Synergistic Effect of Human Papillomavirus and Environmental Factors on Skin Squamous Cell Carcinoma, Basal Cell Carcinoma, and Melanoma: Insights from a Taiwanese Cohort.

Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96-7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70-5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14-5.74), and melanoma (aHR = 4.36, 95% CI: 2.76-6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health.

The lower incidence of endometrial cancer after sodium-glucose cotransporter 2 inhibitors administration in type 2 diabetes mellitus population: a nationwide cohort study.

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population.

Impact of CD44 genetic variants on clinicopathological characteristics of uterine cervical cancer patients.

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.

Evaluating the Efficacy and Safety of Aspirin for Primary Cardiovascular Prevention in Asian Patients with Type 2 Diabetes: A Population-Based and Propensity Score-Matched Study.

The risk of developing cardiovascular disease is significantly higher for individuals with diabetes compared to those without. Aspirin has been widely used for primary prevention in diabetic patients. However, evidence is limited in the Asian population. We aimed to compare the effectiveness and safety of aspirin versus placebo for primary cardiovascular prevention in the Asian population with type 2 diabetes. In this study, we performed propensity score matching with non-aspirin users from January 2006 to December 2015 (n = 37,095 in each group after matching, PSM). We analyzed the incidence risk of all-cause mortality, composite cardiovascular events, and hospitalized major bleeding. The propensity score-matched (PSM) cohort of patients who received aspirin within one year of diabetes diagnosis was compared with the non-aspirin diabetic (DM) cohort. Baseline characteristics were balanced between the two groups. The median follow-up duration was 78 months. Aspirin users exhibited a slightly but significantly lower rate of all-cause mortality (HR: 0.92; 95% CI: 0.87 to 0.96). However, they also had a significantly higher composite cardiovascular risk (HR: 1.34; 95% CI: 1.28-1.40), including non-fatal acute myocardial infarction (HR: 1.33; 95% CI: 1.18 to 1.50), non-fatal ischemic stroke (HR: 1.38; 95% CI: 1.30 to 1.45), heart failure (HR: 1.18; 95% CI: 1.09 to 1.27), and coronary revascularization (HR: 1.94; 95% CI: 1.73 to 2.17). Aspirin users also faced a significantly higher risk of hospitalized major bleeding (HR: 1.08; 95% CI: 1.03 to 1.14). The presence of one or more additional risk factors did not influence the effectiveness and safety outcomes of aspirin, according to stratified analysis. In conclusion, in this real-world Asian diabetic population, aspirin was associated with a significantly lower mortality risk but also with higher risks of cardiovascular events and hospitalized bleeding. Aspirin may not play a role in the primary prevention of cardiovascular disease in such patients, regardless of additional risk factors.

Topographic and Surgical Risk Factors for Early Myopic Regression between Small Incision Lenticule Extraction and Laser In Situ Keratomileusis.

Our objective was to evaluate the topographic and surgical factors of early myopic regression between laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). A retrospective case-control study was conducted, and 368 and 92 eyes were enrolled in the LASIK and SMILE groups via propensity score matching (PSM). Visual acuity, refractive status, axial length, and topographic/surgical parameters were collected. Multiple linear regression was applied to the yield coefficient and the 95% confidence interval (CI) of the parameters. The cumulative incidence of early myopic regression was higher in the LASIK group (p < 0.001). In the SMILE group, a lower central corneal thickness (CCT) thinnest value and a higher corneal cylinder associated with early myopic regression were observed; meanwhile, in the LASIK group, a lower CCT thinnest value, a higher steep corneal curvature, a larger optic zone, and a lower flap thickness related to early myopic regression were observed (all p < 0.05). In the SMILE group, a higher CCT difference correlated with early myopic regression was observed compared to the LASIK group (p = 0.030), and higher steep corneal curvature and lower cap/flap thickness (both p < 0.05) correlated with early myopic regression were observed in the LASIK group compared to the SMILE group. In conclusion, CCT differences significantly influence early myopic regression in the SMILE group; meanwhile, corneal curvature and flap thickness affect early myopic regression principally in the LASIK group.

The use of sodium-glucose cotransporter 2 inhibitors and the incidence of uveitis in type 2 diabetes: a population-based cohort study.

Introduction: To survey the potential correlation between the application of sodium-glucose cotransporter 2 (SGLT2) inhibitors and the incidence of uveitis in individuals with type 2 diabetes mellitus (T2DM). Material and methods: A retrospective cohort study using the National Health Insurance Research Database (NHIRD) was conducted. The T2DM patients using SGLT2 inhibitors and those taking other anti-diabetic medications were assigned to the SGLT2 group and the control group, respectively, with a 1 : 2 ratio via the propensity score-matching (PSM) method. The major outcome in this study is the development of uveitis according to the diagnostic codes. The Cox proportional hazard regression was adopted to yield the adjusted hazard ratio (aHR) with 95% confidence interval (CI) between the groups. Results: There were 147 and 371 new uveitis episodes in the SGLT2 and control groups after the follow-up period up to 5 years. The incidence of uveitis in the SGLT2 group (aHR = 0.736, 95% CI: 0.602-0.899, p = 0.0007) was significantly lower than that in the control group after adjusting for the effect of all the confounders. In the subgroup analyses, the SGLT2 inhibitors showed a higher correlation with low uveitis incidence in T2DM patients aged under 50 than T2DM individuals aged over 50 years (p = 0.0012), while the effect of SGLT2 inhibitors on the incidence of anterior and posterior uveitis development was similar (p = 0.7993). Conclusions: The use of SGLT2 inhibitors could be an independent protective factor for uveitis development in T2DM population.

Deoxyshikonin triggers apoptosis in cervical cancer cells through p38 MAPK-mediated caspase activation.

Deoxyshikonin (DSK) is a biological component derived from Lithospermum erythrorhizon. Although DSK possesses potential anticancer activities, whether DSK exerts anticancer effects on cervical cancer cells is incompletely explored. This study was aimed to investigate the anticancer activity of DSK against cervical cancer cells and its molecular mechanisms. Cell viability was evaluated by MTT assay. Level of phosphorylation and protein was determined using Western blot. Involvement of signaling kinases was assessed by specific inhibitors. Our results revealed that DSK reduced viability of human cervical cell in a dose-dependent fashion. Meanwhile, DSK significantly elicited apoptosis of HeLa and SiHa cells. Apoptosis microarray was used to elucidate the involved pathways, and the results showed that DSK dose-dependently diminished cellular inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and XIAP, and induced cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-8/9/3. Furthermore, we observed that DSK significantly triggered activation of ERK, JNK, and p38 MAPK (p38), and only inhibition of p38 diminished the DSK-mediated pro-caspases cleavage. Taken together, our results demonstrate that DSK has anti-cervical cancer effects via the apoptotic cascade elicited by downregulation of IAPs and p38-mediated caspase activation. This suggests that DSK could act as an adjuvant to facilitate cervical cancer management.

The Genetic Variants of Long Noncoding RNA MEG3 and Its Association to the Clinical Features of Diabetic Retinopathy.

PURPOSE: This study aimed to investigate the potential correlation between the single-nucleotide polymorphism (SNP) of maternally expressed gene 3 (MEG3) and the clinical manifestations of diabetic retinopathy (DR). METHODS: Five loci of MEG3 SNPs including rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G) and rs11160608 (A/C) were genotyped by TaqMan allelic discrimination in 457 non-DR patients and 280 DR individuals. RESULTS: The distribution frequency of MEG3 SNP rs7158663 GA (AOR: 0.683, 95% CI: 0.478-0.975, p = 0.036) and MEG3 SNP rs7158663 GA + AA (AOR: 0.686, 95% CI: 0.487-0.968, p = 0.032) were significantly lower in the DR group. And the MEG3 SNP rs7158663 GA + AA (AOR: 0.610, 95% CI: 0.377-0.985, p = 0.043) demonstrated a significantly lower distribution frequency in the male DR group. Besides, the DR patients with MEG3 SNP rs7158663 GA + AA genotype showed a significantly lower HbA1c level than the DR patients with MEG3 SNP rs7158663 GG genotype (7.29 ± 1.23 versus 7.74 ± 1.49, p = 0.013). Moreover, in the analysis using data from gene expression data series database, a higher MEG3 level was significantly correlated to a lower miR-182 level in the database (p = 0.0114). CONCLUSIONS: In this study, the distribution frequency of MEG3 SNP rs7158663 GA + AA genotype was lower in DR, while the DR would develop under lower HbA1c level in DM patients with this MEG3 SNP variant.

Corneal Endothelial Morphology and Ocular Biometric Indexes in Premature Children With and Without Retinopathy of Prematurity.

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP). Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups. Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis. Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.

Comparison of myopic control between orthokeratology contact lenses and defocus incorporated multiple segments spectacle lenses.

Purpose: The purpose of this study was to compare the differences in myopic control effects between orthokeratology (OK) contact lenses and defocus incorporated multiple segments (DIMS) spectacle lenses. Methods: A retrospective cohort study was conducted that included patients who had received OK lens, DIMS spectacle lens or single-vision spectacle treatments. A total of 54 eyes from 27 individuals, 38 eyes from 19 individuals and 42 eyes from 21 individuals were enrolled into the OK lens, DIMS and control groups, respectively. The primary outcomes were the changes in the spherical equivalent refraction (SER) and axial length (AXL) among the groups. A repeated-measure ANCOVA was adopted to calculate the SER progression and AXL elongation of the OK lens group compared with the DIMS group. Results: The difference in the SER progression was clinically non-significant in the OK lens group compared with the DIMS and control groups (P = 0.001). The total AXL elongation results were similar between the OK lens and DIMS groups, but these were lower than in the control group (P = 0.005). The repeated-measure ANCOVA revealed that the SER progression difference during the study interval was clinically non-significant in the OK lens group when compared with the DIMS group (P = 0.028). The AXL elongation results between the OK lens and DIMS populations did not illustrate a significant difference (P = 0.607). In a subgroup analysis of moderate astigmatism, better AXL control was observed in the DIMS subgroup compared with the OK lens subgroup (P = 0.016). Conclusions: The OK lens demonstrated a clinically non-significant effect on the SER and AXL controls compared with the DIMS spectacle lens.

Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model.

Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-ß), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.

Association between gabapentin use and risk of dementia in adults with chronic pain: A nested case-control study.

STUDY OBJECTIVE: To explore the association between gabapentin use and the risk of dementia in patients with chronic pain, considering the rising concerns of dementia in an aging population and the potential cognitive impacts of chronic pain management. DESIGN: A nested case-control study utilizing data from a longitudinal health insurance database. SETTING: The study is based on a longitudinal health insurance database spanning 2000-2019 in Taiwan. PATIENTS: A total of 201,492 patients aged 50 years and older diagnosed with chronic pain between 2001 and 2017 were included. The study focused on individuals with chronic pain, excluding those diagnosed with dementia a year before or after their chronic pain diagnosis. INTERVENTION: Analysis of gabapentin prescription history was conducted, considering the cumulative dose from the chronic pain diagnosis date to the dementia diagnosis date or equivalent period for controls. MEASUREMENT: Data included demographics, gabapentin prescription history, and comorbidities. Logistic regression was used to estimate odds ratios for dementia risk. MAIN RESULTS: No significant difference in the risk of dementia was found between low and high cumulative doses of gabapentin. The adjusted odds ratio for dementia risk associated with gabapentin use was 0.91 (95 % C.I. 0.83-1.01), indicating no substantial increase in risk. CONCLUSION: Long-term Gabapentin therapy for chronic pain is not associated with a differential risk of dementia across dosage levels, irrespective of age or gender. Further study into its potential cognitive impacts is essential.

A Cost-Effective Model for Predicting Recurrent Gastric Cancer Using Clinical Features.

This study used artificial intelligence techniques to identify clinical cancer biomarkers for recurrent gastric cancer survivors. From a hospital-based cancer registry database in Taiwan, the datasets of the incidence of recurrence and clinical risk features were included in 2476 gastric cancer survivors. We benchmarked Random Forest using MLP, C4.5, AdaBoost, and Bagging algorithms on metrics and leveraged the synthetic minority oversampling technique (SMOTE) for imbalanced dataset issues, cost-sensitive learning for risk assessment, and SHapley Additive exPlanations (SHAPs) for feature importance analysis in this study. Our proposed Random Forest outperformed the other models with an accuracy of 87.9%, a recall rate of 90.5%, an accuracy rate of 86%, and an F1 of 88.2% on the recurrent category by a 10-fold cross-validation in a balanced dataset. We identified clinical features of recurrent gastric cancer, which are the top five features, stage, number of regional lymph node involvement, Helicobacter pylori, BMI (body mass index), and gender; these features significantly affect the prediction model's output and are worth paying attention to in the following causal effect analysis. Using an artificial intelligence model, the risk factors for recurrent gastric cancer could be identified and cost-effectively ranked according to their feature importance. In addition, they should be crucial clinical features to provide physicians with the knowledge to screen high-risk patients in gastric cancer survivors as well.

The Association between Ovarian Cancer and the Incidence of Newly Developed Dry Eye Disease: A Nationwide Population-Based Study.

We aim to investigate the potential correlation between the presence of ovarian cancer and the development of dry eye disease (DED) via the usage of the Longitudinal Health Insurance Database (LHID) of Taiwan. A retrospective cohort study was executed, and patients with ovarian cancer were selected according to the diagnostic and procedure codes. One ovarian cancer patient was matched to four non-ovarian cancer participants which served as control group, and a total of 4992 and 19,968 patients constructed the ovarian cancer and control groups, respectively. The primary outcome in the current study is the development of DED according to the diagnostic and procedure codes. Cox proportional hazard regression was utilized to produce the adjusted hazard ratio (aHR) and related 95% confidence interval (CI) of DED between the two groups. There were 542 and 2502 DED events observed in the ovarian cancer group and the control group, respectively. The ovarian cancer group illustrated a significantly higher incidence of DED development than the control group after the adjustment of several confounders (aHR: 1.10, 95% CI: 1.01-1.21, p = 0.040). In the subgroup analysis stratified by age, ovarian cancer patients aged older than 60 years showed a higher incidence of DED compared to the non-ovarian cancer population (aHR: 1.19, 95% CI: 1.08-1.28, p = 0.011). In addition, ovarian cancer patients with a disease duration longer than five years also showed higher incidence of DED formation than the non-ovarian cancer population (aHR: 1.13, 95% CI: 1.04-1.22, p = 0.027). In conclusion, the presence of ovarian cancer is associated with higher incidence of subsequent DED, especially in those older than 60 years and with a disease interval of more than five years.

Correlation Between Low Cytoplasmic Expression of XBP1 and the Likelihood of Surviving Hepatocellular Carcinoma.

BACKGROUND/AIM: Our objectives in this study were to (i) evaluate the clinical significance of X-box-binding protein 1 (XBP1) expression in cases of hepatocellular carcinoma (HCC) and (ii) assess the potential of XBP1 to be used as a prognostic biomarker. PATIENTS AND METHODS: The expression of XBP1 protein in 267 HCC tissue specimens was measured using immunohistochemistry in order to characterize the associations among XBP1 expression, clinicopathological factors and survival outcomes. Survival analysis using follow-up data was used to assess the prognostic value of XBP1 in cases of HCC. Immunohistochemistry revealed a significant decrease in cytoplasmic XBP1 protein expression in HCC tumor tissue. RESULTS: Immunoreactivity results showed that low cytoplasmic XBP1 expression was significantly associated with vascular invasion, as well as poor 5-year overall survival and long-term disease-specific (DSS) and disease-free (DFS) survival rates. Kaplan-Meier survival curves further confirmed a significant association between low cytoplasmic XBP1 protein expression and poor DSS and DFS. Univariate and multivariate analyses revealed that XBP1 expression, tumor differentiation, vascular invasion, tumor stage, and the rate of recurrence were linked to DSS, while low cytoplasmic XBP1 expression remained an independent predictor of poor DSS. Our analysis also revealed that XBP1 expression, tumor differentiation, vascular invasion, and T classification were linked to DFS, while low cytoplasmic XBP1 expression remained an independent predictor of poor DFS. CONCLUSION: Low cytoplasmic XBP1 protein expression may play an important role in the pathogenesis of HCC, which suggests that XBP1 could potentially be targeted to benefit therapeutic strategies for HCC.

The association between endometrial cancer and subsequent diabetic retinopathy severity: A retrospective nationwide study.

OBJECTIVE: The endometrial cancer is a disorder with elevated oxidative stress. The high oxidative stress resulting from hyperglycemia can lead to diabetic retinopathy (DR) development which is a complication of type 2 diabetes mellitus. Accordingly, we aim to evaluate the potential relationship between the endometrial cancer and following DR development. METHODS: A retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. Individuals diagnosed with endometrial cancer were matched to the non-endometrial cancer patients in a 1:4 ratio. The major outcomes are the presence of DR, diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) according to diagnostic codes. Cox proportional hazard regression was used to show the adjusted hazard ratio (aHR) with 95% confidence interval (CI) of major outcomes between groups. RESULTS: There were 99 (2.3%), 20 (0.5%), and 14 (0.3%) cases with DR, DME and PDR in the endometrial cancer group, respectively. Another 303 (1.8%), 35 (0.2%), and 27 (0.2%) with DR, DME and PDR were observed in the control group, respectively. The endometrial cancer group revealed a significantly higher incidence of DR compared with the control group (aHR 1.51, 95% CI 1.20-1.90, P < 0.001). The cumulative probability of DR was also higher in the endometrial cancer group than in the control group (P < 0.001). The relationship between endometrial cancer and DR was significantly higher in patients aged over 70 years (P = 0.008). In addition, a higher incidence of DR was found during the first 5 years after the endometrial cancer diagnosis (P < 0.001). CONCLUSIONS: The endometrial cancer correlates to a higher incidence of subsequent DR, especially within first 5 years of endometrial cancer diagnosis.

Refraction and topographic risk factors for early myopic regression after small-incision lenticule extraction surgery.

We sought to evaluate the topographic risk factors for early myopic regression after small-incision lenticule extraction (SMILE). A retrospective case‒control study was conducted, and individuals who underwent SMILE surgery were enrolled. Among them, 406 and 14 eyes were categorized into the nonregression and regression groups, respectively. The preoperative and postoperative parameters in the two groups were collected, including spherical refraction (SE), axial length (AXL) and topographic data. A generalized linear model was adopted to analyze the difference in each parameter between the two groups. After 6 months, UCVA decreased in the regression group, and SE increased in the regression group (both P < 0.05). The increase in the CCT at the thinnest point (P = 0.044), flat corneal curvature (P = 0.012) and TCRP (P = 0.001) were significantly greater in the regression group. Regarding the risk factors for myopic regression, preoperative SE, preoperative sphere power, preoperative AXL, preoperative flat corneal curvature, preoperative SA, early postoperative SE, early postoperative sphere power, early postoperative AXL and early postoperative CCT difference were significantly greater in the regression group (all P < 0.05). The SE, sphere power, AXL, preoperative flat corneal curvature, preoperative SA, and postoperative CCT difference correlate with early myopic regression after SMILE.

Tricetin suppresses the cell migration and BMP-6 expression through p38 signaling pathways in human retinal pigment epithelium cells.

Proliferative vitreoretinopathy (PVR) is a visual-threatening disease, which cause from the migration of retinal pigment epithelium (RPE). Tricetin, a family of flavonoids, can inhibit the metastasis of several cancers. Herein, we aim to evaluate the possible effect of tricetin on inhibiting ARPE-19 cells migration. The Boyden chamber assay, wound healing assay, RNA sequencing, and Western blot analysis were applied in our experiment. The results revealed that tricetin inhibited the cell migration abilities of ARPE-19 cells. Moreover, using RNA sequencing technology, we revealed that tricetin repressed bone morphogenetic protein-6 (BMP-6) gene expressions in ARPE-19 cells. Overexpression of BMP-6 resulted in significant restoration of cell migration capabilities of tricetin-treated ARPE-19 cells. Furthermore, tricetin suppressed the phosphorylation of the p38 signaling pathway. Moreover, blocking the p38 pathway also inhibits BMP-6 expression and migration in the ARPE-19 cells. In conclusion, this study revealed that tricetin inhibits the ARPE-19 cell migration mainly via the suppression of BMP-6 expression and p38 signaling pathway.

Curcumin Analog L48H37 Induces Apoptosis in Human Oral Cancer Cells by Activating Caspase Cascades and Downregulating the Inhibitor of Apoptosis Proteins through JNK/p38 Signaling.

L48H37 is a synthetic curcumin analog that has anticancer potentials. Here, we further explored the anticancer effect of L48H37 on oral cancer cells and its mechanistic acts. Cell cycle distribution was assessed using flow cytometric analysis. Apoptosis was elucidated by staining with PI/Annexin V and activation of the caspase cascade. Cellular signaling was explored using apoptotic protein profiling, Western blotting, and specific inhibitors. Our findings showed that L48H37 significantly reduced the cell viability of SCC-9 and HSC-3 cells, resulting in sub-G1 phase accumulation and increased apoptotic cells. Apoptotic protein profiling revealed that L48H37 increased cleaved caspase-3, and downregulated cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) in SCC-9 cells, and the downregulated cIAP1 and XIAP in both oral cancer cells were also demonstrated by Western blotting. Meanwhile, L48H37 triggered the activation of caspases and mitogen-activated protein kinases (MAPKs). The involvement of c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) in the L48H37-triggered apoptotic cascade in oral cancer cells was also elucidated by specific inhibitors. Collectively, these findings indicate that L48H37 has potent anticancer activity against oral cancer cells, which may be attributed to JNK/p38-mediated caspase activation and the resulting apoptosis. This suggests a potential benefit for L48H37 for the treatment of oral cancer.

Evaluation of the clinical significance of long non-coding RNA MALAT1 genetic variants in human lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most frequent histological subtype of lung cancer, which is the most common malignant tumor and the main cause of cancer-related mortality globally. Recent reports revealed that long non-coding RNA (lncRNA) of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in tumorigenesis and metastasis development in lung cancer. However, the contribution of MALAT1 genetic variants to the development of LUAD is unclear, especially in epidermal growth factor receptor (EGFR) mutation status. In this study, 272 LADC patients with different EGFR status were recruited to dissect the allelic discrimination of the MALAT1 polymorphisms at rs3200401, rs619586, and rs1194338. The findings of the study showed that MALAT1 polymorphisms rs3200401, rs619586, and rs1194338 were not associated to LUAD susceptibility; however, rs3200401 polymorphisms was significantly correlated to EGFR wild-type status and tumor stages in LUAD patients in dominant model (p=0.016). Further analyses using the datasets from The Cancer Genome Atlas (TCGA) revealed that lower MALAT1 mRNA levels were associated with the advanced stage, and lymph node metastasis in LADC patients. In conclusion, our results showed that MALAT1 rs3200401 polymorphisms dramatically raised the probability of LUAD development.