Inhibition of cisplatin-induced Acsl4-mediated ferroptosis alleviated ovarian injury.

Given that the severity of the chemotherapy-induced ovarian damage, effective fertility preservation is a necessary part of the treatment process. Ferroptosis is a regulated cell death triggered by excessive phospholipid peroxidation caused by iron and the role of ferroptosis in chemotherapy-induced ovarian damage remains unclear. In this study, we demonstrated that cisplatin treatment caused the accumulation of iron ions which induced ferroptosis in ovarian tissue. And our results show that ferrostatin-1 was able to suppress the ovarian injury and granulosa cell death caused by cisplatin (Cis) in vivo and in vitro. At the same time, we observed significant changes in the expression levels of Acyl-CoA synthetase long-chain family member 4 (Acsl4) and glutathione peroxidase 4 (GPX4). Similarly, Rosiglitazone, an inhibitor of Acsl4, administration alleviated the ovary damage of the mice undergoing chemotherapy. Further mechanistic investigation showed that cisplatin increased the expression level of specificity protein 1 (SP1), and SP1 could bind to the promoter of Acsl4 to increased Acsl4 transcription. Overall, ferroptosis plays an important role in Cis induced ovarian injury, and inhibition of ferroptosis protects ovarian tissues from damage caused by cisplatin, and for the first time, we have identified the potential of Fer-1 and Rosi to protect ovarian function in female mice undergoing chemotherapy.

Association between contrast sensitivity function and structural damage in primary open-angle glaucoma.

AIMS: To evaluate the association between contrast sensitivity function (CSF) and glaucomatous structural damage in primary open-angle glaucoma (POAG). METHODS: A cross-sectional study was performed with 103 patients (103 eyes) aged 25-50 years who had POAG without any other ocular disease. CSF measurements were obtained by the quick CSF method, a novel active learning algorithm that covers 19 spatial frequencies and 128 contrast levels. The peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell complex (mGCC), radial peripapillary capillary (RPC) and macular vasculature were measured by optical coherence tomography and angiography. Correlation and regression analyses were used to assess the association of area under log CSF (AULCSF), CSF acuity and contrast sensitivities at multiple spatial frequencies with structural parameters. RESULTS: AULCSF and CSF acuity were positively associated with pRNFL thickness, RPC density, mGCC thickness and superficial macular vessel density (p<0.05). Those parameters were also significantly associated with contrast sensitivity at 1, 1.5, 3, 6, 12, 18 cycles per degree spatial frequencies (p<0.05) and, the lower the spatial frequency, the higher the correlation coefficient. RPC density (p=0.035, p=0.023) and mGCC thickness (p=0.002, p=0.011) had significant predictive value for contrast sensitivity at 1 and 1.5 cycles per degree, with adjusted R 2 of 0.346 and 0.343, respectively. CONCLUSIONS: Full spatial frequency contrast sensitivity impairment, most notably at low spatial frequencies, is a characteristic change in POAG. Contrast sensitivity is a potential functional endpoint for the measurement of glaucoma severity.

Comparative single-center study between modified laparoscopic radical hysterectomy and open radical hysterectomy for early-stage cervical cancer.

BACKGROUND: Since the release of the LACC trial results in 2018, the safety of laparoscopic radical hysterectomy (LRH) for cervical cancer has received huge attention and heated discussion. We developed modified laparoscopic radical hysterectomy (MLRH) incorporating a series of measures to prevent tumor spillage, which has been performed in our center since 2015. OBJECTIVE: Present study retrospectively analyzed relevant indicators of MLRH and evaluated disease-free survival (DFS) primarily in the treatment of early cervical cancer compared with open surgery. METHODS: Patients with 2014 International Federation of Gynecology and Obstetrics clinical stages 1B1 and 2A1 cervical cancer who underwent radical hysterectomy in the gynecological department of our hospital from October 2015 to June 2018 were enrolled retrospectively in this study. Patients were divided into two groups based on the surgical procedure: open radical hysterectomy (ORH) group (n = 336) and MLRH group (n = 302). Clinical characteristics, surgical indices, and survival prognosis were analyzed, including 2.5-year overall survival (OS) rate, 2.5-year DFS rate, recurrence rate, and recurrence pattern. RESULTS: Compared to the ORH group, the MLRH group exhibited a longer operative time, longer normal bladder function recovery time, less intraoperative blood loss volume, and more harvested pelvic lymph nodes (P < 0.05). No significant differences were observed in postoperative complications, the 2.5-year OS, 2.5-year DFS, and recurrence rate between the two groups (P > 0.05); however, the recurrence pattern was significantly different (P < 0.05). The MLRH group mainly exhibited local single metastasis (7/11), whereas the ORH group mainly exhibited distant multiple metastases (14/16). Stratified analysis revealed that overall survival rate was higher in the MLRH group than in the ORH group in patients with stage 1B1 and middle invasion (P < 0.05). CONCLUSION: MLRH does not show a survival disadvantage in the treatment of early-stage cervical cancer when compared with open surgery. In addition, MLRH shows a survival advantage in patients with stage 1B1 and middle 1/3 invasion. Considering this is a retrospective study, further prospective study is necessary for more sufficient data support. TRIAL REGISTRATION: Present research is a retrospective study. The study had retrospectively registered on Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ), and the registered number is ChiCTR1900026306.

Predictors of angle widening after laser iridotomy in Chinese patients with primary angle-closure suspect using ultrasound biomicroscopy.

AIM: To assess the predictive value of baseline parameters of ultrasound biomicroscopy (UBM) for angle widening after prophylactic laser peripheral iridotomy (LPI) in patients with primary angle-closure suspect (PACS). METHODS: Angle-opening distance (AOD), trabecular iris angle (TIA), iris thickness, trabecular-ciliary process angle, and trabecular-ciliary process distance were measured using UBM performed before and two weeks after LPI. Iris convexity (IC), iris insertion, angulation, and ciliary body (CB) size and position were graded. Uni- and multivariate regression analyses were used to determine factors predicting the change in AOD (ΔAOD500, calculated as an angle width change before and after LPI) in all quadrants and in subgroup quadrants based on IC. RESULTS: In 94 eyes of 94 patients with PACS, LPI led to angle widening with increases in AOD500 and TIA (P<0.01). Multivariable regression analysis showed that IC (P<0.001), CB position (P=0.007) and iris insertion (P=0.049) were significantly predictive for ΔAOD500. All quadrants were categorized into extreme IC (27.8%), moderate IC (62.3%), and absent IC (9.9%) subgroups. The AOD500 increased by 220% and no other predictive factor was found in the extreme IC quadrants. The AOD500 increased by 55%, and baseline iris angulation was predictive for smaller changes in ΔAOD500 in the moderate IC quadrants. CONCLUSION: In PACS patients, quadrants with greater iris bowing predict substantial angle widening after LPI. Quadrants with a flatter iris, anteriorly positioned CB, and basal iris insertion are associated with less angle widening after LPI. Quadrants with iris angulation as well as a flatter iris configuration predict a smaller angle change after LPI.

CCDC68 Upregulation by IL-6 Promotes Endometrial Carcinoma Progression.

The elevation of circulating interleukin 6 (IL-6) is one of the major molecular characteristics of endometrial carcinoma. In this study, we investigated the role of coiled-coil domain-containing 68 (CCDC68) in IL-6-associated endometrial carcinoma progression. CCDC68 expression levels and the activation of IL-6 pathway were detected by qPCR and Western blot. Stable CCDC68 knockdown Ishikawa and RL-95 cells were created to investigate cancer cell proliferation, migration, and invasion with or without IL-6 administration. Kaplan-Meier's analysis was used to determine the correlation between CCDC68 expression and overall survival or recurrence-free survival in endometrial carcinoma patients. CCDC68 expression level is significantly uregulated by IL-6 stimulation. Increased CCDC68 expression predicts poor prognosis in endometrial carcinoma patients. CCDC68 knockdown dramatically inhibit IL-6-associated cancer cell proliferation, migration, invasion, and downregulate the expression of proto-oncogenes in endometrial carcinoma cells. CCDC68 acts as a cancer-promoting factor in IL-6-stimulated endometrial carcinoma cells, and blocking the expression of CCDC68 might be a novel therapeutic strategy for the endometrial carcinoma treatment.

Inhibition of cell proliferation and migration after HTRA1 knockdown in retinal pigment epithelial cells.

PURPOSE: The purpose of this study was to investigate the role of HtrA serine peptidase 1 (HTRA1) in the proliferation and migration of cells of the human retinal pigment epithelial cell line ARPE-19, and the possible mechanisms involved. METHODS: ARPE-19 cells were transduced by a recombinant lentiviral vector carrying HTRA1-shRNA to knockdown HTRA1 expression. Subsequent HTRA1 gene and HTRA1 protein levels in these cells and control cells were detected by quantitative real-time PCR and Western blot, respectively. Changes in cell proliferation and migration associated with the inhibition of HTRA1 expression were assessed, as well as changes in the mRNA levels of transforming growth factor beta 1 (TGFB1), bone morphogenetic protein 4 (BMP4), and bone morphogenetic protein 2 (BMP2). RESULTS: The recombinant lentivirus carrying HTRA1-shRNA was successfully generated, as evidenced by reduced levels of HTRA1 mRNA and HTRA1 protein in ARPE-19 cells. The knockdown of HTRA1 in ARPE-19 cells was associated with reduced cellular proliferation and migration, and increased mRNA levels of TGF-ß1, BMP4, and BMP2. CONCLUSIONS: Silence of the HTRA1 gene was associated with significantly higher levels of TGF-ß1, BMP4, and BMP2 mRNA and reduction in the proliferation and migration of ARPE-19 cells.

Morphologic changes in the anterior chamber in patients with cortical or nuclear age-related cataract.

PURPOSE: To assess and compare the morphologic changes in the anterior segment in eyes with nuclear or cortical age-related cataract using Scheimpflug imaging. SETTING: Peking University People's Hospital, Beijing, China. DESIGN: Case-control study. METHODS: Patients with nuclear or cortical age-related cataract were recruited. The grade of nuclear opalescence or cortical opacity was assessed using the Lens Opacities Classification System III (LOCS III). A group of elderly subjects with a clear lens and normal vision served as the control group. Anterior chamber depth (ACD), anterior chamber volume (ACV), and lens thickness were evaluated using Scheimpflug imaging (Pentacam). RESULTS: Two hundred sixty-nine patients (330 eyes) were recruited. Thirty eyes were enrolled for each nuclear opalescence and cortical grade. The control group comprised 30 eyes (19 subjects). In eyes with age-related cataract, lens thickness increased with an increase in cortical opacity, whereas the ACD and ACV values decreased. The ACD was inversely correlated with LOCS III grades for nuclear opalescence (r = -0.197, P = .004), nuclear color (r = -0.195, P = .005), and cortical opacity (r = -0.508, P<.005). There were significant differences in lens thickness, ACD, and ACV between nuclear color, nuclear opalescence, and cortical opacity for LOCS III grades 3, 4, and 5, respectively. CONCLUSIONS: There were significant differences in lens thickness, ACD, and ACV between nuclear and cortical age-related cataracts. The ACD decreased more in eyes with cortical cataract, suggesting that the risk for angle-closure glaucoma may be greater in cases of cortical opacity in which lens expansion is greater. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Association of c3 gene polymorphisms with neovascular age-related macular degeneration in a chinese population.

PURPOSE: The purpose of this study was to determine whether the genetic polymorphisms of complement factor 3 (C3) are associated with neovascular age-related macular degeneration (AMD) in the Chinese population. METHODS: A total of 123 unrelated Chinese Han patients with neovascular AMD and 130 control subjects were recruited. Their six single-nucleotide polymorphisms (SNPs) in the C3 gene, one in the complement factor H (CFH) gene and two in the complement factor B (CFB) gene were characterized. Their genotypes, allele frequencies, and odds ratios were analyzed. RESULTS: The G allele of the C3 IVS2 rs2250656, but not other tested C3 SNPs of rs2230205, rs10411506, rs2230199, rs339392, and rs163913, was significantly associated with a reduced risk for AMD in the Chinese population (OR 0.605, 95% CI 0.39-0.93, p = 0.023), even after adjusting for age, gender, smoking status, CFH rs1061170, CFB rs4151667, and CFB rs641153 allele status (OR 0.58, 95% CI 0.35-0.96, p = 0.033). However, the C3 haplotype of A-A-C-A-T-T was identified as a statistically significant risk factor for neovascular AMD (OR 1.41, 95% CI 1.02-1.94). Furthermore, the C allele of the CFH rs1061170, but not the CFB rs4151667 and rs641153, was significnatly associated with increased risk for AMD (OR 3.09, 95% CI 1.55-6.15, p < 0.001). CONCLUSION: The G allele of C3 IVS2 rs2250656 may be a significantly protective factor for neovascular AMD in the Chinese population. This, together with low MAF of C3 R102G, may be partially responsible for the low prevalence of AMD in the Chinese population.

Late postoperative capsular block syndrome versus liquefied after-cataract.

We report the case of a 76-year-old Chinese man who had uneventful cataract phacoemulsification and hydrophilic acrylic intraocular lens (IOL) implantation 6 years previously. He presented with decreased vision; a homogeneous milky substance was found between the posterior chamber IOL and the posterior capsule without IOL displacement or a change in the refractive status. The milky substance was aspirated from the capsular bag. Biochemical analysis showed the concentrations of proteins and Ca(++) in the milky liquid were higher than those in the aqueous humor. Protein identification by mass spectrometry indicated that the milky liquid contained a high concentration of alpha-crystallin and beta-crystallin.