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

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

Myopia prevalence and ocular biometry in children and adolescents at different altitudes: a cross-sectional study in Chongqing and Tibet, China.

OBJECTIVE: To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China. DESIGN: Cross-sectional study. SETTING: The study included children and adolescents aged 6-18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet. PARTICIPANTS: A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study. METHODS: All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6-8, 9-11, 12-14 and 15-18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m)). RESULTS: There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, -0.63 (-2.00, 0.13) vs -0.88 (-2.88, -0.13), p<0.001), shorter AL (23.45±1.02 vs 23.92±1.19, p<0.001), lower prevalence of myopia (39.7% vs 47.6%, p=0.008) and flatter mean curvature power of the cornea (Km, 43.06±1.4 vs 43.26±1.36, p=0.014) than the Chongqing group. Further analysis based on age subgroups revealed that the Tibet group had a lower prevalence of myopia and higher SE in the 12-14, and 15-18 years old groups, shorter AL in the 9-11, 12-14 and 15-18 years old groups, and lower AL to corneal radius of curvature ratio (AL/CR) in all age subgroups compared with the Chongqing group, while Km was similar between the two groups in each age subgroup. Simple linear regression analysis showed that SE decreased with age in both the Tibet and Chongqing groups, with the Tibet group exhibiting a slower rate of decrease (p<0.001). AL and AL/CR increased with age in both the Tibet and Chongqing groups, but the rate of increase was slower in the Tibet group (p<0.001 of both). Multiple linear regression analysis revealed that AL had the greatest effect on SE in both groups, followed by Km. In addition, the children and adolescents in Tibet presented thinner corneal thickness (CCT, p<0.001), smaller white to white distance (WTW, p<0.001), lower IOP (p<0.001) and deeper anterior chamber depth (ACD, p=0.015) than in Chongqing. Comparison of altitude subgroups showed that the prevalence of myopia (p=0.002), SE (p=0.031), AL (p=0.001) and AL/CR (p<0.001) of children at different altitudes was statistically different but the Km (p=0.189) were similar. The highest altitude, Tengchen County, exhibited the lowest prevalence of myopia and greatest SE among children, and the mean AL also decreased with increasing altitude. CONCLUSIONS: Myopia prevalence in Tibet was comparable with that in Chongqing for students aged 6-8 and 9-11 years but was lower and myopia progressed more slowly for students aged 12-14 and 15-18 years than in Chongqing, and AL was the main contributor for this difference, which may be related to higher ultraviolet radiation exposure and lower IOP in children and adolescents at high altitude in Tibet. Differences in AL and AL/CR between Tibet and Chongqing children and adolescents manifested earlier than in SE, underscoring the importance of AL measurement in myopia screening.

Genipin ameliorates diabetic retinopathy via the HIF-1α and AGEs-RAGE pathways.

BACKGROUND: Traditional Chinese medicine (TCM) is useful in disease treatment and prevention. Genipin is an active TCM compound used to treat diabetic retinopathy (DR). In this study, a network pharmacology (NP)-based approach was employed to investigate the therapeutic mechanisms underlying genipin administration in DR. METHODS: The potential targets of DR were identified using the gene expression omnibus (GEO) database. TCM database screening and NP were used to predict the potential active targets and pathways of genipin in DR. Cell viability was tested in vitro to determine the effects of different doses of glucose and genipin on Human Retinal Microvascular Endothelial Cells (hRMECs). CCK-8, CCK-F, colony formation, CellTiter-Lum, Annexin V-FITC, wound healing, Transwell, tube-forming, reactive oxygen species (ROS), and other assay kits were used to detect the effects of genipin on hRMECs during high levels of glucose. In vivo, a streptozotocin (STZ)-mouse intraocular genipin injection (IOI.) model was used to explore the effects of genipin on diabetes-induced retinal dysfunction. Western blotting was performed to identify the cytokines involved in proliferation, apoptosis, angiogenesis, ROS, and inflammation. The protein expression of the AKT/ PI3K/ HIF-1α and AGEs/ RAGE pathways was also examined. RESULTS: Approximately 14 types of TCM, and nearly 300 active ingredients, including genipin, were identified. The NP approach successfully identified the HIF-1α and AGEs-RAGE pathways, with the EGR1 and UCP2 genes, as key targets of genipin in DR. In the in vitro and in vivo models, we discovered that high glucose increased cell proliferation, apoptosis, angiogenesis, ROS, and inflammation. However, genipin application regulated cell proliferation and apoptosis, inhibited angiogenesis, and reduced ROS and inflammation in the HRMECs exposed to high glucose. Furthermore, the retinal thickness in the genipin-treated group was lower than that in the untreated group. AKT/ PI3K/ HIF-1α and AGEs/ RAGE signaling was increased by high glucose levels; however, genipin treatment decreased AKT/ PI3K and AGEs/ RAGE pathway expressions. Genipin also increased HIF-1α phosphorylation, oxidative phosphorylation of ATP synthesis, lipid peroxidation, and the upregulation of oxidoreductase. Genipin was found to protect HG-induced hRMECs and the retina of STZ-mice, based on; 1 the inhibition of UCP2 and Glut1 decreased intracellular glucose, and glycosylation; 2 the increased presence of HIF-1α, which increased oxidative phosphorylation and decreased substrate phosphorylation; 3 the increase in oxidative phosphorylation from ATP synthesis increased lipid peroxidation and oxidoreductase activity, and; 4 the parallel effect of phosphorylation and glycosylation on vascular endothelial growth factor (VEGF), MMP9, and Scg3. CONCLUSION: Based on NP, we demonstrated the potential targets and pathways of genipin in the treatment of DR and confirmed its effective molecular mechanism in vitro and in vivo. Genipin protects cells and tissues from high glucose levels by regulating phosphorylation and glycosylation. The activation of the HIF-1α pathway can also be used to treat DR. Our study provides new insights into the key genes and pathways associated with the prognosis and pathogenesis of DR.

Comparing letrozole and mifepristone pre-treatment in medical management of first trimester missed miscarriage: a prospective open-label non-inferiority randomised controlled trial.

OBJECTIVE: To investigate whether letrozole pre-treatment is non-inferior to mifepristone pre-treatment, followed by misoprostol, for complete evacuation in the medical treatment of first-trimester missed miscarriage. DESIGN: Prospective open-label non-inferiority randomised controlled trial. SETTING: A university-affiliated hospital. POPULATION: We recruited 294 women diagnosed with first-trimester missed miscarriage who opted for medical treatment. METHODS: Participants were randomly assigned to: (i) the mifepristone group, who received 200 mg mifepristone orally followed 24-48 h later by 800 µg misoprostol vaginally; or (ii) the letrozole group, who received 10 mg letrozole orally once-a-day for 3 days, followed by 800 µg misoprostol vaginally on the third (i.e. last) day of letrozole administration. MAIN OUTCOME MEASURES: The primary outcome was the rate of complete evacuation without surgical intervention at 42 days post-treatment. Secondary outcomes included induction-to-expulsion interval, adverse effects, women's satisfaction, number of doses of misoprostol required, duration of vaginal bleeding, pain score on the day of misoprostol administration and other adverse events. RESULTS: The complete evacuation rates were 97.8% (95% CI 95.1%-100%) and 97.2% (95% CI 94.4%-99.9%) in the letrozole and mifepristone groups, respectively (p ≤ 0.001 for non-inferiority). The mean induction-to-tissue expulsion interval in the letrozole group was longer compared with the mifepristone group (15.4 vs 9.0 h) (p = 0.03). The letrozole group had less heavy post-treatment bleeding and an earlier return of menses. There were no statistically significant differences in the number of doses of misoprostol required, the duration of vaginal bleeding, the pain score on the day of misoprostol administration and the rate of other adverse events between the two groups. The majority of the women (91.2% and 93.9% in the letrozole and mifepristone groups, respectively) were satisfied with their treatment option. CONCLUSIONS: Letrozole is non-inferior to mifepristone as a pre-treatment, followed by misoprostol, for the medical treatment of first-trimester missed miscarriage.

Effectiveness and the nomogram of small incision lenticule extraction in the correction of myopic anisometropia in adults.

AIM: To evaluate the safety, effectiveness, and predictability of small incision lenticule extraction (SMILE) for the treatment of anisometropia, and to explore the personalized design scheme of SMILE in correcting adult myopia anisometropia based on the nomogram. METHODS: It's a prospective cohort study. Patients with anisometropic myopia of refractive difference ≥ 2.0 diopters (D) who underwent SMILE between September 2020 and March 2021 were enrolled. Clinical features and visual function were assessed preoperatively and at 1wk, 1, 3, and 6mo after the operation. The examination included tests for uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive errors, effectiveness index (preoperative CDVA/postoperative UDVA), safety index (postoperative CDVA/preoperative CDVA), nomogram and stereoscopic function. Paired t-test, Wilcoxon signed-rank test and repeated-measures analyses of variance were used for continuous variables, and Pearson Chi-squared test was used for categorical variables. RESULTS: The study involved 45 consecutive patients (average age: 25.0±6.9y; 82 out of 90 eyes underwent SMILE, while 8 eyes were not operated). The average preoperative spherical equivalent (SE) was -4.74±0.22 D. Six months after surgery, the effectiveness index was 1.05±0.12, and the safety index was 1.09±0.11. Seventy eyes (85.4%) exhibited SE correction error within ±0.5 D. The percentage of eyes with Titmus stereoscopic function equal to or less than 200″ significantly increased from 55.6% preoperatively to 88.9% postoperatively (P<0.05). There was statistically significant difference between higher myopia eyes and contralateral eyes in average nomogram value/spherical refraction ratio. CONCLUSION: SMILE is safe, effective and predictable in correcting myopic anisometropia, and it improves stereoscopic visual function of anisometropia patients. The precise and individualized design of the nomogram is a vital element to ensure the balance of both eyes after SMILE.

Comprehensive evaluation of functional vision, quality of life, and cognitive ability in pediatric uveitis.

BACKGROUND: Pediatric uveitis may cause severe impairment of vision in children and affect their quality of life as well as cognitive ability. This study aims to evaluate the functional vision, visual-related and health-related quality of life, and cognitive ability in pediatric uveitis. METHODS: Children with uveitis aged 5-16 years old completed six validated instruments to assess functional visual ability with Cardiff Visual Ability Questionnaire for Children (CVAQC), vision-related quality of life with Impact of Vision Impairment for Children (IVI-C), health-related quality of life with Pediatric Quality of Life Inventory (PedsQL), cognitive ability with Chinese Wechsler Intelligence Scale for Children (C-WISC), and depression and anxiety evaluation with Hospital Anxiety and Depression Scale (HAD). RESULTS: The CVAQC, IVI-C, and PedsQL scores of pediatric uveitis were significantly lower than that of normal levels. Full-scale intelligence quotient (IQ) and performance IQ were significantly lower in pediatric uveitis patients with impaired vision in their best eye (visual acuity < 0.3) compared to those with a vision equal to or better than 0.3. Verbal IQ was significantly lower in male pediatric uveitis patients with impaired vision compared to those with a vision equal to or better than 0.3. Additionally, parents of pediatric uveitis patients with impaired vision generally had lower educational levels than parents of those with a vision equal to or better than 0.3. CONCLUSIONS: Impaired vision caused by pediatric uveitis has a significant impact on children's functional visual ability and quality of life. The development of cognitive function in pediatric uveitis is also significantly hindered.

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

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

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

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

Efficacy of cataract surgeries performed during blindness prevention programs in Chongqing, China: a multicenter prospective study.

OBJECTIVE: To determine the efficacy of cataract surgeries in blindness prevention programs in Chongqing. METHODS: During February-December 2019, we prospectively enrolled 487 patients (592 eyes) undergoing cataract surgery during blindness prevention programs in 6 Chongqing district/county hospitals (experimental group) and 481 patients (609 eyes) undergoing cataract surgery in the First Affiliated Hospital of Chongqing Medical University (controls). Uncorrected visual acuity (UCVA), refractive status, best corrected visual acuity (BCVA), slit lamp examination, and visual function/quality of life (VF-QOL) questionnaire scores were evaluated preoperatively, and at 1 and 6 months postoperatively. RESULTS: In the experimental group, UCVA, BCVA, and VF-QOL scores at 1 and 6 months were better than the preoperative values (P < 0.05), but lower than the control-group values (P < 0.05). Rates of good UCVA and BCVA outcomes (≤ 0.5 logMAR) in the experimental group were 76.2% and 87.6%, respectively, at 1 month and 68.9% and 83.1%, respectively, at 6 months. Most eyes in the experimental (82.1%) and control (89.5%) groups had refractive errors within ± 1 D at 1 month. At 6 months, posterior capsule opacification (PCO) was more common in the experimental group (20.9% vs. 15.0%, P < 0.05). At 6 months, the main causes of visual impairment (UCVA > 0.5 logMAR) in the experimental group were uncorrected refractive errors (33.0%), PCO (29.5%), and fundus diseases (33.9%). CONCLUSION: Cataract surgeries in blindness prevention programs in Chongqing significantly improved visual acuity, VF, and QOL, but underperformed compared to surgeries in the tertiary teaching hospital.

Functional and morphological evaluation of the meibomian glands and ocular surface assessment at high altitude.

Purpose: To compare the function and morphology of the meibomian glands and the ocular surface of individuals from highland and lowland. Methods: This was a randomized controlled trial. The study was performed with 104 individuals (51 individuals from the highland and 53 individuals from the lowland). Detailed eye examinations comprising tear meniscus height, lipid layer grading, non-invasive Keratograph tear breakup time (NIKBUT), and scoring of the meibomian glands from the upper and lower eyelids of the individuals were performed by Keratograph 5M (OCULUS, Wetzlar, Germany). Symptoms related to dry eye disease were assessed using the Ocular Surface Disease Index (OSDI). Results: In the highland group, tear meniscus height was lower (P = 0.024), lipid layer grade, as well as all the meiboscores were higher (P < 0.05) than that in the lowland group. The OSDI (P = 0.018) and the percentage of dry eye disease were also higher as compared to that of the lowland group (P = 0.032). The first NIKBUT and average NIKBUT did not differ significantly between groups. The frequency of plugged meibomian gland orifices was greater in the lowland group compared to the highland group (P = 0.036). Conclusion: It was observed that dry eye disease was more common in the highland group. The morphological changes of meibomian gland dropout were significant in highlanders as demonstrated objectively with Keratograph 5M. Our study may raise a concern for environmental influences on ocular surface changes.

Three-Dimensional Quantitative Description of the Implantable Collamer Lens in the Ocular Anterior Segment of Patients With Myopia.

PURPOSE: To describe the 3-dimensional (3D) location of the implantable collamer lens (ICL) quantitatively in the posterior ocular chamber of patients with myopia. DESIGN: Cross-sectional study. METHODS: To obtain visualization models before and after mydriasis, an automatic 3D imaging method based on swept-source optical coherence tomography was created. Parameters like the ICL lens volume (ILV), the tilt of the ICL and crystalline lens, the vault distribution index, and topographic maps were evaluated to describe the ICL location. Using a paired sample t test and the Wilcoxon signed rank test, the difference between nonmydriasis and postmydriasis conditions was compared. RESULTS: The study investigated 32 eyes from 20 patients. The 3D central vault did not differ significantly before (P = .994) or after mydriasis (P = .549) compared with the 2D central vault. After mydriasis, the 5-mm ILV decreased by 0.85 mm2 (P = .016), and the vault distribution index increased significantly (P = .001). The ICL and the crystalline lens exhibited tilt (nonmydriasis: ICL total tilt 3.78 ± 1.85 degrees, lens total tilt 4.03 ± 1.53 degrees; postmydriasis: ICL total tilt 3.84 ± 1.56 degrees, lens total tilt 4.09 ± 1.64 degrees). The phenomenon of asynchronous tilt of the ICL and lens was found in 5 eyes, leading to the spatially asymmetric distribution of the ICL-lens distance. CONCLUSION: The 3D imaging technique provided exhaustive and reliable data for the anterior segment. The visualization models offered multiple perspectives on the ICL in the posterior chamber. Before and after mydriasis, the intraocular ICL position was described by the 3D parameters.

Crosstalk between heat shock factor 1 and signal transducer and activator of transcription 3 mediated by interleukin-8 autocrine signaling maintains the cancer stem cell phenotype in liver cancer.

BACKGROUND AND AIM: Liver cancer stem cells (LCSCs) cause therapeutic refractoriness and relapse in hepatocellular carcinoma. Heat shock factor 1 (HSF1) plays versatile roles in multiple cancers. However, the role of HSF1 in LCSCs is not well understood. This study investigated the function and signal mechanisms of HSF1 in maintaining LCSC phenotypes. METHODS: We established two LCSC lines, HepG2-R and HuH-7-R. Constitutive activation of HSF1 was observed in these LCSCs. Specific short hairpin RNAs (shRNAs) and chemical inhibitors were used to identify the relationship between HSF1 expression and LCSCs phenotypes. RESULTS: We revealed a concomitant activation modality involving HSF1 and STAT3 in LCSCs and liver cancer tissues. We also found that liver cancer patients whose HSF1 and STAT3 mRNA expression levels were high presented with unfavorable clinicopathological characteristics. Moreover, the secretion of interleukin-8 (IL-8) was elevated in the LCSC medium and was directly regulated by HSF1 at the transcriptional level. In turn, IL-8 activated HSF1 and STAT3 signaling, and a neutralizing IL-8 antibody inhibited HSF1 and STAT3 activity, reduced cancer stem cell marker expression, and decreased LCSC microsphere formation. Simultaneous intervention with HSF1 and STAT3 led to synergistically suppressed stemness acquisition and growth suppression in the LCSCs in vivo and in vitro. CONCLUSIONS: Our study indicates that IL-8 mediates the crosstalk between the HSF1 and Stat3 signaling pathways in LCSCs and that the combined targeting of HSF1 and STAT3 is a promising treatment strategy for patients with advanced liver cancer.

Comparisons of visual outcomes between bilateral implantation and mix-and-match implantation of three types intraocular lenses.

PURPOSE: To compare binocular static visual acuity (SVA), stereopsis, contrast sensitivity (CS) and dynamic visual acuity (DVA) of 5 combinations of bifocal intraocular lenses (IOLs), trifocal IOLs and extended-depth-of-focus (EDOF) IOLs in age-related cataract patients. METHODS: Two hundred and ninety-two eyes of 146 patients who underwent cataract surgery in the ophthalmology department of the First Affiliated Hospital of Chongqing Medical University were involved. Subgroups included group MM (33patients, bilaterally bifocal IOL, ZMB00), group TT (31patients, bilaterally trifocal IOL, AT LISA tri839MP), group XX (34patients, bilaterally EDOF IOL, ZXR00), group MX (25patients, bifocal IOL, ZMB00 + EDOF IOL, ZXR00) and group TX (23patients, trifocal IOL, AT LISA tri839MP + EDOF IOL, ZXR00). The uncorrected SVAs (UDVA, UIVA and UNVA), uncorrected DVAs (UDDVA, UIDVA and UNDVA), near and distance stereopsis, and CS were assessed 3 months postoperatively. RESULTS: Subgroups of TT, XX, MX and TX showed better UIVA than MM (bP = 0.039, 0.021, 0.035 and 0.037, respectively). MX showed better UNVA than MM and TX (bP = 0.031 and 0.013, respectively). MX group had the optimal outcomes of both near and distance stereopsis. In the UDDVA, XX group and MX group showed better outcomes than TX group at 24 fps (frames per second) (bP = 0.019 and 0.023, respectively). XX group and MX group showed optimal outcomes at all speeds of UIDVA (P = 0.001, 0.005, 0.003 and 0.005, respectively). As the speed increased, the XX group and the MX group showed better UNDVA than the MM group and the TT group (P = 0.019, 0.002 and 0.003, respectively). CONCLUSIONS: Mix-and-match implantation of bifocal IOLs and EDOF IOLs provides excellent and stable binocular visual outcomes including SVA, stereopsis and DVA in distant and near distances.

Myopia progression and associated factors of refractive status in children and adolescents in Tibet and Chongqing during the COVID-19 pandemic.

Objectives: To investigate myopia progression and associated factors of refractive status among children and adolescents in Tibet and Chongqing in China during the COVID-19 pandemic. Methods: A population-based cross-sectional study was conducted to compare rates of myopia and high myopia, axial length (AL), spherical equivalent (SE), outdoor activity time, digital device use, and frequency of visual examinations for children and adolescents affected by myopia in Chongqing and Tibet in 2021. Results: A total of 2,303 students from Chongqing and 1,687 students from Tibet were examined. The overall prevalence of myopia and high myopia in these two groups were 53.80 and 7.04% vs. 43.86 and 1.30%, respectively in each case. The Chongqing students had a longer AL than the group from Tibet (23.95 vs. 23.40 mm, respectively; p < 0.001). The mean SE of the students with myopic parents in Tibet was lower than that of the students in Chongqing with myopic parents (-2.57 ± 2.38 diopters (D) vs. -2.30 ± 2.34 D, respectively) (p < 0.001). Conversely, the mean SE of the students from urban areas in Chongqing was lower than that of the students in Tibet (-2.26 ± 2.25 D vs. -1.75 ± 1.96 D, respectively; p < 0.001). The Chongqing students exhibited lower SE (-2.44 ± 2.22 D) than their Tibetan counterparts (mean SE: -1.78 ± 1.65 D (p = 0.0001) when spending more than 2.5 h outdoors. For example, 61.35% of the students in Tibet spent more than 2.5 h outdoors daily, compared with 43.04% of the students in Chongqing. Correspondingly, the proportion of students using digital devices in Tibet (64.43%) was lower than that in Chongqing (100%). For the latter, 38.62% of the students in Chongqing spent more than 2.5 h online using digital devices compared to 10.49% of the students in Tibet. Greater monitoring of visual status was observed for the Chongqing students (mean SE: -1.90 ± 1.98 D) compared with students in Tibet (mean SE: -2.68 ± 1.85 D) (p = 0.0448), with the frequency of optimal examinations being every 6 months. Outdoor activity time was identified as a common risk factor for myopia in both of the populations examined, with odds ratios (ORs) of 1.84 (95% CI: 1.79-1.90) in Chongqing and 0.84 (95% CI: 0.73-0.96) in Tibet. Digital screen time was associated with myopia and high myopia in Chongqing, with ORs of 1.15 (95% CI: 1.08-1.22) and 1.06 (95% CI: 0.94-1.77), respectively. Digital screen time was also found to be a risk factor for high myopia in Tibet (OR: 1.21, 95% CI: 0.77-1.61). The type of digital devices used was also associated with myopia and high myopia in Tibet (OR: 1.33, 95% CI: 1.06-1.68 and OR: 1.49, 95% CI: 0.84-2.58, respectively). Finally, examination frequency was found to correlate with high myopia in the Tibet group (OR: 1.79, 95% CI: 0.66-2.71). Conclusion: Based on our data, we observed that the prevalence of refractive errors in children and adolescents was significantly lower in Tibet than in Chongqing. These results are potentially due to prolonged outdoor activity time, and the type and time of use for digital devices that characterize the group of children and adolescents from Tibet. It is recommended that parents and children in Chongqing would benefit from increased awareness regarding myopia progression and its prevention.

The Effectiveness and Rotational Stability of Vertical Implantation of the Implantable Collamer Lens for the Treatment of Myopia.

PURPOSE: To explore the effectiveness and rotational stability of vertical implantation of the Implantable Collamer Lens (ICL) (STAAR Surgical) to treat myopia. METHODS: This was a prospective, randomized, controlled study, including 78 eyes from 46 patients with myopia who underwent ICL implantation. The patients were randomly divided into vertical and horizontal implantation groups. At 1 day, 1 week, 1 month, and 3 months after surgery, rotational stability was evaluated using the postoperative axis deviation from the intended axis by the digital anterior segment photograph. The vault, crystalline lens rise, anterior chamber depth, manifest refraction spherical equivalent, intraocular pressure, and visual acuity values were obtained before and after surgery. RESULTS: A 3-month follow-up period showed significant differences between the efficacy indexes in the horizontal (1.11 ± 0.02) and vertical (1.13 ± 0.02) groups (P = .455). No significant difference was observed in the postoperative manifest refraction spherical equivalent between the horizontal (-0.27 ± 0.18 diopters) and vertical (0.01 ± 0.08 diopters) groups (P = .151). Also, no statistically significant difference was observed in the corneal endothelial cells and intraocular pressure between groups (P = .555, P = .464). The rotation angle of the horizontal group was greater at 1 week, 1 month, and 3 months (3.14° ± 2.13°, 2.97° ± 2.01°, 3.27° ± 2.12°, respectively) compared to that of the vertical group (1.30° ± 1.29°, 1.85° ± 1.60°, 1.74° ± 1.33°, respectively) (P < .001 for all). From 1 week to 3 months, the changing angle of horizontal (0.31° ± 1.86°) and vertical (0.49° ± 1.33°) ICL rotation displayed a positive correlation with the changing vault of horizontal (48.41 ± 86.02 mm) and vertical (39.64 ± 78.43 mm) ICL rotation (r = 0.242, 0.335, P = .033, .037). CONCLUSIONS: The study supports great efficacy and safety in both vertical and horizontal implantation, with the vertical implantation group displaying better stability. [J Refract Surg. 2022;38(10):641-647.].

Extracellular vesicles microRNA-592 of melanoma stem cells promotes metastasis through activation of MAPK/ERK signaling pathway by targeting PTPN7 in non-stemness melanoma cells.

Melanoma, one of the most aggressive malignancies, its high mortality and low survival rates are associated with effective metastatic colonization. Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in MME programing. Published studies show that melanoma EVs can educate MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous cancer cells within the MME that alter the course of metastasis has not been investigated at the mechanistic level. In this study, melanoma parental cells (MPCs) and paired derivative cancer stem cell line melanoma stem cells (MSCs) that were derived from melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for melanoma metastasis. We characterized miR-592, a relatively novel microRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target protein tyrosine phosphatase non-receptor type7 (PTPN7), a phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis, melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC melanoma cells.

Corneal morphological changes after small incision lenticule extraction for myopic anisometropia.

Purpose: This research aims to study the corneal morphological changes in adult patients with myopic anisometropia after small incision lenticule extraction (SMILE) and the safety, efficacy, and predictability of clinical outcomes. Methods: This was a prospective cohort study. Patients with myopic anisometropia [refractive difference >2.0 diopters (D)] were included in this study who underwent SMILE at our hospital from September 2019 to March 2021. For the two eyes of each patient, the one with higher myopia was defined as group A, and the fellow eye was group B. The follow-up time points were set as 1 week, 1 month, 3 months, and 6 months after the surgery. The data collected were uncorrected and best-corrected distance visual acuity (UDVA and CDVA), spherical equivalent (SE), efficacy and safety indexes, posterior corneal elevation (PCE), anterior and posterior corneal radius of curvature in the 3 mm area at the center of the thinnest point of the cornea (ARC and PRC), and higher-order aberrations (HOAs). Results: The study included 36 patients (72 eyes), and the mean age was 25.2 ± 6.4 years. The preoperative SEs were -6.45 ± 1.25 D in group A and -3.76 ± 1.29 D in group B. Six months after surgery, the SEs in groups A and B were -0.09 ± 0.50 D and 0.07 ± 0.47 (P = 0.059), respectively. The efficacy indexes were 1.06 ± 0.16 in group A and 1.07 ± 0.14 in group B (P = 0.750). The safety indexes were 1.08 ± 0.14 in group A and 1.12 ± 0.15 in group B (P = 0.173). The PCE was significantly reduced at 6 months after surgery in pagebreak both groups (P < 0.05). The ARC was significantly higher than before the surgery (P < 0.05) in the two groups. The two groups showed significant increases in total HOAs, coma 90°, and spherical aberrations (P < 0.05). Conclusion: SMILE is predictable, effective, and safe in correcting myopic anisometropia. The postoperative changes in HOAs are characteristic.

Analysis of the Effectiveness of SMILE, FS-LASIK, and SBK in Myopic Patients and the Impact in UCVA and Tear Film Stability.

The aim of the present study was to investigate the effect of femtosecond laser small incision stromal lens extraction (SMILE), femtosecond laser-assisted excimer laser keratomileusis (FS-LASIK), and anterior elastic sublaminar laser keratomileusis (SBK) in myopic patients, and their effects on uncorrected visual acuity (UCVA) and tear film stability. 600 myopic patients admitted to our hospital from January 2020 to December 2021 were selected for the study and divided into SMILE group (200 patients, SMILE treatment), FS-LASIK group (200 patients, FS-LASIK treatment), and SBK group (200 patients, SBK treatment) according to the random number table method. Uncorrected visual acuity (UCVA), tear breakup time (BUT), tear secretion function test (Sit), and corneal higher-order image aberration global higher-order aberration (HOAS) were compared among the three groups. The UCVA values before operation, 2 weeks after operation, 1 month after operation, and 3 months after operation in the three groups were similar, and the BUT, Sit value, and HOAS of corneal higher-order image difference in the three groups were similar, and the differences were not statistically significant (P > 0.05). The BUT, Sit value, and HOAS of corneal higher-order image difference at 1 and 3 months after surgery in the SMILE group were higher than those in the FS-LASIK and SBK groups, and the differences were statistically significant (P < 0.05). SMILE, FS-LASIK, and SBK are effective in the treatment of myopia, which can effectively improve the uncorrected visual acuity and help the patients to recover their normal visual ability, but SMILE is more effective in tear film stability and corneal higher-order aberrations.

The clinical characteristics and prognostic factors of 410 patients with natural killer/T-cell lymphoma.

PURPOSE: To investigate the clinical characteristics and prognostic factors of natural killer/T-cell lymphoma (NKTCL). METHODS: We retrospectively reviewed 410 NKTCL patients admitted to our lymphoma center from 2000 to 2019. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method, and the differences between the study groups were compared by the log-rank test. RESULTS: The median age of the 410 patients was 44 (range 8-84), and the 5-year OS and PFS were 61.2% and 38.4%, respectively. For patients with stage I/II, the 5-year PFS rate was 57.5%, and the 5-year OS rate was 77.2%. For patients with stage III/IV, the 5-year PFS rate was 17.4%, and the 5-year OS rate was 43.7%. Compared to the patients who received radiotherapy alone or chemotherapy alone as their initial treatment, the patients who received combined chemoradiotherapy had longer PFS (P = 0.013). Independent prognostic factors for OS were stage III/IV (P = 0.001), elevated IPI/aaIPI score (P = 0.019), elevated PINK score (P < 0.001) and elevated plasma EBV-DNA (P = 0.003). An elevated PINK score (P < 0.001) was an independent prognostic factor for PFS. CONCLUSION: Stage III/IV, elevated IPI/aaIPI score, elevated PINK score and elevated plasma EBV-DNA were independent prognostic factors for OS. Elevated PINK score was an independent prognostic factor for PFS. In stage III/IV patients, the patients who received combined chemoradiotherapy had significantly longer PFS.

CD5-positive marginal zone lymphoma: Clinicopathological features and survival outcomes.

BACKGROUND: CD5 expression in different B-cell lymphomas has different clinicopathological and prognosis and the value of CD5 expression in marginal zone lymphoma is undefined. METHODS: Clinicopathological features, survival outcomes of marginal zone lymphoma were retrospectively analyzed in 204 patients. We classified patients into (i) CD5-positive marginal zone lymphoma (ii) CD5-negative marginal zone Lymphoma, Fisher's exact test was used to compare the CD5-positive and CD5-negative marginal zone lymphoma. Progression-free survival (PFS) and overall survival (OS) curves were summarized by Kaplan-Meier method and compared using the log-rank test. RESULTS: Of the 204 patients, 48 (23.53%) were CD5-positive. The 5-year PFS and OS rates for CD5-positive marginal zone lymphoma were 64.80% and 84.10%, there was no significant difference between CD5-positive and CD5-negative (P > 0.05). Diffuse large B cell lymphoma (DLBCL) transformation was pathologically indicated in 6 patients, of which 5 (83.33%) patients were CD5-positive marginal zone lymphoma. CONCLUSION: CD5 expression in marginal zone lymphoma is not relevant to the prognosis of the patients, but CD5-positive marginal zone lymphoma seems more likely to transformation to diffuse large B-cell lymphoma.