Genome wide association study and meta-analysis identified multiple new risk loci for freckles in 4813 Chinese individuals.

Freckle is a prevalent pigmentary dermatosis with an obvious hereditary component. Dozens of freckles risk loci have been discovered through research on multiple traits or other diseases, rather than as an independent trait. To discover novel variants associated with freckles, we performed GWAS and meta-analysis in 4813 Chinese individuals. We conducted GWAS and meta-analysis of two cohorts: 197 patients and 1603 controls (Cohort I), and 336 patients and 2677 controls (Cohort II), both from China. Then we performed linkage disequilibrium (LD) analysis, eQTL study, and enrichment analysis with association results for functional implications. Finally, we discovered 59 new SNPs and 13 novel susceptibility genes associated with freckles (Pmeta <5 × 10-8), which has enriched the genetic research on freckles.

A retrospective analysis of transudative pleural effusion due to fibrosing mediastinitis.

BACKGROUND: Pleural effusion caused by fibrosing mediastinitis is rarely reported. This study aimed to summarize the clinical manifestations, diagnosis and treatment of transudative pleural effusion due to fibrosing mediastinitis. METHODS: Medical records and follow-up data of 7 patients with transudative pleural effusion due to fibrosing mediastinitis in Beijing Chaoyang Hospital between May 2014 and Feb 2018 were retrospectively analyzed. RESULTS: These patients included 4 males and 3 females, with an average age of (64 ± 9) years. There were 3 left-sided effusions, 2 right-sided effusions and 2 bilateral effusions. Previous or latent tuberculosis was found in 6 patients. Pulmonary hypertension was indicated by echocardiography in all the 7 patients. Computed tomography pulmonary angiography (CTPA) of all the 7 cases showed increased soft tissue images visible in the mediastinum and bilateral hilus, different degrees of stenosis or occlusion in the pulmonary artery and pulmonary vein. In addition, 4 cases were found of right middle lobe atelectasis with a mediastinal window setting. There was interstitial pulmonary edema on the side of pleural effusion with a lung window setting. All the 7 patients were treated with intermittent drainage of pleural effusion combined with diuretic therapy. Five patients were treated with antituberculosis therapy. Up to now, two patients died of right heart failure and respiratory failure after 2 and 16 months respectively; The remaining 5 patients were still in follow up. CONCLUSION: Fibrosing mediastinitis can lead to pulmonary vein stenosis or occlusion, and thus cause transudative pleural effusion, which can be detected by CTPA. Pulmonary hypertension, long time of cough, and a history of tuberculosis are common in these patients. The common therapy is intermittent drainage of pleural effusion combined with diuretic therapy.

Intratumoral metabolic heterogeneity by 18F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.

BACKGROUND: The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). METHODS: This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. RESULTS: The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001). CONCLUSION: HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.

Novel l-Cysteine Incomplete Degradation Method for Preparation of Procyanidin B2-3'-O-Gallate and Exploration of its in Vitro Anti-inflammatory Activity and in Vivo Tissue Distribution.

In this study, an effective method for preparation of bioactive galloylated procyanidin B2-3'-O-gallate (B2-3'-G) was first developed by incomplete depolymerization of grape seed polymeric procyanidins (PPCs) using l-cysteine (Cys) in the presence of citric acid. The structure-activity relationship of B2-3'-G was further evaluated in vitro through establishing lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. The results suggested that the better protective effects of B2-3'-G against inflammation were attributed to its polymerization degree and the introduction of the galloyl group, compared to its four corresponding structural units. In vivo experiments demonstrated that the B2-3'-G prototype was distributed in plasma, small intestine, liver, lung, and brain. Remarkably, B2-3'-G was able to penetrate the blood-brain barrier and appeared to play an important role in improving brain health. Furthermore, a total of 18 metabolites were identified in tissues. Potential metabolic pathways, including reduction, methylation, hydration, desaturation, glucuronide conjugation, and sulfation, were suggested.

Promoting OH- Adsorption and Diffusion Enables Ultrahigh Capacity and Rate Capability of Nickel Sulfide Cathode for Aqueous Alkaline Zn-Based Batteries.

Aqueous alkaline Zn-based batteries (AAZBs) possess great promise for large-scale applications thanks to their higher discharging plateau and unique reaction mechanism. However, the capacity and rate capability of Ni-based cathodes are still unsatisfactory due to their insufficient OH- adsorption and diffusion ability. Herein, heterostructured Ni3 S2 /Ni(OH)2 nanosheets with outstanding electrochemical performance are synthesized via a facile chemical etching strategy. The heterostructured Ni3 S2 /Ni(OH)2 nanosheet cathode shows significantly increased capacity and rate capability due to its boosted OH- adsorption and diffusion ability compared to Ni3 S2 . Consequently, the assembled Zn//Ni3 S2 /Ni(OH)2 cell can deliver an ultrahigh capacity of 2.26 mAh cm-2 , an excellent rate performance (0.91 mAh cm-2 at 100 mA cm-2 ) and a satisfying cycling stability (1.01 mAh cm-2 at 20 mA cm-2 after 500 cycles). Moreover, a prominent energy density of 3.86 mWh cm-2 is obtained, which exceeds the majority of recently reported AAZBs. This work is expected to provide a new modification direction for developing high-performance nickel sulfide cathode for AAZBs.

Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis.

Currently, there is no consensus on whether maintenance dialysis increases cancer risk in patients with end-stage renal disease (ESRD). Therefore, this study was to systematically evaluate the risk of cancer among ESRD patients undergoing maintenance dialysis. Related studies on the impact of maintenance dialysis on cancer risk were retrieved from PubMed, Embase, Cochrane Library, and other databases from their respective inceptions to 19 February 2021. ESRD patients receiving maintenance dialysis were classified into cancer including non-melanoma skin cancer (NMSC) and cancer excluding NMSC. Standardized incidence ratio (SIR) with its 95% confidence interval (95% CI) was calculated to assess cancer risk. Fourteen studies were included in the meta-analysis. The risk of cancer in patients undergoing maintenance dialysis (with or without NMSC) was significantly higher than controls both in cancer including NMSC (SIR = 1.38, 95% CI: 1.27-1.49, P < 0.001) and cancer excluding NMSC (SIR = 1.34, 95% CI: 1.23-1.47, P < 0.001). Subgroup results identified the higher risk of cancer incidence in both men and women receiving maintenance dialysis. Meanwhile, elevated excess risks were observed among patients with younger age and shorter follow-up time (P < 0.001). Meanwhile, the combined SIR of bladder, cervix, colorectum, kidney, liver, thyroid, tongue, and other cancers were all increased (P < 0.05). ESRD patients undergoing dialysis has higher risk of cancer.

CircRNA Circ_0000118 Regulates Malignancy of Cervical Cancer Cells by Regulating miR-211-5p/miR-377-3p/AKT2 Axis.

CircRNAs are implicated in the development of several cancers. Nevertheless, the involvement of circ_0000118 in the development of cervical cancer (CC) remains unclear. Circ_0000118 levels in tumor tissues and cells were examined by qRT-PCR. The function of circ_0000118 in regulating the malignancy of CC cells was investigated using functional assays, including CCK-8, colony formation, transwell, and tube formation experiments. The functional interaction between circ_0000118 and microRNAs were validated by dual-luciferase activity assay and RNA precipitation experiments. In vivo mouse model was employed to assess the effect of circ_0000118 in the tumorigenesis of CC cells. Circ_0000118 was overexpressed in CC cells and tissues. Loss-of-function experiments demonstrated that circ_0000118 knockdown impaired the proliferation and tumor sphere formation, as well as the angiogenic potential of CC cells. RNA interaction experiments confirmed that circ_0000118 sponged miR-211-5p and miR-377-3p. AKT2 was found to be a target gene negatively modulated by miR-211-5p and miR-377-3p. AKT2 overexpression rescued the inhibition of circ_0000118 downregulation on CC cells. Our study suggested that circ_0000118 functions as an oncogenic factor in progression of CC by maintaining AKT2 level through targeting miR-211-5p and miR-377-3p as a ceRNA (competitive endogenous RNA), which provides novel therapeutic target in the management of CC.

Defect Engineering Triggers Exceptional Sonodynamic Activity of Manganese Oxide Nanoparticles for Cancer Therapy.

Sonodynamic therapy (SDT) has received increasing interest in cancer treatment, but its clinical application is still constrained by the low activity of sonosensitizers and their unclear mechanism. Herein, a kind of oxygen-deficient manganese oxide (MnOx) nanoparticles with greatly enhanced sonodynamic activity and good biocompatibility is developed as an advanced sonosensitizer. The introduced oxygen defects can remarkably enhance the electrical conductivity of manganese oxide (MnO) nanoparticles and serve as charge trapping sites to prohibit the electron-hole pair recombination upon ultrasound (US) irradiation. Such distinct merits promote the generation of reactive oxygen species (ROS), making MnOx as a decent sonosensitizer for SDT, and thus endowing MnOx with higher ROS production under US irradiation. As a demonstration, the MnOx nanoparticles decorated by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (MnOx-DSPE-PEG), a biocompatible coverage to enhance the dispersion ability, achieve a superior tumor killing efficiency of 96%, substantially higher than the MnO-DSPE-PEG counterpart (9%). Our experimental results also reveal that MnOx-DSPE-PEG nanoparticles induce the death of tumor cells by targeting polyunsaturated fatty acids in their membrane with US-triggered ROS. Furthermore, the as-designed sonosensitizers exhibit negligible toxicity toward the treated mice.

Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice.

CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin. Camk4-deficient (Camk4-/-) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice. There are more macrophages and fewer IL-17A+γδ TCR+ cells in the skin of IMQ-treated Camk4-/- mice compared to IMQ-treated WT mice. CaMK4 inhibits IL-10 production by macrophages, thus allowing excessive psoriatic inflammation. Deletion of Camk4 in macrophages alleviates IMQ-induced psoriatic inflammation in mice. In keratinocytes, CaMK4 inhibits apoptosis as well as promotes cell proliferation and the expression of pro-inflammatory genes such as S100A8 and CAMP. Taken together, these data indicate that CaMK4 regulates IMQ-induced psoriasis by sustaining inflammation and provides a potential target for psoriasis treatment.

Ultrathin-FeOOH-Coated MnO2 Sonosensitizers with Boosted Reactive Oxygen Species Yield and Remodeled Tumor Microenvironment for Efficient Cancer Therapy.

Sonodynamic therapy (SDT) typically suffers from compromised anticancer efficacy owing to the low reactive oxygen species (ROS) yield and complicated tumor microenvironment (TME) which can consume ROS and support the occurrence and development of tumors. Herein, ultrathin-FeOOH-coated MnO2 nanospheres (denoted as MO@FHO) as sonosensitizers which can not only facilitate ultrasound (US)-triggered ROS but also tune the TME by hypoxia alleviation, H2 O2 consumption as well as glutathione (GSH) depletion are designed. The FeOOH coating will boost the production yield of singlet oxygen (1 O2 ) and hydroxyl radicals (• OH) by inhibiting the recombination of US-initiated electron-hole pairs and Fenton-like reaction, respectively. Additionally, the catalase-like and GSH peroxidase-like activities of MO@FHO nanospheres enable them to break the TME equilibrium via hypoxia alleviation and GSH depletion. The combination of high ROS yield and fundamental destruction of TME equilibrium results in satisfactory antitumor outcomes, as demonstrated by the high tumor suppression efficacy of MO@FHO on MDA-MB-231-tumor-bearing mice. No obvious toxicity is detected to normal tissues at therapeutic doses in vivo. The capability to modulate the ROS production and TME simultaneously can afford new probability for the development of advanced sonosensitizers for synergistic comprehensive cancer therapy.

An update of the long-term outcome of patients with nonspecific pleurisy at medical thoracoscopy.

BACKGROUND: Medical thoracoscopy (MT) is recommended in patients with undiagnosed exudative pleural effusion and offers a degree of diagnostic sensitivity for pleural malignancy. However, not all patients who undergo MT receive an exact diagnosis. Our previous investigation from 2014 summarized the long-term outcomes of these patients with nonspecific pleurisy (NSP); now, we offer updated data with the goal of refining our conclusions. METHODS: Between July 2005 and August 2018, MT with pleural biopsies were performed in a total of 1,254 patients with undiagnosed pleural effusions. One hundred fifty-four patients diagnosed with NSP with available follow-up data were included in the present study, and their medical records were reviewed. RESULTS: A total of 154 patients were included in this study with a mean follow-up duration of 61.5 ± 43.7 months (range: 1-180 months). No specific diagnosis was established in 67 (43.5%) of the patients. Nineteen patients (12.3%) were subsequently diagnosed with pleural malignancies. Sixty-eight patients (44.2%) were diagnosed with benign diseases. Findings of pleural nodules or plaques during MT and the recurrence of pleural effusion were associated with malignant disease. CONCLUSIONS: Although most NSP patients received a diagnosis of a benign disease, malignant disease was still a possibility, especially in those patients with nodules or plaques as noted on the MT and a recurrence of pleural effusion. One year of clinical follow-up for NSP patients is likely sufficient. These updated results further confirm our previous study's conclusions.

Pleural effusion-based nomogram to predict outcomes in unselected patients with multiple myeloma: a large single center experience.

Pleural effusion (PE) is prevalent in unselected "real-life" populations of multiple myeloma (MM). However, its prognostic value on MM is currently elusive. This study aimed to explore the role of PE on MM prognosis and to develop a novel prognostic nomogram for a cohort of Chinese patients with MM. Patients diagnosed with MM form 2000 through 2017 were retrospectively enrolled. PE was evaluated by chest computed tomography (CT) scans. Independent predictors of overall survival (OS) were identified using a multivariable Cox regression model performed on variables selected by the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram was constructed based on these variables. The concordance index (C-index) and the calibration curve were used to evaluate the predictive performance of the nomogram. Among 861 patients analyzed, 368 patients developed PE. Multivariate cox regression and restricted mean survival time (RMST) analyses revealed that patients with PE experienced worse OS vs. patients without PE. A nomogram predictive of OS was constructed using PE, plasma cell proportion, international staging system (ISS) stage, Charlson comorbidity index (CCI), 1q21 gain, and autologous hematopoietic stem cell transplantation (HSCT). The nomogram showed satisfactory discrimination in the derivation cohort (C-index=0.729) and the validation cohort (C-index=0.684), outperforming the Durie-Salmon (DS) and ISS staging systems. Moreover, the nomogram accurately classified patients into two distinct high- and low-risk groups. PE is frequently encountered in the disease course for MM patients. We derivated and validated a novel nomogram for MM based on PE, outperforming the DS/ISS staging systems.

[Predictive performance of population pharmacokinetic software on vancomycin steady-state trough concentration].

OBJECTIVE: To estimate the predictive performance of the population pharmacokinetics software JPKD-vancomycin on predicting the vancomycin steady-state trough concentration, and to analyze the related factors affecting the predictive performance. METHODS: The clinical data of patients who were treated with vancomycin and received therapeutic drug monitoring (TDM) admitted to Suzhou Hospital Affiliated to Nanjing Medical University from July 2013 to December 2018 were enrolled. All patients were designed an empirical vancomycin regimen (initial regimen) according to vancomycin medication guidelines. Steady-state trough concentrations of vancomycin were determined at 48 hours after the first dose and 0.5 hour before the next dose. Dosage regimen was adjusted when steady-state trough concentration was not in 10-20 mg/L (adjustment regimen), and then the steady-state trough concentration was determined again 48 hours after adjustment. First, the JPKD-vancomycin software was used to calculate the initial regimen and predict the steady-state trough concentration according to the results calculated by classic pharmacokinetic software Vancomycin Calculator. Second, the JPKD-vancomycin software was used to adjust the vancomycin dosage regime and predict the steady-state trough concentration of adjustment regimen. The weight residual (WRES) between the predicted steady-state trough concentration (Cpre) and the measured steady-state trough concentration (Creal) was used to evaluate the ability of the JPKD-vancomycin software for predicting the vancomycin steady-state trough concentration. The TDM results of initial regimen were divided into accurate prediction group (WRES < 30%) and the inaccurate prediction group (WRES ≥ 30%) according to the WRES value. Patient and disease characteristics including gender, age, weight, height, the length of hospital stay, comorbidities, vasoactive agent, mechanical ventilation, smoking history, postoperative, obstetric patients, trauma, laboratory indicators, vancomycin therapy and TDM results were collected from electronic medical records. Univariate and multivariate Logistic regression analysis was used to screen the related factors that influence the predictive performance of JPKD-vancomycin software, and the receiver operating characteristic (ROC) curve was drawn to evaluate its predictive value. RESULTS: A total of 310 patients were enrolled, and 467 steady-state trough concentrations of vancomycin were collected, including 310 concentrations of initial regimen and 157 concentrations of adjustment regimen. Compared with the initial regimen, the WRES of adjusted regimen was significantly reduced [14.84 (6.05,22.89)% vs. 20.41 (11.06,45.76)%, P < 0.01], and the proportion of WRES < 30% increased significantly [82.80% (130/157) vs. 63.87% (198/310), P < 0.01]. These results indicated that JPKD-vancomycin software had a better accuracy prediction for steady-state trough concentration of the adjusted regimen than the initial regimen. There were 198 concentrations in the accurate prediction group and 112 in the inaccurate prediction group. Univariate Logistic regression analysis showed that women [odds ratio (OR) = 0.466, 95% confidence interval (95%CI) was 0.290-0.746, P = 0.002], low body weight (OR = 0.974, 95%CI was 0.953-0.996, P = 0.022), short height (OR = 0.963, 95%CI was 0.935-0.992, P = 0.014), low vancomycin clearance (CLVan; OR < 0.001, 95%CI was 0.000-0.231, P = 0.023) and postoperative patients (OR = 1.695, 95%CI was 1.063-2.702, P = 0.027) were related factors affecting the predictive performance of JPKD-vancomycin software. Multivariate Logistic regression analysis indicated that women (OR = 0.449, 95%CI was 0.205-0.986, P = 0.046), low CLVan (OR < 0.001, 95%CI was 0.000-0.081, P = 0.015) and postoperative patients (OR = 2.493, 95%CI was 1.455-4.272, P = 0.001) were independent risk factors for inaccurate prediction of JPKD-vancomycin software. The ROC analysis indicated that the area under ROC curve (AUC) of the CLVan for evaluating the accuracy of JPKD-vancomycin software in predicting vancomycin steady-state trough concentration was 0.571, the sensitivity was 56.3%, and the specificity was 57.1%. The predictive performance of JPKD-vancomycin software was decreased when CLVan was lower than 0.065 L×h-1×kg-1. CONCLUSIONS: JPKD-vancomycin software had a better predictive performance for the vancomycin steady-state trough concentrations of adjustment regimen than initial regimen. JPKD-vancomycin software had a poor predictive performance when the patient was female, having low CLVan, and was postoperative. The predictive performance of JPKD-vancomycin software was decreased when CLVan was lower than 0.065 L×h-1×kg-1.

miR­494 inhibits cancer­initiating cell phenotypes and reverses resistance to lapatinib by downregulating FGFR2 in HER2­positive gastric cancer.

In gastric cancer, >15% of cases are associated with the amplification of human epidermal growth factor receptor 2 (HER2), which leads to poor clinical outcomes. Lapatinib, a potent ATP­competitive inhibitor, is a small, orally active molecule, which inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1. The activation of receptor tyrosine kinases can contribute to lapatinib resistance in HER2­positive gastric cancer. The aim of the present study was to explore the effects of miR­494 and FGFR2 in regulation of cancer­initiating cell phenotypes and therapeutic efficiency of lapatinib in HER2­positive gastric cancer. Western blot analysis was used to identify that the expression of fibroblast growth factor receptor 2 (FGFR2), a receptor tyrosine kinase, was upregulated in gastric cancer tissues. Formation of cancer initiating cells (CICs) and resistance to lapatinib were determined using sphere growth assay and MTT assay, respectively. The overexpression of FGFR2 promoted the generation of cancer­initiating cells (CICs) and resistance to lapatinib in HER2­positive gastric cancer YCC1 cells. In addition, it was observed that overexpression of microRNA (miR)­494 downregulated the protein expression of FGFR2, inhibited the formation of CICs and reversed lapatinib resistance in YCC1­F cells (HER2­positive, FGFR2 overexpressing and lapatinib­resistant gastric cancer cells). Therefore, it was concluded that miR­494 inhibited the CIC phenotype and reversed resistance to lapatinib by inhibiting FGFR2 in HER2­positive gastric cancer.

Diagnostic Accuracy of Interleukin-27 between Tuberculous Pleural Effusion and Malignant Pleural Effusion: A Meta-Analysis.

BACKGROUND: The concentration assay of pleural effusion interleukin-27 (IL-27) has raised concern for diagnosing tuberculous pleurisy. Compared with malignant pleural effusion (MPE), the concentration of IL-27 in tuberculous pleural effusion (TPE) increased significantly. Accurate differentiating diagnosis is essential for choosing treatment for pleural effusion. OBJECTIVE: The present meta-analysis is aimed at determining the accuracy of IL-27 in the differential diagnosis between TPE and MPE. MATERIAL AND METHOD: After having retrieved the published studies, we combined the sensibility (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of IL-27 in the diagnosis of TPE compared to MPE using a fixed-effect model. The summary receiver operating characteristic curve was applied to estimate the overall test performance. RESULTS: In total, 550 patients (285 patients with TPE and 265 patients with MPE), included in 7 case-control studies, were enrolled. The summary assessments for IL-27 in the diagnosis between TPE and MPE were: SEN 0.93 (95% CI 0.90-0.96), SPE 0.97 (95% CI 0.94-0.98), PLR 25.88 (95% CI 13.84-48.39), NLR 0.07 (95% CI 0.05-0.11), and DOR 333.26 (95% CI 146.10-760.19), respectively. The maximal joint SEN and SPE was 0.95; the area under the curve was 0.99. CONCLUSION: IL-27 determination is a relatively accurate test for the diagnosis of TPE, which has very high SEN and SPE for discriminating TPE from MPE. The results of IL-27 assays should be interpreted in parallel with clinical findings and the results of conventional tests.

18F-FDG PET/CT and ultrasonogrpahy in differentiated thyroid carcinoma patients with elevated serum levels of antithyroglobulin antibody, negative Tg and whole body 131I scan.

OBJECTIVE: In the follow-up of patients with differentiated thyroid cancer (DTC), several patients had elevated serum levels of antithyroglobulin antibody (TgAb), undetectable serum thyroglobulin (Tg), and negative radioiodine whole body scan (131I-WBS). We describe the use of neck ultrasonography (US) and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging in these patients to investigate this clinically challenging problem and propose treating. SUBJECTS AND METHODS: A total of 49 DTC patients with elevated serum levels of TgAb (>115IU/mL), undetectable Tg and negative 131I-WBS were divided into two groups (positive and negative) according to the neck US findings. Differences in the rate of recurrence between the two groups were investigated. The diagnostic value of 18F-FDG PET/CT in these patients was evaluated. RESULTS: Among the 49 patients, the rate of recurrence of patients with positive neck US was 50%, which was significantly higher than that of patients with negative neck US (17.24%; P=0.014). The sensitivity, specificity, and positive predictive values of 18F-FDG PET/CT imaging in diagnosing the clinical status of these patients were 93.33%, 70.59% and 58.33%, respectively. After the 18F-FDG PET/CT scan, clinical management was changed in 14 patients. Nine patients were operated and five underwent 131I ablation therapy. CONCLUSION: In the 49 DTC patients with elevated serum levels of TgAb but negative findings in serum Tg and in 131I-WBS, neck US and 18F-FDG PET/CT imaging supported the clinical diagnosis and suggested subsequent treatment.

Dendritic cell nuclear protein-1 regulates melatonin biosynthesis by binding to BMAL1 and inhibiting the transcription of N-acetyltransferase in C6 cells.

Dendritic cell nuclear protein-1 (DCNP1) is a protein associated with major depression. In the brains of depression patients, DCNP1 is up-regulated. However, how DCNP1 participates in the pathogenesis of major depression remains unknown. In this study, we first transfected HEK293 cells with EGFP-DCNP1 and demonstrated that the full-length DCNP1 protein was localized in the nucleus, and RRK (the residues 117-119) composed its nuclear localization signal (NLS). An RRK-deletion form of DCNP1 (DCNP1ΔRRK) and truncated form (DCNP11-116), each lacking the RRK residues, did not show the specific nuclear localization like full-length DCNP1 in the cells. A rat glioma cell line C6 can synthesize melatonin, a hormone that plays important roles in both sleep and depression. We then revealed that transfection of C6 cells with full-length DCNP1 but not DCNP1ΔRRK or DCNP11-116 significantly decreased the levels of melatonin. Furthermore, overexpression of full-length DCNP1, but not DCNP1ΔRRK or DCNP11-116, in C6 cells significantly decreased both the mRNA and protein levels of N-acetyltransferase (NAT), a key enzyme in melatonin synthesis. Full-length DCNP1 but not DCNP1ΔRRK or DCNP11-116 was detected to interact with the Nat promoter and inhibited its activity through its E-box motif. Furthermore, full-length DCNP1 but not the mutants interacted with and repressed the transcriptional activity of BMAL1, a transcription factor that transactivates Nat through the E-box motif. In conclusion, we have shown that RRK (the residues 117-119) are the NLS responsible for DCNP1 nuclear localization. Nuclear DCNP1 represses NAT expression and melatonin biosynthesis by interacting with BMAL1 and repressing its transcriptional activity. Our study reveals a connection between the major depression candidate protein DCNP1, circadian system and melatonin biosynthesis, which may contribute to the pathogenesis of depression.

Successful thrombolytic therapy of post-operative massive pulmonary embolism after ultralong cardiopulmonary resuscitation: a case report and review of literature.

BACKGROUND AND AIMS: Cardiac arrest caused by massive pulmonary embolism (PE) is highly refractory to conventional resuscitation. Thrombolytic therapy has been considered to be an effective way to massive PE. METHODS: We reported a case of successful thrombolytic therapy of post-operative massive PE after 90-min cardiopulmonary resuscitation (CPR) and reviewed the relevant literature. RESULTS: We presented the case of a 48-year-old woman with surgery of varicosis of great saphenous vein who suffered from a massive PE with circulatory arrest refractory to 90 min of aggressive CPR. Thrombolysis was given only as a single dose of 50 mg of recombinant tissue plasminogen activator. Rapid haemodynamic and clinical improvement followed the bolus dose. The patient was discharged later without neurological or other sequelae. An extensive literature search of the PubMed database only identified 11 cases of massive PE with cardiac arrest during the perioperative period with a survival rate was 88.9%. The time period of CPR before thrombolysis or anti-coagulation was 15-90 min. CONCLUSIONS: Thrombolytic therapy is useful to achieve the return of spontaneous circulation in the resuscitation of patients with cardiac arrest secondary to massive PE during the perioperative period, even in the prolong resuscitation.