Survival time prediction in patients with high-grade serous ovarian cancer based on 18F-FDG PET/CT- derived inter-tumor heterogeneity metrics.

BACKGROUND: The presence of heterogeneity is a significant attribute within the context of ovarian cancer. This study aimed to assess the predictive accuracy of models utilizing quantitative 18F-FDG PET/CT derived inter-tumor heterogeneity metrics in determining progression-free survival (PFS) and overall survival (OS) in patients diagnosed with high-grade serous ovarian cancer (HGSOC). Additionally, the study investigated the potential correlation between model risk scores and the expression levels of p53 and Ki-67. METHODS: A total of 292 patients diagnosed with HGSOC were retrospectively enrolled at Shengjing Hospital of China Medical University (median age: 54 ± 9.4 years). Quantitative inter-tumor heterogeneity metrics were calculated based on conventional measurements and texture features of primary and metastatic lesions in 18F-FDG PET/CT. Conventional models, heterogeneity models, and integrated models were then constructed to predict PFS and OS. Spearman's correlation coefficient (ρ) was used to evaluate the correlation between immunohistochemical scores of p53 and Ki-67 and model risk scores. RESULTS: The C-indices of the integrated models were the highest for both PFS and OS models. The C-indices of the training set and testing set of the integrated PFS model were 0.898 (95% confidence interval [CI]: 0.881-0.914) and 0.891 (95% CI: 0.860-0.921), respectively. For the integrated OS model, the C-indices of the training set and testing set were 0.894 (95% CI: 0.871-0.917) and 0.905 (95% CI: 0.873-0.936), respectively. The integrated PFS model showed the strongest correlation with the expression levels of p53 (ρ = 0.859, p < 0.001) and Ki-67 (ρ = 0.829, p < 0.001). CONCLUSIONS: The models based on 18F-FDG PET/CT quantitative inter-tumor heterogeneity metrics exhibited good performance for predicting the PFS and OS of patients with HGSOC. p53 and Ki-67 expression levels were strongly correlated with the risk scores of the integrated predictive models.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Analysis on Intraoperative Electrocorticogram Characteristics for Evaluating the Risk of Postoperative Epilepsy.

Epilepsy is one of the most common complications after craniotomy, which happens suddenly and does great harm. There still lacks of effective prediction method during the operation. The main purpose of this paper is to explore the correlation between the characteristics of intraoperative electrocorticogram (ECoG) and postoperative epilepsy, and select effective features to establish a prediction model. This retrospective study uses intraoperative ECoG recordings of 144 patients with cerebrovascular diseases undergoing cerebral revascularization surgeries. The cases are divided into subtypes of ischemic and hemorrhagic. Nine types of ECoG features are designed on different frequency bands indicating clinical information, power spectrum, complexity, sequence change, and information quantity, while their changes in different surgical stages are also considered. Then statistical analysis is used to obtain features significantly related to postoperative epilepsy (p<0.05). The sparse representation method is used on these features to further screen and reduce the redundancy, and then machine learning methods are used to establish a prediction model for postoperative epilepsy. The accuracy, sensitivity and specificity of the best prediction model can achieve 0.817, 0.800 and 0.833 respectively under 5-fold cross validation.Clinical Relevance-This study explores the correlation between the characteristics of intraoperative ECoG and postoperative epilepsy, investigates the possibility to use the ECoG features and machine learning algorithms to assess the risk of postoperative epilepsy during the surgery. Further results are expected to provide reference for preventive measures to reduce the occurrence of postoperative epilepsy.

The impact of liver abscess formation on prognosis of patients with malignant liver tumors after transarterial chemoembolization.

Purpose: Liver abscess is a rare and serious complication after transarterial chemoembolization (TACE) for liver cancer; however, its impact on the prognosis is unclear. This retrospective study examined the outcomes of patients with liver abscess formation following TACE for malignant liver tumors to elucidate the impact of liver abscess formation on the prognosis of these patients. Methods: From January 2017 to January 2022, 1,387 patients with malignant tumors underwent 3,341 sessions of TACE at our hospital. Clinical characteristics of patients at baseline and follow-up were examined, including treatment and outcome of liver abscess, tumor response to the TACE leading to liver abscess, and overall survival time. Results: Of 1,387 patients, 15 (1.1%) patients with liver abscess complications after TACE resulted in a total of 16 (0.5%) cases of liver abscess after 3,341 TACE sessions (including one patient with two events). After antibiotic or percutaneous catheter drainage (PCD) treatment, all the infections associated with liver abscesses were controlled. In the PCD group, eight patients died before drainage tube removal, one retained the drainage tube until the end of follow-up, and five underwent drainage tube removal; the mean drainage tube removal time was 149.17 ± 134.19 days. The efficacy of TACE leading to liver abscess was evaluated as partial response (18.75%), stable disease (37.5%), and progressive disease (43.75%). Eleven patients died during the follow-up period owing to causes unrelated to infections caused by liver abscesses. The survival rates at 3 months, 6 months, 1 year, and 5 years were 86.7%, 50.9%, 25.5%, and 17%, respectively. Conclusion: Patients with liver abscess formation following TACE for malignant liver tumors experienced prolonged drainage tube removal time after PCD; while this condition did not directly cause death, it indirectly contributed to a poor prognosis in these patients.

MicroRNA-139-5p suppresses non-small cell lung cancer progression by targeting ATAD2.

MiR-139-5p is a suppressor in multiple types of cancer. However, whether miR-139-5p affects NSCLC is unknown. In this study, miR-139-5p expression in clinical samples was examined by real-time PCR and in situ hybridization (ISH). MiR-139-5p mimic was transfected to monitor NSCLC cell behaviors. Potential target was predicated using bioinformatics database. Next, whether miR-139-5p impacted cell behaviors via regulation of its predicted target gene were further evaluated. The result revealed that miR-139-5p was lower in NSCLC samples/cells. MiR-139-5p restrained A549 cell proliferation, accelerated apoptosis, and inhibited the ß-catenin signaling. ATAD2 was a predicted target of miR-139-5p, and it was highly expressed in NSCLC tissues. ATAD2 overexpression abolished the miR-139-5p's anti-tumor effect on cell proliferation and apoptosis. TWS119 (a ß-catenin signaling activator) partially reversed miR-139-5p overexpression-induced suppression of cell proliferation and promotion of cell apoptosis. In tumor xenografts, miR-139-5p restrained tumor growth. MiR-139-5p was a tumor suppressor in NSCLC by regulating the oncogene ATAD2 and ß-catenin signaling. Our study provides a promising target for cancer treatment.

Upregulated LncRNA H19 Sponges MiR-106a-5p and Contributes to Aldosterone-Induced Vascular Calcification via Activating the Runx2-Dependent Pathway.

BACKGROUND: Excess aldosterone is implicated in vascular calcification (VC), but the mechanism by which aldosterone-MR (mineralocorticoid receptor) complex promotes VC is unclear. Emerging evidence indicates that long-noncoding RNA H19 (H19) plays a critical role in VC. We examined whether aldosterone-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through H19 epigenetic modification of Runx2 (runt-related transcription factor-2) in a MR-dependent manner. METHODS: We induced in vivo rat model of chronic kidney disease using a high adenine and phosphate diet to explore the relationship among aldosterone, MR, H19, and VC. We also cultured human aortic VSMCs to explore the roles of H19 in aldosterone-MR complex-induced osteogenic differentiation and calcification of VSMCs. RESULTS: H19 and Runx2 were significantly increased in aldosterone-induced VSMC osteogenic differentiation and VC, both in vitro and in vivo, which were significantly blocked by the MR antagonist spironolactone. Mechanistically, our findings reveal that the aldosterone-activated MR bound to H19 promoter and increased its transcriptional activity, as determined by chromatin immunoprecipitation, electrophoretic mobility shift assay, and luciferase reporter assay. Silencing H19 increased microRNA-106a-5p (miR-106a-5p) expression, which subsequently inhibited aldosterone-induced Runx2 expression at the posttranscriptional level. Importantly, we observed a direct interaction between H19 and miR-106a-5p, and downregulation of miR-106a-5p efficiently reversed the suppression of Runx2 induced by H19 silencing. CONCLUSIONS: Our study clarifies a novel mechanism by which upregulation of H19 contributes to aldosterone-MR complex-promoted Runx2-dependent VSMC osteogenic differentiation and VC through sponging miR-106a-5p. These findings highlight a potential therapeutic target for aldosterone-induced VC.

Kaempferol attenuates nonalcoholic fatty liver disease in type 2 diabetic mice via the Sirt1/AMPK signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases with limited treatment options. Moreover, its prevalence is doubled in type 2 diabetes mellitus (T2DM). Kaempferol (KAP) is a flavonoid compound that has been suggested to have beneficial effects on NAFLD, but studies on the mechanism are lacking, especially in the diabetic state. Herein, we investigated the effect of KAP on NAFLD associated with T2DM and its underlying mechanism in vitro and in vivo. The results of in vitro studies indicated that KAP treatment (10-8-10-6 M) significantly reduced lipid accumulation in oleic acid-induced HepG2 cells. Moreover, in the T2DM animal model of db/db mice, we confirmed that KAP (50 mg/kg) significantly reduced lipid accumulation and improved liver injury. Mechanistic studies in vitro and in vivo showed that Sirtuin 1 (Sirt1)/AMP-activated protein kinase (AMPK) signal was involved in KAP regulation of hepatic lipid accumulation. KAP treatment activated Sirt1 and AMPK, upregulated the levels of fatty acid oxidation-related protein proliferator activated receptor gamma coactivator 1α (PGC1α); and downregulated lipid synthesis-related proteins, including acetyl-coA carboxylase (ACC), fatty acid synthase (FASN), and sterol regulatory element-binding protein 1 (SREBP1). Furthermore, the curative effect of KAP on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPK. Collectively, these findings suggest that KAP may be a potential therapeutic agent for NAFLD associated with T2DM by regulating hepatic lipid accumulation through activation of Sirt1/AMPK signaling.

Fibronectin leucine-rich transmembrane protein 2 drives monocyte differentiation into macrophages via the UNC5B-Akt/mTOR axis.

Upon migrating into the tissues, hematopoietic stem cell (HSC)-derived monocytes differentiate into macrophages, playing a crucial role in determining innate immune responses towards external pathogens and internal stimuli. However, the regulatory mechanisms underlying monocyte-to-macrophage differentiation remain largely unexplored. Here we divulge a previously uncharacterized but essential role for an axon guidance molecule, fibronectin leucine-rich transmembrane protein 2 (FLRT2), in monocyte-to-macrophage maturation. FLRT2 is almost undetectable in human monocytic cell lines, human peripheral blood mononuclear cells (PBMCs), and mouse primary monocytes but significantly increases in fully differentiated macrophages. Myeloid-specific deletion of FLRT2 (Flrt2ΔMyel ) contributes to decreased peritoneal monocyte-to-macrophage generation in mice in vivo, accompanied by impaired macrophage functions. Gain- and loss-of-function studies support the promoting effect of FLRT2 on THP-1 cell and human PBMC differentiation into macrophages. Mechanistically, FLRT2 directly interacts with Unc-5 netrin receptor B (UNC5B) via its extracellular domain (ECD) and activates Akt/mTOR signaling. In vivo administration of mTOR agonist MYH1485 reverses the impaired phenotypes observed in Flrt2ΔMyel mice. Together, these results identify FLRT2 as a novel pivotal endogenous regulator of monocyte differentiation into macrophages. Targeting the FLRT2/UNC5B-Akt/mTOR axis may provide potential therapeutic strategies directly relevant to human diseases associated with aberrant monocyte/macrophage differentiation.

NONHSAG028908.3 sponges miR­34a­5p to promote growth of colorectal cancer via targeting ALDOA.

Colorectal cancer (CRC) is an aggressive tumor, whose development is considered to be modulated by certain long non­coding RNAs (lncRNAs). Therefore, the aim of the present study was to investigate the regulatory mechanism of lncRNA NONHSAG028908.3 on CRC. Data from The Cancer Genome Atlas (TCGA) database revealed that NONHSAG028908.3 was increased in CRC tissues compared with normal tissues (P<0.001). The results of reverse transcription­quantitative PCR indicated that NONHSAG028908.3 was upregulated in four types of CRC cells compared with that in NCM460, a normal colorectal cell line. MTT, BrdU, and flow cytometric assays were applied to evaluate CRC cell growth. The migratory and invasive abilities of CRC cells were detected using wound healing and Transwell assays. Silencing of NONHSAG028908.3 inhibited proliferation, migration, and invasion of CRC cells. A dual­luciferase reporter assay demonstrated that NONHSAG028908.3 served as a sponge to combine with microRNA (miR)­34a­5p. MiR­34a­5p suppressed the aggressiveness of CRC cells. The effects induced by NONHSAG028908.3 knockdown were partly reversed by inhibition of miR­34a­5p. Furthermore, miR­34a­5p, a target of NONHSAG028908.3, modulated aldolase, fructose­bisphosphate A (ALDOA) expression in a negative feedback manner. Suppression of NONHSAG028908.3 notably decreased ALDOA expression, which was rescued via silencing of miR­34a­5p. Moreover, suppression of ALDOA revealed the inhibitory action on CRC cell growth and migration. In summary, the data of the present study indicate that NONHSAG028908.3 may positively regulate ALDOA via sponging miR­34a­5p, thereby promoting malignant activities in CRC.

Spermidine suppresses the activation of hepatic stellate cells to cure liver fibrosis through autophagy activator MAP1S.

BACKGROUND AND AIMS: Liver diseases present a wide range of fibrosis, from fatty liver with no inflammation to steatohepatitis with varying degrees of fibrosis, to established cirrhosis leading to HCC. In a multivariate analysis, serum levels of spermidine were chosen as the top metabolite from 237 metabolites and its levels were drastically reduced along with progression to advanced steatohepatitis. Our previous studies that showed spermidine supplementation helps mice prevent liver fibrosis through MAP1S have prompted us to explore the possibility that spermidine can alleviate or cure already developed liver fibrosis. METHODS: We collected tissue samples from patients with liver fibrosis to measure the levels of MAP1S. We treated wild-type and MAP1S knockout mice with CCl4 -induced liver fibrosis with spermidine and isolated HSCs in culture to test the effects of spermidine on HSC activation and liver fibrosis. RESULTS: Patients with increasing degrees of liver fibrosis had reduced levels of MAP1S. Supplementing spermidine in mice that had already developed liver fibrosis after 1 month of CCl4 induction for an additional 3 months resulted in significant reductions in levels of ECM proteins and a remarkable improvement in liver fibrosis through MAP1S. Spermidine also suppressed HSC activation by reducing ECM proteins at both the mRNA and protein levels, and increasing the number of lipid droplets in stellate cells. CONCLUSIONS: Spermidine supplementation is a potentially clinically meaningful approach to treating and curing liver fibrosis, preventing cirrhosis and HCC in patients.

Clinical characteristics and prognosis of patients with healthcare-associated cholecystitis receiving percutaneous cholecystostomy.

PURPOSE: Acute cholecystitis occurring outside the hospital setting is categorized as community-acquired cholecystitis (CAC). In contrast, it would be classified as a healthcare-associated cholecystitis (HAC) when it is associated with healthcare risk factors. This study aimed to compare the clinical characteristics of HAC to those of CAC and analyze their difference in prognosis after percutaneous cholecystostomy (PC). METHODS: A retrospective study was conducted for patients with acute cholecystitis who underwent PC between January 1, 2017, and June 30, 2020, in our hospital. Patients with HAC and CAC were compared in terms of demographics, laboratory tests, isolated pathogens, treatment response after PC, mortality, complications, and subsequent management. RESULTS: A total of 247 patients with a mean age of 68 years were enrolled, among whom 131 patients (53.0%) were male. Twenty patients (8.1%) had HAC, and 227 patients (91.9%) had CAC. Patients with HAC were more likely to present with the following: fever (65.0% vs 35.7%; p = 0.010), acalculous cholecystitis (50.0% vs 20.3%; p = 0.002), and a history of malignancy (50.0% vs 15.4%; p < 0.001), poorer clinical responses to PC treatment (75.0% vs 93.0%; p = 0.006), longer length of stay (14.15 days vs 7.62 days; p < 0.001), and higher all-cause mortality (30.0% vs 9.7%; p = 0.006). In addition, a relatively small number of patients with HAC underwent cholecystectomy in subsequent management (35.0% vs 69.2%; p = 0.002). CONCLUSIONS: In conclusion, compared to patients with CAC, those with HAC had more atypical symptoms, poorer clinical response to PC, longer hospital stay, and higher all-cause mortality, which makes the acceptability of PC treatment questionable.

Localization Evaluation of Primary Middle Ear Cholesteatoma With Fusion of Turbo Spin-Echo Diffusion-Weighted Imaging and High-Resolution Computed Tomography.

OBJECTIVE: The aim of the study is to evaluate the application of high-resolution computed tomography (HRCT) and turbo spin-echo diffusion-weighted imaging (TSE-DWI) fusion imaging for localization of middle ear cholesteatomas. METHODS: Eighty-six patients with clinically suspected middle ear cholesteatomas were enrolled prospectively. Ear TSE-DWI and HRCT scans were performed using a postprocessing workstation to generate a TSE-DWI-CT fusion image. Subsequently, all the enrolled patients received surgical treatment. According to the STAM system (difficult access sites [S], the tympanic cavity [T], the attic [A], and the mastoid [M]), the agreement between the localization of lesions evaluated by HRCT, TSE-DWI, and TSE-DWI-CT fusion images and the intraoperatively recorded localization were computed using Cohen κ statistic. RESULTS: Based on the pathological results, the enrolled patients were divided into a cholesteatoma (n = 50) and a noncholesteatoma group (n = 36). The area under the receiver operator characteristic curve for diagnosis of cholesteatoma with TSE-DWI-CT fusion imaging was identical to that using the TSE-DWI images (0.924 vs 0.924, P > 0.05), but was significantly higher than that with HRCT imaging (0.924 vs 0.767, P = 0.0005). Furthermore, the diagnostic sensitivity and specificity of TSE-DWI-CT fusion imaging for cholesteatomas were 96.0% and 88.9%, respectively. Depending on whether the cholesteatoma extended to the mastoid, TSE-DWI-CT fusion imaging demonstrated good agreement with the intraoperative record for localization of lesions (κ = 0.808) and had a high accuracy of localization by the STAM system. CONCLUSIONS: Turbo spin-echo-DWI-CT fusion images have a very high diagnostic value for the preoperative localization of cholesteatomas.

Thoracic perivascular adipose tissue inhibits VSMC apoptosis and aortic aneurysm formation in mice via the secretome of browning adipocytes.

Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes.

Development and validation of a deep learning model for survival prognosis of transcatheter arterial chemoembolization in patients with intermediate-stage hepatocellular carcinoma.

PURPOSE: We aimed to develop a deep learning-based approach to evaluate both time-to-progression (TTP) and overall survival (OS) prognosis of transcatheter arterial chemoembolization (TACE) in treatment-naïve patients with intermediate-stage hepatocellular carcinoma (HCC) and compare the approach's performance with those of radiomics and clinical models. METHODS: EfficientNetV2 was used to build a prognosis model for treatment-naïve patients with HCC. Data of 414 intermediate-stage HCC patients from one participant center were collected to construct the training and validation datasets (70%:30%) for TTP prognosis, while data of 129 intermediate-stage HCC patients from another participant center were collected as the test dataset for both TTP and OS prognosis. Three radiomics and three clinical models were then constructed for comparison. RESULTS: Patients with EfficientNetV2-based model score ≤ 0.5 had better TTP than those with higher scores (hazard ratio [HR]: 0.32, 95%CI: 0.22-0.46, P < 0.0001; HR: 0.28, 95%CI: 0.20-0.41, P < 0.0001; and HR: 0.55, 95%CI: 0.36-0.88, P = 0.005 in the training, validation, and test datasets, respectively). Patients with model score ≤ 0.5 had better OS (38.8 months vs 20.9 months, HR: 0.58, 95%CI: 0.37-0.90, P = 0.008). Compared with the radiomics (intra-tumoral and peri-tumoral) and three clinical models, the EfficientNetV2-based model showed better survival prognosis for TACE (P < 0.05) in the test dataset. CONCLUSIONS: The EfficientNetV2-based model enables assessment of both TTP and OS prognosis of TACE in treatment-naïve, intermediate-stage HCC. Patients with lower scores will benefit from TACE. The model can potentially be used by clinicians to improve decision making regarding TACE treatment choices.

microRNA-206 prevents hepatocellular carcinoma growth and metastasis via down-regulating CREB5 and inhibiting the PI3K/AKT signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most common cancers and has continued to increase in incidence worldwide. Moreover, the involvement of microRNAs (miRs) has been reported in the development and progression of HCC. Here, we investigated the role of miR-206 in HCC growth and metastasis. HCC-related microarray datasets were harvested to screen differentially expressed miRNAs in HCC samples followed by prediction of downstream target genes. The dual-luciferase reporter assay verified the target-binding relationship between miR-206 and CREB5. The human HCC cell line MHCC97-H was cultured in vitro and transfected with miR-206 mimic/inhibitor or sh-/oe-CREB5 for analyzing MHCC97-H cell biological functions. The orthotopic xenograft model of HCC mice was constructed to observe the tumorigenic ability of HCC cells in vivo. Bioinformatics analysis found that miR-206 may be involved in HCC growth and metastasis by targeting CREB5 and regulating PI3K/AKT signaling pathway. In vivo animal experiments found that CREB5 was significantly overexpressed in mouse HCC tissues. In HCC cells, miR-206 can target down-regulate the expression of CREB5, thereby inhibiting the activation of PI3K/AKT signaling pathway. Furthermore, in vitro cell experiments confirmed that overexpression of miR-206 could inhibit the PI3K/AKT signaling pathway by down-regulating CREB5 expression, thereby inhibiting the proliferation, migration and invasion of HCC cells. In conclusion, our results revealed that miR-206 could down-regulate the expression of CREB5 and inhibit the activation of PI3K/AKT signaling pathway, thereby preventing HCC growth and metastasis.Abbreviations: HCC: hepatocellular carcinoma; HBV or HCV: hepatitis B or C virus; miRNAs: microRNAs; CREB: cAMP response element-binding protein; CRE: cAMP response elements.

Radiogenomics: A Valuable Tool for the Clinical Assessment and Research of Ovarian Cancer.

ABSTRACT: A new interdisciplinary approach based on medical imaging phenotypes, gene expression patterns, and clinical parameters, referred to as radiogenomics, has recently been developed for biomarker identification and clinical risk stratification in oncology, including for the assessment of ovarian cancer. Some radiological phenotypes (implant distribution, lymphadenopathy, and texture-derived features) are related to specific genetic landscapes (BRCA, BRAF, SULF1, the Classification of Ovarian Cancer), and integrated models can improve the efficiency for predicting clinical outcomes. The establishment of databases in medical images and gene expression profile with large sample size and the improvement of artificial intelligence algorithm will further promote the application of radiogenomics in ovarian cancer.

Cross-sectional analysis of gonadal hormone expression and relevant factors in female centenarians in Hainan, China. / ä¸­å›½æµ·å—ç™¾å²å¥³æ€§è€äººæ€§è ºæ¿€ç´ è¡¨è¾¾ç‰¹å¾åŠå ³è”å› ç´ çš„æ¨ªæ–­é¢åˆ†æž.

OBJECTIVES: Gonadal hormone is essential for the health of postmenopausal women, however, few studies have focused on the epidemiological distribution of gonadal hormones in postmenopausal women in very late postmenopausal women. This study aims to investigate and analyze the differences of serum gonadal hormone content and its influential factors among female centenarians in Hainan, China. METHODS: The questionnaire and physical examination data of 741 female centenarians and 401 elderly females in Hainan Province were collected, and venous blood samples were taken to detect the indexes of lipid metabolism, bone metabolism, and gonadal hormone. The differences of gonadal hormones and relavant factors in female centenarians were analyzed and compared. RESULTS: The serum levels of estradiol and progesterone of female centenarians were significantly higher than those of the elderly females (both P<0.001). The serum levels of estradiol and testosterone of ethnic minority centenarians were higher than those in Han nationality (P<0.001), and the serum estradiol and testosterone concentrations were relatively higher when the daily activities were more than 10 min (both P<0.05). Serum estradiol concentration was negatively correlated with apolipoprotein A-I, high density lipoprotein, triglyceride and bone formation markers such as calcium, inorganic phosphorus and vitamin D3, and was positively correlated with the special sequence of ß-collagen (markers of bone resorption) (all P<0.01). CONCLUSIONS: For the extremely late postmenopausal women (such as centenarians), there may be characteristic expressions of gonadal hormones, especially estradiol. There is an unprotective correlation of serum estradiol with lipid metabolism index and bone metabolism index in female centenarians, so it is necessary to evaluate the estrogen content and the use of estrogen therapy in postmenopausal women.

AMP-activated protein kinase α1 phosphorylates PHD2 to maintain systemic iron homeostasis.

BACKGROUND: Iron is essential for all mammalian life, and either a deficiency or excess of iron can cause diseases. AMP-activated protein kinase (AMPK) is a critical regulator of metabolic homeostasis; however, it has not been established whether AMPK regulates iron metabolism. METHODS: Iron, hepcidin and ferroportin levels were examined in mice with global and hepatocyte-specific knockout of AMPKα1 and AMPKα2. Primary AMPKα1 or AMPKα2 deleted hepatocytes were isolated and cultured in hypoxia condition to explore PHD2, HIF and hydroxylated HIF1α levels. We performed immunoprecipitation, in vitro AMPK kinase assay and site-direct mutant assay to detect phosphorylation sites of PHD2. We also obtained liver tissues from patients with anaemia of chronic disease undergoing surgery, AMPKα1 and hydroxylated HIF1α levels were measured by immunohistochemical analysis. RESULTS: We found that mice with global deficiency of AMPKα1, but not AMPKα2, exhibited hypoferraemia as well as iron sequestration in the spleen and liver. Hepatocyte-specific, but not myeloid-specific, ablation of AMPKα1 also reduced serum iron levels in association with increased hepcidin and decreased ferroportin protein levels. Mechanistically, AMPKα1 directly phosphorylated prolyl hydroxylase domain-containing (PHD)2 at serines 61 and 136, which suppressed PHD2-dependent hydroxylation of hypoxia-inducible factor (HIF)1α and subsequent regulation of hepatic hepcidin-related iron signalling. Inhibition of PHD2 hydroxylation ameliorated abnormal iron metabolism in hepatic AMPKα1-deficient mice. Furthermore, we found hepatic AMPKα/PHD2/HIFα/ hepcidin axes were highly clinically relevant to anaemia of chronic disease. CONCLUSION: In conclusion, these observations suggest that hepatic AMPKα1 has an essential role in maintaining iron homeostasis by PHD2-dependent regulation of hepcidin, thus providing a potentially promising approach for the treatment of iron disturbances in chronic diseases.

Experimental realization of visible gas sensing technology based on spatial heterodyne spectroscopy.

Based on the characteristics of optical absorption gas sensing technology (OA-GST) and spatial heterodyne spectroscopy (SHS), a novel type of visual gas sensing technology (V-GST) can present the invisible gas information in the form of two-dimensional visual fingerprint, which has attracted people's attention. In this paper, we have realized the NO2 detection of V-GST in the laboratory environment for the first time. Experimental results show that: V-GST not only has different interferogram response to different spectra, but also has good response to different concentrations of NO2, which lays a foundation for the application of this technology in gas sensing. And the average classification recognition rate of the system for different band NO2 response data is over 80%, which verifies the effectiveness of the V-GST in gas detection.

LncRNA ILF3-AS1 promotes cell migration, invasion and EMT process in hepatocellular carcinoma via the miR-628-5p/MEIS2 axis to activate the Notch pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are essential indicators for hepatocellular carcinoma. LncRNAs can exert the same functions as their antisense mRNAs. ILF3 is an oncogene in hepatocellular carcinoma. ILF3 divergent transcript (ILF3-AS1) is the antisense RNA of ILF3, and has been reported as an oncogene in various cancers. AIMS: To explore the role of lncRNA ILF3-AS1 in malignant phenotypes of hepatocellular carcinoma cells. METHODS AND RESULTS: RT-qPCR analysis revealed that ILF3-AS1 was significantly upregulated in hepatocellular carcinoma cells. The hepatocellular carcinoma cell viability was suppressed by silenced ILF3-AS1. Transwell and wound healing assays showed that ILF3-AS1 downregulation inhibited cell invasion and migration. The levels of proteins associated with epithelial-mesenchymal transition (EMT) process and the Notch pathway were detected by western blot analysis. Luciferase reporter, RNA pull down and RIP assays were used to investigate the relationship between ILF3-AS1 and downstream target genes. ILF3-AS1 competed with meis homeobox 2 (MEIS2) for miR-628-5p in hepatocellular carcinoma cells. ILF3-AS1 elevated the levels of key proteins on the Notch pathway. Rescue assays demonstrated that MEIS2 reversed the antitumor effects of silenced ILF3-AS1 on hepatocellular carcinoma. In vivo assays demonstrated that ILF3-AS1 silencing inhibited the hepatocellular carcinoma tumor growth. CONCLUSIONS: ILF3-AS1 promoted hepatocellular carcinoma progression via the Notch pathway and miR-628-5p/MEIS2 axis.