical cystectomy (network communication distance of nearly 3000 km) was performed on patient diagnosed with T2N0M0 stage bladder cancer using a domestically produced "MicroHand" surgical robot. RESULTS: The network delay, operative time, blood loss, intraoperative complications, postoperative recovery, and hospitalisation time were recorded. The 5G network was used throughout the operation, with an average total delay of 254 ms. The operation went well and the patient recovered smoothly. CONCLUSIONS: Ultra-remote clinical laparoscopic surgery can be performed safely and smoothly. More importantly, our model can provide insights for promoting the future development of telesurgery in China.

Acute kidney injury in patients with primary nephrotic syndrome: influencing factors and coping strategies.

BACKGROUND: Acute kidney injury (AKI) is a frequent and serious complication in patients with primary nephrotic syndrome (PNS). We aimed to evaluate the influencing factors of AKI in patients with PNS, to provide implications for the clinical management and nursing care of patients with PNS. METHODS: PNS patients who were treated in the Department of Nephrology in our hospital from January 1, 2020 to July 31, 2021 were included. The clinical characteristics and pathological type of PNS patients were evaluated. Pearson correlation and Logistic regression analysis were performed to analyze the related risk factors of AKI in patients with PNS. RESULTS: A total of 328 patients with PNS were included, the incidence of AKI in PNS patients was 28.05%. Pearson correlation analysis showed that diabetes(r = 0.688), pulmonary infection (r = 0.614), albumin (r = 0.779), serum creatinine (r = 0.617), uric acid (r = 0.522), blood urea nitrogen (r = 0.616), renal tubular casts (r = 0.707) were correlated with AKI in PNS patients (all P < 0.05). Logistic regression analysis indicated that diabetes (OR2.908, 95%CI1.844 ~ 4.231), pulmonary infection(OR3.755, 95%CI2.831 ~ 4.987), albumin ≤ 24 g/L (OR1.923, 95%CI1.214 ~ 2.355), serum creatinine ≥ 90 µmol/L (OR2.517, 95%CI2.074 ~ 3.182), blood urea nitrogen ≥ 6.5 mmol/L (OR1.686, 95%CI1.208 ~ 2.123), uric acid ≥ 390 µmol/L (OR2.755, 95%CI2.131 ~ 3.371), renal tubular casts(OR1.796, 95%CI1.216 ~ 2.208) were the independently influencing factors of AKI in PNS patients (all P < 0.05). CONCLUSIONS: AKI is common in PNS patients. Actively controlling diabetes and pulmonary infection, strengthening nutrition support and renal function monitoring are essential to reduce the occurrence of AKI in PNS patients.

PMEPA1 Stimulates the Proliferation, Colony Formation of Pancreatic Cancer Cells via the MAPK Signaling Pathway.

BACKGROUND: Prostate transmembrane protein androgen-induced 1 (PMEPA1) is reportedly highly expressed in pancreatic cancer (PC). However, its biological role and associated mechanisms have not been addressed in PC progression. METHODS: PMEPA1 mRNA expression and survival outcome of PC patients were evaluated via the GEPIA website. Lentiviral-mediated shRNA knockdown and ectopic expression of PMEPA1 were implemented in the pancreatic cancer cell line PANC1 cells. CCK-8 and colony formation assays were carried out to assess the biological function of PMEPA1 in PANC1 proliferation and viability. Dual-luciferase reporter assays and RT-qPCR were used to assess the interactive relationship between PMEPA1 and the MAPK signaling pathway. RESULTS: By analyzing the data from GEPIA, we found that PMEPA1 mRNA expression is overexpressed in PC tissues compared with matched nontumor tissues. PMEPA1-high PC patients are predicted to have a worse prognosis than PMEPA1-low PC patients. We found that PMEPA1 shRNA suppressed PANC1 proliferation and colony formation capacity, while enforced expression of PMEPA1 yielded the opposite results. Mechanical investigations showed that PMEPA1 exerts its tumor-promoting function in pancreatic cancer via activation of the MAPK signaling pathway. CONCLUSION: PMEPA1 promotes the progression of PC at least partially by activating the MAPK signaling pathway; thus, the PMEPA1/MAPK axis may be a potential therapeutic target in pancreatic cancer.

Corrigendum: MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/ß-catenin pathway.

[This corrects the article DOI: 10.1038/srep08087.].

Inhibition of complement C3 might rescue vascular hyporeactivity in a conscious hemorrhagic shock rat model.

BACKGROUND: Vascular hyporeactivity in severe hemorrhagic shock could induce refractory hypotension and is an important cause of death. The global acute inflammatory response induced in shock triggers the over-expression of reactive oxygen species, NO, ET1 and TNF-α, which play essential roles in the pathology of vascular hyporeactivity. This leads to a hypothesis that inhibition of the complement system, the mediator of the inflammatory cascade, might be a promising therapeutic exploration for vascular hyporeactivity. METHODS: We use cobra venom factor (CVF) and the soluble form of CR1 (sCR1) which deplete or inhibit complement C3 respectively to examine its role in vascular hyporeactivity in a conscious hemorrhagic shock rat model. RESULTS: We first confirmed the over-activation of C3 during shock and the down-regulation effects of CVF and sCR1 on C3. Then, both CVF and sCR1 could significantly mitigate the over-expression of serum NO, ET-1, TNF-α and reactive oxygen species. Finally, the vascular reactivity of superior mesenteric arteries (SMA) was examined in vitro, which confirmed the massive reduction of vascular reactivity in shock, which was significantly rescued by both CVF and sCR1. CONCLUSIONS: Inhibition of C3 might improve the reactivity of SMA to norepinephrine during hemorrhagic shock possibly through the downregulation of NO, ET1, TNF-α and reactive oxygen radicals.

Hepatic falciform ligament clear cell myomelanocytic tumor: A case report and a comprehensive review of the literature on perivascular epithelioid cell tumors.

BACKGROUND: The objective of the study was to explore the clinical expression, radiological and pathological features, differential diagnosis, and biological behavior of a clear cell myomelanocytic tumor. In a case involving a clear cell myomelanocytic tumor located in the hepatic falciform ligament, we evaluated clinical expression, radiological characteristics, histopathology, immunohistochemistry, and biological behavior; we also reviewed the relevant literature. CASE PRESENTATION: Clear cell myomelanocytic tumor is a benign soft-tissue neoplasm that often occurs in women, and is expressed as a painless mass. The falciform ligament is its most frequent site of occurrence. The imaging characteristics of this lesion were uneven enhancement in the arterial phase, continuing to strengthen in the venous phase, and equal density in the balance phase. Histological and immunohistochemical analysis revealed the main transparent epithelioid cells and smooth muscle spindle cells to be HMB-45(+), smooth muscle actin(+), and melan-A (+). CONCLUSION: Hepatic vascular epithelioid cell tumors are very rare mesenchymal neoplasms. Few studies have investigated this tumor in the hepatic falciform ligament; consequently, its diagnosis and the selection of an appropriate treatment and follow-up protocol are challenging. Treatment outcome remains unpredictable. Therefore, clear cell myomelanocytic tumor should be viewed as a tumor with uncertain malignant potential requiring long-term follow-up.

MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/ß-catenin pathway.

Accumulating evidences indicate that microRNAs play a vital role in regulating tumor progression. However, the roles of miR-148b in hepatocellular carcinoma (HCC) are still largely unknown. In this study, our data showed that miR-148b was significantly downregulated in 40 pairs of human HCC tissues. Further, the deregulated miR-148b was significantly correlated with larger tumor size, more tumor number, metastasis and worse prognosis in HCC. Overexpression of miR-148b inhibited HCC HepG2 cells proliferation and tumorigenicity. Further, miR-148b induced cells apoptosis by activating caspase- 3 and caspase-9, and induced S phase arrest by regulating cyclinD1 and p21, and also inhibited cell invasion. Data from the dual-luciferase reporter gene assay showed that WNT1 was a direct target of miR-148b, and overexpressed WNT1 inversely correlated with miR-148b levels in HCC tissues. Silencing of WNT1 inhibited the growth of HCC cells, and also induced cells apoptosis and inhibited invasion, which is consistent with the effects of miR-148b overexpression. MiR-148b downregulated expression of WNT1, ß-catenin and C-myc, while upregulated E-cadherin expression. We conclude that the frequently downregulated miR-148b can regulate WNT1/ß-catenin signalling pathway and function as a tumor suppressor in HCC. These findings suggest that miR-148b may serve as a novel therapeutic target for HCC.

[Role of microRNA-223 and its target gene oncogene c-myc in hepatocellular carcinoma pathogenesis].

To investigate the regulatory role of microRNA-223 (miR-223) on c-myc and its role in hepatocarcinogenesis. miR-223 and c-myc mRNA expressions in normal tissue, paraneoplastic tissue, liver cancer tissue and liver cancer cells were tested with microRNA microarray and quantitative real-time PCR (qRT-PCR). C-myc protein expression was detected by Western blot. MiR-223 mimic was transfected into HepG2 cells and the expression changes of c-myc mRNA and protein were tested with qRT-PCR and Western blot respectively. MiR-223 was down-regulated by 61.53% and 30.77% respectively in hepatocellular carcinoma and adjacent tissues as compared to normal liver tissues and the expression of miR-223 was also decreased in HepG2 cell as compared to fetal liver cells L02, whereas the expressions of c-myc mRNA and protein increased in paraneoplastic and HCC tissues compared with normal liver tissues. It prompts that the expressions of miR-223 and c-myc are negatively correlated. No obvious difference found among c-myc mRNA expressions after miR-223 mimics transfection. The c-myc abnormal high-expression may play a dynamic role in hepatocarcinogenesis due to the miR-223 down-regulation.

microRNA-450a targets DNA methyltransferase 3a in hepatocellular carcinoma.

microRNAs (miRNAs) have been proven to play key regulatory roles in hepatocarcinogenesis. In the present study, the possible role of microRNA-450a (miR-450a) in hepatocarcinogenesis was investigated. Our study revealed that miR-450a was significantly down-regulated in hepatocellular carcinoma (HCC) tissues compared with that in normal liver (NL) and para-tumorous (PT) tissues, and miR-450a expression in HepG2 cells was significantly lower than that in L02 cells. Both the mRNA and protein levels of the miR-450a potential target gene, DNA methyltransferase 3a (DNMT3a), were obviously higher in HCC compared with levels in the NL and PT tissues. We further identified DNMT3a as the direct target gene for miR-450a, and ectopic miR-450a expression in HepG2 cells caused the down-regulation of DNMT3a and an inhibition of cell proliferation. Taken together, these findings suggest that miR-450a plays an important regulatory role in hepatocarcinogenesis through inhibition of DNMT3a expression, and miR-450a may be a potential target for the treatment of HCC.