Relationship of mTORC1 and ferroptosis in tumors.

Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

Continuous 24-hour intraocular pressure monitoring in normal Chinese adults using a novel contact lens sensor system.

AIMS: To investigate the physiological nyctohemeral intraocular pressure (IOP) rhythms of normal Chinese adults using a novel contact lens sensor system (CLS) that can output IOP in millimetres of mercury (mm Hg) continuously. METHODS: Fifty-nine eyes of 59 normal Chinese adults completed 24-hour IOP monitoring using the novel CLS. A descriptive analysis was conducted on the 24-hour IOP mean, peak and acrophase, trough and bathyphase, fluctuation, and mean amplitude of intraocular pressure excursion (MAPE). The continuous data were analysed at several periods (diurnal period, 08:00-20:00 hours; nocturnal period, 22:00-06:00 hours; sleep time, 0:00-06:00 hours), and compared between right and left eyes, males and females, and different age ranges (<30, and ≥30), respectively. RESULTS: Normal adults had a lower peak, higher trough, smaller fluctuation and smaller MAPE (p<0.05 for all comparisons) but non-significantly different mean (p=0.695) in the nocturnal period or sleep time compared with the diurnal period. The 24-hour IOP peak and trough showed the frequency of occurrence ranging from 1.69% to 15.25% at an interval of 2 hours. No IOP parameter showed significant difference between right and left eyes (p>0.1 for all comparisons). The male group had larger 24-hour and diurnal IOP fluctuation and MAPE (p<0.05 for all comparisons). Subjects aged 30 or over had higher 24-hour and diurnal mean, higher peak, and larger MAPE (p<0.05 for all comparisons). CONCLUSION: Continuous 24-hour IOP output from the CLS in normal Chinese was stable with a comparable mean level between day and night, as well as scattered acrophase and bathyphase. The 24-hour IOP mean increased with age, and IOP variations were positively correlated to age and male sex.

Early impairment of magnocellular visual pathways mediated by isolated-check visual evoked potentials in primary open-angle glaucoma: a cross-sectional study.

OBJECTIVE: To explore different performances in the magnocellular (MC) and parvocellular (PC) visual pathways in patients with primary open-angle glaucoma (POAG) and to objectively assess impairment in early stage of POAG. METHODS AND ANALYSIS: This is a cross-sectional study. MC and PC visual pathways were assessed using isolated-check visual evoked potential (ic-VEP). Visual acuity, intraocular pressure, fundus examination, optical coherence tomography and visual field were measured. Signal-to-noise ratios (SNRs), mediated by ic-VEP were recorded. The Spearman's correlation analysis was used to estimate the relationships between visual functions and structures. Receiver-operating-characteristic (ROC) curves were used to estimate the accuracy in detection of early POAG. RESULTS: 60 participants (30 early POAG eyes and 30 age-matched control subjects) were recruited. MC visual pathway showed a non-linear response function, while PC visual pathway was a linear response function as contrast increased. Early POAG eyes exhibited significantly weaker initial contrast gains and lower maximum responses in the MC visual pathway (p=0.001, p=0.004, respectively). The SNRs at 8% and 32% depths of modulation (DOM) were significantly correlated with temporal-side retinal nerve fibre layer (RNFL) thickness in early POAG in MC-biased stimulation (p=0.017, p=0.020, respectively). The areas under ROC of 16% DOM were 0.780 (sensitivity 80.0%, specificity 63.3%) with the cut-off SNR of 2.07. CONCLUSIONS: The MC visual pathway was damaged in the early stage of POAG. The SNRs at 8% and 32% DOM of MC-biased stimulation were significantly correlated with temporal-side RNFL thickness in early POAG, which helped in understanding the mechanisms of visual impairment in the early stage of POAG.

The role of TGF-ß in the tumor microenvironment of pancreatic cancer.

Pancreatic cancer (PC) is an aggressive malignant tumor with low rate of surgical resection and poor prognosis. Transforming growth factor-ß (TGF-ß) is a cytokine that has both protumor and antitumor activities, depending on tumor microenvironment. The interaction between TGF-ß signaling and the tumor microenvironment in PC is complex. Here, we reviewed the role of TGF-ß in the tumor microenvironment of PC, highlighting producers of TGF-ß and TGF-ß responders in the tumor microenvironment of PC.

Rare Pseudo-Chediak-Higashi Inclusions in Therapy-Related Acute Myeloid Leukemia with Myelodysplasia-Related Changes.

BACKGROUND: Defined as rare large azurophilic cytoplasmic inclusions, Pseudo-Chediak-Higashi granules mimic those in granulocytes cytoplasm of Chediak-Higashi syndrome. Rare cases of hematopoietic and lymphoid tissues tumors showed Pseudo-Chediak-Higashi inclusions in cytoplasm, some of which presented with unusual morphological characteristics. METHODS: Herein, we report the first case, in which rare pseudo-Chediak-Higashi inclusions were observed in therapy-related acute myeloid leukemia with myelodysplasia-related changes (t-AML-MRC). RESULTS: The rare pseudo-Chediak-Higashi inclusions may be positive for Sudan black, and some scholars think that these rare inclusions are a kind of dysgranulopoiesis. CONCLUSIONS: The case highlights the significance of an integrated diagnostic work-up, with an interesting effect for morphology.

Hemophagocytic Lymphohistiocytosis Appearing During Blast Phase of Chronic Myeloid Leukemia.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening illness with rapid progression and high mortality and is associated with genetic defects or can be induced by malignancies or severe infections. Most of the hematological malignancy-related HLH reported was accompanied by lymphoid neoplasms. METHODS: Here, we present an unusual case of HLH with co-existing blast phase of chronic myeloid leukemia (CML-BP). RESULTS: A diagnosis of AML-M5 with most likely concomitant HLH was made based on the clinical features, morphology, flow cytometry immunophenotyping, and genetics. Moreover, clinical characteristics were more suggestive of myeloid blast phase CML than de novo AML with the positive p210 BCR-ABL1. However, disease-causing mutations of HLH were not available, the patient probably had secondary malignancy-associated HLH induced by an acute infection. CONCLUSIONS: The case focuses on the contribution of bone marrow morphological examination in getting the first diagnostic clue of CML-BP concomitant with HLH.

Intraocular pressure and diurnal fluctuation of open-angle glaucoma and ocular hypertension: a baseline report from the LiGHT China trial cohort.

AIMS: To report the baseline intraocular pressure (IOP) characteristics and its diurnal fluctuation in the Laser in Glaucoma and Ocular Hypertension China cohort. METHODS: 622 primary open-angle glaucoma (POAG) patients and 149 ocular hypertension (OHT) patients were recruited at Zhongshan Ophthalmic Center from 2015 to 2019. Standardised ocular examinations were performed including IOP measurement using the Goldmann applanation tonometer. Daytime phasing IOP was recorded at 8:00, 10:00, 11:30, 14:30, 17:00 hour. RESULTS: The mean baseline IOP was 20.2 mm Hg for POAG patients and 24.4 mm Hg for OHT. Multiple regression analysis revealed that thicker central corneal thickness (CCT) was correlated with higher IOP in both POAG and OHT. Male gender and younger age were correlated with higher IOP only for POAG. As for diurnal IOP fluctuation, mean IOP fluctuation was 3.4 mm Hg in POAG eyes and 4.4 mm Hg in OHT. The peak and trough IOP occurred at 8:00 and 14:30 hour in both POAG and OHT eyes. CONCLUSIONS: Younger age, male gender and thicker CCT are correlated to higher IOP in POAG patients while only thicker CCT is related to higher IOP in OHT patients. Peak IOP appears mostly at early morning or late afternoon and trough value occurs mostly at early afternoon.

Cysteine Metabolism in Tumor Redox Homeostasis.

Cysteine (Cys) is a semi-essential nutrient amino acid that plays an important role in cells through endogenous production and various transport systems. Intracellular Cys can be used as a precursor of protein synthesis to maintain cell homeostasis and to generate sulfur-containing substances, including glutathione (GSH), hydrogen sulfide (H2S), and taurine. There have been quite a few reports that Cys is related to tumor occurrence and development, and its level is closely related to tumor proliferation, invasion, and metastasis. Moreover, it helps in maintaining the tumor redox balance and increasing drug resistance. This review aims to summarize the production and metabolism of Cys and its role in tumors, with special emphasis on the potential therapeutic value of Cys in tumors to improve the quality of life of cancer patients.

Corneal Stiffness and Modulus of Normal-Tension Glaucoma in Chinese.

PURPOSE: To assess and compare the corneal biomechanics of normal-tension glaucoma (NTG), high-tension glaucoma (HTG), and normal controls based on stiffness and modulus. The correlations among central corneal thickness (CCT), visual field, retinal nerve fiber layer (RNFL) thickness, and corneal biomechanics in glaucoma eyes were also evaluated. DESIGN: A prospective, cross-sectional, comparative study. METHODS: This study included 334 eyes of 108 NTG patients, 113 HTG patients, and 113 control subjects at Zhongshan Ophthalmic Center, Sun Yat-Sen University. Corneal biomechanics were evaluated using a corneal indentation device (CID) and corneal visualization Scheimpflug technology (Corvis ST). Visual field and RNFL thickness were obtained using standard automated perimetry and spectral-domain optical coherence tomography. One-way analyses of variance with Bonferroni post hoc tests and a multivariable linear regression analysis with adjustment were conducted. Correlations among corneal biomechanical parameters, CCT, visual field, and RNFL thickness were analyzed. RESULTS: The corneal stiffness of the NTG patients (71.0 ± 10.9 N/m) was significantly lower than that of the HTG patients (77.3 ± 15.6 N/m; P = .001) and the CCT- and IOP-matched normal controls (75.6 ± 11.0 N/m; P = .023). The patients in the NTG group had lower corneal stiffness than those in the control group (ß = -4.88, 95% CI -9.002, -0.758; P = .020) after adjusting for confounders. Stiffness was positively correlated with CCT in the NTG group (P = .028) but not in the HTG group (P = .509). There was no significant correlation (P > .05) between corneal biomechanics, visual field, or RNFL thickness. CONCLUSIONS: The corneas of NTG patients were softer than those of HTG patients and controls, as assessed by CID, which were associated with thinner CCT. These might suggest different ocular biomechanical properties in NTG and HTG.

Evidence-based nursing intervention can improve the treatment compliance, quality of life and self-efficacy of patients with lung cancer undergoing radiotherapy and chemotherapy.

OBJECTIVE: To investigate the improvement effect of evidence-based nursing intervention on treatment compliance, quality of life and self-efficacy of patients with lung carcinoma (LC) undergoing radiotherapy and chemotherapy. METHODS: From May 2018 to August 2019, 183 patients with LC who received radiotherapy and chemotherapy in our hospital were selected and divided into two groups in accordance with different nursing methods. Among them, 85 patients who received routine nursing intervention were included in the control group (CG), and 98 patients who received evidence-based nursing intervention were included in the research group (RG). The improvement of pulmonary function indexes [(FVC), forced expiratory volume in one second (FEV1), ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC)] was observed before and after nursing. The pain degree was evaluated by the visual analogue scale (VAS). The treatment compliance between groups was compared. The psychological emotions of the patients were evaluated by a self-rating anxiety scale (SAS) and a self-rating depression scale (SDS). The General Self-efficacy Scale (GSES) was applied to assess the self-efficacy and the Quality of Life (SF-36) scale was applied to evaluate the quality of life. The incidence of secondary infection was observed in the two groups. The nursing satisfaction was evaluated by a nursing satisfaction questionnaire made by our hospital. RESULTS: After nursing, the improvement of FEV1, FVC and FEV1/FVC levels in the RG were obviously better than that in the CG; The scores of VAS, SAS and SDS and total incidence of secondary infection in the RG were obviously lower than those in the CG; The treatment compliance, GSES and SF-36 scores, and nursing satisfaction scores of patients in the RG were obviously higher than that in the CG. CONCLUSION: Evidence-based nursing intervention can improve treatment compliance, lung function, self-efficacy and quality of life for patients with LC undergoing radiotherapy and chemotherapy.

Wide Corneal Epithelial Thickness Mapping in Eyes With Topical Antiglaucoma Therapy Using Optical Coherence Tomography.

Purpose: The purpose of this study was to assess the corneal epithelial thickness (CET) of the 9-mm diameter zone in patients treated using topical antiglaucoma medications and to evaluate the factors associated with CET changes. Methods: Seventy-five patients treated using topical antiglaucoma medications and 65 healthy subjects were included in this cross-sectional study. Each patient completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent examinations including the Schirmer I test, tear breakup time (TBUT), and fluorescein staining. CET mapping of the 9-mm diameter zone was performed using RTVue XR. The CET of the different analyzed zones was compared between groups. The relationship between CET and confounding factors was investigated. Results: The patient group had a significantly shorter TBUT, shorter Schirmer I test, and greater fluorescein staining than those of the control group (all P < 0.05). The mean CET of patients with glaucoma was significantly lower than that of controls in the central, paracentral, mid-peripheral, and peripheral zones (all P < 0.001). Age affected the CET in the paracentral, mid-peripheral, and peripheral zones (all P < 0.01). The number of medications affected the CET in the central, paracentral, and mid-peripheral zones (all P < 0.05). The duration of treatment affected the CET in the central and peripheral zones (all P < 0.05). Conclusions: Use of topical IOP-lowering medications leads to epithelial thinning in the 9-mm diameter zone in glaucomatous eyes. Epithelial protection should be considered in older patients and patients treated with multiple medications from the early stages of long-term topical antiglaucoma therapy. Translational Relevance: The 9-mm diameter CET mapping by using widefield optical coherence tomography (OCT) can be a valuable and convenient method to assess the ocular surface damage in patients with topical antiglaucoma therapy.

Corneal Biometric Parameters and Refractive Properties in Microcornea With Normal Axial Length.

PURPOSE: The purpose of this study was to evaluate the features of and relationships among corneal diameter, central corneal thickness (CCT), endothelial cell density (ECD), and corneal refractive properties in cases of microcornea (MC) with normal axial length. METHODS: We included 22 patients (35 eyes) with MC and cataracts and 41 patients (48 eyes) with isolated cataracts as age-matched controls. They were divided into patients with MC younger than 18 years (MC-child), patients with MC 18 years or older (MC-adult), children with congenital cataracts (CCs), and adults with senile cataracts (SCs). Corneal diameter, axial and anterior chamber length, and keratometry were measured; central corneal endothelial cell imaging was performed. RESULTS: The mean horizontal corneal diameter was 7.71 ± 1.51 and 8.78 ± 0.52 mm in MC-child and MC-adult groups, respectively, and 11.89 ± 0.59 and 11.52 ± 2.42 mm in child and adult controls, respectively. The mean CCT was 641.26 ± 63.37 (MC-child) and 617.38 ± 45.40 mm (MC-adult), and 554.92 ± 34.64 (CC) and 551.58 ± 28.47 mm (SC). The mean ECD was 2898.47 ± 443.90 (MC-child) and 2825.81 ± 484.65 cells/mm 2 (MC-adult), and 3155.13 ± 372.67 (CC) and 2749.33 ± 399.63 cells/mm 2 (SC). The average keratometry was 44.22 ± 3.14 D (MC-child) and 43.86 ± 2.59 D (MC-adult), and 44.19 ± 1.44 D (CC) and 43.94 ± 1.34 D (SC). CONCLUSIONS: Patients with MC and normal axial length possess specific parameters, including significantly smaller corneal diameter and thicker CCT than the patients in the control groups. There were no significant differences in ECD and average keratometry. These parameters should be taken into account in the follow-up and treatment.

Laser in Glaucoma and Ocular Hypertension Trial (LIGHT) in China - A Randomized Controlled Trial: Design and Baseline Characteristics.

PURPOSE: To describe the baseline characteristics of a trial to evaluate whether selective laser trabeculoplasty (SLT), as a first-line treatment, provides superior economic and health-related quality of life outcomes to medical treatment in China. DESIGN: The LiGHT China trial is an unmasked, single-center, pragmatic, randomized controlled trial. METHODS: A total of 771 previously undiagnosed patients with primary open angle glaucoma (POAG, 622 patients) or ocular hypertension (OHT, 149 patients) at Zhongshan Ophthalmic Center were recruited from March 2015 to January 2019. Subjects were randomized to SLT-1st (followed by medication then surgery when required) or Medicine-1st (medication followed by surgery when required). The primary outcome was health-related quality of life (HRQL). The secondary outcomes were clinical outcomes, cost, cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, visual function, and safety. RESULTS: The mean age of POAG patients was 49.8 years and 38.8 years for OHT. The median intraocular pressure was 20 mm Hg for the 1,105 POAG eyes and 24 mm Hg for the 271 OHT eyes. POAG eyes had thinner central cornea thickness (CCT, 536 µm) than OHT eyes (545 µm). Median mean deviation of the visual field in POAG eyes was -4.2 dB. Median refractive error was -1.5 D for OHT eyes and -1.25 D for POAG eyes. There was no difference between POAG and OHT patients on baseline scores of GUI, GSS and VF-14. The difference between OHT and POAG on the EQ-5D-5L was 0.024. CONCLUSIONS: Compared with participants in the LiGHT UK trial, participants in this trial were younger, more myopic and had more severe visual field defects.

Comparison of Biomechanically Corrected Intraocular Pressure Obtained by Corvis ST and Goldmann Applanation Tonometry in Patients With Open-angle Glaucoma and Ocular Hypertension.

PRECIS: Biomechanically corrected intraocular pressure (bIOP) measurements provided by the new Corvis ST (CST) were higher than measurements obtained with Goldman applanation tonometry (GAT) in eyes with ocular hypertension (OHT) or open-angle glaucoma (OAG). PURPOSE: To compare bIOP obtained with a new version of CST with GAT measurements in patients with OAG and OHT, and to identify factors affecting IOP measurement differences between these methods. METHODS: A total of 122 eyes with OAG or OHT were enrolled. Sixty eyes were treated with prostaglandin analogs (PGA) and 62 eyes with selective laser trabeculoplasty (SLT). IOP was measured with CST, followed by GAT. Central corneal thickness (CCT) was measured with ultrasound pachymetry. Measurements obtained with these 2 approaches were compared. RESULTS: The overall mean IOP was 15.2±3.0 mm Hg and 14.1±3.2 mm Hg with the CST and GAT, respectively (r=0.74; P<0.0001). There was a 1.17 mm Hg bias between tonometers, with 95% limits of agreement of -2.66 to 5.01 mm Hg. According to multivariate regression analysis, differences between bIOP and GAT-IOP were associated with CCT (P=0.001) and age (P=0.007) in the PGA group, but only with CCT in the SLT group (P=0.002). bIOP and GAT-IOP values were influenced by age (PGA: P=0.014; SLT: P=0.006) and CCT (PGA: P=0.007; SLT: P=0.032), respectively. CONCLUSIONS: BIOP values were higher and less affected by CCT than GAT-IOP values in eyes with OAG and OHT. However, these measurements may not be interchangeable in the clinic.

[The impact of telmisartan on angiotensin converting enzyme 2 mRNA expression in monocyte-derived macrophages of diabetic hypertensive patients].

OBJECTIVE: To investigate the effects of telmisartan on the expression of angiotensin converting enzyme 2 (ACE2) mRNA in monocyte-derived macrophages of hypertensive patients accompanied with diabetes. METHODS: 62 essential hypertensive patients accompanied with diabetes were randomly divided into two groups: regular treatment group, and telmisartan group. Then the content of ACE and ACE2 in serum was detected by ELISA, and the expression of ACE mRNA and ACE2 mRNA in monocyte-derived macrophages of patients was detected by RT-PCR before and after having been treated. RESULTS: (1) After having been treated for 4 weeks and 12 weeks, the blood pressure of the patients in two groups were decreased significantly, Comparing with regular group, telmisartan group seemed to have more obvious therapeutic effect (P < 0.05); (2) After having been treated for 12 weeks, glycosylated hemoglobin diseased in both group, but there was no significant difference between the two group (P > 0.05); (3) In telmisartan group, the content of ACE2 in serum was increased after having been treated for 12 weeks than that in regular treatment group, [(23.9 ± 8.2) U/L vs (16.3 ± 8.9) U/L, P < 0.05]; and the expression of ACE2 mRNA in monocyte-derived macrophages in telmisartan group was obviously increased after 12 weeks comparing with regular treatment group (0.73 ± 0.06 vs 0.51 ± 0.04, P < 0.01). CONCLUSION: The role of telmisartan in decreasing blood pressure and it's advantage to the metabolism of glucose are partly related with the up-regulation of ACE2 mRNA.

Antagonism of 5-HT(2A) receptors inhibits the expression of pronociceptive mediator and enhances endogenous opioid mechanism in carrageenan-induced inflammation in rats.

We have recently reported that treatment with the 5-HT(2A) receptor antagonist ketanserin in the inflamed paw raises the nociceptive threshold above normal level (hypoalgesia) and this response is naloxone-reversible. The present study aimed to investigate neurochemical changes at the site of inflammation and in dorsal root ganglia (DRG) and the spinal cord following the blockade of 5-HT(2A) receptors. Intraplantar injection of ketanserin (20 µg) inhibited carrageenan-induced increase in CGRP immunoreactivity-positive neurons in DRG. On the other hand, administration of ketanserin (20 µg) and 5-HT (10 µg), but not vehicle, enhanced and inhibited recruitment of ß-endorphin-expressing immune cells, respectively, in subcutaneous loci of inflamed hindpaw. Moreover, the treatment with ketanserin increased the number of endomorphine-containing cells in the inflamed paw and µ-opioid receptor-expressing neurons in DRG at L4-5 but reduced the expression of endomorphine in superficial layers of the lumbar spinal cord. The present study provided evidence at the cellular level showing that the blockade of 5-HT(2A) receptors inhibited inflammation-associated increase in pronociceptive mediator, and that the pronociceptive property of 5-HT is mediated by the suppression of inflammation-activated opioid mechanism. Therefore, targeting the 5-HT(2A) receptors in the site of inflammation may be a promising approach to inhibit inflammatory pain.