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OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.
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Injúria Renal Aguda , Dexmedetomidina , Ratos , Animais , Dexmedetomidina/efeitos adversos , Cisplatino/toxicidade , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/patologia , Rim/patologia , Interleucina-1beta , Caspases/efeitos adversosRESUMO
Pyroptosis is a type of programmed cell death mediated by the Gasdermin family. It is triggered in response to pathogen infection or other danger signals. The activation of Gasdermins leads to pyroptosis and the release of large amounts of inflammatory cytokines. Pyroptosis plays a crucial role in combating pathogen infections, as it helps to eliminate infected cells and activate the immune system. However, pathogens have already developed sophisticated strategies to evade or inhibit pyroptosis, allowing them to persist and facilitate infection. This review provides an overview of the discovery of pyroptosis and its importance in anti-infectious immunity. We also discuss several new strategies for inhibiting pyroptosis by pathogens. A thorough learning of the occurrence and regulation of pyroptosis may reveal the pathogenesis of related infectious diseases and contribute to developing effective anti-infective therapeutic strategies.
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Evasão da Resposta Imune , Piroptose , Piroptose/imunologia , Humanos , AnimaisRESUMO
Transcription and pre-mRNA splicing are coupled to promote gene expression and regulation. However, mechanisms by which transcription and splicing influence each other are still under investigation. The ATPase Prp5p is required for pre-spliceosome assembly and splicing proofreading at the branch-point region. From an open UV mutagenesis screen for genetic suppressors of prp5 defects and subsequent targeted testing, we identify components of the TBP-binding module of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex, Spt8p and Spt3p. Spt8Δ and spt3Δ rescue the cold-sensitivity of prp5-GAR allele, and prp5 mutants restore growth of spt8Δ and spt3Δ strains on 6-azauracil. By chromatin immunoprecipitation (ChIP), we find that prp5 alleles decrease recruitment of RNA polymerase II (Pol II) to an intron-containing gene, which is rescued by spt8Δ. Further ChIP-seq reveals that global effects on Pol II-binding are mutually rescued by prp5-GAR and spt8Δ. Inhibited splicing caused by prp5-GAR is also restored by spt8Δ. In vitro assays indicate that Prp5p directly interacts with Spt8p, but not Spt3p. We demonstrate that Prp5p's splicing proofreading is modulated by Spt8p and Spt3p. Therefore, this study reveals that interactions between the TBP-binding module of SAGA and the spliceosomal ATPase Prp5p mediate a balance between transcription initiation/elongation and pre-spliceosome assembly.
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RNA Helicases DEAD-box/metabolismo , Splicing de RNA , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Alelos , Genes Fúngicos/genética , Genoma Fúngico/genética , Mutação , Fenótipo , Ligação Proteica , RNA Polimerase II/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética , Especificidade por Substrato , Fatores de Transcrição/deficiência , Fatores de Transcrição/genéticaRESUMO
Objective To investigate the clinicopathological features,immunohistochemical characteristics,diagnosis,treatment and prognosis of intrathyroid thymic carcinoma.Methods Clinical data of 7 patients with intrathyroid thymic carcinoma were retrospectively reviewed.Histological examination and immunohistochemical staining were performed on the surgically resected tumors.The infection of Epstein-Barr virus(EBV)was detected by EBER in situ hybridization.Results The 7 patients included 5 males and 2 females.The age ranged from 40 to 71 years,with a median of 54 years.The tumors were located in the thyroid gland,with the maximum diameter ranging from 2.2 cm to 6.0 cm and the average maximum diameter of(4.0±1.2)cm.All the patients underwent thyroid gland resection and local lymph node dissection.After operation,all the cases were treated with radiotherapy and five of them additionally received chemotherapy.Six patients were followed up for 10-163 months,all of whom were still alive,including 2 patients with recurrence in situ,1 patient with homolateral cervical lymph node metastasis and the rest with no recurrence or metastasis.CK-pan,P63,CD5 and CD117 were expressed in all the cases,while TTF-1,TG,CT and PAX8 were negative.One case of them expressed SYN and CgA.Ki-67 proliferation index ranged from 10% to 90%.EBER in situ hybridization showed negative results in all 7 cases.Conclusions Intrathyroid thymic carcinoma is a relatively low-grade malignant tumor.The combination of immunohistochemical CD5,CD117 and monoclonal PAX8 is helpful in the diagnosis and differential diagnosis of intrathyroid thymic carcinoma.EBV may not be involved in the development of intrathyroid thymic carcinoma.Thyroid gland resection plus central lymph node dissection is an important treatment measure for intrathyroid thymic carcinoma.For patients with regional lymph node metastasis and obvious peripheral tissue invasion,postoperative radiotherapy with/without chemotherapy can effectively delay the disease progression.
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Infecções por Vírus Epstein-Barr , Timoma , Neoplasias do Timo , Pré-Escolar , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias do Timo/terapiaRESUMO
Doublesex is highly conserved and sex-specifically spliced in insect sex-determination pathways, and its alternative splicing (AS) is regulated by Transformer, an exonic splicing activator, in the model system of Drosophila melanogaster. However, due to the lack of a transformer gene, AS regulation of doublesex remains unclear in Lepidoptera, which contain the economically important silkworm Bombyx mori and thousands of agricultural pests. Here, we use yeast three-hybrid system to screen for RNA-binding proteins that recognize sex-specific exons 3 and 4 of silkworm doublesex (Bm-dsx); this approach identified BxRBP1/Lark binding to the exon 3, and BxRBP2/TBPH and BxRBP3/Aret binding to the exon 4. Investigation of tissues shows that BxRBP1 and BxRBP2 have no sex specificity, but BxRBP3 has - three of its four isoforms are expressed with a sex-bias. Using novel sex-specific silkworm cell lines, we find that BxRBP1 and BxRBP3 directly interact with each other, and cooperatively function as splicing repressors. Over-expression of BxRBP1 and BxRBP3 isoforms efficiently inhibits splicing of the exons 3 and 4 in the female-specific cells and generates the male-specific isoform of Bm-dsx. We also demonstrate that the sex-determination upstream gene Masc regulates alternatively transcribed BxRBP3 isoforms. Thus, we identify a new regulatory mechanism of doublesex AS in the silkworm, revealing an evolutionary divergence in insect sex-determination.
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Processamento Alternativo , Bombyx/genética , Proteínas de Ligação a DNA/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Bombyx/metabolismo , Proteínas de Ligação a DNA/metabolismo , Éxons , Feminino , Genes de Insetos , Proteínas de Insetos/química , Masculino , Sinais de Localização Nuclear , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Caracteres Sexuais , Transcrição GênicaRESUMO
PURPOSE: Anti-angiogenic agents have shown promise for treating advanced hepatocellular carcinoma (HCC), and the primary mechanism of low-dose metronomic chemotherapy using traditional cytotoxic drugs is anti-angiogenic. This study evaluated the efficacy of metronomic capecitabine and thalidomide after cool-tip radiofrequency ablation (RFA), relative to RFA alone, for treating patients with HCC. METHODS AND MATERIALS: Patients with HCC were randomly apportioned to a test group (n = 22) receiving metronomic chemotherapy with capecitabine and thalidomide after RFA, or a control group (n = 28) receiving RFA only. Serum circulating endothelial cells (CECs) and vascular endothelial growth factor (VEGF) were measured in all patients before and 1 month after RFA treatment. Enhanced computed tomography or ultrasound imaging was performed to evaluate efficacy during 12 months of follow-up. The treatment groups were further stratified as HCC within or outside the Milan criteria for transplantation. RESULTS: One month post-treatment, the tumour response rate (TRR), including complete response and partial response rate, of the test and control groups was statistically similar. At 12 months, the TRR of the test group (68.2%) was significantly higher than that of the control group (35.7%). In the test group, the TRR of patients whose tumour burdens were outside the Milan criteria was significantly higher than that of the control group. One month post-treatment, CECs and VEGF levels of the test group were significantly lower than baseline, while those of the control group were significantly higher. At the end of the 12-month follow-up, there was a progression-free survival (PFS) benefit of 2 months in the test group. CONCLUSION: Metronomic capecitabine and thalidomide after RFA significantly reduced recurrence of HCC and extended PFS, especially for HCC outside the Milan criteria, perhaps via reduction of serum CECs and VEGF levels and inhibition of tumour angiogenesis.
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Administração Metronômica , Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Talidomida/administração & dosagem , Adulto , Idoso , Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Células Endoteliais , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Talidomida/uso terapêutico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
PURPOSE: Our aim was to evaluate the results of short-segment pedicle instrumentation with screw insertion in the fracture level and find factors predicting kyphosis recurrence in thoracolumbar burst fractures. METHODS: We retrospectively analysed 122 patients with thoracolumbar burst fracture who were divided into two groups: kyphosis recurrence and no kyphosis recurrence. Pre-operative radiographic data comprising Cobb angle (CA), regional angle, anterior vertebra height (AVH), upper intervertebral angle, vertebral wedge angle (VWA), pre-anteroposterior A/P approach, superior endplate fracture, load-sharing classification (LSC) score and clinical data including age, visual analogue scale (VAS) score, thoracolumbar injury classification and severity score were compared between groups. T test, Pearson's chi-square and multivariate logistic regression were calculated for variables. RESULTS: CA, VWA and AVH were significantly corrected after surgery. CA changed from 23.7 to 3.0 (p <0.001), VWA from 38.7 to 9.6 (p <0.001) and AVH from 48.8 % to 91.2 % (p <0.001). These parameters were well maintained during the follow-up period with a mild, tolerant loss of correction. Neurological function and pain were significantly improved without deterioration. Age, pre-A/P and pre-AVH < 50 % influenced kyphosis recurrence (p = 0.032, 0.026, 0.011, respectively). CONCLUSIONS: Short-segment pedicle instrumentation including the fractured vertebra was effective in treating thoracolumbar burst fractures. The loss of correction at follow-up after implant removal was associated with age, A/P ratio and anterior vertebral height < 50 %.
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Parafusos Ósseos/efeitos adversos , Fixação Interna de Fraturas/métodos , Cifose/cirurgia , Vértebras Lombares/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Adulto , Idoso , Remoção de Dispositivo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: For the purpose of skeletal muscle engineering, primary myoblasts (Mb) and adipogenic mesenchymal stem cells (ADSC) can be co-cultured and myogenically differentiated. Electrospun composite nanofiber scaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability Although growth differentiation factor 11 (GDF11) has been proposed as a rejuvenating circulating factor, restoring skeletal muscle function in aging mice, some studies have also described a harming effect of GDF11. Therefore, the aim of the study was to analyze the effect of GDF11 on co-cultures of Mb and ADSC on poly-ε-caprolactone (PCL)-collagen I-polyethylene oxide (PEO)-nanofibers. RESULTS: Human Mb were co-cultured with ADSC two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-PEO-nanofibers. Differentiation media were either serum-free with or without GDF11, or serum containing as in a conventional differentiation medium. Cell viability was higher after conventional myogenic differentiation compared to serum-free and serum-free + GDF11 differentiation as was creatine kinase activity. Immunofluorescence staining showed myosine heavy chain expression in all groups after 28 days of differentiation without any clear evidence of more or less pronounced expression in either group. Gene expression of myosine heavy chain (MYH2) increased after serum-free + GDF11 stimulation compared to serum-free stimulation alone. CONCLUSIONS: This is the first study analyzing the effect of GDF11 on myogenic differentiation of Mb and ADSC co-cultures under serum-free conditions. The results of this study show that PCL-collagen I-PEO-nanofibers represent a suitable matrix for 3D myogenic differentiation of Mb and ADSC. In this context, GDF11 seems to promote myogenic differentiation of Mb and ADSC co-cultures compared to serum-free differentiation without any evidence of a harming effect.
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Células-Tronco Mesenquimais , Nanofibras , Humanos , Camundongos , Animais , Alicerces Teciduais , Polietileno/metabolismo , Polietileno/farmacologia , Poliésteres/metabolismo , Poliésteres/farmacologia , Células-Tronco Mesenquimais/metabolismo , Mioblastos/metabolismo , Diferenciação Celular , Polietilenoglicóis/metabolismo , Polietilenoglicóis/farmacologia , Colágeno/metabolismo , Colágeno/farmacologia , Proteínas Morfogenéticas Ósseas/metabolismo , Fatores de Diferenciação de Crescimento/metabolismoRESUMO
For the purpose of skeletal muscle tissue engineering, different cell types have been investigated regarding their myogenic differentiation potential, including co-cultured myoblasts and adipogenic mesenchymal stromal cells (Mb/ADSC). As neural cells enhance synaptic junction formation, the aim of this study was to co-culture Schwann cells (SCs) with Mb/ADSC on biocompatible electrospun aligned poly-ε-polycaprolacton (PCL)-collagen I-nanofibers. It was hypothesized that SCs, as part of the peripheral nervous system, promote the myogenic differentiation of Mb/ADSC co-cultures. Mb/ADSC were compared to Mb/ADSC/SC regarding their capacity for myogenic differentiation via immunofluorescent staining and gene expression of myogenic markers. Mb/ADSC/SC showed more myotubes after 28 days of differentiation (p ≤ 0.05). After 28 days of differentiation on electrospun aligned PCL-collagen I-nanofibers, gene expression of myosin heavy chains (MYH2) and myogenin (MYOG) was upregulated in Mb/ADSC/SC compared to Mb/ADSC (p ≤ 0.01 and p ≤ 0.05, respectively). Immunofluorescent staining for MHC showed highly aligned multinucleated cells as possible myotube formation in Mb/ADSC/SC. In conclusion, SCs promote myogenic differentiation of Mb/ADSC. The co-culture of primary Mb/ADSC/SC on PCL-collagen I-nanofibers serves as a physiological model for skeletal muscle tissue engineering, applicable to future clinical applications.
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Células-Tronco Mesenquimais , Nanofibras , Caproatos , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Lactonas , Células-Tronco Mesenquimais/metabolismo , Mioblastos/metabolismo , Células de SchwannRESUMO
In Drosophila, presenilin is an aspartyl protease that plays important roles in the development and calcium homeostasis. It has been expressed all through the fly developmental process. The loss of Drosophila presenilin (DPS) function causes significantly decreased Notch signaling and neuron apoptosis and increased cytoplasm calcium. This subsequently led to impaired long term memory and cognitive deficits. Therefore, study of DPS is one of the most popular models for Alzheimer's disease research, and has provided important insights into the pathological mechanisms of AD. This review is to summarize the AD related function of DPS gene.
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Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Presenilinas/genética , Sequência de Aminoácidos , Animais , Apoptose , Cálcio/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Humanos , Dados de Sequência Molecular , Neurônios/citologia , Neurônios/metabolismo , Presenilinas/metabolismo , Alinhamento de Sequência , Transdução de SinaisRESUMO
OBJECTIVE: To investigate the CT and MR features of "inferior vena cava(IVC) reverse-flow" sign and "jet-blood" sign in Budd-Chiari Syndrome (BCS). METHODS: The liver CT and/or MRI plain scan and dynamic enhancement of 107 cases of BCS diagnosed by DSA and/or clinic were collected, including 17 patients with hepatic vein obstruction type, 79 patients with IVC obstruction type, and 11 patients with mixed type. The manifestations of IVC reverse-flow sign and jet-blood sign in the latter two type BCS (90cases) imaging were analyzed. RESULTS: 1) The incidence of IVC reverse-flow sign in the IVC obstruction type and mixed type was 93.3 %(83/90), which was manifested as: The contrast agent was shown below the level of renal veins in the hepatic arterial phase enhancement, while no contrast agent was shown above it at the same time. 2) The incidence of jet-blood sign in membrane-perforated subtype was 100 %(15/15) or 16.7 %(15/90), which was manifested as: The low density/signal dots appeared within full of contrast agent at the superior liver segment IVC on axial slices in arterial phase of CT/MRI enhancement, or the low signal line within agent presented above the IVC membrane on coronal image in equilibrium phase of MR enhancement. 3) Other imaging findings: 75 cases of membrane, 18 cases of membrane calcification, 27 cases of abnormal hepatic vein, 76 cases of abnormal structure of IVC, 18 cases of thrombus/cancer embolus in hepatic vein and/or IVC. There were 65 cases of abnormal liver appearance; 71 cases of abnormal liver enhancement; 21 cases of hepatic vein unsynchronous enhancement. Anastomotic branches among the hepatic veins open with comma sign in 54 cases; dilatation of intraspinal and paravertebral veins, azygos and hemiazygos veins in 90 cases(100 %, 90/90) or 96 cases(89.7 %, 96/107). CONCLUSIONS: The "IVC reverse-flow" sign is a specific CT and MR sign of IVC type and mixed type BCS, and the "jet-blood" sign is a characteristic CT and MR sign of membrane-perforated subtype BCS.
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Síndrome de Budd-Chiari , Síndrome de Budd-Chiari/diagnóstico por imagem , Veias Hepáticas/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Veia Cava Inferior/diagnóstico por imagemRESUMO
Radiotherapy is one of the important treatment modalities for malignant tumors. Conventional fractionation is the most commonly-used radiotherapy mode, but it has disadvantages such as long treatment time and low efficiency, etc. With the advancement of radiotherapy equipment and technology, moderately hypofractionated radiotherapy has become the standard treatment for tumors such as breast cancer and prostate cancer, etc. However, the efficacy and safety of moderately hypofractionated radiotherapy have not been fully confirmed in a wider range of tumors. In this article, the application, efficacy, and safety of moderately hypofractionated radiotherapy in malignant tumors were reviewed.
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OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy (abbreviated as “national centralized procurement policy”) in Guangxi Zhuang Autonomous Region prefecture, and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators (such as availability, affordability, and drug safety) and eighteen third-level indicators (such as completion rate of agreed purchase volume, affordability level, drug revenue proportion) were introduced, guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation (in 2019 and 2020) in terms of differences and change trends. RESULTS In terms of accessibility, the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%, the proportion of diseases involved and median completed procurement rate were 40.16%, and 287.82% respectively, and the total centralized delivery rate was 97.20%. In terms of affordability, the total reduction amplitude in drug price was 74.80% from 2019 to 2022; the charge for medicine per capita in hospitalization, the proportion of medicine used for outpatient service and hospitalization, decreased by 17.61%, 10.22%, and 20.10% in order; the burden levels on medical fares for patients were all below 1 in addition to chronic diseases, and anti-tumor drugs. In terms of the impact on medicine, the ratio of adverse drug reaction event cases in 2022 was 66.00%, an increase of 1.29% compared to the previous; since the implementation of the policy, 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation, and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance, the public medical institutions achieved generic substitution for originator drugs mostly until 2022; about 9.12% of drugs that were non- centrally purchased in the same category were used; 63.39% of people under investigation did not show a need for a second dressing change; drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand, attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic, conducting clinically comprehensive evaluation of selected drugs, and improving reasonable allocation strategy, etc.
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Objective: To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation. Methods: This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized. Results: The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations. Conclusions: Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.
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Criança , Recém-Nascido , Humanos , Masculino , Adolescente , Síndrome de Zellweger/diagnóstico , Hipotonia Muscular , Estudos Retrospectivos , Mutação da Fase de Leitura , Sequenciamento do Exoma , Mutação , ATPases Associadas a Diversas Atividades Celulares/genéticaRESUMO
Vesicles possessing poly(ethylene glycol) (PEG) chains on their surface have been described as a blood-persistent drug delivery system with potential applications for intravenous drug administration. In this research with different molecular weights (400-10,000g/mol) of PEG, a series of Chol-PEG(m) conjugates were generated by the DCC (N,N'-dicyclohexylcarbodiimide, DCC)/(4-dimethylaminopyridine, 4-DMAP) esterification method, and confirmed by FT-IR and (1)H NMR spectrum. Then their properties in aqueous solution were studied by electron microscopy images, associative behavioral and systematic tensiometric studies over a wide concentration range. In order to elucidate the application of this Chol-PEG(m) in vesicles, conventional nonionic surfactant vesicles (niosomes) composed of span 60 and cholesterol were prepared and the influence of various hydrophilic chains of the Chol-PEG(m) conjugates was investigated. Results indicated that all the niosomes prepared, with or without Chol-PEG(m) composition were similar in micrograph with diameter between 120 nm and 180 nm. The fixed aqueous layer thickness (FALT) around niosomes increased as Chol-PEG(m) chain length increase, particularly in the Chol-PEG(10,000) modified niosomes with 9.33+/-0.67 nm. In vitro release experiments indicated that release rate of nimodipine from Chol-PEG(m) modified niosomes was enhanced. Chol-PEG(m) modified niosomes showed greater accumulative release than that of plain niosomes over a period of 24 h. These studies have shed some light on the suitability of Chol-PEG(m) containing niosome preparation.
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Colesterol/química , Polietilenoglicóis/química , Tensoativos/química , Colesterol/síntese química , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Polietilenoglicóis/síntese química , Reologia , Tensão Superficial , ViscosidadeRESUMO
BACKGROUND: Surgical wound closure directly influences spinal surgical efficiency and several postoperative complications. The traditional suture technique is time-consuming and associated with greater rates of complications. Bidirectional absorbable barbed sutures seem to compensate for some of the limitations of traditional suture; however, they rarely are reported in spinal surgery. We designed a novel suture technique for use in thoracolumbar spinal surgery. METHODS: The data of 189 patients with traumatic thoracolumbar fractures were analyzed between bidirectional barbed suture closure and traditional interrupted suture closure. Data of operative time, wound closure time, length of incision, intraoperative blood loss, complications of wound dehiscence and postoperative hematoma, cost, and neurologic status were collected. RESULTS: No significant differences were observed in the baseline demographics of included patients. Compared with the traditional suturing group, the barbed sutures decreased the mean operative time (P = 0.037), suture time (P < 0.01), and mean suturing time (P < 0.01) significantly, although no statistically significant differences were found in blood loss (P = 0.724) and neurologic functional scores (preoperative: P = 0.901; 3 months after surgery: P = 0.208; final follow-up assessments: P = 0.163), and no statistically significant differences were found in rates of postoperative infection, hematoma, and wound dehiscence. CONCLUSIONS: Our findings suggest that the novel knotless barbed suture has comparable strength to traditional sutures, with the advantage of less suturing time. It is an efficient, safe technique, and alternative choice for patients with thoracolumbar fracture after posterior surgery.
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Vértebras Lombares/cirurgia , Duração da Cirurgia , Fraturas da Coluna Vertebral/cirurgia , Técnicas de Sutura/tendências , Vértebras Torácicas/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico , Técnicas de Sutura/normas , Vértebras Torácicas/lesõesRESUMO
Objective:To evaluate the clinical application of online adaptive radiotherapy based on iterative cone-beam computed tomography (iCBCT) for the pelvic malignancies.Methods:This was a prospective clinical trial of iCBCT guided online adaptive radiotherapy for pelvic malignancies in Department of Radiation Oncology, Peking Union Medical College Hospital. Clinical data of 13 patients with pelvic malignancies who received online adaptive radiotherapy from August to November, 2022 were preliminarily analyzed (2 cases of cervical cancer, 4 postoperative cervical cancer, 3 postoperative endometrial cancer, 3 bladder cancer and 1 prostate cancer). The feasibility of online adaptive radiotherapy, adaptive radiotherapy time, the frequency and magnitude of edits for organs at risk and target volume, target volume coverage and organs at risk doses were analyzed. Statistical analysis was performed by SPSS software. Data conforming to normal distribution were described by Mean±SD, and data with non-normal distribution were expressed by M ( Q1, Q3). Data with homogeneous variances were analyzed by t-test, and data with non-normal distribution or heterogeneous variances were analyzed by nonparametric test. Results:The average adaptive time was 15 min and 38 s (from acceptance of acquired CBCT scan to completion of the final plan selection). 85.4% (830/972 fractions) of influencer structures (system-defined organs adjacent to and with high impact on the generation of clinical target volume and planning target volume, primarily bladder, rectum and small intestine in pelvic neoplasms) automatically generated by artificial intelligence required no edits or minor editors, and 89.8% (491/547 fractions) of clinical target volume automatically generated by artificial intelligence required no edits or minor editors. The adapted plan was adopted in 98.5% (319/324 fractions) of radiotherapy fractions. Compared with the scheduled plan, the adapted plan showed better target volume coverage and reduced the dose of organs at risk.Conclusions:iCBCT guided online adaptive radiotherapy for the pelvic malignancies can be achieved within clinically acceptable timeslots. In addtion, better dose coverage of target volume shows the advantages of online adaptive radiotherapy.
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@#AIM: To evaluate the efficacy of mycophenolate mofetil(MMF)on the prevention of relapse and visual prognosis of patients in neuromyelitis optica spectrum disorders(NMOSD)with AQP4 antibody positive optic neuritis. <p>METHODS: We retrospectively reviewed 11 patients with initial diagnosis of NMOSD and AQP4 antibody positive optic neuritis from January 2017 to December 2019. Among the 11 patients, 3 were male and 8 were female. The unique core clinical manifestation of NMOSD was optic neuritis. The onset age was 36.3±6.0(27-47)years old. Duration of the disease was 3.4±1.4(2.2-6.8)a. MMF was added in the relieving period of NMOSD for 1a or over 1a. Annualized relapsing rate(ARR), best corrected vision activity(BCVA)and adverse reactions of MMF were recorded.<p>RESULTS: The median time of MMF treatment was 18(12, 36)mo. The ARR was 0.66/a at baseline and 0.16/a after the treatment. There were 91% of the patients had decreased ARR and 82% of them had no clinical relapse. The patients had significant improvement on ARR after MMF treatment(<i>P</i><0.05 ). In total, there was no significant difference between the mean BCVA after treatment and that at baseline(<i>P</i>>0.05). Of the 11 patients, 3 patients had side effects(27%), including 1 patient with elevated liver transaminase(9%), and 2 patients with mild gastrointestinal reaction(18%)during follow-up period. None of them discontinued MMF due to adverse events.<p>CONCLUSION: MMF treatment for AQP4 antibody positive NMOSD can reduce the ARR of optic neuritis to a certain extent and protect the visual function of patients.
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Selective laser melting (SLM) is raised as one kind of additive manufacturing (AM) which is based on the discrete-stacking concept. This technique can fabricate advanced composites with desirable properties directly from 3D CAD data. In this research, 316L stainless steel (316L SS) and different fractions of calcium silicate (CaSiO3) composites (weight fractions of calcium silicate are 0%, 5%,10% and 15%, respectively) were prepared by SLM technique with a purpose to develop biomedical metallic materials. The relative density, tensile, microhardness and elastic modulus of the composites were tested, their microstructures and fracture morphologies were observed using optical microscope (OM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). It was found that the addition of CaSiO3 particles influenced the microstructure and mechanical properties of specimens significantly. The CaSiO3 precipitates from the overlap of adjacent tracks and became the origin of the defects. The tensile strength of specimens range 320-722MPa. The microhardness and elastic modulus are around 250HV and 215GPa respectively. These composites were ductile materials and the fracture mode of the composites was mixed mode of ductile and brittle fracture. The 316L SS/CaSiO3 composites can be a potential biomedical metallic materials in the medical field.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Compostos de Cálcio/química , Lasers , Silicatos/química , Aço Inoxidável/química , Módulo de Elasticidade , Resistência à TraçãoRESUMO
Objective:To compare and analyze the value of X-ray examination and MRI in the diagnosis of subacromial impingement syndrome.Methods:Sixty patients with shoulder pain and weakness in Beijing Tiantan Hospital, Capital Medical University from January 2019 to May 2021 were selected. All patients underwent X-ray and MRI. Taking clinical diagnosis as the gold standard, the diagnostic efficacy of X-ray and MRI in subacromial impact syndrome was compared and analyzed.Results:The consistency between MRI and gold standard was good ( Kappa = 0.769, P<0.01), and the consistency between X-ray and gold standard was general ( Kappa = 0.464, P<0.01); there was no significant difference between X-ray examination and MRI examination of acromion morphological classification, subacromial space classification ( P>0.05); The sensitivity of MRI was higher than that of X-ray, and the difference was statistically significant ( χ2 = 4.00, P<0.05). There was no difference between MRI and X-ray, and the difference was not statistically significant ( χ2 = 0.25, P>0.05). Conclusions:X-ray and MRI are complementary to each other in the diagnosis of subacromial impingement syndrome. X-ray examination should be carried out first, and MRI should be carried out when necessary.