Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation.

BACKGROUND: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. METHODS: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. RESULTS: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. CONCLUSION: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.

Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway.

BACKGROUND: Glycation is an important step in aging and oxidative stress, which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics. Inhibition of the formation of advanced glycation end products (AGEs) and their cell toxicity can be a useful therapeutic strategy in the prevention of diabetic retinopathy (DR). Gardenia jasminoides Ellis (GJE) fruit is a selective inhibitor of AGEs. Genipin is an active compound of GJE fruit, which can be employed to treat diabetes. AIM: To confirm the effect of genipin, a vital component of GJE fruit, in preventing human retinal microvascular endothelial cells (hRMECs) from AGEs damage in DR, to investigate the effect of genipin in the down-regulation of AGEs expression, and to explore the role of the CHGA/UCP2/glucose transporter 1 (GLUT1) signal pathway in this process. METHODS: In vitro, cell viability was tested to determine the effects of different doses of glucose and genipin in hRMECs. Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry, immunofluorescence, wound healing assay, transwell assay, and tube-forming assay were used to detect the effect of genipin on hRMECs cultured in high glucose conditions. In vivo, streptozotocin (STZ) induced mice were used, and genipin was administered by intraocular injection (IOI). To explore the effect and mechanism of genipin in diabetic-induced retinal dysfunction, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) assays were performed to explore energy metabolism and oxidative stress damage in high glucose-induced hRMECs and STZ mouse retinas. Immunofluorescence and Western blot were used to investigate the expression of inflammatory cytokines [vascular endothelial growth factor (VEGF), SCG3, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-18, and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3)]. The protein expression of the receptor of AGEs (RAGE) and the mitochondria-related signal molecules CHGA, GLUT1, and UCP2 in high glucose-induced hRMECs and STZ mouse retinas were measured and compared with the genipin-treated group. RESULTS: The results of CCK-8 and colony formation assay showed that genipin promoted cell viability in high glucose (30 mmol/L D-Glucose)-induced hRMECs, especially at a 0.4 µmol/L dose for 7 d. Flow cytometry results showed that high glucose can increase apoptosis rate by 30%, and genipin alleviated cell apoptosis in AGEs-induced hRMECs. A high glucose environment promoted ATP, ROS, MMP, and 2-NBDG levels, while genipin inhibited these phenotypic abnormalities in AGEs-induced hRMECs. Furthermore, genipin remarkably reduced the levels of the pro-inflammatory cytokines TNF-α, IL-1ß, IL-18, and NLRP3 and impeded the expression of VEGF and SCG3 in AGEs-damaged hRMECs. These results showed that genipin can reverse high glucose induced damage with regard to cell proliferation and apoptosis in vitro, while reducing energy metabolism, oxidative stress, and inflammatory injury caused by high glucose. In addition, ROS levels and glucose uptake levels were higher in the retina from the untreated eye than in the genipin-treated eye of STZ mice. The expression of inflammatory cytokines and pathway protein in the untreated eye compared with the genipin-treated eye was significantly increased, as measured by Western blot. These results showed that IOI of genipin reduced the expression of CHGA, UCP2, and GLUT1, maintained the retinal structure, and decreased ROS, glucose uptake, and inflammation levels in vivo. In addition, we found that SCG3 expression might have a higher sensitivity in DR than VEGF as a diagnostic marker at the protein level. CONCLUSION: Our study suggested that genipin ameliorates AGEs-induced hRMECs proliferation, apoptosis, energy metabolism, oxidative stress, and inflammatory injury, partially via the CHGA/UCP2/GLUT1 pathway. Control of advanced glycation by IOI of genipin may represent a strategy to prevent severe retinopathy and vision loss.

Evaluation of childhood developing via optical coherence tomography-angiography in Qamdo, Tibet, China: A prospective cross-sectional, school-based study.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a new and reliable machine used to evaluate retinal structure and macular perfusion in children. The use of OCTA under bad condition such as high altitude, low atmospheric oxygen, and low humidity, in children is rarely. AIM: To quantify the macular micro-vasculature in healthy children of various ages using OCTA in Qamdo. METHODS: Design: Prospective cross-sectional, school-based study. Three hundred and forty-seven normal students from 9 schools in 4 different areas in Qamdo were included. OCTA was performed on a 3 mm × 3 mm area centered on the macular region and macular cube 512 × 128 showed details in macular. Early treatment of diabetic retinopathy study Vessel Flow Density (VD) of the macular central vascular plexus density (CVD), inner vascular plexus density (IVD), full vascular plexus density (FVD), and the size of the foveal avascular zone (FAZ) were measured. All these results corrected by t/s = 3.382 × 0.01306 × (axial length-1.82). The differences were compared among various ages, sexes and living environments. RESULTS: The mean FAZ area in all eyes was 0.27 mm2 ± 0.12 mm2. The mean foveal thickness (MFT) in the macular cube was 227.64 µm ± 23.51 µm. Compared with girls, boys had a lager FAZ (P = 0.0029). Among the different age groups, MFT (P < 0.001) and FVD (P < 0.0001), IVD (P < 0.0001), and CVD (P = 0.0050) increased with age. FAZ areas were not correlated with age (P = 0.8853) or others (MFT, area). CONCLUSION: OCTA can use to evaluate macular perfusion in children. Our data bridge the gap between structural OCT and perfusion density in children in high altitude. Even though these were not a longitudinal study, it may provide us with hints about retina development during puberty and clinical implications of OCTA in children.

Machine Learning Prediction Model and Risk Factor Analysis of Reoperation in Recurrent Lumbar Disc Herniation Patients After Percutaneous Endoscopic Lumbar Discectomy.

OBJECTIVE: To investigate the risk factors of reoperation after percutaneous endoscopic lumbar discectomy (PELD) due to recurrent lumbar disc herniation (rLDH) and to establish a set of individualized prediction models. METHODS: Patients who underwent PELD successfully from January 2016 to February 2022 in a single institution were enrolled in this study. Six methods of machine learning (ML) were used to establish an individualized prediction model for reoperation in rLDH patients after PELD, and these models were compared with logistics regression model to select optimal model. RESULTS: A total of 2603 patients were enrolled in this study. 57 patients had repeated operation due to rLDH and 114 patients were selected from the remaining 2546 nonrecurrent patients as matched controls. Multivariate logistic regression analysis showed that disc herniation type (P < .001), Modic changes (type II) (P = .003), sagittal range of motion (sROM) (P = .022), facet orientation (FO) (P = .028) and fat infiltration (FI) (P = .001) were independent risk factors for reoperation in rLDH patients after PELD. The XGBoost AUC was of 90.71%, accuracy was approximately 88.87%, sensitivity was 70.81%, specificity was 97.19%. The traditional logistic regression AUC was 77.4%, accuracy was about 77.73%, sensitivity was 47.15%, specificity was 92.12%. CONCLUSION: This study showed that disc herniation type (extrusion, sequestration), Modic changes (type II), a large sROM, a large FO and high FI were independent risk factors for reoperation in LDH patients after PELD. The prediction efficiency of XGBoost model was higher than traditional Logistic regression analysis model.

[Effects of Biochar on Antibiotic Environmental Behaviors in Soil: A Meta-analysis].

Biochar, as a soil amendment for synergizing the reduction of pollution and carbon emissions, shows great potential and future prospects in controlling antibiotic contamination. In order to research the effects of biochar on antibiotic behaviors in soil systematically, a Meta-analysis was conducted based on 20 studies published from 2011 to 2021. The results showed that the adsorption and degradation of antibiotics in the soil were significantly affected by the application rate and property of biochar. A 2% biochar application dose seemed to be the highest effect size (ES) of 0.19 on adsorption, while there was a significant effect (ES=0.23) on the degradation when the application rate was 5%. The specific surface area, polarity, stability, and aromaticity of biochar could increase the partition coefficient significantly, and the ES was 0.11, 0.13, 0.09, and 0.18, respectively, whereas the effects of antibiotic transport on the dose and property of biochar were insignificant. Biochar also indirectly controlled antibiotic behavior by altering the soil environment. However, the response of the coupling mechanism in antibiotic behaviors on biochar application into soil is still unclear. Moreover, the long-term and negative effects of biochar application in the field are still lacking basic data.

[Effect of Aging on Adsorption of Tetracycline by Microplastics and the Mechanisms].

As new pollutants, microplastics (MPs) can adsorb antibiotics in the water environment and migrate together as carriers. However, microplastics will age continuously in the environment, and their adsorption capacity and adsorption mechanism will change accordingly. With polyethylene (PE) and polystyrene (PS) as the target MPs, which were irradiated by ultraviolet (UV-254), the changes in the physical and chemical properties of MPs before and after aging, such as the color, surface morphology, and functional groups, were compared, and their effects on the adsorption of tetracycline (TC) as well as the related mechanism were explored. The results showed that the pseudo-second-order model could better fit the adsorption process, the adsorption equilibrium was reached within 24 hours, the adsorption capacity of aged MPs for TC was significantly higher than that of original MPs, and the adsorption capacity of PS was higher than that of PE. Langmuir and Freundlich isothermal adsorption equations could both describe the adsorption isothermal test data, and the adsorption of TC on MPs was a spontaneous and endothermic physical adsorption process, whereas aging had no obvious effect on the adsorption thermodynamic characteristics of MPs. With the increase in pH value, the adsorption capacity first increased and then decreased. The maximum adsorption capacity of MPs before and after aging was reached at pH=5. UV aging increased the specific surface area of MPs, generating oxygen-containing functional groups such as -C＝O, -OH, and O＝C＝O, changing the physical and chemical properties of MPs, and thus changing the adsorption mechanism of MPs for TC. Compared with the original PE MPs, in addition to hydrophobic distribution, van der Waals forces, and electrostatic interactions, pore filling was also an important adsorption mechanism of aged PE. The main adsorption mechanisms of original PS microplastics were hydrophobic distribution, van der Waals forces, electrostatic interaction, and π-π interaction, whereas there was hydrogen bonding for aged PS.

[Effects of Histone Methyltransferase Inhibitors on the Survival, Apoptosis and Cell Cycle of Raji Cells].

OBJECTIVE: To determine the effects of three histone methylase inhibitors UNC1999, DZNep and GSK343 on the survival, apoptosis and cell cycle of non-hodgkin's lymphoma Raji cells. METHODS: PCR amplified 16 and 18 exons of enhancer of zeste homolog 2 ( EZH2) gene were detected. The expression of EZH2 in normal adult lymphocytes and Raji cells was detected by Western blot. The Raji cells were treated by UNC1999, DZNep and GSK343, followed by CCK-8 assays analyzing cell survival, flow cytometry detecting cell apoptosis and cell cycle, and Western blot detecting the expressions of EZH2 and H3K27 me3. RESULTS: The Sanger sequencing results showed that the Raji cells did not carry Y641 and A677 mutation sites of EZH2. The Western blot results showed high expressions of EZH2 in the Raji cells. The results of CCK-8 showed that UNC1999, DZNep and GSK343 inhibited cell survival, and the weakest effect was from DZNep. The flow cytometric assay showed that UNC1999, DZNep and GSK343 promoted apoptosis of the Raji cells, and the effect of UNC1999 was stronger than that of GSK343 and DZNep. The cell cycle was arrested at phase G 1/G 0 after treatment of the Raji cells with the three inhibitors, with UNC1999 triggering the most significant changes. The Western blot showed that UNC1999 and GSK343 inhibited the histone methylase activity of EZH2 and significantly reduced the expression of H3K27 me3. CONCLUSION: EZH2 inhibitors can inhibit cell survival, promote cell apoptosis and arrest cell cycle at phase G 1/G 0 of Raji cells through reducing the expression of H3K27me3. UNC1999 has a stronger effect than GSK343 and DZNep.

Activated complement classical pathway in a murine model of oxygen-induced retinopathy.

AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy (OIR). METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75%±2% oxygen from postnatal 7d (P7) to P12 and then recovered in room air. For the control group, the litters were raised in room air. At the postnatal 17d (P17), gene expressions of the complement components of the classical pathway (CP), the mannose-binding lectin (MBL) pathway and the alternative pathway (AP) in the retina were determined by quantitative real-time polymerase chain reaction (RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting. RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery. The expressions of C1qb and C4b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B (CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H (CFH) genes were higher. The protein synthesis of the key components involved in the CP (C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1 (MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant. CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.

Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis.

BACKGROUND: Previous studies yielded controversial results about the alteration of lipid profiles in patients with subclinical hypothyroidism. We performed a meta-analysis to investigate the association between subclinical hypothyroidism and lipid profiles. MATERIAL AND METHODS: We searched PubMed, Cochrane Library, and China National Knowledge Infrastructure articles published January 1990 through January 2014. Dissertation databases (PQDT and CDMD) were searched for additional unpublished articles. We included articles reporting the relationship between subclinical hypothyroidism and at least 1 parameter of lipid profiles, and calculated the overall weighted mean difference (WMD) with a random effects model. Meta-regression was used to explore the source of heterogeneity among studies, and the Egger test, Begg test, and the trim and fill method were used to assess potential publication bias. RESULTS: Sixteen observational studies were included in our analysis. Meta-analysis suggested that the serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and total triglyceride levels were significantly increased in patients with subclinical hypothyroidism compared with euthyroidism individuals; the WMD were 12.17 mg/dl, 7.01 mg/dl, and 13.19 mg/dl, respectively (P<0.001 for all). No significant difference was observed for serum high-density lipoprotein cholesterol (HDL-C). Match strategy was the main source of heterogeneity among studies in TC and LDL-C analysis. Potential publication bias was found in TC and LDL-C analysis by the Egger test or Begg test and was not confirmed by the trim and fill method. CONCLUSIONS: Subclinical hypothyroidism may correlate with altered lipid profile. Previous studies had limitations in the control of potential confounding factors and further studies should consider those factors.

[Synergistic effects of low temperature in winter and ebb tide at night on Sonneratia apetala seedlings growth and key eco-physiological traits].

By setting up a set of simulated tidal systems with different air- and water temperature and tidal flood conditions, this paper studied the synergistic effects of low temperature in winter and ebb tide at night on the growth and key eco-physiological traits of Sonneratia apetala seedlings. Low air temperature depressed the seedlings growth, but the reduction in the seedling height and basal stem diameter was compensated 41.2% and 44.6%, respectively by a 5 degrees C increase of water temperature. Low air temperature (15 degrees C) reduced the leaf Fv/Fm significantly, indicating a dramatic reduction in the leaf photosynthetic capacity, whereas the flooded tide with higher water temperature could not compensate this damage. The flooded tide with high air temperature increased the proline and soluble sugar contents in mature leaves, which could protect the mature leaves from cold damage. When extreme cold events occurred, the flooded tide at night worked as a heat storage medium, which alleviated the cold damage on the seedlings growth and leaf physiological traits, and promoted the survival rate of S. apetala seedlings.