Changes in posterior corneal elevation after small incision lenticule extraction for different myopic diopters.

AIM: To study the changes and effect factors of posterior corneal surface after small incision lenticule extraction (SMILE) with different myopic diopters. METHODS: Ninety eyes of 90 patients who underwent SMILE were included in this retrospective study. Patients were allocated into three groups based on the preoperative spherical equivalent (SE): low myopia (SE≥-3.00 D), moderate myopia (-3.00 D>SE>-6.00 D) and high myopia (SE≤-6.00 D). Posterior corneal surfaces were measured by a Scheimpflug camera preoperatively and different postoperative times (1wk, 1, 3, 6mo, and 1y). Posterior mean elevation (PME) at 25 predetermined points of 3 concentric circles (2-, 4-, and 6-mm diameter) above the best fit sphere was analyzed. RESULTS: All surgeries were completed uneventfully and no ectasia was found through the observation. The difference of myopia group was significant at the 2-mm ring at 1 and 3mo postoperatively (1mo: P=0.017; 3mo: P=0.018). The effect of time on ΔPME was statistically significant (2-mm ring: P=0.001; 4-mm ring: P<0.001; 6-mm ring: P<0.001). The effect of different corneal locations on ΔPME was significant except 1wk postoperatively (1mo: P=0.000; 3mo: P=0.000; 6mo: P=0.001; 1y: P=0.001). Posterior corneal stability was linearly correlated with SE, central corneal thickness, ablation depth, residual bed thickness, percent ablation depth and percent stromal bed thickness. CONCLUSION: The posterior corneal surface changes dynamically after SMILE. No protrusion is observed on the posterior corneal surface in patients with different degrees of myopia within one year after surgery. SMILE has good stability, accuracy, safety and predictability.

Insulin resistance is associated with the presence and severity of retinopathy in patients with type 2 diabetes.

BACKGROUND: To assess the relationship between novel insulin resistance (IR) indices and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: This is a cross-sectional study involving 2211 patients. The study outcomes were DR events. The study exposures were IR indices including estimated glucose disposal rate (eGDR), natural logarithm of glucose disposal rate (lnGDR), metabolic insulin resistance score (METS-IR), triglyceride glucose index-body mass index (TyG-BMI), triglyceride glucose index-waist-to-hip ratio (TyG-WHR), and triglyceride/high-density lipoprotein cholesterol(TG/HDL-c ratio). We used binary and multivariate ordered logistic regression models to estimate the association between different IR indices and the presence and severity of DR. Subject work characteristic curves were used to assess the predictive power of different IR indices for DR. RESULTS: DR was present in 25.4% of participants. After adjusting for all covariates, per standard deviation (SD) increases in eGDR (ratio [OR] 0.38 [95% CI 0.32-0.44]), lnGDR (0.34 [0.27-0.42]) were negatively associated with the presence of DR. In contrast, per SD increases in METS-IR (1.97 [1.70-2.28]), TyG-BMI (1.94 [1.68-2.25]), TyG-WHR (2.34 [2.01-2.72]) and TG/HDL-c ratio (1.21 [1.08-1.36]) were positively associated with the presence of DR. eGDR was strongly associated with severity of DR. Of all variables, eGDR had the strongest diagnostic value for DR (AUC = 0.757). CONCLUSIONS: Of the six IR indices, eGDR was significantly associated with the presence and severity of DR in patients with type 2 diabetes. eGDR has a good predictive value for DR. Thus, eGDR maybe a stronger marker of DR.

The halogen substitution strategy of inorganic skeletons triggers dielectric and band gap regulation of hybrid perovskites.

Organic-inorganic hybrid perovskites (OIHPs) with dielectric switching functions have aroused comprehensive scientific interest, benefitting from their promising applications in sensors and information storage. However, to date, most of these materials discovered thus far possess a single function and are limited in their applicability, failing to meet the requirements of diverse applications. Moreover, the discovery of these materials has been largely serendipitous. Building multifunctional OIHPs with dielectric switching and semiconductors remains a daunting task. In this context, by introducing [C7H16N]+ as cations and in combination with lead halide with semiconducting properties, two OIHPs [C7H16N]PbI3 (1) and [C7H16N]PbBr3 (2) ([C7H16N]+ = (cyclopropylmethyl) trimethylammonium) have been successfully designed. They have dielectric switching properties close to 253 and 279 K and semiconducting behavior with band gaps of 2.67 and 3.22 eV. The phase transition temperature increased by 26 K through halogen substitution. In summary, our findings in this study provide insights into the application of the halogen substitution regulation strategy and open up new possibilities for designing perovskite semiconductors with dielectric switching functionality.

Impaired Sensitivity to Thyroid Hormones is Associated with Mild Cognitive Impairment in Euthyroid Patients with Type 2 Diabetes.

Purpose: The prevalence of mild cognitive impairment (MCI) in patients with type 2 diabetes (T2D) is rapidly increasing. Thyroid hormones are key regulators of cognitive function in adults. The purpose of this study was to investigate the relationship between thyroid hormone sensitivity and MCI in euthyroid T2D patients. Patients and Methods: A total of 400 euthyroid T2D patients were enrolled in this cross-sectional study, including 218 patients with normal cognition and 182 MCI patients. The Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function. The free triiodothyronine to free thyroxine (FT3/FT4) ratio was calculated as a measure of peripheral sensitivity to thyroid hormones; the thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI) and thyroid feedback quantile-based index (TFQI) were calculated as measures of central sensitivity to thyroid hormones. Linear regression analysis and logistic regression analysis were performed to explore the relationships between these indices of thyroid hormone sensitivity and the MoCA score and MCI, respectively. Results: Compared with the normal cognitive function group, patients in the MCI group had higher TSHI, TT4RI and TFQI but a lower FT3/FT4 ratio (P<0.05). The MoCA score was positively correlated with the FT3/FT4 ratio but negatively correlated with TSHI, TT4RI and TFQI (P< 0.05). Multivariate logistic regression analysis showed that a low FT3/FT4 ratio and high TSHI, TT4RI and TFQI were independently associated with MCI (P<0.05). After adjustment for confounding factors, the odds ratio (OR) for the association between MCI and the highest tertile of the FT3/FT4 was 0.455 (95% CI: 0.264-0.785), for the highest tertile of TSHI, the OR was 2.380 (95% CI: 1.376-4.119), for the highest tertile of TT4RI, the OR was 2.342 (95% CI:1.353-4.054), and for the highest tertile of TFQI, the OR was 2.536 (95% CI: 1.466-4.387) (P< 0.05). Conclusion: Impaired sensitivity to thyroid hormones is associated with MCI in euthyroid T2D patients.

Relationship Between Index of Cardiac Electrophysiological Balance, Frontal QRS-T Angle and Retinopathy in People with Type 2 Diabetes.

Background: Diabetic retinopathy (DR) is strongly associated with cardiovascular disease, which is a risk factor for sudden cardiac death (SCD). The index of cardiac electrophysiological balance (iCEB) and the frontal QRS-T angle are recommended to predict the risk of ventricular arrhythmias more than other ECG parameters. However, the relationships between these two markers and DR have not yet been explored. The aim of this study was to investigate the variation in the iCEB, corrected iCEB (iCEBc) and frontal QRS-T angle in different stages of DR and determine whether there are associations between these markers and DR. Methods: The sample comprised 665 patients with Type 2 diabetes mellitus (T2DM) who were classified into three groups: no DR (NDR), mild to moderate non-proliferative DR (NPDR), and vision-threatening DR (VTDR). Twelve-lead ECG was performed and the QT, QTc, QRS duration, iCEB, iCEBc and frontal QRS-T angle were recorded and compared across the groups. Results: The VTDR group had a significantly higher iCEBc and frontal QRS-T angle than the NDR and NPDR groups. After controlling for confounding variables, the correlations between the iCEBc (OR=2.217, 95% CI=1.464-3.358, P<0.001), frontal QRS-T angle (OR=1.017, 95% CI=1.008-1.025, P<0.001) and DR risk remained (P<0.05). Subjects in the fourth iCEBc quartile (adjusted OR=2.612, 95% CI=1.411-4.834, p=0.002) had a much higher chance of developing DR compared to those in the first quartile. In comparison to the first frontal QRS-T angle quartile, subjects in the third (adjusted OR=1.998, 95% CI=1.167-3.422, P=0.012) and fourth (adjusted OR=2.430, 95% CI=1.420-4.160, P=0.001) frontal QRS-T angle quartiles had significantly greater risks of DR. Conclusion: With the progression of DR, the iCEBc and frontal QRS-T angle increase. An increased iCEBc and frontal QRS-T angle are associated with an increased risk of DR.

Is approaching sedentary behaviour or physical activity a reward? An EEG study.

OBJECTIVE: To understand why individuals (do not) exercise, our study examined differences in approach and avoidance tendencies towards physical activity and sedentary behaviours among runners and non-runners, especially at the neural level. METHODS: Using electroencephalography (EEG), 31 participants completed an approach-avoidance task. RESULTS: We found that at the behavioural level, non-runners were faster to approach sedentary behaviour relative to runners. However, at the neural level, they both had a tendency to avoid physical activity. Specifically, avoiding physical activity had less conflict monitoring (smaller N1), required more cognitive processes (larger P3), and was more neurologically efficient (higher alpha coherence). CONCLUSIONS: These results supported the theory of effort minimization in physical activity (TEMPA), with both runners and non-runners regarding sedentary behaviour as a reward. DATA AVAILABILITY STATEMENT: The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Thymosin α-1 Reverses M2 Polarization of Tumor-Associated Macrophages during Efferocytosis.

The immunologic effects of chemotherapy-induced tumor cell death are not completely understood. Accumulating evidence suggests that phagocytic clearance of apoptotic tumor cells, also known as efferocytosis, is an immunologically silent process, thus maintaining an immunosuppressive tumor microenvironment (TME). Here we report that, in the breast tumor microenvironment, thymosin α-1 (Tα-1) significantly reverses M2 polarization of IL10-producing tumor-associated macrophages (TAM) during efferocytosis induced by apoptotic cells. Mechanistically, Tα-1, which bound to phosphatidylserine on the surface of apoptotic tumor cells and was internalized by macrophages, triggered the activation of SH2-containing inositol 5'-phosphatase 1 (SHIP1) through the lysosomal Toll-like receptor 7 (TLR7)/MyD88 pathway, subsequently resulting in dephosphorylation of efferocytosis-activated TBK1 and reduction of efferocytosis-induced IL10. Tα-1 combined with epirubicin chemotherapy markedly suppressed tumor growth in an in vivo breast cancer model by reducing macrophage-derived IL10 and enhancing the number and function of tumor-infiltrating CD4+ and CD8+ T cells. In conclusion, Tα-1 improved the curative effect of chemotherapy by reversing M2 polarization of efferocytosis-activated macrophages, suggesting that Tα-1 injection immediately after chemotherapy may contribute to highly synergistic antitumor effects in patients with breast cancer. SIGNIFICANCE: Thymosin α-1 improves the curative effect of chemotherapy by reversing efferocytosis-induced M2 polarization of macrophages via activation of a TLR7/SHIP1 axis.

A Novel PIFA/KOH Promoted Approach to Synthesize C2-arylacylated Benzothiazoles as Potential Drug Scaffolds.

To discover an efficient and convenient method to synthesize C2-arylacylated benzothiazoles as potential drug scaffolds, a novel [bis(trifluoroacetoxy)iodo]benzene(PIFA)/KOH synergistically promoted direct ring-opening C2-arylacylation reaction of 2H-benzothiazoles with aryl methyl ketones has been developed. Various substrates were tolerated under optimized conditions affording the C2-arylacylation products in 70-95% yields for 38 examples. A plausible mechanism was also proposed based on a series of controlled experiments.

Increased cGAS/STING signaling components in patients with Mooren's ulcer.

AIM: To explore the expression of cGAS/STING signaling components in Mooren's ulcer (MU). METHODS: Samples were obtained from ten MU patients, and eight residual corneal-scleral rings of healthy donor corneas for controls. Human corneal epithelial cells (HCECs) were used to evaluate the effect of cGAS/STING signaling pathway. Immunohistochemistry (IHC) and Western blot were used to examine the expression of cGAS, STING, and phosphorylated interferon regulatory factor 3 (p-IRF3) in MU tissues. The expression of interferon-ß (IFN-ß) and interferon-stimulated genes (ISGs) was quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The protein levels of cGAS and STING in MU samples were significantly elevated when compared with the healthy controls by Western blot and IHC. After stimulation with cGAMP, real-time PCR and ELISA showed a dramatic increase of IFN-ß and ISGs (containing CXCL10, IFIT1, and IL-6) in HCECs. Moreover, HCECs treated with cGAMP was characterized by increased phosphorylation and more nuclear translocation of IRF3. Meanwhile, increased p-IRF3 was observed in MU samples via IHC and Western blot. CONCLUSION: The pronounced expression of cGAS/STING signaling components in the patients with MU and probably contribute to the onset and development of MU.

CK-3, A Novel Methsulfonyl Pyridine Derivative, Suppresses Hepatocellular Carcinoma Proliferation and Invasion by Blocking the PI3K/AKT/mTOR and MAPK/ERK Pathways.

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis that highly expresses phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (ERK). The PI3K/AKT/mTOR and MAPK/ERK signaling pathways play a crucial role in HCC tumor formation, cell cycle, apoptosis and survival. However, no effective targeted therapies against these pathways is available, mainly due to the extensive and complex negative feedback loops between them. Here we used CK-3, a dual blocker of the PI3K/AKT/mTOR and MAPK/ERK pathways, against HCC cell lines to verify its anti-tumor activity in vitro. CK-3 exhibited cytotoxic activity against HCC, as demonstrated with MTT and colony formation assays. The anti-metastatic potential of CK-3 was demonstrated with wound healing and cell invasion assays. The ability of CK-3 to block both the PI3K/AKT/mTOR and MAPK/ERK pathways was also confirmed. CK-3 induced the apoptosis of Hep3B cells, while Bel7402 cells died via mitotic catastrophe (MC). Oral administration of CK-3 also inhibited the subcutaneous growth of BEL7402 cells in nude mice. Simultaneous PI3K/AKT/mTOR and MAPK/ERK pathway inhibition with CK-3 may be superior to single pathway monotherapies by inhibiting their feedback-regulation, and represents a potential treatment for HCC.

Identification and Functional Prediction of Long Non-Coding RNAs in Dilated Cardiomyopathy by Bioinformatics Analysis.

Dilated cardiomyopathy (DCM) is a relatively common cause of heart failure and the leading cause of heart transplantation. Aberrant changes in long non-coding RNAs (lncRNAs) are involved in DCM disorder; however, the detailed mechanisms underlying DCM initiation and progression require further investigation, and new molecular targets are needed. Here, we obtained lncRNA-expression profiles associated with DCM and non-failing hearts through microarray probe-sequence re-annotation. Weighted gene co-expression network analysis revealed a module highly associated with DCM status. Then eight hub lncRNAs in this module (FGD5-AS1, AC009113.1, WDFY3-AS2, NIFK-AS1, ZNF571-AS1, MIR100HG, AC079089.1, and EIF3J-AS1) were identified. All hub lncRNAs except ZNF571-AS1 were predicted as localizing to the cytoplasm. As a possible mechanism of DCM pathogenesis, we predicted that these hub lncRNAs might exert functions by acting as competing endogenous RNAs (ceRNAs). Furthermore, we found that the above results can be essentially reproduced in an independent external dataset. We observed the localization of hub lncRNAs by RNA-FISH in human aortic smooth muscle cells and confirmed the upregulation of the hub lncRNAs in DCM patients through quantitative RT-PCR. In conclusion, these findings identified eight candidate lncRNAs associated with DCM disease and revealed their potential involvement in DCM partly through ceRNA crosstalk. Our results facilitate the discovery of therapeutic targets and enhance the understanding of DCM pathogenesis.

Indications for penetrating keratoplasty and anterior lamellar keratoplasty during 2010-2017.

AIM: To review the indications of penetrating keratoplasty (PK) and anterior lamellar keratoplasty (ALK) at Qingdao Eye Hospital, Shandong Eye Institute, Qingdao, China, from 2010 to 2017. METHODS: The data of all patients undergoing PK or ALK from January 2010 to December 2017 was retrospectively reviewed, with the indications during 2010-2013 and 2014-2017 compared. RESULTS: A total of 1869 eyes were included, among which 1405 eyes (75.2%) had PK and 464 eyes (24.8%) had ALK. The leading indications were suppurative keratitis (36.8%), keratoconus (15.5%), herpes keratitis (13.1%), and regraft (10.5%). In eyes undergoing PK, the top four indications were suppurative keratitis (38.7%), herpes keratitis (15.3%), keratoconus (12.6%), and regraft (12.5%) during 2014-2017, with the proportion of suppurative keratitis and herpes keratitis decreased while regraft and keratoconus increased compared with 2010-2013. In eyes with ALK, suppurative keratitis (30.8%), keratoconus (24.1%), corneal dystrophies and degenerations (10.6%), and corneal dermoid tumor (9.7%) were the top four indications, and there was no significant difference for the proportion of each indication between 2010-2013 and 2014-2017. CONCLUSION: Suppurative keratitis is the most common indication for PK and ALK at Qingdao Eye Hospital during 2010-2017, followed by keratoconus, herpes keratitis, and regraft. In eyes treated with PK, the proportion of suppurative keratitis and herpes keratitis decrease while regraft and keratoconus increase during 2014-2017 compared with 2010-2013.

Novel ADAM-17 inhibitor ZLDI-8 inhibits the proliferation and metastasis of chemo-resistant non-small-cell lung cancer by reversing Notch and epithelial mesenchymal transition in vitro and in vivo.

Acquired drug-resistant non-small cell lung cancer (NSCLC) has strong proliferation ability and is prone to epithelial-mesenchymal transition (EMT) and subsequent metastasis. Notch pathway mediates cell survival and EMT and is involved in the induction of multidrug resistance (MDR). ZLDI-8 is an inhibitor of Notch activating/cleaving enzyme ADAM-17 we found before. However, the effects of ZLDI-8 on resistant NSCLC was unclear. Here, we demonstrated for the first time that ZLDI-8 could induce apoptosis in lung cancer, especially in chemotherapy-resistant non-small cell lung cancer cells, and also inhibit migration, invasion and EMT phenotype of drug-resistant lung cancer. ZLDI-8 inhibits the Notch signaling pathway, thereby regulating the expression of survival/apoptosis and EMT-related proteins. Moreover, ZLDI-8 suppresses multidrug-resistant lung cancer xenograft growth in vivo and blocks metastasis in a tail vein injection mice model. Therefore, ZLDI-8 is expected to be an effective agent in the treatment of drug-resistant lung cancer.

Unexplained infertility patients have increased serum IL-2, IL-4, IL-6, IL-8, IL-21, TNFα, IFNγ and increased Tfh/CD4 T cell ratio: increased Tfh and IL-21 strongly correlate with presence of autoantibodies.

Infertility is a disease of the reproductive system that affects millions of people globally. Reproductive failure is a major medical issue adversely affecting human health in the 21st century. Many factors contribute to infertility, including immune conditions which may lead to immune infertility (immunologic infertility). It is known that specific T helper cells (Th) and their cytokines are involved in the stages of infertility. The aim of this study is to provide a new diagnostic approach to immunologic infertility by investigating the correlation of follicular helper T cells (Tfh) and their secreted cytokines with the autoantibodies in peripheral blood samples from immunologically infertile patients. Thirty (30) patients suffering from immune infertility and 20 control subjects were selected as the sample base for this study. The levels of Tfh, 20 cytokines and 4 antibodies were evaluated for this investigation and evaluated using flow cytometry, antibody chip and ELISA technologies. It was found that, in immunologically infertile patients, Tfh cell numbers were significantly higher than those in the control group. Likewise, seven (7) serum cytokines were expressed to a greater degree in infertile patients compared to the control group. Finally, four (4) antibodies were found to be higher in immunologically infertile patients. The results show that, among patients with immunologic infertility, the levels of Tfh cells and IL-21 were increased significantly in peripheral blood samples and correlate positively with the autoantibodies. IL-12 was positively correlated with the two antibodies, while TNFα was negatively correlated with two additional antibodies. The detection and quantification of Tfh cells, IL-21, IL-12 and TNFα may provide new diagnostic indicators to screen for immunologic infertility.