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1.
Bone Joint J ; 102-B(2): 177-185, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009426

RESUMO

AIMS: To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). METHODS: This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). RESULTS: There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. CONCLUSION: Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177-185.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/cirurgia , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/cirurgia , Sacro/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/tratamento farmacológico , Criança , Terapia Combinada , Curetagem/métodos , Feminino , Tumor de Células Gigantes do Osso/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
2.
Chem Commun (Camb) ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31976501

RESUMO

Reported herein is a visible-light-catalyzed photoredox atom-transfer radical cyclization (ATRC) halo-alkylation of 1,6-dienes with α-halo-ketones as the ATRC reagent. This process exhibits high atom economy, high step economy, and high redox economy, which can directly construct a 4-bromo-3,3-dialkyl-octahydro-indol-2-one core under mild conditions in one pot, and lutidine is found to be the key promoter for this ATRC process.

3.
Eur J Pharmacol ; 867: 172807, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751575

RESUMO

Adolescence is a critical neurodevelopmental period for both excitatory and inhibitory (E/I) neurotransmission and often witnesses the typical onsets of schizophrenia. One possibility is that disruptions in adolescent neurodevelopmental processes may produce schizophrenia-like behavioral and neurobiological abnormalities. We previously reported that subchronic treatment of adolescent animals with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 induced cognitive deficits and reduced interneuron densities in rat medial prefrontal cortex, and these changes persisted one week after MK-801 exposure. However, it remains unclear how this treatment may affect E/I balance in hippocampus, which has long been associated with the pathophysiology of schizophrenia. Here, we examined hippocampal E/I biomarkers in adolescent rats treated with MK-801 (0.2 mg/kg, i.p., 14 days) and found increases in the ratio of the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular gamma-aminobutyric acid (GABA) transporter (VGAT) 24 h and 7 days after MK-801 exposure. Interestingly, the increased VGluT1/VGAT ratio at the two time points was driven by upregulated VGluT1 expression and downregulated VGAT expression, respectively. The decrease in VGAT expression persisted 14 days after MK-801 exposure and recovered two weeks later. No alterations in hippocampal interneuron densities were observed. Behaviorally, the treatment decreased prepulse inhibition at 24 h but not 14 days, after MK-801 exposure. Taken together, these results demonstrate that subchronic NMDA receptor blockade during adolescence induces long-term, but not permanent, E/I imbalance in the rat hippocampus, which could be attributed to the dysregulation of glutamatergic transmission in the short term and of GABAergic transmission in the long term.

4.
CNS Neurosci Ther ; 26(2): 270-277, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31368639

RESUMO

AIMS: To investigate clinical characteristics and surgery outcomes of young children with focal cortical dysplasia (FCD) type II. METHODS: Young children (onset age ≤6 years) with FCDII who underwent epileptic surgery in Children Epilepsy Center of Peking University First Hospital in 2014-2018 were followed up for at least 6 months after surgery. RESULTS: One hundred and twelve children with FCDII were included, with median age of onset 0.9 years (0.01-5.9), who underwent surgery at 4.1 years old (0.8-16.2). Focal seizures were most frequent (90.2%) and epileptic spasms presented in 23 (20.5%) cases. Epileptic encephalopathy was not uncommon (12.5%), associated with earlier epilepsy onset and higher rate of bilateral onset on ictal EEG (OR = 0.213, 9.059; P = .041, .004). At the last follow-up, 88.4% achieved seizure-free. Before surgery, 49.1% showed moderate/severe developmental delay, associated with earlier seizure onset and higher rate of history of epileptic encephalopathy (OR = 0.740, 5.160, P = .023, .042). For 48 children with preoperatively moderate/severe developmental delay, DQ rank at 6 months postsurgery was improved in only four cases. CONCLUSION: For young children with FCDII, they tend to present with epileptic encephalopathies and show moderate/severe developmental delay before surgery. The seizure outcome was favorable after surgery. For children with preoperatively moderate/severe developmental delay, developmental outcome at 6 months after surgery was not satisfactory.

5.
Ann Transl Med ; 7(18): 477, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31700913

RESUMO

Background: The interaction between platelets and macrophages plays an important role in the development and progression of atherosclerosis (AS). This study aimed to investigate the role of platelet microparticles (PMPs) in the development of foam cells. Methods: PMPs are generated by activating platelets with thrombin and separated by ultracentrifugation. The macrophages were treated with PMPs, the phagocytosis of oxidized low-density lipoprotein (Ox-LDL) and formation of foam cells were evaluated by flow cytometry and confocal microscopy, respectively, and the inflammatory factors cytokines in the supernatant were detected by ELISA. Results: PMPs significantly increase the phagocytosis of Ox-LDL and elevated foam cell formation of macrophages. IL-1ß content in the supernatant of macrophages peaked around 2-4 h and declined to normal level after 6-8 h; IL-6 content peaked at 4 h and then decreased to normal level. TNF-α content peaked at 2-4 h. Conclusions: The microparticles from activated platelets can increase the phagocytosis of Ox-LDL and the production of inflammatory cytokines by macrophages, which is related to the development of AS.

6.
J Surg Oncol ; 120(8): 1497-1504, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31705571

RESUMO

BACKGROUND AND OBJECTIVES: Few reports have investigated patient experiences following total en bloc sacrectomy. The aims of this study were to obtain a deeper understanding of patients' personal experiences, needs, and satisfaction with the treatment to reveal areas in which perioperative and long-term patient care can be improved. METHODS: A qualitative design was applied to examine patient experiences and supportive care needs. Patients treated between 2007 and 2017 were identified from our institutional database. RESULTS: A total of 28 survivors were interviewed (13 females, age 13-75 years). Eight themes were identified: the effect of surgery on patients' (a) daily lives, (b) social activities, (c) work or school activities, (d) and family lives; (e) acceptance of ostomy surgery; (f) need for guidance regarding long-term rehabilitation; (g) satisfaction with the medical services provided in the hospital; and (h) satisfaction with the treatment outcomes. CONCLUSION: Total en bloc sacrectomy can yield satisfactory oncological outcomes; however, the procedure is a life-changing event for patients and their families. Physicians must provide long-term support and guidance after surgery to enable patients to fully understand and cope with the changes in their lives.


Assuntos
Neoplasias Ósseas/terapia , Sobreviventes de Câncer/psicologia , Pessoas com Deficiência/psicologia , Qualidade de Vida , Sacro/cirurgia , Atividades Cotidianas , Adolescente , Adulto , Idoso , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Estomia/psicologia , Satisfação do Paciente , Adulto Jovem
7.
ACS Appl Mater Interfaces ; 11(49): 45467-45478, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31718131

RESUMO

Most of the existing single-component nanostructures cannot provide comprehensive diagnostic information, and their treatment strategies always have to combine other therapeutics as a complementary for effective biomedical application. Here, we adopted a facile approach to design a theranostic nanoflower (NF) with robust efficacy for comprehensive tumor diagnosis and quadruple synergistic cancer therapy. The NF is equipped with a metallic hybrid of several functional elements and flower-like superstructures and thus shows excellent in vitro and in vivo theranostic performance. It shows high X-ray attenuation coefficiency for the Bi element, strong near-infrared (NIR) plasmon absorbance and singlet oxygen (1O2) generation ability for the Mo element, and great photothermal conversion efficiency (54.7%) because of enhanced photoabsorption of the petal structure. Moreover, the NF realizes a very high doxorubicin-loading efficiency (90.0%) and bimodal pH/NIR-responsive drug release, posing a promise as a controlled drug carrier. The NF also shows excellent performance at trimodal magnetic resonance/X-ray computed tomography/photoacoustic imaging for comprehensive tumor diagnosis. To our best knowledge, it is the first time that integrating at least seven functions into one biomedical nanomaterial for well-rounded tumor theranostics has been reported. This "all-in-one" NF opens a new perspective in developing novel and efficient multifunctional nanotheranostics.

8.
J Org Chem ; 84(22): 14760-14769, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31642323

RESUMO

An efficient method was successfully developed to obtain cyclic ß-amino ketones via visible-light photoredox catalysis. With this catalytic system, vinyl azides and N-Ph pyrrolidines react to form cyclic ß-amino ketones by α-amino radical addition. This method provides a simple, mild, straightforward, and novel paradigm to prepare important ß-amino ketones.

9.
Exp Ther Med ; 18(5): 3439-3449, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31602219

RESUMO

Glioblastoma (GBM), characterized by high morbidity and mortality, is one of the most common lethal diseases worldwide. To identify the molecular mechanisms that contribute to the development of GBM, three cohort profile datasets (GSE50161, GSE90598 and GSE104291) were integrated and thoroughly analyzed; these datasets included 57 GBM cases and 22 cases of normal brain tissue. The current study identified differentially expressed genes (DEGs), and analyzed potential candidate genes and pathways. Additionally, a DEGs-associated protein-protein interaction (PPI) network was established for further investigation. Then, the hub genes associated with prognosis were identified using a Kaplan-Meier analysis based on The Cancer Genome Atlas database. Firstly, the current study identified 378 consistent DEGs (240 upregulated and 138 downregulated). Secondly, a cluster analysis of the DEGs was performed based on functions of the DEGs and signaling pathways were analyzed using the enrichment analysis tool on DAVID. Thirdly, 245 DEGs were identified using PPI network analysis. Among them, two co-expression modules comprising of 30 and 27 genes, respectively, and 35 hub genes were identified using Cytoscape MCODE. Finally, Kaplan-Meier analysis of the hub genes revealed that the increased expression of calcium-binding protein 1 (CABP1) was negatively associated with relapse-free survival. To summarize, all enriched Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways may participate in mechanisms underlying GBM occurrence and progression, however further studies are required. CABP1 may be a key gene associated with the biological process of GBM development and may be involved in a crucial mechanism of GBM progression.

10.
Clin Biomech (Bristol, Avon) ; 70: 203-208, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31655451

RESUMO

BACKGROUND: Reconstruction after total sacrectomy is a difficult problem in the field of orthopedic oncology. Current reconstruction methods have not completely solved the problems associated with instrumentation failure. The purpose of this study was to evaluate the biomechanical properties of a 3D-printed total sacrum prosthesis and to conduct biomechanical comparisons between the total sacrum prosthesis and rod-screw systems for lumbosacral reconstruction after total sacrectomy. METHODS: Three types of reconstruction were explored, and corresponding finite element models were simulated: four-rod reconstruction, four-rod plus anterior column reconstruction, and 3D-printed total sacrum prosthesis reconstruction. A vertical load of 600 N was applied to the L4 vertebra, and the bilateral acetabula were set as the boundary with six degrees of freedom fixed, simulating the bipedal standing position. FINDINGS: The order of the reconstructions according to decreasing maximum von Mises stress was as follows: four-rod reconstruction > four-rod plus anterior column reconstruction >3D-printed total sacrum prosthesis reconstruction. The order of reconstructions according to decreasing L5 shift-down displacement was as follows: four-rod reconstruction >3D-printed total sacrum prosthesis reconstruction > four-rod plus anterior column reconstruction. INTERPRETATION: Compared with the rod-screw systems, the total sacrum prosthesis reconstruction has the biomechanical advantages of a more uniform stress distribution, a lower peak stress and better stability and can thus serve as an alternative choice for reconstruction after total sacrectomy.

11.
Orthop Surg ; 11(5): 819-825, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31489784

RESUMO

OBJECTIVE: Limb salvage in pediatric patients remains a challenge. We describe a staged strategy. The procedure includes: (i) tumor removal and non-hinged static endoprosthesis reconstruction; (ii) leg length discrepancy (LLD) correction by shoe lift or distraction osteogenesis; and (iii) maturity reconstruction by regular endoprosthesis. The aim of the study was to investigate the results of non-hinged static megaprosthesis reconstruction and staged LLD correction in the treatment of malignant tumors in the distal femur in children. METHODS: Non-hinged megaprostheses were implanted in 12 pediatric patients with osteosarcoma in the distal femur. The prosthesis consists of a femoral component with constrained condylar knee (CCK) design, and a tibial component with a small-diameter press-fit stem and derotation fins. A posterior stabilizing polyethylene component is fixed on the tibial component. The cases were prospectively followed up with focus on the growth rate of adjacent uninvolved bone in the salvaged limb, joint stability, knee stability, function outcome, length discrepancy, and surgery-related complications. RESULTS: There were five girls and seven boys included in the study, with an average age at the time of primary surgery of 10.0 years (range, 8-12 years). All the tumors were located in the distal femur. The average follow up was 76.3 months (range, 24-139 months). The Ligament Augmentation and Reconstruction System (LARS) ligament was used in two patients to enhance the soft tissue reattachment and reconstruct medial collateral ligament (MCL). Ten patients were alive at the final follow-up and two had died of lung metastases. Expected LLD was 6.7 cm (range, 3.0-13.2 cm) at initial surgery. At the final follow-up, nine patients reached skeletal maturity and the actual LLD at the femur was 5.3 cm (range, 3.0-10.1 cm), excluding 1 cm correction at initial surgery by endoprosthesis. The proximal tibia physis showed an average of 86.7% (range, 56.5%-100%) growth of the contralateral side. The mean reduction in tibial length was 1.2 cm (range, 0.5-4.7 cm). Six patients received distraction osteogenesis at a mean length of 5.4 cm (range, 3.0-9.1 cm). Range of knee movement was between 85° and 125°, with an average of 102.5°. The Musculoskeletal Tumor Society 93 score of patients alive was 80.6 (range, 60-90). CONCLUSION: Non-hinged static megaprosthesis followed by LLD correction with shoe lift or staged distraction osteogenesis appears to be an alternative option to treat children with malignant bone tumors around the knee.

12.
World Neurosurg ; 132: 4-6, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31421302

RESUMO

The endoscopic endonasal transsphenoidal (EET) approach for skull base tumors has become increasingly popular. We know that bone defects in the skull base can cause cerebrospinal fluid rhinorrhea, but for patients who need to be intubated through the nose, the tube can enter the brain through a skull base bone defect. Nasogastric tube feeding into the brain is a rare occurrence, and this situation can occur only in the case of a skull base defect. We treated a patient with an unusual complication after the EET approach for pituitary adenoma resection. This particular case suggests that bone defects after EET surgery can not only cause cerebrospinal fluid rhinorrhea but also allow the entry of a nasogastric tube into the brain. For patients with a history of EET surgery, endoscopy-assisted gastric tube implantation can be performed if necessary.


Assuntos
Adenoma/cirurgia , Contusão Encefálica/etiologia , Intubação Gastrointestinal/efeitos adversos , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Base do Crânio/cirurgia , Idoso , Contusão Encefálica/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Nutrição Enteral , Feminino , Humanos , Cavidade Nasal , Neuroendoscopia , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X
13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(7): 850-853, 2019 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-31298002

RESUMO

Objective: To analyze the effectiveness of free vascularized fibula grafts (FVFG) for extensive bone defects after resection of lower limb malignant bone tumors. Methods: Between November 2015 and July 2018, 15 cases of lower limb malignant bone tumors were treated. There were 12 males and 3 females with an average age of 12.3 years (range, 9-21 years). There were 11 cases of osteosarcoma and 4 cases of Ewing's sarcoma. The tumor located at middle femur in 8 cases, lower femur in 4 cases, and middle tibia in 3 cases. The disease duration was 2-6 months (mean, 3.2 months). The tumor was completely removed, and the length of the bone defect was 8-23 cm (mean, 17.7 cm). The bone defect was repaired by FVFG, and combined inactivated tumor bone was used in 8 cases of femoral bone defect. Results: The average operation time was 280 minutes (range, 180-390 minutes). The average blood loss was 310 mL (range, 200-480 mL). All incisions healed by first intention. All patients were followed up 2-24 months with an average of 14.5 months. Bone healing achieved in all patients at 9-18 months (mean, 12.3 months) after operation except 1 patient which was followed up only 2 months. The fibula grafts had active metabolism and the average bone metabolism score was 184 (range, 111-257) in effected side and 193 (range, 127-259) in contralateral side. There was no difference between bilateral sides. The average Enneking score was 24.6 (range, 20-30) at last follow-up. No ankle instability or paralysis of common peroneal nerve occurred. Conclusion: FVFG appeared very efficient in repair of extensive bone defect after resection of lower limb malignant bone tumor.


Assuntos
Neoplasias Ósseas , Transplante Ósseo , Fíbula , Osteossarcoma , Adolescente , Adulto , Neoplasias Ósseas/cirurgia , Criança , Feminino , Fíbula/transplante , Humanos , Extremidade Inferior , Masculino , Osteossarcoma/cirurgia , Tíbia , Adulto Jovem
14.
Thorac Cardiovasc Surg Rep ; 8(1): e20-e23, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31263655

RESUMO

Background The majority of adult primary tracheal tumors are malignant; however, as one type of benign tumors, lipoma is extremely uncommon. Case Description We report a case where lipoma was first misdiagnosed as bronchial asthma, followed by sudden aggravation of dyspnea after trauma, and computed tomography (CT) examination of the neck and chest confirmed a tracheal tumor. Through multiple bronchoscopy interventions and placements of a tracheal stent, little therapeutic benefit was discovered, and resection of the tracheal tumor combined with tracheal end-to-end anastomosis was performed to ultimately achieve a cure. Conclusion Primary tracheal tumors should be highly suspected in patients with recurrent and gradually worsening dyspnea; timely cervical, thoracic CT and bronchoscopy can provide an accurate diagnosis. Surgical radical resection is the only way to cure all benign tracheal tumors such as lipoma.

15.
Chin Med J (Engl) ; 132(14): 1689-1699, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31268909

RESUMO

BACKGROUND: Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain. METHODS: Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group, n = 32) or normal housing conditions (control group, n = 32). At 15 months of age, 16 mice were randomly selected from each group for a series of behavioral tests, including two depression-related tasks (the sucrose preference test and the tail suspension test). Three days following the last behavioral test, eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV)- and calretinin (CR)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons, and the expression levels of vesicular transporters of glutamate-1 (VGluT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC], hippocampus, and amygdala). RESULTS: Behaviorally, compared with the control group, adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ±â€Š1.97% vs. 43.11 ±â€Š2.85%, t(22) = 3.417, P = 0.003) and reduced latency to immobility in the tail suspension test (92.77 ±â€Š25.08 s vs. 33.14 ±â€Š5.95 s, t(25) = 2.394, P = 0.025), but did not affect anxiety-like behaviors and pre-pulse inhibition. At the neurobiologic level, adolescent stress down-regulated PV, not CR, inter-neuron density in the mPFC (F(1, 39) = 19.30, P < 0.001), and hippocampus (F(1, 42) = 5.823, P = 0.020) and altered the CR, not PV, inter-neuron density in the amygdala (F(1, 28) = 23.16, P < 0.001). The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09, all P < 0.004), which suggests stress-induced hypoexcitability in these regions. CONCLUSIONS: Chronic stress during adolescence increased depression-like behaviors in aged mice, which may be associated with the E/I imbalance in stress-sensitive brain regions.


Assuntos
Envelhecimento/fisiologia , Depressão/metabolismo , Depressão/fisiopatologia , Animais , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Transtorno Depressivo/metabolismo , Transtorno Depressivo/fisiopatologia , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Parvalbuminas/metabolismo , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Ácido gama-Aminobutírico/metabolismo
16.
Phytother Res ; 33(8): 2044-2055, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31209937

RESUMO

Mulberry leaf was reported that it has antidiabetic activity, although the mechanisms underlying the function have not been fully elucidated. In the present study, the results of network pharmacology suggested that mulberry leaves could regulate key biological process in development of diabetes, and the process implicates multiple signaling pathways, such as JAK-STAT, MAPK, VEGF, PPAR, and Wnt. Then, the research in vitro indicated that mulberry leaves remarkably ameliorated high glucose-induced epithelial to mesenchymal transition, which was characterized with significant reduction of intracellular reactive oxygen species (ROS) levels as well as downregulation of NADPH oxidase subunits NOX1, NOX2, and NOX4, and it was found to be connected with the ERK1/2 signaling pathway in human tubular epithelial cells (HK-2). Moreover, the results of bioinformatics and the dual luciferase report showed that ZEB1 might be a target gene of miR-302a; decreased miR-302a and increased ZEB1 expressions could significantly promote epithelial to mesenchymal transition. However, mulberry leaves could reverse these modulations. Our results demonstrated that network pharmacology could provide a guidance role for traditional Chinese medicine research, and mulberry leaves could be of benefit in preventing high glucose-induced EMT in HK-2 cells, which proved that it was related to the upregulation of miR-302a by targeting ZEB1 and the inhibition of NADPH oxidase/ROS/ERK1/2 pathway.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Células Epiteliais/metabolismo , Nefropatias/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Morus/química , NADPH Oxidases/metabolismo , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Nefropatias/patologia
17.
World Neurosurg ; 129: 531-537.e1, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207371

RESUMO

BACKGROUND: Primary malignancies involving the mobile spine often require total en bloc spondylectomy with complex mechanical reconstruction, which can be augmented with novel application of the 3-dimensional (3D)-printing technique. CASE DESCRIPTION: A 51-year-old man presented with a 12-month history of progressive thigh pain and lower limb motor function loss, 36 months after T12-L4 instrumentation and fusion for giant cell tumor (GCT) of the L2 vertebrae before referral. The patient subsequently underwent successful curative management of recurrent GCT through denosumab treatment, L1-L3 total en bloc spondylectomy (TES), and a novel lumbopelvic reconstruction method with a 3D-printed lumbar vertebrae and screw-rod system. CONCLUSIONS: To our knowledge, this is the first reported case of multilevel lumbar TES for GCT reconstructed using a 3D-printed vertebrae. Although TES-specifically in the lumbosacral spine-remains challenging due to its unique anatomy and increased risk of neurologic insult, it is an effective option for curative management of GCTs.


Assuntos
Tumor de Células Gigantes do Osso/cirurgia , Impressão Tridimensional , Procedimentos Cirúrgicos Reconstrutivos/métodos , Neoplasias da Coluna Vertebral/cirurgia , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia
18.
J Cell Physiol ; 234(11): 20501-20509, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31074022

RESUMO

The present study aimed to construct prospective models for tumor grading of rectal carcinoma by using magnetic resonance (MR)-based radiomics features. A set of 118 patients with rectal carcinoma was analyzed. After imbalance-adjustments of the data using Synthetic Minority Oversampling Technique (SMOTE), the final data set was randomized into the training set and validation set at the ratio of 3:1. The radiomics features were captured from manually segmented lesion of magnetic resonance imaging (MRI). The most related radiomics features were selected using the random forest model by calculating the Gini importance of initial extracted characteristics. A random forest classifier model was constructed using the top important features. The classifier model performance was evaluated via receive operator characteristic curve and area under the curve (AUC). A total of 1,131 radiomics features were extracted from segmented lesion. The top 50 most important features were selected to construct a random forest classifier model. The AUC values of grade 1, 2, 3, and 4 for training set were 0.918, 0.822, 0.775, and 1.000, respectively, and the corresponding AUC values for testing set were 0.717, 0.683, 0.690, and 0.827 separately. The developed feature selection method and machine learning-based prediction models using radiomics features of MRI show a relatively acceptable performance in tumor grading of rectal carcinoma and could distinguish the tumor subjects from the healthy ones, which is important for the prognosis of cancer patients.

19.
Medicine (Baltimore) ; 98(22): e15787, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145303

RESUMO

Since the standard reconstructive option after large segmental resection of proximal humeral tumors remained controversial, we designed and applied plate-prosthesis composite (PPC) for this circumstance. The purposes of the study were to: compare the functional outcome, implant survival (IS), surgical risk of PPC with those of conventional proximal humeral prosthesis (PHP); and describe the design and reconstructive procedure of PPC.Twenty patients (11 males, 9 females), who received intraarticular proximal humeral resection without preservation of abductor mechanism, were included in this study, with a mean resection length accounting for 72.5% (range, 61.9-81.8%) of whole humeral length. According to the reconstructive options, we categorized patients into PPC group (9 patients) and PHP group (11 patients). PPC was a semi-custom-made endoprosthesis, with modular proximal part same as PHP and custom-made distal part including dumpy stem and composite lateral anatomic plate for distal humerus. The mechanical prosthetic complication was defined as the imaging evidence regardless of reoperation. The IS was defined as the time from surgery to the occurrence of mechanical prosthetic complication.The mean follow-up time was 40.1 months (range, 14-129). The Musculoskeletal Tumor Society 93 scores of PPC and PHP group showed no significant difference (73.3% vs 70.0%, P = .46). Compared to PHP group, PPC group showed significantly lower mechanical prosthetic complication rates (0 vs 45.4%, P = .03) and better IS (86.0 vs 59.3 ±â€Š21.7 months, P = .028). Moreover, the comparison of surgical time (3.2 vs 3.3 hours, P = .60), blood loss (288.9 vs 376.4 mL, P = .15) and perioperative complication rates (11.1% vs 18.2%, P = .58) between 2 groups showed no differences.For reconstruction after large segmental resection of proximal humeral tumors, PPC achieved better IS while maintained similar functional outcome compared to conventional PHP without influencing the complexity and safety of surgery.


Assuntos
Membros Artificiais , Neoplasias Ósseas/cirurgia , Placas Ósseas , Aloenxertos Compostos , Úmero/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Adolescente , Adulto , Idoso , Neoplasias Ósseas/patologia , Criança , Feminino , Humanos , Úmero/patologia , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Ombro/cirurgia , Resultado do Tratamento , Adulto Jovem
20.
Chin Med J (Engl) ; 132(13): 1582-1590, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31045908

RESUMO

BACKGROUND: Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations. One deleterious effect of early-life stress that manifests in later life is sleep disturbance, but this has not been examined in aged mice and the underlying neural mechanisms remain unknown. Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation, this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities. METHODS: Twenty aged male C57BL/6 mice (>16 months, n = 10 per group) were used in this study. During post-natal days 2 to 9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16 to 17 months old, their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition was analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry. Group comparisons were carried out using Student t test or analysis of variances when appropriate. RESULTS: Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 h (697.97 ±â€Š77.47 min vs. 631.33 ±â€Š34.73 min, t17 = 2.376, P = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ±â€Š62.07 min vs. 723.54 ±â€Š39.21 min, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ±â€Š8.98 min vs. 89.39 ±â€Š12.69 min, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1, 16) = 81.04, P < 0.001). CONCLUSION: Early adverse experiences disrupt sleep behaviors in aged mice, which might be associated with the excitatory-inhibitory imbalance in the NAc.


Assuntos
Núcleo Accumbens/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Eletroencefalografia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sono/fisiologia , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Vigília/fisiologia , Ácido gama-Aminobutírico/metabolismo
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