[Clinical analysis of 12 cases of ovarian yolk sac tumor].

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 µg/L) were significantly higher than normal (<25 µg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Interrelationship between platelets and BUN in postmenopausal patients with coronary heart disease: findings of the NHANES from 2003 to 2016.

OBJECTIVE: During menopause, women are more likely to develop coronary heart disease (CHD) due to the significant changes in body metabolism brought on by the loss of estrogen. The purpose of this study was to investigate the independent association between platelet parameters and blood urea nitrogen (BUN) in postmenopausal patients with coronary artery disease in order to clarify the function performed by platelet parameters and BUN in thrombosis. PATIENTS AND METHODS: We took information from the NHANES between 2003 and 2016. Platelet count (PC), mean platelet volume (MPV), and PC/MPV were the independent variables, BUN was the dependent variable, and age, race, marital status, body mass index (BMI), inflammation indicators, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were the covariates. RESULTS: BUN decreased with increasing PC in postmenopausal heart disease patients after controlling for other factors. When PC/MPV was less than 30.5, there was a strong negative correlation with BUN. In addition, there was a strong positive correlation with BUN when MPV was less than 9.3 fL. CONCLUSIONS: The findings of this study will contribute to a better understanding of the mechanisms underlying thrombosis in postmenopausal women with CHD and offer fresh perspectives on how to create novel antithrombotic medications for an aging population.

Crizotinib in patients with tumors harboring ALK or ROS1 rearrangements in the NCI-MATCH trial.

The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8-90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3-75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting.

Circ_0061140 promotes metastasis of bladder cancer through adsorbing microRNA-1236.

We detected some serious inaccuracies and mistakes. Therefore, the article, "Circ_0061140 promotes metastasis of bladder cancer through adsorbing microRNA-1236, by F. Feng, A.-P. Chen, X.-L. Wang, G.-L. Wu, published in Eur Rev Med Pharmacol Sci 2020; 24 (10): 5310-5319-DOI: 10.26355/eurrev_202005_21313-PMID: 32495864" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21313.

Circ_0061140 promotes metastasis of bladder cancer through adsorbing microRNA-1236.

OBJECTIVE: The purpose of this study was to investigate the expression characteristics of circular RNA circ_0061140 in bladder cancer (BCa), and to further explore its effects on invasiveness and migration capacity of BCa cells, as well as its possible potential mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression level of circ_0061140 in tumor tissue samples and paracancerous ones collected from 42 patients with BCa, and the interplay between circ_0061140 level and the clinical indicators, as well as the prognosis of BCa patients were analyzed. Meanwhile, qRT-PCR was also used to verify circ_0061140 expression in BCa cell lines. In addition, a circ_0061140 knockdown model was constructed using Lentiviral in BCa cell lines, including T24 and 253j, and the effect of circ_0061140 on BCa cell functions and its underlying mechanisms were explored using Cell Counting Kit-8 (CCK-8), transwell, and cell wound healing assays. RESULTS: qPCR results showed that the expression level of circ_0061140 in tumor tissues of BCa patients was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with patients with low expression of circ_0061140, patients with high expression of circ_0061140 had worse prognosis and higher incidence of lymph node or distant metastasis. Compared with those in the negative control group, the proliferation and invasion, as well as the metastasis ability of BCa cells in the sh-circ_0061140 group, were remarkably attenuated. In addition, bioinformatics and Luciferase reporter gene assay demonstrated that circ_0061140 can specifically bind to microRNA-1236. At the same time, the results of qPCR revealed that the expression levels of circ_0061140 and microRNA-1236 were negatively correlated in the tumor tissues of BCa patients. Finally, cell recovery experiment indicated that silencing microRNA-1236 reversed the impact of the knockdown of circ_0061140 on the ability of BCa cells to proliferate and invade, suggesting that the two may regulate each other. CONCLUSIONS: Circ_0061140 level was found remarkably elevated in BCa tissues, as well as in cell lines, which was closely relevant to the incidence of lymph node or distant metastasis of BCa patients. In addition, circ_0061140 may enhance the proliferation rate and invasion ability of BCa cells through the modulation of microRNA-1236.

[Effect of GPX4 on proliferation and metastasis of renal clear cell carcinoma and its relationship with expression of IGF-1R and COX-2].

Objective: To investigate the effect of human glutathione peroxidase 4 (GPX4) on the proliferation and metastasis of renal clear cell carcinoma and its relationship with the expression of IGF-1R and COX-2. Methods: Culture of human normal tubular cell line HK-2 and human renal clear cell carcinoma Caki-1, A498, Caki-2, 786-o in vitro. Detection of GPX4 mRNA and protein expression in different cell lines by quantitative real-time PCR (RT-PCR) and Western blot assay. Overexpression of GPX4 cell lines, including blank carrier (Vector) and overexpress GPX4 (oeGPX4) group, and interference with GPX4 renal clear cell carcinoma cell lines, including random sequence (shControl), interference GPX4#1 (shGPX4#1) and interference GPX4#2 (shGPX4#2) group by lentiviral transfection. RT-PCR technology and Western blot were used to detect the expression of GPX4, IGF-1R and COX-2 mRNA and protein. CCK-8 assay was used to detect the relative proliferation of cells at 0, 24, 48, 72 and 96 h in each group. Transwell invasion and migration assay to detect the invasion and migration ability of cells of each group. Results: GPX4 is highly expressed in renal clear cell carcinoma cell lines compared to human normal tubular cell lines; The expression of GPX4, IGF-1R and COX-2 mRNA was significantly increased in oeGPX4 cells compared with Vector cells, the expression of GPX4,IGF-1R and COX-2 mRNA was significantly decreased in shGPX4#1 and shGPX4#2 compared with shControl cells; oeGPX4 cells significantly increased proliferative capacity compared to Vector cells at 72 and 96 h, the proliferation of shGPX4#1 and shGPX4#2 cells was significantly lower than that of shControl cells at 72 and 96 h; The number of invading and migrating cells of oeGPX4 cells was significantly higher than that of Vector cells, the number of invasive and migrating cells in shGPX4#1 and shGPX4#2 cells was significantly lower than that in shControl cells. Conclusion: GPX4 is highly expressed in renal clear cell carcinoma cells, which is positively correlated with the expression of IGF-1R and COX-2, and can promote cell proliferation and metastasis in vitro.

Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: results from the NCI-MATCH trial (EAY131) subprotocol Q.

BACKGROUND: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors. METHODS: Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq™ (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed. RESULTS: Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0-9; unknown in one patient). Median HER2 CN was 17 (range 7-139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% [90% confidence interval 14.2% to 39.2%]. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay. CONCLUSION: T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.

Epitaxial thin films of pyrochlore iridate Bi2+xIr2-yO7-δ: structure, defects and transport properties.

While pyrochlore iridate thin films are theoretically predicted to possess a variety of emergent topological properties, experimental verification of these predictions can be obstructed by the challenge in thin film growth. Here we report on the pulsed laser deposition and characterization of thin films of a representative pyrochlore compound Bi2Ir2O7. The films were epitaxially grown on yttria-stabilized zirconia substrates and have lattice constants that are a few percent larger than that of the bulk single crystals. The film composition shows a strong dependence on the oxygen partial pressure. Density-functional-theory calculations indicate the existence of BiIr antisite defects, qualitatively consistent with the high Bi: Ir ratio found in the films. Both Ir and Bi have oxidation states that are lower than their nominal values, suggesting the existence of oxygen deficiency. The iridate thin films show a variety of intriguing transport characteristics, including multiple charge carriers, logarithmic dependence of resistance on temperature, antilocalization corrections to conductance due to spin-orbit interactions, and linear positive magnetoresistance.

Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.

BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. 18F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes 18F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. METHODS: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with 18F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with 18F-FES 1-5 days post administration of Z-endoxifen. RESULTS: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. CONCLUSION: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

[The progress of glucocorticoids via postauricular injection in treatment of sudden hearing loss].

Corticosteroids are commonly accepted and recommended for treating sudden hearing loss.In recent years，postauricular delivery attracts attention due to the advantage of high drug concentration in cochlear and minimal side effects.This article reviews the published literature related the application of glucocorticoids via postauricular injection in treatment of sudden hearing loss and its animal experiments, speculates the possible pathway that drugs enter inner ear, and put forward the idea of treating facial nerve diseases via postauricular injection.

Magnetic properties of uncultivated magnetotactic bacteria and their contribution to a stratified estuary iron cycle.

Of the two nanocrystal (magnetosome) compositions biosynthesized by magnetotactic bacteria (MTB), the magnetic properties of magnetite magnetosomes have been extensively studied using widely available cultures, while those of greigite magnetosomes remain poorly known. Here we have collected uncultivated magnetite- and greigite-producing MTB to determine their magnetic coercivity distribution and ferromagnetic resonance (FMR) spectra and to assess the MTB-associated iron flux. We find that compared with magnetite-producing MTB cultures, FMR spectra of uncultivated MTB are characterized by a wider empirical parameter range, thus complicating the use of FMR for fossilized magnetosome (magnetofossil) detection. Furthermore, in stark contrast to putative Neogene greigite magnetofossil records, the coercivity distributions for greigite-producing MTB are fundamentally left-skewed with a lower median. Lastly, a comparison between the MTB-associated iron flux in the investigated estuary and the pyritic-Fe flux in the Black Sea suggests MTB play an important, but heretofore overlooked role in euxinic marine system iron cycle.

Noninvasive identification and assessment of functional brown adipose tissue in rodents using hyperpolarized ¹³C imaging.

OBJECTIVE: The recent identification of functional depots of brown adipose tissue (BAT) in adult humans has potential implications for the treatment of obesity. In order to evaluate new therapies aimed at inducing the production of more BAT or activating BAT in humans, it will be important to develop noninvasive methods to assess the functional state of the tissue in vivo. In this study, we investigate the feasibility of using hyperpolarized (13)C imaging to noninvasively identify functional, activated BAT in an in vivo rodent model, in less than 1 min, following an infusion of pre-polarized [1-(13)C] pyruvate. DESIGN: Hyperpolarized (13)C imaging was used to monitor BAT metabolic conversion of pre-polarized [1-(13)C] pyruvate in rats during baseline and norepinephrine (NE)-stimulated conditions. RESULTS: Activated BAT, stimulated by NE injection, can be detected in rats by increased conversion of pre-polarized [1-(13)C] pyruvate into its downstream products (13)C bicarbonate and [1-(13)C] lactate. The colocalization of the (13)C signal to interscapular BAT was validated using hematoxylin-eosin histological staining. CONCLUSION: The radiation-free nature and recent translation into the clinic of the hyperpolarized (13)C-imaging test may potentially facilitate trials of therapeutics targeting BAT activation in humans.

Imaging considerations for in vivo 13C metabolic mapping using hyperpolarized 13C-pyruvate.

One of the challenges of optimizing signal-to-noise ratio (SNR) and image quality in (13)C metabolic imaging using hyperpolarized (13)C-pyruvate is associated with the different MR signal time-courses for pyruvate and its metabolic products, lactate and alanine. The impact of the acquisition time window, variation of flip angles, and order of phase encoding on SNR and image quality were evaluated in mathematical simulations and rat experiments, based on multishot fast chemical shift imaging (CSI) and three-dimensional echo-planar spectroscopic imaging (3DEPSI) sequences. The image timing was set to coincide with the peak production of lactate. The strategy of combining variable flip angles and centric phase encoding (cPE) improved image quality while retaining good SNR. In addition, two aspects of EPSI sampling strategies were explored: waveform design (flyback vs. symmetric EPSI) and spectral bandwidth (BW = 500 Hz vs. 267 Hz). Both symmetric EPSI and reduced BW trended toward increased SNR. The imaging strategies reported here can serve as guidance to other multishot spectroscopic imaging protocols for (13)C metabolic imaging applications.

In vivo 13 carbon metabolic imaging at 3T with hyperpolarized 13C-1-pyruvate.

We present for the first time dynamic spectra and spectroscopic images acquired in normal rats at 3T following the injection of (13)C-1-pyruvate that was hyperpolarized by the dynamic nuclear polarization (DNP) method. Spectroscopic sampling was optimized for signal-to-noise ratio (SNR) and for spectral resolution of (13)C-1-pyruvate and its metabolic products (13)C-1-alanine, (13)C-1-lactate, and (13)C-bicarbonate. Dynamic spectra in rats were collected with a temporal resolution of 3 s from a 90-mm axial slab using a dual (1)H-(13)C quadrature birdcage coil to observe the combined effects of metabolism, flow, and T(1) relaxation. In separate experiments, spectroscopic imaging data were obtained during a 17-s acquisition of a 20-mm axial slice centered on the rat kidney region to provide information on the spatial distribution of the metabolites. Conversion of pyruvate to lactate, alanine, and bicarbonate occurred within a minute of injection. Alanine was observed primarily in skeletal muscle and liver, while pyruvate, lactate, and bicarbonate concentrations were relatively high in the vasculature and kidneys. In contrast to earlier work at 1.5 T, bicarbonate was routinely observed in skeletal muscle as well as the kidney and vasculature.

Parasitic diseases of cultured marine finfishes and their surveillance in China.

More than 40 species of marine fishes are cultured in China and a wide variety of parasites are reported as lethal pathogens of these fishes in culture conditions. In the case of net cages, the culture facilities provides a good substrate for monogenean eggs to become entangled and the intensive aggregation of fishes facilitates the transmission of parasites between hosts. Relatively thorough studies on parasitic pathogens of marine fishes in China predominately concern the ciliate Cryptocaryon irritans and capsalid monogeneans (mainly Benedenia sp. and Neobenedenia sp.). Although nearly all such reports are related to treatment procedures, no single method has proved to be adequate for the effective control of these parasitic pathogens in marine cultured fishes. The National Fisheries Technology Extension Center (NFTEC) has established surveillance systems to monitor the diseases of aquaculture, including the parasitic diseases of maricultured fishes. The national monitoring stations for diseases of cultured marine fishes are distributed in the coastal counties or cities and provide remote in situ diagnoses of diseased fishes. International cooperation and effort are required for the control of parasitic diseases of marine finfish because of both the increasing international trade of eggs (seed) and larvae and commercial products in terms of live marine finfishes, which can readily result in the transmission of pathogens.

Establishing an index arbitrage model by applying neural networks method--a case study of Nikkei 225 index.

This paper applies the neural network method to establish an index arbitrage model and compares the arbitrage performances to that from traditional cost of carry arbitrage model. From the empirical results of the Nikkei 225 stock index market, following conclusions can be stated: (1) The basis will get enlarged for a time period, more profitability may be obtained from the trend. (2) If the neural network is applied within the index arbitrage model, twofold of return would be obtained than traditional arbitrage model can do. (3) If the T_basis has volatile trend, the neural network arbitrage model will ignore the peak. Although arbitrageur would lose the chance to get profit, they may reduce the market impact risk.

Inducible, pharmacogenetic approaches to the study of learning and memory.

Here we introduce a strategy in which pharmacology is used to induce the effects of recessive mutations. For example, mice heterozygous for a null mutation of the K-ras gene (K-ras+/-) show normal hippocampal mitogen-activated protein kinase (MAPK) activation, long-term potentiation (LTP) and contextual conditioning. However, a dose of a mitogen-activated/extracellular-signal-regulated kinase (MEK) inhibitor, ineffective in wild-type controls, blocks MAPK activation, LTP and contextual learning in K-ras+/- mutants. These indicate that K-Ras/MEK/MAPK signaling is critical in synaptic and behavioral plasticity. A subthreshold dose of NMDA receptor antagonists triggered a contextual learning deficit in mice heterozygous for a point mutation (T286A) in the alphaCaMKII gene, but not in K-ras+/- mutants, demonstrating the specificity of the synergistic interaction between the MEK inhibitor and the K-ras+/- mutation. This pharmacogenetic approach combines the high temporal specificity that pharmacological manipulations offer, with the molecular specificity of genetic disruptions.