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BACKGROUND: Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. METHODS: Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. RESULTS: In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). CONCLUSIONS: The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.
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Asma , Óxido Nítrico , Espirometria , Humanos , Asma/tratamento farmacológico , Asma/metabolismo , Asma/diagnóstico , Asma/fisiopatologia , Projetos Piloto , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Volume Expiratório Forçado , Teste da Fração de Óxido Nítrico Exalado , Ritmo Circadiano , Escarro/metabolismo , Eosinófilos/metabolismo , Expiração , Testes Respiratórios/métodosRESUMO
BACKGROUND: The mortality of pneumonia in older adults surpasses that of other populations, especially with the prevalence of coronavirus disease 2019 (COVID-19). Under the influence of multiple factors, a series of geriatric syndromes brought on by age is one of the main reasons for the poor prognosis of pneumonia. This study attempts to analyze the impact of geriatric syndrome on the prognosis of pneumonia. METHODS: This is a prospective cross-sectional study. Patients over 65 years old with COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) were included in the research. General characteristics, laboratory tests, length of stay (LOS), and comprehensive geriatric assessment (CGA) were collected. Multivariate regression analysis to determine the independent predictors of the severity, mortality, and LOS of COVID-19. At the same time, the enrolled subjects were divided into three categories by clustering analysis of 10 CGA indicators, and their clinical characteristics and prognoses were analyzed. RESULTS: A total of 792 subjects were included in the study, including 204 subjects of SN-CAP (25.8%) and 588 subjects (74.2%) of COVID-19. There was no significant difference between non-severe COVID-19 and SN-CAP regarding mortality, LOS, and CGA (P > 0.05), while severe COVID-19 is significantly higher than both (P < 0.05). The Barthel Index used to assess the activities of daily living was an independent risk factor for the severity and mortality of COVID-19 and linearly correlated with the LOS (P < 0.05). The cluster analysis based on the CGA indicators divided the geriatric pneumonia patients into three groups: Cluster 1 (n = 276), named low ability group, with the worst CGA, laboratory tests, severity, mortality, and LOS; Cluster 3 (n = 228), called high ability group with the best above indicators; Cluster 2 (n = 288), named medium ability group, falls between the two. CONCLUSION: The Barthel Index indicates that decreased activities of daily living are an independent risk factor for the severity, mortality, and LOS of geriatric COVID-19. Geriatric syndrome can help judge the prognosis of pneumonia in older adults.
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COVID-19 , Infecções Comunitárias Adquiridas , Avaliação Geriátrica , Humanos , Idoso , Estudos Transversais , Masculino , Feminino , Avaliação Geriátrica/métodos , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/diagnóstico , Prognóstico , Estudos Prospectivos , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/diagnóstico , Tempo de Internação/estatística & dados numéricos , Índice de Gravidade de Doença , SARS-CoV-2 , Pneumonia/mortalidade , Pneumonia/epidemiologia , Fatores de Risco , Atividades CotidianasRESUMO
This paper focuses on the speed control of a permanent magnet synchronous motor (PMSM) for electric drives with model uncertainties and external disturbances. Conventional sliding mode control (CSMC) can only converge asymptotically in the infinite domain and will cause unacceptable sliding mode chattering. To improve the performance of the PMSM speed loop in terms of response speed, tracking accuracy, and robustness, a hybrid control strategy for a fixed-time-convergent sliding mode controller (FSMC) with a fixed-time-convergent sliding mode observer (FSMO) is proposed for PMSM speed regulation using the fixed-time control theory. Firstly, the FSMC is proposed to improve the convergence speed and robustness of the speed loop, which can converge to the origin within a fixed time independent of the initial conditions. Then, the FSMO is used as a compensator to further enhance the robustness of the speed loop and attenuate sliding mode chattering. Finally, simulation and experimental results show that the proposed method can effectively improve the dynamic performance and robustness of the PMSM speed control system.
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BACKGROUND: PARP inhibitor (PARPi), as a kind of DNA damage repair inhibitor, has been shown to be effective in various solid tumors and hematologic malignancies. Natural killer/T cell lymphoma (NKTCL) is a highly aggressive malignancy, the treatment of which has long been a major challenge in the clinic. Here, we investigated the efficacy and mechanism of PARPi, and the therapeutic value of PARPi combined with cisplatin in NKTCL. METHODS: The cell proliferation, cell apoptosis, and cell cycle of NKTCL cells were detected respectively by CCK-8 and flow cytometry. The changes of mRNA expression and protein level were measured respectively by mRNA-sequencing, quantitative real-time PCR, western blotting, and immunofluorescence. LMO2 expression was detected by immunohistochemistry and western blotting. Targeted knockdown of LMO2 was conducted by short hairpin RNA. The tumor xenograft models were established to evaluate the efficacy of drugs in vivo. RESULTS: PARPi inhibited cell proliferation, promoted cell apoptosis, and induced S-phase cell cycle arrest in NKTCL cells. PARPi led to the accumulation of DNA damage by blocking DNA repair and DNA replication. Additionally, LMO2 deficiency reduced the sensitivity of NKTCL cells to PARPi. Finally, the combination of PARPi and cisplatin exhibited significant synergistic effects both in vitro and in vivo. CONCLUSIONS: In summary, we found that PARPi exerted an anti-tumor effect via LMO2 and synergized with cisplatin in NKTCL, which provides the theoretical basis for the clinical application of PARPi.
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Antineoplásicos , Linfoma de Células T , Linfoma , Humanos , Cisplatino/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Células Matadoras Naturais , RNA Mensageiro , Proteínas Proto-Oncogênicas/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/farmacologia , Proteínas com Domínio LIM/farmacologiaRESUMO
BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. METHODS: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry. RESULTS: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model. CONCLUSIONS: In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL.
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Linfoma de Células T , Receptores de Antígenos Quiméricos , Animais , Camundongos , Receptores de Antígenos Quiméricos/genética , Citocinas , Modelos Animais de Doenças , Linfócitos TRESUMO
Natural killer/T cell lymphoma (NKTCL) is a highly aggressive hematological malignancy. However, there is currently no consensus on therapies for refractory/relapsed patients. In this study, we investigated the synergistic anticancer effect and potential mechanism of combining chidamide, a histone deacetylases (HDACs) inhibitor, and etoposide, a DNA-damaging agent, in NKTCL. We demonstrated that chidamide or etoposide alone dose- and time-dependently inhibited the cell viability of NKTCL cell lines, YT, NKYS and KHYG-1. Functional experiments suggested that combined chidamide and etoposide treatment exerted synergistic antiproliferation effect and enhanced cell apoptotic death in vitro and in vivo. Furthermore, the expression of DNA damage related proteins was detected and we also examined the alternations in histone acetylation, cell cycle progression, and mitochondrial membrane potential (MMP). The results suggested that increased histone acetylation, cell cycle arrest at the G2/M phase and loss of MMP, converging to greater DNA damage, might account for the synergism of the combination of chidamide and etoposide in NKTCL. Taken together, our study provides an evident for possible application on combining HDACs inhibitors and DNA-damaging agents for the treatment of NKTCL.
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Aminopiridinas , Benzamidas , Etoposídeo , Linfoma de Células T Periférico , Humanos , Linhagem Celular Tumoral , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Sinergismo FarmacológicoRESUMO
The treatment of natural killer/T-cell lymphoma (NKTCL) presents an onerous challenge, and a search for new therapeutic targets is urgently needed. Poly ADP-ribose polymerase inhibitors (PARPi) were initially used to treat breast and ovarian cancers with BRCA1/2 mutations. Their excellent antitumor efficacy led to a series of clinical trials conducted in other malignancies. However, the exploration of PARPi and their potential use in combination treatments for NKTCL remains unexplored. We treated NKTCL cell lines with fluzoparib (a novel inhibitor of PARP) and chidamide (a classical inhibitor of HDACs) to explore their cytotoxic effects in vitro. Then, their antitumor efficacy in vivo was confirmed in YT-luciferin xenograft mouse models. Fluzoparib or chidamide alone inhibited NKTCL cell proliferation in a dose-dependent manner. Cotreatment with both drugs synergistically induced excessive accumulation of DNA double-strand breaks and massive apoptotic cell death by inhibiting the DNA damage repair pathway, as shown by the decreased protein levels of p-ATM, p-BRCA1, p-ATR, and Rad51. Moreover, the combination treatment apparently increased the level of intracellular reactive oxygen species (ROS) to enhance apoptosis, and pretreatment with an ROS scavenger reduced the proapoptotic effect by 30-60% in NKTCL cell lines. In vivo, this combined regimen also showed synergistic antitumor effects in xenograft mouse models. The combination of fluzoparib and chidamide showed synergistic effects against NKTCL both in vitro and in vivo and deserves further exploration in clinical trials.
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Linfoma de Células T , Linfoma , Humanos , Camundongos , Animais , Proteína BRCA1 , Espécies Reativas de Oxigênio , Proteína BRCA2 , Células Matadoras Naturais , Linhagem Celular TumoralRESUMO
Ag2S quantum dot (QD) photodetectors (PDs) have attracted a lot of attention in the field of imaging system and optical communication. However, the current Ag2S PDs mainly works in the near-infrared band, and its detection ability in the visible band remains to be strengthened. In this paper, we used poly(3-hexylthiophene) (P3HT) with high carrier mobility and Ag2S QDs to construct heterojunction PD. Stronger absorption in blends with polymer P3HT compared to single Ag2S QDs. The optical absorption spectra show that the Ag2S/P3HT has strong light absorption peak at 394 and 598 nm. The results show that P3HT significantly enhances the absorption of Ag2S QDs from the visible to near-infrared band. The output characteristics, transfer characteristics and fast switching capability of the device at 405 nm, 532 nm and 808 nm were tested. The device has the responsivity of 6.05 A W-1, 83.72 A W-1and 37.31 A W-1under 405 nm, 532 nm and 808 nm laser irradiation. This work plays an important role in improving the detection performance of Ag2S QDs and broadening its applications in photoelectric devices for weak light and wide spectrum detection.
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BACKGROUND: Echocardiography (ECHO) and cardiac magnetic resonance imaging (MRI) are used to observe changes in the left ventricular structure in patients with breast and gastric cancer after 6 cycles of chemotherapy. Based on the observed values, we aimed to evaluate the cardiotoxicity of anthracyclines in cancer patients and to analyze the consistency of the two examination methods in assessing left ventricular function after chemotherapy. METHODS: From January 2020 to January 2022, the data of 80 patients with malignant tumors who received anthracycline chemotherapy (breast cancer, n = 40; gastric cancer, n = 40) and 40 healthy volunteers (Control group) were retrospectively collected. Serum high-sensitivity cardiac troponin T (hs-cTnT) levels were detected by an automatic immunoassay analyzer. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were measured by cardiac MRI and 2-dimensional ECHO using the biplane Simpson's method. RESULTS: Compared with baseline values, serum high-sensitivity cardiac troponin T (hs-cTnT) levels were significantly increased in patients with breast cancer and gastric cancer after 6 cycles of chemotherapy (P < 0.05). In addition, LVEDV, LVESV and LVEF measured with MRI were higher than those detected by ECHO in cancer patients after 6 cycles of chemotherapy (P < 0.05). And the Bland-Altman plot analysis showed that LVEDV, LVESV and LVEF measured by the two examination methods were in good agreement. CONCLUSION: Breast and gastric cancer patients exhibited elevated levels of hs-cTnT after 6 cycles of chemotherapy, indicating potential cardiotoxicity. Additionally, cardiac MRI and 2-dimensional ECHO showed good agreement in assessing left ventricular function, with ECHO tending to underestimate volume measurements compared to MRI.
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Neoplasias da Mama , Policetídeos , Neoplasias Gástricas , Humanos , Feminino , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Função Ventricular Esquerda , Volume Sistólico , Antraciclinas/efeitos adversos , Cardiotoxicidade , Estudos Retrospectivos , Troponina T , Imageamento por Ressonância Magnética , Neoplasias da Mama/tratamento farmacológico , Ecocardiografia , Antibióticos Antineoplásicos , Espectroscopia de Ressonância MagnéticaRESUMO
Sweet cherry (Prunus avium L.) has become an important economic fruit in China, mainly produced in Shandong Province. In recent years, the planting area of Aba Prefecture in Sichuan Province has increased. In June 2022, sweet cherry brown leaf spot was found in a cherry plantation (100ha) in Wenchuan County (30°54'50.21â³N, 103°24'49.10â³E), with an incidence of 50 - 70%. The symptoms appeared as brown circular spots on the leaf, gradually expanding until multiple lesions coalesced to form large irregular brown spots; eventually entire leaves were killed. To isolate the causal pathogens, 10 diseased trees were randomly selected from an orchard, one diseased leaf was taken from each tree, and samples (4×4 mm2) were cut from the border between diseased and healthy tissues of 10 diseased leaves, surface sterilized with 75% ethanol for 30 sec, washed three times with sterilized water, dried on sterilized filter paper and placed on potato dextrose agar (PDA). After 5d at 25â, five morphologically similar colonies were obtained, colony appears yellow fluffy and released a large amount of red-orangepigment. Microscopy revealed circular to ovoid, verrucose, and multicellular conidia measuring 20×25 µm diameter (n = 30) were produced on the mycelia. The morphological characteristics were consistent with the description of Epicoccum nigrum (Lima et al 2011). To further identify the strains, the internal transcribed spacer (ITS), ß-tubulin, and RNA polymerase second largest subunit (RPB2) gene regions were amplified with ITS1/ITS4 , Bt2a/Bt2b, and 5f2/7cr (White et al. 1990; Glass and Donaldson 1995; Sung et al. 2007), respectively. BLAST analysis revealed that the ITS, ß-tubulin, and RPB2 sequences were 99.2%, 100% and 99.6% homologous, with those of E. nigrum (KU204750.1, OL782123.1, and MW602294.1), respectively. The sequences of the five isolates were identical; and those of representative strain TY3 were deposited in GenBank (ITS, OP410968; ß-tubulin, OR502448; RPB2, OP484927). Maximum likelihood phylogenetic analyses were performed for the combined data set with ITS , ß-tubulin and RPB2 using MEGA6 under the Tamura-Nei model (Tamura et al. 1993). Isolate TY3 clustered with E. nigrum type strain CBS 505.85. The pathogenicity of TY3 was tested on 10 sweet cherry trees aged 3 years (there were about 50 leaves per plant). Five plants were sprayed with 50 mL of spore suspension (1×105 spores/mL), while the controls (Five plants) were sprayed with 50 mL of sterile water. All plants were in closed plastic bags to maintain high humidity, placed in a greenhouse, and incubated at 25âwith a 12-h photoperiod. Twelve days after inoculation, 35% of the inoculated leaves showed lesions; that were consistent with those observed in the field, and the control group was asymptomatic. To confirm Koch´s postulates, two isolates were taken from the margins of leaf lesions and both were confirmed to be E. nigrum based on morphological observations and molecular identification using ITS ß-tubulin, and RPB2 sequences. This is the first report of brown leaf spot caused by E. nigrum on P. avium in China. This discovery needs to be considered in developing and implementing disease management programs in sweet cherry production.
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To improve their spatial resolution and detection capabilities, future ground-based optical telescopes will have a size of 30 m, and the aperture of space telescopes will be increased to 10 m. Such large optical systems necessitate the development of large integrated testing equipment. In this study, spectrum and system alignment measurements and wavefront quality checking were performed using the sub-aperture detection method and a fiber-connected Photonics Scanning Pentaprism (PSP). First, the system was aligned using an optical truss, ensuring that the optical axis was properly positioned. Second, using a sub-aperture light beam though the entrance pupil, light spots were formed on the focal plane and transmitted to the spectrometer via fibers to obtain the corresponding spectral components. Then, by taking measurements at different system positions, a full-aperture spectrum response could be reached. Lastly, by photon-integrated interference on the focal plane, intensity interference fringes could be projected at the entrance pupil of the system. And the wavefront quality of the system could be verified by observing the fringe deformation. The measurement accuracy of the optical axis of the system is better than 2 mrad. The spectral measurement accuracy was better than 5%, and the wavefront measurement accuracy surpassed 0.1 wavelengths (1 wavelength = 633 nm). This study effectively enhanced the detection and in situ calibration capabilities of large telescope systems, ensuring that the performance requirements can be met in the design of future telescopes.
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Linear active disturbance rejection control (LADRC) has been widely used to improve the tracking accuracy and anti-disturbance performance of telescope servo control under disturbances. However, the linear extended state observer (LESO) is sensitive to noise, and its bandwidth is limited by the resonant frequency of the telescope. To enhance the LARDC's ability to attenuate disturbances, a novel cascade anti-disturbance structure (NCADS) with LADRC on the outer speed loop and a nonlinear disturbance observer (NDOB) on the inner current loop is proposed. The NDOB compensates for the dominant disturbance through feedforwarding the q-axis current reference, and the LESO compensates for the residual disturbance on the outer speed loop. First, the NCADS is introduced in a three-closed-loop control framework of PMSM. Then, the design method of the controller for each loop and the NDOB are presented, the parameter-tuning method based on bandwidth is demonstrated, and the convergence of the NDOB is proved. Furthermore, to improve the searching and tracking efficiency of wide-field survey telescopes, the nonlinear tracking differentiator (NTD) was modified to plan the transition process of the position loop, which only needs to set the maximum speed and acceleration of the telescope. Finally, simulations and experiments were performed on a 2.5-m-wide field survey telescope. The experimental results verify that the proposed NCADS method has a better anti-disturbance performance and higher tracking precision than the conventional method, and the improved NTD method does not need to tune parameters and achieved a fast and smooth transition process of the position loop.
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Telescópios , Projetos de Pesquisa , AceleraçãoRESUMO
BACKGROUND: Progressive hemifacial atrophy often causes lip vermilion defects in patients. In this study, we described a one-stage repair method for lip defects in progressive hemifacial atrophy using a lip vermilion mucosal flap or combined dermal fat flap graft. PATIENTS AND METHODS: Patients diagnosed with progressive hemifacial atrophy with lip vermilion defects from 2010 to 2022 were included in this study. Based on the severity and location of the patient's lip defect, a lip vermilion mucosal flap was designed and transferred to the lip defect or combined with a hip dermal fat flap for one-stage repair of the lip morphology. Lip morphology and function of patients were followed up after surgery. RESULTS: A total of 22 patients were enrolled in this study, including 15 patients with lip defects on the upper lip alone and 7 patients with both upper and lower lip defects. Follow-up six months to two years postoperatively, all patients recovered uneventfully without complications. The repaired lips of the patient had a full and symmetrical morphology with no visible scarring. Two patients experienced transient dysesthesia of the lips postoperatively and both returned to normal after three months. All patients had good lip closure with normal dietary and speech function. CONCLUSIONS: The method we described for repairing lip defects in progressive hemifacial atrophy can achieve satisfactory aesthetic and functional lip results. The distinct advantage of this approach is that the patients undergo only one-stage operation and it can be used to repair both upper and lower lip defects.
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OBJECTIVE: This study aimed to investigate the prevalence of obstructive sleep apnoea (OSA) in patients with craniofacial microsomia (CFM) through polysomnography (PSG) and the relationship with the severity of CFM. METHODS: This study reviewed patients of CFM with pre-operative PSG data between January 2005 and September 2023. Patients were grouped according to the Pruzansky-Kaban classification. OSA was diagnosed and severity was assessed by the obstructive apnea-hypopnea index. The Pediatric Sleep Questionnaire was used to investigate OSA-related signs and symptoms. The χ 2 test and Fisher's exact test were used to compare between groups. Univariate logistic regression was used to identify risk factors associated with OSA. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 121 patients with CFM were included in the study with 3 bilateral and 118 unilateral patients. In total, 86 patients (71.07%) were diagnosed with OSA. The prevalence of OSA in type IIa, type IIb and type III was 72.97%, 78.33%, and 47.62%. There was no statistically significant difference in the prevalence of OSA between type IIa and type IIb (p > .05). The difference in the prevalence of OSA between type III and type II was statistically significant (p < .05). Snoring was the most common symptom among the patients of CFM with OSA. CONCLUSIONS: Patients with CFM have a higher incidence of OSA based on PSG in type II and type III patients. The incidence of OSA did not correlate positively with the severity of CFM, with type III patients having certain particularities.
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Hypophosphatasia (HPP) is a rare genetic disorder mainly characterized by skeletal dysplasia that results from a deficiency in tissue-nonspecific alkaline phosphatase (TNSALP), which is encoded by the alkaline phosphatase (ALPL) gene. Odontohypophosphatasia (odonto-HPP) is a mild form of HPP characterized by oral symptoms, such as premature loss of primary teeth. This study was to describe a 4-year-old boy with premature loss of primary teeth who was diagnosed with odonto-HPP. X-ray radiography and laboratory examinations were performed for the diagnosis. Genetic etiology was revealed by whole-exome sequencing. A novel combination of two variants in the ALPL gene was identified in this case; this combination resulted in the odonto-HPP phenotype. c.346G>A (p.Ala116Thr) was inherited from the proband's father, whereas c.1563C>G (p.Ser521Arg) was inherited from the proband's mother. The proband's 8-year-old sister was a heterozygous carrier of c.346G>A (p.Ala116Thr) in the ALPL gene. Thus far, the proband's sister has been asymptomatic. Our findings indicate that c.346G>A is a pathogenic genetic alteration; c.1563C>G might cause a predisposition to the dental phenotype in combination with c.346G>A. It is important for pediatric dentists to consider a diagnosis of odonto-HPP in children with premature loss of primary teeth.
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Hipofosfatasia , Desmineralização do Dente , Humanos , Hipofosfatasia/genética , Hipofosfatasia/patologia , Fosfatase Alcalina/genética , Desmineralização do Dente/genética , MutaçãoRESUMO
Mesenchymal stem cells (MSCs) have shown great potential as important therapeutic tools for dental pulp tissue engineering, with the maintenance and enhancement of their stemness being crucial for successful therapeutic application in vivo and three-dimensional (3D) spheroid formation considered a reliable technique for enhancing their pluripotency. Human exfoliated deciduous tooth stem cells (SHED) were cultured in a low attachment plate to form aggregates for five days. Then, the resulting spheroids were analyzed for pluripotent marker expression, paracrine secretory function, proliferation, signaling pathways involved, and distribution of key proteins within the spheroids. The results indicated that 3D spheroid formation significantly increased the activation of the transforming growth factor beta (TGF-ß)/Smad signaling pathway and upregulated the secretion and mRNA expression levels of TGF-ß, which in turn enhanced the expression of pluripotency markers in SHED spheroids. The activation of the TGF-ß/Smad signaling pathway through 3D spheroid formation was found to preserve the stemness properties of SHED. Thus, understanding the mechanisms behind pluripotency maintenance of SHED culture through 3D spheroid formation could have implications for the therapeutic application of MSCs in regenerative medicine and tissue engineering.
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Células-Tronco Mesenquimais , Células-Tronco , Humanos , Células-Tronco/metabolismo , Células-Tronco Mesenquimais/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Transdução de Sinais , Dente Decíduo , Células Cultivadas , Polpa DentáriaRESUMO
In this article, we report a low-threshold random laser enhanced by TiN nanoparticles (NPs) suspended randomly in gain solutions. Results show that the random laser with TiN NPs has a lower threshold than the random laser with TiO2 NPs and the underlying mechanisms are discussed in detail. The localized surface plasmon resonance of individual TiN NPs increases the pump efficiency and strengthens the fluorescence amplification efficiency of the DCM. The multiple scattering of integral TiN NPs extends the dwelling time of light in random systems, which provides more possibilities for the light amplification in the gain medium. Then, the random laser threshold as a function of the number density of TiN NPs is studied. Results show that the optimum number density of TiN NPs for the lowest-threshold random lasers is about 1.468 × 1012ml-1. When we substitute the ethanol solution with the nematic liquid crystal (NLC), the random laser threshold can be further decreased to 5.11 µJ/pulse, which is about 7.7 times lower than that of DCM dye solution with TiN NPs under the same conditions. These findings provide a cost-effective strategy for the realization of low-threshold random lasers with high-quality.
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Bendamustine has been shown to have anti-tumor activities in hematological malignancies, but the role of bendamustine in natural killer (NK)/T cell lymphoma (NKTCL) treatment is unclear. Our study has shown that bendamustine had potent growth-inhibitory and apoptosis-inducing effects on NKTCL cells. Interestingly, we noticed that the combination of either gemcitabine or etoposide results in additive or synergistic cytotoxicity. Bendamustine induced mitochondria-mediated apoptosis in concentration- and time-dependent manners in NKTCL cells, shown as down-regulation of Bcl-2 and activation of cleavage of caspases 3, 7, 9 and poly adenosinediphosphate-ribose polymerase (PARP). Bendamustine arrested NKTCL cells in G2/M phase, with downregulation of expression of cyclin B1 and upregulation of expression of p-cdc2, p-cdc25c and p-P53. Furthermore, we confirmed that bendamustine activated DNA damage response (DDR) directly or through Ataxia Telangiectasia Mutated Protein (ATM)/Chk2 and ATR/Chk1 pathway and increased the intracellular reactive oxygen species (ROS) level in NKTCL cells, which caused G2/M phase arrest and apoptosis. Bendamustine also inhibited phosphorylation of transcriptional factor STAT3, contributing to cell apoptosis and proliferation inhibition. Finally, we verified the effect of bendamustine on NKTCL cells in vivo. It showed that bendamustine dramatically inhibited the growth of the subcutaneous tumor, with no obvious impact on mice weight. These findings demonstrate that bendamustine activates DDR pathway, induces the accumulation of intracellularROS level as well as inhibition of STAT3, leading to cell apoptosis and G2/M cell cycle arrest in NKTCL cells, which indicates that bendamustine dramatically suppressed NKTCL both in vitro and in vivo and provides a potential therapeutic strategy in the treatment of NK/T lymphoma.
Assuntos
Linfoma de Células T , Linfoma , Animais , Apoptose , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/farmacologia , Cloridrato de Bendamustina/farmacologia , Cloridrato de Bendamustina/uso terapêutico , Caspases/metabolismo , Caspases/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Ciclina B1/metabolismo , Ciclina B1/farmacologia , Etoposídeo , Humanos , Camundongos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ribose/farmacologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Magnetic resonance feature tracking (MR-FT) is an imaging technique that quantifies both global and regional myocardial strain. Currently, conventional MR-FT provides a superior signal and contrast-to-noise ratio but has a relatively low temporal resolution. A higher temporal resolution MR-FT technique may provide improved results. PURPOSE: To explore the impact of higher temporal resolution on left ventricular (LV) myocardial strain measurements using MR-FT. STUDY TYPE: Prospective. POPULATION: One hundred and fifty-three participants including five healthy subjects and patients with various cardiac diseases referred to MR for cardiac assessment. FIELD STRENGTH: 3 T, balanced steady-state free precession sequence with and without compressed sensing (temporal resolution: 10 msec and 40 msec, respectively). ASSESSMENT: Conventional (40 msec) and higher (10 msec) temporal resolution data were acquired in all subjects during the same scanning session. Global circumferential strain (GCS), global longitudinal strain (GLS), and global radial strain (GRS) as well as peak systolic and diastolic strain rates (SRs) were measured by MR-FT and compared between the two temporal resolutions. We also performed subgroup analyses according to heart rates (HRs) and LV ejection fraction (LVEF). STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, linear regression analyses, Bland-Altman plots. A P value <0.05 was considered to be statistically significant. RESULTS: GCS and GRS were significantly higher in the 10-msec temporal resolution studies compared to the 40-msec temporal resolution studies (GCS: -13.00 ± 6.58% vs. -12.51 ± 5.76%; GRS: 21.97 ± 14.54% vs. 20.62 ± 12.52%). In the subgroup analyses, significantly higher GLS, GCS, and GRS values were obtained in subjects with LVEF ≥50%, and significantly higher GCS and GRS values were obtained in subjects with HRs <70 bpm when assessed with the 10-msec vs. the 40-msec temporal resolutions. All the peak systolic and diastolic SRs were significantly higher in the higher temporal resolution acquisitions. This was also true for all subgroups. DATA CONCLUSIONS: Higher temporal resolution resulted in significantly higher cardiac strain and SR values using MR-FT and could be beneficial, particularly in patients with LVEF ≥50% and HR <70 bpm. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.
Assuntos
Ventrículos do Coração , Função Ventricular Esquerda , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Volume Sistólico , Função Ventricular Esquerda/fisiologiaRESUMO
For large ground-based telescopes, static and dynamic disturbances would greatly degrade the optical performance. This is especially true for wide field survey telescopes with prime focus optics. The estimation of disturbance effects on large telescopes is becoming increasingly important during the design phase. Therefore, a wide field survey telescope with 2.5 m aperture and 3.5 deg field of view is studied in this research. This telescope is under construction now, and its first light is expected at the beginning of 2023. The estimation method for the optical performance under static and dynamic disturbances in the temporal domain and the active compensation method to improve the optical alignment, are investigated, which is a supplement for the simulation in the frequency domain. First, based on the mechanical model, the optical misalignment is established, where the deviation of the primary mirror is obtained from the length gauges and the deviation of the corrector is computed using the fitting method. Second, a method for compensating the static and dynamic disturbances is proposed, improving the optical performance. This method uses the disturbed primary mirror as the reference, and the corrector is actively controlled to align with it. Finally, a series of experimental tests and numerical simulations is conducted. The results show that the mechanical modeling error is within 10% and the maximum optical misalignment is reduced from 12''/0.27 to 0.2''/0.006mm for static disturbance and from 1.3''/0.03 to 0.4''/0.01mm for dynamic disturbance. Through active compensation, the telescope optical property is greatly improved. The modeling method and the simulation process mentioned in this research can also be used in the other relevant fields.