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1.
Reprod Biol Endocrinol ; 18(1): 16, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32113479

RESUMO

BACKGROUND: To investigate the effectiveness of the GnRH-a ultra-long protocol, GnRH-a long protocol, and GnRH-a short protocol used in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with endometriosis. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, Elsevier Science Direct, OA Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Science and Technology Journal database, and the China Biology Medicine disc for randomized controlled trials (RCTs) and observational studies (non-RCTs) to evaluate the efficacy of the GnRH-a ultra-long protocol, GnRH-a long protocol, and GnRH-a short protocol in IVF-ET in infertile patients with endometriosis. RESULTS: A total of 21 studies in compliance with the standard literature were included, and RCT and non-RCT studies were analyzed separately. This meta-analysis showed that the GnRH-a ultra-long protocol could improve the clinical pregnancy rate of infertile patients in RCT studies, especially in patients with stages III-IV endometriosis (RR = 2.04, 95% CI: 1.37~3.04, P < 0.05). However, subgroup analysis found the different down-regulation protocols provided no significant difference in improving clinical outcomes in patients with endometriosis in the non-RCT studies. CONCLUSION: This study suggests that the GnRH-a ultra-long protocol can improve the clinical pregnancy rate of the patients with stages III-IV endometriosis in RCT studies. Although it is generally believed that the results of RCT are more reliable, the conclusions of the non-RCT studies cannot be easily neglect, which let us draw conclusions more cautious.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32139295

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) are commonly used to treat intrahepatic recurrent liver cancers. However, there is no information regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma (ICC) after resection. METHODS: A total of 275 patients with localized recurrent ICC who received either TACE (n = 183) or PMCT (n = 92) were studied. A propensity score matching analysis was performed to compare prognostic impact of TACE and PMCT. Prognostic factors for TACE and PMCT were identified respectively. Predictive nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve values. RESULTS: Both TACE and PMCT provided curativeness in partial patients (5-year overall survival: 21.4% and 6.1%, respectively), but TACE provided better survival benefit in both overall patients (hazard ratio [HR] = 0.71; 95% confidence interval [CI]: 0.50-0.97; P = 0.034) and propensity score matching analysis (HR = 0.69; 95% CI: 0.47-0.98; P = 0.041). Independent prognostic factors for TACE were tumor size >5 cm, poor differentiation, and major resection, whereas poor differentiation, hepatitis B virus infection, cholelithiasis, and lymph node metastasis were identified for PMCT. Both predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70, respectively. CONCLUSIONS: TACE provided better survival benefits compared to PMCT. However, there was a disparity in prognostic factors, suggesting evaluation of the two nomograms may be supportive in modality selection. Further prospective validation studies are required for the results to be applied in clinical medicine.

3.
J Pharm Biomed Anal ; 185: 113212, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32143114

RESUMO

The root tuber of Ophiopogon japonicus (Thunb.) Ker-Gawl ("Maidong" in Chinese), with steroidal saponins and homoisoflavonoids as its representative chemical compositions, is a representative medicinal herbs with multiple major producing areas. This study aimed to distinguish the O. japonicas samples from Zhejiang and Sichuan by using an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS)-based metabolome analysis. Firstly, a global chemical constituent identification of O. japonicas was carried out by using both automatic and manual methods. An integrated steroidal saponins structural identification strategy in O. japonicas based on exact mass information, fragmentation characteristics and retention time was developed. Overall, 135 steroidal saponins, 47 homoisoflavonoids and 9 other metabolites were quickly identified or tentatively identified from the MSE continuum data. Furthermore, multivariate statistical analysis revealed that O. japonicas from Zhejiang and Sichuan can clearly be separated and some markers were screened. Moreover, some major active components including total soluble sugar, total soluble polyphenol, total flavonoid, total saponin and 10 specific compounds were analyzed quantitatively. In general, these results showed that there were many differences between the metabolic profile data of O. japonicas from different producing areas, O. japonicas from Sichuan showed higher level steroidal saponins and samples from Zhejiang had higher contents of homoisoflavonoids specifically, and indicated that metabolite profiling by UPLC/Q-TOF MS is an effective approach for the discrimination of medicinal herbs from different geographical origins.

4.
J Electrocardiol ; 59: 158-163, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32146202

RESUMO

OBJECTIVE: Circumferential pulmonary vein isolation (CPVI) is a common procedure that is performed on patients with atrial fibrillation (AF). However, AF may recur in some patients after treatment. This study assesses the association between autonomic modulation and late recurrence after CPVI and between autonomic modulation and ablation lesion quality. METHODS: We prospectively enrolled 72 patients with paroxysmal AF who underwent CPVI from January 2017 to January 2018. Pre- and post-ablation 24 h electrocardiograms were performed to document heart rate variability (HRV), which represents cardiac autonomic function. The intraablation force-time integral (FTI) was used to indicate the extent of ablation injury. Patients were followed up for 12 months after the procedure and cases of AF recurrence were recorded. RESULTS: Changes in HRV decreased after the procedure, which was correlated with FTI (ΔSDNN: r = -0.26, P = 0.03; ΔrMMSD: r = -0.28, P = 0.02; ΔlnHF: r = -0.22, P = 0.04; ΔLnLF: r = -0.29, P = 0.01). Patients without AF recurrence had more pronounced ΔLF (-21.84 ± 33.21% vs. -8.68 ± 34.59%, P = 0.01) and ΔHF (-17.26 ± 16.61% vs. -1.28 ± 9.81%, P = 0.01) than patients with recurrence. Multivariate regression analysis showed that both ΔLF (HR: 1.07, P = 0.04) and ΔHF (HR: 1.11, P = 0.01) were associated with AF recurrence. After adjusting for FTI, ΔLF was no longer associated with AF recurrence (HR: 1.05, P = 0.10). ΔHF remained associated with AF recurrence (HR: 1.08, P = 0.03), but the correlation coefficient was decreased (HR: 1.08, P = 0.03). CONCLUSION: Decreased autonomic nerve function is a valid predictor of AF recurrence and is indicated by the extent of ablation injury, which is independently associated with AF recurrence after CPVI.

5.
Biomed Res Int ; 2020: 8970340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190687

RESUMO

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

6.
J Asian Nat Prod Res ; : 1-7, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32189519

RESUMO

One new phenolic glycoside, methyl 3,4-dihydroxyphenylacetate-4-O-[2-O-ß-D-apisoyl-6-O-(2-hydroxybenzoyl)]-ß-D-glucopyranoside (1), together with 10 known compounds (2-11), were isolated from the roots of Datura metel. The structures of these compounds were elucidated on the basis of their spectroscopic data. Furthermore, the in vitro anti-inflammatory activities of compounds 1-11 were evaluated.

7.
Mol Ther ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32053770

RESUMO

Caspase-8, a well-characterized initiator of apoptosis, has also been found to play non-apoptotic roles in cells. In this study, we reveal that caspase-8 can induce cell death in a special way, which does not depend on activation of caspases and mitochondrial initiation. Instead, we prove that caspase-8 can cause lysosomal deacidification and thus lysosomal membrane permeabilization. V-ATPase is a multi-subunit proton pump that acidifies the lumen of lysosome. Our results demonstrate that caspase-8 can bind to the V0 domain of lysosomal Vacuolar H+-ATPase (V-ATPase), but not the V1 domain, to block the assembly of functional V-ATPase and alkalinize lysosomes. We further demonstrate that the C-terminal of caspase-8 is mainly responsible for the interaction with V-ATPase and can suffice to inhibit survival of cancer cells. Interestingly, regardless of the protein level, it is the expression rate of caspase-8 that is the major cause of cell death. Taken together, we identify a previously unrevealed caspase-8-mediated cell death pathway different form typical apoptosis, which could render caspase-8 a particular physiological function and may be potentially applied in treatments for apoptosis-resistant cancers.

8.
Am J Ophthalmol ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32061756

RESUMO

PURPOSE: To investigate the involvement of growth hormone-releasing hormone (GHRH)-GH signaling in pathogenesis of proliferative diabetic retinopathy (PDR). DESIGN: Experimental laboratory study. METHODS: Vitreous humor, aqueous humor and serum were obtained from 36 eyes of 36 patients with or without type-2 diabetes from 2017-2019. For histological examination, six fibrovascular membranes were excised from eyes with active PDR. Three fibrovascular membranes were excised from non-diabetic patients with proliferative vitreoretinopathy (PVR) as controls. RESULTS: In PDR, the fibrovascular tissues consisted of a mature region containing fibrocytes, and an immature region populated by abundant polymorphonuclear leukocytes in a fibrinogen meshwork. Clusters of leukocytes were found adhering to the vascular walls. In PVR, no fibrinogen and polymorphonuclear leukocyte was observed in the fibrovascular membranes. The levels of GHRH and GH in PDR were significantly increased (P < 0.001), with 1.8-fold and 72.8-fold in vitreous humor, and 2-fold and 4.9-fold in aqueous humor, respectively, when compared with corresponding levels in controls. No significant difference was detected for insulin-like growth factor-1. Immunohistochemistry showed intense expression of GHRH and its receptor GHRH-R in polymorphonuclear leukocytes, vascular endothelial cells and fibrocytes in fibrovascular membranes of PDR. GHRH staining was not detectable in infiltrating cells within the fibrovascular membrane of PVR. CONCLUSIONS: These findings reveal a possible involvement of GHRH/GHRH-R in fibrinous inflammation that might contribute to the formation of fibrovascular membrane in PDR through mediating activities of leukocytes, vascular endothelial cells and fibrocytes. Targeting GHRH/GHRH-R may be considered as a potential therapeutic approach for the treatment of PDR.

9.
Chemphyschem ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040267

RESUMO

As the first discovered organoboron compound with photochromic property, B(ppy)Mes2 (ppy=2-phenylpyridine, Mes=mesityl) displays rich photochemistry that constitutes a solid foundation for wide applications in optoelectronic fields. In this work, we investigated the B(ppy)Mes2 to borirane isomerization mechanisms in the three lowest electronic states (S0 , S1 , and T1 ) based on the complete active space self-consistent field (CASSCF) and its second-order perturbation (CASPT2) methods combined with time-dependent density functional theory (TD-DFT) calculations. Our results show that the photoisomerization in the S1 state is dominant, which is initiated by the cleavage of the B-Cppy bond. After overcoming a barrier of 0.5 eV, the reaction pathway leads to a conical intersection between the S1 and S0 states (S1 /S0 )x , from which the decay path may go back to the reactant B(ppy)Mes2 via a closed-shell intermediate (Int1-S0 ) or to the product borirane via a biradical intermediate (Int2-S0 ). Although triplet states are probably involved in the photoinduced process, the possibility of the photoisomerization in T1 state is very small owing to the weakly allowed S1 →T1 intersystem crossing and the high energy barrier (0.77 eV). In addition, we found the photoisomerization is thermally reversible, which is consistent with the experimental observations.

10.
J Endourol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952455

RESUMO

Objectives: We conduct a study to assess the outcome of Micro-Ultrasonic probe combined with ultrasound-guided mini-percutaneous nephrolithotomy for upper ureteral and renal stones. Methods:The data of 119 patients(123 kidney units) underwent Micro-Ultrasonic lithotripsy combined with mini-percutaneous nephrolithotomy was retrospective reviewed. The group included 96 males and 23 females. All procedure of puncture and dilation were guided by ultrasound solely. The data was analyze by SPSS. Results:The mean operation time was 32.6 minutes (range, 10 - 110 minutes). The mean time of lithotripsy and stone removal was 14.5 minutes (3 - 100 minutes). The mean postoperative length of stay was 2.7 days (1 - 7 days). Besides, stone free rate of discharge was 95.9% (118/123). The mean hemoglobin drop was 11.6 mg/dL (range, 1-26 mg/dL). Grade I, II and IIIa complications were observed in 4, 1 and 1 patients, respectively. Subgroup analyze was done to compare the outcomes of 20mm or less vs 21mm or more calculi. There was a longer operation duration (40 vs 29 minutes) and lower stone free rate in the 21mm or more calculi subgroup. Conclusions:Micro-Ultrasonic probe combined with ultrasound-guided mini-percutaneous nephrolithotomy is an effective and safety procedure to treat patients with upper ureteral and renal stones with higher stone free rate but lower complications.

11.
Eur J Ophthalmol ; : 1120672120901702, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31984763

RESUMO

PURPOSE: To present a relatively uncommon case with a secondary iris cyst in the anterior chamber and its successful management with an anterior chamber mass excision surgery. CASE REPORT: A 46-year-old Chinese woman presented with a dark shadow in her left eye for 6 months without any other discomfort. She had a history of blunt ocular trauma by a badminton strike 3 years ago. Slit-lamp examination showed a small, nearly circular, sharply demarcated, and movable mass in the anterior chamber OS, which could change its position with head tilt. The anterior segment optical coherence tomography revealed a well-circumscribed cystic lesion in the anterior chamber with higher reflective outer layer and lower internal reflectivity. An anterior chamber mass removal surgery was performed without recurrence up to 1 year. CONCLUSION: Secondary free-floating iris cyst following a blunt trauma is rarely reported. It is relatively stable and nonprogressive so it may remain asymptomatic for a long time. Appropriate imaging techniques are necessary for facilitating diagnosis and therapy. Therapeutic management should be considered if visual symptoms arise, especially when complications occur.

12.
Gastroenterology ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31972238

RESUMO

BACKGROUND AND AIMS: The relationship between serum cholesterol level and development of hepatocellular carcinoma (HCC) remains unclear. We investigated the effects of serum cholesterol level on development of liver tumors in mice. METHODS: We performed studies with C57BL/6J mice, mice with disruption of the low-density lipoprotein receptor gene (Ldlr-/-mice), and mice with conditional deletion of nature killer (NK) cells (NKdele mice). Some C57BL/6J and NKdele mice were given injections of diethylinitrosamine to induce liver tumor formation. Mice were placed on a normal diet (ND) or high-cholesterol diet (HCD) to induce high serum levels of cholesterol. We also studied mice with homozygous disruption of ApoE (ApoE-/- mice), which spontaneously develop high serum cholesterol. C57BL/6J and NKdele mice on the ND or HCD were implanted with Hep1-6 (mouse hepatoma) cells and growth of xenograft tumors and lung metastases were monitored. Blood samples were collected from mice and analyzed by biochemistry and flow cytometry; liver and tumor tissues were collected and analyzed by histology, immunohistochemistry, and RNA-sequencing analysis. NK cells were isolated from mice and analyzed for cholesterol content, lipid raft formation, immune signaling, and changes in functions. We obtained matched tumor tissues and blood samples from 30 patients with HCC and blood samples from 40 healthy volunteers; levels of cholesterol and cytotoxicity of NK cells were measured. RESULTS: C57BL/6J mice on HCD and ApoE-/- mice with high serum levels of cholesterol developed fewer and smaller liver tumors and lung metastases after diethylinitrosamine injection or implantation of Hep1-6 cells than mice on ND. Liver tumors from HCD-fed mice and ApoE-/- mice had increased numbers of NK cells compared to tumors from ND-fed mice. NKdele mice or mice with antibody-based depletion for NK cells showed similar tumor number and size in ND and HCD groups after diethylinitrosamine injection or implantation of Hep1-6 cells. NK cells isolated from C57BL/6J mice fed with HCD had increased expression of NK cell-activating receptors (natural cytotoxicity triggering receptor 1 and natural killer group 2, member D), markers of effector function (granzyme B and perforin), and cytokines and chemokines compared with NK cells from mice on ND; these NK cells also had enhanced cytotoxic activity against mouse hepatoma cells, accumulated cholesterol, increased lipid raft formation, and immune signaling activation. NK cells isolated from HCD-fed Ldlr-/- mice did not have increased cholesterol content or cytotoxic activity against mouse hepatoma cells compared with ND-fed Ldlr-/- mice. Serum levels of cholesterol correlated with number and activity of NK cells isolated from human HCCs. CONCLUSIONS: Mice with increased serum levels of cholesterol due to an HCD or genetic disruption of ApoE develop fewer and smaller tumors after injection of hepatoma cells or a chemical carcinogen. We found cholesterol to accumulate in NK cells and activate their effector functions against hepatoma cells. Strategies to increase cholesterol uptake by NK cells can be developed for treatment of HCC.

13.
PLoS One ; 15(1): e0228184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995591

RESUMO

BACKGROUND: The existing diagnostic techniques for detecting schistosomiasis turkestanica, such as aetiological assays, identify infection by parasitic worms via the incubation of miracidia from faeces or observing eggs under microscopy. However, they are limited in the diagnosis of low-grade and prepatent infections, which lead to a high misdetection rates. Therefore, a new method for parasite diagnosis with increased sensitivity is urgently needed. METHODS: Goats in Nimu County (Tibet, China) infected with Schistosoma turkestanicum in an epidemic area were selected according positivity for the infection by faecal examination. Adult worms were collected, eggs were extracted by the sodium hydroxide (NaOH) erosion method, and soluble worm antigen preparation (SWAP) and soluble egg antigen (SEA) were isolated. The best coating concentration of the antigens and the best degree of dilution for serum were determined by square array experiments, and the optimal blocking solution and serum diluents were selected. The specificity, sensitivity and crossover of the ELISA method were determined using 48 samples of goat sera positive for S. turkestanicum, 100 samples of goat sera negative for S. turkestanicum, and 54 samples of buffalo sera positive for S. japonicum. Serological assays were established with samples from goats naturally grazed in a rural area of Nimu County, Tibet Province, by using the indirect ELISA method for the diagnosis of schistosomiasis, and faeces were collected for miracidia hatching. The sensitivity of the two detection methods was compared. RESULTS: Eggs of S. turkestanicum were distributed in the host duodenum and small intestine. Eggs in the host intestinal wall were extracted by the NaOH erosion method, which provided intact eggs with reduced impurities. The testing results obtained by isolating SEA were more stable than those obtained by using SWAP and less affected by the coating concentration and serum dilution. Additionally, the value of positive serum/negative (P/N) serum for SEA was much higher than that for SWAP. The optimal coating concentration of SEA was 0.5 µg/ml, and the optimal serum dilution was 1:100. The specificity and sensitivity of the indirect ELISA based on SEA (S. turkestanicum) were both 100%, and no cross-reactivity was found with schistosomiasis japonica. An epidemiological survey of goats in naturally infected areas showed that the prevalence rate of schistosomiasis turkestanica was 93%, and the infection rate increased with the ages of the goats. CONCLUSION: We aimed to develop a sensitive method to utilize in the mass field screening of livestock. As a diagnostic antigen, SEA (S. turkestanicum) was more suitable for serological testing than SWAP (S. turkestanicum). The indirect ELISA using SEA (S. turkestanicum) exhibited good sensitivity, specificity and no cross-reactivity with schistosomiasis japonica. The degree of infectivity and prevalence of S. turkestanicum infection in endemic areas are serious and should be a focus of concern among local departments.

14.
J Hazard Mater ; 384: 121395, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31628057

RESUMO

Dissolved organic matter (DOM) is regarded as the environmentally friendly substance. Strong complexes could be formed between DOM and heavy metals. Thus, the distribution, bioavailability, toxicity, and fate of heavy metals could be controlled in the environment. The widely spread method for characterizing metal-organic interactions is restricted to combine parallel faction analysis (PARAFAC) with the complexation model. However, a DOM PARAFAC component always contains two or more peaks. Therefore, the traditional method cannot reveal the inner changes of PARAFAC components or whether all the DOM peaks in one PARAFAC component are bound with metal during the metal-organic binding process. In this work, two-dimensional correlation spectroscopy (2DCOS) combined with PARAFAC and the complexation model were employed to reveal the binding speed and ability of different fluorescent peaks from DOM PARAFAC components during the binding process of mercury (Hg2+) to DOM. The results in this study showed that during the Hg2+-DOM binding process, fluorescent peaks in tryptophan-like component all presented Hg2+-binding ability. However, only humic-like component ligands showed Hg2+-binding ability. With these promising results, the true Hg2+ binding rate and ability of different DOM ligands can be revealed, which is helpful for addressing environmental pollution.

15.
J Anesth ; 34(1): 95-103, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31535218

RESUMO

Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics. Although opioid-based therapeutic agents received attention to manage severe pain, their adverse drug effects and mortality rate associated with opioids overdose are the major concerns. Evidences from clinical trials showed therapeutic benefits of cannabis, especially delta-9-tetrahydrocannabinol and cannabinoids reduced neuropathic pain intensity in various conditions. Also, there are reports on using combination cannabinoid therapies for chronic pain management. The association of cannabis dependence and addiction has been discussed much and the reports mentioned that it can be comparatively lower than other substances such as nicotine and alcohol. More countries have decided to legalise the medicinal use of cannabis and marijuana. Healthcare professionals should keep themselves updated with the changing state of medical cannabis and its applications. The pharmacokinetics and safety of medical cannabis need to be studied by conducting clinical research. The complex and variable chemically active contents of herbal cannabis and methodological limitations in the administration of cannabis to study participants, make the clinical research difficult.

16.
Genes Chromosomes Cancer ; 59(5): 325-329, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31774608

RESUMO

Both EWSR1 and TFE3 are well-known oncogenes. EWSR1 encodes an RNA-binding protein involved in multiple soft tissue tumors, including Ewing's sarcoma/peripheral neuroectodermal tumor, desmoplastic small round cell tumor, soft tissue clear cell sarcoma (malignant melanoma of soft parts), extraskeletal myxoid chondrosarcoma, and myxoid liposarcomas. TFE3 regulates both Golgi and lysosomal homeostasis and is rearranged in renal cell carcinoma (RCC), alveolar soft part sarcoma, epithelioid hemangioendothelioma, and perivascular epitheloid cell tumors (PEComas). In this report, we found a rare case of RCC with a fusion between 5' EWSR1 and 3' TFE3. The fusion product retained most functional motifs of TFE3. The oncogenic mechanism likely involves TFE3 overexpression through its juxtaposition with the regulatory elements of EWSR1 and its translocation to the nucleus, resulting in the deregulation of Golgi and lysosomal homeostasis. This is a second case of RCC containing EWSR1-TFE3 fusion.

17.
Risk Anal ; 40(1): 117-133, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29694683

RESUMO

Hurricane track and intensity can change rapidly in unexpected ways, thus making predictions of hurricanes and related hazards uncertain. This inherent uncertainty often translates into suboptimal decision-making outcomes, such as unnecessary evacuation. Representing this uncertainty is thus critical in evacuation planning and related activities. We describe a physics-based hazard modeling approach that (1) dynamically accounts for the physical interactions among hazard components and (2) captures hurricane evolution uncertainty using an ensemble method. This loosely coupled model system provides a framework for probabilistic water inundation and wind speed levels for a new, risk-based approach to evacuation modeling, described in a companion article in this issue. It combines the Weather Research and Forecasting (WRF) meteorological model, the Coupled Routing and Excess STorage (CREST) hydrologic model, and the ADvanced CIRCulation (ADCIRC) storm surge, tide, and wind-wave model to compute inundation levels and wind speeds for an ensemble of hurricane predictions. Perturbations to WRF's initial and boundary conditions and different model physics/parameterizations generate an ensemble of storm solutions, which are then used to drive the coupled hydrologic + hydrodynamic models. Hurricane Isabel (2003) is used as a case study to illustrate the ensemble-based approach. The inundation, river runoff, and wind hazard results are strongly dependent on the accuracy of the mesoscale meteorological simulations, which improves with decreasing lead time to hurricane landfall. The ensemble envelope brackets the observed behavior while providing "best-case" and "worst-case" scenarios for the subsequent risk-based evacuation model.

18.
Leuk Lymphoma ; 61(4): 919-926, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31842651

RESUMO

Genetic variants have been identified in the majority of myelodysplastic syndromes (MDS) patients and have considerably influenced the diagnosis, classification, risk stratification and treatment of MDS. To explore the prognostic significance of genomic variants and build a new prognostic scoring model, we performed next-generation sequencing of 51 known genes in 499 Chinese patients with MDS. Ultimately, the TP53, GATA2, DNMT3A, age and the revised International Prognostic Scoring System (IPSS-R) risk stratification were included in a new Cox model and divided into three prognostic categories, and had a better prediction of overall survival. The C-index of the new prognostic scoring model (0.772) was clearly better than IPSS-R risk stratification (0.717), which was validated in 163 cases. Moreover, the new model was also suitable for the prediction of OS for patients undergoing allogeneic hematopoietic stem cell transplantation. The inclusion of genomic variants and age into the IPSS-R could improve prognostic algorithms for MDS patients.

19.
Chemosphere ; 240: 124744, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31557643

RESUMO

The heterogeneous reactions of α-Al2O3 particles with a mixture of ozone (∼50 ppm) and isoprene (∼50 ppm) were studied as a function of relative humidities (RHs). The reactions were monitored in real time through the microscopic Fourier transform infrared (micro-FTIR) spectrometer. The results show that the presence of ozone leads to the rapid conversion of isoprene to carboxylate (COO-) ions on the surfaces of α-Al2O3 particles in the initial stage. The water significantly suppresses the formation of the carboxylate ions. For the isoprene ozonolysis reaction on the α-Al2O3 particles, the reactive uptake coefficient is strongly suppressed by over a factor of 8 when the RH increases from 8% to 89%. The negative correlation between RH with the secondary organic aerosol (SOA) produced by isoprene ozonolysis plays a key role in the actual atmospheric environment under high humidity. Our results may provide insight into the ozonolysis process of biogenic alkenes over mineral aerosol surfaces with the influence of RHs.


Assuntos
Butadienos/química , Hemiterpenos/química , Modelos Químicos , Ozônio/química , Aerossóis , Umidade , Água
20.
PeerJ ; 7: e8025, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799070

RESUMO

Chloroplasts are typically inherited from the female parent and are haploid in most angiosperms, but rare intra-individual heteroplasmy in plastid genomes has been reported in plants. Here, we report an example of plastome heteroplasmy and its characteristics in Gentiana tongolensis (Gentianaceae). The plastid genome of G. tongolensis is 145,757 bp in size and is missing parts of petD gene when compared with other Gentiana species. A total of 112 single nucleotide polymorphisms (SNPs) and 31 indels with frequencies of more than 2% were detected in the plastid genome, and most were located in protein coding regions. Most sites with SNP frequencies of more than 10% were located in six genes in the LSC region. After verification via cloning and Sanger sequencing at three loci, heteroplasmy was identified in different individuals. The cause of heteroplasmy at the nucleotide level in plastome of G. tongolensis is unclear from the present data, although biparental plastid inheritance and transfer of plastid DNA seem to be most likely. This study implies that botanists should reconsider the heredity and evolution of chloroplasts and be cautious with using chloroplasts as genetic markers, especially in Gentiana.

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