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BACKGROUND: Spontaneous abortion is a common complication of pregnancy that can lead to adverse physical and psychological outcomes for women. Vitamin D is reported to be associated with reproductive functions, whereas its casual effects on abortion remains unclear. MATERIALS AND METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between serum 25 hydroxyvitamin D [25(OH)D] concentration and the risk of spontaneous abortion. GWAS summary data of 25(OH)D were used as exposure, and data of spontaneous abortion was considered as outcome. A retrospective study was additionally conducted to verify the MR results. RESULTS: MR estimates showed that a higher 25(OH)D level was potentially associated with decreased risk of spontaneous abortion (IVW, OR = 0.98, 95%CI = 0.90-1.06; MR Egger, OR = 0.94, 95%CI = 0.84-1.05; Weighted median, OR = 0.93, 95%CI = 0.82-1.06; Weighted mode, OR = 0.93, 95%CI = 0.84-1.03), though the P-value was not statistically significant. The retrospective study also produced consistent result of Vitamin D's protective role to spontaneous abortion. The P-value was very close to statistical significance (P = 0.053). CONCLUSIONS: This study reports the potential protective role of serum 25(OH)D concentration to spontaneous abortion, suggesting that increased vitamin D levels may decrease the risk of abortion. Further larger prospective studies and/or even randomized controlled trials are needed to confirm causal relationship between vitamin D and abortion.
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Aborto Espontáneo , Análisis de la Aleatorización Mendeliana , Vitamina D , Humanos , Femenino , Aborto Espontáneo/epidemiología , Vitamina D/sangre , Vitamina D/análogos & derivados , Estudios Retrospectivos , Embarazo , Adulto , Estudio de Asociación del Genoma CompletoRESUMEN
BACKGROUND: Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets. METHODS: Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset. RESULTS: MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes. CONCLUSION: Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.
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PURPOSE: Myopia, especially high myopia (HM), represents a widespread visual impairment with a globally escalating prevalence. This study aimed to elucidate the genetic foundations associated with early-onset HM (eoHM) while delineating the genetic landscape specific to Shaanxi province, China. METHODS: A comprehensive analysis of whole-exome sequencing was conducted involving 26 familial trios displaying eoHM. An exacting filtration protocol identified potential candidate mutations within acknowledged myopia-related genes and susceptibility loci. Subsequently, computational methodologies were employed for functional annotations and pathogenicity assessments. RESULTS: Our investigation identified 7 genes and 10 variants associated with HM across 7 families, including a novel mutation in the ARR3 gene (c.139C>T, p.Arg47*) and two mutations in the P3H2 gene (c.1865T>C, p.Phe622Ser and c.212T>C, p.Leu71Pro). Pathogenic mutations were found in syndromic myopia genes, notably encompassing VPS13B, TRPM1, RPGR, NYX and RP2. Additionally, a thorough comparison of previously reported causative genes of syndromic myopia and myopia risk genes with the negative sequencing results pinpointed various types of mutations within risk genes. CONCLUSIONS: This investigation into eoHM within Shaanxi province adds to the current understanding of myopic genetic factors. Our results warrant further functional validation and ocular examinations, yet they provide foundational insights for future genetic research and therapeutic innovations in HM.
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Secuenciación del Exoma , Predisposición Genética a la Enfermedad , Mutación , Linaje , Humanos , Femenino , Masculino , Predisposición Genética a la Enfermedad/genética , Adulto , China/epidemiología , Análisis Mutacional de ADN , Miopía Degenerativa/genética , Miopía Degenerativa/diagnóstico , Niño , Adolescente , Miopía/genética , Miopía/epidemiología , Adulto JovenRESUMEN
The purpose of this paper is to systematically summarize the gene polymorphisms associated with osteoporosis(OP)susceptibility in Zhuang ethnic group in Guangxi.These genes mainly encode vitamin D receptor,estrogen receptor,calcitonin receptor,and adiponectin.The genotype and allele distribution frequency were compared between Zhuang ethnic group and other ethnic groups,which can clarify the existing genes and the potential gene polymorphism associated with OP in Zhuang ethnic group.The findings provide a representative solution for the subsequent research on the genes associated with OP susceptibility in ethnic minorities.
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Etnicidad , Osteoporosis , Humanos , Etnicidad/genética , China , Polimorfismo Genético , Frecuencia de los Genes , Osteoporosis/genéticaRESUMEN
Purpose: NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. Methods: Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. Results: Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. Conclusions: Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.
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Productos Biológicos , Síndromes Periódicos Asociados a Criopirina , Niño , Humanos , Lactante , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Síndromes Periódicos Asociados a Criopirina/diagnóstico , Síndromes Periódicos Asociados a Criopirina/tratamiento farmacológico , Síndromes Periódicos Asociados a Criopirina/genética , Mutación , Variación GenéticaRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting an unmet clinical need for more effective therapies. This study aims to evaluate the causal relationship between 4,489 plasma proteins and CRC to identify potential therapeutic targets for CRC. METHODS: We conducted two-sample Mendelian randomization (MR) analysis to examine the causal effects of plasma proteins on CRC. Mediation analysis was performed to assess the indirect effects of plasma proteins on CRC through associated risk factors. In addition, we conducted a phenome-wide association study using the UK Biobank dataset to examine associations between these plasma proteins and other phenotypes. RESULTS: Out of 4,489 plasma proteins, MR analysis revealed causal associations with CRC for 23 proteins, including VIMP, MICB, TNFRSF11B, C5orf38 and SLC5A8. Our findings also confirm the associations between reported risk factors and CRC. Mediation analysis identified mediating effects of proteins on CRC outcomes through risk factors. Furthermore, MR analysis identified 154 plasma proteins are causally linked to at least one CRC risk factor. CONCLUSIONS: Our study evaluated the causal relationships between plasma proteins and CRC, providing a more complete understanding of potential therapeutic targets for CRC.
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Neoplasias Colorrectales , Proteoma , Humanos , Proteoma/genética , Análisis de la Aleatorización Mendeliana , Factores de Riesgo , Proteínas Sanguíneas , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Transportadores de Ácidos MonocarboxílicosRESUMEN
Müller cells play an integral role in the development, maintenance, and photopic signal transmission of the retina. While lower vertebrate Müller cells can differentiate into various types of retinal neurons to support retinal repair following damage, there is limited neurogenic potential of mammalian Müller cells. Therefore, it is of great interest to harness the neurogenic potential of mammalian Müller cells to achieve self-repair of the retina. While multiple studies have endeavored to induce neuronal differentiation and proliferation of mammalian Müller cells under defined conditions, the efficiency and feasibility of these methods often fall short, rendering them inadequate for the requisites of retinal repair. As the mechanisms and methodologies of Müller cell reprogramming have been extensively explored, a summary of the reprogramming process of unlocking the neurogenic potential of Müller cells can provide insight into Müller cell fate development and facilitate their therapeutic use in retinal repair. In this review, we comprehensively summarize the progress in reprogramming mammalian Müller cells and discuss strategies for optimizing methods and enhancing efficiency based on the mechanisms of fate regulation.
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Aims: Observational studies have shown that sleep pattern is associated with age-related macular degeneration (AMD), but whether sleep pattern is a causal factor for AMD remains unclear. This study aims to use Mendelian randomization (MR) analysis to investigate the potential causal relationship between sleep traits and AMD. Methods: This is a two-sample MR study. The single-nucleotide polymorphisms associated with AMD and early AMD were selected as the outcome from two different genome-wide association studies (GWAS): the early AMD GWAS with 14,034 cases and 91,214 controls, and AMD GWAS with 3,553 cases and 147,089 controls. The datasets of sleep duration, daytime dozing, and sleeplessness were used as exposure, which comprised nearly 0.46 million participants. Inverse-variance weighted method was used as the main result, and comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the impact of potential horizontal pleiotropy. Results: Through MR analysis, we found that sleep duration was significantly associated with AMD (OR = 0.983, 95% CI = 0.970-0.996, P-value = 0.01). We also found suggestive evidence for the association of genetically predicted sleep duration with early AMD, which showed a consistent direction of effect with a marginal significance (OR = 0.724, 95% CI = 0.503-1.041, P-value = 0.08). Sensitivity analyses further supported the robustness of the causal relationship between sleep duration and AMD. However, we were unable to determine the relationship between daytime dozing or sleeplessness and AMD (including early AMD) (P-value > 0.05). Conclusion: Sleep duration affects the causal risk for AMD; that is, longer sleep duration reduces the risk of AMD, while shorter sleep duration increases the risk of AMD. Although the influence is minimal, keeping adequate sleep duration is recommended, especially for patients with intermediate or advanced AMD.
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Purpose: Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between the inner and the outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse and study the resulting phenotype. Methods: We used Cep250 KO mice and untargeted metabolomics to uncover potential mechanisms underlying retinal degeneration. Long-term follow-up studies using optical coherence tomography (OCT) and electroretinography (ERG) were performed. Results: OCT and ERG results demonstrated gradual thinning of the outer nuclear layer (ONL) and progressive attenuation of the scotopic ERG responses in Cep250-/- mice. More TUNEL signal was observed in the ONL of these mice. Immunostaining of selected OS proteins revealed mislocalization of these proteins in the ONL of Cep250-/- mice. Interestingly, untargeted metabolomics analysis revealed arginine-related metabolic pathways were altered and enriched in Cep250-/- mice. Mis-localization of a key protein in the arginine metabolism pathway, arginase 1 (ARG1), in the ONL of KO mice further supports this model. Moreover, adeno-associated virus (AAV)-based retinal knockdown of Arg1 led to similar architectural and functional alterations in wild-type retinas. Conclusions: Altogether, these results suggest that dysregulated arginine metabolism contributes to retinal degeneration in Cep250-/- mice. Our findings provide novel insights that increase understanding of retinal degeneration in ciliopathy disorders.
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Ciliopatías , Degeneración Retiniana , Animales , Ratones , Arginina , Ratones Noqueados , RetinaRESUMEN
BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear. METHODS: In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs = 11,304,110). RESULTS: MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10-8). In addition, level of ApoA is also positively associated with risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10-6). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR = 0.77, 95% CI: 0.71-0.84, P = 5.02 × 10-10). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results. CONCLUSION: This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.
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Although the cell atlas of the human ocular anterior segment of the human eye was revealed by single-nucleus RNA sequencing, whether subtypes of lens stem/progenitor cells exist among epithelial cells and the molecular characteristics of cell differentiation of the human lens remain unclear. Single-cell RNA sequencing is a powerful tool to analyse the heterogeneity of tissues at the single cell level, leading to a better understanding of the processes of cell differentiation. By profiling 18,596 cells in human lens superficial tissue through single-cell sequencing, we identified two subtypes of lens epithelial cells that specifically expressed C8orf4 and ADAMTSL4 with distinct spatial localization, a new type of fibre cells located directly adjacent to the epithelium, and a subpopulation of ADAMTSL4+ cells that might be lens epithelial stem/progenitor cells. We also found two trajectories of lens epithelial cell differentiation and changes of some important genes during differentiation.
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Cristalino , Humanos , Cristalino/metabolismo , Epitelio , Células Epiteliales/metabolismo , Ojo , Diferenciación Celular , Análisis de Secuencia de ARNRESUMEN
Purpose: Little is known about whether sugar intake is a risk factor for myopia, and the influence of glycemic control remains unclear, with inconsistent results reported. This study aimed to clarify this uncertainty by evaluating the link between multiple glycemic traits and myopia. Methods: We employed a two-sample Mendelian randomization (MR) design using summary statistics from independent genome-wide association studies. A total of six glycemic traits, including adiponectin, body mass index, fasting blood glucose, fasting insulin, hemoglobin A1c (HbA1c), and proinsulin levels, were used as exposures, and myopia was used as the outcome. The inverse-variance-weighted (IVW) method was the main applied analytic tool and was complemented with comprehensive sensitivity analyses. Results: Out of the six glycemic traits studied, we found that adiponectin was significantly associated with myopia. The genetically predicted level of adiponectin was consistently negatively associated with myopia incidence: IVW (odds ratio [OR] = 0.990; P = 2.66 × 10-3), MR Egger (OR = 0.983; P = 3.47 × 10-3), weighted median method (OR = 0.989; P = 0.01), and weighted mode method (OR = 0.987; P = 0.01). Evidence from all sensitivity analyses further supported these associations. In addition, a higher HbA1c level was associated with a greater risk of myopia: IVW (OR = 1.022; P = 3.06 × 10-5). Conclusions: Genetic evidence shows that low adiponectin levels and high HbA1c are associated with an increased risk of myopia. Given that physical activity and sugar intake are controllable variables in blood glycemia treatment, these findings provide new insights into potential strategies to delay myopia onset.
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Adiponectina , Miopía , Humanos , Estudio de Asociación del Genoma Completo , Hemoglobina Glucada , AzúcaresRESUMEN
Adenine base editors (ABEs) are novel genome-editing tools, and their activity has been greatly enhanced by eight additional mutations, thus named ABE8e. However, elevated catalytic activity was concomitant with frequent generation of bystander mutations. This bystander effect precludes its safe applications required in human gene therapy. To develop next-generation ABEs that are both catalytically efficient and positionally precise, we performed combinatorial engineering of NG-ABE8e. We identify a novel variant (NG-ABE9e), which harbors nine mutations. NG-ABE9e exhibits robust and precise base-editing activity in human cells, with more than 7-fold bystander editing reduction at some sites, compared with NG-ABE8e. To demonstrate its practical utility, we used NG-ABE9e to correct the frequent T17M mutation in Rhodopsin for autosomal dominant retinitis pigmentosa. It reduces bystander editing by â¼4-fold while maintaining comparable efficiency. NG-ABE9e possesses substantially higher activity than NG-ABEmax and significantly lower bystander editing than NG-ABE8e in rice. Therefore, this study provides a versatile and improved adenine base editor for genome editing.
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Adenina , Edición Génica , Sistemas CRISPR-Cas , Humanos , MutaciónRESUMEN
Purpose: To investigate the deficits in contrast sensitivity in patients with Fuchs uveitis syndrome (FUS) and to explore the potential relationship between contrast sensitivity and ocular structure. Methods: In this prospective study, 25 patients with FUS and 30 healthy volunteers were recruited. Eyes were divided into three groups: FUS-affected eyes (AE), fellow eyes (FE), and healthy eyes. The contrast sensitivity function (CSF) of all participants was evaluated using the quick CSF (qCSF) method. Fundus photographs were collected for the analysis of refractive media, and vascular density (VD) was assessed using optical coherence tomography angiography (OCTA). Data were analyzed and compared using the generalized estimating equation (GEE). Results: The CSF of AE was significantly lower than that of FE and controls, while no significant difference was observed between FE and controls. Contrast sensitivity was negatively correlated with the grade of haze. No significant correlation was found between visual function and VDs in FUS eyes. Conclusions: We found that the CSF of FUS-affected eyes was significantly reduced, and the visual impairment was predominantly caused by the refractive media turbidity.
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Purpose: Abundant retinal microRNA-183 cluster (miR-183C) has been reported to be a key player in photoreceptor development and functionality in mice. However, whether there is a protagonist in this cluster remains unclear. Here, we used a mutant mouse model to study the role of miR-96, a member of miR-183C, in photoreceptor development and functionality. Methods: The mature miR-96 sequence was removed using the CRISPR/Cas9 genome-editing system. Electroretinogram (ERG) and optical coherence tomography (OCT) investigated the changes in structure and function in mouse retinas. Immunostaining determined the localization and morphology of the retinal cells. RNA sequencing was conducted to observe retinal transcription alterations. Results: The miR-96 mutant mice exhibited cone developmental delay, as occurs in miR-183/96 double knockout mice. Immunostaining of cone-specific marker genes revealed cone nucleus mislocalization and exiguous Opn1mw/Opn1sw in the mutant (MT) mouse outer segments at postnatal day 10. Interestingly, this phenomenon could be relieved in the adult stages. Transcriptome analysis revealed activation of microtubule-, actin filament-, and cilia-related pathways, further supporting the findings. Based on ERG and OCT results at different ages, the MT mice displayed developmental delay not only in cones but also in rods. In addition, a group of miR-96 potential direct and indirect target genes was summarized for interpretation and further studies of miR-96-related retinal developmental defects. Conclusions: Depletion of miR-96 delayed but did not arrest photoreceptor development in mice. This miRNA is indispensable for mouse photoreceptor maturation, especially for cones.
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MicroARNs , Células Fotorreceptoras Retinianas Conos , Animales , Electrorretinografía , Ratones , Ratones Noqueados , MicroARNs/metabolismo , Células Fotorreceptoras Retinianas Conos/metabolismo , Células Fotorreceptoras Retinianas Bastones/metabolismoRESUMEN
Uveitis is the most common form of intraocular inflammatory disease and is a significant cause of visual impairment worldwide. Aetiologically, uveitis can also be classified into infectious uveitis and non-infectious uveitis. The common non-infectious forms of uveitis include acute anterior uveitis (AAU), Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, birdshot chorioretinopathy (BSCR), sarcoid uveitis. In addition, a few monogenic autoinflammatory disorders can also cause uveitis, such as Blau Syndrome and haploinsufficiency of A20 (HA20). Although the exact pathogenesis of non-infectious uveitis is still unclear, it is well-recognised that it involves both genetic and environmental risk factors. A hallmark of uveitis is its strong associations with human leucocyte antigens (HLA). For examples, AAU, BD and BSCR are strongly associated with HLA-B27, HLA-B51, and HLA-A29, respectively. In uveitis studies, multiple GWAS have successfully been conducted and led to identification of novel susceptibility loci, for example, IL23R has been identified in BD, VKH and AAU. In this review, we summarize the latest progress on the genetic associations of both HLA and non-HLA genes with major forms of uveitis, including AAU, BD, VKH, BSCR, sarcoid uveitis, Blau Syndrome and HA20, and potential future research directions.
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Artritis , Síndrome de Behçet , Sarcoidosis , Sinovitis , Uveítis Anterior , Uveítis , Síndrome de Behçet/genética , Antígenos HLA/genética , Antígeno HLA-B27 , Humanos , Sarcoidosis/genética , Uveítis/genética , Uveítis Anterior/genéticaRESUMEN
BACKGROUND: Emerging evidence shows that periodontal disease (PD) may increase the risk of Coronavirus disease 2019 (COVID-19) complications. Here, we undertook a two-sample Mendelian randomization (MR) study, and investigated for the first time the possible causal impact of PD on host susceptibility to COVID-19 and its severity. METHODS: Summary statistics of COVID-19 susceptibility and severity were retrieved from the COVID-19 Host Genetics Initiative and used as outcomes. Single nucleotide polymorphisms associated with PD in Genome-wide association study were included as exposure. Inverse-variance weighted (IVW) method was employed as the main approach to analyze the causal relationships between PD and COVID-19. Three additional methods were adopted, allowing the existence of horizontal pleiotropy, including MR-Egger regression, weighted median and weighted mode methods. Comprehensive sensitivity analyses were also conducted for estimating the robustness of the identified associations. RESULTS: The MR estimates showed that PD was significantly associated with significantly higher susceptibility to COVID-19 using IVW (OR = 1.024, P = 0.017, 95% CI 1.004-1.045) and weighted median method (OR = 1.029, P = 0.024, 95% CI 1.003-1.055). Furthermore, it revealed that PD was significantly linked to COVID-19 severity based on the comparison of hospitalization versus population controls (IVW, OR = 1.025, P = 0.039, 95% CI 1.001-1.049; weighted median, OR = 1.030, P = 0.027, 95% CI 1.003-1.058). No such association was observed in the cohort of highly severe cases confirmed versus those not hospitalized due to COVID-19. CONCLUSIONS: We provide evidence on the possible causality of PD accounting for the susceptibility and severity of COVID-19, highlighting the importance of oral/periodontal healthcare for general wellbeing during the pandemic and beyond.
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COVID-19 , Enfermedades Periodontales , COVID-19/genética , Estudio de Asociación del Genoma Completo , Humanos , Análisis de la Aleatorización Mendeliana , Enfermedades Periodontales/complicaciones , Enfermedades Periodontales/genética , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Heterotopic cesarean scar pregnancy (HCSP) is very rare and has a high risk of massive uterine bleeding. Preservation of concurrent intrauterine pregnancy (IUP) is one of the great challenges in the management of HCSP. No universal treatment protocol has been established when IUP is desired to be preserved. CASE SUMMARY: We report a case of HCSP at 8+ wk gestation in a 34-year-old woman with stable hemodynamics. A two-step intervention was applied. Selective embryo aspiration was performed first, and surgical removal of ectopic gestational tissue by suction and curettage was performed 2 d later. Both steps were performed under ultrasound guidance. The patient had an uneventful course, and a healthy baby was delivered at 34+6 wk gestation. CONCLUSION: Selective embryo aspiration followed by suction and curettage was successful in the preservation of IUP in the management of HCSP. This approach is an alternative option for HCSP in the first trimester when the IUP is desired to be preserved.
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BACKGROUND: Deep endometriosis (DE) is the most aggressive subtype of endometriosis. The diagnosis may be challenging, and no biomarkers that can discriminate women with DE from those without DE have been developed. AIM: To evaluate the role of blood hemostatic parameters and inflammatory indices in the prediction of DE. METHODS: This case-control study was performed at the Women's Hospital, Zhejiang University School of Medicine between January 2015 and December 2016. Women with DE and women with benign gynecologic disease (control group) eligible for gynecological surgery were enrolled. Routine plasma hemostatic parameters and inflammatory indices were obtained before surgery. Univariate and multivariate analysis were performed. Receiver operating characteristic (ROC) curves were generated, and areas under the curve (AUC) were calculated to assess the predictive values of the selected parameters. RESULTS: A total of 126 women were enrolled, including 31 with DE and 95 controls. Plasma fibrinogen (Fg, P < 0.01), international normalized ratio (P < 0.05), and C-reactive protein levels (P < 0.01) were significantly higher in women with DE compared with controls. Plasma hemoglobin (HB) levels (P < 0.05) and shortened thrombin time (P < 0.05) were significantly lower in women with DE than in controls. Plasma Fg levels [adjusted OR (aOR) 2.12, 95%confidence interval (CI): 1.31-3.75] and plasma HB levels (aOR 0.48, 95%CI: 0.29-0.78) were significantly associated with DE (both P < 0.05). ROC analysis showed that the diagnostic value of Fg or HB alone for DE was limited. The AUC of the combination of both markers as a dual marker index was 0.773 with improved sensitivity (67.7%) and specificity (78.9%) at cutoffs of 3.09 g/L and 126 g/L, respectively. CONCLUSION: The combination of Fg and HB was a reliable predictor of DE. A larger study is needed to confirm the findings.
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Purpose: To characterize the quality of life and mental health status of patients with uveitis and investigate predictors of psychological problems.Methods: A total of 245 patients and 105 controls were enrolled in this cross-sectional study. Quality of life, psychological status, socio-demographic and clinical data were obtained from questionnaires and medical records. Multivariate regression analyses and Receiver Operating Characteristic (ROC) were applied to obtain the model predicting psychological problems of patients.Results: Of 245 patients, 16.7% and 26.5% (P< .0001) screened positive for anxiety and depression, respectively. The model predicting anxiety was comprised of low annual household income and poor self-reported visual function (P= .029,P< .0001, respectively), with an AUC of ROC of 0.744. The model predicting depression was comprised of poor self-reported visual function and ocular complications (P< .0001, P= .012, respectively), with an AUC of 0.78.Conclusions: Economic hardship, ocular complications, and poor self-reported visual function are predictors of mental problems in patients with uveitis.