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1.
Medicine (Baltimore) ; 99(3): e18856, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011506

RESUMO

RATIONALE: Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease. It is often associated with extrahepatic autoimmune disorders. However, the concurrence of PBC and Sjögren syndrome (SS) with the subsequent onset of autoimmune hemolytic anemia (AIHA) is extremely rare. PATIENT CONCERNS: This study investigated a 60-year-old woman admitted to our hospital with complaints of xerostomia for 5 years, pruritus for 3 years, and abnormal liver function for 3 months. DIAGNOSES: The patient was suffering from typical clinical PBC and SS, and developed decompensated liver cirrhosis after 32 months of ursodeoxycholic acid (UDCA) therapy. In May 2018, she was readmitted to the hospital with a high fever of 39 °C, coughing, and sever fatigue without remission after 3 days of cephalosporin antibiotic therapy. During the clinical course of PBC, her antimitochondrial antibodies (AMA) titers fluctuated from 1:1000 to negative and then to weakly positive, determined by indirect immunofluorescence (IIF), immunoblotting, and enzyme-linked immunosorbent assay (ELISA) based on recombinant mitochondrial antigens; furthermore, her titers of anti-gp210, an antinuclear antibody (ANA), increased sharply. Laboratory tests and imaging were performed to diagnose PBC and SS in September 2015. However, she was subsequently diagnosed with AIHA after 32 months of UDCA therapy based on the identification of pancytopenia, increased reticulocyte (RET) count, and a positive result from the direct Coombs test. INTERVENTIONS: UDCA, hepatic protectant, albumin infusion, chest drainage, rational antibiotic use, diuretics, and methylprednisolone were used to treat the patient. OUTCOMES: Liver cirrhosis was complicated by the development of AIHA, which became severe at 42 months of follow-up. LESSONS: This is the first case report showing a patient with comorbid PBC and SS, as well as the sequential development of AIHA with decreased AMA and increased anti-gp210 titers; this may have been due to immunodeficiency. These findings stress the importance of the serological screening of ANA profile, as well as repeated measurement of ANA and AMA to track PBC progression and prognosis.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Autoanticorpos/imunologia , Colangite/imunologia , Mitocôndrias/imunologia , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Síndrome de Sjogren/imunologia , Anemia Hemolítica Autoimune/terapia , Autoanticorpos/sangue , Colangite/terapia , Terapia Combinada , Feminino , Humanos , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/terapia , Testes de Função Hepática , Pessoa de Meia-Idade , Complexo de Proteínas Formadoras de Poros Nucleares/sangue , Síndrome de Sjogren/terapia
2.
J Comput Assist Tomogr ; 44(1): 20-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939877

RESUMO

OBJECTIVES: The purpose of this study was to evaluate whether quantitative analysis of lower leg muscle enhancement measured from dynamic computed tomographic angiography (dyn-CTA) could be used for diagnosis of peripheral arterial occlusive disease. METHODS: Patients (N = 35) with known peripheral arterial occlusive disease underwent the dyn-CTA of calves first. Five minutes later, standard CTA of the peripheral runoff from the diaphragm to the toes was performed. A runoff score was assigned by radiologists as a reference standard for each of 4 lower leg artery segments. The lower leg muscle enhancement measured from the dyn-CTA was analyzed by using quantitative kinetic parameters, including initial enhancement (E1), peak enhancement (Epeak), and enhancement ratio (ER) calculated from average time attenuation curves. In addition, histogram of lower leg muscle enhancement was evaluated by using the first enhanced phase images. RESULTS: Lower extremities were diagnosed as a normal group (n = 22) with each vessel segment score equals to 1 or lower and runoff score, 7 or lower, and otherwise as an ischemia group (n = 48). Average ± SD E1 is 91.4% ± 8.5% and 82.3% ± 10.7%, Epeak is 122.7% ± 10.4% and 115.6% ± 11.1%, and ER is 0.75 ± 0.05 and 0.72 ± 0.09 for normal and ischemia group, respectively. Statistical analysis showed that average E1 and Epeak for the ischemia group were significantly lower (P < 0.05) than the normal group. The histogram analysis demonstrated that mean and median of muscle enhancement in the ischemia group were significantly smaller (P < 0.05), and coefficient of variation (CV) was significantly larger (P < 0.05) than the normal group. There were weak negative correlations (r = -0.42, P < 0.05) between runoff scores and E1 and Epeak, and weak positive correlation (r = 0.40, P < 0.05) between runoff scores and CV. The receiver operating characteristics analysis between the 2 groups had area under the curve of 0.77 and 0.76 for E1 and CV, respectively. CONCLUSIONS: Lower leg muscle enhancement measured from the dyn-CTA could be assessed quantitatively to assist diagnosis of ischemia in clinical practice.


Assuntos
Arteriopatias Oclusivas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Extremidade Inferior/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico por imagem , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação
3.
Thorac Cancer ; 11(3): 748-753, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989777

RESUMO

BACKGROUND: The ProCore 25-gauge needle is a novel specifically designed puncture needle for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which may improve the puncture efficiency of the procedure while ensuring the diagnostic rate. The aim of the present study was to evaluate the diagnostic accuracy, mRNA yield, and complication rate of 25-gauge needles compared to those of 22-gauge needles in the evaluation of mediastinal and hilar lymphadenopathy. METHODS: A total of 39 patients undergoing EBUS-TBNA at our institution were evaluated. All the procedures were performed by an experienced endoscopist formally trained in interventional pulmonology. Both the traditional 22-gauge and ProCore 25-gauge needles were used at each lymph node station. For all specimens obtained via EBUS-TBNA, 50 µL was used to extract mRNA and detect the RNA concentration, whereas the other part was sent to the pathological evaluation. χ2 test and t-test were performed to determine the differences between the two types of the needles. A P-value of <0.05 was considered significant. RESULTS: A total of 88 lymph nodes were punctured by the two needles separately. The diagnostic accuracy for each puncture between the two needles did not show any significant difference (P > 0.05). No serious procedure-related complications were reported. In addition, the mRNA concentration did not differ between the two types of needles (P > 0.05). CONCLUSION: The ProCore 25-gauge needle gained a similar diagnostic yield with less puncture time and frequency compared with the 22-gauge needle.

4.
World Neurosurg ; 134: e243-e248, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629147

RESUMO

BACKGROUND: Selection of approach for subaxial cervical fracture-dislocation (SCFD) is controversial. The questions of whether a posterior ligamentous structure (PLS) can be functionally healed in patients with SCFD and how long this healing process takes are critical in these patients. METHODS: This study retrospectively enrolled 394 patients with SCFD who underwent anterior decompression, reduction, and fusion between January 2002 and December 2017. The definition of functional healing of PLS was based on evaluations of clinical function and radiographic stability of PLS. RESULTS: Follow-up was available for 354 patients (89.8%). The PLS of 339 cases was functionally healed at the first follow-up interval without any posterior surgical intervention. No hardware failure or progressive cervical kyphosis was observed at further follow-up. At 12 months postoperatively, interbody fusion was satisfactory. However, the other 15 patients experienced nonhealing PLS at 8 weeks postoperatively and developed cervical deformity at further follow-up. Five patients refused revision surgery; the other 10 patients obtained solid fusion after revision surgeries. CONCLUSIONS: Among 354 patients with SCFD and treated by single anterior reduction and fixation, simple PLS injury without any bony instability at the posterior column of the cervical spine can be functionally healed in 95.8% of patients by external fixation for 8 weeks. Whether this finding is applicable to various types of SCFD should be verified in further prospective studies with larger samples.

5.
Aging Cell ; 19(2): e13062, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31782607

RESUMO

The decline in DNA repair capacity contributes to the age-associated decrease in genome integrity in somatic cells of different species. However, due to the lack of clinical samples and appropriate tools for studying DNA repair, whether and how age-associated changes in DNA repair result in a loss of genome integrity of human adult stem cells remains incompletely characterized. Here, we isolated 20 eyelid adipose-derived stem cell (ADSC) lines from healthy individuals (young: 10 donors with ages ranging 17-25 years; old: 10 donors with ages ranging 50-59 years). Using these cell lines, we systematically compared the efficiency of base excision repair (BER) and two DNA double-strand break (DSB) repair pathways-nonhomologous end joining (NHEJ) and homologous recombination (HR)-between the young and old groups. Surprisingly, we found that the efficiency of BER but not NHEJ or HR is impaired in aged human ADSCs, which is in contrast to previous findings that DSB repair declines with age in human fibroblasts. We also demonstrated that BER efficiency is negatively associated with tail moment, which reflects a loss of genome integrity in human ADSCs. Mechanistic studies indicated that at the protein level XRCC1, but not other BER factors, exhibited age-associated decline. Overexpression of XRCC1 reversed the decline of BER efficiency and genome integrity, indicating that XRCC1 is a potential therapeutic target for stabilizing genomes in aged ADSCs.

6.
PeerJ ; 7: e8096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31788359

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.

7.
Front Genet ; 10: 980, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681420

RESUMO

Seed dormancy and germination are important agronomic traits in wheat (Triticum aestivum L.) because they determine pre-harvest sprouting (PHS) resistance and thus affect grain production. These processes are regulated by Gibberellic Acid-Stimulated Regulator (GASR) genes. In this study, we identified 37 GASR genes in common wheat, which were designated TaGASR1-37. Moreover, we identified 40 pairs of paralogous genes, of which only one had a Ka/Ks value greater than 1, indicating that most TaGASR genes have undergone negative selection. Chromosomal location and duplication analysis revealed 25 pairs of segmentally duplicated genes and seven pairs of tandemly duplicated genes, suggesting that large-scale duplication events may have contributed to the expansion of TaGASR gene family. Microarray analysis of the expression of 18 TaGASR genes indicated that these genes play diverse roles in different biological processes. Using wheat varieties with contrasting seed dormancy phenotypes, we investigated the expression patterns of TaGASR genes and the corresponding seed germination index phenotypes in response to water imbibition, exogenous ABA and GA treatment, and low- and high-temperature treatment. Based on these data, we identified the TaGASR34 gene as potentially associated with seed dormancy and germination. Further, we used a SNP mutation of the TaGASR34 promoter (-16) to develop the CAPS marker GS34-7B, which was then used to validate the association of TaGASR34 with seed dormancy and germination by evaluating two natural populations across environments. Notably, the frequency of the high-dormancy GS34-7Bb allele was significantly lower than that of the low-dormancy GS34-7Ba allele, implying that the favorable GS34-7Bb allele has not previously been used in wheat breeding. These results provide valuable information for further functional analysis of TaGASR genes and present a useful gene and marker combination for future improvement of PHS resistance in wheat.

8.
BMC Med Genomics ; 12(1): 151, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684971

RESUMO

BACKGROUND: During human pregnancy, placental trophectoderm cells release extracellular vesicles (EVs) into maternal circulation. Trophoblasts also give rise to cell-free DNA (cfDNA) in maternal blood, and has been used for noninvasive prenatal screening for chromosomal aneuploidy. We intended to prove the existence of DNA in the EVs (evDNA) of maternal blood, and compared evDNA with plasma cfDNA in terms of genome distribution, fragment length, and the possibility of detecting genetic diseases. METHODS: Maternal blood from 20 euploid pregnancies, 9 T21 pregnancies, 3 T18 pregnancies, 1 T13 pregnancy, and 2 pregnancies with FGFR3 mutations were obtained. EVs were separated from maternal plasma, and confirmed by transmission electronic microscopy (TEM), western blotting, and flow cytometry (FACS). evDNA was extracted and its fetal origin was confirmed by quantitative PCR (qPCR). Pair-end (PE) whole genome sequencing was performed to characterize evDNA, and the results were compared with that of cfDNA. The fetal risk of aneuploidy and monogenic diseases was analyzed using the evDNA sequencing data. RESULTS: EVs separated from maternal plasma were confirmed with morphology by TEM, and protein markers of CD9, CD63, CD81 as well as the placental specific protein placental alkaline phosphatase (PLAP) were confirmed by western blotting or flow cytometry. EvDNA could be successfully extracted for qPCR and sequencing from the plasma EVs. Sequencing data showed that evDNA span on all 23 pairs of chromosomes and mitochondria, sharing a similar distribution pattern and higher GC content comparing with cfDNA. EvDNA showed shorter fragments yet lower fetal fraction than cfDNA. EvDNA could be used to correctly determine fetal gender, trisomies, and de novo FGFR3 mutations. CONCLUSIONS: We proved that fetal DNA could be detected in EVs separated from maternal plasma. EvDNA shared some similar features to plasma cfDNA, and could potentially be used to detect genetic diseases in fetus.

9.
Proteins ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31697409

RESUMO

We explored the stability of the dengue virus envelope (E) protein dimer since it is widely assumed that the E protein dimer is stabilized by drug ligands or antibodies in an acidic environment, neutralizing the virus's ability to fuse with human cells. During this process, a large conformational change of the E protein dimer is required. We performed Molecular Dynamics simulations to mimic the conformational change and stability of the dimer in neutral and acidic conditions with the well-tempered metadynamics method. Furthermore, as a few neutralizing antibodies discovered from dengue patients were reported, we used the same simulation method to examine the influence of a selected antibody on the dimer stability in both neutral and acidic conditions. We also investigated the antibody's influence on a point-mutated E protein that had been reported to interrupt the protein-antibody interaction and result in more than 95% loss of the antibody's binding ability. Our simulation results are highly consistent with the experimental conclusion that binding of the antibody to the E protein dimer neutralizes the virus, especially in a low pH condition, while the mutation of W101A or N153A significantly reduces the antibody's ability in stabilizing the E protein dimer. We demonstrate that well-tempered metadynamics can be used to accurately explore the antibody's interaction on large protein complexes such as the E protein dimer, and the computational approach in this work is promising in future antibody development.

10.
J Magn Reson Imaging ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675174

RESUMO

BACKGROUND: Preoperative estimation of hepatocellular carcinoma (HCC) recurrence after conventional transcatheter arterial chemoembolization (c-TACE) is crucial for subsequent follow-up and therapy decisions. PURPOSE: To evaluate the associations of radiomics models based on pretreatment contrast-enhanced MRI, a clinical-radiological model and a combined model with the recurrence-free survival (RFS) of patients with HCC after c-TACE, and to develop a radiomics nomogram for individual RFS estimations and risk stratification. STUDY TYPE: Retrospective. POPULATION: In all, 184 consecutive HCC patients. FIELD STRENGTH/SEQUENCE: 1.5T or 3.0T, including T2 WI, T1 WI, and contrast-enhanced T1 WI. ASSESSMENT: All HCC patients were randomly divided into the training (n = 110) and validation datasets (n = 74). Radiomics signatures capturing intratumoral and peritumoral expansion (1, 3, and 5 mm) were constructed, and the radiomics models were set up using least absolute shrinkage and selection operator (LASSO) Cox regression. Clinical-radiological features were identified by univariate and multivariate Cox regression. The clinical-radiological model and the combined model fusing the radiomics signature with the clinical-radiological risk factors were developed by a multivariate Cox proportional hazard model. A radiomics nomogram derived from the combined model was established. STATISTICAL TESTS: LASSO Cox regression, univariate and multivariate Cox regression, Kaplan-Meier analysis were performed. The discrimination performance of each model was quantified by the C-index. RESULTS: Among the different peritumoral expansion models, only the 3-mm peritumoral expansion model (C-index, 0.714) showed a comparable performance (P = 0.4087) to that of the portal venous phase intratumoral model (C-index, 0.727). The combined model showed the best performance and the C-index was 0.802. Kaplan-Meier analysis showed that the cutoff values of the combined model relative to a median value (1.7426) perfectly stratified these patients into high-risk and low-risk subgroups. DATA CONCLUSION: The combined model is more valuable than the clinical-radiological model or radiomics model alone for evaluating the RFS of HCC patients after c-TACE, and the radiomics nomogram can be used to preoperatively and individually estimate RFS. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 4 J. MAGN. RESON. IMAGING 2019.

11.
PeerJ ; 7: e7362, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380152

RESUMO

Proteins interact with small molecules to modulate several important cellular functions. Many acute diseases were cured by small molecule binding in the active site of protein either by inhibition or activation. Currently, there are several docking programs to estimate the binding position and the binding orientation of protein-ligand complex. Many scoring functions were developed to estimate the binding strength and predict the effective protein-ligand binding. While the accuracy of current scoring function is limited by several aspects, the solvent effect, entropy effect, and multibody effect are largely ignored in traditional machine learning methods. In this paper, we proposed a new deep neural network-based model named DeepBindRG to predict the binding affinity of protein-ligand complex, which learns all the effects, binding mode, and specificity implicitly by learning protein-ligand interface contact information from a large protein-ligand dataset. During the initial data processing step, the critical interface information was preserved to make sure the input is suitable for the proposed deep learning model. While validating our model on three independent datasets, DeepBindRG achieves root mean squared error (RMSE) value of pKa (-logKd or -logKi) about 1.6-1.8 and R value around 0.5-0.6, which is better than the autodock vina whose RMSE value is about 2.2-2.4 and R value is 0.42-0.57. We also explored the detailed reasons for the performance of DeepBindRG, especially for several failed cases by vina. Furthermore, DeepBindRG performed better for four challenging datasets from DUD.E database with no experimental protein-ligand complexes. The better performance of DeepBindRG than autodock vina in predicting protein-ligand binding affinity indicates that deep learning approach can greatly help with the drug discovery process. We also compare the performance of DeepBindRG with a 4D based deep learning method "pafnucy", the advantage and limitation of both methods have provided clues for improving the deep learning based protein-ligand prediction model in the future.

12.
Ther Clin Risk Manag ; 15: 803-810, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417267

RESUMO

Purpose: This study aimed to evaluate Atorvastatin (ATO)-associated hepatotoxicity using prescription sequence symmetry analysis (PSSA), based on a health insurance database of a Chinese population living in Jiangsu Province, China. Methods: Patients prescribed ATO and hepatoprotective drugs in 2017 were identified, and the run-in period was determined based on the "waiting-time" distribution. Adjusted sequence ratio (ASR) and 95% confidence interval (95% CI) were calculated to estimate the risk of ATO-associated hepatotoxicity under different time intervals or based on gender and age stratification. Results: A total of 2,549 patients, with 1,518 filling the ATO prescription first and 1,031 filling the ATO prescription second, were analyzed. After setting the run-in period as 30 days and the time interval as 15, 30, 60, 90, 120, and 180 days, the ASRs were 1.492 (95% CI: 1.367-1.652), 1.399 (95% CI: 1.308-1.508), 1.280 (95% CI: 1.213-1.357), 1.292 (95% CI: 1.234-1.356), 1.278 (95% CI: 1.226-1.336), and 1.274 (95% CI: 1.229-1.323), respectively. No significant difference was observed between different genders and ages (χ2=0.161, P=0.688; χ2=1.565, P=0.211, respectively). Conclusion: This is the first study conducted in a real-world setting to evaluate the relationship between ATO and hepatotoxicity using the PSSA in a Chinese population. We found a 1.3- to 1.5-fold increase in risk of hepatotoxicity following ATO, with the greater risk occurring within the first 30 days of treatment.

13.
ACS Omega ; 4(6): 9710-9719, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31460061

RESUMO

Herbal medicine has been used to countermine various diseases for centuries. However, most of the therapeutic targets underlying herbal therapy remain unclear, which largely slow down the novel drug discovery process from natural products. In this study, we developed a novel computational pipeline for assisting de novo identification of protein targets for herbal ingredients. The pipeline involves pharmacophore comparison and reverse ligand-protein docking simulation in a high throughput manner. We evaluated the pipeline using three traditional Chinese medicine ingredients such as acteoside, quercetin, and epigallocatechin gallate as examples. A majority of current known targets of these ingredients were successfully identified by the pipeline. Structural comparative analyses confirmed that the predicted ligand-target interactions used the same binding pockets and binding modes as those of known ligand-target interactions. Furthermore, we illustrated the mechanism of actions of the ingredients by constructing the pharmacological networks on the basis of the predicted target profiles. In summary, we proposed an efficient and economic option for large-scale target exploration in the herb study. This pipeline will be particularly valuable in aiding precise drug discovery and drug repurposing from natural products.

14.
Br J Radiol ; 92(1102): 20190109, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31287733

RESUMO

OBJECTIVE: Dermatomyositis (DM) and polymyositis (PM) make up the largest group of potentially treatable myopathies and require early diagnosis. This study investigates whether the edema of thigh muscles in DM/PM can be quantitatively assessed by a novel accelerated T2 mapping technique-GRAPPATINI. METHODS: Three conventional MR sequences and GRAPPATINI accelerated T2 mapping of bilateral thighs from 20 patients (7 DM and 13 PM) and 10 healthy volunteers were prospectively carried out on a 3 T MR scanner. Afterwards, T2 values of 477 thigh muscles from the patients and the healthy controls were manually measured. In addition, the correlations between T2 values and serum muscle enzymes in patients were also analyzed. RESULTS: The new GRAPPATINI technique made quantitative T2 mapping of bilateral thighs feasible with a scanning time of only 2 min 18 s. Moreover, GRAPPATINI-generated T2 values of muscles from patients were markedly higher than those from healthy subjects (p < 0.001). GRAPPATINI accelerated T2 mapping appeared a more sensitive technique in that some DM/PM muscles appearing normal per conventional MRI had increased T2 relaxation time. Furthermore, GRAPPATINI-generated T2 values of DM/PM thigh muscles positively correlated with serum enzyme levels (p < 0.001), which reflected the severity of myopathy. CONCLUSION: GRAPPATINI can significantly shorten acquisition time of T2 mapping and may potentially be applied clinically in DM and PM. ADVANCES IN KNOWLEDGE: GRAPPATINI acceleration makes T2 mapping feasible in clinical practice in providing quantitative information regarding thigh muscle inflammation in DM and PM.


Assuntos
Dermatomiosite/diagnóstico por imagem , Edema/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Músculo Esquelético/diagnóstico por imagem , Polimiosite/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Coxa da Perna/diagnóstico por imagem , Fatores de Tempo
15.
Nucleic Acids Res ; 47(16): 8563-8580, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31291457

RESUMO

Creating access to DNA double-strand break (DSB) sites in the chromatin context is an essential step during the repair process, but much remains to be determined about its regulatory mechanisms. Here, using a novel reporter cassette for simultaneous detection of homologous recombination (HR) and nonhomologous end joining (NHEJ) at the same chromosomal site, we report that the efficiency of HR but not NHEJ negatively correlates with nucleosome density. We demonstrate that PARP1 is required for HR by modulating nucleosome density at damage sites. Mechanistic studies indicate that the ATPase domain of BRG1 and the ZnF domain of SIRT1 interact with poly-ADP ribose (PAR) in response to DNA damage, and are responsible for bringing the two factors to broken DNA ends. At DNA damage sites, BRG1 and SIRT1 physically interact, whereupon SIRT1 deacetylates BRG1 at lysine residues 1029 and 1033, stimulating its ATPase activity to remodel chromatin and promote HR.


Assuntos
DNA Helicases/genética , DNA/genética , Proteínas Nucleares/genética , Nucleossomos/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Reparo de DNA por Recombinação , Sirtuína 1/genética , Fatores de Transcrição/genética , Sítios de Ligação , Linhagem Celular , Linhagem Celular Tumoral , Cloroquina/farmacologia , DNA/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , DNA Helicases/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Células HEK293 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Proteínas Nucleares/metabolismo , Nucleossomos/química , Nucleossomos/efeitos dos fármacos , Fenantrenos/farmacologia , Ftalazinas/farmacologia , Piperazinas/farmacologia , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismo
16.
Theor Appl Genet ; 132(11): 2947-2963, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31324930

RESUMO

KEY MESSAGE: Three major loci for pre-harvest sprouting tolerance (PHST) were mapped on chromosomes 1AL, 3BS, and 6BL, and two CAPS and one dCAPS markers were validated. Sixteen lines with favorable alleles and increased PHST were identified. Pre-harvest sprouting (PHS) significantly affects wheat grain yield and quality. In the present study, the PHS tolerance (PHST) of 192 wheat varieties (lines) was evaluated by assessment of field sprouting, seed germination index, and period of dormancy in different environments. A high-density Illumina iSelect 90K SNP array was used to genotype the panel. A genome-wide association study (GWAS) based on single- and multi-locus mixed linear models was used to detect loci for PHST. The single-locus model identified 23 loci for PHST (P < 0.0001) and explained 6.0-18.9% of the phenotypic variance. Twenty loci were consistent with known quantitative trait loci (QTLs). Three single-nucleotide polymorphism markers closely linked with three major loci (Qphs.ahau-1A, Qphs.ahau-3B, and Qphs.ahau-6B) on chromosomes 1AL, 3BS, and 6BL, respectively, were converted to two cleaved amplified polymorphic sequences (CAPS) and one derived-CAPS markers, and validated in 374 wheat varieties (lines). The CAPS marker EX06323 for Qphs.ahau-6B co-segregated with a novel major QTL underlying PHST in a recombinant inbred line population raised from the cross Jing 411 × Wanxianbaimaizi. Linear regression showed a clear dependence of PHST on the number of favorable alleles. Sixteen varieties showing an elevated degree of PHST were identified and harbored more than 16 favorable alleles. The multi-locus model detected 39 marker-trait associations for PHST (P < 0.0001), of which five may be novel. Six loci common to the two models were identified. The combination of the two GWAS methods contributes to efficient dissection of the complex genetic mechanism of PHST.


Assuntos
Germinação/genética , Triticum/genética , Alelos , Mapeamento Cromossômico , Estudos de Associação Genética , Marcadores Genéticos , Genótipo , Desequilíbrio de Ligação , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sementes/fisiologia , Triticum/fisiologia
17.
Br J Radiol ; 92(1099): 20190073, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31166700

RESUMO

OBJECTIVES: To evaluate the value of preoperative MRI features and laboratory indicators in predicting the early response of hepatocellular carcinoma (HCC) to transcatheter arterial chemoembolization (TACE) combined with high-intensity focused ultrasound (HIFU) treatment and to establish a preoperative prediction model. METHODS: A total of 188 patients with 223 tumors who underwent TACE/HIFU treatment from January 2011 to June 2017 were included. Tumors were divided into three groups (< 2 cm, 2 - 5 cm,> 5 cm) and classified as non-complete response (NCR) and complete response (CR) cohorts according to the Response Evaluation Criteria in Cancer of the Liver (RECICL) 2015 revised version. Univariate analysis and multivariate logistic regression analysis were used to determine independent predictors, and receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic power of each predictor. The prediction model was derived on the ß coefficient of the multivariate regression analysis of the predictors. RESULTS: Irregular margins in the 2 - 5 cm group were closely related to early NCR. Irregular margins, arterial peritumoral enhancement and abnormal alpha-fetoprotein (AFP) were independent predictors of early NCR in the > 5 cm group. The prediction model of this group suggests that irregular margins combined with arterial peritumoral enhancement and abnormal AFP combined with irregular margins and arterial peritumoral enhancement predict an increased risk of early NCR. CONCLUSION: Irregular margins of 2 - 5 cm tumors and irregular margins, arterial peritumoral enhancement, and abnormal AFP of tumors > 5 cm can be applied to predict the early response of HCC to TACE/HIFU treatment. ADVANCES IN KNOWLEDGE: TACE combined with HIFU treatment may be able to significantly improve survival in patients with advanced HCC. Conventional MRI features and laboratory indicators are readily available without complex post-processing. It is feasible to predict the response of HCC after TACE/HIFU treatment based on preoperative conventional MRI features and laboratory indicators, the combination of multiple features predicts high-risk of non-complete response.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Tratamento por Ondas de Choque Extracorpóreas/métodos , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética/métodos , Cuidados Pré-Operatórios/métodos , Adulto , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Artigo em Inglês | MEDLINE | ID: mdl-31153830

RESUMO

BACKGROUND/PURPOSE: Occult HBV infection (OBI) could have serious clinical consequences in patients receiving immunosuppressive therapy. We aimed to investigate the prevalence of OBI in Chinese patients with autoimmune hepatitis (AIH) and to analyze its clinical and virological features. METHODS: 103 AIH cases were enrolled. Hepatitis B virus (HBV) serological markers were screened by chemiluminescence. HBV-DNA were detected by nest-PCR and real-time PCR. HBV genotyping and mutation analysis were performed by Sanger sequencing. RESULTS: Twenty-four out of 103 (23.30%) AIH patients had OBI as evidenced by positive HBV-DNA and negative hepatitis B surface antigen (HBsAg). HBV genotype C is the predominant genotype (57.89%), which had more amino acid (AA) substitutions in S region than that of B-genotype group (P = 0.001). The distribution of AA substitution in the 'α' determinant region between genotype C and B were significantly different (P = 0.042). In addition to those already reported OBI-associated AA substitutions (e.g., sG145R and sV184A), some new OBI-associated AA substitutions (e.g., sV106A, sC137* and sL176P) were found in AIH patients in our study. Three out of 24 (12.50%) OBI patients were diagnosed as decompensated cirrhosis, one patient with S deletion mutation and two patients with HBV extensive AA substitutions. CONCLUSIONS: There was a higher proportion of AIH patients with OBI than the general population in China, which can be either seropositive or seronegative-OBI in AIH patients is associated with some specific AA substitutions. The presence of deletion mutations and the extent of AA substitutions in the HBV S region may have predictive clinical implications.

19.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(4): 410-415, 2019 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-30983186

RESUMO

Objective: To investigate the effectiveness of modified direction-changeable lumbar Cage in transforaminal lumbar interbody fusion (TLIF). Methods: A retrospective analysis was made of 161 patients with single segment L 4 or L 5 isthmic spondylolisthesis treated between January 2013 and December 2015. According to the implantation of Cage, they were divided into trial group (85 cases, modified direction-changeable lumbar Cage implanted in TLIF) and control group (76 cases, traditional nondirection-changeable Cage implanted in TLIF). There was no significant difference in the general data of gender, age, disease duration, slippage segment, and slippage grade between the two groups ( P>0.05). The intraoperative implantation time of Cage, Cage position adjustments times, fluoroscopy times during implantation of Cage, fluoroscopy exposure time, and total operation time were recorded and compared between the two groups. Visual analogue scale (VAS) and Oswestry disability index (ODI) scores were used to evaluate the effectiveness of the patients before operation, and at 3, 6, and 12 months after operation, and the incidence of complications was recorded and analyzed. CT examinations were performed at 6 and 12 months after operation, and lumbar fusion was evaluated by Bridwell criteria. Results: The intraoperative implantation time of Cage, Cage position adjustments times, fluoroscopy times during implantation of Cage, fluoroscopy exposure time, and total operation time in trial group were significant less than those in control group ( P<0.05). All the 161 patients were followed up 12-18 months (mean, 14.3 months). There was 1 case of dural sac tear in the trial group and 1 case of superficial infection in the control group; no complication such as dural tear and infection occurred in other patients. The fusion rate was 76.5% (64/85) in the trial group and 57.9% (44/76) in the control group at 6 months after operation, showing significant difference ( χ 2=6.44, P=0.02); at 12 months after operation, the fusion rate was 96.5% (82/85) in the trial group and 90.8% (69/76) in the control group (including 3 cases of Cage displacement and 4 cases of screw breakage), showing no significant difference in the fusion rate between the two groups ( χ 2=1.54, P=0.26). The VAS and ODI scores of the two groups decreased gradually at 3, 6, and 12 months after operation, and improved significantly when compared with those before operation ( P<0.05). There was no significant difference in VAS and ODI scores between the two groups before and after operation ( P>0.05). Conclusion: Both Cages can obtain the similar effectiveness. The modified direction-changeable lumbar Cage can significantly reduce the fluoroscopy times and radiation dose during TLIF, shorten the operation time, and effectively reduce the radiation exposure of patients and medical staff.


Assuntos
Fusão Vertebral , Espondilolistese , Humanos , Vértebras Lombares , Estudos Retrospectivos , Fusão Vertebral/instrumentação , Espondilolistese/cirurgia , Resultado do Tratamento
20.
BMC Musculoskelet Disord ; 20(1): 148, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954072

RESUMO

BACKGROUND: Surgical treatment is mainly used for atlantoaxial tuberculosis with neurological damage. However, the anatomic structure around the atlantoaxial joint is complex, and the position of vertebral body is deep, which increases the difficulty of the operation and it is challenging for the surgeon to develop surgical strategy. The purpose of this study was to evaluate the clinical outcomes of one-stage combined anterior and posterior surgical treatment approach for atlantoaxial tuberculosis with neurological impairment. METHODS: From January 2005 to January 2015, 12 patients suffering from atlantoaxial tuberculosis with neurological impairment were surgically treated by one-stage combined anterior and posterior approach. Preoperative CT scanning and MRI imaging showed unilateral or bilateral lateral mass destruction of the atlas, and varying destruction degrees of odontoid process, loss of atlantoaxial stability, and tuberculosis focus into the spinal canal resulting in the corresponding spinal cord compression in all patients. The preoperative neurological classifications were Class C for 4 cases, D for 8 cases according to the American Spinal Injury Association (ASIA) system. Quadruple sensitive anti-TB drug treatment was used in all 12 patients preoperative and postoperative. Patients' clinical symptoms and neurological function recovery were evaluated by comparing the Visual Analogue Scale (VAS) score, Neck Disability Index (NDI), Japanese Orthopedic Association (JOA) score and ASIA grading before operation and at the final follow-up. RESULTS: Mean surgical duration was 263.3 ± 43.6 min. Intraoperative blood loss was averagely 529.2 ± 169.8 ml. The average fusion period was 7.3 ± 1.5 months. No instrumentation loosening, migration or breakage was observed during the follow-up of 6.5 ± 2.9 years. The VAS, NDI and JOA scores were significantly changed to 1.00 ± 0.95, 9.50 ± 3.34 and 15.42 ± 1.44 at last follow-up (P < 0.05). The neurological function of all 12 patients was recovered to Class E according to the ASIA grading system. CONCLUSION: In the treatment of atlantoaxial tuberculosis with neurological impairment, one-stage combined anterior and posterior surgical approach have the ability to complete debridement and decompression, and reconstruction of the stability of the upper cervical spine.


Assuntos
Desbridamento/métodos , Descompressão Cirúrgica/métodos , Compressão da Medula Espinal/cirurgia , Fusão Vertebral/métodos , Tuberculose da Coluna Vertebral/terapia , Adulto , Antituberculosos/uso terapêutico , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/patologia , Articulação Atlantoaxial/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Desbridamento/efeitos adversos , Descompressão Cirúrgica/efeitos adversos , Quimioterapia Combinada/métodos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Processo Odontoide/diagnóstico por imagem , Processo Odontoide/patologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Fusão Vertebral/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tuberculose da Coluna Vertebral/complicações , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/patologia , Adulto Jovem
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