Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 141
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Food Chem ; 305: 125440, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31494496

RESUMO

Tea (Camellia sinensis) contains two active glutamate decarboxylases (CsGADs), whose unclear properties were examined here. CsGAD1 was 4-fold higher than CsGAD2 in activity. Their Km values for L-glutamate were around 5 mM. CsGAD1 and CsGAD2 performed best at 55 and 40 °C, respectively, and were both stimulated by calcium/calmodulin (Ca2+/CaM). Over 40 °C, their calmodulin-binding domains degraded. CsGADs were most active at pH 5.6, and were stimulated by Ca2+/CaM at pH 5.6-6.6, but inactivated at pH 3.6. Ca2+/CaM restored the CsGAD1 activity suppressed by inhibitors. CsGADs and CsCaM were localized to the cytosol. CsGAD1 was more highly expressed in most tissues, while CsGAD2 expression was more induced under stresses. The characteristics we first elucidated here revealed that CsGAD1 is the predominant isoform in tea plant, with CsGAD2 exhibiting a supplementary role under certain conditions. The information will contribute to regulation of GABA tea quality.

2.
Medicine (Baltimore) ; 98(47): e17982, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764808

RESUMO

RATIONALE: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is an infection-associated encephalitis/encephalopathy syndrome that is predominately caused by a virus. MERS has no direct association with central nervous system (CNS) infections or inflammation. Non-CNS infections may cause reversible lesion in the splenium of corpus callosum. Recently, there have been reports of many patients with hyponatremia related MERS. Interleukin-6 (IL-6) was also found elevated in serum and in cerebrospinal fluid (CSF) in patients with MERS. The role of IL-6 in the non-osmotic release of vasopressin is crucial. Persistent hyponatremia may be linked to this effect. The following is a case report of MERS secondary to encephalitis, complicated by hyponatremia. We will summarize the latest research and progress regarding MERS. PATIENT CONCERNS: A 31-year-old man was admitted to our department with a 5-day history of fever and headache. His initial diagnosis was encephalitis and hyponatremia; during this period the patient also developed MERS secondary to the encephalitis. DIAGNOSES: Encephalitis was diagnosed by reviewing the history of fever, headache, neck rigidity and Kerning sign (+) on clinical examination. Lab tests revealed: serum VCA IgG (+), EBNA-1 IgG (-), EBV IgM (-), and inflammation in the analysis of CSF. Cranial MRI+C showed that the blood vessels on the surface of the brain were obviously increasing and thickening and diffuse slow waves were detected on the electroencephalogram (EEG). The patient's hyponatremia aggravated on the third day of hospitalization. On the fourth day of hospitalization, the patient was somnolent, apathetic, and slow. Magnetic resonance imaging (MRI) of the brain, with a T2-weighted fluid attenuated inversion recovery image, showed high-signal intensity in the splenium of the corpus callosum (SCC) on the fifth day of hospitalization. Diffusion-weighted imaging (DWI) showed splenial hyperintensity as a "boomerang sign" and reduced diffusion on apparent diffusion coefficient (ADC) maps. Cranial MRI findings returned to normal after 1 month. The diagnosis of MERS was confirmed. INTERVENTIONS: We administered an intravenous drip infusion of acyclovir and prescribed oral sodium supplementation. OUTCOMES: The patient's neurological symptoms gradually improved. The MRI lesion in the SCC disappeared on the 30th day. LESSONS: In patients with encephalitis accompanied by hyponatremia, elevated IL-6 or urinary ß2-microglobulin (ß2MG), and exacerbations such as sudden somnolence, delirium, confusion, and seizures, the possibility of secondary MERS should be investigated, in addition to the progression of encephalitis.

3.
J Org Chem ; 84(22): 14487-14497, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31599586

RESUMO

We reported herein an unexpected cinchona alkaloid-derived squaramide-catalyzed asymmetric two-component Ugi-type reaction of α-aryl-substituted isocyanoacetates with C,N-cyclic azomethine imines, which provides concise access to optically active C1-oxazole-substituted tetrahydroisoquinolines in good yields (86-93%) and high enantioselectivities (up to 98% enantiomeric excess) under mild conditions.

4.
Gigascience ; 8(8)2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505654

RESUMO

BACKGROUND: Recent developments in single-cell RNA sequencing (scRNA-seq) platforms have vastly increased the number of cells typically assayed in an experiment. Analysis of scRNA-seq data is multidisciplinary in nature, requiring careful consideration of the application of statistical methods with respect to the underlying biology. Few analysis packages exist that are at once robust, are computationally fast, and allow flexible integration with other bioinformatics tools and methods. FINDINGS: ascend is an R package comprising tools designed to simplify and streamline the preliminary analysis of scRNA-seq data, while addressing the statistical challenges of scRNA-seq analysis and enabling flexible integration with genomics packages and native R functions, including fast parallel computation and efficient memory management. The package incorporates both novel and established methods to provide a framework to perform cell and gene filtering, quality control, normalization, dimension reduction, clustering, differential expression, and a wide range of visualization functions. CONCLUSIONS: ascend is designed to work with scRNA-seq data generated by any high-throughput platform and includes functions to convert data objects between software packages. The ascend workflow is simple and interactive, as well as suitable for implementation by a broad range of users, including those with little programming experience.

5.
Can J Surg ; 62(4): 249-258, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31348632

RESUMO

Background: Total hip arthroplasty (THA) is increasingly performed in younger patients despite the lack of comprehensive assessment of long-term outcomes. We systematically reviewed the contemporary literature to assess the 1) indications, 2) implant selection and long-term survivorship, 3) complication and reoperation rates and 4) radiographic and functional outcomes of primary THA in patients younger than 55 years. Methods: We searched the Embase and MEDLINE databases for English-language articles published between 2000 and 2018 that reported outcomes of primary THA in patients younger than 55 years with a minimum follow-up duration of 10 years. Results: Thirty-two studies reporting on 3219 THA procedures performed in 2434 patients met our inclusion criteria. The most common preoperative diagnoses were avascular necrosis (1044 [32.4%]), osteoarthritis (870 [27.0%]) and developmental dysplasia of the hip (627 [19.5%]). Modular implants (3001 [93.2%]), cementless fixation (2214 [68.8%]) and metal-on-polyethylene bearings (1792 [55.7%]) were frequently used. The mean 5- and 10-year survival rates were 98.7% and 94.6%, respectively. Data on survival beyond 10 years were heterogeneous, with values of 27%­99.5% at 10­14 years, 59%­84% at 15­19 years, 70%­77% at 20­24 years and 60% at 25­30 years. Rates of dislocation, deep infection and reoperation for any reason were 2.4%, 1.2% and 16.3%, respectively. The mean Harris Hip Score improved from 43.6/100 to 91.0/100. Conclusion: Total hip arthroplasty in patients younger than 55 years provides reliable outcomes at up to 10 years. Future studies should evaluate the outcomes of THA in this population at 15­20 years' follow-up.

6.
J Arthroplasty ; 34(11): 2718-2723, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31353250

RESUMO

BACKGROUND: Nonunion and proximal trochanteric migration is a known complication of trochanteric osteotomy. This study examines the effect of osteotomy length on proximal greater trochanter (GT) migration. METHODS: We analyzed 113 modified trochanteric slide osteotomies and 73 extended trochanteric osteotomies performed between 2008 and 2016. All osteotomies were fixed using cerclage wires and had minimum 6-month radiographic follow-up. Spearman correlations were used to assess association between osteotomy length and GT migration distance. Chi-squared test and logistic regression were used to assess association between patient and surgical factors and GT migration >1 cm. Receiver operating characteristic curves were constructed to determine the optimal cutoff osteotomy length for predicting GT migration >1cm. RESULTS: Mean osteotomy length was 6.1 cm (range 3-12) for modified trochanteric slide osteotomies and 14.8 cm (range 8-23) for extended trochanteric osteotomies. Osteotomy length was negatively correlated (r = -0.340, P < .001) with GT migration distance. Longer osteotomy length was protective against GT migration >1 cm (odds ratio 0.67, P = .002). Receiver operating characteristic curve analysis demonstrated an optimal cutoff osteotomy length of 9.8 cm for predicting GT migration >1 cm (sensitivity 0.971, specificity 0.461). Among osteotomies <10 cm, those fixed using at least one distal wire below the lesser trochanter and vastus ridge demonstrated less mean GT migration (3.86 vs 7.12 mm, P = .009) and higher mean union rate (68.8% vs 31.2%, P < .001). CONCLUSION: Osteotomies shorter than 10 cm are at higher risk of developing proximal GT migration >1 cm. A distal cerclage wire below the lesser trochanter and vastus ridge may help decrease the amount of GT migration. LEVEL OF EVIDENCE: Prognostic Level IV.

7.
Cancer Med ; 8(11): 5137-5147, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31343111

RESUMO

In the era of rituximab, the International Prognostic Index (IPI) has been inefficient in initial risk stratification for patients with R-CHOP-treated diffuse large B-cell lymphoma (DLBCL). To estimate the predictive values of PET/CT quantitative parameters and three prognostic models consisting of baseline and interim parameters for three-year progression-free survival (PFS), we conducted an analysis of 85 patients in China with DLBCL underwent baseline and interim PET/CT scans and treated at the Department of Hematology of Peking University Third Hospital from November 2012 to November 2017. The PET/CT parameters, viz. the baseline and interim values of standardized uptake value (SUVmax ), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG), and their rates of change, were analyzed by a receiver operating characteristics curve, Kaplan-Meier analysis, and log-rank test. Besides, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) was also included in the multivariate Cox hazards model. Owing to the strong correlation between TMTV and TLG at baseline and interim (Pearson's correlation coefficient, r = 0.823, P-value = 0.000, and 0.988, P-value = 0.000, respectively), only TLG was included in the multivariate Cox hazards model, where TLG0  > 1036.61 g and %ΔSUVmax  < 86.02% showed predictive value independently (HR = 10.42, 95% CI 2.35-46.30, P = 0.002, and HR = 4.86, 95% CI 1.27-18.54, P = 0.021, respectively). Replacing TLG in the equation, TMTV0 and TMTV1 both showed significantly predictive abilities like TLG (HR = 8.22, 95% CI 1.86-32.24, P = 0.005, and HR = 2.96, 95% CI 1.16-7.54, P = 0.023, respectively). After dichotomy, NCCN-IPI also gave a significant performance (P = 0.035 and P = 0.010, respectively, in TLG and TMTV models). The baseline variables, that is, TMTV0 , TLG0 and dichotomized NCCN-IPI, and the interim variables TMTV1 and %ΔSUVmax , presented independent prognostic value for PFS. In prognostic model 2 (TLG0  + %ΔSUVmax ), the group with TLG0  > 1036.61 g and %ΔSUVmax  < 86.02% recognized 19 (82.6%) of the relapse or progression events, which showed the best screening ability among three models consisting of baseline and interim PET/CT parameters.

8.
J Allergy Clin Immunol ; 144(3): 777-787.e9, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31102698

RESUMO

BACKGROUND: The airway epithelium maintains mucosal homeostasis and effectively responds to pathogens. The roles of the epithelial NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in human rhinovirus (hRV) infection and its effects mediating epithelial functional changes remain poorly understood. OBJECTIVE: We investigated the mechanisms and cellular functions mediated by the epithelial NLRP3 inflammasome on hRV infection. METHODS: Using models of primary human nasal epithelial progenitor cells and differentiated human nasal epithelial cells (hNECs) infected by hRV, we functionally examined key factors for NLRP3 inflammasome activation, cell death, and mucus production. Furthermore, NLRP3 and IL-1ß in human epithelium from nasal mucosal inflammation induced by hRV were evaluated. RESULTS: The inflammasome-mediated IL-1ß secretion and pyroptosis in human nasal epithelial progenitor cells and hNECs on hRV infection were dependent on the DDX33/DDX58-NLRP3-caspase-1-GSDMD axis. In differentiated hNECs hRV could also promote major airway epithelial mucin (MUC5AC) production through this axis. Our results further confirmed that the NLRP3 inflammasome signaling pathway was responsible for suppressing hRV replication in airway epithelium. Finally, hRV infection in chronically inflamed nasal mucosa was associated with epithelial mucus hyperproduction, whereas NLRP3 and IL-1ß expression levels were significantly increased in hRV-infected epithelium with goblet cell hyperplasia compared with normal epithelium without viral infection. CONCLUSION: The current study showed that the NLRP3 inflammasome signaling axis could functionally mediate hRV-induced inflammation, pyroptosis, and mucus production in airway epithelium, which might be an essential mechanism associated with hRV-induced airway remodeling.

9.
PLoS One ; 14(4): e0215240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30995275

RESUMO

BACKGROUND: The Tuberculin Skin Test (TST) is a relatively simple test for detecting latent tuberculosis infection (LTBI) but requires regular quality assurance to ensure proper technique for administration and reading. The objective of this study was to estimate the accuracy and reproducibility of an mhealth approach (the mTST) to measure the size of swelling immediately following TST administration (TST injection bleb) and after 48-72 hours (TST induration). METHODS: Five non-clinical and one clinical reviewer measured the size of TST injection blebs, and TST indurations using smartphone acquired photos of sites of TST administration and readings in patients, or saline injections in volunteers. The reference standard was the onsite measurement (measured by an experienced TB nurse) of the actual TST injection bleb, or induration. Agreement of reviewers' measurements with the reference standard, as well as agreement within and between reviewers, was estimated using Cohen's kappa coefficient. RESULTS: Using the mTST method to assess bleb size in 64 photos of different TST injections, agreement between reviewers, and the reference standard was very good to excellent (κ ranged from 0.75 to 0.87), and within-reviewer reproducibility of readings was excellent (κ ranged from 0.86 to 0.96). Using the mTST method to assess TST induration in 72 photos, reviewers were able to detect no induration (<5mm) and induration of 15mm or greater with accuracy of 95% and 92% respectively, but accuracy was only 20% and 77% for reactions of 5-9mm and 10-14mm respectively. CONCLUSION: The mTST approach appears to be a reliable tool to assess TST administration. The mTST approach was accurate to read indurations of 0-4mm or 15+mm, but less accurate for reactions of 5-14mm. We believe the mTST approach could be useful for training and quality assurance in locations where on-site supervision is not possible.

10.
J Microbiol Methods ; 158: 44-51, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30703447

RESUMO

(R)-2-(4-hydroxyphenoxy)propionic acid ((R)-HPOPA) is an important intermediate for the synthesis of optically pure aryloxyphenoxypropionic acid herbicides. Regioselective hydroxylation of (R)-2-phenoxypropionic acid ((R)-POPA) by microbes is one of the most useful methods for the industrial production of (R)-HPOPA. In this study, we designed and optimized a rapid throughput assay for screening (R)-HPOPA producing bacterial/fungal strains which can regioselectively hydroxylate (R)-POPA. (R)-HPOPA could react with 4-aminoantipyrine (4-AAP) in the presence of potassium hexacyanoferrate (K3[Fe(CN)6]) to form indoxyl antipyrine, an orange-red chromophore, that can easily spectrophotometrically be determined at 550 nm. During the verification of the assay we observed an average recovery rate of between 97.3% and 104.5%. Apart from the rapid throughput, no obvious differences in detection (R)-HPOPA in the culture broth samples were found between our rapid throughput multiplate assay and a high-performance liquid chromatography method. Our optimized assay method is simple, rapid and accurate with high repeatability. It has the potential for high throughput screening (about 3000-5000 samples/day) of the (R)-HPOPA producing strains.

11.
Ann Surg Oncol ; 26(4): 961-968, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30675702

RESUMO

OBJECTIVE: The aim of this study was to determine the impact of postmastectomy radiotherapy (PMRT) on reoperation rates in women with breast cancer undergoing mastectomy and breast reconstruction. METHODS: Between June 2001 and December 2015, 832 breast cancer patients treated with mastectomy and breast reconstruction with (n = 159) or without (n = 673) PMRT were analyzed retrospectively. Reoperations following breast reconstruction were categorized into the following three types: anticipated, unanticipated, and others. Multivariable logistic regression models were used to evaluate the impact of PMRT on overall and unanticipated reoperations according to different breast reconstruction types after adjusting for relevant covariates. RESULTS: With a median follow-up of 58.5 months, a total of 1298 operations were performed in 832 breast cancer patients. The rates of overall and unanticipated reoperations were 46.2% and 7.7%, respectively. Multivariable analysis showed that PMRT was not associated with overall reoperations in either implant-based reconstruction patients (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.43-2.37, p = 0.995) or autologous reconstruction patients (OR 0.85, 95% CI 0.52-1.40, p = 0.533); however, the impact of PMRT on unanticipated reoperations differed by reconstruction type. In patients who received implant-based reconstructions, PMRT was associated with a 3.05-fold (95% CI 1.20-7.75, p = 0.019) higher odds of unanticipated reoperations, while there was no difference in patients who underwent autologous reconstruction (OR 1.17, 95% CI 0.51-2.66, p = 0.713). Delayed reconstruction or delayed-immediate reconstructions were associated with an increased risk of both overall and unanticipated reoperations in both reconstruction cohorts. CONCLUSIONS: PMRT appears to be associated with an increased risk of unanticipated reoperations among patients receiving implant-based reconstruction, but not among those receiving autologous reconstruction. The risk of reoperation should be taken into consideration when selecting the appropriate breast reconstruction type when PMRT is planned.


Assuntos
Neoplasias da Mama/radioterapia , Mamoplastia , Mastectomia/métodos , Complicações Pós-Operatórias , Radioterapia Adjuvante , Reoperação , Adolescente , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Org Biomol Chem ; 17(3): 639-645, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30575842

RESUMO

An efficient organocatalytic asymmetric tandem conjugate addition-protonation of α-substituted isocyanoacetates to 2-chloroacrylonitrile catalyzed by dihydroquinine-derived thiourea has been investigated, affording the corresponding adducts with two non-adjacent tertiary-quaternary stereocenters in excellent yields (up to 99%) along with good to excellent diastereo- and enantioselectivities (up to 20 : 1 dr, up to 95% ee) under mild conditions. The adduct can also be transformed into chiral γ-lactam by synthetic transformations.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30439485

RESUMO

BACKGROUND: The indication for internal mammary node irradiation (IMNI) after preoperative systemic therapy in breast cancer remains vague. This study was designed to evaluate the effect of IMNI in clinical stage II-III breast cancer patients after preoperative systemic therapy and surgery. METHODS: Between August 2005 and December 2013, 497 patients with clinical stage II-III breast cancer underwent anthracycline- or taxane-based preoperative systemic therapy, surgery and postoperative radiotherapy. A median dose of 50Gy (range, 46-60Gy) in 25 fractions was delivered to the chest wall/breast with (n=236) or without IMNI (n=261). Disease-free survival (DFS) and overall survival (OS) rates with or without IMNI were evaluated using Kaplan-Meier method and compared with log-rank test. Propensity score matching (PSM) was performed to adjust for the unbalanced characteristics between the two groups. Prognostic factors associated with survival were evaluated by univariate and multivariate analysis. RESULTS: The median follow-up time was 64 months. Patients with IMNI presented with more advanced clinical T stage, pathological N stage, positive lymph-vascular invasion and medically/centrally located disease (p<0.05). The 5-year DFS and OS rates were 73.7% and 86.3% in the IMNI group, and 71.5% and 86.7% in the non-IMNI group, respectively (P>0.05). Multivariate analysis demonstrated that IMNI was an independent prognostic factor for DFS (P=0.018) and resulted in a borderline improvement in OS (P=0.067). After PSM, characteristics were well balanced. The 5-year DFS rates of IMNI and non-IMNI group were 76.8% and 63.4%, respectively (P=0.030), and the 5-year OS rate was 88.9% and 84.1%, respectively (P=0.083). IMNI was independently prognostic for DFS (P=0.014) and OS (P=0.047) in matched patients. CONCLUSION: IMNI improves survival outcomes in clinical stage II-III breast cancer patients after preoperative systemic therapy. Further prospective studies are warranted to identify the role of IMNI in the preoperative systemic therapy setting.

14.
J Oncol ; 2018: 4736263, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298090

RESUMO

Purpose: This study examines factors associated with outcomes following salvage radiation and systemic therapy for breast cancer patients who developed isolated locoregional recurrence (ILRR) after mastectomy alone, while focusing on the prognostic significance of constructed biologic subtype in this setting. Methods and Materials: 269 postmastectomy patients in total treated for ILRR were included. Cumulative incidence of locoregional control (LRC), distant metastasis (DM)-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were calculated using Kaplan-Meier method. For statistical analysis, biologic subtypes were constructed from hormonal receptors (Rec) and HER2, consisting of Rec+/HER2-, Rec+/HER2+, Rec-/HER2+, and Rec-/HER2-. The association of clinic-pathological and treatment-related parameters with outcomes was evaluated using a Cox regression model. Results: At a median follow-up of 65 months, 56 (20.8%) patients failed to secure LRC after radiotherapy, and 165 patients (61.3%) developed DM. Overall, the actuarial 5-year LRC, DMFS, DFS, and OS rate was 77.3%, 45.6%, 43.9%, and 66.8%, respectively. Multivariate analysis revealed that constructed biologic subtype represented the most significant prognostic factor for any outcome. Compared to patients with Rec+/HER2- disease, those with Rec-/HER2- had significantly poorer 5-year LRC (84.2% versus 58.3%, HR = 4.36, P < 0.001) and worse survivals including 5-year DMFS (63.0% versus 15.8%, HR = 4.28, P < 0.001), DFS (59.7% versus 13.6%, HR=3.92, P < 0.001), and OS (87.8% versus 22.3%, HR = 8.55, P < 0.001). Other factors associated with reduced LRC were no radical surgery and involved field irradiation alone, whereas factors associated with poor survivals included positive nodes at primary diagnosis and regional recurrence. Conclusions: Constructed biologic subtypes remained to be predictive of both disease control and survivals after salvage radiation for postmastectomy ILRR. Notably, Rec-/HER2- patients were demonstrated to be at high risk of locoregional failure and subsequent DM and tended to have worse survivals despite salvage therapies.

15.
Cell Rep ; 25(2): 398-412.e6, 2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30304680

RESUMO

Colorectal cancer (CRC) onset is profoundly affected by Western diet. Here, we report that high-fat (HF) diet-induced, organ-specific colonic lysine homocysteinylation (K-Hcy) increase might promote CRC onset by impeding DNA damage repair. HF chow induced elevated methionyl-tRNA synthetase (MARS) expression and K-Hcy levels and DNA damage accumulation in the mouse and rat colon, resulting in a phenotype identical to that of CRC tissues. Moreover, the increased copy number of MARS, whose protein product promotes K-Hcy, correlated with increased CRC risk in humans. Mechanistically, MARS preferentially bound to and modified ataxia-telangiectasia and Rad3-related protein (ATR), inhibited ATR and its downstream effectors checkpoint kinase-1 and p53, and relieved cell-cycle arrest and decreased DNA damage-induced apoptosis by disrupting the binding of ATR-interacting protein to ATR. Inhibiting K-Hcy by targeting MARS reversed these effects and suppressed oncogenic CRC cell growth. Our study reveals a mechanism of Western-diet-associated CRC and highlights an intervention approach for reversing diet-induced oncogenic effects.

16.
JBJS Rev ; 6(7): e2, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29979233

RESUMO

BACKGROUND: The indications and technique for the transtrochanteric approach to the hip have evolved greatly since its initial popularization in the 1960s. The purpose of this systematic review was to assess current uses of this approach on the basis of indications, osteotomy technique, trochanteric fixation method, complications, and functional outcome. METHODS: A comprehensive search of MEDLINE and Embase databases from January 2000 to July 2017 was performed in accordance with the PRISMA guidelines. Articles were divided into 3 major categories on the basis of the type of hip surgery performed: (1) primary arthroplasty, (2) revision arthroplasty, and (3) joint-preserving procedures. Patient data were then analyzed according to these 3 categories. RESULTS: Seventy-six studies (5,028 hips), mainly of Level-IV evidence, were included. Four types of osteotomy were reported for a variety of indications. Rates of nonunion were 6.0% (303 of 5,028) across all studies, 4.2% (39 of 921) for primary arthroplasty, 6.7% (114 of 1,690) for revision arthroplasty, and 4.4% (56 of 1,278) for joint-preserving procedures. Rates of dislocation were 1.5% (14 of 921) for primary arthroplasty and 4.6% (77 of 1,690) for revision arthroplasty. The rate of osteonecrosis after joint-preserving procedures was 1.1% (14 of 1,278). Rates of deep infection were 1.1% (55 of 5,028) across all studies, 0.1% (1 of 921) for primary arthroplasty, 2.1% (36 of 1,690) for revision arthroplasty, and 0.6% (8 of 1,278) for joint-preserving procedures. CONCLUSIONS: The transtrochanteric approach remains useful in cases requiring extensile exposure of the acetabulum or femoral medullary canal. However, trochanteric complications continue to pose a clinical challenge. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

17.
Org Biomol Chem ; 16(25): 4641-4649, 2018 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-29901066

RESUMO

We have developed an efficient diastereo- and enantioselective Mannich/cyclization cascade reaction of α-substituted isocyanoacetates with 4-aryl-3-carbonyl-1,2,5-thiadiazole-1,1-dioxide type cyclic sulfamide ketimines cooperatively catalyzed by cinchona alkaloid-derived squaramide and AgOAc. The corresponding optically active 2,3,3a,4-tetrahydroimidazo[1,5-b][1,2,5]thiadiazole-1,1-dioxide derivatives were obtained in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >20 : 1 dr, up to 94% ee).

18.
JBJS Rev ; 6(6): e4, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29894341

RESUMO

BACKGROUND: The optimal system for greater trochanteric fixation following osteotomy or fracture remains unknown. This systematic review aims to synthesize the available English-language literature on 5 commonly reported trochanteric fixation methods to quantify and compare rates of complications and reoperation. METHODS: A comprehensive search of MEDLINE and Embase databases from January 1946 to June 2017 was performed for articles in English describing fixation of trochanteric osteotomies and fractures using wires, cables, cable-plate devices, claw or locking plates, and trochanteric bolts. Pooled mean rates of complications and reoperation with 95% confidence intervals (CIs) were analyzed using a random-effects model. RESULTS: Fifty-seven studies involving 10,956 hips were eligible for inclusion. Five studies had Level-III evidence and 52 had Level-IV evidence. The pooled mean rate of nonunion was 4.17% (95% CI, 3.21% to 5.13%; I = 79%) for wires, 5.07% (95% CI, 0.37% to 9.77%; I = 74%) for cables, 16.11% (95% CI, 10.85% to 21.37%; I = 89%) for cable-plate systems, 9.60% (95% CI, 2.23% to 16.97%; I = 59%) for claw or locking plates, and 12.42% (95% CI, 3.41% to 21.43%; I = 75%) for trochanteric bolts. Substantial heterogeneity in the data precluded formal statistical comparison of outcomes and complications between implants. CONCLUSIONS: Available literature on the various trochanteric fixation implants is heterogeneous and consists primarily of retrospective case series. Based on the current literature, it is difficult to support the use of one implant over another. Despite superior mechanical properties, rates of complication and reoperation following cable-plate fixation remains suboptimal, especially in complex revision scenarios. Additional rigorous prospective randomized and cohort studies are needed to make definitive recommendations regarding the most reliable method of trochanteric fixation. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

19.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(3): 340-345, 2018 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-29643042

RESUMO

OBJECTIVE: To obtain stable primary cultures of human malignant meningioma cells and establish an intracranial in-situ tumor model in nude mice. METHODS: Ten surgical specimens of highly suspected malignant meningioma were obtained with postoperative pathological confirmation. Primary malignant meningioma cells were cultured from the tissues using a modified method and passaged. After identification with cell immunofluorescence, the cultured cells were inoculated into the right parietal lobe of 6 nude mice using stereotaxic apparatus and also transplanted subcutaneously in another 6 nude mice. The nude mice were executed after 6 weeks, and HE staining and immunohistochmistry were used to detect tumor growth and the invasion of the adjacent brain tissues. RESULTS: The primary malignant meningioma cells were cultured successfully, and postoperative pathology reported anaplastic malignant meningioma. Cell immunofluorescence revealed positivity for vimentin and EMA in the cells, which showed a S-shaped growth curve in culture. Flow cytometry revealed a cell percentage in the Q3 area of (95.99∓2.58)%. Six weeks after transplantation, tumor nodules occurred in the subcutaneous tumor group, and the nude mice bearing the in situ tumor showed obvious body weight loss. The xenografts in both groups contained a mean of (36∓5.35)% cells expressing Ki-67, and the intracranial in situ tumor showed obvious invasion of the adjacent peripheral brain tissues. CONCLUSION: We obtained stable primary cultures of malignant meningioma cells and successfully established a nude mouse model bearing in situ human malignant meningioma.

20.
J Arthroplasty ; 33(7): 2050-2056, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29573913

RESUMO

BACKGROUND: Controversy remains over the surgical management of large osteochondral lesions of the femoral head in young, active patients. The purpose of this study is to assess midterm clinical and radiographic outcomes after fresh osteochondral allograft transplantation (OAT) for large femoral head lesions at minimum 2-year follow-up. METHODS: A retrospective review of prospectively collected data was performed for 22 patients under the age of 50 years with defined femoral head osteochondral lesions who underwent fresh OAT between 2008 and 2015. Patients were assessed clinically using the modified Harris Hip Score (mHHS) preoperatively and at each follow-up visit. Postoperative radiographs were evaluated for graft integrity and Kellgren & Lawrence Grade for osteoarthritis severity. Complications and reoperation were assessed by chart review. Kaplan-Meier survivorship analyses with 95% confidence intervals were performed for the end point of conversion to total hip arthroplasty. RESULTS: At a mean follow-up of 68.8 months (26-113), the mean mHHS improved significantly (P < .001) from 48.9 (19-84) to 77.4 (35-98). Sixteen of 22 patients (72.7%) had an mHHS ≥70 at the latest follow-up. Arthritic progression, as indicated by an increase in the Kellgren & Lawrence Grade, occurred in 4 of 22 hips (18.2%). Five patients (22.7%) underwent conversion to total hip arthroplasty. Graft survivorship was 86.4 ± 7.3% at 2 years, 78.5 ± 10.0% at 5 years, and 67.3 ± 13.5% at 9 years. CONCLUSION: Fresh OAT may be a viable treatment option for osteochondral defects of the femoral head in young, active patients with minimal preexisting joint deformity.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA