Two-Dimensional Peripheral Refraction and Higher-Order Wavefront Aberrations Induced by Orthokeratology Lenses Decentration.

Purpose: The purpose of this study was to explore two-dimensional peripheral refraction and higher-order aberrations (HOAs) induced by orthokeratology lens decentration. Methods: Two-dimensional peripheral refraction and HOAs in a rectangular field (horizontally 60 degrees and vertically 36 degrees) were obtained using an open-view Hartmann-Shack wavefront sensor. The peripheral field was divided into 8 regions according to a combination of superior (UZ) or inferior (LZ) and a value, 1 (T25 to T30), 2 (T20 to T25), 3 (N20 to N25), or 4 (N25 to N30). The decentration of the lens was evaluated based on the change of power in the front of the tangential corneal map. All measurements were taken at the baseline and 1 month after lens fitting. Results: In total, 134 myopic children (age = 12.47 ± 1.70 years, SER = -2.44 ± 1.10 diopters [D]) were recruited. In general, horizontally asymmetrical change was observed in relative peripheral refraction (RPR), spherical aberration (SA), and horizontal coma. The root-mean square of higher order aberration (RMSHOA) and vertical coma demonstrated radial symmetrical change and vertically asymmetric change, respectively. Relative peripheral myopia was significantly increased after the treatment, with more myopic refraction in the temporal side. RPR changes in UZ2, UZ3, UZ4, LZ1, and LZ2 were related to the amount of lens decentration (r ≈ 0.4, P < 0.05). All HOAs increased after lens fitting (around 0.03 um, 0.02 um, 0.04 um, and 0.41 um for SA, horizontal COMA, vertical COMA, and RMSHOA in the periphery region). Conclusions: RPR and HOAs are related to lens decentration, which might contribute to the efficacy of orthokeratology. Translational Relevance: The study found a decentration-related optical feature after 1 month of lens wear, which is a suggested protective factor in myopia treatment. The findings might provide new insights for customized contact lens myopia treatment based on optics.

Two-dimensional peripheral refraction in adults.

Peripheral refraction has been studied for decades; however, its detection and description are somehow simplistic and limited. Therefore, their role in visual function and refractive correction, as well as myopia control, is not completely understood. This study aims to establish a database of two-dimensional (2D) peripheral refraction profiles in adults and explore the features for different central refraction values. A group of 479 adult subjects were recruited. Using an open-view Hartmann-Shack scanning wavefront sensor, their right naked eyes were measured. The overall features of the relative peripheral refraction maps showed myopic defocus, slight myopic defocus, and hyperopic defocus in the hyperopic and emmetropic groups, in the mild myopic group, and in other myopic groups, respectively. Defocus deviations with central refraction vary in different regions. The defocus asymmetry between the upper and lower retinas within 16° increased with the increase of central myopia. By characterizing the variation of peripheral defocus with central myopia, these results provide rich information for possible individual corrections and lens design.

Relative Myopic Defocus in the Superior Retina as an Indicator of Myopia Development in Children.

Purpose: To investigate the role of peripheral refraction in children's myopization. Methods: This 2-year study included 214 children (8-15 years old). Refraction across the retina (field of view: 60° × 36°) was measured with a custom-made aberrometer every year. Three datasets were established: dataset 1, 214 subjects from baseline to the first-year visit; dataset 2, 152 subjects from baseline to the second-year visit; and dataset 3, 59 initial emmetropes from baseline to the second-year visit. The baseline refraction of different retina regions was correlated with the central myopic shift, and was compared among groups with different levels of myopic shift. Results: In datasets 1 and 2, the refraction distribution across the retina was significantly different among the subjects who were initially emmetropes but not among those who were initially hyperopic or myopic. Refraction in the central vertical retina, especially in the superior retina (r = -0.5, P < 0.001), was significantly correlated with the myopic shift for emmetropes in that subjects with more relative myopia in the superior retina manifested greater central myopic shifts. In dataset 3, 21 subjects remained emmetropic after 2 years, 15 subjects became myopic at the 1-year visit, and 23 subjects became myopic at the 2-year visit. No difference was found for the relative peripheral refraction in all of the peripheral regions between the stage prior to and after the onset of myopia. Conclusions: Relative myopic defocus in the superior retina could be a predictor of central myopia shift. Changes in relative peripheral refraction are more likely a consequence of myopia progression rather than a cause.

Two-Dimensional Peripheral Refraction and Image Quality for Four Types of Refractive Surgeries.

PURPOSE: To provide a comprehensive investigation of the optical quality across the visual field for current mainstream types of refractive surgeries. METHODS: Sixty eyes from 60 adults who received refractive surgery of either femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), Q-value guided customized laser in situ keratomileusis (Q-LASIK), small incision lenticule extraction (SMILE), or Implantable Collamer Lens (ICL) (STAAR Surgical) implantation were included in this study. Refraction and optical aberrations from a visual field of horizontal 60° (from temporal 30° to nasal 30°) and vertical 36° (from superior 20° to inferior 16°) were measured using a custom-made Hartmann-Shack wavefront peripheral sensor. Refractive error, higher order aberrations, point spread function (PSF), and Strehl ratio were compared among these groups prior to and after the surgical procedures, respectively. RESULTS: All types of surgical procedures achieved an almost plano refraction in the central retina. This was also the case in the peripheral retina for the three types of laser refractive surgeries. However, residual peripheral relative hyperopic defocus was observed after ICL implantation. In all groups prior to the surgery, PSFs showed increasing distortion with eccentricity and arrow-like shape pointing toward the central fovea in the periphery in diagonals. Degradation of the PSFs was diminished by all three types of laser refractive surgeries, whereas ICL implantation made the peripheral distortion more prominent. CONCLUSIONS: Although ICL implantation produced a similar impact on refractive correction and objective optical quality in the central vision compared with other laser refractive surgeries, its outcome on the peripheral optics is different. The impact of this difference on visual performance deserves notice and warrants further investigation. [J Refract Surg. 2023;39(1):40-47.].

HOXC10 indicates poor survival outcome in gastric cancer and promotes G1/S cell cycle transition through transcriptional repression of p21.

Homeobox (HOX) genes encode proteins that function as transcription factors during embryogenesis and tumorigenesis. We have previously reported upregulation of HOXC10 in gastric cancer (GC) tissues using cDNA microarray analysis. Though the functional role of HOXC10 in GC has been briefly reported, its specific mechanism is not fully understood. We analyzed the expression of HOXC10 in GC tissues, as well as its correlation with the survival outcome. By in vitro and in vivo assays, we further investigated the role of HOXC10 on cell cycle control and proliferation. Finally, we screened potential downstream targets of HOXC10 by cDNA microarray and explored the role of HOXC10 in p21 transcriptional repression through a dual luciferase reporter and chromatin immunoprecipitation. We illustrated the upregulation of HOXC10 in GC tissues and high HOXC10 expression related to poor survival outcome. Multivariable COX regression analysis showed that HOXC10 was an independent predictor of survival (HR=1.863; 95% CI: 1.076-3.225). Functionally, HOXC10 could promote GC cell proliferation and tumor growth in nude mice. Overexpression of HOXC10 accelerated G1/S cell cycle transition, whereas knocking down HOXC10 induced cell cycle arrest at the G1 phase. Critical factors of G1/S cell cycle transition including p21, CDK2, and c-Myc, were regulated by HOXC10. Importantly, an inverse correlation between p21 and HOXC10 expression in GC cell lines and tissues was observed. HOXC10 could directly bind to the promoter region of p21 and repress its transcriptional activity. Collectively, we identified HOXC10 as a predictor of poor prognosis in GC patients, and a novel transcriptional regulator of p21 in the G1/S cell cycle transition.

Transcutaneous Electrical Acustimulation Improves Irritable Bowel Syndrome With Constipation by Accelerating Colon Transit and Reducing Rectal Sensation Using Autonomic Mechanisms.

INTRODUCTION: Slow colon transit and visceral hypersensitivity are recognized as major pathophysiological mechanisms in irritable bowel syndrome with constipation (IBS-C). However, there is a lack of therapies targeting both abdominal pain and colonic motility. This study was designed to investigate the long-term effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) in patients with IBS-C. METHODS: Fifty-two patients with IBS-C were randomized into 2 groups: daily TEA for 4 weeks (n = 26) and daily sham-TEA for 4 weeks (n = 26). The number of complete spontaneous bowel movements per week (CSBMs/week, primary outcome), Irritable Bowel Syndrome Severity Scoring System, Patient Assessment of Constipation Quality of Life, visual analog scale (VAS) pain score, colonic transit time, and anorectal physiology were evaluated before treatment and at the end of the treatment. Colonic transit was assessed with radiopaque markers. Electrocardiograms were recorded for assessing autonomic functions. RESULTS: (i) TEA improved constipation and abdominal pain. After the treatment, the number of CSBMs/week during the last week in the TEA group was higher than that in the sham-TEA group (3.5 ± 1.6 vs 2.3 ± 0.6, P = 0.002). Similar effects were also noted in the visual analog scale pain score ( P = 0.002) and Irritable Bowel Syndrome Severity Scoring System score ( P = 0.025). In addition, there was a significant improvement in the quality of life of patients with constipation. The Patient Assessment of Constipation Quality of Life total score was significantly decreased in the TEA group ( P = 0.004). (ii) Compared with sham-TEA, TEA improved colon transit ( P = 0.002) and increased the threshold of rectal sensation (desire to defecate, P = 0.004; maximum tolerability, P < 0.001). (iii) TEA increased vagal activity, compared with sham-TEA ( P < 0.05); at the end of the treatment, the vagal activity was significantly correlated with colon transit and the CSBMs/week. DISCUSSION: TEA improves constipation and symptoms of IBS by accelerating colon transit and reducing rectal sensation, possibly mediated by using the autonomic mechanisms.

Instrument for fast whole-field peripheral refraction in the human eye.

An instrument for fast and objective measurement of the peripheral refraction in the human eye is presented. The apparatus permits the automatic estimation of both defocus and astigmatism at any retinal eccentricity by scanning a near infrared beam. The design includes a Hartmann-Shack wavefront sensor and a steering mirror, which operate in combination with a compounded eyepiece for wide field operation. The basic scanning protocol allows the estimation of refraction in a circular retinal patch of 50 deg diameter (±25 from central fixation) in 3 sec. Combined with additional fixation points, wider retinal fields can be sampled to achieve a whole field. The instrument underwent calibration and testing, and its performance for real eyes was assessed in 11 subjects of varying age and refraction. The results show high repeatability and precision. The instrument provides a new tool for the investigation of peripheral optics in the human eye.

Prodrug polymeric micelles integrating cancer-associated fibroblasts deactivation and synergistic chemotherapy for gastric cancer.

BACKGROUND: The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy. METHODS: Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo. RESULTS: Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC. CONCLUSION: TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC.

Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer.

INTRODUCTION: Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). METHODS: mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis­associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. RESULTS: Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan-Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. CONCLUSIONS: We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It's assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

"Sweet tooth"-oriented SN38 prodrug delivery nanoplatform for targeted gastric cancer therapy.

Most cancer cells employ overexpression of glucose transports (GLUTs) to satisfy glucose demand ("Sweet Tooth") for increased aerobic glycolysis rates. GLUT1, one of the most widely expressed GLUTs in numerous cancers, was identified as a prognosis-related biomarker of gastric cancer via tissue array analysis. Herein, a "Sweet Tooth"-oriented SN38 prodrug delivery nanoplatform (Glu-SNP) was developed for targeted gastric cancer therapy. For this purpose, a SN38-derived prodrug (PLA-SN38) was synthesized by tethering 7-ethyl-10-hydroxycamptothecin (SN38) to biocompatible polylactic acid (PLA) with the appropriate degree of polymerization (n = 44). The PLA-SN38 conjugate was further assembled with glycosylated amphiphilic lipid to obtain glucosamine-decorated nanoparticles (Glu-SNP). Glu-SNP exhibited potent antitumor efficiency both in vitro and in vivo through enhanced cancer cell-specific targeting associated with the overexpression of GLUT1, which provides a promising approach for gastric cancer therapy.

Two-dimensional peripheral refraction and retinal image quality in orthokeratology lens wearers.

Orthokeratology (O-K) is a common procedure that uses rigid contact lenses to reshape the cornea while worn overnight. Beyond the correction of refractive error, it has been suggested that this approach can also be used to reduce myopia progression, possibly because it induces changes in peripheral optics. As this hypothesis remains unproven, the aim of the present study was to explore changes in peripheral retinal optical quality in a group of myopic children following O-K treatment. We provide a comprehensive description of optical characteristics in a group of myopes before and after achieving stable corneal reshaping using overnight O-K lenses. These characteristics extended across the central visual field (60° horizontal x 36° vertical) as measured with a custom Hartmman-Shack wavefront sensor. After corneal reshaping, peripheral refraction was found to be asymmetrically distributed, with a myopic relative refraction of approximately 3D in the temporal retina. Astigmatism and higher order aberrations also increased in the temporal side. Based on corneal topography following treatment, subjects were divided into two groups: Centred Treatment (CT, decentration ∈ [-0.5 + 0.5] mm) and Slightly Decentred Treatment (subjects with more decentred lenses). The process was also modelled by ray-tracing simulation. The results indicate that increased myopia in the temporal retina is caused by the decentration of lenses towards the temporal side. Peripheral optics differ significantly following O-K lens treatment, but further research is required to determine whether this is likely to affect myopia progression.

Effect of Cuttlebone on Healing of Indomethacin-Induced Acute Gastric Mucosal Lesions in Rats.

The continuing use of nonsteroidal anti-inflammatory drugs (NSAIDs) usually increases the side effects such as peptic ulcer and acute gastric lesions in the gastrointestinal tract. Cuttlebone (CB), isolated from Sepiella maindroni de Rochebrune, was reported to have antioxidant activities, but its role in the treatment of indomethacin-induced gastric lesions has not yet been confirmed. In this research, we investigate the protective effect of cuttlebone on indomethacin-related ulcers in rats and possible mechanisms. Here, gastric ulcers were induced by oral administration of indomethacin, and then the rats were treated with omeprazole (4 mg/kg) or different doses (750, 1500, and 3000 mg/kg of body weight) of cuttlebone. We evaluated lesion index, inflammation score, and a series of oxidant/antioxidant parameters. The data demonstrated that cuttlebone could protect against gastric ulcers induced by indomethacin in a dose-dependent manner (positive correlation). Also, these effects were associated with attenuating the expression of malonaldehyde (MDA) and increasing the levels of some protective ingredients like epidermal growth factor (EGF), prostaglandin E2 (PGE2), and superoxide dismutase (SOD). Thus, considering its ability to protect indomethacin-induced acute gastric mucosal lesions and the underlying mechanisms, CB might be a potential candidate for treating gastric damage caused by NSAIDs.

Two-Dimensional, High-Resolution Peripheral Refraction in Adults with Isomyopia and Anisomyopia.

Purpose: The purpose of this study was to investigate the two-dimensional peripheral refraction in fellow eyes of patients with isomyopia and anisomyopia. Methods: Sixty-eight young adults were recruited, including 25 isomyopes with interocular differences (IODs) of foveal refraction < 1.00 D and 43 anisomyopes with IOD > 1.50 D. Peripheral refraction across an area of the visual field of 60° × 36° with a resolution of 1° was measured using a custom-made Hartmann-Shack wavefront sensor. The retinal area was divided into 3 × 3 zones for comparison between the fellow eyes. Results: There was no difference of refraction in all corresponding zones between the fellow eyes in the isomyopic group (all P > 0.05). The IODs between more myopic (MM) eyes and less myopic (LM) eyes in the anisomyopic group ranged from -1.40 to approximately -2.46 D (all P <0.001), which was flagged in the center and attenuated in peripheral zones by varied magnitudes. In the stratification analysis for different levels of anisomyopia, the nasal retina first presented significant relative hyperopic shifts compared to the center, followed by the temporal retina. In contrast, the superior and inferior periphery only differed from the center when the central IOD was greater than 3.00 D. Conclusions: The two-dimensional peripheral refraction patterns showed a mirror symmetry between the fellow eyes of a patient with isomyopia. However, in the anisomyopic group, peripheral refraction showed significantly relative hyperopic shift when compared with the center and developed with a varied rate in different areas. These findings may indicate an asymmetrical variation in the peripheral refraction patterns during myopia progression.

MiR-129-5p induces cell cycle arrest through modulating HOXC10/Cyclin D1 to inhibit gastric cancer progression.

MicroRNAs (miRNAs) play important roles in posttranscriptional regulation and may serve as targets for the diagnosis and treatment of cancers. Nevertheless, a comprehensive understanding of miRNAs profiles in gastric cancer progression is still lacking. Here, we report that miR-129-5p is downregulated in gastric cancer by analyzing TCGA database (n = 41) and clinical tumor samples (n = 60). MiR-129-5p transfection suppressed gastric cancer cell proliferation through inducing G1 phase arrest in vitro and inhibit xenograft tumor growth in vivo. MiR-129-5p directly targeted the 3' untranslated regions (3' UTR) of HOXC10 mRNA and downregulated its expression. Importantly, miR-129-5p could reverse the oncogenic effect induced by HOXC10. We systemically screened the downstream target of HOXC10 by ChIP sequencing, and found that HOXC10 could transcriptionally regulate the expression of Cyclin D1 and facilitate G1/S cell cycle transition. Notably, high levels of HOXC10 and Cyclin D1 were related with poor prognosis of gastric cancer patients (n = 90). These findings reveal a novel role of miR-129-5p/HOXC10/Cyclin D1 axis in modulating cell cycle and gastric tumorigenesis, which might provide potential prognostic biomarkers and therapeutic targets for gastric cancer patients.

The Adaptation and Acceptance of Defocus Incorporated Multiple Segment Lens for Chinese Children.

PURPOSE: We investigated the adaptability and acceptance of a novel spectacle lens design that was recently reported to achieve a significant antimyopia effect. DESIGN: A prospective, cross-over study. METHODS: Twenty children were recruited to wear both Defocus Incorporated Multiple Segments (DIMS) and single vision (SV) lens, with a random assignment of which type of lens was experienced first. For each type of lens, high and low contrast central distant visual acuity (VA) and high contrast mid-peripheral near VA were measured at both 500 lux and 50 lux ambient illuminance after 30 minutes' and a week's wearing of the lens. A self-developed questionnaire was applied to evaluate the visual discomfort at the 1-week visit. All quantitative data were analyzed by paired t test, while qualitative data were analyzed with the χ2 or Wilcoxon signed-rank tests. RESULTS: Central VA was not affected by DIMS lens compared with SV lens in all circumstances (all P > .05). However, the mid-peripheral near VA was found to reduce by approximately 0.06 logarithm of minimal angle of resolution unit in 2 of 4 quadrants (500 lux; P < .05) and in 3 quadrants (50 lux; P < .05) for DIMS lenses. No improvement was detected in the 1-week visit. Mid-peripheral blurred vision was the main visual complaint, which was noticed only once or twice a day. Being aware of the average antimyopic efficacy, 90% of children subjects preferred DIMS lenses. CONCLUSION: Mid-peripheral vision through DIMS lenses was slightly affected compared with SV lenses. Otherwise, DIMS lenses received good tolerance and acceptance by Chinese children.

An Objective Comparison of Light Intensity and Near-Visual Tasks Between Rural and Urban School Children in China by a Wearable Device Clouclip.

PURPOSE: To compare light intensity and near-visual tasks objectively between rural and urban children. METHODS: Clouclip, a wearable device, was applied to assess metrics of these two factors in 78 fifth-grade students from an urban and from a rural school. RESULTS: The light intensity experienced by urban students was found significantly lower both in the school period (614.05 ± 178.77 vs. 918.41 ± 257.81 lux, P < 0.001) and on the weekend (444.53 ± 216.65 vs. 882.21 ± 536.67 lux, P < 0.001). The duration of exposure to bright light (>1000 lux) was also substantially shorter for urban students. Although no significant difference was found in near work-related behaviors during the school period and the weekend, for the after-school period the urban students had a shorter average viewing distance (30.94 ± 4.14 vs. 34.81 ± 3.93 cm, P < 0.001), a longer accumulated duration of near work (2.25 ± 0.53 vs. 1.95 ± 0.46 hours, P = 0.010), a greater time ratio of near work (56% ± 14% vs. 49% ± 14%, P = 0.045), and a greater time ratio of excessively close near work (49% ± 13% vs. 40% ± 12%, P = 0.001). CONCLUSIONS: Our data indicate there were substantial differences in light exposure and near-work metrics between the two regions. The correlation between these differences and the discrepancy in regional myopia prevalence needs further investigation. TRANSLATIONAL RELEVANCE: The objective quantification of these metrics might help explain the varied myopia prevalence among regions.

Two-dimensional Peripheral Refraction and Retinal Image Quality in Emmetropic Children.

The relationship between the optical properties of the eye in the periphery and myopia development is still under debate. To further clarify this issue, we provide here baseline data of two-dimensional peripheral optics results in a group of emmetropic Chinese children. Peripheral aberrations were measured under cycloplegia by using an open-view Hartmann-Shack wavefront sensor (VPR, Voptica SL, Spain). This instrument allows to measure fast in the horizontal visual field from temporal 30° to nasal 30° every 1°. Two-dimensional (2D) maps were retrieved from a series of horizonal scans taken every 4° from 20° superior to 16° inferior covering a visual field of 60 × 36°. A relatively homogeneous pattern of the 2D relative peripheral refraction was found across all these emmetropic subjects. Using cluster analysis followed by manual visual refinement, the 2D maps were identified to fit into four categories. More than 70% of the subjects showed a nearly flat horizontal refraction with a slightly myopic shift in the superior retina. Peripheral astigmatism was quite constant across subjects and similar to that expected theoretically. Peripheral aberrations were also similar to those in the fovea for a large retinal area. These baseline data would offer an important reference to compare with the future evolution with time, as well as with other refractive or age groups of subjects, to better understand the role of peripheral optical properties in myopia development.

Klotho-mediated targeting of CCL2 suppresses the induction of colorectal cancer progression by stromal cell senescent microenvironments.

Senescent microenvironments play an important role in tumor progression. Here, we report that doxorubicin (DOX)-pretreated or replicative senescent stromal cells (WI-38 and HUVEC) promote colorectal cancer (CRC) cell growth and invasion in vitro and in vivo. These pro-tumorigenic effects were attenuated by exogenous administration of Klotho, an anti-aging factor. We subsequently identified several senescence-associated secretory phenotype (SASP)-associated genes, including CCL2, which were significantly upregulated in both types of senescent stromal cells during replication and DNA damage-induced senescence. Importantly, we found that the secretion of CCL2 by senescent stromal cells was significantly higher than that seen in nonsenescent cells or in senescent cells pretreated with Klotho. Notably, CCL2 was found to accelerate CRC cell proliferation and invasion, while this effect could be blocked by administration of a specific CCR2 antagonist. We further show that Klotho can suppress NF-κB activation during DOX-induced senescence and thus block CCL2 transcription. Low expression of Klotho, or high expression of CCL2 in patient tumor tissues, correlated with poor overall survival of CRC patients. Collectively, our findings suggest that senescent stromal cells are linked to progression of CRC. Klotho can suppress the senescent stromal cell-associated triggering of CRC progression by inhibiting the expression of SASP factors including CCL2. The identification of key SASP factors such as CCL2 may provide potential therapeutic targets for improving CRC therapy.

Prognostic value of resected lymph nodes numbers for Siewert II gastroesophageal junction cancer.

We aim to evaluate whether resected lymph nodes (RLNs) numbers have prognostic value in patients with gastroesophageal junction cancers (GEJ, Siewert type II). Patients with gastroesophageal junction cancers were identified from the Surveillance Epidemiology and End Results (SEER) registry between 1988 to 2013. Multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze risk factors for overall survival (OS) and cause-specific survival(CSS). A total of 8396 patients who underwent surgeries and had reginal lymph nodes examined were identified. Kaplan-Meier analysis indicated that more numbers of resected lymph nodes (RLNs) were associated with better survival. The five-year OS rates for 1-20 and 21-90 RLNs were 26.8% and 32.4%, with a median survival time of 62 and 72 months, respectively (P < 0.001). The five-year CSS rates were 32.2% and 37.2% in each group, with median survival time of 90 and 101 months, respectively (P < 0.001). Cox regression multivariate analysis showed that year of diagnosis, age, sex, marital status, grade, seer histology, tumor histology, lymph node ratio (LNR) and RLNs as a categorical variable were all significant prognostic factors for both OS and CSS. RLN count is an independent prognostic factor for Siewert type II GEJ cancer patients and patients can achieve better overall and cancer-specific survival with more than 20 RLNs dissected.

Validation of the American Joint Committee on Cancer (AJCC) 8th edition stage system for gastric cancer patients: a population-based analysis.

BACKGROUND: Our aim was to validate the American Joint Committee on Cancer (AJCC) 8th edition stage system for gastric cancer in the Western world and to compare several modifications between the 7th and 8th edition systems. METHODS: Eligible patients having undergone surgical resection of gastric cancer during 2004-2011 from the Surveillance, Epidemiology, and End Results (SEER) database were included in the current study. Survival differences were assessed by Kaplan-Meier curve and log-rank tests. The discriminative power of the AJCC 8th and 7th editions was compared by Harrell's concordance index (c-index). RESULTS: Patients with pN3a and pN3b presented distinct survival outcomes, especially for cases in which more than 15 lymph nodes were examined. The overall (OS) and cancer-specific survival (CSS) c-indices for the 8th edition were largely comparable with c-indices for the 7th edition throughout the cohort. Notably, the new edition improved the power of discrimination slightly in OS and CSS (c-indices: 0.717, 0.744) compared with the 7th edition (c-indices: 0.712, 0.739) for patients for whom 15 or more lymph nodes were examined. The analysis of stage migration in the new edition revealed nonhomogeneous survival outcomes in stages IIIB and IIIC. CONCLUSION: The AJCC 8th stage system for gastric cancer performs as well as the AJCC 7th edition in the United States (USA). Importantly, when more than 15 lymph nodes are examined, the discriminatory performance of the new edition is improved.