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BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.
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Cardiotoxicidade , Doxorrubicina , Exossomos , Momordica charantia , Fator 2 Relacionado a NF-E2 , Animais , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/metabolismo , Momordica charantia/química , Exossomos/metabolismo , Ratos , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ratos Sprague-Dawley , Proteína Sequestossoma-1/metabolismoRESUMO
PURPOSE: Human post mortem studies have described the topographical patterns of tau pathology in progressive supranuclear palsy (PSP). Recent advances in tau PET tracers are expected to herald the next era of PSP investigation for early detection of tau pathology in living brains. This study aimed to investigate whether 18F-Florzolotau PET imaging may capture the distribution patterns and regional vulnerability of tau pathology in PSP, and to devise a novel image-based staging system. METHODS: The study cohort consisted of 148 consecutive patients with PSP who had undergone 18F-Florzolotau PET imaging. The PSP rating scale (PSPrs) was used to measure disease severity. Similarities and differences of tau deposition among different clinical phenotypes were examined at the regional and voxel levels. An 18F-Florzolotau pathological staging system was devised according to the scheme originally developed for post mortem data. In light of conditional probabilities for the sequence of events, an 18F-Florzolotau modified staging system by integrating clusters at the regional level was further developed. The ability of 18F-Florzolotau staging systems to reflect disease severity in terms of PSPrs score was assessed by analysis of variance. RESULTS: The distribution patterns of 18F-Florzolotau accumulation in living brains of PSP showed a remarkable similarity to those reported in post mortem studies, with the binding intensity being markedly higher in Richardson's syndrome. Moreover, 18F-Florzolotau PET imaging allowed detecting regional vulnerability and tracking tau accumulation in an earlier fashion compared with post mortem immunostaining. The 18F-Florzolotau staging systems were positively correlated with clinical severity as reflected by PSPrs scores. CONCLUSIONS: 18F-Florzolotau PET imaging can effectively capture the distribution patterns and regional vulnerability of tau pathology in PSP. The 18F-Florzolotau modified staging system holds promise for early tracking of tau deposition in living brains.
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Paralisia Supranuclear Progressiva , Humanos , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Proteínas tau/metabolismoRESUMO
Objective: To develop a web-based machine learning server to predict lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC) patients. Methods: Clinical data for PTC patients who underwent primary thyroidectomy at our hospital between January 2015 and December 2020, with pathologically confirmed presence or absence of any LLNM finding, were retrospectively reviewed. We built all models from a training set (80%) and assessed them in a test set (20%), using algorithms including decision tree, XGBoost, random forest, support vector machine, neural network, and K-nearest neighbor algorithm. Their performance was measured against a previously established nomogram using area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), precision, recall, accuracy, F1 score, specificity, and sensitivity. Interpretable machine learning was used for identifying potential relationships between variables and LLNM, and a web-based tool was created for use by clinicians. Results: A total of 1135 (62.53%) out of 1815 PTC patients enrolled in this study experienced LLNM episodes. In predicting LLNM, the best algorithm was random forest. In determining feature importance, the AUC reached 0.80, with an accuracy of 0.74, sensitivity of 0.89, and F1 score of 0.81. In addition, DCA showed that random forest held a higher clinical net benefit. Random forest identified tumor size, lymph node microcalcification, age, lymph node size, and tumor location as the most influentials in predicting LLNM. And the website tool is freely accessible at http://43.138.62.202/. Conclusion: The results showed that machine learning can be used to enable accurate prediction for LLNM in PTC patients, and that the web tool allowed for LLNM risk assessment at the individual level.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/patologia , Metástase Linfática/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Fatores de Risco , Linfonodos/patologia , Aprendizado de MáquinaRESUMO
BACKGROUND: Tubular adenocarcinoma of the colon, which originates from the epithelium of the glands, is a major health concern worldwide. However, it is difficult to detect at an early stage. The lack of biomarkers is a main barrier to the diagnosis and treatment of tubular adenocarcinoma. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted protein that induces the expression of matrix metalloproteinase-9 (MMP-9) and is involved in various tumors. NGAL and MMP-9 have been reported to be associated with tumorigenesis and development. They may have potential as biomarkers for diagnosis of tubular adenocarcinoma of the colon. AIM: To determine whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon. METHODS: Samples were collected from surgically excised tissue from various patients. The content of pro-gastrin-releasing peptide (pro-GRP) in the serum was measured by an electrochemiluminescence immunoassay. The expression patterns of NGAL and MMP-9 and the relationship between NGAL and MMP-9 were examined by quantitative real-time PCR, Western blotting and immunohistochemical analysis. RESULTS: In this study, we found that NGAL and MMP-9 can be used as biomarkers for the detection of tubular adenocarcinoma of the colon and that their combination improved diagnostic accuracy. By analyzing the expression of NGAL in tubular adenocarcinoma at different levels, we found that NGAL expression was significantly upregulated in primary tubular adenocarcinoma tissues compared with normal tissues. The upregulation of NGAL expression was strongly correlated with both the degree of differentiation and the disease stage (I-III), indicating that NGAL could serve as a diagnostic biomarker for tubular adenocarcinoma. When using NGAL as a biomarker for diagnosis, the accuracy was similar to that achieved with the widely used biomarker pro-GRP, suggesting that NGAL is reliable. Moreover, the expression of MMP-9 was also strongly correlated with the differentiation stage, demonstrating that MMP-9 could be used as a biomarker to indicate the progression of tubular adenocarcinoma of the colon. More importantly, the combination of NGAL and MMP-9 produced a more accurate diagnosis of tubular adenocarcinoma, and these results were further confirmed by immunohistochemical analysis of tissue sections. CONCLUSION: Our study demonstrated that both NGAL and MMP-9 can be used as biomarkers for the diagnosis of colon tubular adenocarcinoma and that the results could be further improved by combining them.
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BACKGROUND: Based on the location and size of the fracture block, open reduction and internal fixation can be employed or assisted for shoulder arthroscopy in the treatment of glenoid fractures. However, the treatment of lower part of glenoid fractures through a novel axillary approach has not been reported so far. CASE SUMMARY: A 22-year-old right-handed man was transferred to our outpatient clinic because of right shoulder injury during a traffic accident. X-ray examination after admission suggested the fracture of the lower part of the right glenoid and an ipiselial proximal humeral fracture. Three-dimensional (3D) computed tomography (CT) further suggested that the size of the fracture block of the lower part of the right glenoid was 3.4 mm × 16.2 mm. The patient was diagnosed as the fracture of the lower part of the glenoid, also known as bony Bankart lesion without shoulder dislocation. After general anesthesia, the patient was surgically treated with the open reduction internal fixation through a novel axillary approach. 3D CT and shoulder joint function were reexamined at 12 mo of follow-up, showing acceptable recovery. CONCLUSION: This case report describes a novel axillary approach adopted in an open reduction with cannulated screw and wire anchor internal fixation. After a follow-up for more than 12 mo, 3D CT and shoulder joint function examinations display a good recovery.
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The lateral habenula plays a central role in reward and punishment processing and has been suggested to drive the cardinal symptom of anhedonia in depression. This hypothesis is largely based on observations of habenula hypermetabolism in animal models of depression, but the activity of habenula and its relationship with clinical symptoms in patients with depression remains unclear. High-resolution functional magnetic resonance imaging (fMRI) and computational modelling were used to investigate the activity of the habenula during a probabilistic reinforcement learning task with rewarding and punishing outcomes in 21 unmedicated patients with major depression and 17 healthy participants. High-resolution anatomical scans were also acquired to assess group differences in habenula volume. Healthy individuals displayed the expected activation in the left habenula during receipt of punishment and this pattern was confirmed in the computational analysis of prediction error processing. In depressed patients, there was a trend towards attenuated left habenula activation to punishment, while greater left habenula activation was associated with more severe depressive symptoms and anhedonia. We also identified greater habenula volume in patients with depression, which was associated with anhedonic symptoms. Habenula dysfunction may contribute to abnormal response to punishment in patients with depression, and symptoms such as anhedonia.
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Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Habenula/fisiopatologia , Motivação , Adulto , Anedonia , Potenciais Evocados , Feminino , Lateralidade Funcional , Humanos , Aprendizagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Punição , Reforço Psicológico , Recompensa , Adulto JovemRESUMO
BACKGROUND: Anhedonia is a cardinal feature of major depression and is hypothesized to be driven by low motivation, in particular blunted reward sensitivity. It has been suggested to be a marker that represents a genetic predisposition to this disorder. However, little is known about the mechanisms underlying this heightened risk in unaffected first-degree relatives of patients with major depression. We previously demonstrated abnormal reward biases in acutely depressed patients. The present study aimed to examine the development of reward bias in first-degree relatives of patients with major depression. METHODS: Forty-seven first-degree relatives of patients with major depression (26 females, age 18-52) and 60 healthy controls with no family history of depression (34 females, age 21-48) were recruited. A probabilistically rewarded difficult visual discrimination task, in which participants were instructed about the contingencies, was used to assess blunted reward sensitivity. A response bias towards the more frequently rewarded stimulus (termed "reward bias") was the primary outcome variable in this study. Participants also completed self-reported measures of anhedonia and depressive symptoms. RESULTS: Compared with the control group, relatives of patients with major depression with sub-clinical depressive symptoms displayed a blunted reward bias. Relatives without symptoms displayed largely intact motivational processing on both self-report and experimental measures. The degree of anhedonia was associated with attenuated reward bias in first-degree relatives of patients with major depression, especially in those with sub-clinical symptoms. LIMITATIONS: The study did not include a depressed patient group, which restricted our ability to interpret the observed group differences. CONCLUSIONS: Blunted reward sensitivity may be largely manifested in a subgroup of relatives with high levels of depressive symptoms.
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Anedonia , Transtorno Depressivo Maior/psicologia , Relações Familiares , Recompensa , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Autorrelato , Adulto JovemRESUMO
Accompanying the beneficial improvement in litter size from genetic selection for high-prolificacy sows, within-litter variation in birth weight has increased with detrimental effects on post-natal growth and survival due to an increase in the proportion of piglets with low birth-weight. Causes of within-litter variation in birth weight include breed characteristics that affect uterine space, ovulation rate, degree of maturation of oocytes, duration of time required for ovulation, interval between ovulation and fertilization, uterine capacity for implantation and placentation, size and efficiency of placental transport of nutrients, communication between conceptus/fetus and maternal systems, as well as nutritional status and environmental influences during gestation. Because these factors contribute to within-litter variation in birth weight, nutritional status of the sow to improve fetal-placental development must focus on the following three important stages in the reproductive cycle: pre-mating or weaning to estrus, early gestation and late gestation. The goal is to increase the homogeneity of development of oocytes and conceptuses, decrease variations in conceptus development during implantation and placentation, and improve birth weights of newborn piglets. Though some progress has been made in nutritional regulation of within-litter variation in the birth weight of piglets, additional studies, with a focus on and insights into molecular mechanisms of reproductive physiology from the aspects of maternal growth and offspring development, as well as their regulation by nutrients provided to the sow, are urgently needed.
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Peso ao Nascer/fisiologia , Tamanho da Ninhada de Vivíparos/fisiologia , Estado Nutricional/fisiologia , Prenhez/fisiologia , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Suínos/fisiologia , Animais , Bovinos , Feminino , Masculino , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Disease-associated mutations in GJB2 gene are one of the major reasons that can cause non-syndromic sensorineural hearing loss (NSHL). GJB2 gene deafness has various clinical phenotypes. This study aims to analyze characteristics and relationships of clinical phenotypes through analyzing 1481 NSHL cases and 190 GJB2 deafness patients (with dual gene mutations). PATIENTS AND METHODS: All the patients diagnosed as deaf disease molecular diagnostics were obtained from the people's liberation army general hospital from March 2007 to March 2011. The accession number of GJB2 was NM_004004 in GenBank, and sequence alignment and annotation were performed using GeneTool software. RESULTS: In NSHL patients, mutated allele frequency in GJB2 was 20.57%, and the preponderant type was c.235delC (11.84%) followed by c.109G>A (3.75%). Mutation rate of double allelic gene was 16.18%, including 8.43% of homozygous mutation rate and 7.75% of recombination heterozygosis mutation. Moreover, auditory threshold of GJB2 biallelic marker was associated with ages of onset, while no significant correlation was detected with disease time and whether the inner ear malformation. Similar clinical phenotype could be detected between patients with c.109G>A dual gene mutation and dual gene mutation. However, in the aspect of hearing impairment, the phenomenon of pathopoiesia caused by mutation of c.109G>A was poorer than the other mutations, and even near those patients without pathogenic mutations. CONCLUSION: Our study further shows the definite relationship of clinical phenotype and genotype in GJB2 gene correlated deafness, and these results can provide basis for revealing pathogenesis, gene diagnosis and consult of deafness. The level of evidence in the study is level 4 (case series).
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Conexinas/genética , Perda Auditiva/genética , Adolescente , Criança , Pré-Escolar , China , Conexina 26 , Feminino , Genótipo , Humanos , Lactente , Masculino , Fenótipo , Adulto JovemRESUMO
Bulk HgS itself has proven to be a technologically important material; however, the poor stability and weak emission of HgS nanocrystals have greatly hindered their promising applications. Presently, a critical problem is the uncontrollable growth of HgS NCs and their intrinsic surface states which are susceptible to the local environment. Here, we address the issue by an ion-tuning approach to fabricating stable, highly fluorescent Cd:HgS/CdS NCs for the first time, which efficiently tuned the band-gap level of HgS NCs, pushing their intrinsic states far away from the surface, reducing the strong interaction of the environment with surface states and hence drastically boosting the exciton transition. As compared to bare HgS NCs, the obtained Cd:HgS/CdS NCs exhibited tunable luminescence peaks from 724 to 825 nm with an unprecedentedly high quantum yield up to 40% at room temperature and excellent thermal and photostability. Characterized by TEM, XRD, XPS, and AAS, the resultant Cd:HgS/CdS NCs possessed a zinc-blende structure and was composed of a homogeneous alloyed HgCdS structure coated with a thin-layer CdS shell. The formation mechanism of Cd:HgS/CdS NCs was proposed. These bright, stable HgS-based NCs presented promising applications as fluorescent inks for anticounterfeiting and as excellent light converters when coated onto a blue-light-emitting diode.
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Compostos de Cádmio/química , Nanopartículas/químicaRESUMO
CONCLUSION: The hearing conditions of the centenarians were quite poor as regards hearing thresholds and speech detection ability. OBJECTIVE: To investigate hearing conditions of centenarians. METHODS: A total of 54 centenarians in Rizhao and Linyi Districts in Shandong Province were investigated to assess hearing conditions of centenerians comprehensively by questionnaire investigation, pure-tone audiometry, acoustic immitance, intelligence evaluation, and speech detection scores. Also, 135 individuals were recruited as controls and divided into four groups according to their age: 45-59 years, 60-69 years, 70-79 years, and 80-89 years. RESULTS: The hearing thresholds of the centenarians were dramatically higher than those of the control group (p < 0.05) and all centenarians suffered moderate to profound hearing loss according to the World Health Organization (WHO) criteria. Few centenarians had normal level of speech detection scores. All centenarians showed descending hearing curve, and the hearing threshold of the male centenarians at 8000 Hz was higher than that of the females (p = 0.047). There was a significant air-bone conduction gap in the centenarians (p < 0.05).
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Limiar Auditivo , Testes Auditivos , Presbiacusia/diagnóstico , Presbiacusia/epidemiologia , Testes de Impedância Acústica , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros , Condução Óssea , Estudos de Casos e Controles , China , Estudos Transversais , Feminino , Humanos , Inteligência , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reflexo Acústico , Teste do Limiar de Recepção da FalaRESUMO
Near-infrared (NIR)-emitting nanocrystals have enormous potential as an enabling technology for applications ranging from tunable infrared lasers to biological labels. Mercury chalcogenide NCs are one of the attractive NCs with NIR emission; however, the potential toxicity of Hg restricts their diverse applications. Herein, we synthesized low-toxic, highly luminescent and stable GSH-capped HgS/ZnS core/shell NCs by an aqueous route for the first time. The core/shell structure was characterized by using TEM, XRD and XPS, which provide evidence for the shell growth. After the successful growth of an appropriate ZnS shell around HgS NCs, poorly luminescent HgS NCs converted into ultra-bright HgS/ZnS NCs, substantially increasing photoluminescence quantum yield up to 43.8% at room temperature. The fluorescence peak of HgS/ZnS NCs was successfully tuned in a wide NIR window ranging from 785 nm to 1060 nm with high emission efficiency by controlling the synthetic pH values. Significantly, an in vitro cytotoxicity study clearly demonstrated that the HgS/ZnS NCs exhibited good biocompatibility as evidenced by the cell viability retained above 80% at a dose of HgS/ZnS NCs up to 150 µg mL-1. More importantly, the low-toxic NIR-emitting HgS/ZnS NCs have proved to be an effective fluorescent label in in vitro and in vivo imaging. The penetration depth reached 2 cm in a nude mouse with distinct separation of autofluorescence and NCs' fluorescence, giving excellent contrast at all depths. The novel highly-luminescent NIR-emitting HgS/ZnS NCs open up new possibilities for highly-sensitive, highly spectrally resolved and multicolor imaging in biomedical applications.
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TECTA-related deafness can be inherited as autosomal-dominant nonsyndromic deafness (designated DFNA) or as the autosomal-recessive version. The α-tectorin protein, which is encoded by the TECTA gene, is one of the major components of the tectorial membrane in the inner ear. Using targeted DNA capture and massively parallel sequencing (MPS), we screened 42 genes known to be responsible for human deafness in a Chinese family (Family 3187) in which common deafness mutations had been ruled out as the cause, and identified a novel mutation, c.257-262CCTTTC>GCT (p. Ser86Cys; p. Pro88del) in exon 3 of the TECTA gene in the proband and his extended family. All affected individuals in this family had moderate down-sloping hearing loss across all frequencies. To our knowledge, this is the second TECTA mutation identified in Chinese population. This study demonstrates that targeted genomic capture, MPS, and barcode technology might broaden the availability of genetic testing for individuals with undiagnosed DFNA.
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Surdez/genética , Proteínas da Matriz Extracelular/genética , Mutação , Povo Asiático/genética , Audiometria de Tons Puros , China , Análise Mutacional de DNA , Surdez/fisiopatologia , Feminino , Proteínas Ligadas por GPI/genética , Humanos , Masculino , Linhagem , Gravidez , Diagnóstico Pré-NatalRESUMO
Hypodermin A (HA), a serine protease secreted by first-instar larvae of Hypoderma lineatum (Diptera: Oestridae) is associated with inflammatory and the specific immune responses in cattle hosts. In the present study, the cDNA sequence of HA was synthesized, and found to have fifteen amino acids which differed from the sequence available in GenBank. We then examined the association between recombinant HA and guinea-pig complement component 3 (C3) through a co-immunoprecipitation assay. Cos7 cells stably expressing HA were generated, and were found to be more resistant to lysis by guinea-pig C3 than the controls. HA was also able to degrade the C6 and C5b-9 of guinea-pig C3. The presumed DNA binding site of HA with guinea-pig C3 was detected by an electrophoretic mobility shift assay (EMSA). In contrast, after stable transfection, mHA was unable to reduce the amount of C3 or to inhibit its cytotoxicity, while HA could degrade guinea-pig C3 and inhibit the complement pathway. The findings suggest that recombinant HA could serve as an immunosuppressive agent against organ rejection after xenotransplantation.
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Proteínas do Sistema Complemento/metabolismo , Serina Endopeptidases/farmacologia , Sequência de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , DNA Complementar/genética , Dados de Sequência MolecularRESUMO
OBJECTIVE: To investigate whether quantifiable changes in serum levels of hepatitis B e antigen (HBeAg) in response to 24 weeks of pegylated-interferon alfa-2a (Peg-IFN-a 2a) treatment are predictive of therapeutic efficacy at 48 weeks of treatment in HBeAg-positive chronic hepatitis B (CHB) patients and to investigate the efficacy of using an individualized antiviral treatment strategy. METHODS: Ninety-six HBeAg-positive CHB patients with detectable HBeAg at week 24 of Peg-IFN-a 2a treatment were categorized according to the quantitative change in HBeAg (vs. pre-treatment baseline): group A, HBeAg decline more than 2 log; group B, HBeAg decline between 1 - 2 log; group C, HBeAg decline less than 1 log, which was then randomly divided into two sub-groups: C1 and C2. Group A, B, and C1 patients continued the original therapy for an additional 24 weeks, while group C2 patients were supplemented with lamivudine (3TC + Peg-IFN-a 2a) for the additional 24 weeks of treatment. All patients underwent liver biopsy at the end of treatment (week 48), and HBV covalently-closed circular (ccc)DNA was quantified as a measure of therapeutic efficacy. A, B, and C1 between-group multiple comparisons were made by the Nemenyi test; C1 and C2 between-group comparison was made by the Mann-Whitney U test. The significance of between-group differences in decreased HBV cccDNA vs. HBeAg/anti-HBe seroconversion was made by the Chi-squared test. RESULTS: At week 48, the mean decrease of serum HBV cccDNA in each group was: A, 5.8 log10 copy/ml; B, 3.8 log10 copy/ml; C1, 2.8 log10 copy/ml; C2, 5.7 log10 copy/ml. Statistically significant differences were observed for group A vs. B and C1 (P less than 0.01) and C1 vs. C2 (P less than 0.01); however, the difference between group B and C1 did not reach statistical significance (P = 0.19). The mean decrease of HBeAg in each group was: A, 2.7 log10 S/CO; B, 1.9 log10 S/CO; C1, 0.9 log10 S/CO; C2, 1.6 log10 S/CO. Statistically significant differences were observed for group A vs. B and C1 (P less than 0.01) and C1 vs. C2 (P less than 0.01). The rate of patients who achieved undetectable HBV DNA in each group was: A, 87.5%; B, 34.5%; C1, 17.4%; C2, 85.0%. Statistically significant differences were observed for group A vs. B and C1 (P less than 0.01) and C1 vs. C2 (P less than 0.01). The HBeAg seroconversion rates were: A, 75.0%; B, 24.1%; C1, 13.0%; C2, 25.0%. Statistically significant differences were observed only for group A vs. B and C1 (P less than 0.01). Finally, group A achieved greater reduction in levels of cccDNA in liver tissues than B or C1 (P less than 0.01); however, the differences between B and C1 and between C1 and C2 did not reach statistical significance. CONCLUSION: CHB patients who showed an HBeAg decline of more than 2 log at week 24 of Peg-IFN-a 2a treatment had better treatment outcome at week 48 than those who showed HBeAg decline less than 2 log at week 24. Augmenting the Peg-IFN-a 2a treatment with 3TC can improve the clinical response. A change of quantifiable HBeAg at week 24 of Peg-IFN-a 2a treatment may be a useful predictor of therapeutic efficacy of a 48-week antiviral regimen.
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Antivirais/uso terapêutico , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Feminino , Humanos , Lamivudina/uso terapêutico , Masculino , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
Overexpression of calbindin-D(28k) (CaBP-28 k) induces neurite outgrowth in dopaminergic neuronal cells and could provide some protection to dopaminergic neurons against the pathological process in Parkinson's disease. Transgenic mice CaBP-28 k overexpression and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models were generated, and the effect of midbrain dopamine neurons in ethology was also assessed. Tyrosine hydroxylase (TH)-immunoreactive neurons were counted, and the concentration of total protein and dopamine (DA) of striatum corpora was measured in four animal models. Results showed that the positive TH cells, content of DA, and ability of ethology in MPTP-induced transgenic mice were significantly higher than that in MPTP-induced wild-type mice. The findings demonstrate that overexpression of CaBP-28 k could provide protection for DA neurons from neurodegeneration. It would provide a potential strategy in the treatment of Parkinson's diseases.
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Fármacos Neuroprotetores/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Proteína G de Ligação ao Cálcio S100/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Comportamento Animal , Western Blotting , Calbindinas , Caspase 3/metabolismo , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doença de Parkinson/enzimologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Substância Negra/enzimologia , Substância Negra/metabolismo , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
BACKGROUND: The Snaith-Hamilton-Pleasure-Scale (SHAPS) is a self-reported scale evaluating anhedonia for neuropsychiatric disorders. It has demonstrated with impressive psychometric properties and advantages in its applicability over other similar instruments. However, very few studies have been conducted to examine the clinical utility of the SHAPS in the context of Chinese settings. The current study aimed to examine the clinical utility of the translated version of the SHAPS in the Chinese clinical settings. METHODS: A Chinese version of SHAPS was administered to 336 college students to examine the internal consistency and test-retest reliability at a 4-week interval. Moreover, the translated SHAPS was also administered to 141 patients with major depression, 72 patients with schizophrenia, and 72 healthy controls to examine its clinical discrimination. RESULTS: The internal consistency of the SHAPS for the non-clinical sample and test-retest reliability at a 4- week interval were 0.85 and 0.64, respectively. Moreover, the SHAPS also showed an excellent internal consistency (alpha was 0.93) and a one-factor solution with the first factor accounted for 51.53% of the variance in the clinical psychiatric samples. ANOVA of the SHAPS total score indicated that the patients with depression scored significantly more anhedonia than the patients with schizophrenia and healthy controls (p<0.001), and the patients with schizophrenia scored significantly more anhedonia than the healthy controls (P<0.02). CONCLUSIONS: These findings suggest that the Chinese version of the SHAPS is a useful and promising instrument in assessing anhedonia for clinical patients and non-clinical individuals in the Chinese settings.
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Anedonia , Povo Asiático/psicologia , Transtorno Depressivo Maior/diagnóstico , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Adulto , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , AutorrelatoRESUMO
[18]F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is sensitive in detecting a variety of malignancies; however, the specificity is low in differential infections or inflammatory diseases from tumors. We present the case of a female with right cervical lymphadenopathy and fever for 3 weeks who underwent an 18F-FDG PET/CT scan. The imaging showed multiple lymph node enlargement and agglomeration with increased metabolic activity even with the involvement in the abdomen, giving the impression of malignant lymphoma. However, biopsy of the affected nodes proved it to be Kikuchi-Fujimoto disease and the patient was cured after steroid therapy.
Assuntos
Linfadenite Histiocítica Necrosante/diagnóstico , Linfoma/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18/farmacocinética , Linfadenite Histiocítica Necrosante/diagnóstico por imagem , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/metabolismo , Linfoma/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeAssuntos
Fator de Crescimento do Tecido Conjuntivo/metabolismo , Hepatite B Crônica/metabolismo , Fígado/metabolismo , Adulto , Feminino , Hepatite B Crônica/patologia , Humanos , Imuno-Histoquímica , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/metabolismo , Adulto JovemRESUMO
BACKGROUND: Few clinical data are available regarding the effect of Ginkgo biloba extract (EGb 761) on liver microcirculation and fibrosis. This randomized, controlled trial is to investigate the effect of Ginko biloba extract EGb 761 on liver fibrosis and hepatic microcirculation in patients with chronic hepatitis B. METHODS: Sixty-four patients with chronic hepatitis B were randomized for intention-to-treat. Thirty-two patients were assigned to treated group receiving EGb 761 plus polyunsaturated phosphatidylcholine (Essentiale), 32 patients received Essentiale as controls. Blood samples were taken for measurement of transforming growth factor beta-1 (TGF-ß1), platelet activate factor (PAF), endothelin 1 (ET-1). Twenty-six patients in treated group and 21 patients in control group underwent liver biopsies for histology before and after treatment. Ultrastructural study for sinusoidal microcirculation before and after treatment was carried out on 10 randomly selected patients in each group. RESULTS: In the treated group, after EGb 761 treatment, there was a significant reduction of blood TGF- ß1, PAF and ET-1 (p<0.05), whereas this was not observed in the controls. After treatment in both groups, there were significant decrease of ALT, TBil and PT (p<0.05), and significant increase of ALB (p<0.05). Hepatic inflammation and fibrosis significantly alleviated in the treated group, but not in the controls. After EGb 761 treatment, electron microscopy showed red blood cell aggregates and microthrombosis disappeared or decreased in sinusoids; collagen deposits in sinusoidal lumen and Disse space reduced; sinusoidal capillarization alleviated. CONCLUSIONS: EGb 761 can improve sinusoidal microcirculation, alleviate inflammation and inhibit fibrosis through multiple mechanisms, it is effective in the treatment of chronic liver diseases.