SENP1-Sirt3 Signaling Controls Mitochondrial Protein Acetylation and Metabolism.

Sirt3, as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolic adaption to various stresses. However, how to regulate Sirt3 activity responding to metabolic stress remains largely unknown. Here, we report Sirt3 as a SUMOylated protein in mitochondria. SUMOylation suppresses Sirt3 catalytic activity. SUMOylation-deficient Sirt3 shows elevated deacetylation on mitochondrial proteins and increased fatty acid oxidation. During fasting, SUMO-specific protease SENP1 is accumulated in mitochondria and quickly de-SUMOylates and activates Sirt3. SENP1 deficiency results in hyper-SUMOylation of Sirt3 and hyper-acetylation of mitochondrial proteins, which reduces mitochondrial metabolic adaption responding to fasting. Furthermore, we find that fasting induces SENP1 translocation into mitochondria to activate Sirt3. The studies on mice show that Sirt3 SUMOylation mutation reduces fat mass and antagonizes high-fat diet (HFD)-induced obesity via increasing oxidative phosphorylation and energy expenditure. Our results reveal that SENP1-Sirt3 signaling modulates Sirt3 activation and mitochondrial metabolism during metabolic stress.

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Association between programmed cell death ligand-1 expression in patients with cervical cancer and apparent diffusion coefficient values: a promising tool for patient´s immunotherapy selection.

OBJECTIVE: To investigate the associations between apparent diffusion coefficient (ADC) values extracted from three different region of interest (ROI) position approaches and programmed cell death ligand-1 (PD-L1) expression, and evaluate the performance of the nomogram established based on ADC values and clinicopathological parameters in predicting PD-L1 expression in cervical cancer (CC) patients. METHODS: Through retrospective recruitment, a training cohort of 683 CC patients was created, and a validation cohort of 332 CC patients was prospectively recruited. ROIs were delineated using three different methods to measure the mean ADC (ADCmean), single-section ADC (ADCss), and the minimum ADC of tumors (ADCmin). Logistic regression was employed to identify independent factors related to PD-L1 expression. A nomogram was drawn based on ADC values combined with clinicopathological features, its discrimination and calibration performances were estimated using the area under the curve (AUC) of receiver operating characteristic and calibration curve. The clinical benefits were evaluated by decision curve analysis. RESULTS: The ADCmin independently correlated with PD-L1 expression. The nomogram constructed with ADCmin and other independent clinicopathological-related factors: FIGO staging, pathological grade, parametrial invasion, and lymph node status demonstrated excellent diagnostic performance (AUC = 0.912 and 0.903, respectively), good calibration capacities, and greater net benefits compared to the clinicopathological model in both the training and validation cohorts. CONCLUSION: ADCmin independently correlated PD-L1 expression, and the nomogram established with ADCmin and clinicopathological independent prognostic factors had a strong predictive performance for PD-L1 expression, thereby serving as a promising tool for selecting cases eligible for immunotherapy. CLINICAL RELEVANCE STATEMENT: The minimum ADC can serve as a reliable imaging biomarker related to PD-L1 expression; the established nomogram combines the minimum ADC and clinicopathological factors that can assist clinical immunotherapy decisions.

AMPK activation coupling SENP1-Sirt3 axis protects against acute kidney injury.

Acute kidney injury (AKI) is a critical clinical condition that causes kidney fibrosis, and it currently lacks specific treatment options. In this research, we investigate the role of the SENP1-Sirt3 signaling pathway and its correlation with mitochondrial dysfunction in proximal tubular epithelial cells (PTECs) using folic acid (FA) and ischemia-reperfusion-induced (IRI) AKI models. Our findings reveal that Sirt3 SUMOylation site mutation (Sirt3 KR) or pharmacological stimulation (metformin) protected mice against AKI and subsequent kidney inflammation and fibrosis by decreasing the acetylation level of mitochondrial SOD2, reducing mitochondrial reactive oxygen species (mtROS), and subsequently restoring mitochondrial ATP level, reversing mitochondrial morphology and alleviating cell apoptosis. In addition, AKI in mice was similarly alleviated by reducing mtROS levels using N-acetyl-L-cysteine (NAC) or MitoQ. Metabolomics analysis further demonstrated an increase in antioxidants and metabolic shifts in Sirt3 KR mice during AKI, compared with Sirt3 wild-type (WT) mice. Activation of the AMPK pathway using metformin promoted the SENP1-Sirt3 axis and protected PTECs from apoptosis. Hence, the augmented deSUMOylation of Sirt3 in mitochondria, activated through the metabolism-related AMPK pathway, protects against AKI and subsequently mitigated renal inflammation and fibrosis through Sirt3-SOD2-mtROS, which represents a potential therapeutic target for AKI.

The effects of continuous straw returning strategies on SOC balance upon fresh straw incorporation.

Continuous straw returning is widely encouraged for augmenting soil organic carbon (SOC) in arable lands. However, the magnitude of changes in net SOC related to native SOC mineralization and new SOC development upon fresh straw incorporation remains elusive, particularly in soils after continuous straw returning with different strategies. To address this, soil that had undergone nine years of straw returning with different strategies (NS, non-straw returning; DS, direct straw returning; IS, indirect straw returning) was incubated with fresh 13C-labeled straw for 45 days. Fresh straw incorporation stimulated native SOC-derived CO2 emission in DS soil, which in turn promoted straw-derived CO2 emission in IS soil. Overall, the amounts of newly developed SOC from straw (2.41-2.59 g C/kg soil) overcompensated for the native SOC losses (0.91-1.37 g C/kg soil) by mineralization, and led to net C sequestration in all treatments. No obvious difference was found in the amounts of SOC sequestrated from straw between the DS and NS soils, while the amount of native SOC mineralization increased by 40-50% in the DS soil relative to other treatments, thus resulting in lower net C sequestration in the DS soil (1.21 g C/kg soil) than IS and NS soil (1.43 and 1.65 g C/kg for IS and NS soil, respectively). Spearman's correlation analyses indicated a significant (p < 0.01) and positive correlation between SOC contents and native soil C mineralization, while the soil microbial index played a greater role in influencing fresh straw sequestration (p < 0.01). In conclusion, the DS soil showed a weaker effect on SOC sequestration than IS after 9 years of practices, upon fresh straw incorporation. This difference may be attributed to the magnitude of native SOC mineralization in the soil. Besides the straw-C input rate, results emphasize that native soil C protection should be also considered in long-term SOC sequestration practices.

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China.

BACKGROUND: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. METHODS: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). RESULTS: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3-5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. CONCLUSION: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. TRIAL REGISTRATION: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

Large area MCP-PMT design with good time performance.

A new large area photomultiplier tube based on the microchannel plates (MCP-PMT) with high collection efficiency (CE) and good time performance is proposed in this paper. A novel focusing system with two cylindrical and a conical barrels is designed to generate the accelerating and focusing electric field. A three-dimensional model is developed by CST Studio Suite to validate its feasibility. Finite Integral Technique and Monte Carlo method are combined to simulate the process. Results predict that CE of the novel MCP-PMT is expected to be 100%. TTS of the photoelectrons from the whole photocathode achieves 1.2 ns. Differ from other large area PMTs, it performs well in the geomagnetic field.

Overview of adjuvant radiotherapy on survival, failure pattern and toxicity in stage I to II endometrial carcinoma: a long-term multi-institutional analysis in China.

BACKGROUND: This research aimed to provide an overview of the impact of adjuvant vaginal brachytherapy (VBT) and external beam pelvic radiotherapy (EBRT) with or without VBT on survival in stage I to II EC patients in China from a long-term multi-institutional analysis. METHODS: We retrospectively analyzed stage I to II EC patients from 13 institutions treated between 2003 and 2015. All patients underwent surgical staging and received adjuvant RT. Patients were divided into groups of low-risk (LR), intermediate-risk (IR), high-intermediate-risk (HIR) and high-risk (HR). Survival statistics, failure pattern, and toxicity of different radiation modalities in different risk groups were analyzed. RESULTS: A total of 1048 patients were included. HR disease represented 27.6%, HIR 17.7%, IR 27.7% and LR 27.1%, respectively. Endometrioid adenocarcinoma (EAC) and non-endometrioid carcinoma (NEC) accounted for 92.8 and 7.2%. A total of 474 patients received VBT alone and 574 patients received EBRT with or without VBT. As for EAC patients, the 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rate was: 94.6, 90.4, 93.0 and 91.6%, respectively. For LR patients, EBRT (with or without VBT) seemed to be a risk factor. With the higher risk category, the survival benefit of EBRT gradually became remarkable. EBRT (with or without VBT) significantly increased DFS, LRFS and DMFS compared to VBT alone in the HR group (p < 0.05). Distant metastasis was the main failure pattern for all risk groups. As for NEC patients, the 5-year OS, DFS, LRFS and DMFS rate was: 93.4, 87.2, 91.7 and 89.3%, respectively. As for toxicity, EBRT (with or without VBT) significantly increased the incidence of grade 1-2 gastrointestinal, urinary, and hematological toxicity. CONCLUSIONS: For stage I to II EC patients, EAC accounted for the majority and had better prognosis than NEC. For EAC patients, VBT alone resulted in comparable survival to EBRT in the LR, IR and HIR groups, while EBRT significantly increased survival in the HR group. EBRT had higher rate of toxicity than VBT.

Treatment optimization of pelvic external beam radiation and/or vaginal brachytherapy for patients with stage I to II high-risk Endometrioid adenocarcinoma: a retrospective multi-institutional analysis.

BACKGROUND: For stage I to II high-risk endometrioid adenocarcinoma patients, the optimal adjuvant radiotherapy modality remains controversial. The present study sought to optimize the treatment of pelvic external beam radiation (EBRT) with/or vaginal brachytherapy (VBT) for high-risk endometrioid adenocarcinoma patients in multiple radiation oncology centers across China. METHODS: This article retrospectively reviewed stage I to II patients with resected endometrioid adenocarcinoma treated at 13 radiation centers from 1999 to 2015. Patients were eligible if they had high-risk features (stage IB Grade 3 disease or stage II Grade 1-3 disease) on the basis of ESMO-ESGO-ESTRO risk group consensus. RESULTS: A total of 218 patients were included. Fifty-one patients received EBRT, 25 patients received VBT, and 142 patients were administered EBRT combined with VBT. The three groups were comparable in baseline characteristics, except the proportion of stage IB and Grade 3 disease in the VBT group was significantly higher and their age was older. Survival analysis showed that OS, DFS, LRFS and DMFS were significantly different among the three groups. Two out of three groups were compared with each other, and results demonstrated that DFS, LRFS and DMFS were worse in the VBT group than in the EBRT or EBRT + VBT group. The 3-year OS rates were 95.2, 85.2 and 95.1% in the EBRT, VBT and EBRT + VBT groups, respectively (p = 0.043). There was no significant difference in survival outcomes between EBRT group and EBRT + VBT group. A propensity matching analysis was performed to eliminate group differences. The results demonstrated that DFS and LRFS were significantly improved in the pelvic radiation group compared to the VBT group. Distant failure accounted for most of the failure patterns. Patients in the VBT group had significantly increased local and regional recurrence rates than patients in the EBRT or EBRT + VBT group. Acute and chronic radiation-induced toxicities were well tolerated for all patients. CONCLUSION: For patients with postoperative stage I to II high-risk endometrioid adenocarcinoma, compared with VBT alone, radiotherapy modalities including EBRT significantly improved DFS, LRFS and DMFS with tolerable adverse effects. Overall survival was not significantly different between EBRT and EBRT + VBT modalities.

SUMOylation-Mediated Response to Mitochondrial Stress.

Mitochondrial stress is considered as a factor that reprograms the mitochondrial biogenesis and metabolism. As known, SUMOylation occurs through a series of stress-induced biochemical reactions. During the process of SUMOylation, the small ubiquitin-like modifier (SUMO) and its specific proteases (SENPs) are key signal molecules. Furthermore, they are considered as novel mitochondrial stress sensors that respond to the signals produced by various stresses. The responses are critical for mitochondrial homeostasis. The scope of this review is to provide an overview of the function of SUMOylation in the mitochondrial stress response, to delineate a SUMOylation-involved signal network diagram, and to highlight a number of key questions that remain answered.

Vaginal dose of radical radiotherapy for cervical cancer in China: a multicenter study.

BACKGROUND: The posterior-inferior border of symphysis (PIBS) point system is a novel vaginal dose-reporting method and is a simple and reliable method proposed by the Medical University of Vienna proposed for both external-beam radiotherapy (EBRT) and brachytherapy (BT). In this multicenter study, we sought to first evaluate the vaginal radiation dose in Chinese cervical cancer patients according to the PIBS point system and then to analyze the factors influencing the dose distribution. METHODS: We collected data from the medical records of 936 cervical cancer patients who underwent concurrent radiochemotherapy at 13 different institutions in China. Radiation doses at points A, PIBS+ 2 cm, PIBS and PIBS-2 cm, International Commission on Radiation Units (ICRU)-R and ICRU-B were measured. RESULTS: The median total doses in EQD2α/ß = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 82.5 (52.7-392.1) Gy, 56.2 (51.4-82.1) Gy and 2.6 (0.9-7.4) Gy, respectively. The median total doses in EQD2α/ß = 3 at ICRU-R and ICRU-B were 77.5 (54.8-132.4) Gy and 79.9 (60.7-133.7) Gy, respectively. The mean vaginal reference length (VRL) was 4.6 ± 1.0 cm (median, 4.5 cm). In patients with VRL ≤4.5 cm, the mean total doses in EQD2α/ß = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 128.5, 60.7 and 0.8 Gy, respectively. In patients with VRL > 4.5 cm, the mean total doses at these three points were 68.9, 0.5 and 54.5 Gy, respectively. Classification of patients revealed significant differences (P < 0.05) between these two groups. CONCLUSIONS: With the PIBS point system, Chinese patients with a shorter VRL of < 4.5 cm received higher radiation doses at the PIBS+ 2 cm, PIBS and PIBS-2 cm points than European and American patients. Further studies are required to establish the dose-effect relationships with these points as references. The study was registered as a clinical trial (NCT03257475) on August 22, 2017.

Efficacy and safety of edaravone in treatment of amyotrophic lateral sclerosis-a systematic review and meta-analysis.

BACKGROUND: Based on the results of randomized, double-blind, placebo-controlled trials, the benefit and safety of edaravone in the treatment of amyotrophic lateral sclerosis remain controversial. We performed a meta-analysis to evaluate the efficacy and safety of edaravone in the treatment of this disease. METHODS: We searched PubMed, the Cochrane Library, and Embase from the inception of electronic data to April 2018. We included randomized, double-blind, placebo-controlled trials reporting amyotrophic lateral sclerosis patients receiving 60-mg intravenous edaravone or intravenous saline placebo for 24 weeks. The primary efficacy evaluation was changed in Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to after the trial. Measure of safety was the frequency of investigated adverse events and serious adverse events. Data synthesis and analysis and evaluation of risk of bias were performed using RevMan 5.3 software. Heterogeneity among studies was evaluated with the I2 statistic. RESULTS: A total of 367 patients were analyzed across three randomized controlled trials (183 patients receiving intravenous edaravone; 184 receiving placebo). A difference in ALSFRS-R score between groups at 24 weeks was found (mean difference [MD] = 1.63, 95% confidence interval [CI] 0.26-3.00, P = .02). No differences in the frequency of adverse events (odds ratio [OR] = 1.22, 95% CI 0.68-2.19, P = .50) or serious adverse events (OR = 0.71, 95% CI 0.43-1.19, P = .20) were found. CONCLUSION: Intravenous edaravone is efficacious in amyotrophic lateral sclerosis patients, with no severe adverse effects. Additional reliable randomized controlled trials with larger sample sizes will further assess the efficacy and safety of edaravone in amyotrophic lateral sclerosis. CLINICAL TRIAL REGISTRATION: The systematic review and meta-analysis was registered in the international prospective register of systematic reviews. (PROSPERO registration number: CRD42018096191; http://www.crd.york.ac.uk/PROSPERO .).

1.23 µm emission of Er/Pr-doped water-free fluorotellurite glasses.

To investigate the relatively unexplored 1.2 µm region, we identified a near-infrared emission at around 1.23 µm from Er3+/Pr3+-codoped water-free fluorotellurite glass with a composition of 60TeO2-30ZnF2-10NaF (TZNF60, mol. %). Under the condition of pumping with the 488 nm optical parametric oscillator (OPO) laser system, the directly measured lifetime (τ(f)) at 1.23 µm in Er/Pr-codoped fluorotellurite glasses is about 111.2 µs, much longer than that of Er-doped fluorotellurite glass (80.1 µs). The stimulated emission cross section (σ(em)) and quantum efficiency (η) for Er3+:4S3/2→4I11/2 transition are greatly enhanced when appropriate Pr3+ ions are incorporated. These advances arise partially from the absence of the hydroxyl (OH) group and low phonon energy with the addition of a large amount of fluorides into oxide-based host glasses. With high quantum efficiency (56.2%) and a large stimulated cross section (4.03×10(-21) cm2), Er3+/Pr3+-codoped TZNF60 glass is regarded as promising material for the development of optical amplification and laser operation at the relatively unexplored 1.2 µm region.

Multiring large-mode-area delivery fiber for high power.

The study presents a novel design of multiring delivery fiber with large mode area for high power. Using a FiberCAD method, we investigated a fiber whose core is surrounded by alternative low- and high-index rings. Based on our calculation, the effective area is 400 µm2 at 1.08 µm, larger than the ~280 µm2 of conventional step-index fiber (20/400). The macrobending loss at 1.08 µm is estimated to be 1×10(-3) dB/m, approximately one-third that of conventional step-index fiber (20/400). The single-mode operation can be achieved by the macrobending loss contrast between the fundamental mode (<1 dB/m) and high-order mode (>100 dB/m). The results indicate that multiring delivery fiber fabricated by modified chemical vapor deposition process is a promising candidate for high-power transmission.

[Sexual development characteristics and sex hormone levels in obese male adolescents].

OBJECTIVE: To investigate the characteristics of sexual development and sex hormone levels in obese male adolescents. METHODS: We included 156 obese male adolescents with micropenis and microorchidia in an observation group and 50 healthy ones in a control group. We measured the body mass index (BMI), penile natural length and testicular volume, investigated the incidence of spermatorrhea and the age of the first spermatorrhea, detected the levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), total testosterone (TT), free testosterone (FT), progesterone (P) and estradiol (E2) using radioimmunoassay, and calculated TT/E2 and testosterone secretion index (TSI). RESULTS: Compared with the healthy controls, the obese adolescents showed significantly higher BMI ([20.4 +/- 1.6] vs [27.1 +/- 2.2] kg/m2, P < 0.05), but shorter penile natural length ([6.7 +/- 2.1] vs [5.6 +/- 1.7] cm, P < 0.05) and lower testis volume ([9.9 +/- 3.1] vs [7.6 +/- 2.3] cm3, P < 0.05). The incidence of spermatorrhea was significantly decreased in the observation group in comparison with that of the control (chi2 = 17.335, P < 0.05), but there was no significant difference in the age of the first spermatorrhea between the two groups (P > 0.05). The levels of LH, E2 and P were remarkably higher in the observation group than in the control ([7.82 +/- 2.14] vs [5.39 +/- 1.76] mIU/ml, P < 0.05; [48.57 +/- 8.34] vs [8.61 +/- 4.08] pg/ml, P < 0.01; and [1.25 +/- 0.58] vs [0.64 +/- 0.19] ng/ml, P < 0.05), while TT and FT were markedly lower in the former than in the latter ([0.73 +/- 0.20] vs [1.47 +/- 0.41] ng/ml, P < 0.01 and [5.09 +/- 2.60] vs [11.28 +/- 4.72] pg/ml, P < 0.01), and so were the TT/E2 ratio and TSI (0.015 +/- 0.004 vs 0.173 +/- 0.037 and 0.098 +/- 0.026 vs 0.272 +/- 0.084, P < 0.01). BMI was correlated positively to PRL and E2, but negatively to TT, FT, TT/E2 and TSI (P < 0.05); the penile natural length positively to TT, FT, TT/E2 and TSI, but negatively to E2 (P < 0.05); and the mean testis volume positively to TT, FT, TT/E2 and TSI, but negatively to LH, PRL and E2 (P < 0.05). CONCLUSION: Testis dysplasia and alteration of sex hormone levels exist in obese male adolescents. Obesity and fat accumulation lead to increased E2 and decreased TT and FT, particularly the reduction of TT/E2 and TSI, which suggest that the body fat content has an important influence on the development of the male reproductive system.

Preoperative serum CA125 level and age at diagnosis: An effective prognosis prediction tool for patients with early-stage endometrial cancer.

OBJECTIVE: To investigate the combined predictive value of the preoperative serum cancer antigen 125 (CA125) level and age at diagnosis among patients with early-stage endometrial cancer (EC) after initial treatment. METHODS: We retrospectively analyzed data from patients with early-stage EC from 1999 to 2015 in multiple institutions in China. All 447 patients received postoperative adjuvant radiotherapy for FIGO 2009 stage I and II EC with complete data on preoperative serum CA125 levels. All patients were divided into four groups according to the ESMO-ESGO-ESTRO risk classification. The predictive probability of 5-year overall survival (OS) and the sensitivity and specificity of CA125 and age were calculated. RESULTS: The median follow-up time was 59 months (3-201 months). The 5-year OS and disease-free survival rates were 94.4% and 89.1%. Multivariate analysis showed that the preoperative CA125 level and age at diagnosis were independent prognostic factors for 5-year OS. The area under the curve for CA125 combined with age at diagnosis for 5-year OS was .692, and the corresponding sensitivity and specificity were 68.2% and 68.2% (p < .002), which were significantly better than the corresponding values for CA125 or age alone. After all 447 patients were divided into four groups according to CA125 combined with age, the 5-year OS of the elderly and higher CA125 group was only 73.7%. CONCLUSIONS: Although preoperative CA125 had limited sensitivity in predicting the prognosis for early-stage EC after initial treatment, it remains a useful serum marker for risk assessment of early-stage EC. Combining CA125 with age may increase its predictive sensitivity.

Intense 2.7 µm emission of Er3+-doped water-free fluorotellurite glasses.

By physical and chemical dehydration techniques, a group of Er3+-doped water-free fluorotellurite glasses with a composition of 60TeO2-30ZnF2-10NaF(TZNF60,mol%)+x Er2O3(wt%,x=0~1.5) were fabricated. Under 978 nm excitation, the 4I(11/2)→4I(13/2) emission of Er3+ ions in TZNF60-glass was investigated: τ(f) is of 1.07~1.93 ms and emission bandwidth is about 163 nm at 2.71 µm, which benefits from the absence of OH groups and the decreased phonon energy with the addition of fluorides. In contrast, 1.25Er-TZNF60 glass is proposed to be a promising material for mid-infrared fiber lasers at around 2.7 µm.

Intense red upconversion emission of Yb/Tm/Ho triply-doped tellurite glasses.

By conventional melting and quenching methods, 3Yb2O3-0.2Tm2O3-xHo2O3 (wt%, x=0.2~1.2) was doped into an easily fiberized tellurite glass with composition of 78TeO2-10ZnO-12Na2O (mol%) to form YTH-TZN78 glasses. Under 976 nm excitation, the direct sensitizing effect of Yb ions (Yb→Ho) and indirect sensitizing and self-depopulating effects of Tm ions (Yb→Tm→Ho) were found to present intense red upconversion emission at 657 nm (Red, Ho:5F5→5I8) and were responsible for the absence of the usually observed 484 nm emission (Blue, Tm:1G4→3H36). Regardless of the dopant concentration of Ho ions, the intensity of the red emission at 657 nm (Red, Ho:5F5→5I8) is about three times stronger than that of the green one at 543 nm (Green, Ho:5S2→5I8). For this certain red emission at 657 nm, 0.4 wt% Ho2O3-doped YTH-TZN78 glass was found to present the highest emission intensity and is therefore determined as a promising active tellurite glass for red fiber laser development.

NR4A1 promotes LEF1 expression in the pathogenesis of papillary thyroid cancer.

The morbidity of papillary thyroid cancer (PTC) is on the rise, but its pathogenesis is still poorly understood. NR4A1 is a transcription factor primarily involving a wide range of pathophysiological responses, but its relationship with PTC malignancy remains unclear. This study demonstrates that high NR4A1 expression is strongly associated with poor survival outcomes in PTC patients. The depletion of NR4A1 significantly inhibited the proliferation of PTC cells by negating the LEF1-mediated oncogenic alteration. Mechanistically, NR4A1 directly binds to the promoter region of LEF1 and leads to crosstalk with histone acetylation and DNA demethylation to transcriptionally upregulate LEF1 expression, subsequently promoting downstream growth-related genes expressions in PTC. In the light of our findings, NR4A1 may be an emerging driving factor in PTC pathogenesis and progression.