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1.
Ann Oncol ; 31(4): 517-524, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32151507

RESUMO

BACKGROUND: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. PATIENTS AND METHODS: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. RESULTS: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). CONCLUSIONS: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

2.
Synapse ; : e22154, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32189403

RESUMO

Levetiracetam (LEV) is a widely prescribed antiepileptic drug (AED), but its actions on neuronal function are not fully characterized. Since this drug is believed to enter neurons by binding to a vesicular protein during endocytosis, we used motor axons of the crayfish opener neuromuscular junction to examine potential impacts of LEV on axon excitability. Two electrode current clamp (TECC) from the inhibitory axon of the opener showed that LEV reduced action potential (AP) amplitude (APamp ) and suppressed synaptic transmission, although the latter occurred with a longer delay than the reduction in APamp . Comparison of antidromic and orthodromic conducting APs in LEV suggested that this drug preferentially reduced excitability of the proximal axon, despite the expectation that it entered the axon at the terminals and should affect the distal branches first. Results presented here suggest that LEV modulates axonal excitability, which may in turn contribute to its antiepileptic effects.

3.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): 209-214, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32164090

RESUMO

Objective: To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). Methods: 30 patients infected with novel coronavirus referred to jianghan university hospital between January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, laboratory investigation and Radiographic features. Results: The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine blood test revealed WBC<4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte count<1.0×10(9)/L occurred in 12 petients (40%),abnormal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white blood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and albumin levels in peripheral blood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed bilateral pneumonia,4 patients (13.33%) showed bilateral multiple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and bilateral pneumonia were both increased in the patients infected in unprotected period. Conclusion: Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged, white blood cell count, lymphocyte count, D-dimer and albumin level significantly changed and were prone to be complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus , Febre , Pessoal de Saúde , Transmissão de Doença Infecciosa do Paciente para o Profissional , Pneumonia Viral , Adulto , Índice de Massa Corporal , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Tosse/etiologia , Dispneia/etiologia , Feminino , Febre/classificação , Febre/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Contagem de Leucócitos , Fígado/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica , Fatores de Tempo , Adulto Jovem
4.
Carbohydr Polym ; 236: 116058, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32172873

RESUMO

Three kinds of methods based on extrusion and 3D printing and different acidic solutions (formic acid (FA), acetic acid (AA), glycolic acid (GA) and lactic acid (LA)) were applied for manufacturing the CS ducts. The tensile properties and preliminary cytotoxicity were measured for selecting the optimal ratio of CS slurry. The 3D printability of CS slurry was also studied. The tensile strength, Young's modulus, and fracture strain were tested for evaluating the degree of mechanical matching to soft-tissue. The optimal solvent to CS was 30 wt.% GA solution. The CS slurry possessing shear-thinning properties was suitable for 3D printing. The tensile strength, Young's modulus, and fracture strain of the CS rods were 10.98 ±â€¯0.61 MPa, 12.38 ±â€¯1.19 MPa, and 146.03 ±â€¯15.05 %, correspondingly. The CS ducts manufactured by 3D printing had an excellent mechanical matching to soft-tissue, outstanding biocompatibility and have great potential for soft-tissue restorations.

5.
Gene Ther ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111977

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

6.
AJNR Am J Neuroradiol ; 41(3): 400-407, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32029466

RESUMO

BACKGROUND AND PURPOSE: Gliomas are highly heterogeneous tumors, and optimal treatment depends on identifying and locating the highest grade disease present. Imaging techniques for doing so are generally not validated against the histopathologic criterion standard. The purpose of this work was to estimate the local glioma grade using a machine learning model trained on preoperative image data and spatially specific tumor samples. The value of imaging in patients with brain tumor can be enhanced if pathologic data can be estimated from imaging input using predictive models. MATERIALS AND METHODS: Patients with gliomas were enrolled in a prospective clinical imaging trial between 2013 and 2016. MR imaging was performed with anatomic, diffusion, permeability, and perfusion sequences, followed by image-guided stereotactic biopsy before resection. An imaging description was developed for each biopsy, and multiclass machine learning models were built to predict the World Health Organization grade. Models were assessed on classification accuracy, Cohen κ, precision, and recall. RESULTS: Twenty-three patients (with 7/9/7 grade II/III/IV gliomas) had analyzable imaging-pathologic pairs, yielding 52 biopsy sites. The random forest method was the best algorithm tested. Tumor grade was predicted at 96% accuracy (κ = 0.93) using 4 inputs (T2, ADC, CBV, and transfer constant from dynamic contrast-enhanced imaging). By means of the conventional imaging only, the overall accuracy decreased (89% overall, κ = 0.79) and 43% of high-grade samples were misclassified as lower-grade disease. CONCLUSIONS: We found that local pathologic grade can be predicted with a high accuracy using clinical imaging data. Advanced imaging data improved this accuracy, adding value to conventional imaging. Confirmatory imaging trials are justified.

7.
J Appl Microbiol ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32091657

RESUMO

AIMS: Paclitaxel is a type of broad-spectrum anticancer drug in short supply. The price of acetyl-CoA (17 709 677·4 USD mol-1 ), which is the acetyl group donor for the enzymatic synthesis of the intermediate, baccatin Ⅲ, is still the bottleneck of the mass production of paclitaxel. This study reports a novel acetyl group donor, which could substantially reduce the cost of production. METHODS AND RESULTS: In this study, a substrate spectrum with 14 kinds of representative acetyl-donor substitutes predicted by computer-aided methods was tested in a 10-deacetylbaccatin Ⅲ-10-O-acetyltransferase (DBAT) heterogeneous-expressed open-whole-cell catalytic system. The results of computer prediction and experimental analysis revealed the rule of the acetyl-donor compounds based on this substrate spectrum. N-acetyl-d-glucosamine (30·95 USD mol-1 , about 572 202-fold cheaper than acetyl-CoA) is selected as a suitable substitute under the rule. The yield when using N-acetyl-d-glucosamine as acetyl donor in open-whole-cell catalytic system was 2·13-fold of that when using acetyl-CoA. In the in vivo system, the yield increased 24·17%, which may indicate its cooperation with acetyl-CoA. CONCLUSION: The success of open-whole-cell synthesis and in vivo synthesis of baccatin Ⅲ by adding N-acetyl-d-glucosamine as acetyl substrate demonstrates that it is a useful substrate to improve the yield of baccatin Ⅲ. SIGNIFICANCE AND IMPACT OF THE STUDY: All these findings provided a potential acetyl-donor substitute for acetyl-CoA, as well as a low cost and efficient method of preparing paclitaxel through baccatin Ⅲ semi-synthesis.

9.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(0): E016, 2020 Feb 17.
Artigo em Chinês | MEDLINE | ID: mdl-32062957

RESUMO

Objective: To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). Methods: 30 patients infected with novel coronavirus referred to jianghan university hospital between January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, laboratory investigation and Radiographic features. Results: The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine blood test revealed WBC <4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte count <1.0×10(9)/L occurred in 12 petients (40%),abnormal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white blood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and albumin levels in peripheral blood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed bilateral pneumonia,4 patients (13.33%) showed bilateral multiple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and bilateral pneumonia were both increased in the patients infected in unprotected period. Conclusion: Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged , white blood cell count, lymphocyte count, D-dimer and albumin level significantly changed and were prone to be complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.

10.
Nanoscale ; 12(4): 2587-2595, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31939948

RESUMO

Vortex-mediated magnetization reversal in individual ultra-small (∼100 nm) ferromagnetic particles at low temperatures is studied by nanoSQUID magnetometry. At zero applied bias field, the flux-closure magnetic state (vortex) and the quasi uniform configuration are bi-stable. This stems from the extremely small size of the nanoparticles that lies very close to the limit of single-domain formation. The analysis of the temperature-dependent (from 0.3 to 70 K) hysteresis of the magnetization allows us to infer the nature of the ground state magnetization configuration. The latter corresponds to a vortex state as also confirmed by electron holography experiments. Based on the simultaneous analysis of the vortex nucleation and annihilation data, we estimate the magnitude of the energy barriers separating the quasi single-domain and the vortex state and their field dependence. For this purpose, we use a modified power-law scaling of the energy barriers as a function of the applied bias field. These studies are essential to test the thermal and temporal stability of flux-closure states stabilized in ultra-small ferromagnets.

11.
Zhonghua Yi Xue Za Zhi ; 100(2): 136-140, 2020 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-31937054

RESUMO

Objective: Tuberous sclerosis complex (TSC) is a multi-system disease with TSC1 and TSC2 genes as the pathogenic genes. The purpose of our study was to analyze the gene mutation in patients with TSC with epilepsy as the main clinical manifestation. The relationship between genotype and phenotype, scalp EEG in patients was analyzed. Methods: The peripheral blood was extracted from 43 patients and their families. TSC gene was detected by second-generation sequencing. Long-term video EEG monitoring and MRI examination were performed to determine the onset area, seizure type and location of nodules. Results: 39 patients had TSC gene mutation, 4 patients did not detect the gene mutation.11 had TSC1 mutations and 28 had TSC2 mutations. 22 mutations were de novo. Patients with TSC2 mutations had earlier seizure and more nodules than patients with TSC1 mutations, but no significant difference in intelligence and spasm were observed. 28 patients had focal origin of scalp EEG, of which 85.7% of TSC2 mutations patients had focal origin. Conclusions: Patients of TSC2 mutations always has an early onset age. Although MRI shows multiple nodules, the onset of EEG is mainly focal origin.


Assuntos
Esclerose Tuberosa , Análise Mutacional de DNA , Eletroencefalografia , Genótipo , Humanos , Mutação , Fenótipo , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa
12.
Osteoarthritis Cartilage ; 28(3): 363-374, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926268

RESUMO

OBJECTIVE: To explore whether Mitofusin 2 (Mfn2) is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). METHODS: We detected the protein content of Mfn2 in degenerated human nucleus pulposus (NP) tissues and investigated the effects of Mfn2 knockdown and Mfn2 overexpression on rat nucleus pulposus cells (NPCs) under oxidative stress by using a range of biological techniques. Afterwards, we confirmed the effects of Mfn2 overexpression on NPCs in vivo and further evaluated the therapeutic action of adenovirus (AV)-Mfn2 injection in a rodent IVDD model. RESULTS: Mfn2 expression was decreased in human NP tissues during IVDD. Mfn2 knockdown aggravated the impairment of autophagic flux, mitochondrial dysfunction and cellular apoptosis in rat NPCs after Tert-Butyl hydroperoxide (TBHP) treatment, while Mfn2 overexpression significantly reversed these alterations. Besides, Mfn2 overexpression promoted an ROS (reactive oxygen species)-dependent mitophagy via PINK1 (PTEN-induced putative kinase 1)/Parkin pathway in TBHP-treated NPCs. Inhibition of autophagy with chloroquine (CQ) disordered the protective effects of Mfn2 overexpression on NPCs. Furthermore, Mfn2 overexpression in discs by AV-Mfn2 injection ameliorated the development of IVDD in rats. CONCLUSION: Mfn2 repression is deeply involved in the pathogenesis of IVDD with its impairment on autophagy, leading to the aggravation of mitochondrial dysfunction and apoptotic cell death, which ought to be a promising therapeutic target for IVDD.

13.
Osteoarthritis Cartilage ; 28(2): 137-145, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629022

RESUMO

OBJECTIVE: Tramadol has been widely used among patients with osteoarthritis (OA); however, there is paucity of information on its cardiovascular risk. We aimed to examine the association of tramadol with risk of myocardial infarction (MI) among patients with OA. DESIGN: Among OA patients aged 50-90 years without history of MI, cancer, or opioid use disorder in The Health Improvement Network database in the United Kingdom (2000-2016), three sequential propensity-score matched cohort studies were assembled, i.e., (1) patients who initiated tramadol or naproxen (negative comparator); (2) patients who initiated tramadol or diclofenac (positive comparator); and (3) patients who initiated tramadol or codeine (a commonly used weak opioid). The outcome was incident MI over six-months. RESULTS: Among tramadol and naproxen initiators (n = 33,024 in each cohort), 77 (4.8/1000 person-years) and 46 (2.8/1000 person-years) incident MI occurred, respectively. The rate difference (RD) and hazard ratios (HR) for incident MI with tramadol initiation were 1.9 (95% confidence interval [CI] 0.6 to 2.3)/1000 person-years and 1.68 (95% CI 1.16 to 2.41) relative to naproxen initiation, respectively. Among tramadol and diclofenac initiators (n = 18,662 in each cohort), 58 (6.4/1000 person-years) and 47 (5.1/1000 person-years) incident MIs occurred, respectively. The corresponding RD and HR for incident MI were 1.2 (95%CI -2.1 to 14.1)/1000 person-years and 1.24 (95%CI 0.84 to 1.82), respectively. Among tramadol and codeine initiators (n = 42,722 in each cohort), 127 (6.1/1000 person-years) and 103 (5.0/1000 person-years) incident MI occurred, respectively, and the corresponding RD and HR were 1.1 (95%CI:-0.3 to 2.5)/1000 person-years and 1.23 (95%CI:0.95 to 1.60), respectively. CONCLUSIONS: In this population-based cohort of patients with OA, the six-month risk of MI among initiators of tramadol was higher than that of naproxen, but comparable to, if not lower than, those of diclofenac or codeine.

15.
J Nutr Health Aging ; 24(1): 107-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31886816

RESUMO

OBJECTIVES: We explored the associations between depressive symptoms and supplemental calcium and vitamin D intake in older adults. DESIGN: This was a prospective cohort study. PARTICIPANTS: 8,527 older adults aged ≥60 years from Zhejiang Major Public Health Surveillance Program (ZPHS) without depressive symptoms at baseline survey. MEASUREMENTS: Participants were divided into non-supplementation, calcium (Ca), vitamin D, and calcium plus vitamin D (CaD) groups based on their supplemental intake during the past year. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Binary logistic regression analyses were performed to examine the association between depressive symptoms and supplemental intake. RESULTS: When compared to the non-supplementation group, the Ca group exhibited a significant odds ratio (OR) of 0.731 (95% CI: 0.552-0.967, P=0.028). After adjusting for age, sex, and Ca food sources, the OR was even smaller for the CaD group (OR: 0.326; 95% CI: 0.119-0.889, P=0.029). Additionally, our results indicated that taking Ca supplements ≥4 days/week yielded a significant OR of 0.690 (95% CI: 0.492-0.968) after full adjustment. Taking CaD supplements ≥4 days/week yielded a significant OR of 0.282 (95% CI: 0.089-0.898) after adjusting for age, sex, and Ca food sources. CONCLUSIONS: Supplemental intake of Ca or CaD ≥4 days/week can decrease the risk of depressive symptoms in older adults, although CaD supplements may be more effective.

16.
J Colloid Interface Sci ; 560: 34-39, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31648084

RESUMO

Transition metal oxides show great potential as electrocatalysts, owing to the low cost and rich chemical states. However, the limited surface areas, low intrinsic activity and poor hydrogen evolution reaction (HER) activity greatly restrict the application for overall water splitting. Herein, we have constructed S doped NiCo2O4 nanosheet arrays by Ar plasma (Ar-NiCo2O4|S) to enhance active sites and boost catalytic kinetics. Consequently, the Ar-NiCo2O4|S shows the improved performances for HER and oxygen evolution reaction (OER). Further, as bifunctional electrocatalysts, Ar-NiCo2O4|S exhibit a voltage of 1.63 V at 10 mA cm-2, as well as good stability.

17.
Zhonghua Fu Chan Ke Za Zhi ; 54(12): 826-832, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874472

RESUMO

Objective: To analyze risk factors, cardiovascular complications, time of death, gestational age of delivery and offspring outcomes in the maternal deaths with cardiovascular diseases (CVD). Methods: Totally 4 112 cases of pregnant women with CVD in Shanghai obstetric heart disease intensive care unit within 26 years (from January 1993 to December 2018) were collected, and 20 maternal deaths within these cases were analyzed retrospectively. Results: (1) Among the 20 deaths, structural heart diseases accounted for 90% (18/20), pregnancy induced heart diseases was 10% (2/20) while there was no dysfunctional heart disease. The mortality of pregnant women with CVD was 0.486% (20/4 112). (2) The following risk factors were common in these women, getting pregnant without counselling (95%, 19/20) , New York Heart Association classⅢ or Ⅳcardiac function (70%, 14/20), complicated with pulmonary hypertension (75%, 15/20) and prior heart events (60%, 12/20). And 85% (17/20) deaths occurred in puerperium, 15% (3/20) occurred before labor,while no death occurred during labor. And 65% (13/20) deaths died due to heart failure, 20% (4/20) deaths were due to pulmonary hypertension crisis, 5% (1/20) died on sudden cardiac arrest, rupture of aortic dissection and sudden death, respectively. Conclusions: Women with CVD should get pregnant after strict evaluation. Pulmonary hypertension is one of the most severe contraindications to pregnancy, especially in patients with moderate to severe pulmonary hypertension. The puerperium period is a critical period that threatens the safety of these patients. Since heart failure is the most common cause of death, it is necessary to prevent and treat heart failure and to monitor heart function dynamically, especially in those with structural abnormal heart diseases. Moreover, it is also of importance to standardize antenatal care and to identify the severity of heart diseases in time.


Assuntos
Doenças Cardiovasculares/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Morte Materna , Mortalidade Materna , Complicações Cardiovasculares na Gravidez/etiologia , Adulto , Causas de Morte , China/epidemiologia , Feminino , Humanos , Serviços de Saúde Materna/organização & administração , Mortalidade Materna/tendências , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/mortalidade , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco
18.
Eur Rev Med Pharmacol Sci ; 23(23): 10453-10458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31841199

RESUMO

OBJECTIVE: Mutations in phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a tumor suppressor gene, lead to altered sensitivity to drugs and radiation in various types of cancer. Restoring PTEN expression in tumor cells can increase radiosensitivity by inhibiting the repair of DNA double-strand breaks (DSBs). Thus, determining the mechanism of action of this protein may lead to novel therapeutic strategies. MATERIALS AND METHODS: In this study, we transduced U251 cells with a lentiviral vector expressing PTEN to examine the mechanism of radiosensitization. Specifically, we examined the formation of radiation-induced DNA DSBs and apoptosis, as well as the expression of several proteins involved in repairing DSBs (p53, ataxia-telangiectasia mutated, DNA-dependent protein kinase C, Ku70-80). RESULTS: Our results showed that PTEN transduction sensitized U251 cells to X-rays, increasing the number of DSBs per cell and fraction of cells undergoing apoptosis. Additionally, the average size of γH2AX nuclear foci was increased following irradiation. These findings were accompanied by a PTEN-dependent irradiation-independent increase in p53 levels and decrease in phosphorylated Ku70/80 levels. CONCLUSIONS: Our results suggest that PTEN affects radiosensitivity by reducing DSB repair and by enhancing the p53 pathway, leading to increased apoptosis.

19.
Eur J Neurol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31770481

RESUMO

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) remains unclear. Voxel-based morphometry (VBM) detects local structural differences in brain tissue such as grey matter volume (GMV) between groups, which is helpful in understanding the pathophysiology of PD. Published VBM studies of GMV changes in PD have shown inconsistent results. Therefore, a voxel-wise meta-analysis of VBM studies was conducted to detect consistent GMV changes in PD. METHODS: The published literature was searched comparing whole-brain GMV between PD patients and healthy controls (HCs) using VBM. Coordinates were extracted for the clusters of significant GMV differences between PD patients and HCs. The meta-analysis was performed by seed-based d mapping software. RESULTS: A total of 63 studies with 2867 PD patients and 1990 HCs were included. Significant GMV reductions in some brain regions were detected in PD patients, which were involved in the basal ganglia, theory of mind, vocal and visual networks. These findings remained largely unchanged in the jackknife sensitivity analysis, and no significant heterogeneity or publication bias was detected. CONCLUSIONS: Parkinson's disease patients have GMV reductions in a number of brain regions involved in specific networks. These findings provide morphological evidence for the pathophysiology of PD.

20.
Zhonghua Yan Ke Za Zhi ; 55(11): 834-841, 2019 Nov 11.
Artigo em Chinês | MEDLINE | ID: mdl-31715680

RESUMO

Objective: To summarize the clinical and pathological characteristics of IgG4-related ophthalmic disease (IgG4-ROD) involving the lacrimal gland. Methods: A retrospective case series study. Forty cases (56 eyes) of lacrimal gland lesions were collected in Tianjin Eye Hospital from January 2003 to January 2018 and confirmed by histopathology as lymphocyte and plasma cell infiltration with fibrosis of lacrimal gland tissue, excluding lymphoma, epithelial tumor, mesenchymal tumor and metastasis tumor. The clinical manifestations, serological and imaging examination of the patients were analyzed. Meanwhile, HE staining and immunohistochemical staining of IgG and IgG4 were performed on the pathological specimens. According to the diagnostic criteria, the cases were divided into the IgG4-ROD group and the non-IgG4-ROD group. The clinical and pathological characteristics of the two groups were statistically analyzed by Pearson chi-square and signed-rank test. Results: In the 40 cases (56 eyes), there were 15 cases (25 eyes) of IgG4-ROD and 25 cases (31 eyes) of non-IgG4-ROD. Statistically significant differences were observed between the two groups in the clinical and pathological characteristics (all P<0.05). About the distribution of eyes position, there were 10 binocular cases and 5 monocular cases in the IgG4-ROD group, and 6 binocular cases and 19 monocular cases in non-IgG4-ROD group (χ2=7.111).There were 21 eyes in the IgG4-ROD group and 5 eyes in the non-IgG4-ROD group about ptosis (χ2=25.631), 4 eyes in the IgG4-ROD group and 21 eyes in the non-IgG4-ROD group about ocular protrusion (χ2=14.992), 23 eyes in the IgG4-ROD group and 15 eyes in the non-IgG4-ROD group about the clear boundary of the tumor (χ2=12.069), 4 eyes in the IgG4-ROD group and 18 eyes in the non-IgG4-ROD group about the involvement of other orbital tissues (χ2=10.266) and 7 cases in the IgG4-ROD group and 3 cases in the non-IgG4-ROD group about the association with other systemic diseases (χ2=6.009). Compared with the non-IgG4-ROD group, the IgG4-ROD group had a heavier lymphocyte and plasma cell infiltration (+++,++,+; 10, 4, 1 vs. 6, 5, 12 eyes, Z=-3.153), and more lymphoid follicles (+++,++,+; 3, 6, 4 vs. 1, 2, 7 eyes, Z=-3.339), interstitial fibrosis was mostly striate (10 vs. 5 eyes, χ2=8.711), and there were a large number of IgG4+ plasma cells [96 (67, 135) vs. 4 (0, 12) cells per high power field, Z=-5.271] and ratio of IgG4+ plasma cells/IgG+ plasma cells [0.570 (0.500, 0.754) vs. 0.046 (0.000, 0.143), Z=-5.268, all P<0.05). Among the 10 cases of IgG4-ROD with serological examination, 9 cases showed elevated serum in IgG and IgG4. The ultrasonography and CT findings showed the lacrimal gland lesions in the IgG4-ROD group were mostly spindle or kidney shaped with clear boundaries, while the lesions in non-IgG4-ROD were mostly round or irregular with unclear boundaries. Conclusions: The lacrimal gland lesions of IgG4-ROD are characterized by bilaterally spindle or kidney shaped enlargement with clear boundaries. They are more associates with other systemic diseases. The pathological characteristics are a large number of IgG4+ plasma cells infiltration among the lacrimal gland tissue, interstitial striate fibrosis and a large number of lymphoid follicles. (Chin J Ophthalmol, 2019, 55: 834-841).


Assuntos
Doença Relacionada a Imunoglobulina G4/fisiopatologia , Doenças do Aparelho Lacrimal/fisiopatologia , Humanos , Aparelho Lacrimal/fisiopatologia , Plasmócitos/patologia , Estudos Retrospectivos
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