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Abstract Background and aims Diabetic kidney disease (DKD) is a common complication of type 2 diabetes mellitus (T2DM) that leads to systemic inflammation. Maternally expressed gene 3 (MEG3) is a tumor suppressor that is involved in inflammation regulation. The current study investigated the association between DKD and the prevalence of the single-nucleotide polymorphisms (SNPs) of MEG3. Methods A total of 706 and 735 patients were included in the DKD and non-DKD groups, respectively. The five SNPs of MEG3, namely rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G), and rs11160608 (A/C), were genotyped using TaqMan allelic discrimination. Results Our results revealed that, in the DKD group, the distribution of the GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.703, 95% CI: 0.506–0.975, P = 0.035). In addition, in the pre-ESRD DKD subgroup, the distribution of the TG + GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.637, 95% CI: 0.421–0.962, P = 0.032). In addition, among men in the DKD subgroup, the distribution of the GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.630, 95% CI: 0.401–0.990, P = 0.045). Glycated hemoglobin (HbA1c) level was significantly higher in all T2DM patients with the wild-type genotype of the MEG3 SNP rs3087918 (P = 0.020). In addition, HbA1c levels were significantly higher in male patients and male DKD patients with the wild-type genotype of the MEG3 SNP rs3087918 (P = 0.032 and 0.031, respectively). Conclusion MEG3 SNP rs3087918 is significantly less prevalent in patients with DKD, and the SNP rs3087918 of MEG3 is associated with lower HbA1c levels.

Abstract To evaluate the efficiency, predictability, and residual astigmatism between first- and second-generation keratorefractive lenticule extraction (KLEx) surgeries in a prominent astigmatism population. A retrospective cohort study was conducted, and individuals who underwent first- and second-generation KLEx surgeries were enrolled. A total of 31 and 35 eyes were categorized into first and second KLEx groups, respectively. Visual acuity, refraction, topographic parameters, and surgical indices were recorded. Independent t tests were used to compare the postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and residual astigmatism between the two groups. The difference in UDVA was not significant three months after KLEx surgery (P = 0.509), and the SEs three months after surgery also presented similar values between the two groups (P = 0.552). The first KLEx group demonstrated greater residual astigmatism than did the second KLEx group throughout the three-month follow-up period (all P

Abstract To investigate the relationship between preoperative blood glucose levels and long-term all-cause mortality in patients with osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous vertebroplasty (VP). This single-center retrospective study involved a chart review of patients admitted for VP to treat OVCF between 2013 and 2020. Patients with pathological or multiple fractures or those who did not undergo bone mineral density assessment were excluded. All relevant information was collected from electronic medical records. The survival status of all patients was confirmed at the end of March 2021. Cox proportional hazard models with multivariate adjustments were used to examine the effects of blood glucose levels on all-cause mortality. Overall, 131 patients were retrospectively analyzed (mean age: 75.8 ± 9.3 years, male patients: 26.7%) with a median follow-up period of 2.1 years. Preoperative hyperglycemia (hazard ratio: 2.668, 95% confidence interval [CI] 1.064, 6.689; p = 0.036) and glucose levels (hazard ratio: 1.007, 95% CI 1.002–1.012; p = 0.006) were found to be independently associated with a higher risk of all-cause mortality. This correlation remained significant even after adjusting for age and sex, and other factors and comorbidities that might affect outcomes (hazard ratio: 2.708, 95% CI 1.047, 7.003, p = 0.040 and 1.007; 95% CI 1.001, 1.013, p = 0.016, respectively). Furthermore, a history of diabetes mellitus was not a significant factor influencing long-term all-cause mortality. Preoperative glucose levels were found to be independently associated with survival outcomes in patients with OVCF who underwent VP. Conversely, diabetes mellitus was not associated with long-term all-cause mortality. Our findings highlight that preoperative hyperglycemia is a risk factor for long-term mortality in this aging surgical population.

BackgroundWe aim to evaluate lifestyle and nutritional factors that lead to dry eye disease (DED) in a depressed population using data from the Taiwan BioBank (TWB).MethodsA retrospective case–control study was conducted, and patients with depression based on a questionnaire were selected as the depression group. Each patient in the depression group was matched by age and sex to two individuals without depression, and a total of 3,754 and 7,508 patients constituted the depression and non-depression groups, respectively. Based on the questionnaire, the primary outcome was the presence of DED. Additionally, the chi-square test and interaction test were applied to survey the effect of lifestyle and nutritional factors on DED in the depression and non-depression groups.ResultsThere were 822 (21.90%) and 958 (12.76%) DED patients in the depression and non-depression groups, respectively, and the incidence of DED was significantly higher in the depression group (p

Abstract 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

Objective To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED).Materials and methods This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences.Results In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p .05).Conclusions Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.

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.

Abstract The early development of the gut microbiome is governed by multiple factors and has significantly long-term effects on later-in-life health. To minimize inter-individual variations in the environment, we determined developmental trajectories of the gut microbiome in 28 healthy neonates during their stay at a postpartum center. Stool samples were collected at three time points: the first-pass meconium within 24 h of life, and at 7 and 28 days of age. Illumina sequencing of the V3–V4 region of 16S rRNA was used to investigate microbiota profiles. We found that there was a distinct microbiota structure at each time point, with a significant shift during the first week. Proteobacteria was most abundant in the first-pass meconium; Firmicutes and Actinobacteria increased with age and were substituted as the major components. Except for a short-term influence of different delivery modes on the microbiota composition, early microbiome development was not remarkably affected by gravidity, maternal intrapartum antibiotic treatment, premature rupture of membranes, or postnatal phototherapy. Hence, our data showed a similar developmental trajectory of the gut microbiome during the first month in healthy neonates when limited in environmental variations. Environmental factors external to the host were crucial in the early microbiome development.

Abstract Background To evaluate the possible topographic and surgical risk factors for high postoperative residual astigmatism in patients who undergo small-incision lenticule extraction (SMILE) surgery and have different myopia degrees. Methods A retrospective cohort study was conducted, and patients who underwent SMILE surgery were enrolled. A total of 80 and 150 eyes from 40 to 75 individuals, respectively, were selected as the low myopia and high myopia groups. The demographic data, visual acuity, refraction, topographic parameters and surgical settings were recorded. Multiple linear regression with interaction tests were performed to survey the risk factors for high postoperative residual astigmatism in each group. Results Five (6.25%) and 9 (6.00%) eyes presented with high postoperative residual astigmatism in the low myopia and high myopia groups, respectively, but these differences were not significant (P = 0.569). A steep corneal curvature was correlated with a greater risk of high postoperative residual astigmatism in the low myopia group (P = 0.015), while a higher degree of cycloplegic cylinder power, steeper corneal curvature, greater topographic cylinder power, smaller optic zone and longer incision length were associated with a high rate of postoperative residual astigmatism in the high myopia group (all P

Penetrating keratoplasty (PK) is a corneal surgery that is employed to repair the full-thickness corneal lesion. This study aimed to survey the possible systemic risk factors of infectious keratitis after penetrating keratoplasty (PK) via the Taiwan National Health Insurance Research Database (NHIRD). A retrospective case–control study was conducted, and 327 patients who received the PK were enrolled after exclusion. The main outcome was the development of infectious keratitis, and people were divided into those with infectious keratitis and those without the outcome. Cox proportional hazard regression was conducted to produce adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of specific demographic indexes and systemic diseases on infectious keratitis. There were 68 patients who developed infectious keratitis after the whole follow-up period. The diabetes mellitus (DM) (aHR: 1.440, 95% CI: 1.122–2.874, p = 0.0310) and chronic ischemic heart disease (aHR: 1.534, 95% CI: 1.259–3.464, p = 0.0273) groups demonstrated a significant association with infectious keratitis. The DM group also revealed significant influence on infectious keratitis development in all the subgroups (all p < 0.05). Nevertheless, the effect of chronic ischemic heart disease on infectious keratitis was only significant on those aged older than 60 years (p = 0.0094) and both sexes (both p < 0.05). In conclusion, the presence of DM and chronic ischemic heart disease are associated with infectious keratitis after PK. However, local risk factors for infectious keratitis developed in those receiving PK had not been evaluated.

The aim of this study is to survey the effectiveness of preservative-free artificial tears containing hyaluronic acid (HA) on post-cataract surgery dry eye disease (DED) prevention. A retrospective cohort study was performed, and patients that received cataract surgeries were divided into either an HA group or non-HA group depending on the artificial tear they used. A total of 37 and 74 eyes were enrolled into the HA and non-HA groups, respectively, after the selection. The primary outcomes are postoperative superficial keratitis and multiple (>3) DED symptoms. The generalized linear model was utilized to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of primary outcomes between the two groups. There were 10 and 2 episodes of superficial keratitis in the non-HA group and HA group, respectively, and the HA group demonstrated a significantly lower incidence of superficial keratitis (p < 0.001). Moreover, 13 and 5 patients developed multiple DED symptoms in the non-HA and HA groups, and the HA group illustrated fewer multiple DED symptoms (p = 0.024). The lower preoperative tear break-up time (TBUT) was correlated with superficial keratitis in the HA group (p = 0.043), while old age, low preoperative TBUT and ocular surface staining were associated with superficial keratitis in the non-HA group (all p < 0.05). Lower preoperative TBUT was correlated with multiple DED symptoms in the HA group (p = 0.020), while female sex, low preoperative TBUT and any DED symptoms were associated with multiple DED symptoms in the non-HA group (all p < 0.05). In conclusion, the usage of preservative-free artificial tears containing HA is associated with lower postoperative DED events.

We aimed to survey the potential correlation between biometric parameters and postoperative outcomes after implanting extended depth-of-focus (EDOF) intraocular lenses (IOLs) and trifocal IOLs. A retrospective cohort study was conducted, and patients receiving EDOF or trifocal IOL implantations were included. In total, 36 and 26 eyes were enrolled in the EDOF and trifocal groups, respectively. The primary outcomes of this study were the postoperative uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), and spherical equivalent (SE). The generalized linear model was applied to evaluate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) of primary outcomes in patients with different biometric characters. The final UDVA of the EDOF group was significantly better than that of the trifocal group (p = 0.020), and the UNVA and SE did not show significant differences between the two groups throughout the postoperative period (all p > 0.05). In a multivariable analysis, the UDVA was significantly better in the EDOF group than in the trifocal group (p = 0.038). For the subgroup analysis, the high axial length (AXL) value correlated to a lower postoperative UDVA in the EDOF group (both p < 0.05). Additionally, a large white-to-white (WTW) diameter was related to worse postoperative UNVA in the trifocal group (p = 0.042), and a high AXL was associated with higher SE in both the EDOF and trifocal groups (both p < 0.05). In conclusion, a high AXL correlates to worse postoperative outcomes in both the EDOF and trifocal IOLs, and trifocal IOL outcomes could be affected by large WTW diameters.

In this study, we aim to evaluate the risk factors of myopia undercorrection in recipients of second-generation keratorefractive lenticule extraction (KLEx) surgery. A retrospective case–control study was performed, and patients who received second-generation KLEx surgery were enrolled. The cases with myopia undercorrection were matched to non-myopia undercorrection cases with a 1:4 ratio according to age, and a total of 22 and 88 eyes were categorized into the undercorrection and control groups, respectively. Demographic, refractive, topographic, and surgical data were collected preoperatively. A generalized linear model was operated to evaluate the potential risk factors for myopia undercorrection. The uncorrected distance visual acuity (UDVA) at three months postoperation was significantly better in the control group (p = 0.006), and residual myopia and SE were significantly higher in the undercorrection group during the whole follow-up period (all p < 0.001). The UDVA value showed a trend of improvement in the control group (p < 0.001), and the changes to SE and residual myopia were significantly lower in the control group (both p < 0.001). Regarding the risk factors for myopia undercorrection in the whole population and the high-myopia population, a higher manifest sphere power, higher steep keratometry (K), higher topographic cylinder, lower central corneal thickness (CCT) at apex, higher CCT difference and lower residual stromal thickness (RST) correlated to myopia undercorrection (all p < 0.05). In the low-myopia population, only higher myopia and lower RST correlated to myopia undercorrection (both p < 0.05). In conclusion, a high-sphere power and irregular topographic pattern correlated to myopia undercorrection after the second KLEx surgery, especially for individuals with high myopia.

In this study, we aimed to investigate the effect of different hyaluronic acid (HA)-containing artificial tears on dry eye disease (DED) treatment in combination with intense pulsed light (IPL) therapy. A retrospective cohort study was conducted, and the participants received IPL therapy and HA-containing artificial tears. There were 42 and 40 eyes in the 0.10% and 0.15% HA groups after selection, respectively. The main outcomes were the postoperative non-invasive tear break-up time (NITBUT), Schirmer II test results, ocular surface stain, and numbers of DED-related symptoms. A generalized linear model was utilized to produce the adjusted odds ratio (aOR) and 95% confidence interval (CI) of the main outcomes between groups. At the three-month follow-up, the NITBUT was significantly higher in the 0.15% HA group (p = 0.023), and the NITBUT recovery was also significantly better in the 0.15% HA group compared to the 0.10% HA group (p = 0.039). The multiple DED-related symptoms significantly correlated with no DED symptom improvement in both the 0.10% and 0.15% HA groups (both p < 0.05), while the low pre-treatment NITBUT was marginally related to no DED symptom improvement in the 0.10% HA group (p = 0.047). A low NITBUT and Schirmer II test result correlated with no DED symptom improvement in both the groups (all p < 0.05). In conclusion, the application of 0.10% and 0.15% HA-containing artificial tears revealed similar effects to IPL therapy for DED.

We aim to evaluate the effectiveness of an acupuncture steam-warming eye mask (ASEM) on dry eye disease (DED) in visual display terminal (VDT) users. This prospective randomized clinical trial included VDT users with DED-related features who were randomly assigned to the ASEM group (ASEM for 2 weeks, 20 participants) or the steam-warming eye mask (SEM) group (SEM for 2 weeks, 20 participants). The tear film break-up time (TBUT), Schirmer test, tear meniscus height, ocular surface staining scores, eyelid and meibomian gland exam, subjective symptoms, and quality of life (QoL) scores before and after treatment were collected. A generalized linear mixed model was applied to compare the improvement of symptoms and signs between the two groups. After the 2-week treatment, all the subjective symptoms and questionnaire scores in the ASEM group improved significantly (all p < 0.05), whereas the feelings of relaxation, comfortable, and refreshment did not change in the SEM group (both p > 0.05). The TBUT, tear meniscus height, and meibum quality in the lower eyelid were significantly better in the ASEM group than the SEM group (all p < 0.05), whereas no significant changes were observed in the Schirmer test and ocular surface staining scores. Compared with the SEM group, the ASEM group experienced a stronger feeling of refreshment (p = 0.013), lower sensation of ocular discharge (p = 0.031), higher TBUT (p = 0.045), better meibomian gland expressibility of both eyelids (both p < 0.05), and better meibum quality of both eyelids (both p < 0.05), even after adjustments for age and sex. In conclusion, comparing with SEM, ASEM can improve some subjective DED symptoms, tear film stability, and meibum status in VDT users.

We aim to investigate the potential risk factors for undercorrection in those who have received extend depth-of-focus (EDOF) intraocular lens (IOL) implantation. A retrospective case-control study was conducted in which patients who had received one type of EDOF IOL implantation were included. The patients were divided into the residual group and non-residual group according to the final postoperative sphere power. The preoperative data include the refractive, topographic, endothelial, and biometric parameters obtained. A generalized linear model was generated to yield the adjusted odds ratio (aOR) and 95% confidence interval (CI) of each parameter of the residual myopia. One month postoperatively, the UDVA was better in the non-residual group than in the residual group (p = 0.010), and the final SE was significantly higher in the residual group than in the non-residual group (p < 0.001). In the multivariable analysis, the high preoperative cycloplegia sphere power, higher TCRP, higher corneal cylinder power, and longer AXL significantly correlated to the presence of postoperative residual myopia (all p < 0.05). Furthermore, the higher preoperative cycloplegia sphere power, higher TCRP, higher corneal cylinder power, longer AXL, larger ACD, and larger WTW were significantly associated with postoperative residual myopia in the high-myopia population (all p < 0.001), while the higher preoperative cycloplegia sphere power, higher TCRP, and longer AXL were related to postoperative residual myopia in the low-myopia population (all p < 0.05). In conclusion, high preoperative myopia and corneal refractive power correlate to high risk of residual myopia after EDOF IOL implantation, especially in the high-myopia population.

We aimed to evaluate the postoperative visual and refractive outcomes between the first- and second-generation keratorefractive lenticule extraction (KLEx) surgeries. A retrospective cohort study was conducted and patients who had received first- and second-generation KLEx surgeries were enrolled. A total of 80 and 80 eyes were categorized into the first and second KLEx groups after exclusion, respectively. The primary outcomes were the postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and safety indexes. An independent t-test and generalized estimate equation were implemented to compare the primary outcomes between the two groups. After the KLEx surgery, the UDVA showed no significant difference between the two groups throughout the study period (all p > 0.05), and the postoperative SE and safety index were also statistically identical between the two groups during the follow-up interval (all p > 0.05). There was a similar trend of visual recovery between the two groups (aOR: 0.967; 95% CI: 0.892–1.143; p = 0.844), while the amplitude of the SE change was significantly lower in the second KLEx group (aOR: 0.760; 95% CI: 0.615–0.837; p = 0.005). Nine and two unintended initial dissection of the posterior plane (UIDPP) occurred intraoperatively in the first and second KLEx groups, respectively, and the second group showed a lower risk of UIDPP (p = 0.032). In conclusion, the efficiency, predictability, and safety are similar between first- and second-generation KLEx surgeries.

In this study, we aimed to evaluate the association between the severity of coronary heart disease (CHD) and the subsequent severity of blepharitis. This retrospective population-based cohort study was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. The participants with a CHD diagnosis were divided into mild CHD and severe CHD groups at a 1:2 ratio, according to whether percutaneous coronary intervention (PCI) was performed. The main outcomes were the development of blepharitis and severe blepharitis with the application of antibiotics. Cox proportional hazard regression was performed to obtain the adjusted hazard ratio (aHR) for blepharitis, with a 95% confidence interval (CI) between the groups. There were 22,161 and 15,369 blepharitis events plus 9597 and 4500 severe blepharitis episodes in the mild and severe CHD groups, respectively. The severe CHD group showed a significantly higher incidence of blepharitis development (aHR, 1.275; 95% CI: 1.051–1.912, p = 0.0285), whereas the incidence of severe blepharitis was not significantly different between the groups (aHR, 0.981; 95% CI: 0.945–1.020, p = 0.3453). The cumulative probability of blepharitis was significantly higher in the severe CHD group than in the mild CHD group (p < 0.001). In the subgroup analyses, the correlation between severe CHD and blepharitis was more significant in patients older than 70 years compared to the younger group (p = 0.0115). In conclusion, severe CHD is associated with a higher incidence of blepharitis than mild CHD, and this correlation is more prominent in individuals older than 70 years.

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.

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.

BackgroundThe role of upfront cytoreductive nephrectomy remains debatable in the present era of tyrosine kinase inhibitors and immune checkpoint inhibitors. Here, we aimed to evaluate the outcomes of metastatic renal cell carcinoma patients treated with upfront CN and modern systemic therapies.MethodsUsing the TriNetX network database, we identified patients, in the period from 2008 to 2022, who were diagnosed with metastatic renal cell carcinoma, receiving first-line systemic therapies with tyrosine kinase inhibitors or immune checkpoint inhibitors. Their overall survivals were evaluated using the Kaplan-Meier method as well as multivariable regressions.ResultsWe identified 11,094 patients with metastatic renal cell carcinoma. Of them, 2,914 (43%) patients in the tyrosine kinase inhibitor cohort (n = 6,779), and 1,884 (43.7%) in the immune checkpoint inhibitors cohort (n = 4315) underwent upfront cytoreductive nephrectomy. Those receiving upfront cytoreductive nephrectomy showed survival advantages with either tyrosine kinase inhibitor (Hazard ratio 0.722, 95% Confidence interval 0.67-0.73, pConclusionsUpfront cytoreductive nephrectomy was associated with an improved overall survival for patients with metastatic renal cell carcinoma receiving either first-line tyrosine kinase inhibitors or immune checkpoint inhibitors. Our results support a clinical role of upfront cytoreductive nephrectomy in the modern era.

Several studies have shown that liver resection (LR) confers better survival outcomes in intermediate- and advanced-stage hepatocellular carcinoma (HCC) patients. However, the postoperative recurrence rate is high, and little is known about the survival benefits of LR for recurrent HCC patients who have already received systemic treatment. This study aimed to evaluate the impact of LR on recurrent advanced-stage HCC patients who received sorafenib as a systemic treatment. In this study, 147 advanced HCC patients were enrolled between 1 January 2012 and 31 December 2019. Two study groups were classified, based on whether they underwent LR or not. To reduce the possible selection bias, a propensity score matching (PSM) analysis was performed. The primary study endpoint was set as overall survival (OS), and the secondary endpoint was set as progression-free survival (PFS). Our study results revealed that advanced HCC patients who received sorafenib with LR had a longer OS than did those without LR, whether before or after PSM (15.0 months vs. 6.0 months, HR 0.45, 95% CI 0.31–0.67, p < 0.001; 15.0 months vs. 5.0 months, HR 0.46, 95% CI 0.28–0.76, p = 0.001). Similar results were obtained in PFS, before or after PSM (4.14 months vs. 2.60 months, HR 0.60, 95% CI 0.40–0.89, p = 0.01; 4.57 months vs. 2.63 months, HR 0.58, 95% CI 0.34–0.97, p = 0.037). Multivariate analysis showed that the experience of LR was independent of other factors associated with better OS and PFS, whether before or after PSM (p < 0.05). Therefore, advanced HCC patients who have undergone liver resection should be encouraged to continue sorafenib treatment to improve prognosis.

Abstract To investigate the prognostic value of the geriatric nutritional risk index (GNRI) in patients with upper tract urothelial cell carcinoma (UTUC) receiving radical nephroureterectomy (RNU). Between January 2001 and December 2015, we enrolled 488 patients with UTUC underwent RNU in Taichung Veterans General Hospital. GNRI before radical surgery was calculated based on serum albumin level and body mass index. The malnutritional status was defined as GNRI

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.

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.

This study aimed to evaluate the potential association between coronary heart disease (CHD) severity and the subsequent dry eye disease (DED) with a different severity through the use of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was conducted. The CHD population was further divided into a severe CHD that had received coronary artery bypass graft (CABG) surgery group and a mild CHD that had received medicine group, then matched with a 1:2 ratio, and 29,852 and 14,926 CHD patients were put into the severe CHD and mild CHD groups, respectively. The primary outcomes were the development of DED and severe DED after CHD diagnosis. The Cox proportional hazards regression was used to produce the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of DED and severe DED between groups. There were 3440 and 1276 DED cases in the mild CHD and severe CHD groups, respectively. And another 37 and 48 severe CHD events were observed in the mild and severe CHD groups, respectively. The incidence of severe DED in the severe CHD group was significantly higher compared to the mild CHD group (aHR: 5.454, 95% CI: 1.551–7.180, p = 0.0001). The cumulative probabilities of DED and severe DED were significantly higher in the severe CHD group than the mild CHD group (both p < 0.0001). In the subgroup analysis, the correlation between severe CHD and DED was higher in the patients aged older than 70 years (p < 0.0001). In conclusion, severe CHD is associated with a higher incidence of severe DED with a higher cumulative incidence.

Stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine 4 (CXCR4) have been demonstrated to play critical roles in diabetic retinopathy (DR). This study investigated whether single-nucleotide polymorphisms (SNPs) of SDF-1 and its receptor CXCR4 are correlated with diabetic retinopathy (DR). Three SDF-1 SNPs, namely, rs1801157 (G/A), rs2297630 (G/A), and rs266085 (T/C), and two CXCR4 SNPs, namely, rs2228014 (C/T) and rs6430612 (C/T), were chosen and genotyped via the TaqMan allelic discrimination for 454 non-DR subjects and 276 DR individuals. Our results revealed that subjects carrying SDF-1 SNP rs2297630 GA (AOR: 2.962, 95% CI: 1.279-6.861, p = 0.011) and SDF-1 SNP rs2297630 GA + AA (AOR: 3.095, 95% CI: 1.394-6.872, p = 0.006) had significantly higher risk in the non-proliferative diabetic retinopathy (NPDR) groups than in the non-DR group. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal revealed that SDF-1 SNP rs2297630 GA and AA genotypic variants have higher SDF-1 expression than the GG wild-type alleles (p = 0.000016). In conclusion, our findings revealed that SDF-1 SNP rs2297630 was associated with NPDR.

Abstract Odontogenic rhinosinusitis is a subtype of rhinosinusitis associated with dental infection or dental procedures and has special bacteriologic features. Previous research on the bacteriologic features of odontogenic rhinosinusitis has mainly used culture-dependent methods. The variation of microbiota between odontogenic and nonodontogenic rhinosinusitis as well as the interplay between the involved bacteria have not been explored. Therefore, we enrolled eight odontogenic rhinosinusitis cases and twenty nonodontogenic rhinosinusitis cases to analyze bacterial microbiota through 16S rRNA sequencing. Significant differences were revealed by the Shannon diversity index (Wilcoxon test p = 0.0003) and PERMANOVA test based on weighted UniFrac distance (Wilcoxon test p = 0.001) between odontogenic and nonodontogenic samples. Anaerobic bacteria such as Porphyromonas, Fusobacterium, and Prevotella were significantly dominant in the odontogenic rhinosinusitis group. Remarkably, a correlation between different bacteria was also revealed by Pearson’s correlation. Staphylococcus was highly positively associated with Corynebacterium, whereas Fusobacterium was highly negatively correlated with Prophyromonas. According to our results, the microbiota in odontogenic rhinosinusitis, predominantly anaerobic bacteria, was significantly different from that in nonodontogenic rhinosinusitis, and the interplay between specific bacteria may a major cause of this subtype of rhinosinusitis.

Abstract We aim to investigate the association of mood disorders with age-related macular degeneration (AMD). This retrospective cohort study used data from 2000 and 2016 from National Health Insurance Research Database (NHIRD) in Taiwan. Patients with AMD diagnosis formed the exposed group, and an age- and sex-matched group without AMD served as the nonexposed group. Main outcomes were the incidence of mood disorders including psychological counseling, behavior therapy, sleep or anxiety-related disorders, and major depressive disorders (MDDs) in the exposed and non-exposed groups. The Cox proportional hazard regression analysis was used to evaluate the incidence and adjusted hazard ratio (aHR) of mood disorders. A total of 5916 and 11,832 individuals with and without AMD were enrolled into the exposed and nonexposed groups. There were 1017 (17.19%) and 1366 (11.54%) episodes of mood disorders occurred in the exposed and nonexposed groups, respectively. The aHRs of any psychological counseling, behavioral therapy, sleep or anxiety-related disorders, and MDD were significantly higher in patients with AMD than in those without AMD (all P 70 years, and women without AMD. In conclusion, AMD occurrence leads to an increased rate of mood disorders, particularly among those with dry-AMD, middle aged participants (aged 50–70), and women.

IntroductionPsoriasis (PSO) is a chronic skin condition that affects a variety of disorders, especially the cardiovascular system. This study investigated the association between PSO and peripheral arterial disease (PAOD).MethodsA retrospective cohort study design was carried out between 2000 and 2018. The exposure subject was a newly diagnosed PSO. The diagnosis of PSO was never elaborated as a comparison subject. Balanced heterogeneity of the two groups was used by propensity score matching. The cumulative incidence of PAOD between the two groups was performed using Kaplan-Meier analysis. The Cox proportional hazard model was used to measure the risk of PAOD risk hazard ratio.ResultsAfter matching the 1: 1 propensity score, 15,696 subjects with PSO and the same number of subjects without the diagnosis of PSO were recruited. The PSO subject had a higher risk of PAOD than the non-PSO subject (adjusted HR = 1.25; 95% CI = 1.03-1.50). In the 40-64-year-old subgroup, the subject of PSO exhibited an increased risk of PAOD than the subject without PSO.ConclusionPsoriasis is associated with an increased risk of peripheral arterial disease and curative care is necessary to reduce the risk of PAOD..

We aim to investigate the myopic control effect of high-concentration atropine (ATR) and dual-focus contact lenses (DFCLs). A retrospective cohort study was conducted. A total of 182 eyes in 91 individuals who used high-concentration ATR (0.125%) and another 70 eyes in 35 individuals who used DFCLs were enrolled in the ATR and DFCL groups, respectively. The primary outcomes were spherical equivalent refraction (SER) progression and axial length (AXL) elongation. The generalized estimate equation was utilized to yield the adjusted odds ratio (aOR) and 95% confidence interval (CI) of cycloplegic SER progression and AXL elongation between groups. According to the multivariable analysis, the change in cycloplegic SER progression was similar between the DFCL and ATR groups (aOR: 1.305, 95% CI: 0.247–2.515, p = 0.803). The DFCL group demonstrated a numerically higher rate of AXL elongation compared to the ATR group (aOR: 1.530, 95% CI: 0.980–1.894, p = 0.051). In the subgroup analysis, cycloplegic SER progression was insignificant between ATR and DFCL users in different subgroups (all p > 0.05). The DFCL patients with moderate astigmatism and high AXL (both p < 0.001) presented a high risk of AXL elongation. In conclusion, DFCL usage demonstrated similar myopic control of cycloplegic SER and AXL compared to high-concentration ATR, while DFCLs showed lower AXL control, mainly in patients with moderate astigmatism and high AXL.

Abstract Background Age-related macular degeneration (AMD) leads to gradual central vision loss and eventual irreversible blindness. Melatonin, an endogenous hormone, exhibits anti-inflammatory and antitumor effects; however, the role it plays in AMD remains unclear. Herein, we investigated the anti-AMD molecular mechanism of melatonin after sodium iodate (NaIO3) treatment of ARPE-19 cells in vitro and in animal models with the goal of improving the therapeutic effect. Results The in vitro results showed that melatonin protected against NaIO3-induced cell viability decline, mitochondrial dysfunction and apoptosis in ARPE-19 cells, and melatonin also alleviated NaIO3-induced reactive oxygen species (ROS) production, mitochondrial dysfunction and mitophagy activation. Melatonin reduced NaIO3-induced mitophagy activation through HIF-1α-targeted BNIP3/LC3B transcription, whereas ROS inhibition realized with N-acetylcysteine (NAC, a ROS inhibitor) combined with melatonin reduced the effect of NaIO3 on mitophagy. An animal model of AMD was established to confirm the in vitro data. Mouse tail vein injection of NaIO3 and melatonin was associated with enhanced repair of retinal layers within 7 days, as observed by optical coherence tomography (OCT) and hematoxylin and eosin (H&E) staining. A reduction in BNIP3 and HIF-1α levels, as determined by immunohistochemistry (IHC) assay, was also observed. Conclusions These results indicate that melatonin attenuated NaIO3-induced mitophagy of ARPE-19 cells via reduction in ROS-mediated HIF-1α targeted BNIP3/LC3B signaling in vitro and in vivo. Melatonin may be a potential therapeutic drug in the treatment of AMD.

Background: The risk of invasive Candida infection (ICI) is high in patients with perforated peptic ulcer (PPU) who received laparotomy or laparoscopic surgery, but the risk factors and predictors of morbidity outcomes remain uncertain. This study aims to identify the risk factors of ICI in surgical critically ill PPU patients and to evaluate the impact on patient's outcomes. Methods: This is a single-center, retrospective study, with a total of 170 surgical critically ill PPU patients. Thirty-seven patients were ICI present and 133 were ICI absent subjects. The differences in pulmonary complications according to invasive candidiasis were determined by the Mann–Whitney U test. Evaluation of predictors contributing to ICI and 90-day mortality was conducted by using multivariate logistic regression analysis. Results: Candida albicans was the primary pathogen of ICI (74.29%). The infected patients had higher incidence of bacteremia (p

Abstract Successful weaning from ventilators not only improves the quality of life of patients, but also reduces medical expenses. The aim of this study was to explore the association between nutritional provision and successful ventilator weaning. In this retrospective study data from the Respiratory Care Center of Chung Shan Medical University Hospital between October, 2017 and July, 2019 on patient characteristics, amount of nutrition delivered, and clinical outcomes were retrieved. A total of 280 ventilated patients were enrolled and divided into successful extubation and failed weaning groups. There were 178 males (63.6%) and 102 females (36.4%) with a mean age of 67.3 ± 16.9 years. The successful extubation group consisted of patients who tended towards ideal body weight during the weaning process (BMI 23.9 ± 5.0 versus 22.7 ± 4.8 kg/m2, p

BackgroundPsoriasis is a chronic autoimmune disease involving both environmental and genetic risk factors. Maternal psoriasis often results in poor pregnancies that influence both mothers and newborns. However, the influence of paternal psoriasis on the newborn remains unknown. The aim of this study was to investigate whether paternal psoriasis is associated with increased risk of adverse neonatal outcomes, within a nationwide population-based data setting.MethodsSingleton pregnancies were identified in the Taiwan National Health Insurance database and National Birth Registry between 2004-2011 and classified into four study groups according to whether mothers and spouses had psoriasis (paternal(−)/maternal(−), paternal(+)/maternal(−), paternal(−)/maternal(+), and paternal(+)/maternal(+)). Data were analyzed retrospectively. Adjusted odds ratios (aOR) or hazard ratios (aHR) were calculated to evaluate the risk of neonatal outcomes between groups.ResultsA total of 1,498,892 singleton pregnancies were recruited. Newborns of fathers with psoriasis but not of mothers with psoriasis were associated with an aHR (95% CI) of 3.69 (1.65–8.26) for psoriasis, 1.13 (1.06–1.21) for atopic dermatitis and 1.05 (1.01–1.10) for allergic rhinitis. Newborns of mothers with psoriasis but not of fathers with psoriasis were associated with an aOR (95% CI) of 1.26 (1.12-1.43) for low birth weight (

Background: The inconsistency in decisions to commence oral feeding indicates that health professionals require clearer guidelines to determine when to initiate oral feeding in preterm infants. This study applied the Taiwan version of Preterm Oral Feeding Readiness Assessment Scale (TW-POFRAS) to clinical decision-making, especially for preterm infants with a birth weight less than 1,500 g or gestational age (GA) less than 32 weeks. Methods: This was a single-center observational cross-sectional study and 81 preterm infants were recruited. Lengths of stay from admission to initial one-meal oral feeding, to one-day all-meal oral feeding, and to discharge were analyzed. Scale scores, physician orders, and smooth oral intake of 5 mL of milk were analyzed. Kappa coefficients were examined to determine concordances within the results. Results: At least moderate concordance was evident (k = 0.492). Most preterm infants can begin to consume one meal of the least 5 mL of milk smoothly and proceed to consume a full day of meals with a week; they are typically discharged from the hospital within a month, except for those with a birth weight less than 1,500 g or a GA less than 32 weeks. For 17 of 81 participants, assessment results for physician orders, 5-mL milk consumption, and scale scores were inconsistent. Participants with a birth weight less than 1,500 g or GA less than 32 weeks were able to meet the 5-mL standard by the postmenstrual age of 35 weeks, at latest. Conclusion: We recommend that TW-POFRAS should be used in conjunction with physicians’ clinical decision-making for oral feeding readiness for preterm infants in the NICU.

Abstract Progressive structural changes in osteoarthritis (OA) involve synovial inflammation and angiogenesis, as well as activation of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-8, and the angiogenic factor vascular endothelial growth factor (VEGF). The endogenous hormone melatonin (N-acetyl-5-methoxytryptamine) is involved in antioxidative and anti-inflammatory activities, but how it antagonizes OA progression via its specific receptors is unclear. Here, we demonstrate that the MT1 melatonin receptor, but not the MT2 receptor, is highly expressed in normal tissue and only minimally in OA tissue. By targeting the MT1 receptor, melatonin reversed OA-induced pathology and effectively reduced levels of TNF-α, IL-8, and VEGF expression in OA synovial fibroblasts and synovium from rats with severe OA. Interestingly, we found that the anabolic activities of melatonin involved the MT1 receptor, which upregulated microRNA-185a through the PI3K/Akt and ERK signaling pathways in OA synovial fibroblasts. Our investigation confirms the role of the MT1 receptor in melatonin-induced anti-catabolic effects in OA disease.

ObjectivesThe treatment landscape for metastatic renal cell carcinoma changed a lot in the last few years. This study aimed to assess the treatment sequences and outcomes for metastatic renal cell carcinoma in a real-world setting.Materials and methodsWe enrolled patients with metastatic renal cell carcinomawho received first-line systemic treatment with tyrosin kinase inhibitors monotherapy, ipilimumab plus nivolumab, or pembrolizumab plus axitinibbetween January2009 and May 2023 on the database of TriNetX network. Overall survival, time on treatment and time to next treatment were evaluated using Kaplan-Meiermethod.ResultsTotally, 4183 received tyrosine kinase inhibitor monotherapy, 1555 received ipilimumab plus nivolumab, and 559 received axitinib plus pembrolizumab. Median time on treatment was 2.5 months for the tyrosine kinase inhibitor monotherapy cohort, 5.4 months for the ipilimumab plus nivolumab cohort, and 8.3 months for the pembrolizumab plus axitinib cohort. Median time to next treatment was 16.6 months for both the tyrosine kinase inhibitor monotherapy and ipilimumab plus nivolumab cohorts, and 22.1 months for the pembrolizumab plus axitinib cohort. Median overall survival was 42.2 months for the tyrosine kinase inhibitor monotherapy cohort, 39.7monthsfor the ipilimumab plus nivolumab cohort, and not reached for the pembrolizumab plus axitinib cohort. In comparison with the tyrosine kinase inhibitor monotherapy cohort, patients in the pembrolizumab plus axitinib cohort showed survival benefit (log-rank p = 0.0168) in overall survival, but not the case in the ipilimumab plus nivolumab cohort.ConclusionThere was a trend toward using first-line immuno-oncology based therapy for patients with metastatic renal cell carcinoma in a real-world practice. Axitinib plus pembrolizumuab cohort had survival benefits over tyrosine kinase inhibitor and ipilimumab plus nivolumab cohorts, while patients in the ipilimumab plus nivolumab cohort had more distant metastases and comorbidities.

Abstract Background The effect of diabetic retinopathy (DR) on the development of sight-threatening cataracts was assessed using the National Health Insurance Research Database of Taiwan. Methods Patients diagnosed with diabetes mellitus (DM) and DR were enrolled in the study group. Age- and sex-matched DM individuals without DR and patients without DM served as the DM control group and non-DM control group, respectively, both with 1:4 ratios. The outcome was set as the performance of cataract surgery. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (aHR) of DR considering multiple factors underlying cataract formation. Results A total of 3297 DR patients, 13,188 DM control patients and 13,188 non-DM control subjects were enrolled. The study group included 919 events of sight-threatening cataracts (27.87%), the DM control group included 1108 events (8.40%), and the non-DM control group included 957 events (7.26%). A multivariable analysis indicated that the study group presented a higher aHR of cataract surgery (2.93, 95% CI: 2.60–3.30) and a higher cumulative probability of cataract surgery than both the DM control and non-DM control groups (both log rank P

Abstract Metastasis-associated protein 2 (MTA2) is a transcription factor that is highly associated with matrix metalloproteinase 12 (MMP12). Thus, we hypothesized that MTA2 may regulate MMP12 expression and is involved in cervical cancer metastasis. Results showed that MTA2 and MMP12 were highly expressed in cervical cancer cells, and MTA2 knockdown reduced MMP12 expression and inhibited the metastasis of cervical cancer cells in xenograft mice. MMP12 knockdown did not influence the viability of cervical cancer cells but clearly inhibited cell migration and invasion both in vitro and in vivo. MMP12 was highly expressed in cervical tumor tissues and correlated with the poor survival rate of patients with cervical cancer. Further investigations revealed that p38 mitogen-activated protein kinase (p38), mitogen-activated protein kinase kinase 3 (MEK3), and apoptosis signal-regulating kinase 1 (ASK1) were involved in MMP12 downregulation in response to MTA2 knockdown. Results also demonstrated that p38-mediated Y-box binding protein1 (YB1) phosphorylation disrupted the binding of AP1 (c-Fos/c-Jun) to the MMP12 promoter, thereby inhibiting MMP12 expression and the metastatic potential of cervical cancer cells. Collectively, targeting both MTA2 and MMP12 may be a promising strategy for the treatment of cervical cancer.

Abstract It remained inconclusive whether patients with peptic ulcer disease had a higher risk of head and neck cancer (HNC). Therefore, we enrolled 109,360 patients with peptic ulcer disease and matched for age and sex with 218,720 controls from the Taiwan National Health Insurance Research Database between January 1, 1997 and December 31, 2013.The HNC incidence rate was 1.33-fold higher in the peptic ulcer group than in the control group (7.52 vs. 5.68 per 100,00 person-years; crude relative risk: 1.33; 95% confidence interval [CI]: 1.08–1.63) after > 6 years of follow-up. However, in the peptic ulcer subgroup with H. pylori treatment, HNC risk was not significantly different from that of the control group (crude relative risk: 1.12; 95% CI: 0.86–1.46). Moreover, the population with peptic ulcers had the highest risk of laryngeal and hypopharyngeal cancer (adjusted HR: 2.27 [95% CI: 1.16–4.44] and 2.00 [95% CI, 1.13–3.55]), respectively. This observational study suggested that peptic ulcer disease is associated with an increased incidence of laryngeal and hypopharyngeal cancer and H. pylori treatment may have a role in preventing HNC in patients with peptic ulcer disease.

Background and objectives: The objective of this study is to elucidate peripheral occlusion artery disease (PAOD) as a risk factor for cellulitis. Materials and Methods: This is a retrospective population-based cohort study. The database is the Longitudinal Health Insurance Database, which covers two million beneficiaries from the entire population of the 2010 registry for beneficiaries in Taiwan. The PAOD group is composed of patients who were newly diagnosed with PAOD from 2001 to 2014. The non-PAOD group is composed of patients who were never diagnosed with PAOD from 2001 to 2015. All patients were followed until the onset of cellulitis, death, or until the end of 2015. Results: Finally, 29,830 patients who were newly diagnosed with PAOD were included in the PAOD group, and 29,830 patients who were never diagnosed with PAOD were included in the non-PAOD group. The incidence densities (ID) of cellulitis were 26.05 (95% CI = 25.31–26.80) patients per 1000 person-years in the PAOD group and 49.10 (95% CI = 48.04–50.19) in the non-PAOD group. The PAOD group had an increased risk of cellulitis (adjusted HR = 1.94, 95% CI = 1.87–2.01) compared to the non-PAOD group. Conclusions: Patients with PAOD were associated with a higher risk of subsequent cellulitis compared to patients without PAOD.

Neovascular age-related macular degeneration (AMD) is described as abnormal angiogenesis in the retina and the leaking of fluid and blood that generates a huge, dark, blind spot in the center of the visual field, causing severe vision loss in over 90% of patients. Bone marrow-derived endothelial progenitor cells (EPCs) contribute to pathologic angiogenesis. Gene expression profiles downloaded from the eyeIntegration v1.0 database for healthy retinas and retinas from patients with neovascular AMD identified significantly higher levels of EPC-specific markers (CD34, CD133) and blood vessel markers (CD31, VEGF) in the neovascular AMD retinas compared with healthy retinas. Melatonin is a hormone that is mainly secreted by the pineal gland, and is also produced in the retina. Whether melatonin affects vascular endothelial growth factor (VEGF)-induced EPC angiogenesis in neovascular AMD is unknown. Our study revealed that melatonin inhibits VEGF-induced stimulation of EPC migration and tube formation. By directly binding with the VEGFR2 extracellular domain, melatonin significantly and dose-dependently inhibited VEGF-induced PDGF-BB expression and angiogenesis in EPCs via c-Src and FAK, NF-κB and AP-1 signaling. The corneal alkali burn model demonstrated that melatonin markedly inhibited EPC angiogenesis and neovascular AMD. Melatonin appears promising for reducing EPC angiogenesis in neovascular AMD.

Long noncoding RNAs (lncRNAs) have been proven to play critical roles in diabetic retinopathy (DR). This study investigated whether the single nucleotide polymorphism (SNP) of long intergenic noncoding RNA 00673 (LINC00673) affects the clinical characteristics of diabetic retinopathy (DR). A total of three loci of LINC00673 SNPs (rs6501551, rs9914618, and rs11655237) were genotyped using TaqMan allelic discrimination in 276 and 454 individuals with and without DR, respectively. Our results revealed that LINC00673 SNP rs11655237 CT genotype (AOR: 1.592, 95% CI: 1.059–2.395, p = 0.026), CT + TT genotype (AOR: 1.255, 95% CI: 1.029–1.531, p = 0.025), and allele T (AOR: 1.185, 95% CI: 1.004–1.397, p = 0.044) yielded higher ratios in the non-proliferative diabetic retinopathy (NPDR) subgroup than in the non-DR group. Furthermore, the interval of diabetes mellitus (DM) was significantly shorter in the LINC00673 SNP rs11655237 CT + TT variant than that in the LINC00673 SNP rs11655237 wild type (10.44 ± 7.10 vs. 12.98 ± 8.34, p = 0.009). In conclusion, the LINC00673 SNP rs11655237 T allele is associated with a higher probability of NPDR development. Patients with the LINC00673 SNP rs11655237 CT + TT variant exhibited a short DM interval.

Type 2 diabetes (T2D) and liver cirrhosis remain significant public health threats in Taiwan. These conditions are reported to be associated with the rs738409 polymorphism of the patatin-like phospholipase domain-containing protein three gene (PNPLA3) in European populations. We assessed the effect of T2D and PNPLA3 rs738409 polymorphism on liver cirrhosis among Taiwan Biobank (TWB) participants. In total, 17,985 participants in TWB had their health records linked to the National Health Insurance Research Database (NHIRD). Participants included those who visited the assessment centers between 2008 and 2015, with an age range between 30 and 70 years of age. We performed logistic regression analysis to investigate the odds ratios (OR) for liver cirrhosis among participants based on the T2D status and rs738409 genotypes. Genotyping was performed using the Axiom Genome-Wide TWB Array Plate. In our analysis, 150 of the 17,619 eligible participants were identified as cirrhosis cases. Based on the univariate analysis, liver cirrhosis was positively associated with T2D (OR, 1.83; 95% CI 1.23–2.70) whereas, the variant rs738409 was not (regardless of the genetic model). The variant and T2D, however, showed significant interactions in the additive, genotype, and dominant models (p values of 0.0302, 0.0395, and 0.0455, respectively). We observed a statistically significant association between T2D and liver cirrhosis and variant rs738409 with an OR of 1.71 (95% CI, 1.03–2.84) for individuals carrying a G allele compared to those with a C allele and 2.92 (95% CI 1.07–7.99) for GG compared to CC individuals. According to our study, Taiwanese adults with T2D and the rs738409 GG genotype are more likely to develop liver cirrhosis.

Background Fluoroquinolones are first‐line antibiotics recommended for the treatment of complicated urinary tract infections (UTIs), with frequent reports of adverse effects of aortic aneurysm (AA) and aortic dissection (AD). We examined whether fluoroquinolones can increase the risk of AA and AD in patients with UTIs in the Taiwanese population. Methods and Results We used the National Health Insurance Research Database to identify patients diagnosed with UTIs under single antibiotic treatment of fluoroquinolones and first‐, second‐, or third‐generation cephalosporins. An AA and AD diagnosis within a year constituted the study event. Multivariable analysis with a multiple Cox regression model was applied for comparing the hazard risk of AA and AD between fluoroquinolones and first‐ or second‐generation cephalosporins. Propensity score matching was performed to reduce the potential for bias caused by measured confounding variables. Among 1 249 944 selected patients with UTIs, 28 568 patients were assigned to each antibiotic group after propensity score matching. The incidence of AA and AD was not significantly different between the fluoroquinolones and first‐ or second‐generation cephalosporins (adjusted HR [aHR], 0.86 [95% CI, 0.59–1.27]). However, the mortality increased in the fluoroquinolones group (aHR, 1.10 [95% CI, 1.04–1.16]). Conclusions Compared with first‐ or second‐generation cephalosporins, fluoroquinolones were not associated with increased risk of AA and AD in patients with UTI. However, a significant risk of mortality was still found in patients treated with fluoroquinolones. The priority is to control infections with adequate antibiotics rather than exclude fluoroquinolones considering the risk of AA and AD for patients with UTI.

MTA2 is involved in tumor proliferation and metastasis. However, the role of MTA2 in cervical cancer thus far has not been identified. In this study, we report that elevated expression of MTA2 negatively correlates with Kallikrein-10 (KLK10) expression and poor prognosis of cervical cancer patients. Knockdown of MTA2 substantially inhibited tumor cell migration and invasion, and it enhanced KLK10 expression of the cervical cancer cells in vitro and in vivo. Functionally, shMTA2-mediated suppression of cell mobility was significantly restored by knockdown of KLK10. We also found that Sp1 (transcription factor specificity protein 1) is critical for shMTA2-induced transcriptional upregulation of KLK10 and subsequent biological functions. Furthermore, we found that the expression of miR-7 is elevated by MTA2 silencing and then by direct inhibition of Sp1 expression. Knockdown of Sp1 additively enhanced KLK10 expression in MTA2-knocked down cervical cancer cells, suggesting that the miR-7/Sp1 axis acts as an effector of MTA2 to impact KLK10 levels and mobility of cervical cancer cells. Taken together, our findings provide new insights into the physiological relationship between MTA2 and KLK10 via regulating the miR-7/Sp1 axis, and they provide a potential therapeutic target in cervical cancer.

Patients with oral cavity squamous cell carcinoma (OCSCC) who develop distant metastasis (DM) face poor outcomes, and effective prediction models of DM are rare. A total of 595 patients with OCSCC were retrospectively enrolled in this study. Because pathological N staging significantly influences the development and mechanisms of DM, the patients were divided into nodal-negative (pN−) and -positive (pN+) groups. Clinical outcomes, prognoses, and prediction models were analyzed separately for both groups. Overall, 8.9% (53/595) of these patients developed DM. Among the DM cases, 84.9% (45/53) of them developed DM within the first 3 years. The median overall survival, locoregional recurrence-free survival, time until DM development, and postmetastatic survival were 19.8, 12.7, 14.6, and 4.1 months, respectively. Distinguishing patients who only developed locoregional recurrence from those with DM according to locoregional conditions was difficult. Age, surgical margin, and early locoregional recurrence were predictors of DM that were independent of time until DM in the pN− group; the lymphocyte-to-monocyte ratio, presence of lymphovascular invasion, and early locoregional recurrence in the pN+ group were determined. If one point was scored for each factor, then two scoring systems were used to classify the patients into low- (score = 0), intermittent- (score = 1), or high- (score = 2 or 3) risk for the pN− and pN+ groups. According to this scoring system, the 3-year DM rates for the low, intermittent, and high risk subgroups were 0.0%, 5.9%, and 17.8% for the pN− group and 7.1%, 44.9%, and 82.5% for the pN+ group, respectively. These systems also effectively predicted DM, and the areas under the curve predicted DM occurring within the first 3 years were 0.744 and 0.820 for the pN− and pN+ groups, respectively. In conclusion, effective scoring models were established for predicting DM.

Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) has been reported to play an oncogenic role in certain cancer types; however, the role of SPOCK1 in the progression of clear cell renal cell carcinoma (ccRCC) remains elusive. Here, higher SPOCK1 transcript and protein levels were observed in ccRCC tissues compared to normal tissues and correlated with advanced clinical stages, larger tumor sizes, and lymph node and distal metastases. Knockdown and overexpression of SPOCK1 in ccRCC cells led to decreased and increased cell clonogenic and migratory/invasive abilities in vitro as well as lower and higher tumor growth and invasion in vivo, respectively. Mechanistically, the gene set enrichment analysis (GSEA) database was used to identify the gene set of epithelial-to-mesenchymal transition (EMT) pathways enriched in ccRCC samples with high SPOCK1 expression. Further mechanistic investigations revealed that SPOCK1 triggered the Snail/Slug–matrix metalloproteinase (MMP)-2 axis to promote EMT and cell motility. Clinical ccRCC samples revealed SPOCK1 to be an independent prognostic factor for overall survival (OS), and positive correlations of SPOCK1 with MMP-2 and mesenchymal-related gene expression levels were found. We observed that patients with SPOCK1high/MMP2high tumors had the shortest OS times compared to others. In conclusion, our findings reveal that SPOCK1 can serve as a useful biomarker for predicting ccRCC progression and prognosis, and as a promising target for treating ccRCC.

Protodioscin (PD) is a steroidal saponin with various pharmacological activities, including neuro-protective, anti-inflammatory, and anti-tumor activities. However, the effect of PD on human osteosarcoma (OS) cells is unclear. In this study, we found that PD significantly inhibits the growth of human HOS and 143B OS cells through the upregulation of apoptotic-related proteins (cleaved caspase-3, cleaved caspase-9, and cleaved PARP) and mitophagy-related proteins (LC3B and NIX), which contribute to the induction of apoptosis, and MMP (mitochondrial membrane potential) dysfunction and mitophagy. The inhibition of LC3 or NIX was shown to decrease apoptosis and mitophagy in PD-treated OS cells. The knockdown of p38MAPK by siRNA decreased mitochondrial dysfunction, autophagy, mitophagy, and the NIX/LC3B expression in the PD-treated OS cells. A binding affinity analysis revealed that the smaller the KD value (−7.6 Kcal/mol and −8.9 Kcal/mol, respectively), the greater the binding affinity in the PD-NIX and PD-LC3 complexes. These findings show the inhibitory effects of PD-induced mitophagy in human OS cells and may represent a novel therapeutic strategy for human OS, by targeting the NIX/LC3 pathways.