Upregulation of proBDNF/p75NTR signaling in immune cells and its correlation with inflammatory markers in patients with major depression.

ProBDNF is the precursor protein of brain-derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and p75 neurotrophic receptors (p75NTR) in major depressive disorder (MDD) were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n = 32) and normal donors (n = 20). We examined the expression of proBDNF and inflammatory markers and their correlative relationship in patients with major depression. Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Finally, the role of proBDNF/p75NTR signal in inflammatory immune activity of PBMCs was verified in vitro experiments. Inflammatory cytokines in PBMC from MDD patients were increased and correlated with the major depression scores. The levels of IL-1ß and IL-10 were also positively correlated with the major depression scores, while the levels of TNF-α and IL-6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin were positively correlated with IL-1ß. Q-PCR and Western blots showed proBDNF, p75NTR, and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T cells. The number of proBDNF and p75NTR positive CD4+ and CD8+ T cells from MDD patients was increased and subsequently reversed after therapeutic management. Exogenous proBDNF protein or p75ECD-Fc treatment of cultured PBMC affected the release of inflammatory cytokines in vitro. ProBDNF promoted the expression of inflammatory cytokines, while p75ECD-Fc inhibited the expression of inflammatory cytokines. Given there was an inflammatory response of lymphocytes to proBDNF, it is suggested that proBDNF/p75NTR signaling may upstream inflammatory cytokines in MDD. Our data suggest that proBDNF/p75NTR signaling may not only serve as biomarkers but also may be a potential therapeutic target for MDD.

BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated apoptosis.

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.

Is Kidney Function Associated with Age-Related Macular Degeneration?: Findings from the Asian Eye Epidemiology Consortium.

PURPOSE: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies. METHODS: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m2. A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups. MAIN OUTCOME MEASURES: Odds ratio (OR) of early and late AMD. RESULTS: Among 51 253 participants (mean age, 54.1 ± 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P = 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P = 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P ≥ 0.149). CONCLUSIONS: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Enhanced response over wavelength range of 7-12 µm for quantum wells in asymmetric micro-pillars.

Efficient coupling in broad wavelength range is desirable for wide-spectrum infrared light detection, yet this is a challenge for intersubband transition in semiconductor quantum wells (QWs). High-Q cavities mostly intensify the absorption at peak wavelengths but with shrinking bandwidth. Here, we propose a novel approach to expand the operating spectral range of the Quantum Well Infrared Photodetectors (QWIPs). By processing the QWs into asymmetric micro-pillar array structure, the device demonstrates a substantial enhancement in spectral response across the wavelength from 7.1 µm to 12.3 µm with guided mode resonance (GMR) effects. The blackbody responsivity is then increased by 3 times compared to that of the 45° polished edge-coupled counterpart. Meanwhile, the dark current density remains unchanged after the deep etching process, which will benefit the electrical performance of the detector with reduced volume duty ratio. In contrast to the symmetric micro-pillar array that contains simple resonance mode, the detectivity of QWIP in asymmetric pillar structure is found to be improved by 2-4 times within the range of 9.5 µm to 15 µm.

Clinical metabolomics characteristics of diabetic kidney disease: A meta-analysis of 1875 cases with diabetic kidney disease and 4503 controls.

AIMS: Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD. MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis. RESULTS: The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (p < 0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered. CONCLUSIONS: We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.

Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Zonular instability-associated morphologic features in eyes with primary angle closure disease using the swept-source anterior segment - optical coherence tomography system.

BACKGROUND: This study aims to investigate the morphologic features of the crystalline lens in Primary Angle Closure Disease (PACD) patients with zonular instability during cataract surgery using the swept-source CASIA 2 Anterior Segment-Optical Coherence Tomography (AS-OCT) system. METHODS: A total of 398 eyes (125 PACD eyes with zonular instability, 133 PACD eyes with zonular stability, and 140 cataract patient controls) of 398 patients who underwent cataract surgery combined or not glaucoma surgery between January 2021 and January 2023 were enrolled. The crystalline lens parameters were measured by CASIA2 AS-OCT. Then, logistic regression was performed to evaluate the risk factors associated with zonular instability. RESULTS: The results revealed that PACD eyes had a more anterior lens equator position, a steeper anterior curvature of lens, shorter Axial Length (AL), shallower Anterior Chamber Distance (ACD), higher Lens Vault (LV) and thicker Lens Thickness (LT), when compared to eyes in the cataract control group. Furthermore, PACD eyes in the zonular instability group had steeper front R, front Rs and Front Rf, flatter back Rf, thicker lens anterior part thickness, higher lens anterior-to-posterior part thickness ratios, shallower ACD, and greater LV, when compared to PACD eyes with zonular stability. The logistic regression analysis, which was adjusted for age and gender, revealed that zonular instability was positively correlated with anterior part thickness, lens anterior-to-posterior part thickness ratio, and LV, but was negatively correlated with lens anterior radius and ACD. CONCLUSION: Steeper anterior curvature, increased lens anterior part thickness, higher anterior-to-posterior part thickness ratio, shallower ACD, and greater LV are the anatomic features of PACD eyes associated with zonular instability.

The Effects of Health Education and the Sunrise Model of Nursing Care on Blood Pressure Control and Psychological Status in Elderly Patients with Hypertension.

Objective: Our aim was to investigate the effect of health education and a positive attitude nursing model on blood pressure (BP) control and psychological status in elderly patients with hypertension (HTN). Methods: A total of 80 elderly patients with HTN in the Affiliated Hangzhou First People's Hospital in China were selected as the study participants. They were randomly divided into a control group and an observation group, with 40 patients in each group. The control group received the routine nursing intervention, while the observation group received health education and the positive attitude nursing intervention based on the nursing care in the control group. The BP control effect, changes in systolic and diastolic BP, psychological status and nursing satisfaction were compared in the 2 groups. Results: The BP control rate in the control group was 77.5% and was 95.0% in the observation group, which was significantly better (P < .05). Before the intervention, there was no significant difference in average systolic and diastolic BP between the 2 groups (P > .05); after the intervention, average systolic and diastolic BP in the observation group were significantly lower than in the control group (P < .05). Before the intervention, there was no significant difference in Self-rating Anxiety Scale (SAS) and Self-rating Anxiety Scale (SDS) scores between the 2 groups (P > .05). After the intervention, the SAS and SDS scores in the observation group were significantly better than those in the control group (P < .05). The nursing satisfaction in the control group was 75.0% and was 95.0% in the observation group, which was significantly higher (P < .05). Conclusion: Compared with routine nursing intervention, the health education and positive attitude nursing intervention can further improve BP control, psychological status and satisfaction and recognition level of elderly patients with HTN; it can be an important clinical nursing intervention.

Atrial Fibrillation Detection with Single-Lead Electrocardiogram Based on Temporal Convolutional Network-ResNet.

Atrial fibrillation, one of the most common persistent cardiac arrhythmias globally, is known for its rapid and irregular atrial rhythms. This study integrates the temporal convolutional network (TCN) and residual network (ResNet) frameworks to effectively classify atrial fibrillation in single-lead ECGs, thereby enhancing the application of neural networks in this field. Our model demonstrated significant success in detecting atrial fibrillation, with experimental results showing an accuracy rate of 97% and an F1 score of 87%. These figures indicate the model's exceptional performance in identifying both majority and minority classes, reflecting its balanced and accurate classification capability. This research offers new perspectives and tools for diagnosis and treatment in cardiology, grounded in advanced neural network technology.

Association between personality traits and psychological distress among postmenopausal women with coronary heart disease: A cross-sectional survey and mediation analysis.

Postmenopausal women with negative personality characteristics are at an increased risk of psychological disorders, yet little is known about the mechanism underlying the relationship between type D personality and psychological distress in postmenopausal women with coronary disease. This study assessed the mediating roles of perceived social support and self-perceived burden in the relationship between type D and psychological distress based on the equity theory and stress-buffering model. Demographic characteristics, type D, psychological distress, perceived social support, and self-perceived burden were completed by 335 participants with self-reported questionnaires using a cross-sectional design in Southeast China. The results revealed that perceived social support and self-perceived burden both separately and serially mediated the relationship between type D personality and psychological distress. Effective intervention strategies aimed at improving perceived social support or reducing self-perceived burden may be beneficial in reducing psychological distress.

Establishment and characterization of Lesch-Nyhan syndrome rabbit model.

Lesch-Nyhan syndrome (LNS) is a congenital defect disease that results in defective purine metabolism. It is caused by pathogenic variants of the HPRT gene. Its clinical symptoms mainly include high uric acid levels, gout, and kidney stones and damage. The mechanism of LNS has not been fully elucidated, and no cure exists. Animal models have always played an important role in exploring causative mechanisms and new therapies. This study combined CRISPR/Cas9 and microinjection to knock out the HPRT gene to create an LNS rabbit model. A sgRNA targeting exon 3 of HPRT gene was designed. Subsequently, Cas9 mRNA and sgRNA were injected into rabbit zygotes, and injected embryos were transferred to the uterus. The genotype and phenotype of rabbits were analyzed after birth. Four infant rabbits (named R1, R2, R3 and R4), which showed varying levels of gene modification, were born. The gene-editing efficiency was 100%. No wild-type sequences at the target HPRT gene were detected in R4 rabbit. Next, 6-thioguanine drug testing confirmed that HPRT enzymatic activity was deficient in R4 infant rabbit. HE staining revealed kidney abnormalities in all infant rabbits. Overall, an sgRNA capable of knocking out the HPRT gene in rabbits was successfully designed, and HPRT gene-modified rabbits were successfully constructed by using CRISPR/Cas9 technology and microinjection. This study provides a new nonrodent animal model for studying LNS syndrome.

Serum Metabolomic Profiles for Distinguishing Lung Cancer From Pulmonary Tuberculosis: Identification of Rapid and Noninvasive Biomarker.

BACKGROUND: Pulmonary tuberculosis (PTB) and lung cancer (LC) have similar clinical symptoms and atypical imaging findings, which are easily misdiagnosed. There is an urgent need for a noninvasive and accurate biomarker to distinguish LC from PTB. METHODS: A total of 694 subjects were enrolled and divided into discovery set (n = 122), identification set (n = 214), and validation set (n = 358). Metabolites were identified by multivariate and univariate analyses. Receiver operating characteristic curve were used to evaluate the diagnostic efficacy of biomarkers. RESULTS: Seven metabolites were identified and validated. Phenylalanylphenylalanine for distinguishing LC from PTB yielded an area under the curve of 0.89, sensitivity of 71%, and specificity of 92%. It also showed good diagnostic abilities in discovery set and identification set. Compared with that in healthy volunteers (median [interquartile range], 1.57 [1.01, 2.34] µg/mL), it was elevated in LC (4.76 [2.74, 7.08] µg/mL; ratio of median, [ROM] = 3.03, P < .01) and reduced in PTB (1.06 [0.51, 2.09] µg/mL; ROM = 0.68, P < .05). CONCLUSIONS: The metabolomic profile of LC and PTB was described and a key biomarker identified. We produced a rapid and noninvasive method to supplement existing clinical diagnostic examinations for distinguishing LC from PTB.

Establishment of a prognostic signature for lung adenocarcinoma using cuproptosis-related lncRNAs.

OBJECTIVE: To establish a prognostic signature for lung adenocarcinoma (LUAD) based on cuproptosis-related long non-coding RNAs (lncRNAs), and to study the immune-related functions of LUAD. METHODS: First, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate COX analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate COX analysis were performed to analyze the cuproptosis-related lncRNAs, and a prognostic signature was established. Second, univariate COX analysis and multivariate COX analysis were performed for independent prognostic analyses. Receiver operating characteristic (ROC) curves, C index, survival curve, nomogram, and principal component analysis (PCA) were performed to evaluate the results of the independent prognostic analyses. Finally, gene enrichment analyses and immune-related function analyses were also carried out. RESULTS: (1) A total of 1,297 cuproptosis-related lncRNAs were screened. (2) A LUAD prognostic signature containing 13 cuproptosis-related lncRNAs was constructed (NIFK-AS1, AC026355.2, SEPSECS-AS1, AL360270.1, AC010999.2, ABCA9-AS1, AC032011.1, AL162632.3, LINC02518, LINC0059, AL031600.2, AP000346.1, AC012409.4). (3) The area under the multi-indicator ROC curves at 1, 3, and 5 years were AUC1 = 0.742, AUC2 = 0.708, and AUC3 = 0.762, respectively. The risk score of the prognostic signature could be used as an independent prognostic factor that was independent of other clinical indicators. (4) The results of gene enrichment analyses showed that 13 biomarkers were primarily related to amoebiasis, the wnt signaling pathway, hematopoietic cell lineage. The ssGSEA volcano map showed significant differences between high- and low-risk groups in immune-related functions, such as human leukocyte antigen (HLA), Type_II_IFN_Reponse, MHC_class_I, and Parainflammation (P < 0.001). CONCLUSIONS: Thirteen cuproptosis-related lncRNAs may be clinical molecular biomarkers for the prognosis of LUAD.

Targeting immunometabolism against acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions triggered by multiple intra- and extra-pulmonary injury factors, characterized by complicated molecular mechanisms and high mortality. Great strides have been made in the field of immunometabolism to clarify the interplay between intracellular metabolism and immune function in the past few years. Emerging evidence unveils the crucial roles of immunometabolism in inflammatory response and ALI. During ALI, both macrophages and lymphocytes undergo robust metabolic reprogramming and discrete epigenetic changes after activated. Apart from providing ATP and biosynthetic precursors, these metabolic cellular reactions and processes in lung also regulate inflammation and immunity.In fact, metabolic reprogramming involving glucose metabolism and fatty acidoxidation (FAO) acts as a double-edged sword in inflammatory response, which not only drives inflammasome activation but also elicits anti-inflammatory response. Additionally, the features and roles of metabolic reprogramming in different immune cells are not exactly the same. Here, we outline the evidence implicating how adverse factors shape immunometabolism in differentiation types of immune cells during ALI and summarize key proteins associated with energy expenditure and metabolic reprogramming. Finally, novel therapeutic targets in metabolic intermediates and enzymes together with current challenges in immunometabolism against ALI were discussed.

Prospects and challenges of CRISPR/Cas9 gene-editing technology in cancer research.

Cancer, one of the leading causes of death, usually commences and progresses as a result of a series of gene mutations and dysregulation of expression. With the development of clustered regularly interspaced palindromic repeat (CRISPR)/Cas9 gene-editing technology, it is possible to edit and then decode the functions of cancer-related gene mutations, markedly advance the research of biological mechanisms and treatment of cancer. This review summarizes the mechanism and development of CRISPR/Cas9 gene-editing technology in recent years and describes its potential application in cancer-related research, such as the establishment of human tumor disease models, gene therapy and immunotherapy. The challenges and future development directions are highlighted to provide a reference for exploring pathological mechanisms and potential treatment protocols of cancer.

Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper GI tract in cirrhotic patients with esophagogastric varices: 10-year experience from a large tertiary center in China.

BACKGROUND AND AIMS: Treatment strategies for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and esophagogastric varices (EGVs) are complicated and risky. The aim of this study was to assess the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of such patients and explore optimal treatment strategies. METHODS: We retrospectively enrolled 15 patients with cirrhosis and EGV who underwent ESD for early cancers or precancerous lesions of the upper GI tract from January 2012 to December 2021 at our center. Clinical features, endoscopic findings, treatment methods, adverse events, and follow-up data were analyzed. RESULTS: Of the 15 patients, 1 had a platelet count <30 × 1000/mm3. Five were untreated for EGV, 1 was treated after ESD, 6 were treated before ESD, 1 was treated before and during ESD, and 2 were treated during ESD. The R0 resection rate was 100%. Of the 16 mucosal lesions, 15 were endoscopic resection bleeding (ERB)-0 or ERB-c1, and 1 was ERB-c2. No patient experienced deterioration in liver function. The only adverse events were fever in 2 patients and postoperative bleeding in 2 patients. During a median follow-up of 27 months, 1 patient's esophageal high-grade dysplasia recurred at 19 months. No death resulted from the ESD procedure, liver function injury, or GI tumor itself. CONCLUSIONS: ESD is an effective and safe treatment for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and EGV. The incidence of severe adverse events is very low due to the development of individualized clinical treatment strategies.

A novel mechanism for the protection against acute lung injury by melatonin: mitochondrial quality control of lung epithelial cells is preserved through SIRT3-dependent deacetylation of SOD2.

The mitochondrial quality control of lung epithelial cells is disturbed during sepsis, which contributes to abnormal mitochondrial function and acute lung injury. Melatonin is one of the primary hormones secreted by the pineal gland, displaying favorable antioxidative actions in sepsis and cardiopulmonary disease. However, the potential roles and molecular basis of melatonin in lipopolysaccharide (LPS)-treated lung epithelial cells have not been explored and reported. Herein, we investigated whether melatonin could protect against sepsis-induced acute lung injury (ALI) and LPS-treated lung epithelial cells through the mitochondrial quality control as well as its possible molecular targets. Wild type and Sirt3 knockout mice were intratracheally instilled with LPS for 12 h to construct an in vivo acute lung injury model. Both A549 lung epithelial cells and primary alveolar type II (AT-II) cells were used to explore the possible roles of melatonin in vitro by incubating with small interfering RNA against Sirt3. To determine the involvement of the melatonin receptor, cells and mice were treated with si Mtnr1b and luzindole. Melatonin pretreatment significantly inhibited pathological injury, inflammatory response, oxidative stress, and apoptosis in LPS-treated lung tissues and LPS-treated lung epithelial cells. Furthermore, melatonin also shifted the dynamic course of mitochondria from fission to fusion, inhibited mitophagy and fatty acid oxidation in LPS-treated lung epithelial cells in vitro and in vivo. However, SIRT3 inhibition abolished the protective roles of melatonin in acute lung injury. Mechanistically, we found that melatonin increased the activity and expression of SIRT3, which further promoted the deacetylation of SOD2 at K122 and K68. More importantly, melatonin exerted pulmonary protection by activating MTNR1B but not MTNR1A during ALI. Collectively, melatonin could preserve the mitochondrial quality control of lung epithelial cells through the deacetylation of SOD2 in a SIRT3-dependent manner, which eventually alleviated sepsis-induced injury, inflammation, oxidative stress, and apoptosis. Thus, melatonin may serve as a promising candidate against ALI in the future.

Serum antiretinal antibodies and cytokine profiling in autoimmune retinopathy and their association with clinical outcomes.

PURPOSE: Autoimmune retinopathy (AIR) is a group of autoimmune retinal diseases that can cause blindness. The purpose of this study is to investigate the profiles of serum antiretinal antibodies (ARAs) and cytokines and their association with disease diagnosis as well as clinical features in AIR. METHODS: The patients with presumed para (p) and non-paraneoplastic (np) AIR diagnosis, the patients with retinitis pigmentosa and bilateral uveitis as disease controls, and healthy subjects were prospectively enrolled. Western blotting and Luminex multiple cytokine assay/enzyme linked immunosorbent assay were used to determine the presence of serum ARAs and the concentration of cytokines, respectively. Kruskal-Wallis or chi square test was applied to compare the profiles of ARA and cytokines among various groups. The multilevel mixed-effect regression was used to investigate the association of ARA or cytokines with clinical features. RESULTS: No significant difference in the band number and subtypes of serum ARAs was found between AIR patients and their controls. AIR patients had higher concentration of serum IFN-ɤ, CXCL9, or CXCL10 than non-AIR controls. A positive correlation was found between increased number of ARAs and elevated TNF-α in np-AIR patients. Elevated pro-inflammatory cytokines or ARA subtypes (antibody against recoverin and α-enolase) were associated with worse retinal functions or anatomy, including visual acuity, visual field, ERG parameters, and central retinal thickness. CONCLUSIONS: The data of our study demonstrate that detection of serum ARAs has limited value in the diagnosis of AIR. Th1-type cytokines/chemokines or specific ARA subtypes are associated with pathogenesis and disease severity of the AIR.

Topographic Differences in Superficial Macular Vessel Density in Eyes with Early Primary Open-Angle Glaucoma and Normal Tension Glaucoma.

INTRODUCTION: The aim of the study was to compare macular vascular microcirculation in early primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and normal subjects. METHODS: 99 patients with early glaucoma (99 eyes: 60 POAG and 39 NTG) and 78 normal subjects were included. All subjects underwent optical coherence tomography angiography scan at 6 × 6 mm macular area. Macular vessel density (VD) and perfusion density (PD) and 9 sectors were compared between the controls, POAG, and NTG groups. Linear regression analysis was used to investigate the relationship between VD and other variables including macular PD, signal strength (SS), and mean macular ganglion cell-inner plexiform layer (mGCIPL) thickness. RESULTS: Significant losses in total area of VD and PD were detected in POAG and NTG groups compared to the controls (all p < 0.01). There were no significant differences in all inner sectors of macular VD and PD between POAG and controls (all p > 0.05). Except for outer-nasal sector, all other outer sectors of macular VD and PD were significantly lower in POAG than in the controls (all p < 0.01). The inferior-inner sector and all outer sectors of VD and PD were significantly lower in NTG than in the controls (all p < 0.01). Macular VD was significantly correlated with macular PD (r = 0.99, p < 0.001), SS (r = 0.60, p < 0.001), and mGCIPL thickness (r = 0.51, p < 0.001). CONCLUSIONS: Macular microcirculation declined significantly in early POAG and NTG patients. Macular microcirculation loss in the NTG group was more central and nasal compared with that in the POAG group. A decrease in macular VD was correlated with lower macular PD, lower SS, and thinner mGCIPL thickness.

Return to Work Experience of Young and Middle-Aged Patients With Acute Myocardial Infarction: A Longitudinal Qualitative Study.

BACKGROUND: Return to work (RTW) is a critical component of rehabilitation for most young and middle-aged patients after an acute myocardial infarction (AMI). Its success is related to the quality of life and social psychological function of patients, and their social economic growth. However, healthcare professionals often do not deeply understand the patients' experience and their difficulties and coping methods during this process, which limits their ability to institute effective management and support. OBJECTIVE: In this study, we aimed to explore the lived experiences and change processes of young and middle-aged patients with AMI at the different stages of RTW. METHODS: A descriptive qualitative approach was used. Patients aged 20 to 59 years with AMI were recruited from the Department of Cardiology of 3 general hospitals. Data were collected via semistructured interviews. Data analysis was performed by conventional content analysis methods. RESULTS: In total, 18 participants were included. Five main themes emerged: (1) "chaos," (2) "rebuilding," (3) "conflict," (4) "coping," and (5) "benefits." Patients may be more concerned about physical recovery during the initial clinical event. They then begin to plan and adjust for an RTW. Patients in the maintenance phase need strategies to prevent, identify, and respond to conflicts and challenges to maintain long-term stable work. CONCLUSION: We identified several post-AMI stages spanning from the initial illness event to the maintenance of stable work. We described their perceived barriers, coping strategies, and support needs at these various stages. These data are crucial for healthcare professionals to develop improved vocational rehabilitation strategies for patients with AMI.