Interleukin-5 alleviates cardiac remodelling via the STAT3 pathway in angiotensin II-infused mice.

Interleukin-5 (IL-5) has been reported to be involved in cardiovascular diseases, such as atherosclerosis and cardiac injury. This study aimed to investigate the effects of IL-5 on cardiac remodelling. Mice were infused with angiotensin II (Ang II), and the expression and source of cardiac IL-5 were analysed. The results showed that cardiac IL-5 expression was time- and dose-dependently decreased after Ang II infusion, and was mainly derived from cardiac macrophages. Additionally, IL-5-knockout (IL-5-/-) mice were used to observe the effects of IL-5 knockout on Ang II-induced cardiac remodelling. We found knockout of IL-5 significantly increased the expression of cardiac hypertrophy markers, elevated myocardial cell cross-sectional areas and worsened cardiac dysfunction in Ang II-infused mice. IL-5 deletion also promoted M2 macrophage differentiation and exacerbated cardiac fibrosis. Furthermore, the effects of IL-5 deletion on cardiac remodelling was detected after the STAT3 pathway was inhibited by S31-201. The effects of IL-5 on cardiac remodelling and M2 macrophage differentiation were reversed by S31-201. Finally, the effects of IL-5 on macrophage differentiation and macrophage-related cardiac hypertrophy and fibrosis were analysed in vitro. IL-5 knockout significantly increased the Ang II-induced mRNA expression of cardiac hypertrophy markers in myocardial cells that were co-cultured with macrophages, and this effect was reversed by S31-201. Similar trends in the mRNA levels of fibrosis markers were observed when cardiac fibroblasts and macrophages were co-cultured. In conclusions, IL-5 deficiency promote the differentiation of M2 macrophages by activating the STAT3 pathway, thereby exacerbating cardiac remodelling in Ang II-infused mice. IL-5 may be a potential target for the clinical prevention of cardiac remodelling.

Efficacy and safety of pulsed field ablation for accessory pathways: a pilot study.

AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs. METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up. CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.

Identification of an 11-miRNA-regulated and surface-protein genes signature predicts the prognosis of lung adenocarcinoma based on multi-omics study.

Lung adenocarcinoma (LUAD) is one of the most prevalent and lethal cancers worldwide, signifying a critical need for improved prognostic tools. A growing number of studies have highlighted the role of microRNAs (miRNAs) and their regulatory functions in tumorigenesis and cancer progression. In this context, we performed an extensive analysis of bulk RNA- and miRNA-sequencing to identify LUAD-associated prognostic genes. A risk score system based on 11 miRNA-regulated and surface-protein genes was developed, which was later validated by internally and externally using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Further single-cell RNA sequencing analysis revealed significant interactions between various cellular subpopulations within the tumor microenvironment, with the most pronounced differences observed between endothelial and epithelial cells. The mutational analysis highlighted TP53 as a key signaling pathway associated with the risk score. The study underscores that immune suppression, indicated by a positive association with regulatory T cells (Tregs) and an inverse correlation with M1-type macrophages, is prevalent in high-risk LUAD patients. These findings provide a promising prognostic tool for clinical outcomes of LUAD patients, facilitating future development of therapeutic strategies and enhancing our understanding of the regulatory function of miRNAs in LUAD.

Efficacy and safety of pulsed field ablation for accessory pathways: a pilot study.

AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs. METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up. CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.

Incidence and analysis of intraoperative complications in femtosecond laser-assisted cataract surgery: a large-scale cohort study to establish the learning curve.

AIMS: To assess the safety of femtosecond laser-assisted cataract surgery (FLACS) based on surgical parameters and intraoperative complications analysis and to determine the length of the learning curve for FLACS. METHODS: A prospective consecutive cohort study was conducted on Chinese patients who underwent either FLACS (3289 cases) or contemporaneous conventional phacoemulsification cataract surgery (2130 cases). The laser group was divided into four subgroups in chronological order. We recorded intraoperative complication incidences and compared with surgical parameters between groups. Subgroup analysis was conducted to explore the learning curve of FLACS. RESULTS: The laser group had a 4.93% incidence of incomplete capsulotomies and a 1.22% incidence of anterior capsule tears. Subgroup analysis showed significant differences in 8 aspects between the first 250 cases (50 cases per surgeon) and the last 2539 cases, but only 2 aspects differed between the second 250 cases (50 cases per surgeon) and the last 2539 cases. There were no significant differences between the third 250 cases (50 cases per surgeon) and the last 2539 cases. CONCLUSIONS: The intraoperative complications of FLACS were reported, and the learning curve is associated with a significant reduction in the incidence of intraoperative complications. The length of the basic learning curve of FLACS is 100 cases, and the length of the advanced learning curve was 150 cases. This study demonstrated that FLACS is characterised by a relatively straightforward and secure operative technique.

Relay Catalysis for Selective Aerobic Oxidative Esterification of Primary Alcohols with Methanol.

Esters are bulk and fine chemicals and ubiquitous in polymers, bioactive compounds, and natural products. Their traditional synthetic approach is the esterification of carboxylic acids or their activated derivatives with alcohols. Herein, a bimetallic relay catalytic protocol was developed for the aerobic esterification of one alcohol in the presence of a slowly oxidizing alcohol, which has been identified as methanol. A concise synthesis of phlomic acid was executed to demonstrate the practicality and potential of this reaction.

Cholesterol metabolism: physiological regulation and diseases.

Cholesterol homeostasis is crucial for cellular and systemic function. The disorder of cholesterol metabolism not only accelerates the onset of cardiovascular disease (CVD) but is also the fundamental cause of other ailments. The regulation of cholesterol metabolism in the human is an extremely complex process. Due to the dynamic balance between cholesterol synthesis, intake, efflux and storage, cholesterol metabolism generally remains secure. Disruption of any of these links is likely to have adverse effects on the body. At present, increasing evidence suggests that abnormal cholesterol metabolism is closely related to various systemic diseases. However, the exact mechanism by which cholesterol metabolism contributes to disease pathogenesis remains unclear, and there are still unknown factors. In this review, we outline the metabolic process of cholesterol in the human body, especially reverse cholesterol transport (RCT). Then, we discuss separately the impact of abnormal cholesterol metabolism on common diseases and potential therapeutic targets for each disease, including CVD, tumors, neurological diseases, and immune system diseases. At the end of this review, we focus on the effect of cholesterol metabolism on eye diseases. In short, we hope to provide more new ideas for the pathogenesis and treatment of diseases from the perspective of cholesterol.

Cataract-related variant R114C increases ßA3-crystallin susceptibility to environmental stresses by disrupting the protein senior structure.

Congenital cataract is a major cause of childhood blindness worldwide, with crystallin mutations accounting for over 40 % of gene-mutation-related cases. Our research focused on a novel R114C mutation in a Chinese family, resulting in bilateral coronary cataract with blue punctate opacity. Spectroscopic experiments revealed that ßA3-R114C significantly altered the senior structure, exhibiting aggregation, and reduced solubility at physiological temperature. The mutant also displayed decreased resistance and stability under environmental stresses such as UV irradiation, oxidative stress, and heat. Further, cellular models confirmed its heightened sensitivity to environmental stresses. These data suggest that the R114C mutation impairs the hydrogen bond network and structural stability of ßA3-crystallin, particularly at the boundary of the second Greek-key motif. This study revealed the pathological mechanism of ßA3-R114C and may help in the development of potential treatment strategies for related cataracts.

Left atrial appendage closure in patients with left atrial appendage thrombus guided by intracardiac echocardiography.

BACKGROUND: Data regarding left atrial appendage closure (LAAC) in patients with left atrial appendage (LAA) thrombus are limited. Recently published cases have mostly been guided by transesophageal echocardiography. Intracardiac echocardiography (ICE) is now widely used during LAAC procedures. OBJECTIVE: This is the first study to report the feasibility of LAAC in patients with LAA thrombus guided by ICE. METHODS: Patients with persistent LAA thrombus despite anticoagulation or contraindications to anticoagulation who underwent a modified ICE-guided LAAC procedure between June 2021 and April 2023 were included. Periprocedural events and clinical outcomes during follow-up were recorded. RESULTS: A total of 12 patients (mean age 65 ± 7 years; 92% male) were included: 10 with persistent LAA thrombus and 2 with contraindications to anticoagulation. Most of the thrombus was at the apex (n = 6), followed by the body (n = 3) and the ostium (n = 3). A LAmbre device was used and successfully implanted in all patients with the guidance of ICE. No thrombotic material was retrieved from patients with the protection of cerebral protection device (n = 11). No patient experienced severe periprocedural complications. All patients completed transesophageal echocardiography follow-up, and no device-related thrombus or peridevice leak > 3 mm was detected. None of the patients experienced stroke/transient ischemic attack, systemic embolism, or major bleeding events during a median follow-up of 147 days (interquartile range 80-306 days). CONCLUSION: LAAC using the LAmbre device guided by ICE may be feasible in patients with LAA thrombus when performed by experienced operators.

Impact of left atrial appendage orifice diameter on the safety and efficacy of left atrial appendage closure using the LAmbre device.

BACKGROUND: The diameter and shape of the left atrial appendage (LAA) orifices may influence occluder selection and the outcomes of left atrial appendage closure (LAAC) procedure. This study aimed to evaluate the impact of LAA orifice diameter on the safety and efficacy of LAAC using the LAmbre device. METHODS: A total of 133 patients with nonvalvular atrial fibrillation (AF) who underwent LAAC with the LAmbre device between June 2018 and June 2020 were included in this study. The patients were categorized into two groups based on the maximal diameter of the LAA orifice: the large LAA group (n = 45) with a maximal orifice diameter of ≥31 mm, and the normal LAA group (n = 88) with a maximal orifice diameter of <31 mm. The study assessed periprocedural characteristics and long-term clinical follow-up. RESULTS: Successful implantation of the LAmbre device was observed in all patients. The incidence of periprocedural peridevice leakage (PDL) was significantly higher in the large LAA group (P < 0.001), while the incidence of acute pericardial effusion (PE) during the procedure was comparable between the two groups (P = 1.000). After a mean follow-up period of 4.8 ± 1.7 years, three patients in the large LAA group developed delayed PE, while no patients in the normal LAA group did (P = 0.037). Additionally, a larger LAA maximal orifice diameter was associated with a higher prevalence of PDL (P = 0.001) and PE (including both acute and delayed PE) (P = 0.027). The optimal cutoff value of the LAA maximal orifice diameter for predicting PDL and PE after LAAC with the LAmbre device was determined to be 30 mm. CONCLUSION: The findings suggest that the LAmbre device is a safe and feasible option for occluding the LAA, regardless of its orifice diameter. However, it is important to note that a larger LAA orifice diameter may increase the risk of PDL and delayed PE.

Outcomes of Focal Pulsed Field Ablation for Paroxysmal Supraventricular Tachycardia.

BACKGROUND: Pulsed field ablation (PFA) is primarily used for treatment of atrial fibrillation as it provides better safety and efficacy. However, there are limited data available on the use of PFA for paroxysmal supraventricular tachycardia (PSVT). The study sought to describe the outcomes of PSVT ablation with a novel focal contact force (CF)-sensing PFA. METHODS: In this first-in-human pilot study, a focal CF-sensing PFA catheter was used for mapping and ablation navigated with an electroanatomic mapping system (EAMS). Pulsed field energy was delivered as biphasic/bipolar electrical pulse trains with 2000 V/delivery. CF was controlled from 2 g to 10 g during PFA. RESULTS: Procedural acute success was achieved without general anaesthesia or conscious sedation in all 10 patients, including 7 patients diagnosed with typical atrioventricular nodal re-entrant tachycardias and 3 patients with orthodromic reciprocating tachycardias. Successful target ablation time was 2.0 ± 0.5 seconds per patient, and the acute procedural success at the first single site was achieved in 5 patients. The mean skin-to-skin procedure time was 79.4 ± 15 minutes, PFA catheter dwell time was 50.1 ± 14 minutes, and fluoroscopy time was 6.2 ± 7 minutes. Maintenance of sinus rhythm was observed in all patients within 6-month follow-up. No serious adverse events occurred in any subjects during PFA or during the 6-month follow-up. CONCLUSIONS: A focal CF-sensing PFA catheter could effectively, rapidly, and safely ablate PSVT in conscious patients. CLINICAL TRIAL REGISTRATION: NCT05770921.

Clinical outcomes of combined catheter ablation and left atrial appendage closure in elderly patients with nonvalvular atrial fibrillation.

BACKGROUND: Catheter ablation (CA) combined with left atrial appendage closure (LAAC) has emerged as a promising method to relieve symptoms while reducing the incidence of stroke in selected high-risk patients with atrial fibrillation (AF). HYPOTHESIS: We aimed to investigate the clinical outcomes of combined CA and LAAC in elderly patients. METHODS: A total of 316 patients with symptomatic drug-refractory AF who underwent combined CA and LAAC between January 2016 and December 2020 were retrospectively included. Baseline characteristics, periprocedural complications, and clinical events during follow-up were recorded and compared between patients aged ≥ 75 years (n = 66) and <75 years (n = 250). RESULTS: Pulmonary vein isolation and satisfactory LAAC were achieved in all patients. No patients experienced death or stroke/transient ischemic stroke periprocedurally. After a median follow-up of 12.2 (6.7-24.4) months and 11.9 (5.5-23.6) months, the rate of sinus rhythm maintenance was comparable between the two groups (≥75 years: 78.8% vs. <75 years: 80.8%; log-rank test, p = 0.674). The median follow-up periods for clinical outcomes were 27.9 (9.3-44.8) months and 25.2 (10.8-45.7) months, respectively. In patients aged ≥ 75 years, one suffered ischemic stroke, and one experienced major bleeding event. In patients aged < 75 years, four had ischemic stroke, and eight had major bleeding events. Two patients aged < 75 years died during follow-up, while none of the patients aged ≥ 75 years died. CONCLUSIONS: Combining CA and LAAC was feasible, safe and effective in elderly patients with AF.

A Modular Approach for the Synthesis of Natural and Artificial Terpenoids.

Many terpenoids with isoprene unit(s) demonstrating critical biological activities have been isolated and characterized. In this study, we have developed a robust chem-stamp strategy for the construction of the key isoprene unit, which consists of two steps: one-carbon extension of aldehydes to the alkenyl boronates by the boron-Wittig reaction and the rhodium-catalyzed reaction of alkenyl boronates with 2,3-allenols to yield enals. This chem-stamp could readily be applied repeatedly and separately, enabling the modular concise synthesis of many natural and pharmaceutically active terpenoids, including retinal, ß-carotene, vitamin A, tretinoin, fenretinide, acitretin, ALRT1550, nigerapyrone C, peretinoin, and lycopene. Owing to the diversified availability of the starting materials, aldehydes and 2,3-allenols, creation of new non-natural terpenoids has been realized from four dimensions: the number of isoprene units, the side chain, and the two terminal groups.

Correlation between Serum Myosin Light Chain 4 Levels and Recurrence after Radiofrequency Ablation in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia that is harmful to human health. This study aims to explore the relationship between myosin light chain 4 (MYL4) and AF recurrence after radiofrequency ablation (RFA). Patients with AF (n = 85) were enrolled, and healthy subjects (n = 90) with normal sinus rhythm and no previous history of AF were selected as controls. The serum levels of MYL4, transforming growth factor (TGF) -ß1, and procollagen type-I C-terminal propeptide (PICP) were determined. The correlation between MYL4 and atrial fibrosis remodeling indicators (TGF-ß1/PICP) and left atrial diameter (LAD) was analyzed. The influence of MYL4 on AF recurrence after RFA was evaluated, and the independent correlation between them was assessed. Patients with AF and the controls showed no significant differences in age, gender, body mass index, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, white blood cell count, neutrophil/lymphocyte ratio, brain natriuretic peptide, and history of smoking, drinking, hypertension, and diabetes (P > 0.05), but with increased LAD in patients with AF (P < 0.01). Serum MYL4 level was reduced in patients with AF (0.6 ± 0.2) compared with that of controls (0.1 ± 0.6) (P < 0.01), and it was negatively correlated with TGF-ß1, PICP, and LAD (r = -0.2389, P < 0.05; r = -0.5174, P < 0.01; r = -0.3191; P < 0.01). Low levels of MYL4 increased the risk of AF recurrence after RFA (χ2 = 16.64; P < 0.0001). A low MYL4 level in patients with AF showed a poorer prognosis. Serum MYL4 level and AF type were independent risk factors affecting AF recurrence after RFA.

Pericardial effusion following percutaneous left atrial appendage closure using the LAmbre device.

Background: Pericardial effusion (PE) is an uncommon but serious complication that occurs following percutaneous left atrial appendage closure (LAAC). There are few data regarding PE following implantation of the LAmbre device for LAAC. Methods: Patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous LAAC using the LAmbre device at the Arrhythmia Center of Ningbo First Hospital from October 2017 to March 2021 were retrospectively reviewed (n = 133). PE was defined as acute if diagnosed ≤7 days post LAAC (n = 3, 2.3%) or delayed if diagnosed >7 days post LAAC (n = 3, 2.3%). The clinical characteristics and procedural data were compared between patients with PE (PE group, n = 6) and without PE (non-PE group, n = 127). The predictors of PE were analyzed by logistic regression. Results: All patients with PE recovered following treatment by pericardiocentesis. Patients with PE were found to have a higher incidence of congestive heart failure (50.0% vs. 13.4%, P = 0.044) and had larger measured LAA orifice diameters (33.5 mm ± 6.0 mm vs. 28.3 mm ± 5.2 mm, P = 0.018) and landing zone diameters (27.8 mm ± 4.8 mm vs. 23.9 mm ± 4.8 mm, P = 0.054) compared with those without PE. The diameters of the device umbrellas (31.7 mm ± 5.6 mm vs. 26.9 mm ± 5.0 mm, P = 0.026) and covers (36.3 mm ± 4.6 mm vs. 33.4 mm ± 4.0 mm, P = 0.075) implanted were larger in the PE group compared to the non-PE group. Univariate logistic regression revealed that congestive heart failure (OR = 6.47, 95% CI = 1.21-34.71, P = 0.029) and LAA maximal orifice diameter (OR = 1.22, 95% CI = 1.02-1.45, P = 0.027) were both associated with PE following LAmbre device implantation. Conclusions: In this single-center experience, both acute and delayed PE were uncommon in patients with AF following LAmbre device implantation. Congestive heart failure and a larger LAA orifice were identified as predictors for the occurrence of PE.

Non-typical persistent hyperplastic primary vitreous: a rare case report and review of the literature.

BACKGROUND: Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature (PFV), is a clinical entity that traditionally presents with leukocoria, microphthalmia, retinal dysplasia, or eyeball shrinkage which is associated with poor vision. However, there is a dearth of literature on cases of PHPV in adulthood or with asymptomatic occurrence. This report presents the clinical and pathological findings of a non-typical PHPV case and discuss the current knowledge for this condition. CASE PRESENTATION: A 68-year-old healthy male was referred to our outpatient department for evaluation of age-related cataract without other visual symptoms. Preoperative fundus examination occasionally detected an isolated stalk-like band extending to the posterior pole of the eye with normal central vitreous and retina. Other ocular examinations including b-mode ultrasonography, optical coherence tomography did not unveil any abnormalities, which caused diagnostic uncertainty. We referred to cataract surgery along with histopathological study, that revealed characteristics of PHPV including fibrous connective tissues mainly composed of fibrocyte proliferation and a very few capillary vessels. Thereafter, a definitive diagnosis of non-typical PHPV was established. CONCLUSION: Our case is unique due to it was not discovered until adulthood, presence with only age-related cataract, and accompanied with normal central vitreous and retina. Histopathological explorations lead to an accurate diagnosis of the condition. Those results broaden the phenotype spectrums of PHPV and further provide clinical clues for the cognition of the disease.

Cataract-causing variant Q70P damages structural stability of ßB1-crystallin and increases its tendency to form insoluble aggregates.

Congenital cataract is the primary cause of childhood blindness worldwide. As the predominant structural protein, ßB1-crystallin plays an important role in maintaining lens transparency and cellular homeostasis. Numerous cataract-causing mutations of ßB1-crystallin have been identified with unclear pathogenic mechanism. We previously identified the mutation Q70P (Q to P at residue position 70) of ßB1-crystallin linked to congenital cataract in a Chinese family. In this work, we investigated the potential molecular mechanism of ßB1-Q70P in the congenital cataract at the molecular, protein, and cellular levels. We purified recombinant ßB1 wild-type (WT) and Q70P proteins and compared their structural characteristics and biophysical properties by spectroscopic experiments under physiological temperature and environmental stresses (ultraviolet irradiation, heat stress, oxidative stress). Notably, ßB1-Q70P significantly changed the structures of ßB1-crystallin and exhibited lower solubility at physiological temperature. Meanwhile, ßB1-Q70P was prone to aggregation in eukaryotic and prokaryotic cells, and was more sensitive to environmental stresses, along with impaired cellular viability. Furthermore, the molecular dynamics simulation indicated that the mutation Q70P damaged secondary structures and hydrogen bond network of ßB1-crystallin, which were essential for the first Greek-key motif. This study delineated the pathological mechanism of ßB1-Q70P and provided novel insights into treatment and prevention strategies for cataract-associated ßB1 mutations.

Copper-catalyzed aerobic oxidation of primary alcohols to carboxylic acids.

Here, the first copper-catalyzed aerobic oxidation of primary alcohols to carboxylic acids with TEMPO and KHSO4 as the co-catalysts has been developed. The reaction exhibits excellent substrate scope and functional group compatibility under mild conditions. Even the very sensitive chiral alcohols, chiral amino alcohols, and alcohol-containing steroid skeletons may be oxidized to afford the corresponding carboxylic acids or lactones without racemization.

Long-term effects of mild cataract extraction versus laser peripheral iridotomy on anterior chamber morphology in primary angle-closure suspect eyes.

AIM: To compare lens extraction (LE) and laser peripheral iridotomy (LPI) on anterior segment morphology in primary angle-closure suspect (PACS) eyes. METHODS: This prospective clinical trial included 144 patients with PACS who underwent either LPI or LE. Ultrasound biomicroscopy (UBM) and gonioscopy were performed before and 1 month and 2 years after operation. Main outcomes included UBM parameters and the percentage of residual angle closure. RESULTS: At both 1 month and 2 years of follow-up, LE showed a better effect of relieving anterior chamber crowding and widening the drainage angle, as obtaining a larger anterior chamber depth (ACD), angle opening distance, trabecular iris angle (TIA), trabecular iris space area, trabecular ciliary process distance (TCPD) and a smaller iris curvature (I-Curv) and lens vault (LV) (p<0.001). In the LPI group, angle width increased (angle opening distance at 500 µm from the scleral spur, TIA and trabecular iris space area at 500 µm from the scleral spur) and I-Curv decreased (p<0.001) at 1 month postoperatively, with no significant changes in ACD, LV or TCPD. However, at 2 years after LPI, the angle narrowed with the increase in LV over time, and the proportion of residual angle closure also increased from 21.7% to 30.4% (p<0.001). In contrast, after LE, the widened angle width, flattened iris, deepened ACD, decreased LV and increased TCPD all showed good sustainability in the comparison between 1-month and 2-year follow-up. No residual angle closure was observed either at 1 month or 2 years after LE. CONCLUSIONS: LE was prior to LPI in widening the drainage angle. After LPI, there was a narrowing of the angle and an increase in the proportion of residual angle closure over time. LE could achieve a wider angle with no residual angle closure, and the anterior segment parameters were sustainable. TRIAL REGISTRATION NUMBER: ChiCTR1800016511.

Thioredoxin-1 regulates the autophagy induced by oxidative stress through LC3-II in human lens epithelial cells.

Oxidative stress plays a major role in age-related cataract development. The cellular antioxidant protein thioredoxin-1 (Trx-1) and its negative regulator, thioredoxin binding protein-2 (TBP-2), are pivotal in the cellular redox balance during oxidative stress. The aim of this study is to investigate the effect of Trx-1 and TBP-2 on LC3 I/LC3 II in oxidative stress-induced autophagy in human lens epithelial cells (LECs). In our study, LECs were treated with 50 µM H2 O2 for different durations, and the expression of Trx-1 and TBP-2 were measured by RT-PCR and Western blot. Trx-1 activity was evaluated by the thioredoxin activity fluorescent assay. The subcellular localization of Trx-1 and TBP-2 was evaluated by cellular immunofluorescence. The interaction between Trx-1 and TBP-2 was examined by co-immunoprecipitation. The cell viability was detected using CCK-8, and the expression of LC3-II/LC3-I was detected to evaluate the autophagy. The results showed that the mRNA levels of the Trx-1 and TBP-2 were kinetically changed after treatment with H2 O2 for different durations. Exposure to H2 O2 increased the expression of TBP-2 but not Trx-1, while the exposure inhibited Trx-1 activity. TBP-2 was co-localized with Trx-1, and exposure to H2 O2 increased the interaction between TBP-2 and Trx-1. Trx-1 overexpression enhanced the autophagic response under normal circumstances and it might regulate autophagy in the initial phase. This study demonstrates the differential role of Trx-1 in cellular oxidative stress response, oxidative stress increased Trx-1 interaction with TBP-2, and Trx-1/TBP-2 regulated the autophagic response in the initial phase through LC3-II.