Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 334
Filtrar
1.
Orphanet J Rare Dis ; 17(1): 209, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606856

RESUMO

BACKGROUND: Hypospadias is a congenital anomaly of the male urogenital system. Genetics factors play an important role in its pathogenesis. To search for potential causal genes/variants for hypospadias, we performed exome sequencing in a pedigree with three patients across two generations and a cohort of 49 sporadic patients with hypospadias. RESULTS: A novel BRAF variant (NM_004333.6: c.362C > A) was found to co-segregate with the hypospadias phenotype in the disease pedigree. In cells overexpressing the BRAF mutant, the phosphorylation level of p38 MAPK was significantly increased as compared with the cells overexpressing the wild-type BRAF or RASopathy-related BRAF mutant. This variant further led to a reduced transcription level of the SRY gene, which is essential for the normal development of the male reproductive system. In the cohort of sporadic patients, we identified two additional variants in p38 MAPK signaling-related genes (TRIM67 and DAB2IP) potentially associated with hypospadias. CONCLUSION: Our study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias.

2.
Front Genet ; 13: 804202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360850

RESUMO

Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder of connective tissue characterized by crumpled ears, arachnodactyly, camptodactyly, large joint contracture, and kyphoscoliosis. The nature course of CCA has not been well-described. We aim to decipher the genetic and phenotypic spectrum of CCA. The cohort was enrolled in Beijing Jishuitan Hospital and Peking Union Medical College Hospital, Beijing, China, based on Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study (http://www.discostudy.org/). Exome sequencing was performed on patients' blood DNA. A recent published CCA scoring system was validated in our cohort. Seven novel variants and three previously reported FBN2 variants were identified through exome sequencing. Two variants outside of the neonatal region of FBN2 gene were found. The phenotypes were comparable between patients in our cohort and previous literature, with arachnodactyly, camptodactyly and large joints contractures found in almost all patients. All patients eligible for analysis were successfully classified into likely CCA based on the CCA scoring system. Furthermore, we found a double disease-causing heterozygous variant of FBN2 and ANKRD11 in a patient with blended phenotypes consisting of CCA and KBG syndrome. The identification of seven novel variants broadens the mutational and phenotypic spectrum of CCA and may provide implications for genetic counseling and clinical management.

3.
Ann Palliat Med ; 11(2): 560-567, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35249334

RESUMO

BACKGROUND: This population-based, cross-sectional study aimed to assess the correlation between near vision and smartphone usage among people aged ≥50 years in China. METHODS: This study was performed on the ocular health status of residents in Fujian Province, Southeast China. People aged ≥50 years were recruited. The main contents of the survey for the residents included socioeconomic status, uncorrected near visual acuity (UNVA), refractive state, as well as a questionnaire about smartphone usage and visual quality. RESULTS: Smartphone adoption accounted for 67.7% (4,702 individuals) of the total population, which decreased with age in the elderly. Smartphone owners had a higher average UNVA of 0.31±0.18 than non-smartphone owners (0.23±0.14), and the difference was statistically significant (P<0.001). Individuals who used smartphones for a long time usually had better UNVA (Pearson correlation coefficient 0.144, P<0.001). The rates of complaints of distance vision loss, near vision loss, ocular surface discomfort in smartphone users were significantly higher than that of non-users (P<0.001). Also, smartphone adoption and visual quality differed between urban and rural respondents. CONCLUSIONS: Smartphone adoption and usage time in the elderly significantly decreased with age and UNVA, and the performance of visual impairment was not consistent in urban and rural areas.


Assuntos
Envelhecimento , Smartphone , Idoso , China/epidemiologia , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Acuidade Visual
4.
BMC Ophthalmol ; 22(1): 112, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35277140

RESUMO

PURPOSE: To describe the objective and design of the Fujian Eye Study and to introduce the general characteristics and vision condition of this study. METHODS: The Fujian Eye Study (FJES) is a population-based cross-sectional survey on the public eye health status of residents over 50 years old in the entire Fujian Province of Southern China, which contains both urban and rural areas and coastal and inland regions. 10,044 participants were enrolled using a two-stage cluster sampling design and underwent a questionnaire and a series of standard examinations both physical and ocular. The main subgroups of data collection included age, sex, region, refractive error, education background, income, eating habits, smartphone usage in the dark, complaints of eye discomfort, history of chronic diseases, consumption of tobacco, alcohol, or tea. RESULTS: 8211 (81.8%) participants were finally included and were divided into urban populations (4678 subjects) and rural populations (3533 subjects) and coastal residents (6434 subjects) and inland residents (1777 subjects); 4836 participants were female. The mean age was 64.39 (SD 8.87) years (median 64 years; range 50-98 years). 227 (3.33%) had vision impairment (VI), 195 (2.87%) had low vision and 14 (0.21%) were blind. The mean presenting near visual acuity (PNVA) was 0.28 (0.17), the mean presenting distance visual acuity (PDVA) was 0.61 (0.30), and the mean best corrected visual acuity (BCVA) was 0.82 (0.28). CONCLUSIONS: The FJES collected detailed questionnaire information and overall ocular and physical examinations, which provide the opportunity to identify risk factors and images of VI and eye diseases and to evaluate their associations with chronic diseases and basic personal information.


Assuntos
Baixa Visão , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , População Urbana , Transtornos da Visão
5.
Vaccines (Basel) ; 10(3)2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35335114

RESUMO

Aims: To report potential vaccine-induced ocular adverse events following inactivated COVID-19 vaccination (Sinopharm and Sinovac). Methods: This case series took place at a tertiary referral center in the southeast of China (Xiamen Eye Center in Fujian Province) from February 2021 to July 2021. Patients who received the first dose of inactivated COVID-19 vaccine and developed vaccine-related ocular adverse events within 10 days were included. The diagnosis of vaccine-related ocular adverse events was guided by the World Health Organization causality assessment and the Naranjo criteria. Results: Ten eyes of seven patients (two male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30-55 years). The mean time of ocular adverse event manifestations was 4.9 days (range, 1-10 days). Three patients were diagnosed with Vogt-Koyanagi-Harada (VKH)-like uveitis, one with multifocal choroiditis, one with episcleritis, one with iritis, and one with acute idiopathic maculopathy. Two patients received the second dose of vaccine. One patient had exacerbation of VKH, and one patient had no symptoms. An aqueous humor analysis in three patients revealed elevated proinflammatory cytokines and negative virus copy. All the patients had transient ocular disturbance and responded well to steroids. No recurrence was noted during 6 months of follow-up. Conclusions: Potential ocular adverse events should be reported to increase the awareness of the health community for timely detection and proper treatment.

6.
Psychol Res Behav Manag ; 15: 711-723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342312

RESUMO

Background: Whether the pandemic can be effectively prevented and controlled depends on the entire population's adherence to recommendations and preventive behaviors. The present study aimed to investigate the social class differences and internal mechanisms of prevention behaviors in the COVID-19 pandemic. Methods: We conducted an online cross-sectional survey among the general Chinese population at the early stage of the COVID-19 pandemic. The survey website's subscribers could access the questionnaire through the Tencent online platform, and a total of 1948 participants voluntarily completed it. Most of the participants were female (n = 1257, 64.528%), between the ages of 18-29 (n = 999, 51.284%), university graduates (n = 1015, 52.105%), and had an annual family income below 100,000 yuan (n = 1119, 57.444%). The differences in COVID-19 prevention behaviors among different social classes, the mediating role of infectious threat perception and the moderating role of perceived epidemic transparency were examined. Results: 1) There were significant differences in prevention behaviors among different social classes. 2) The level of infectious threat perception played a mediating role in the relationship between social class and prevention behavior. When the individuals were from a lower social class, the level of threat perception and the level of COVID-19 prevention behaviors were also lower. 3) Perceived epidemic transparency played a moderating role in the relationship between social class and COVID-19 prevention behavior. It also played a moderating role in the relationship between social class and infectious threat perception. Conclusion: In the implementation of epidemic prevention and control measures, different social classes should be targeted and guided differently. In particular, lower-class individuals can be guided by improving the perceptions of epidemic transparency and infectious threat.

7.
Am J Ophthalmol Case Rep ; 26: 101404, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35165663

RESUMO

PURPOSE: We report a case of a 19-year-old male who presented with bilateral Vogt-Koyanagi-Harada (VKH)-like panuveitis following an injection of an inactivated Covid-19 vaccine. OBSERVATIONS: A 19-year-old male was referred to our clinic with a 2-week history of blurred vision on both eyes and headaches, 12 hours following the administration of the first dose of an inactivated Covid-19 virus vaccine (Sinovac). He denied any past ocular or medical history. Clinical examination and multimodal imaging tests identified serous retinal detachment and choroidal thickening posteriorly and deep yellow foci in the far peripheral retina. Aqueous humor analysis ruled out viral and bacterial infection including Covid-19, but demonstrated an elevated interleukin-6 level. A workup ruled out systemic infection or autoimmune disease. Although the patient received a single positive T-SPOT result, no other clinical evidence supported active tuberculosis infection. Non-infectious panuveitis was diagnosed and treated with periocular steroids that quickly resolved the serous retinal detachment. CONCLUSIONS AND IMPORTANCE: This is the first report of VKH-like uveitis following an inactivated Covid-19 vaccine, with aqueous humor analysis ruling out viral or bacterial infection and demonstrating an elevated interleukin-6 level. Though rare, VKH-like uveitis may be associated with administration of an inactivated Covid-19 vaccine.

8.
Genome Med ; 14(1): 21, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35209950

RESUMO

BACKGROUND: Identifying breast cancer patients with DNA repair pathway-related germline pathogenic variants (GPVs) is important for effectively employing systemic treatment strategies and risk-reducing interventions. However, current criteria and risk prediction models for prioritizing genetic testing among breast cancer patients do not meet the demands of clinical practice due to insufficient accuracy. METHODS: The study population comprised 3041 breast cancer patients enrolled from seven hospitals between October 2017 and 11 August 2019, who underwent germline genetic testing of 50 cancer predisposition genes (CPGs). Associations among GPVs in different CPGs and endophenotypes were evaluated using a case-control analysis. A phenotype-based GPV risk prediction model named DNA-repair Associated Breast Cancer (DrABC) was developed based on hierarchical neural network architecture and validated in an independent multicenter cohort. The predictive performance of DrABC was compared with currently used models including BRCAPRO, BOADICEA, Myriad, PENN II, and the NCCN criteria. RESULTS: In total, 332 (11.3%) patients harbored GPVs in CPGs, including 134 (4.6%) in BRCA2, 131 (4.5%) in BRCA1, 33 (1.1%) in PALB2, and 37 (1.3%) in other CPGs. GPVs in CPGs were associated with distinct endophenotypes including the age at diagnosis, cancer history, family cancer history, and pathological characteristics. We developed a DrABC model to predict the risk of GPV carrier status in BRCA1/2 and other important CPGs. In predicting GPVs in BRCA1/2, the performance of DrABC (AUC = 0.79 [95% CI, 0.74-0.85], sensitivity = 82.1%, specificity = 63.1% in the independent validation cohort) was better than that of previous models (AUC range = 0.57-0.70). In predicting GPVs in any CPG, DrABC (AUC = 0.74 [95% CI, 0.69-0.79], sensitivity = 83.8%, specificity = 51.3% in the independent validation cohort) was also superior to previous models in their current versions (AUC range = 0.55-0.65). After training these previous models with the Chinese-specific dataset, DrABC still outperformed all other methods except for BOADICEA, which was the only previous model with the inclusion of pathological features. The DrABC model also showed higher sensitivity and specificity than the NCCN criteria in the multi-center validation cohort (83.8% and 51.3% vs. 78.8% and 31.2%, respectively, in predicting GPVs in any CPG). The DrABC model implementation is available online at http://gifts.bio-data.cn/ . CONCLUSIONS: By considering the distinct endophenotypes associated with different CPGs in breast cancer patients, a phenotype-driven prediction model based on hierarchical neural network architecture was created for identification of hereditary breast cancer. The model achieved superior performance in identifying GPV carriers among Chinese breast cancer patients.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Reparo do DNA , Feminino , Predisposição Genética para Doença , Células Germinativas , Mutação em Linhagem Germinativa , Humanos , Mutação , Fenótipo
9.
NPJ Genom Med ; 7(1): 11, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35169139

RESUMO

Pathogenic variants in MYH3 cause distal arthrogryposis type 2A and type 2B3 as well as contractures, pterygia and spondylocarpotarsal fusion syndromes types 1A and 1B. These disorders are ultra-rare and their natural course and phenotypic variability are not well described. In this study, we summarize the clinical features and genetic findings of 17 patients from 10 unrelated families with vertebral malformations caused by dominant or recessive pathogenic variants in MYH3. Twelve novel pathogenic variants in MYH3 (NM_002470.4) were identified: three of them were de novo or inherited in autosomal dominant way and nine were inherited in autosomal recessive way. The patients had vertebral segmentation anomalies accompanied with variable joint contractures, short stature and dysmorphic facial features. There was a significant phenotypic overlap between dominant and recessive MYH3-associated conditions regarding the degree of short stature as well as the number of vertebral fusions. All monoallelic variants caused significantly decreased SMAD3 phosphorylation, which is consistent with the previously proposed pathogenic mechanism of impaired canonical TGF-ß signaling. Most of the biallelic variants were predicted to be protein-truncating, while one missense variant c.4244T>G,p.(Leu1415Arg), which was inherited in an autosomal recessive way, was found to alter the phosphorylation level of p38, suggesting an inhibition of the non-canonical pathway of TGF-ß signaling. In conclusion, the identification of 12 novel pathogenic variants and overlapping phenotypes in 17 affected individuals from 10 unrelated families expands the mutation and phenotype spectrum of MYH3-associated skeletal disorders. We show that disturbances of canonical or non-canonical TGF-ß signaling pathways are involved in pathogenesis of MYH3-associated skeletal fusion (MASF) syndrome.

10.
Life (Basel) ; 12(1)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35054492

RESUMO

Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2-24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35024912

RESUMO

PURPOSE: To investigate the prognostic factors on spectral domain optical coherence tomography (SD-OCT) associated with incomplete subretinal fluid (SRF) absorption in treated-naïve eyes with central serous chorioretinopathy (CSC) after the half-dose verteporfin photodynamic therapy (vPDT). METHODS: Patients with CSC who underwent half-dose vPDT with a follow-up period of more than 3 months were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with the SRF persistence at 3 months after the treatment. RESULTS: A total of 143 patients with 150 eyes were enrolled in this study (102 male and 41 female patients). The rate of complete SRF resolution was 82.7% at 3 months for all cases. The duration of symptoms > 6 months (odds ratio [OR] = 3.135, 95% confidence interval [95% CI] (1.147-8.573), p = 0.026), larger SRF area with base diameter > 3 mm (odds ratio (OR) = 4.051, 95% CI: 1.336-12.284, p = 0.013), and larger flat irregular pigment epithelium detachment (FI-PED) area with base diameter > 1 mm (OR = 3.311, 95% CI: 1.249-8.780, p = 0.016) on OCT B-scans were risk factors for incomplete SRF absorption after half-dose vPDT, while outer nuclear layer (ONL) thickness was not significantly associated with the anatomical outcome (OR = 1.015, 95% CI: 0.995-1.036, p = 0.145). CONCLUSION: The duration of symptoms, baseline SRF, and FI-PED base diameter on SD-OCT were important predictors for the anatomical outcome at 3 months after half-dose vPDT. Further studies are needed to establish a better therapeutic strategy for patients with poor response to half-dose vPDT.

12.
Artigo em Inglês | MEDLINE | ID: mdl-35007200

RESUMO

To enhance the nonlinearity of neural networks and increase their mapping abilities between the inputs and response variables, activation functions play a crucial role to model more complex relationships and patterns in the data. In this work, a novel methodology is proposed to adaptively customize activation functions only by adding very few parameters to the traditional activation functions such as Sigmoid, Tanh, and rectified linear unit (ReLU). To verify the effectiveness of the proposed methodology, some theoretical and experimental analysis on accelerating the convergence and improving the performance is presented, and a series of experiments are conducted based on various network models (such as AlexNet, VggNet, GoogLeNet, ResNet and DenseNet), and various datasets (such as CIFAR10, CIFAR100, miniImageNet, PASCAL VOC, and COCO). To further verify the validity and suitability in various optimization strategies and usage scenarios, some comparison experiments are also implemented among different optimization strategies (such as SGD, Momentum, AdaGrad, AdaDelta, and ADAM) and different recognition tasks such as classification and detection. The results show that the proposed methodology is very simple but with significant performance in convergence speed, precision, and generalization, and it can surpass other popular methods such as ReLU and adaptive functions such as Swish in almost all experiments in terms of overall performance.

13.
ACS Appl Mater Interfaces ; 14(1): 2058-2070, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34978415

RESUMO

Oral gene therapy has emerged as a potential optimal treatment for ulcerative colitis (UC). Nucleic acid drugs possessing versatility can not only inhibit inflammation but realize colon mucosal healing, fulfilling the clinical objective of UC therapy. However, the effective accumulation and distribution of oral nucleic acid drugs in the colon remain a considerable challenge. Furthermore, current delivery systems pay more attention to the accumulation of nucleic acid drugs in the colon, while the distribution of nucleic acid drugs in the colon, which plays a key role in the UC treatment, never catches the attention of researchers. Here, we used miR-320 as a model nucleic acid drug to develop a kind of multistage-responsive nanocomplexes (MSNs) based on polymeric nanocapsules and alginate. MSNs possess the pH responsiveness in the stomach, the enzyme responsiveness in the colonic lumen, and the redox responsiveness in the cytoplasm. In vivo imaging results showed that MSNs reach the colon within 2 h and effectively release miR-320 nanocapsules in the colonic lumen. The nanocapsules can further deliver miR-320 to the submucosal layer and even the muscular layer. Moreover, MSNs decreased the activity of myeloperoxidase and proinflammatory cytokines and exhibited anti-inflammatory activity by inhibiting the phosphorylation of IκBα and AKT, reducing colonic inflammation and enhancing mucosal repair. Therefore, MSNs can successfully alleviate UC by improving the accumulation and distribution of oral nucleic acid drugs in the colon, promoting the clinical translational application of nucleic acid drugs in the treatment of UC.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Materiais Biocompatíveis/farmacologia , Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , MicroRNAs/farmacologia , Nanopartículas/química , Administração Oral , Anti-Inflamatórios não Esteroides/administração & dosagem , Materiais Biocompatíveis/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Teste de Materiais , MicroRNAs/administração & dosagem , Estrutura Molecular
14.
Photodermatol Photoimmunol Photomed ; 38(1): 53-59, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34273202

RESUMO

OBJECTIVE: To study the clinical efficacy, recurrence rate and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with microneedle or CO2 lattice laser (CO2FL), in comparison with intrascar betamethasone injection in the treatment of hypertrophic acne scar. METHODS: Fifty-two patients with hypertrophic acne scars at the mandibular angle were enrolled and assigned to different therapy groups. Sixteen patients were treated with microneedle-assisted incorporation of ALA. Twenty-eight patients underwent CO2FL-assisted incorporation of ALA. Eight patients received standard therapy with intrascar injection of glucocorticoid. Two dermatologists, blinded to the therapy groups, independently evaluated the scars in all patients using the average value of the Vancouver Scar Scale score, which was treated as an integer variable. RESULTS: After three rounds of treatment, there was no significant difference in therapeutic effective rate among the microneedle, laser and topical glucocorticoid groups (93.75% vs 100% vs 100%, P = .855). One out of 16 patients (6.25%) in the microneedle group, no patient (0%) in the laser group and two out of eight patients (25%) in the topical glucocorticoid group had recurrence. The laser group showed a higher rate of adverse effects, which were usually mild and reversible, except for pigmentation. Adverse reactions could be completely subsided within 3 weeks. CONCLUSIONS: Either CO2FL or microneedle combined ALA-PDT for hypertrophic scar, as to topical glucocorticoid therapy, showed equivalent clinical effects but lower recurrence rate within 6 months of follow-up period.


Assuntos
Acne Vulgar , Cicatriz Hipertrófica , Lasers de Gás , Fotoquimioterapia , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Ácido Aminolevulínico , Dióxido de Carbono , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/patologia , Humanos , Resultado do Tratamento
15.
Ophthalmic Res ; 65(1): 14-29, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32781454

RESUMO

INTRODUCTION: The association between age-related macular degeneration and asthma is controversial. Transforming growth factor beta (TGF-ß), which plays a critical role in asthma, has been extensively studied with regard to its function in choroidal neovascularization (CNV). In the present study, we aimed to investigate the role of TGF-ß and the possible mechanism of CNV formation complicated with asthma and to explore the effect of a TGF-ß inhibitor on CNV development in asthma mouse models. METHODS: Laser-induced CNV and ovalbumin-induced asthma mouse models were divided into 5 groups: control group, acute asthma group, chronic asthma group, inhibitor-treated acute asthma group, and inhibitor-treated chronic asthma group. The gene expression patterns of angiogenic cytokines, vascular endothelial growth factor (VEGF) receptors and inflammasomes in the control group, acute asthma group, and chronic asthma group were detected using a QuantiGene Plex 6.0 Reagent System. Fundus fluorescein angiography and histology of CNV lesions stained with haematoxylin-eosin were performed to evaluate CNV formation. Quantitative real-time PCR and western blotting were used to assess TGF-ß1, TGF-ß2, and VEGF expression and Smad2/3, AKT, p38 MAPK, and ERK1/2 signal transduction and phosphorylation in retinal and choroidal tissues from each group. RESULTS: In this study, we verified that laser treatment led to more CNV and vascular leakage in asthmatic mice than that in control mice. The changes were particularly notable in the chronic asthma group. The respective TGF-ß1, VEGF, and phosphorylated Smad2/3 (p-Smad2/3) mRNA and protein levels in retinal and choroidal tissues were significantly upregulated in both the acute and chronic asthma groups. After injection of a TGF-ß inhibitor, a distinct decline in VEGF, TGF-ß1, and p-Smad2/3 protein and mRNA levels was observed, and the mean CNV area also decreased. CONCLUSION: We provide new evidence that asthma could be a risk factor for CNV development via the TGF-ß1/Smad signalling pathway. A TGF-ß inhibitor can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation in asthmatic patients.


Assuntos
Asma , Neovascularização de Coroide , Animais , Asma/complicações , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/etiologia , Modelos Animais de Doenças , Humanos , Camundongos , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta1/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Gene ; 814: 146126, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-34958866

RESUMO

Adolescent idiopathic scoliosis (AIS) is a complex spinal deformity with a prevalence of 1%-3%. Genetic factors have been associated with the etiology of AIS. However, previous studies mainly focused on common single nucleotide polymorphisms which confer modest disease risk. Recently, rare variants in FBN1 and other extracellular matrix genes have been implicated in AIS, suggesting a potential overlapping disease etiology between AIS and hereditary connective tissue disorders (HCTD). In this study, we systematically analyzed rare variants in a set of HCTD-related genes in 302 AIS patients who underwent exome sequencing. We firstly focused on pathogenic variants based on a monogenic inheritance and identified nine disease-associated variants in FBN1, COL11A1, COL11A2 and TGFBR2. We then explored the potential interactions between variants in different genes based on the case-control statistics. We identified three ADAMTSL2-LTBP4 variant pairs in three AIS patients and none in controls. Furthermore, we revealed that the variant pairs identified in these genes could affect the interaction between ADAMTSL2 and LTBP4 and upregulate TGF-ß signaling pathway in human fibroblasts. Our findings implicate that the aberrant interaction between mutated ADAMTSL2 and LTBP4 was associated with AIS.


Assuntos
Proteínas ADAMTS/genética , Proteínas de Ligação a TGF-beta Latente/genética , Escoliose/genética , Adolescente , Estudos de Coortes , Células HEK293 , Humanos , Mutação , Sequenciamento Completo do Exoma
17.
Pattern Recognit ; 124: 108452, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34848897

RESUMO

Due to the irregular shapes,various sizes and indistinguishable boundaries between the normal and infected tissues, it is still a challenging task to accurately segment the infected lesions of COVID-19 on CT images. In this paper, a novel segmentation scheme is proposed for the infections of COVID-19 by enhancing supervised information and fusing multi-scale feature maps of different levels based on the encoder-decoder architecture. To this end, a deep collaborative supervision (Co-supervision) scheme is proposed to guide the network learning the features of edges and semantics. More specifically, an Edge Supervised Module (ESM) is firstly designed to highlight low-level boundary features by incorporating the edge supervised information into the initial stage of down-sampling. Meanwhile, an Auxiliary Semantic Supervised Module (ASSM) is proposed to strengthen high-level semantic information by integrating mask supervised information into the later stage. Then an Attention Fusion Module (AFM) is developed to fuse multiple scale feature maps of different levels by using an attention mechanism to reduce the semantic gaps between high-level and low-level feature maps. Finally, the effectiveness of the proposed scheme is demonstrated on four various COVID-19 CT datasets. The results show that the proposed three modules are all promising. Based on the baseline (ResUnet), using ESM, ASSM, or AFM alone can respectively increase Dice metric by 1.12%, 1.95%,1.63% in our dataset, while the integration by incorporating three models together can rise 3.97%. Compared with the existing approaches in various datasets, the proposed method can obtain better segmentation performance in some main metrics, and can achieve the best generalization and comprehensive performance.

18.
Sci Total Environ ; 805: 150262, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34536861

RESUMO

Plants are either recognized to produce nitrous oxide (N2O) or considered as a medium to transport soil-produced N2O. To date, it is not clear whether in their habitat plants conduit N2O produced in soil or are a natural source. We aimed to understand role of plants in N2O emissions in field conditions. Therefore, rubber plants (Ficus elastica) were planted in the field; then plant and soil chambers were deployed simultaneously to collect gas samples, and 15N site preference (SP) of N2O was evaluated. The mean SP values of plant and soil emitted N2O were -20.85 ± 2.8‰ and -8.85 ± 1.08‰, respectively, and were significantly different (p < 0.0001); while bulk 15N of plant and soil emitted N2O were -10.83 ± 3.33‰ and -22.56 ± 3.37‰, respectively and were similar (p = 0.06). In the current study, soil always acted as a source of N2O, while plants were both source and sink. Plant and soil N2O fluxes had significant positive exponential relationship with both soil and air temperature. Soil water-filled pore space (WFPS) had significant negative linear relationship with only soil N2O fluxes. Plant N2O fluxes had significant positive linear relationship with plant respiration rates and negative linear relationship with plant surface areas. Based on the relationship between plant respiration rates and N2O fluxes, we suggest that mitochondria are the possible sites of N2O formation in plant cells while the relationship between plant surface areas and N2O fluxes suggests that roots are the parts of its formation in natural and field conditions. Our results suggest that plants are a natural source of N2O even at field conditions and challenge a view that plants are a medium to transport soil-produced N2O into the atmosphere.


Assuntos
Óxido Nitroso , Solo , Atmosfera , Óxido Nitroso/análise , Plantas , Água
19.
Invest Ophthalmol Vis Sci ; 62(15): 4, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34860240

RESUMO

Purpose: To investigate the clinical findings in Chinese patients diagnosed with familial exudative vitreoretinopathy (FEVR) and carrying pathogenic mutations. Methods: One hundred twenty unrelated patients with FEVR were enrolled in this study. Genomic DNA and ophthalmic examinations were collected from all the patients and their available relatives. Targeted next-generation sequencing was performed to detect mutations. In silico programs were used to evaluate the pathogenicity of all the mutations. Results: Eighty identified mutations were found in 81 unrelated patients (31/81 in LRP5, 25/81 in FZD4, 12/81 in TSPAN12, 8/81 in NDP, 4/81 in KIF11, and 1/81 in ZNF408). Among those mutations, 53 were novel (23/35 in LRP5, 15/21 in FZD4, 8/11 in TSPAN12, 3/8 in NDP, 3/4 in KIF11, 1/1 in ZNF408). Patients with LRP5, FZD4, TSPAN12, or NDP mutations were mainly classified into stage 4 and stage 5 and one-half of patients with KIF11 mutations were in stage 4. In addition, all the patients in NDP group were found to have bilateral symmetry in FEVR stage. Conclusions: Our results present profound phenotypic variability and a wide mutation spectrum of FEVR in the Chinese population, which could be useful for a precise and comprehensive genetic diagnosis for patients with FEVR in the future.


Assuntos
/genética , Proteínas do Olho/genética , Vitreorretinopatias Exsudativas Familiares/diagnóstico , Vitreorretinopatias Exsudativas Familiares/genética , Mutação/genética , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Feminino , Receptores Frizzled/genética , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Proteínas do Tecido Nervoso/genética , Fenótipo , Tetraspaninas/genética , Fatores de Transcrição/genética
20.
BMC Ophthalmol ; 21(1): 427, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893049

RESUMO

PURPOSE: To study whether retinal pigment epithelium (RPE) disruption and choroidal hyper-transmission on spectral-domain optical coherence tomography (SD-OCT) are signs of inflammatory neovascularization (CNV) in punctate inner choroidopathy (PIC). METHODS: This is a prospective cohort study. Seventeen patients (18 eyes) were diagnosed as PIC without CNV at baseline. Changes of morphological characteristics including choroidal hyper-transmission, hypo-transmission, RPE disruption, and ellipsoid zone (EZ) damage on SD-OCT were observed and recorded at baseline, 4, 8 and 12 weeks, respectively. The occurrence of CNV was detected by OCTA at each visit. Fisher's exact test was used to compare the relationship with each morphological sign and evaluate the predictable capability of secondary CNV in PIC (PIC+CNV) based on the structure changes on OCT. RESULTS: Among the 18 eyes, a total of 5 eyes (27.8%) developed PIC+CNV subsequently within 4 weeks follow-up. At 4, 8 and 12 weeks of follow-up, RPE disruption and choroidal hyper-transmission were found in all 5 PIC+CNV eyes. The incidence of RPE disruption was significant higher in PIC+CNV eyes compared with PIC eyes (P=0.001). PIC eyes with hyper-transmission had a higher risk for developing CNV compared with those without hyper-transmission (P=1.17×10-3). 2 out of 5 PIC+CNV eyes had a choroidal hypo-transmission component adjacent to hyper-transmission zone at 4 weeks of follow-up, and hypo-transmission could be observed in all 5 PIC+CNV eyes at 8 weeks of follow-up. The incidence of choroidal hypo-transmission was significant higher in PIC+CNV eyes than PIC eyes after 8 weeks. EZ damage began to recover at 4 weeks of follow-up and had no significant difference in the PIC eyes and PIC+CNV eyes (P=0.150, 0.196, 0.353). CONCLUSION: The presence of choroidal hyper-transmission and RPE disruption on SD-OCT is associated with the PIC+CNV. SD-OCT imaging facilitates the differentiation and track of the progression of inflammatory lesions and secondary CNV in PIC.


Assuntos
Epitélio Pigmentado da Retina , Síndrome dos Pontos Brancos , Corioide , Humanos , Estudos Prospectivos , Tomografia de Coerência Óptica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...