Circ_0004851 regulates the molecular mechanism of miR-296-3p/FGF11 in the influence of high iodine on PTC.

The prevalence of papillary thyroid cancer (PTC) has been rising in recent years. Despite its relatively low mortality, PTC frequently metastasizes to lymph nodes and often recurs, posing significant health and economic burdens. The role of iodine in the pathogenesis and advancement of thyroid cancer remains poorly understood. Circular RNAs (circRNAs) are recognized to function as competing endogenous RNAs (ceRNAs) that modulate gene expression and play a role in various cancer stages. Consequently, this research aimed to elucidate the mechanism by which circRNA influences the impact of iodine on PTC. Our research indicates that high iodine levels can exacerbate the malignancy of PTC via the circ_0004851/miR-296-3p/FGF11 axis. These insights into iodine's biological role in PTC and the association of circRNA with the disease could pave the way for novel biomarkers and potentially effective therapeutic strategies to mitigate PTC progression.

Prognostic Value of Myosteatosis and Creatinine-to-Cystatin C Ratio in Patients with Pancreatic Cancer Who Underwent Radical Surgery.

BACKGROUND: Myosteatosis is correlated with poor prognosis in some malignancies. The creatinine-to-cystatin ratio (CCR) is revealed to predict gastric cancer prognosis. However, the prognostic abilities of CCR and the combination of CCR and myosteatosis in patients with pancreatic cancer (PC) who underwent radical surgery remains unclear. METHODS: The retrospective cohort study included 215 patients with PC who underwent radical surgery (January 2016-October 2021). Clinicopathological and serological data were collected on admission. Myosteatosis and other body composition indices were assessed by using computed tomography. The cutoff value of CCR was determined by using the Youden index. Risk factors responsible for poor overall survival (OS) and disease-free survival (DFS) were determined by the Cox proportional hazards model. RESULTS: The myosteatosis group included 104 patients (average age, 61.3 ± 9.1 years). The best cutoff value for CCR was 1.09. CCR ≤ 1.09 was an independent predictive biomarker inversely corelated with OS (P = 0.036). Myosteatosis was an independent risk factor associated with OS and DFS (P = 0.032 and P = 0.004, respectively). Patients with concomitant myosteatosis and CCR ≤ 1.09 had the worst OS (P = 0.016). CONCLUSIONS: Myosteatosis and CCR are prognostic biomarkers for survival in PC patients who underwent radical surgery. Patients with the coexistence of myosteatosis and CCR ≤ 1.09 deserve more attention.

Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer.

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.

Correlation of laminin subunit alpha 3 expression in pancreatic ductal adenocarcinoma with tumor liver metastasis and survival.

BACKGROUND: The high mortality rate of pancreatic ductal adenocarcinoma (PDAC) is primarily attributed to metastasis. Laminin subunit alpha 3 (LAMA3) is known to modulate tumor progression. However, the influence of LAMA3 on liver metastasis in PDAC remains unclear. This study aimed to elucidate whether LAMA3 expression is increased in PDAC with liver metastasis. PATIENTS AND METHODS: We extracted information related to LAMA3 expression levels and associated clinicopathological parameters from The Cancer Genome Atlas (TCGA) and four Gene Expression Omnibus (GEO) datasets. Clinicopathological analysis was performed; the Kaplan-Meier Plotter was used to evaluate LAMA3's prognostic effect in PDAC. We retrospectively collected clinicopathological data and tissue specimens from 117 surgically treated patients with PDAC at the Affiliated Hospital of Qingdao University. We assessed LAMA3 expression and investigated its correlation with the clinicopathological traits, clinical outcomes, and hepatic metastasis. RESULTS: Amplified expression of LAMA3 was observed in PDAC tissue compared with normal tissue in the TCGA and GEO databases. High LAMA3 expression was associated with poor overall survival (OS) and relapse-free survival (RFS) in patients with PDAC. LAMA3 expression was significantly enhanced in PDAC tissues than in adjacent tissues. Tumor tissues from patients with PDAC exhibiting liver metastasis showed higher LAMA3 expression than those without liver metastasis. High LAMA3 expression correlated with large tumor size and TNM stage. LAMA3 expression and liver metastasis were independent predictive factors for OS; the former was independently associated with liver metastasis. CONCLUSIONS: LAMA3 expression is elevated in patients with PDAC with liver metastasis and is a predictor of prognosis.

The coexistence of myosteatosis and the creatinine/cystatin C ratio are determinants of outcomes in cholangiocarcinoma patients undergoing curative surgery.

Background: Myosteatosis is a well-established predictor of poor prognosis in many types of cancer, and a decreased Creatinine/Cystatin C ratio (CCR) is a known indicator of unfavorable outcomes in patients with metabolic disorders and cancer. Despite this knowledge, the significance of concurrent CCR and myosteatosis in predicting the prognosis of patients with cholangiocarcinoma (CCA) who undergo radical surgery remains uncertain. Method: Data from 757 patients with cholangiocarcinoma who underwent the first radical resection in the Affiliated Hospital of Qingdao University from January 2017 to March 2022 were collected. According to the inclusion and exclusion criteria, 149 patients were finally included in the retrospective study cohort. Various clinicopathological, serological, and radiological data were collected at admission. Myosteatosis was evaluated using sliceOmatic software on computed tomography (CT) images. The study used receiver operating characteristic (ROC) curve analysis to determine the critical value of CCR, which predicts overall survival (OS) based on the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were employed to identify the risk factors associated with OS and RFS confidently. Results: The group identified as the myosteatosis cohort consisted of 79 patients with an average age of 64.3 ± 7.8 years. The ROC curve analysis revealed an optimal critical CCR value of 10.834. A low CCR ≤ 10.834 and myosteatosis were found to be associated with poor OS and RFS outcomes (P = 0.022; P = 0.017; P = 0.038; P = 0.030 respectively). Moreover, patients with myosteatosis and a CCR ≤ 10.834 had the worst OS and RFS outcomes (P = 0.035; P = 0.027). Conclusion: After radical excision in CCA patients, the presence of myosteatosis and CCR had a negative correlation with prognosis. A more accurate prediction of OS and RFS was possible by combining CCR and myosteatosis, compared to CCR alone.

Scavenging Radionuclide by Shapeable Porous Materials.

Nuclear energy is a competitive and environmentally friendly low-carbon energy source. It is seen as an important avenue for satisfying energy demands, responding to the energy crisis, and mitigating global climate change. However, much attention has been paid to achieving the effective treatment of radionuclide ions produced in nuclear waste. Initially, advanced adsorbents were mainly available in powder form, which meant that additional purification processes were usually required for separation and recovery in industrial applications. Therefore, to meet the practical requirements of industrial applications, materials need to be molded and processed into forms such as beads, membranes, gels, and resins. Here, we summarize the fabrication of porous materials used for capturing typical radionuclide ions, including UO2 2+, TcO4 -, IO3 -, SeO3 2-, and SeO4 2-.

Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.

The effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke: a meta-analysis.

BACKGROUND: Respiratory muscle training is a continuous and standardized training of respiratory muscles, but the evidence of the effects on early stroke patients is not clear. This meta-analysis aimed to investigate the effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke. METHODS: PubMed, Embase, PEDro, ScienceDirect, AMED, CINAHL, and China National Knowledge Infrastructure databases were searched from inception to December 8, 2023 for articles about studies that 1) stroke patients with age ≥ 18 years old. Early stroke < 3 months at the time of diagnosis, 2) respiratory muscle training, including inspiratory and expiratory muscle training, 3) the following measurements are the outcomes: respiratory muscle strength, respiratory muscle endurance, pulmonary function testing, dyspnea fatigue score, and functional capacity, 4) randomized controlled trials. Studies that met the inclusion criteria were extracted data and appraised the methodological quality and risk of bias using the Physiotherapy Evidence Database scale and the Cochrane Risk of Bias tool by two independent reviewers. RevMan 5.4 with a random effect model was used for data synthesis and analysis. Mean differences (MD) or standard mean differences (SMD), and 95% confidence interval were calculated (95%CI). RESULTS: Nine studies met inclusion criteria, recruiting 526 participants (mean age 61.6 years). Respiratory muscle training produced a statistically significant effect on improving maximal inspiratory pressure (MD = 10.93, 95%CI: 8.51-13.36), maximal expiratory pressure (MD = 9.01, 95%CI: 5.34-12.69), forced vital capacity (MD = 0.82, 95%CI: 0.54-1.10), peak expiratory flow (MD = 1.28, 95%CI: 0.94-1.63), forced expiratory volume in 1 s (MD = 1.36, 95%CI: 1.13-1.59), functional capacity (SMD = 0.51, 95%CI: 0.05-0.98) in patients with early stroke. Subgroup analysis showed that inspiratory muscle training combined with expiratory muscle training was beneficial to the recovery of maximal inspiratory pressure (MD = 9.78, 95%CI: 5.96-13.60), maximal expiratory pressure (MD = 11.62, 95%CI: 3.80-19.43), forced vital capacity (MD = 0.87, 95%CI: 0.47-1.27), peak expiratory flow (MD = 1.51, 95%CI: 1.22-1.80), forced expiratory volume in 1 s (MD = 0.76, 95%CI: 0.41-1.11), functional capacity (SMD = 0.61, 95%CI: 0.08-1.13), while inspiratory muscle training could improve maximal inspiratory pressure (MD = 11.60, 95%CI: 8.15-15.05), maximal expiratory pressure (MD = 7.06, 95%CI: 3.50-10.62), forced vital capacity (MD = 0.71, 95%CI: 0.21-1.21), peak expiratory flow (MD = 0.84, 95%CI: 0.37-1.31), forced expiratory volume in 1 s (MD = 0.40, 95%CI: 0.08-0.72). CONCLUSIONS: This study provides good-quality evidence that respiratory muscle training is effective in improving respiratory muscle strength, pulmonary function, and functional capacity for patients with early stroke. Inspiratory muscle training combined with expiratory muscle training seems to promote functional recovery in patients with early stroke more than inspiratory muscle training alone. TRIAL REGISTRATION: Prospero registration number: CRD42021291918.

Chemical characterization and discovery of novel quality markers in Citrus aurantium L. fruit from traditional cultivation areas in China using GC-MS-based cuticular waxes analysis.

Citrus aurantium L. fruit is a commonly used Chinese medicine whose therapeutic effects tends to be affected by growing conditions. In order to gain insights into the effects of growing location on the cuticular wax composition of C. aurantium L. fruit, we analyzed the differences in the wax composition of its fruits collected from different regions. The findings showed that the cuticular waxes in the fruit peels were mainly composed of fatty acids, which differed quantitatively in the chemical profiles of C. aurantium L. samples from different geographical conditions. Particularly, the concentrations of linoleic acid and stearic acid in the total component content of the fruit peel were above 1%, with a greater level in the geo-authentic samples. Thus, GC-MS-based wax analysis was first used for the chemical characterization and quantification of cuticular waxes, which could be considered as a rapid way for evaluating the quality of medicinal fruits.

Cardiac magnetic resonance imaging-derived septum swing index detects pulmonary hypertension: A diagnostic study.

Background and Objectives: Because of pressure differences between the pulmonary artery and aorta, the ventricular septum moves in a swinging motion that is commonly observed on cardiac MR (CMR) cine sequences in patients with pulmonary hypertension (PH). We aimed to assess the use of septum swing index (SSI) derived by CMR for detecting PH. Methods: We retrospectively identified consecutive patients with suspected PH who underwent right heart catheterization (RHC) and CMR at a PH referral center between July 2019 and December 2020. The diagnostic accuracy of SSI for identifying PH (mean pulmonary artery pressure [mPAP] ≥ 25 mmHg) was assessed by receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values. Results: A total of 105 patients (mean age: 47.8 ± 15.0 years; 68 females) were included in the final analysis. SSI and mPAP were negatively correlated in the total study population and patients with PH, but not in patients without PH. SSI was an independent predictor of PH (adjusted odds ratio: 12.9, 95% confidence interval: 3.6 to 45.5, P = 0.003). The area under the curve for SSI was 0.91, with a cut-off value of 0.9673 yielding the best balance of sensitivity (86.4%), specificity (88.2%), positive predictive value (97.4%), negative predictive value (55.6%), and accuracy (86.7%) for detecting PH. Conclusions: Septum swing index was lower in patients with PH and is a simple, reliable method for detecting PH.

Is Metastatic Staging Needed for All Patients with Synchronous Bilateral Breast Cancers?

BACKGROUND: Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge. METHODS: A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging. RESULTS: A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging (p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients. CONCLUSIONS: Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies.