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Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.
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Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Síndromes Mielodisplásicas , Segunda Neoplasia Primária , Humanos , Estudos Retrospectivos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/terapia , Prognóstico , Síndromes Mielodisplásicas/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Indução de Remissão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Objective: To explore the repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness. Methods: A retrospective observational study was conducted. From January 2020 to May 2022, 5 patients admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University and 4 patients admitted to the Department of Burns and Plastic Surgery of Chenzhou First People's Hospital with complex facial defect wounds involving paranasal sinuses met the inclusion criteria, including 6 males and 3 females, aged 35-69 years, including 4 patients with titanium mesh exposure combined with paranasal sinuses injury and 5 patients with tumor involving paranasal sinuses. After an adequate assessment of the damage by a multiple discipline team, titanium mesh removal, paranasal sinus debridement, and paranasal sinus mucosa removal were performed in patients with exposed titanium mesh, and radical tumor resection was performed in patients with tumors, with postoperative skin and soft tissue defects areas of 5.0 cm×2.5 cm to 18.0 cm×7.0 cm, anterior paranasal sinus wall defects/absence areas of 3 cm×2 cm to 6 cm×4 cm, and sinus cavity depths of 1 to 4 cm. Depending on the perforator course of the descending branch of the lateral circumflex femoral artery, the anterolateral femoral chimeric flap or anterolateral femoral myocutaneous flap (with flap area of 9 cm×4 cm to 19 cm×8 cm, muscle size of 5 cm×3 cm×3 cm to 11 cm×6 cm×3 cm) was transplanted to repair the defect, and the donor site wound was sutured directly. The type of tissue flap transplanted, the blood vessel of the recipient area, and the vascular anastomosis way during the operation, the recovery of the donor and recipient areas and the occurrence of complications after operation were observed. The appearance and blood supply of the recipient area and the recurrence of ulcers and tumors were followed up. Results: The anterolateral femoral myocutaneous flap transplantation was performed in 6 patients, and the anterolateral femoral chimeric flap transplantation was performed in 3 patients. The blood vessels in recipient areas were facial arteries and veins in 3 cases and superficial temporal arteries and veins in 6 cases. The superficial temporal arteries and veins were bridged with blood vessels in tissue flaps by flow-through way in 2 patients, and end-to-end anastomosis of blood vessels in donor and recipient areas was performed in 7 patients. After operation, all the tissue flaps survived, and the facial defect wounds were well repaired without cerebrospinal fluid leakage or paranasal sinus secretion leakage, no intracranial infection occurred, and the wounds in donor areas were healed well. Follow-up of 6-35 months after operation showed that all the patients had good blood supply in the recipient area, and the shape was acceptable; 4 patients with exposed titanium mesh had no recurrence of ulceration, and 5 patients with tumor had no local tumor recurrence or metastasis. Conclusions: Based on an adequate assessment of the extent of paranasal sinuses involved in the facial wound and the nature of the defect, good clinical effects can be achieved by using the anterolateral femoral muscle flap or the anterolateral femoral chimeric flap transplantation to repair complex facial defect wounds with open paranasal sinuses.
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Queimaduras , Traumatismos Faciais , Retalho Miocutâneo , Neoplasias , Seios Paranasais , Retalho Perfurante , Lesões dos Tecidos Moles , Feminino , Humanos , Masculino , Queimaduras/cirurgia , Traumatismos Faciais/cirurgia , Retalho Miocutâneo/cirurgia , Neoplasias/cirurgia , Seios Paranasais/cirurgia , Retalho Perfurante/transplante , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Titânio , Resultado do Tratamento , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Objective: To quantitatively evaluate the clinical effect of platelet-rich plasma(PRP) intra-articular injection for early and middle stage knee osteoarthritis(KOA) treatment by 3.0T MRI T2 mapping sequence. Methods: Clinical data of 26 patients with early or middle stage KOA who received treatment from April to December 2021 at Department of Orthopaedic Surgery,the Second Affiliated Hospital,Zhengzhou University were retrospectively analyzed. In total, 8 patients were male and 18 were female,with age of (66.4±12.0)years(range:51 to 94 years). Four patients were bilateral KOA and 22 patients were unilateral KOA.All patients received PRP intra-articular injection. Patients underwent 3.0T MRI T2 mapping sequence scanning pre-treatment,3-month-after and 6-month-after treatment respectively. Those were used to measure and compare T2 values of medial and lateral femoral articular surface and patellofemoral articular surface. Visual analogue scale(VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded and evaluated. The results were analyzed using repeated measure ANOVA followed by Bonferroni multiple comparison test.The correlation between WOMAC scores and T2 values at pre-treatment and 6 months post-treatment was analyzed using Pearson correlation test. Results: After treatment, the patients' International Cartilage Regenerationï¼Joint Preservation Society(ICRS) classification were partly improved(one case improved from grade â ¢ to grade â ¡, one case improved from grade â ¡ to grade â ),and all patients generally improved after treatment in clinical symptoms. Compared with pre-treatment,VAS and WOMAC scores of grade â ,â ¡,and â ¢ of 6-month after treatment were declined significantly(all P<0.05).The T2 values of articular cartilage declined to varying degrees(the decrease in T2 values was about 2.06 ms in grade â , 2.66 ms in grade â ¡, and 3.72 ms in grade â ¢).Three-month (VAS:4.8±1.3,WOMAC:21.5±4.0) and 6-month (VAS:4.2±1.4,WOMAC:17.2±2.9) after treatment, the VAS and WOMAC score were significantly higher than those before treatment (VAS:6.0±1.2, WOMAC:29.0±2.3) (F=48.846, F=346.746;both P<0.01). Multiple comparisons showed a statistically significant difference between pre-treatment and post-treatment VAS (P<0.01) and it also was significantly different between 3-month and 6-month post-treatment (P<0.01).At 3- and 6-month after treatment,WOMAC scores were significantly different from before treatment.And it also was significantly different between 3-month and 6-month post-treatment (P<0.01).There was a statistically significant improvement in T2 values of patellofemoral articular surface, medial and lateral femoral articular surface at pre-treatment((44.64±4.02)ms,(44.17±3.64)ms and(43.53±3.91)ms) and 3-month ((43.19±3.91)ms,(43.24±3.34)ms and (42.47±3.80)ms), 6-month ((41.49±3.64)ms,(41.83±3.15)ms and (41.10±3.42)ms) after treatment(F=148.845,F=73.657,F=86.268;all P<0.01).The results of the multiple comparisons showed a statistically significant difference in the T2 values of medial and lateral femoral articular surface and patellofemoral articular surface at each time point(all P<0.01).The Pearson correlation analysis suggested that the WOMAC score at pre-treatment was positively correlated with the medial condyle (r=0.856,P<0.01) and the patellofemoral joint surface T2 values (r=0.840,P<0.01);The WOMAC score at 6-month post-treatment was positively correlated with the medial condyle (r=0.731,P<0.01) and the patellofemoral joint surface T2 values (r=0.691,P<0.01). Conclusions: In the treatment of early and mid-stage KOA,MRI T2 mapping sequences are able to indicate the integrity of cartilage morphology and quantitatively evaluate cartilage repair. PRP has a good therapeutic effect on cartilage repair and reconstruction.
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Procedimentos Ortopédicos , Osteoartrite do Joelho , Plasma Rico em Plaquetas , Humanos , Feminino , Masculino , Osteoartrite do Joelho/terapia , Estudos Retrospectivos , Imageamento por Ressonância MagnéticaRESUMO
The most common complications after pancreaticoduodenectomy include pancreatic fistula, biliary fistula, delayed gastric emptying, bleeding, and abdominal infection. Although advances in surgery have led to a significant decrease in perioperative mortality in recent years, the risk of complications after pancreaticoduodenectomy remains. Thus, prevention and treatment of various complications are important to improve the prognosis of patients.
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Fístula Pancreática , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/efeitos adversos , Fístula Pancreática/etiologia , Pancreatectomia , Anastomose Cirúrgica/efeitos adversos , Tempo de Internação , Complicações Pós-Operatórias/etiologiaRESUMO
Findings from epidemiological studies suggest that occupational exposure to whole-body vibration (WBV) may increase the risk of miscarriage and contribute to a reduction in fertility rates in both men and women. However, workers exposed to WBV may also be exposed to other risk factors that contribute to reproductive dysfunction. The goal of this experiment was to examine the effects of WBV on reproductive physiology in a rat model. Male and female rats were exposed to WBV at the resonant frequency of the torso (31.5 Hz, 0.3 g amplitude) for 4 hr/day for 10 days. WBV exposure resulted in a significant reduction in number of developing follicles, and decrease in circulating estradiol concentrations, ovarian luteinizing hormone receptor protein levels, and marked changes in transcript levels for several factors involved in follicular development, cell cycle, and steroidogenesis. In males, WBV resulted in a significant reduction in spermatids and circulating prolactin levels, elevation in number of males having higher circulating testosterone concentrations, and marked alterations in levels of transcripts associated with oxidative stress, inflammation, and factors involved in regulating the cell cycle. Based upon these findings data indicate that occupational exposure to WBV contributes to adverse alterations in reproductive physiology in both genders that may lead to reduction in fertility.
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Prolactina , Vibração , Animais , Estradiol , Feminino , Masculino , Ratos , Receptores do LH , TestosteronaRESUMO
OBJECTIVE: To study the protective effect of tacrolimus on vascular endothelium injured by oxidized low-density lipoprotein (ox-LDL) and its mechanism. MATERIALS AND METHODS: Human umbilical vein endothelial cells were used as objects of study, and divided into control group, tacrolimus group and autophagy inhibition group. Control group received no ox-LDL, while tacrolimus group and autophagy inhibition group were treated with ox-LDL (100 µg/mL) for 3 h. Tacrolimus group was pre-treated with tacrolimus (100 nM) for 0.5 h, and the autophagy inhibition group was pre-treated with 3-methyladenine (3-MA) (10 mM) and tacrolimus (100 nM) for 0.5 h. The cell viability was detected via cell counting kit 8 (CCK8) assay, the cell apoptosis ratio was detected via flow cytometry and Hoechst staining, and the releases of superoxide dismutase (SOD), reactive oxygen species (ROS) and other cytokines were detected using the kit. Moreover, the autophagy level was detected via LC3 fluorescence staining, and the autophagy- and apoptosis-related molecules were detected via polymerase chain reaction (PCR) and Western blotting. RESULTS: In the absence of ox-LDL, neither tacrolimus nor 3-MA had an effect on the cell viability. After the addition of ox-LDL, the cell viability was significantly decreased, whereas tacrolimus could alleviate such damage to cells. Flow cytometry and Hoechst staining proved that tacrolimus could reduce the proportion of apoptotic cells induced by ox-LDL, while PCR and Western blotting confirmed the decreased expression of apoptosis-related proteins in tacrolimus group. 3-MA could up-regulate the ratio of apoptosis and the expressions of apoptosis-related proteins. The detection of SOD and ROS showed that ox-LDL could induce the cell oxidative stress injury, whereas tacrolimus could inhibit such an effect. The addition of 3-MA inhibited the effect of tacrolimus. Besides, LC3 fluorescence staining, PCR and Western blotting revealed that ox-LDL could induce the autophagy, while tacrolimus could enhance the autophagy. After the addition of 3-MA, the intracellular autophagy level was significantly inhibited. CONCLUSIONS: Tacrolimus protects vascular endothelial cells from ox-LDL damage through inducing the autophagy.
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Autofagia/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Lipoproteínas LDL/efeitos adversos , Tacrolimo/farmacologia , Adenina/análogos & derivados , Adenina/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Regulação para CimaRESUMO
Percussive riveting is the primary process for attaching the outer sheet metal "skins" of an aircraft to its airframe. Workers using manually-operated riveting tools (riveting hammers and rivet bucking bars) are exposed to significant levels of hand-transmitted vibration (HTV) and are at risk of developing components of hand-arm vibration syndrome (HAVS). To protect workers, employers can assess and select riveting tools that produce reduced HTV exposures. Researchers at the National Institute for Occupational Safety & Health (NIOSH) have developed a laboratory-based apparatus and methodology to evaluate the vibrations of rivet bucking bars. Using this simulated riveting approach, this study investigated the effects of feed force on the vibrations of several typical rivet bucking bars and that transmitted to the bucking bar operator's wrist. Five bucking bar models were assessed under three levels of feed force. The study results demonstrate that the feed force can be a major influencing factor on bucking bar vibrations. Similar feed force effects were observed at the bucking bar operator's wrist. This study also shows that different bucking bar designs will respond differently to variations in feed force. Some bucking bar designs may offer reduced vibration exposures to the bar operator's fingers while providing little attenuation of wrist acceleration. Knowledge of how rivet bucking bar models respond to riveting hammer vibrations can be important for making informed bucking bar selections. The study results indicate that, to help in the appropriate selection of bucking bars, candidate bar models should be evaluated at multiple feed force levels. The results also indicate that the bucking bar model, feed force level, or the bucking bar operator have no meaningful effects on the vibration excitation (riveting hammer), which further suggests that the test apparatus proposed by NIOSH researchers meets the basic requirements for a stable vibration source in laboratory-based bucking bar vibration assessments. This study provides relevant information that can be used to help develop a standardized laboratory-based bucking bar evaluation methodology and to help in the selection of appropriate bucking bars for various workplace riveting applications. RELEVANCE TO INDUSTRY: Because the feed force level can affect HTV exposures to bucking bar operators, the feed force required for specific riveting operations should be an important consideration when selecting bucking bar models. This study provides useful information about bucking bar responses to riveting hammer vibrations; this knowledge can improve bucking bar selections.
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OBJECTIVES: To analyze the related pathogenicity gene mutations in a sudden death of hypertrophic cardiomyopathy ï¼HCMï¼ on whole exome level. METHODS: Whole exome sequencing ï¼WESï¼ was been performed on a sudden death case sample with pathological features of HCM by Illumina® Hiseq 2500 platform. Using hg19 as the reference sequences, the sequencing data were analyzed. Suspicious single nucleotide variants ï¼SNVï¼ were screened, and the conservatism and function were analyzed by the software such as PhyloP, PolyPhen-2, SIFT, etc. RESULTS: After screening, a heterozygous mutation C719R was finally identified in the gene MYBPC3 of this case. CONCLUSIONS: The molecular anatomy on whole exome level by second generation sequencing technology can help to define the molecular mechanism of HCM and provide a new mothed and thought for analysis of death cause.
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Cardiomiopatia Hipertrófica/mortalidade , Morte Súbita , Sequenciamento do Exoma , Exoma/genética , Testes Genéticos/métodos , Adulto , Cardiomiopatia Hipertrófica/genética , Feminino , Heterozigoto , Humanos , Masculino , Dados de Sequência Molecular , MutaçãoRESUMO
New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM.
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Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Cálculos da Dosagem de Medicamento , Mieloma Múltiplo/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/sangue , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Humanos , Modelos Biológicos , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND/OBJECTIVES: Nutritional risk screening (NRS-2002) and routine clinical laboratory measurements (RCLMs) had been shown to have a predictive value in adverse outcomes in some studies, respectively. This study analyzed the association between NRS-2002 and RCLMs and estimated their prospective value in predicting adverse outcomes. SUBJECTS/METHODS: A total of 916 hospitalized patients were screened on admission with NRS-2002 and Subjective Global Assessment; RCLMs, which include blood test, kidney and liver function and electrolytes, were recorded. Diagnosis, nutritional support, surgery, radiotherapy, chemotherapy, complications, mortality and hospital stay during hospitalization were collected. The X(2)-test, odds ratios with 95% confidence intervals, kappa (k) statistic and regression analyses were conducted. RESULTS: An overall 48.1% of the 916 patients were at nutritional risk on admission. Comparing 'at risk' with 'no risk', a significantly higher incidence of abnormality was found not only in nutritional markers but also in other parameters of RCLMs (OR ranged from 1.5 to 3.5). Regression analyses showed that 'at risk' determined at admission was not a significant predictor of adverse outcomes after adjusting for other confounding factors, although it was a strong predictor in univariate analysis, whereas hypoalbuminemia, low total lymphocyte count, abnormality of hepatic and renal function were predictors after adjusting for confounders. CONCLUSIONS: The findings suggest that NRS-2002 might be a global index of 'sickness' rather than be only a nutritional screening tool. It being rated once at admission is insufficient and should be repeated for using it as a predictor, whereas RCLMs routinely measured at admission may be able to be used to predict adverse outcomes.
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Eletrólitos/sangue , Testes de Função Renal/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Testes de Função Hepática/estatística & dados numéricos , Avaliação Nutricional , Estado Nutricional/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Nutricional/métodos , Apoio Nutricional/estatística & dados numéricos , Estudos Prospectivos , Análise de Regressão , Medição de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
Nanoclusters with extra stability at certain cluster sizes are known as magic clusters with exotic properties. The classic Wulff construction principle, which stipulates that the preferred structure of a cluster should minimize its total surface energy, is often invoked in determining the cluster magicity, resulting in close-shelled Mackay icosahedronal clusters with odd-numbered magic sizes of 13, 55, 147, etc. Here we use transition metal clusters around size 55 as prototypical examples to demonstrate that, in the nanometer regime, the classic Wulff construction principle needs to be generalized to primarily emphasize the edge atom effect instead of the surface energy. Specifically, our detailed calculations show that nanoclusters with much shorter total edge lengths but substantially enlarged total surface areas are energetically much more stable. As a consequence, a large majority of the nanoclusters within the 3d-, 4d-, and 5d-transition metal series are found to be fcc or hcp crystal fragments with much lower edge energies, and the widely perceived magic size of 55 is shifted to its nearby even numbers.
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The mechanisms producing strong coupling between electric and magnetic order in multiferroics are not always well understood, since their microscopic origins can be quite different. Hence, gaining a deeper understanding of magnetoelectric coupling in these materials is the key to their rational design. Here, we use ultrafast optical spectroscopy to show that the influence of magnetic ordering on quantum charge fluctuations via the double-exchange mechanism can govern the interplay between electric polarization and magnetism in the charge-ordered multiferroic LuFe2O4.
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We measured the low-lying crystal field levels of Nd3+ in Nd3Ga5SiO14 via magneto-optical spectroscopy and employed the extracted energies, magnetic moments, and symmetries to analyze the magnetic properties and test the spin liquid candidacy of this material. The exchange interaction is surprisingly small, a discovery that places severe constraints on models used to describe the ground state of this system. Further, it demonstrates the value of local-probe photophysical techniques for rare-earth-containing materials where bulk property measurements can be skewed by low-lying electronic structure.
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CD226, a member of cell adhesion molecules, has been widely studied in the immune system; however, its expression in the CNS remains unknown. In our present study, we detected CD226 mRNA and protein in the mouse hippocampus and cerebellum by RT-PCR and Western blotting, respectively. Immunohistochemical studies found that CD226 is primarily located in the hilus of the dentate gyrus and stratum lucidum aligned along the pyramidal cells in the hippocampal CA3 area, the interspaces of granular cells and the somata of the Purkinje cells in the cerebellar cortex during adulthood. Double-staining results revealed that CD226 co-localized well with synaptic marker proteins including synaptophysin, syntaxin and PSD-95. During postnatal development, CD226 could not be detected at its adult locations until postnatal day 12; however, it was temporally expressed in the somata of neighboring or distant nuclei associated with its adult location. These results showed the diverse localization of CD226 in the mouse hippocampus and cerebellum for the first time and suggested its potential role in the CNS.
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Antígenos de Diferenciação de Linfócitos T/metabolismo , Cerebelo/crescimento & desenvolvimento , Cerebelo/metabolismo , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Animais , Animais Recém-Nascidos , Antígenos de Diferenciação de Linfócitos T/genética , Proteína 4 Homóloga a Disks-Large , Guanilato Quinases , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fosfopiruvato Hidratase/metabolismo , Proteínas Qa-SNARE/metabolismo , Sinaptofisina/metabolismoRESUMO
We investigated the series of temperature and field-driven transitions in LuFe2O4 by optical and Mössbauer spectroscopies, magnetization, and x-ray scattering in order to understand the interplay between charge, structure, and magnetism in this multiferroic material. We demonstrate that charge fluctuation has an onset well below the charge ordering transition, supporting the "order by fluctuation" mechanism for the development of charge order superstructure. Bragg splitting and large magneto-optical contrast suggest a low-temperature monoclinic distortion that can be driven by both temperature and magnetic field.
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DNA mismatch repair (MMR) has been shown to play a role in the cytotoxicity of ionizing radiation (IR), as cell lines established from MMR-deficient mice exhibit higher clonogenic survival after IR than do cell lines from wild-type littermates. To test whether this tolerance phenotype would render MMR-deficient animals hypermutable to IR, we compared IR mutagenesis of Pms2-deficient versus wild-type transgenic mice carrying a lambda shuttle vector for mutation detection. In Pms2 nullizygous animals, the mutation frequency in the supFG1 reporter gene was increased from 210 x 10(-5) in untreated animals to 734 x 10(-5) after 6 Gy of IR (an increase of 524 mutants per 10(5)), whereas the frequency in wild-type mice increased from 1.9 x 10(-5) to 10.2 x 10(-5) (an increase of only 8.3 mutants per 10(5)). Similarly, when the lambda cII gene was used as a reporter, the mutation frequency in nullizygous mice was increased from 16.3 x 10(-5) to 42.3 x 10(-5) after IR (an increase of 26.0 x 10(-5)), whereas the frequency in wild-type mice increased from 2.4 x 10(-5) to 9.4 x 10(-5) (an increase of only 7.0 x 10(-5)). The pattern of IR-induced mutations in the MMR-deficient animals was notable for single bp deletions and insertions in mononucleotide repeat sequences, along with a slight increase in transversions. Overall, these results suggest that MMR-deficiency confers hypermutability to IR, and that much of this hypermutability can be attributed to induced instability of simple sequence repeats. Hence, MMR influences not only the survival but also the mutability of cells in response to IR.
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Adenosina Trifosfatases , Pareamento Incorreto de Bases , Enzimas Reparadoras do DNA , Reparo do DNA , Proteínas de Ligação a DNA , Mutagênese/efeitos da radiação , Proteínas de Neoplasias/genética , Tolerância a Radiação/genética , Animais , Sequência de Bases , Cruzamentos Genéticos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Endonuclease PMS2 de Reparo de Erro de Pareamento , Dados de Sequência MolecularRESUMO
We have shown previously that cells lacking myosin II are impaired in multicellular motility. We now extend these results by determining whether myosin contractile function is necessary for normal multicellular motility and shape control. Myosin from mutants lacking the essential (mlcE(-)) myosin light chain retains the ability to form bipolar filaments that bind actin, but shows no measurable in vitro or in vivo contractile function. The contractile function is necessary for cell shape control since mlcE(-) cells, like myosin heavy-chain null mutants (mhcA(-)), were defective in their ability to control their three-dimensional shape. When mixed with wild-type cells in chimeric aggregation streams, the mlcE(-) cells were able to move normally, unlike mhcA(-) cells which accumulated at the edges of the stream and became distorted by their interactions with wild-type cells. When mhcA(-) cells were mixed with mlcE(-) streams, the mhcA(-) cells were excluded. The normal behavior of the mlcE(-) cells in this assay suggests that myosin II, in the absence of motor function, is sufficient to allow movement in this constrained, multicellular environment. We hypothesize that myosin II is a major contributor to cortical integrity even in the absence of contractile function.
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Miosinas/fisiologia , Animais , Linhagem Celular , Movimento Celular , Dictyostelium , Contração Muscular , Cadeias Pesadas de Miosina/fisiologia , Cadeias Leves de Miosina/fisiologiaRESUMO
OBJECTIVE: To study the changes of risk factors of cardiovascular disease in the rural community population after intervention. METHODS: The Beijing Fangshan cardiovascular prevention program was a community-based comprehensive intervention study which was launched from 1991 and ended in 2000 in five communities including three as intervention communities (IC) and two as control communities (CC) in Fangshan, Beijing suburb. The intervention measures were focused on health education and hypertension control. The changes of risk factors of cardiovascular disease in IC and CC were analyzed using random sample in the year 1991, 1995 and 1999, respectively. The risk factors include systolic and diastolic blood pressure (SBP and DBP), body mass index(BMI), serum total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL), smoking, and drinking. RESULTS: From the year 1991 to 1999, the risk factors of cardiovascular disease such as SBP, DBP, smoking rate and drinking rate were reduced in the population of IC. For male in IC, the decline of SBP, DBP, smoking rate, and drinking rate were 1.6 mmHg, 1.1 mmHg, 14.5% (P < 0.01) and 3.7%, respectively. For female of IC, SBP and DBP declined 4.8 mmHg (P < 0.01) and 3.2 mmHg (P < 0.01), respectively. SBP, DBP and smoking rate in the population of CC had a little reduction while BMI, TC and TG increased in both IC and CC. During the period of 1991 to 1999, most cardiovascular risk factors in the population of IC had net reduction compared to that of CC. CONCLUSIONS: Except for BMI and lipids, rural community intervention, as focused on health education and hypertension control, has resulted in the reduction of most risk factors of cardiovascular disease.
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Doenças Cardiovasculares/prevenção & controle , Serviços de Saúde Comunitária , Precauções Universais , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Pressão Sanguínea , China , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fatores de Risco , População Rural , FumarRESUMO
OBJECTIVE: To explore potential effective measures for lowering incidence and mortality of stroke in rural community population of China. METHODS: Beijing Fangshan Cardiovascular Prevention Program (BFCP), under whole population and high risk individuals strategies with measures of health education and hypertension control, were launched in 1991 in five communities including intervention communities (IC), about 66,000 residents, and control communities (CC), about 54,000 residents, in Fangshan, Beijing suburb. RESULT: Incidences of stroke averaged 235.23 per 100,000 and 289.22 per 100,000, for IC and CC respectively, with a statistically significant difference, and mortalities of stroke averaged 80.63 per 100,000 and 98.01 per 100,000, for IC and CC respectively, with a statistically significant difference, during years of 1992 to 1999. The net change of stroke incidence was 126.13 per 100,000 in IC versus CC, with a statistically significant difference. Incidences of stroke increased by 11.63% and 75.27%, for IC and CC respectively, while mortalities of stroke decreased by 46.80% and 22.82%, respectively, for IC and CC from years of 1992 to 1999. CONCLUSION: BFCP has yielded obvious effect on controlling incidence and mortality of stroke in rural community population, but the trend of stroke incidence increasing was still not restrained radically.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Serviços de Saúde Comunitária , Acidente Vascular Cerebral , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Saúde da População Rural , Distribuição por Sexo , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidadeRESUMO
We have examined the interaction between synapsin I, the major phosphoprotein on the membrane of small synaptic vesicles, and brain spectrin. Using recombinant peptides we have localized the synapsin I attachment site upon the beta-spectrin isoform betaSpIISigmaI to a region of 25 amino acids, residues 211 through 235. This segment is adjacent to the actin binding domain and is within the region of the betaSpIISigmaI that we previously predicted as a candidate synapsin I binding domain based upon sequence homology. We used differential centrifugation techniques to quantitatively assess the interaction of spectrin with synaptic vesicles. Using this assay, high affinity saturable binding of recombinant betaSpIISigmaI proteins was observed with synaptic vesicles. Binding was only observed when the 25 amino acid synapsin I binding site was included on the recombinant peptides. Further, we demonstrate that antibodies directed against 15 amino acids of the synapsin I binding domain specifically blocked synaptic transmission in cultured hippocampal neurons. Thus, the synapsin I attachment site on betaSpIISigmaI spectrin comprises a approximately 25 amino acid segment of the molecule and interaction of these two proteins is an essential step for the process of neurotransmission.