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1.
Proc Natl Acad Sci U S A ; 119(19): e2116380119, 2022 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-35500124

RESUMEN

SignificanceThere is a common consensus that lode gold deposits mostly precipitated from metamorphic fluids via fluid boiling and/or fluid-rock interaction, but whether magmatic hydrothermal fluids and the mixing of such fluids with an external component have played a vital role in the formation of lode gold deposits remains elusive. We use garnet secondary ion mass spectrometry oxygen isotope analysis to demonstrate that the world-class Dongping lode gold deposit has been formed by multiple pulses of magmatic hydrothermal fluids and their mixing with large volumes of meteoric water. This study opens an opportunity to tightly constrain the origin of lode gold deposits worldwide and other hydrothermal systems that may have generated giant ore deposits in the Earth's crust.

2.
J Neurosci ; 43(49): 8547-8561, 2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-37802656

RESUMEN

Dysfunctional gene expression in nociceptive pathways plays a critical role in the development and maintenance of neuropathic pain. Super enhancers (SEs), composed of a large cluster of transcriptional enhancers, are emerging as new players in the regulation of gene expression. However, whether SEs participate in nociceptive responses remains unknown. Here, we report a spinal-specific SE (SS-SE) that regulates chronic constriction injury (CCI)-induced neuropathic pain by driving Ntmt1 and Prrx2 transcription in dorsal horn neurons. Peripheral nerve injury significantly enhanced the activity of SS-SE and increased the expression of NTMT1 and PRRX2 in the dorsal horn of male mice in a bromodomain-containing protein 4 (BRD4)-dependent manner. Both intrathecal administration of a pharmacological BRD4 inhibitor JQ1 and CRISPR-Cas9-mediated SE deletion abolished the increased NTMT1 and PRRX2 in CCI mice and attenuated their nociceptive hypersensitivities. Furthermore, knocking down Ntmt1 or Prrx2 with siRNA suppressed the injury-induced elevation of phosphorylated extracellular-signal-regulated kinase (p-ERK) and glial fibrillary acidic protein (GFAP) expression in the dorsal horn and alleviated neuropathic pain behaviors. Mimicking the increase in spinal Ntmt1 or Prrx2 in naive mice increased p-ERK and GFAP expression and led to the genesis of neuropathic pain-like behavior. These results redefine our understanding of the regulation of pain-related genes and demonstrate that BRD4-driven increases in SS-SE activity is responsible for the genesis of neuropathic pain through the governance of NTMT1 and PRRX2 expression in dorsal horn neurons. Our findings highlight the therapeutic potential of BRD4 inhibitors for the treatment of neuropathic pain.SIGNIFICANCE STATEMENT SEs drive gene expression by recruiting master transcription factors, cofactors, and RNA polymerase, but their role in the development of neuropathic pain remains unknown. Here, we report that the activity of an SS-SE, located upstream of the genes Ntmt1 and Prrx2, was elevated in the dorsal horn of mice with neuropathic pain. SS-SE contributes to the genesis of neuropathic pain by driving expression of Ntmt1 and Prrx2 Both inhibition of SS-SE with a pharmacological BRD4 inhibitor and genetic deletion of SS-SE attenuated pain hypersensitivities. This study suggests an effective and novel therapeutic strategy for neuropathic pain.


Asunto(s)
Hipersensibilidad , Neuralgia , Ratas , Masculino , Ratones , Animales , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Hiperalgesia/metabolismo , Ratas Sprague-Dawley , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Neuralgia/metabolismo , Asta Dorsal de la Médula Espinal/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipersensibilidad/metabolismo
3.
Br J Haematol ; 204(5): 1830-1837, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38356434

RESUMEN

Idiopathic multicentric Castleman disease (iMCD) is subclassified into iMCD-thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly (TAFRO) and iMCD-not otherwise specified (NOS) according to the Castleman Disease Collaborative Network (CDCN) consensus criteria. With a deeper understanding of iMCD, a group of patients with iMCD-NOS characterised by polyclonal hypergammaglobulinaemia, plasmacytic/mixed-type lymph node histopathology and thrombocytosis has attracted attention. This group of patients has been previously described as having idiopathic plasmacytic lymphadenopathy (IPL). Whether these patients should be excluded from the current classification system lacks sufficient evidence. This retrospective analysis of 228 patients with iMCD-NOS identified 103 (45.2%) patients with iMCD-IPL. The clinical features and outcomes of patients with iMCD-IPL and iMCD-NOS without IPL were compared. Patients with iMCD-IPL showed a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non-severe patients in the iMCD-IPL group according to the CDCN severity classification. Compared with lymphoma-like treatments, multiple myeloma-like and IL-6-blocking treatment approaches in the iMCD-IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD-IPL and suggest that it should be considered a new subtype of iMCD-NOS.


Asunto(s)
Enfermedad de Castleman , Linfadenopatía , Humanos , Enfermedad de Castleman/patología , Enfermedad de Castleman/mortalidad , Enfermedad de Castleman/clasificación , Enfermedad de Castleman/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Linfadenopatía/patología , Linfadenopatía/etiología , Células Plasmáticas/patología
4.
J Asian Nat Prod Res ; : 1-11, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38945152

RESUMEN

Histone deacetylase 6 (HDAC6) was a potential target for Alzheimer's disease (AD). In this study, a series of novel oxyevodiamine-based HDAC6 inhibitors with a variety of linker moieties were designed, synthesized and evaluated. Compound 12 with a benzyl linker was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC50 value of 6.2 nM and was more than 200 fold selectivity over HDAC1. It also had lower cytotoxicity and higher anti-H2O2 activity in vitro comparing with other derivatives. Compound 12 might be a good lead as novel HDAC6 inhibitor for the treatment of AD.

5.
Acta Pharmacol Sin ; 44(9): 1748-1767, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37095197

RESUMEN

Circular RNAs (ciRNAs) are emerging as new players in the regulation of gene expression. However, how ciRNAs are involved in neuropathic pain is poorly understood. Here, we identify the nervous-tissue-specific ciRNA-Fmn1 and report that changes in ciRNA-Fmn1 expression in spinal cord dorsal horn neurons play a key role in neuropathic pain after nerve injury. ciRNA-Fmn1 was significantly downregulated in ipsilateral dorsal horn neurons after peripheral nerve injury, at least in part because of a decrease in DNA helicase 9 (DHX9), which regulates production of ciRNA-Fmn1 by binding to DNA-tandem repeats. Blocking ciRNA-Fmn1 downregulation reversed nerve-injury-induced reductions in both the binding of ciRNA-Fmn1 to the ubiquitin ligase UBR5 and the level of ubiquitination of albumin (ALB), thereby abrogating the nerve-injury-induced increase of ALB expression in the dorsal horn and attenuating the associated pain hypersensitivities. Conversely, mimicking downregulation of ciRNA-Fmn1 in naïve mice reduced the UBR5-controlled ubiquitination of ALB, leading to increased expression of ALB in the dorsal horn and induction of neuropathic-pain-like behaviors in naïve mice. Thus, ciRNA-Fmn1 downregulation caused by changes in binding of DHX9 to DNA-tandem repeats contributes to the genesis of neuropathic pain by negatively modulating UBR5-controlled ALB expression in the dorsal horn.


Asunto(s)
Neuralgia , ARN Circular , Ratones , Animales , ARN Circular/metabolismo , Regulación hacia Abajo , ADN Helicasas , Hiperalgesia/metabolismo , Asta Dorsal de la Médula Espinal/metabolismo , Neuralgia/etiología
6.
Appl Opt ; 62(3): 725-734, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36821278

RESUMEN

Optomechanical components such as the lens barrels and frames of IR spectrometers produce strong internal stray radiation, which reduces the instrument's SNR and dynamic range. An IR internal stray radiation calculation method based on an analytical model of the view factor is proposed. The mathematical model of the view factor calculation method of typical optomechanical components is established. For any IR optical systems, the internal stray radiation can be quickly and accurately calculated by adjusting the coordinate systems in the calculation method. Based on the proposed method, the internal stray radiation of a double-pass long-wave IR spectrometer was calculated. The calculation results are consistent with the simulation results. The RMS value of the relative error between the calculated value and the simulated value is around 11%. To verify the proposed method, an experiment was conducted to test the internal stray radiation of the long-wave IR spectrometer. The internal stray radiation test results agree with the calculated and simulated results, and the relative error between the test results and the calculation results is within 9%.

7.
Angew Chem Int Ed Engl ; 62(18): e202302521, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-36891989

RESUMEN

Organic nitrates are broadly applied as pharmaceuticals (acting as efficient nitric oxide donor), energetic materials, building blocks in organic synthesis, etc. However, practical and direct methods to access organic nitrates efficiently are still rare, mainly due to the lack of powerful nitrooxylating reagents. Herein, we report bench-stable and highly reactive noncyclic hypervalent iodine nitrooxylating reagents, oxybis(aryl-λ3 -iodanediyl) dinitrates (OAIDNs, 2), which are prepared just by using aryliodine diacetate and HNO3 . The reagents are used to achieve a mild and operationally simple protocol to access diverse organic nitrates. By employing of 2, zinc-catalyzed regioselective nitrooxylation of cyclopropyl silyl ethers is realized efficiently to access the corresponding ß-nitrooxy ketones with high functional-group tolerance. Moreover, a series of direct and catalyst-free nitrooxylations of enolizable C-H bonds are carried out smoothly to afford the desired organic nitrates within minutes by just mixing the substrates with 2 in dichloromethane.

8.
J Org Chem ; 87(5): 3834-3840, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35168320

RESUMEN

A practical copper-catalyzed nitration of electron-rich arenes with trimethylsilyl chloride and guanidine nitrate is reported. A variety of nitrated products were generated in moderate to excellent yields (32-99%) at ambient temperature under acid-free, open-flask, and operationally simple conditions.

9.
J Nat Prod ; 85(5): 1374-1387, 2022 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-35503996

RESUMEN

Eleven new pyranochromones, calomembranone A-K (1-11), two new pyranocoumarins, calopolyanolide E and F (12 and 13), together with six known analogues (14-19) were isolated from the leaves of Calophyllum membranaceum. Their structures and absolute configurations were elucidated by analysis of spectroscopic data, computational calculations, as well as X-ray crystallography of 4 and 9. The anti-inflammatory activities of all the isolates were evaluated by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Structure-activity relationships are also discussed. Compound 7 showed the strongest NO inhibition (IC50 = 0.92 µM). Oral administration of 7 dose-dependently reduced the paw swelling and downregulated neutrophil-to-lymphocyte ratio in the carrageenan-induced acute arthritis mice model. Molecular dynamics simulation and cellular thermal shift assay results indicated that 7 participated in a robust and stable interaction with the active site of TLR4. Compound 7 also suppressed the inflammation in arthritis through the regulation of TLR4 mediated signal transduction via IKK/NF-κB signaling pathway and the consequent reduction of IL-2, IL-4, and IL-5.


Asunto(s)
Artritis , Calophyllum , Animales , Antiinflamatorios , Artritis/inducido químicamente , Artritis/tratamiento farmacológico , Calophyllum/metabolismo , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Ratones , FN-kappa B , Células RAW 264.7 , Receptor Toll-Like 4
10.
Appl Opt ; 61(8): 2125-2139, 2022 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-35297906

RESUMEN

The spaceborne dispersive spectrometer is widely used in environmental, resource, and ocean observations. The coded spectrometer has higher energy advantages than the dispersion spectrometer, so it has great application prospects. In the current study, we developed an off-axis short-wave infrared coded optical system (SICOS) based on curved prism dispersion, and we further explored the design and optimization of the SICOS structure. Finite element analyses of a space-based short-wave infrared coded spectrometer based on curved prism dispersion (SSICS-CPD), including static simulation, modal analysis, sinusoidal vibration mechanical analysis, and random vibration mechanical analysis, were carried out. Simulation results showed that the SICOS support structure had excellent mechanical and thermal stability. As off-axis optical systems cannot meet the requirements of optical position accuracy through centering processing, a point source microscope and three-coordinate measuring machines were employed to complete the high-precision and rapid assembly of the SSICS-CPD. In addition, verification tests of surface shape error, stress relief, random vibration, and optical design parameters were carried out to validate the high stability and imaging performance of the SSICS-CPD. Results showed that the average modulation transfer function in the full field was 0.43 at 16.67 lp/mm, the spectral smile was <0.2 pixels, and the spectral keystone was <0.1 pixels. The design, analysis, assembly, and verification of the SSICS-CPD provide a useful reference for the development of other spaceborne prism dispersion spectrometers.

11.
Chem Biodivers ; 19(7): e202200355, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35621358

RESUMEN

Two new xanthones, calmemxanthone A (1) and calmemxanthone B (2), along with eleven known compounds were isolated from the dried twigs of Calophyllum membranaceum Gardn. et Champ. The structures of compounds 1 and 2 were established by analysis of spectra and mass spectrometry data. The absolute configuration of compound 1 was confirmed by electronic circular dichroism (ECD) spectral analysis. The anti-inflammation action of these compounds were evaluated on lipopolysaccharide (LPS)-induced inflammatory damage to human endometrial stromal cells (HESCs), and the structure-activities of 1-13 were also discussed. Compound 10 presented the anti-inflammation action with an IC50 value of 20.3 µM, that might be relevant to the regulation of NF-κB signaling pathway via the suppression of TRIF, IKKα, and IκBα.


Asunto(s)
Calophyllum , Células Madre Embrionarias Humanas , Xantonas , Antiinflamatorios/farmacología , Calophyllum/química , Humanos , Estructura Molecular , Xantonas/química , Xantonas/farmacología
12.
J Cardiovasc Electrophysiol ; 32(11): 3057-3067, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34427958

RESUMEN

BACKGROUND: ß-Blockers are first-line therapy in patients with long QT syndrome (LQTS). However, ß-blockers had genotype dependent efficacy (LQT1>LQT2>LQT3). Sodium channel blockers have been recommended as add-on therapy for LQT3 patients. However, the pooled effect of sodium channel blockers in all LQTS patients remains unknown. METHODS: We conducted a systematic electronic search of PubMed, Embase, and the Cochrane Library. Fixed effects model was used to assess the effect of sodium channel blockers on QTc, cardiac events (CEs), and the proportion of QTc ≥ 500 ms and QTc ≤ 460 ms in LQTS patients. RESULTS: Pooled analysis of 14 studies with 213 LQTS (9 LQT1 + 63 LQT2 + 135 LQT3 + 6 others) patients showed that sodium channel blockers significantly shortened QTc by nearly 50 ms (mean difference [MD], -49.43; 95% confidence interval [CI], -57.80 to -41.05, p < .001), reduced the incidence of CEs (risk ratio [RR], 0.23; 95% CI, 0.11-0.47; p < .001) and the proportion of QTc ≥ 500 ms (RR, 0.33; 95% CI, 0.24-0.47; p < .001), and increased the proportion of QTc ≤ 460 ms (RR, 10.33; 95% CI, 4.62-23.09; p < .001). Sodium channel blockers significantly shortened QTc both in LQT3 and LQT2 patients, while the QTc shortening effect in LQT3 was superior to that in LQT2 (57.39 vs. 36.61 ms). Mexiletine, flecainide, and ranolazine all significantly shortened QTc, and the QTc shortening effect by mexiletine was the best (60.70 vs. 49.08 vs. 50.10 ms). CONCLUSIONS: Sodium channel blockers can be useful both in LQT3 and LQT2 patients. Mexiletine, flecainide and ranolazine significantly shortened QTc in LQTS patients, and the QTc shortening effect by mexiletine was the best.


Asunto(s)
Síndrome de QT Prolongado , Bloqueadores de los Canales de Sodio , Antagonistas Adrenérgicos beta/uso terapéutico , Electrocardiografía , Flecainida/uso terapéutico , Humanos , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/tratamiento farmacológico , Síndrome de QT Prolongado/genética , Mexiletine/uso terapéutico , Ranolazina/uso terapéutico , Bloqueadores de los Canales de Sodio/uso terapéutico
13.
Appl Opt ; 58(23): 6329-6334, 2019 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-31503778

RESUMEN

A type of hollow gold nanoparticle (HGNP)-modified fiber optic long-range surface plasmon resonance (LRSPR) sensor with sensing self-reference is proposed and demonstrated. HGNPs have a stronger plasmonic field compared to solid GNPs because of the coupling between the inner and outer walls of HGNPs. The intense near-field electronic coupling between long-range surface plasmon polaritons associated with the LRSPR gold layer and localized surface plasmon polaritons of HGNPs leads to localized electromagnetic-field enhancement and LRSPR response signal amplification. Therefore, the HGNP-modified LRSPR sensor possesses a more excellent sensing property compared with the unmodified LRSPR sensor. The long-range resonance dip in the transmission spectrum is shown to shift in response to ambient refractivity change, and the characteristic absorption peak is fixed, allowing to regard it as a reference to improve detection accuracy of the sensors. The mode-field distribution of the sensors is simulated by using the finite element method, and the simulation results show that the electric-field intensity on the HGNP surface is significantly enhanced compared with that of the gold layer surface of the unmodified LRSPR sensor. 1874.79 nm/RIU improvement in sensitivity, 1.42 times improvement in figure of merit (FOM), and approximately 50% reduction in limit of detection (LOD) are achieved for the refractivity measurement of a low-concentration biological solution with the employment of HGNPs in LRSPR sensing experiments. The HGNP-modified LRSPR sensor proposed in this paper has high detection accuracy and FOM and low LOD, and can realize remote real-time online monitoring. Therefore, it has important research value and broad application prospects in the field of biochemical detection.

14.
Cell Physiol Biochem ; 42(1): 34-43, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28490015

RESUMEN

BACKGROUND: Salidroside (SDS) is the main effective ingredient of Rhodiola rosea L with a variety of pharmacologic properties. We aim to investigate the effects of SDS on ventilation induced lung injury (VILI) and explore the possible underlying molecular mechanism. METHODS: Lung injury was induced in male ICR mice via mechanical ventilation (30 ml/kg) for 4h. The mice were divided in four groups:(1) Control group; (2) Ventilation group; (3) SDS group; (4) Ventilation with SDS group. SDS (50 mg/kg) was injected intraperitoneally 1h before operation. Mouse lung vascular endothelial cells (MLVECs) were subjected to cyclic stretch for 4h. RESULTS: It was found that SDS attenuated VILI as shown in HE staining, cell count and protein content levels in BAL fluid, W/D and Evans blue dye leakage into the lung tissue. SDS treatment inhibited the activation of NLRP3 inflammasome and subsequent caspase-1 cleavage as well as interleukin (IL)-1ß secretion both in vivo and in vitro. Moreover, SDS administration up-regulated SIRT1 expression. Importantly, knockdown of SIRT1 reversed the inhibitory effect of SDS on NLRP3 inflammasome activation. CONCLUSIONS: Taken together, these findings indicate that SDS may confer protection against ventilation induced lung injury via SIRT1-de-pendent inhibition of NLRP3 inflammasome activation.


Asunto(s)
Glucósidos/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fenoles/farmacología , Sirtuina 1/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Animales , Líquido del Lavado Bronquioalveolar/química , Caspasa 1/metabolismo , Células Cultivadas , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Ensayo de Inmunoadsorción Enzimática , Glucósidos/uso terapéutico , Inflamasomas/metabolismo , Interleucina-1beta/análisis , Interleucina-1beta/metabolismo , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos ICR , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Fenoles/uso terapéutico , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Sirtuina 1/antagonistas & inhibidores , Sirtuina 1/genética , Estrés Mecánico , Lesión Pulmonar Inducida por Ventilación Mecánica/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/patología , Lesión Pulmonar Inducida por Ventilación Mecánica/prevención & control
15.
Graefes Arch Clin Exp Ophthalmol ; 255(1): 189-195, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27796670

RESUMEN

PURPOSE: To investigate the effects of no correction versus full correction on myopia progression in Chinese children over a period of 2 years. METHODS: Myopia was defined as cycloplegic spherical equivalent (SE) of ≤ -0.50 D. Uncorrection was defined as no spectacles worn, and full correction was defined as when the value of SE subtracted from the dioptric power of the child's current spectacles was less than 0.5 D. Ocular examinations included visual acuity, cycloplegic autorefraction, axial length and vertometer measurements. Questionnaires were completed by parents on behalf of the children. RESULTS: A total of 121 myopic children, with a median age of 12.7 years, were screened from the Anyang Childhood Eye Study, with 65 in the uncorrected group and 56 in the full correction group. At 2-year follow-up, children with no correction had slower myopia progression (-0.75 ± 0.49 D vs. -1.04 ± 0.49 D, P < 0.01) and less axial elongation (0.45 ± 0.18 mm vs. 0.53 ± 0.17 mm, P = 0.02) than children with full correction. In multivariate modeling, adjusting for baseline SE or axial length, age, gender, height, number of myopic parents, age at myopia onset, and time spent in near work and outdoors, children with no correction still had slower myopia progression (-0.76 ± 0.07 vs. -1.03 ± 0.08 D, P < 0.01) and less axial elongation (0.47 ± 0.03 mm vs. 0.51 ± 0.03 mm, P < 0.01). Myopia progression decreased significantly with an increasing amount of undercorrection in all children (r = 0.22, b = 0.16, P = 0.01). CONCLUSION: Our findings suggest that myopic defocus slows the progression of myopia in already myopic children, supporting previous findings from animal studies.


Asunto(s)
Acomodación Ocular/fisiología , Anteojos , Miopía/terapia , Refracción Ocular/fisiología , Agudeza Visual , Longitud Axial del Ojo , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Miopía/fisiopatología , Encuestas y Cuestionarios , Factores de Tiempo
16.
Biomed Environ Sci ; 30(5): 351-362, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28549491

RESUMEN

OBJECTIVE: To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease (KBD) and in an established T-2 toxin- and selenium (Se) deficiency-induced rat model. METHODS: Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and mRNA levels were determined by real-time reverse transcription polymerase chain reaction. RESULTS: Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and mRNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. CONCLUSION: T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.


Asunto(s)
Apoptosis/efectos de los fármacos , Cartílago Articular/fisiopatología , Condrocitos/fisiología , Enfermedad de Kashin-Beck/fisiopatología , Selenio/deficiencia , Toxina T-2/farmacología , Adolescente , Animales , Biomarcadores , Niño , Femenino , Humanos , Enfermedad de Kashin-Beck/etiología , Masculino , Proteínas Matrilinas/genética , Proteínas Matrilinas/metabolismo , Modelos Animales , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
17.
Cochrane Database Syst Rev ; 2: CD009799, 2016 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-26899152

RESUMEN

BACKGROUND: Myopia (near-sightedness or short-sightedness) is a condition in which the refractive power of the eye is greater than required. The most frequent complaint of people with myopia is blurred distance vision, which can be eliminated by conventional optical aids such as spectacles or contact lenses, or by refractive surgery procedures such as photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK). PRK uses laser to remove the corneal stroma. Similar to PRK, LASEK first creates an epithelial flap and then replaces it after ablating the corneal stroma. The relative benefits and harms of LASEK and PRK, as shown in different trials, warrant a systematic review. OBJECTIVES: The objective of this review is to compare LASEK versus PRK for correction of myopia by evaluating their efficacy and safety in terms of postoperative uncorrected visual acuity, residual refractive error, and associated complications. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2015 Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 December 2015. We used the Science Citation Index and searched the reference lists of the included trials to identify relevant trials for this review. SELECTION CRITERIA: We included in this review randomized controlled trials (RCTs) comparing LASEK versus PRK for correction of myopia. Trial participants were 18 years of age or older and had no co-existing ocular or systemic diseases that might affect refractive status or wound healing. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all reports and assessed the risk of bias of trials included in this review. We extracted data and summarized findings using risk ratios and mean differences. We used a random-effects model when we identified at least three trials, and we used a fixed-effect model when we found fewer than three trials. MAIN RESULTS: We included 11 RCTs with a total of 428 participants 18 years of age or older with low to moderate myopia. These trials were conducted in the Czech Republic, Brazil, Italy, Iran, China, Korea, Mexico, Turkey, USA, and UK. Investigators of 10 out of 11 trials randomly assigned one eye of each participant to be treated with LASEK and the other with PRK, but did not perform paired-eye (matched) analysis. Because of differences in outcome measures and follow-up times among the included trials, few trials contributed data for many of the outcomes we analyzed for this review. Overall, we judged RCTs to be at unclear risk of bias due to poor reporting; however, because of imprecision, inconsistency, and potential reporting bias, we graded the quality of the evidence from very low to moderate for outcomes assessed in this review.The proportion of eyes with uncorrected visual acuity of 20/20 or better at 12-month follow-up was comparable in LASEK and PRK groups (risk ratio (RR) 0.98, 95% confidence interval (95% CI) 0.92 to 1.05). Although the 95% CI suggests little to no difference in effect between groups, we judged the quality of the evidence to be low because only one trial reported this outcome (102 eyes). At 12 months post treatment, data from two trials suggest no difference or a possibly small effect in favor of PRK over LASEK for the proportion of eyes achieving ± 0.50 D of target refraction (RR 0.93, 95% CI 00.84 to 1.03; 152 eyes; low-quality evidence). At 12 months post treatment, one trial reported that one of 51 eyes in the LASEK group lost one line or more best-spectacle corrected visual acuity compared with none of 51 eyes in the PRK group (RR 3.00, 95% CI 0.13 to 71.96; very low-quality evidence).Three trials reported adverse outcomes at 12 months of follow-up or longer. At 12 months post treatment, three trials reported corneal haze score; however, data were insufficient and were inconsistent among the trials, precluding meta-analysis. One trial reported little or no difference in corneal haze scores between groups; another trial reported that corneal haze scores were lower in the LASEK group than in the PRK group; and one trial did not report analyzable data to estimate a treatment effect. At 24 months post treatment, one trial reported a lower, but clinically unimportant, difference in corneal haze score for LASEK compared with PRK (MD -0.22, 95% CI -0.30 to -0.14; 184 eyes; low-quality evidence). AUTHORS' CONCLUSIONS: Uncertainty surrounds differences in efficacy, accuracy, safety, and adverse effects between LASEK and PRK for eyes with low to moderate myopia. Future trials comparing LASEK versus PRK should follow reporting standards and follow correct analysis. Trial investigators should expand enrollment criteria to include participants with high myopia and should evaluate visual acuity, refraction, epithelial healing time, pain scores, and adverse events.


Asunto(s)
Queratectomía Subepitelial Asistida por Láser , Miopía/cirugía , Queratectomía Fotorrefractiva , Adulto , Humanos , Queratectomía Subepitelial Asistida por Láser/efectos adversos , Queratectomía Fotorrefractiva/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Agudeza Visual
18.
Clin Exp Ophthalmol ; 44(8): 701-709, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27082378

RESUMEN

BACKGROUND: To report the thickness of the peripapillary retinal nerve fibre layer (pRNFL) in Chinese children and examine its association with refractive error, axial length (AL) and optic disc parameters. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of 2893 seven-year-old children from 11 randomly selected primary schools in Anyang, central China. METHODS: Participants underwent ophthalmic examinations including optical biometry, cycloplegic autorefraction and spectral-domain ocular coherence tomography. MAIN OUTCOME MEASURES: Retinal nerve fibre layer thickness in 16 radial sections, cycloplegic spherical equivalent, AL. RESULTS: The mean (SD) average RNFL thickness was 102.01(8.02) µm. The average RNFL thickness decreased with smaller disc area (r = 0.18, R2 = 0.03, P < 0.0001), bigger cup area (r = -0.11, R2 = 0.01, P < 0.0001), smaller rim area (r = 0.28, R2 = 0.08, P < 0.0001), smaller nerve head volume (r = 0.27, R2 = 0.07, P < 0.0001), longer AL (r = -0.15, R2 = 0.02, P < 0.0001) and a negative spherical equivalent (r = 0.11, R2 = 0.01, P < 0.0001). Hyperopic children had a thicker RNFL than emmetropic children [102.45(8.13) µm vs. 100.81 (7.18) µm, P < 0.001]. Myopic children had thinner RNFL than emmetropic children [99.17 (7.69) µm vs. 100.81 (7.18) µm, P < 0.05]. CONCLUSION: Retinal nerve fibre layer thickness decreased with increasing AL, higher myopia, bigger cup area, smaller disc and rim area, and a smaller nerve head volume, but the coefficient of determination for all these associations was small. The RNFL in myopes was significantly thinner than emmetropes or hyperopes, but with small absolute differences. The study provides RNFL values for healthy 7-year-old Chinese children. Follow up of this cohort to observe the change of RNFL thickness with myopia and possible change in detected associations with age is planned.


Asunto(s)
Hiperopía/fisiopatología , Miopía/fisiopatología , Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología , Pueblo Asiatico/etnología , Longitud Axial del Ojo , Biometría , Niño , Preescolar , China/epidemiología , Estudios Transversales , Emetropía/fisiología , Femenino , Humanos , Hiperopía/etnología , Masculino , Miopía/etnología , Disco Óptico/patología , Refracción Ocular/fisiología , Tomografía de Coherencia Óptica
19.
Graefes Arch Clin Exp Ophthalmol ; 253(8): 1363-8, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26032395

RESUMEN

BACKGROUND: To prospectively observe the effects of undercorrection of myopia on myopia progression and axial elongation in a population of 12-year-old Chinese children. METHODS: A total of 2,267 children in the Anyang Childhood Eye Study were examined at baseline, and 1,769 were followed for 1 year. Ocular examinations included cycloplegic autorefraction, axial length, visual acuity, vertometry, and accommodative lag. Questionnaires were completed by children and parents. Undercorrection of myopia was determined at baseline if presenting visual acuity could be improved by at least 2 lines with subjective refraction. RESULTS: Of 253 myopic children with spectacles and available information, 120 (47.4 %) were undercorrected (-4.63D to -0.50D) and 133 (52.6 %) were fully corrected. In a multivariate model adjusting for age, gender, number of myopic parents, time spent on near work and outdoor activities per day, usage and time for wearing spectacles per day, children with undercorrection had significantly more baseline myopia (P < 0.01) and longer axial length (P = 0.03) than children with full correction. However, there were no significant differences in myopia progression (P = 0.46) and axial elongation (P = 0.96) at 1 year between the two groups of children. The regression analysis showed that myopia progression significantly decreased with increasing amount of undercorrection (r (2) = 0.02, P = 0.02) in all children. Accommodative lag significantly decreased with increasing amounts of undercorrection (P < 0.01). CONCLUSIONS: Based on this 1-year study in Chinese children, undercorrection or full correction of myopia by wearing spectacles did not show any differences in myopia progression or axial elongation.


Asunto(s)
Anteojos , Miopía/diagnóstico , Miopía/terapia , Acomodación Ocular/fisiología , Pueblo Asiatico , Longitud Axial del Ojo/patología , Niño , China/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Miopía/etnología , Estudios Prospectivos , Encuestas y Cuestionarios , Agudeza Visual/fisiología
20.
Optom Vis Sci ; 92(5): 566-72, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25875684

RESUMEN

PURPOSE: To describe distributions of ocular biometry and their associations with refraction in 7- and 14-year-old children in urban areas of Anyang, central China. METHODS: A total of 2271 grade 1 students aged 7.1 ± 0.4 years and 1786 grade 8 students aged 13.7 ± 0.5 years were measured with ocular biometry and cycloplegic refraction. A parental myopia questionnaire was administered to parents. RESULTS: Mean axial length, anterior chamber depth, lens thickness, central corneal thickness, corneal diameter, corneal radius of curvature, axial length/corneal radius of curvature ratio, and spherical equivalent refraction were 22.72 ± 0.76 mm, 2.89 ± 0.24 mm, 3.61 ± 0.19 mm, 540.5 ± 31 µm, 12.06 ± 0.44 mm, 7.80 ± 0.25 mm, 2.91 ± 0.08, and +0.95 ± 1.05 diopters (D), respectively, in 7-year-old children. They were 24.39 ± 1.13 mm, 3.42 ± 0.41 mm, 3.18 ± 0.24 mm, 548.9 ± 33 µm, 12.03 ± 0.43 mm, 7.80 ± 0.26 mm, 3.13 ± 0.14, and -2.06 ± 2.20 D, respectively, in 14-year-old children. Compared with 7-year-old children, the older group had significantly more myopia (-3.0 D), longer axial length (1.7 mm), deeper anterior chamber depth (0.3 mm), thinner lens thickness (-0.2 mm), thicker central corneal thickness (10 µm), and greater axial length/corneal radius of curvature ratio (0.22) (all p < 0.001), as well as smaller corneal diameter (-0.03 mm, p = 0.02) and similar corneal radius of curvature. Sex differences were similar in both age groups, with boys having longer axial length (0.5 mm), deeper anterior chamber depth (0.1 mm), shorter lens thickness (0.03 mm), greater central corneal thickness (5 µm), greater corneal diameter (0.15 mm), and greater corneal radius of curvature (0.14 mm) than girls (all p < 0.01). The most important variables related to spherical equivalent refraction were vitreous length, corneal radius of curvature, and lens thickness. CONCLUSIONS: The 14-year-old group had larger parameter dimensions than the 7-year-old group except for corneal radius of curvature (unchanged) and lens thickness and corneal diameter (both smaller). Boys had large parameter dimensions than girls except for lens thickness (smaller). Axial length, corneal radius of curvature, and lens thickness were the most important determinants of refraction.


Asunto(s)
Pueblo Asiatico/etnología , Biometría/métodos , Hiperopía/etnología , Miopía/etnología , Población Urbana/estadística & datos numéricos , Adolescente , Distribución por Edad , Longitud Axial del Ojo/anatomía & histología , Niño , China/epidemiología , Femenino , Humanos , Masculino , Refracción Ocular/fisiología , Distribución por Sexo , Encuestas y Cuestionarios
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