Complications of high myopia: An update from clinical manifestations to underlying mechanisms.

Background: High myopia is one of the major causes of visual impairment and has an ever-increasing prevalence, especially in East Asia. It is characterized by excessive axial elongation, leading to various blinding complications that extend beyond mere refractive errors and persist immovably after refractive surgery, presenting substantial public health challenge. Main text: High myopia-related complications include lens pathologies, atrophic and tractional maculopathy, choroidal neovascularization, peripheral retinal degenerations and retinal detachment, and glaucoma and heightened susceptibility to intraocular pressure (IOP) elevation. Pathological lens changes characteristic of high myopia include early cataractogenesis, overgrowth of lens, weakened zonules, and postoperative capsular contraction syndrome, possibly driven by inflammatory pathogenesis, etc. Dome-shaped macula and cilioretinal arteries are two newly identified protective factors for central vision of highly myopic patients. These patients also face risks of open-angle glaucoma and IOP spike following intraocular surgery. Morphologic alternations of optic nerve in high myopia can complicate early glaucoma detection, necessitating comprehensive examinations and close follow-up. Anatomically, thinner trabecular meshwork increases this risk; conversely lamina cribrosa defects may offer a fluid outlet, potentially mitigating the pressure. Notably, anxiety has emerged as the first recognized extra-ocular complication in high myopia, with an underlying inflammatory pathogenesis that connects visual stimulus, blood and brain. Conclusions: High myopia induces multiple ocular and potential mental health complications, underscoring the need to develop more effective strategies to improve both physical and emotional well-being of these patients, among which anti-inflammation might possibly represent a promising new target.

Habitual coffee and tea consumption and risk of cataract: A prospective cohort study from the UK Biobank.

BACKGROUND: To study the association of habitual coffee and tea consumption with the risk of cataract. METHODS: This prospective cohort study enrolled UK Biobank participants between 2006 and 2010, and prospectively followed them up for cataract diagnosis. We examined the associations of self-reported intake of tea and coffee and the calculated combined caffeine intake, with the risk of incident cataract. Cox proportional hazards models were analyzed after adjusting for age, sex, race, diabetes, Townsend Index, income, education, smoking and alcohol status. RESULTS: A total of 444,787 UK Biobank participants aged from 37 to 73 years old who had no cataract at baseline were included. Coffee intake of 2-3 cups/day (HR 0.973, 95% CI 0.949-0.998) or tea intake of 4-6 cups/day (HR 0.962, 95% CI 0.934-0.990) or combination caffeine intake of 160.0-235.0 mg/day (HR 0.950, 95% CI 0.925-0.976) were linked with the lowest risk of incident cataract. Cox models with restricted cubic splines showed J-shaped associations of coffee, tea, and combined caffeine intake with the risk of cataract (all p for nonlinear <0.001). CONCLUSIONS: Moderate habitual consumption of coffee and tea is associated with a lower risk of cataract. To maximize the protective effect against cataract, it is advisable to control total caffeine intake from coffee and tea within a range of 160.0-235.0 mg/day.

[Investigation of influencing factors and reference ranges for thyroid function in hospitalized preterm infants at the age of 7 days]. / 7æ—¥é¾„ä½é™¢æ—©äº§å„¿ç”²çŠ¶è ºåŠŸèƒ½å½±å“å› ç´ åŠå‚è€ƒå€¼èŒƒå›´æŽ¢è®¨.

OBJECTIVES: To investigate the influencing factors and reference ranges for thyroid function in preterm infants at the age of 7 days, with the aim of avoiding unnecessary clinical reexamination and intervention. METHODS: A retrospective analysis was performed for the data of 685 preterm infants from January 2020 to January 2023. According to gestational age and birth weight, they were divided into a high-risk group (gestational age <34 weeks or birth weight<2 000 g; 228 infants) and a low-risk group (gestational age ≥34 weeks and birth weight ≥2 000 g;457 infants). The influencing factors for thyroid function were analyzed, and 95% reference range was calculated. RESULTS: Gestational age, birth weight, birth season, sex, and assisted reproduction were the influencing factors for thyroid function (P<0.05). For the preterm infants in the high-risk group, the reference ranges of free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH) were 2.79-5.40 pmol/L, 8.80-25.64 pmol/L, 0.80-2.15 nmol/L, 50.06-165.09 nmol/L, and 0.80-18.57 µIU/mL, respectively. For those in the low-risk group, the reference ranges of these indicators were 3.08-5.93 pmol/L, 11.17-26.24 pmol/L, 1.02-2.27 nmol/L, 62.90-168.95 nmol/L, and 0.69-13.70 µIU/mL, respectively. FT3, FT4, TT3, and TT4 were positively correlated with gestational age (P<0.05); FT3, FT4, TT3, and TT4 were positively correlated with birth weight (P<0.05); TSH was negatively correlated with birth weight (P<0.05). CONCLUSIONS: Thyroid function in preterm infants at the age of 7 days is affected by the factors such as gestational age and birth weight, and the reference ranges of thyroid function in preterm infants at the age of 7 days should be established based on gestational age and birth weight.

Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia.

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.

Tear inflammatory cytokines as potential biomarkers for myopic macular degeneration.

Previous studies have reported that inflammatory cytokine levels increase in the intraocular fluids (aqueous humor and vitreous) of highly myopic eyes, However, there has been currently no study revealing the levels of inflammatory cytokines in tear. Therefore, this study aimed to determine tear cytokine levels of highly myopic eyes, and their relationships with myopic macular degeneration (MMD). This case-control study screened inflammatory cytokines of tear samples from 132 highly myopic and 105 emmetropic eyes using a multiplex cytokine antibody array, and cytokines showing significant intergroup differences were further validated using ProQuantum immunoassays in tear samples from another 60 highly myopic and 60 emmetropic eyes. Ultra-widefield fundus photographs of eyes were classified according to the meta-analyses of the Pathologic Myopia Classification. Associations between tear cytokine levels and MMD category were investigated. As a result, tear levels of interleukin (IL)-6, IL-13 and monocyte chemoattractant protein (MCP)-1 were screened significantly higher in highly myopic eyes than in emmetropic controls (IL-6: 11.70 ± 16.81 versus 8.22 ± 10.76 pg/mL; MCP-1: 63.60 ± 54.40 versus 33.87 ± 43.82 pg/mL; both P < 0.05). Validation assays further demonstrated the elevated concentrations of IL-6 and MCP-1 (IL-6: 13.97 ± 8.41 versus 8.06 ± 7.94 pg/mL, P < 0.001; MCP-1: 32.69 ± 8.41 versus 18.07 ± 8.41 pg/mL, P = 0.003). Tear levels of IL-6 and MCP-1 differed significantly among MMD categories (both P < 0.05). The area under receiver operating characteristic curve were 0.783 and 0.682 respectively (both P < 0.05), when using tear IL-6 and MCP-1 levels to predict the presence of MMD (category ≥2). The ordered logistic regression model also indicated that longer axial length, and higher IL-6 and MCP-1 tear levels were independent predictors of higher MMD category. In our study, highly myopic eyes presented significantly higher levels of tear IL-6 and MCP-1, which may also serve as potential biomarkers for MMD.

CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety.

High myopia is a leading cause of blindness worldwide. It may lead to emotional defects that rely closely on the link between visual sensation and the central nervous system. However, the extent of the defects and its underlying mechanism remain unknown. Here, we report that highly myopic patients exhibit greater anxiety, accompanied by higher CC chemokine ligand 2 (CCL2) and monocyte levels in the blood. Similar findings are found in the mouse model of high myopia. Mechanistic evaluations using GFP-positive bone marrow chimeric mice, parabiotic mouse model, enhanced magnetic resonance imaging, etc., show that highly myopic visual stimulation increases CCL2 expression in eyes, aggravates monocyte/macrophage infiltration into eyes and brains, and disrupts blood-ocular barrier and blood-brain barrier of mice. Conversely, Ccl2-deficient highly myopic mice exhibit attenuated ocular and brain infiltration of monocytes/macrophages, reduced disruption of the blood-ocular barrier and blood-brain barrier, and less anxiety. Substantial alleviation of high myopia-related anxiety can also be achieved with the administration of CCL2-neutralizing antibodies. Our results establish the association between high myopia and anxiety, and implicate the CCL2-mediated inflammatory pathogenesis as an underlying mechanism.

The gp130/STAT3-endoplasmic reticulum stress axis regulates hepatocyte necroptosis in acute liver injury.

AIM: To investigate the effect of the gp130/STAT3-endoplasmic reticulum (ER) stress axis on hepatocyte necroptosis during acute liver injury. METHODS: ER stress and liver injury in LO2 cells were induced with thapsigargin, and in BALB/c mice with tunicamycin and carbon tetrachloride (CCl4). Glycoprotein 130 (gp130) expression, the degrees of ER stress, and hepatocyte necroptosis were assessed. RESULTS: ER stress significantly upregulated gp130 expression in LO2 cells and mouse livers. The silencing of activating transcription factor 6 (ATF6), but not of ATF4, increased hepatocyte necroptosis and mitigated gp130 expression in LO2 cells and mice. Gp130 silencing reduced the phosphorylation of CCl4-induced signal transducer and activator of transcription 3 (STAT3), and aggravated ER stress, necroptosis, and liver injury in mice. CONCLUSION: ATF6/gp130/STAT3 signaling attenuates necroptosis in hepatocytes through the negative regulation of ER stress during liver injury. Hepatocyte ATF6/gp130/STAT3 signaling may be used as a therapeutic target in acute liver injury.

Role of Optic Nerve Head Characteristics in Predicting Intraocular Pressure Spikes after Cataract Surgery in Highly Myopic Eyes.

INTRODUCTION: To evaluate the characteristics of optic nerve head (ONH) in highly myopic eyes and its role in predicting intraocular pressure (IOP) spikes after cataract surgery. METHODS: Patients who are highly myopic and were scheduled for cataract surgery were enrolled in this prospective case series study. IOP was measured preoperatively and at 1 day and 3 days postoperatively. ONH characteristics including area, tilt ratio, lamina cribrosa (LC) thickness, and depth, and the presence of LC defects were evaluated with enhanced depth imaging optical coherence tomography. Factors influencing LC defects and early IOP spike were investigated using multivariate stepwise logistic regression. RESULTS: In total, 200 highly myopic eyes of 200 patients were analyzed: 35.00% had small ONH, 53.00% had ONH tilt, and 14.00% had LC defects. Multivariate analysis demonstrated female patients with larger ONH area and deeper LC tended to have LC defects (all P < 0.05). As to postoperative IOP, IOP change, and incidence of IOP spikes, eyes with small ONH, ONH tilt, and LC defects had similar (all P > 0.05), higher (all P < 0.05), and lower (all P < 0.05) outcomes compared with those without the corresponding characteristic, respectively. Multivariate analysis showed that presence of LC defects and thicker LC were protective factors for early IOP spikes, and axial length > 28 mm was a risk factor (all P < 0.05). CONCLUSION: Female patients with larger ONH area and deeper LC tend to have LC defects, which, together with thicker LC, was correlated with less IOP spikes in highly myopic eyes. TRIAL REGISTRATION: This study was conducted as part of a larger project, the Shanghai High Myopia Study, registered at www. CLINICALTRIALS: gov (accession number NCT03062085).

The Zhu-Lu formula: a machine learning-based intraocular lens power calculation formula for highly myopic eyes.

BACKGROUND: To develop a novel machine learning-based intraocular lens (IOL) power calculation formula for highly myopic eyes. METHODS: A total of 1828 eyes (from 1828 highly myopic patients) undergoing cataract surgery in our hospital were used as the internal dataset, and 151 eyes from 151 highly myopic patients from two other hospitals were used as external test dataset. The Zhu-Lu formula was developed based on the eXtreme Gradient Boosting and the support vector regression algorithms. Its accuracy was compared in the internal and external test datasets with the Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO) 2.0, Kane, Pearl-DGS and Radial Basis Function (RBF) 3.0 formulas. RESULTS: In the internal test dataset, the Zhu-Lu, RBF 3.0 and BUII ranked top three from low to high taking into account standard deviations (SDs) of prediction errors (PEs). The Zhu-Lu and RBF 3.0 showed significantly lower median absolute errors (MedAEs) than the other formulas (all P < 0.05). In the external test dataset, the Zhu-Lu, Kane and EVO 2.0 ranked top three from low to high considering SDs of PEs. The Zhu-Lu formula showed a comparable MedAE with BUII and EVO 2.0 but significantly lower than Kane, Pearl-DGS and RBF 3.0 (all P < 0.05). The Zhu-Lu formula ranked first regarding the percentages of eyes within ± 0.50 D of the PE in both test datasets (internal: 80.61%; external: 72.85%). In the axial length subgroup analysis, the PE of the Zhu-Lu stayed stably close to zero in all subgroups. CONCLUSIONS: The novel IOL power calculation formula for highly myopic eyes demonstrated improved and stable predictive accuracy compared with other artificial intelligence-based formulas.

LONG-TERM PROGRESSION PATTERN OF MYOPIC TRACTIONAL MACULOPATHY: Outcomes and Risk Factors.

PURPOSE: To evaluate the long-term progression pattern of myopic tractional maculopathy and the risk factors. METHODS: The prevalence and grade of myopic tractional maculopathy were assessed with optical coherence tomography at enrollment and at the 2-year follow-up. The severity of posterior staphyloma and the presence of dome-shaped macula were also evaluated. RESULTS: In total, 610 highly myopic eyes of 610 patients were analyzed. The prevalence of epiretinal membrane, myopic retinoschisis, and macular hole increased from 26.7%, 12.1%, and 4.4% at enrollment to 41.1%, 18.2%, and 9.5% at the 2-year follow-up, respectively. Epiretinal membrane progressed in 21.8% of eyes, but visual acuity did not decline significantly in these eyes. Myopic retinoschisis progressed in 6.8% of eyes, and macular hole progressed in 14.8% of eyes. Significantly greater best-corrected visual acuity reduction was detected in the eyes with myopic retinoschisis or macular hole progression than the rest ( P < 0.05). Multivariate analysis showed that longer axial length, more-severe posterior staphyloma, and absence of dome-shaped macula were associated with myopic tractional maculopathy progression. CONCLUSION: In highly myopic eyes, long-term visual acuity was relatively stable in those with epiretinal membrane, but was significantly affected by myopic retinoschisis or macular hole progression. Longer axial length, more-severe posterior staphyloma, and absence of dome-shaped macula were risk factors for myopic tractional maculopathy progression.

Identification of NPF Family Genes in Brassica rapa Reveal Their Potential Functions in Pollen Development and Response to Low Nitrate Stress.

Nitrate Transporter 1/Peptide Transporter Family (NPF) genes encode membrane transporters involved in the transport of diverse substrates. However, little is known about the diversity and functions of NPFs in Brassica rapa. In this study, 85 NPFs were identified in B. rapa (BrNPFs) which comprised eight subfamilies. Gene structure and conserved motif analysis suggested that BrNFPs were conserved throughout the genus. Stress and hormone-responsive cis-acting elements and transcription factor binding sites were identified in BrNPF promoters. Syntenic analysis suggested that tandem duplication contributed to the expansion of BrNPFs in B. rapa. Transcriptomic profiling analysis indicated that BrNPF2.6, BrNPF2.15, BrNPF7.6, and BrNPF8.9 were expressed in fertile floral buds, suggesting important roles in pollen development. Thirty-nine BrNPFs were responsive to low nitrate availability in shoots or roots. BrNPF2.10, BrNPF2.19, BrNPF2.3, BrNPF5.12, BrNPF5.16, BrNPF5.8, and BrNPF6.3 were only up-regulated in roots under low nitrate conditions, indicating that they play positive roles in nitrate absorption. Furthermore, many genes were identified in contrasting genotypes that responded to vernalization and clubroot disease. Our results increase understanding of BrNPFs as candidate genes for genetic improvement studies of B. rapa to promote low nitrate availability tolerance and for generating sterile male lines based on gene editing methods.

Error correction for Mueller matrix ellipsometry based on a reference optical path.

To reduce the error induced by light source fluctuations, motor rotation instability, environment, and other factors in real-time measurements using dual-rotating compensator Mueller matrix ellipsometry (DRC-MME), an error-correction method based on a reference optical path is proposed. A modified Mueller matrix expression was derived theoretically by introducing the reference optical path of the DRC-MME system. Simulation analysis and experimental verification of the air, polarizer, and S i O 2 samples were performed using this method. The absolute error of the Mueller matrix elements of the S i O 2 samples decreased from less than 0.028 to less than 0.008, and the standard deviation decreased from 0.9% to 0.3%. This method has certain guiding significance in improving the measurement accuracy of DRC-MME.

Single-cell RNA sequencing: Inhibited Notch2 signalling underlying the increased lens fibre cells differentiation in high myopia.

High myopia is the leading cause of blindness worldwide. It promotes the overgrowth of lens, which is an important component of ocular refractive system, and increases the risks of lens surgery. While postnatal growth of lens is based on the addition of lens fibre cells (LFCs) supplemented by proliferation and differentiation of lens epithelial cells (LECs), it remains unknown how these cellular processes change in highly myopic eyes and what signalling pathways may be involved. Single-cell RNA sequencing was performed and a total of 50,375 single cells isolated from the lens epithelium of mouse highly myopic and control eyes were analysed to uncover their underlying transcriptome atlas. The proportion of LFCs was significantly higher in highly myopic eyes. Meanwhile, Notch2 signalling was inhibited during lineage differentiation trajectory towards LFCs, while Notch2 predominant LEC cluster was significantly reduced in highly myopic eyes. In consistence, Notch2 was the top down-regulated gene identified in highly myopic lens epithelium. Further validation experiments confirmed NOTCH2 downregulation in the lens epithelium of human and mouse highly myopic eyes. In addition, NOTCH2 knockdown in primary human and mouse LECs resulted in enhanced differentiation towards LFCs accompanied by up-regulation of MAF and CDKN1C. These findings indicated an essential role of NOTCH2 inhibition in lens overgrowth of highly myopic eyes, suggesting a therapeutic target for future interventions.

The relationships between lens diameter and ocular biometric parameters: an ultrasound biomicroscopy-based study.

Purpose: This study aims to explore the relationships between lens diameter (LD) measured with ultrasound biomicroscopy (UBM) and ocular biometric parameters. Methods: Ocular biometric parameters including axial length (AL), white-to-white distance (WTW), anterior chamber depth (ACD), lens thickness (LT) and anterior segment length (ASL) were measured with IOL-Master 700, and the direct measurement of LD was conducted through UBM (ArcScan Insight 100). Relationships between LD and ocular biometric parameters were then investigated. Eyes with AL ≥ 28 mm were defined as eyes with extreme myopia, and eyes with AL < 28 mm were defined as eyes without extreme myopia. Results: A total of 194 eyes from 194 subjects were included. The mean LD was 9.58 ± 0.49 mm, ranging from 8.60 to 10.96 mm. According to univariate analysis, larger LD was associated with elder age, male gender, larger WTW, ACD and ASL (all p < 0.05). Meanwhile, the LD was positively correlated with AL in eyes without extreme myopia (p < 0.05), but not in eyes with extreme myopia (p > 0.05). Backward stepwise regressions revealed that a larger LD was associated with larger WTW, ASL and AL in eyes without extreme myopia (all p < 0.05), while ASL was the only significant variable in eyes with extreme myopia (p < 0.05). Conclusion: Larger WTW, ASL and AL in eyes without extreme myopia, as well as longer ASL in eyes with extreme myopia indicated a larger LD, which provides guidance in personalized surgical choice and promises ideal visual outcomes.

Contrast Sensitivity Function: A More Sensitive Index for Assessing Protective Effects of the Cilioretinal Artery on Macular Function in High Myopia.

Purpose: To assess the benefits of the cilioretinal artery on macular function in high myopia using the quantitative contrast sensitivity function (qCSF) method. Methods: This cross-sectional study was conducted at the Eye and Ear, Nose, and Throat Hospital of Fudan University. In total, 137 highly myopic patients (with axial length [AL] ≥ 26.00 mm) were enrolled and divided into cilioretinal artery absent and present groups based on their fundus photographs. One eye in each patient was randomly selected. Choroid thickness was measured using macular optical coherence tomography. The best-corrected visual acuity (BCVA) was evaluated by Early Treatment Diabetic Retinopathy Study charts, and the area under the log CSF (AULCSF), CSF acuity, and CS at six spatial frequencies were evaluated with the qCSF method. Results: Although no significant BCVA difference was found between the cilioretinal artery absent (97 patients) and present (40 patients) groups, choroid thickness, AULCSF, CSF acuity, and CSF at low and intermediate spatial frequencies (1-6 cycles per degree) were all significantly higher in the cilioretinal artery present group than in the absent group (all P < 0.05). In addition, eyes with temporal cilioretinal arteries exhibited significantly higher AULCSF, CSF acuity, and CSFs at 3 and 6 cycles per degree (all P < 0.05) than those with a nasal one (all P < 0.05). Multivariate analysis showed that better AULCSF was associated with the presence of cilioretinal artery and the interaction of AL and choroid thickness. Conclusions: The cilioretinal artery may associate with the larger choroid thickness in highly myopic eyes and may play a role in preserving qCSF outcomes, which are more sensitive than chart-based acuity tests.

Actual lens positions of three intraocular lenses in highly myopic eyes: an ultrasound biomicroscopy-based study.

AIM: To evaluate the actual lens positions (ALPs) of three intraocular lenses (IOLs) in highly myopic eyes and to identify relevant factors using ultrasound biomicroscopy (UBM). METHODS: Ninety-three highly myopic eyes (93 patients) that underwent uneventful cataract surgery were included: 36 eyes were implanted with Zeiss 409MP IOLs, 27 with Rayner 920H IOLs and 30 with HumanOptics MCX11 IOLs. The prediction error (PE), ALP determined by UBM and the factors associated with ALP at 3 months after surgery were evaluated. RESULTS: The eyes in the MCX11 IOL group had a more hyperopic PE (0.67±0.45 diopters (D)) and greater ALP (4.86±0.39 mm) than those in the 409MP and 920H IOL groups at 3 months after surgery (PE: -0.25±0.54 and -0.16±0.65 D, respectively; ALP: 4.34±0.26 and 4.14±0.32 mm, respectively). The MCX11 IOLs showed more backward bending deformation after surgery than 409MP and 920H IOLs. The radius of curvature of the IOL was negatively correlated with ALP (r=-0.532, p=0.002) in the MCX11 IOL group, but not in the other two groups. Multivariate analysis showed that MCX11 IOLs were more prone to bending in highly myopic eyes with a smaller anterior capsular opening (ß=0.236, p=0.023) and lower implanted power (ß=0.542, p=0.001). CONCLUSION: In highly myopic eyes, IOLs with good capsular support show less backward bending, which result in a more stable lens position and refractive status postoperatively. Severe capsular contraction and low implanted power are risk factors for bending of certain IOLs.

Intracellular alpha-fetoprotein mitigates hepatocyte apoptosis and necroptosis by inhibiting endoplasmic reticulum stress.

BACKGROUND: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies. AIM: To investigate whether and how AFP could regulate ER stress and hepatocyte injury. METHODS: The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence. RESULTS: High levels of intracellular AFP were detected in liver tissues, particularly in the necrotic areas, from patients with chronic liver diseases and mice after carbon tetrachloride (CCl4) administration or induction of ER stress, but not from the controls. The induced intracellular AFP was accompanied by elevated activating transcription factor-6 (ATF6) expression and protein kinase R-like ER kinase (PERK) phosphorylation in mouse livers. ER stress induced AFP expression in LO2 cells and decreased their viability. ATF6, but not PERK, silencing mitigated the ER-stress-induced AFP expression in LO2 cells. Conversely, AFP silencing deteriorated the ER stress-mediated LO2 cell injury and CCl4 administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression. CONCLUSION: ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.

Distribution of Ocular Anterior and Posterior Segment Lengths Among a Cataract Surgical Population in Shanghai.

Purpose: To investigate the distributions of the ocular anterior and posterior segment lengths among a cataract surgical population in Shanghai. Design: Cross-sectional study. Methods: Ocular biometric parameters of 23,462 eyes of 23,462 cataract surgery candidates were reviewed. Axial length (AL), anterior chamber depth (ACD), and lens thickness (LT) were obtained using IOL Master. Anterior segment length (ASL = ACD + LT), posterior segment length (PSL = AL - ASL) and the ratio of ASL to PSL (ASL/PSL) were calculated. Results: The mean ASL was 7.58 ± 0.39 mm, the mean PSL was 17.12 ± 2.64 mm. As the age grew, the ASL increased, and PSL increased firstly then decreased. Male subjects tended to have significantly longer ASL and shorter PSL than female subjects. With the increasing AL, the ASL was firstly decreased to trough at 20-22 mm AL group, then increased gradually, while the PSL increased rapidly. The ASL correlated positively with AL in normal, moderate and highly myopic eyes, negatively in short eyes. The PSL correlated positively with AL across the entire study population. The ASL/PSL was not constant in the eyes with different AL but had a relatively steep downward trend with the increasing AL in the short eyes, then decreased smoothly in normal, moderate and highly myopic eyes. Conclusions: In Chinese cataractous eyes, longer ASL and shorter PSL were associated with elder age and male gender. The change of ASL over AL was not linear, and the ASL was smallest in the eyes with AL of 20-22 mm. The elongation of the eyeball was mainly due to the extension of the posterior segment.

Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells.

Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.