Goldenhar syndrome with limbal neoformation, microtia and skeletal deformities: a case report and literature review.

BACKGROUND: To report a case of a 4-year-old patient with Goldenhar syndrome. CASE PRESENTATION: The author presents a rare case report involving a 4-year-old boy with multiple malformations. A comprehensive examination showed that the patient primarily had a limbal dermoid. He also has bilateral microtia and ear canal deformities. The skull CT scan and spine X-ray showed Maxillofacial Abnormalities and scoliosis. Whole Exome Sequencing revealed potential gene variations related to microtia. Although certain circumstances prevented us from initiating follow-up treatment for the patient, we have provided a detailed account of the diagnostic methodologies used for this condition. CONCLUSIONS: Goldenhar syndrome is a congenital condition, predominantly presenting as sporadic cases. Its diagnosis and management typically necessitate the involvement of multiple disciplines, including otolaryngology and craniofacial surgery. The syndrome encompasses a variety of craniofacial features, which can facilitate early diagnosis and guide subsequent therapeutic interventions.

Seawater intrusion-triggered high fluoride groundwater development on the eastern coast of China.

High-fluoride groundwater is commonly found in coastal areas worldwide, while its formation mechanism remains elusive. Herein, a comprehensive study was performed to identify the major controlling factor of high-fluoride groundwater occurrence along the eastern coast of China. Hydrogeochemical methods were employed to examine the distribution patterns of seawater intrusion and fluoride concentration and the impact of seawater intrusion on the fluoride concentration. The results indicate that seawater intrusion significantly influences the groundwater evolution process in the study areas. The groundwater in Laizhou Bay was affected by brine, and the groundwater in Tianjin and Jiangsu was affected by seawater with a mixing ratio lower than 40% and 20%, respectively. And the fluoride concentration in groundwater from Tianjin, Laizhou Bay, and Jiangsu generally exceeded 1 mg/L, with the average of 2.3 mg/L, 24.9 mg/L, and 34.6 mg/L, respectively. Both the degree of seawater intrusion and the fluoride concentration exhibit a consistent pattern: Laizhou Bay > Tianjin > Jiangsu. Cl- concentration in groundwater varies positively with the F- concentration (y = 0.66x - 1.31). Moreover, the spatial distribution of areas with high-fluoride groundwater mirrors that of seawater intrusion. The high-fluoride groundwater varies spatially and is related to the degree, stage, and type of seawater intrusion. In other words, when seawater intrusion intensifies more or groundwater in the freshwater renewal phase with higher Na+/Ca2+ or the presence of paleo-seawater intrusion with higher fluoride concentration of brine, the concentration of fluoride in groundwater is higher. As seawater intrusion intensifies, the high-fluoride groundwater in the study areas generally poses a higher health risk to human. These findings enhance our comprehension of the mechanisms underpinning high-fluoride groundwater in coastal regions and the environmental ramifications of seawater intrusion.

Metformin protects human lens epithelial cells from high glucose-induced senescence and autophagy inhibition by upregulating SIRT1.

PURPOSE: The aim of this study is to explore whether metformin (MET) protects the human lens epithelial cells (HLECs) from high glucose-induced senescence and to identify the underlying mechanisms. METHODS: A cellular senescence model was established by treating HLE-B3 cells with D-glucose and then intervened with MET. Concentrations of high glucose (HG) and MET were detected using CCK-8 and western blot. qRT-PCR, western blot, and senescence-associated ß-galactosidase (SA-ß-gal) were performed to verify the protective effect of MET on senescent HLE-B3 cells. Additionally, western blot and qRT-PCR were conducted to detect the effects of MET on autophagy-related markers p62 and LC3, as well as SIRT1. RESULTS: In vitro, we observed apparent senescence in human lens epithelial cells (HLECs) under high glucose conditions. This was characterized by increased senescence-associated genes p21 and p53. However, the addition of MET significantly reduced the occurrence of HLECs senescence. We also observed that high glucose inhibited both autophagy and SIRT1, which could be restored by MET. Moreover, we verified that the anti-senescence effect of MET was mediated by SIRT1 using SIRT1 activators and inhibitors. CONCLUSION: We have demonstrated that autophagy and SIRT1 activity are inhibited in HLE-B3 cells using the HG induced senescence model. Furthermore, our results showed that MET can delay senescence by activating SIRT1 and autophagy. These findings suggest that MET may be a promising candidate for alleviating cataract development and provide a direction for further investigation into the underlying molecular mechanisms.

Hydrochemical characteristics and quality assessment of groundwater in Guangxi coastal areas, China.

Groundwater is a main source of water supply in Guangxi Province, China. The urbanization expansion and ocean dynamic may change the groundwater quality, which is an important issue due to its effects on human health. In this paper, the influence of seawater intrusion and anthropogenic activity on the Guangxi coastal aquatic environment was assessed by geochemical and multivariate statistical methods. The result indicated that the chemical composition of groundwater in the study area is obviously associated with seawater and the main groundwater types were Ca·Na-Cl, Ca·Na-HCO3, and Ca-HCO3·Cl. The groundwater evolution path from land to sea in Guangxi is Ca-HCO3 â†’ Na·Mg-Cl. The origin of salts in the study area is mainly controlled by mineral weathering, the hydrogen and oxygen isotopes contents point to the aqueous source of atmospheric precipitation. According to the results of PCA, seawater intrusion and pollution caused by human activities play an increasingly important role in the evolution of groundwater characteristics. Seawater intrusion is the main factor for the increase of groundwater salinity in Guangxi, while domestic sewage, industrial waste, fertilizers, and pesticides may contribute to the nitrate pollution of groundwater, especially in Beihai. The degree of groundwater nitrate pollution is as follows: Fangchenggang < Qinzhou < Beihai, which is associated with the degree of urbanization in the coastal area. Finally, the results of the water quality index (WQI) assessment show that 82.8 % of the samples were classified as excellent, while there is still a need to be vigilant about groundwater pollution caused by seawater intrusion and groundwater pollution. The results will be valuable for sustainable groundwater resource management in Guangxi coastal zone.

Metformin protects lens epithelial cells against senescence in a naturally aged mouse model.

The senescence of lens epithelial cells (LECs) is a major factor leading to age-related cataract (ARC). ARC results in visual impairment and severe vision loss in elderly patients. However, the specific mechanism of ARC remains unclear, and there are no effective therapeutic agents to halt the formation of ARC. This study aimed to assess the underlying mechanism of the formation of ARC and investigate the potential anti-ageing effect of metformin (MET) on ARC. Male C57BL/6 mice were divided into three groups: the control group having young mice (3 months old, n = 40), the naturally aged group (aged 20 months, n = 60) and the MET group (MET, 20 months, n = 60). Mice in the control and the naturally aged groups were fed a standard purified mouse diet ad libitum and water, whereas those in the MET group were fed chows supplemented with 0.1% MET for 10 months. The transparency of the lens and age-associated proteins p21 and p53 were analysed in the LECs of these three groups. Furthermore, we determined the expressions of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway and the effect of MET on this pathway in LECs during the ageing process of ARC. In addition, the relationship between autophagy and the senescence of LECs and the role of MET in the autophagy of LECs during the ageing process of ARC were examined. Our results indicated that age-related inactivation of the AMPK pathway and impairment of autophagy might contribute to the senescence of LECs and the occurrence of ARC. More importantly, these results demonstrated that MET effectively alleviated the senescence of LECs and the formation of ARC probably via inactivation of the AMPK pathway and augmentation of autophagy. These findings revealed that MET can be exploited as a potentially useful drug for ARC prevention. Our study will help in enlightening the development of innovative strategies for the clinical treatment of ARC.

Positive correlation of the serum angiopoietin-like protein 3 levels with the aortic augmentation index in patients with coronary artery disease.

PURPOSE: Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid metabolism and angiogenesis and is elevated in familial hypercholesterolemia, metabolic syndrome, and insulin resistance. This study aims to evaluate the relationship between the fasting serum ANGPTL3 levels and the aortic augmentation index (AIx) in patients with coronary artery disease (CAD). MATERIALS AND METHODS: Fasting blood samples were obtained from 100 patients with CAD. The AIx was measured using a validated tonometry system (SphygmoCor). The serum ANGPTL3 levels were assessed using a commercial enzyme-linked immunosorbent assay kit. RESULTS: The aortic AIx values were higher in female patients with CAD (P=0.003) than those in male patients with CAD. The univariate linear analysis of the aortic AIx values reveals that the height (r=-0.363; P<0.001) and body weight (r=-0.350; P<0.001) were negatively correlated, whereas the age (r=0.202; P=0.044) and logarithmically transformed ANGPTL3 (log-ANGPTL3, r=0.357; P<0.001) were positively correlated with the aortic AIx values in patients with CAD. The multivariate forward stepwise linear regression analysis of the factors significantly associated with the aortic AIx revealed that the height (ß=-0.269; adjusted R2 change=0.123; P=0.007) and serum log-ANGPTL3 level (ß=0.259; adjusted R2 change=0.051; P=0.010) were independent predictors of the aortic AIx values in patients with CAD. CONCLUSION: The fasting serum ANGPTL3 level positively correlated with the aortic AIx values among patients with CAD.

Enhanced antitumor activity in A431 cells via encapsulation of 20(R)-ginsenoside Rg3 in PLGA nanoparticles.

OBJECTIVE: The objective of this study is to investigate the encapsulation of 20(R)-ginsenoside Rg3 (20(R)-Rg3) using polylactic-co-glycolic acid (PLGA) and promotion for its antitumor activity. SIGNIFICANCE: Preparation and evaluation of the antitumor efficacy of 20(R)-Rg3-loaded PLGA nanoparticles were the first reported. The data will be helpful to apply 20(R)-Rg3 efficiently and broadly in new drug form development and clinical cancer treatment. METHODS: The nanoparticles were prepared using emulsion and solvent evaporation methods. The uniform particle size and good dispersion were further confirmed by scanning electron microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to detect cell proliferation after 20(R)-Rg3-loaded PLGA nanoparticles treatment. Western blotting and immunofluorescent staining were used for observation of key proteins related with proliferation and apoptosis. Cell cycle and apoptosis were analyzed by flow cytometer technology. RESULTS AND DISCUSSION: The results showed that the size of 20(R)-Rg3-loaded PLGA was 97.5 nm in diameter, and zeta potential was -28 mV detected by Malvern particle size analyzer. The encapsulation efficiency was 97.5%, and drug loading was 70.2% measured by high-performance liquid chromatography. The in vitro study showed that the encapsulated 20(R)-Rg3 was consecutively released and the release ratio reached to the highest value (19.36%) at the time point of 96 h. The encapsulated 20(R)-Rg3 significantly inhibited the proliferation and induced apoptosis in A431 cancer cells compared with the unencapsulated 20(R)-Rg3, control and PLGA alone. CONCLUSION: 20(R)-Rg3-loaded PLGA nanoparticles was well prepared and characterized. The antitumor activity was increased after PLGA encapsulation. The data will be beneficial to the development of new dosage forms of 20(R)-Rg3 and extensive application.