Video feedback combined with peer role-playing: a method to improve the teaching effect of medical undergraduates.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of implementation of video feedback combined with peer role-playing (PRP) teaching method in medical undergraduates adopting problem-based learning (PBL) teaching mode. METHODS: The undergraduates of five-year clinical medicine who get enrollment of Wuhan local University from 2016 and 2018 were selected to be the research objects. The same grade level is randomly divided into several groups to carry out PBL, with 6-10 students in each group. Following the principle of voluntary participation, 34 students were enrolled in the study group and 33 students in the control group finally. The research regards group as the unit, and study report in group should be carried out to fulfill the research. In the study group, the students were asked to perform PRP report, and the report videos were used for feedback. At the same time, the control group reported by PPT, and the feedback was carried out according to the PPT. At the end of the study, the "Competency Improvement Satisfaction Questionnaire (CISQ)" was distributed to investigate students' satisfaction with this teaching method to improve their ability, Arizona Clinical Interview Score (ACIR) was administered in Chinese by a trained teacher unrelated using PRP method to assess students' clinical inquiry ability and communication skills, and theory test was performed to assess mastery of theoretical knowledge. RESULTS: The results show that the study group is superior to the control group in improving the interest of learning and the ability of independent learning, interpersonal communication and active problem solving. Although it is in terms of the confidence in becoming a real doctor and the ability of teamwork, language expression, clinical thinking cultivated, active knowledge acquired and understood that study group are better than the control group, the difference was not statistically significant. ACIR shows that the study group is significantly better than the control group in organization, timeline planning, and transition statements, openly questioning, smooth progress, and avoiding repetition, summarizing, understandable language, documentation and total score. There is no significant difference in eye contact and no interruption. The differences between the two groups are not statistically significant in terms of responsing to concerns, positive feedback, and additional questions. The theoretical test scores of the study group are significantly higher than those of the control group. CONCLUSION: Video feedback combined with peer role-playing teaching method implemented in medical undergraduates adopting PBL teaching mode is effective, it could stimulate interest in learning actively, improve interpersonal communication ability, improve learning efficiency and clinical knowledge and skills, and improve the confidence of becoming a real doctor. It is worthy of further research and promotion.

Initial dosage optimisation of cyclosporine in Chinese paediatric patients undergoing allogeneic haematopoietic stem cell transplantation based on population pharmacokinetics: a retrospective study.

OBJECTIVE: Improved understanding of cyclosporine A (CsA) pharmacokinetics in children undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) is crucial for effective prevention of acute graft-versus-host disease and medication safety. The aim of this study was to establish a population pharmacokinetic (Pop-PK) model that could be used for individualised therapy to paediatric patients undergoing allo-HSCT in China. DESIGN, SETTING AND PARTICIPANTS: A retrospective analysis of 251 paediatric HSCT patients who received CsA intravenously in the early post transplantation period at Women and Children's Medical Center in Guangzhou was conducted. ANALYSIS MEASURES: The model building dataset from 176 children was used to develop and analyse the CsA Pop-Pk model by using the nonlinear mixed effect model method. The basic information was collected by the electronic medical record system. Genotype was analysed by matrix-assisted time-of-flight mass spectrometry. The stability and predictability of the final model were verified internally, and a validation dataset of 75 children was used for external validation. Monte Carlo simulation is used to adjust and optimise the initial dose of CsA in paediatric allo-HSCT patients. RESULTS: The typical values for clearance (CL) and volume of distribution ([Formula: see text]) were 14.47 L/hour and 2033.53 L, respectively. The body weight and haematocrit were identified as significant variables for V, while only body weight had an impact on CL. The simulation based on the final model suggests that paediatrics with HSCT required an appropriate intravenous dose of 5 mg/kg/day to reach the therapeutic trough concentration. CONCLUSIONS: The CsA Pop-PK model established in this study can quantitatively describe the factors influencing pharmacokinetic parameters and precisely predict the intrinsic exposure to CsA in children. In addition, our dosage simulation results can provide evidence for the personalised medications TRIAL REGISTRATION NUMBER: ChiCTR2000040561.

Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis.

BACKGROUND: Autoimmune uveitis (AU) is the most common ophthalmic autoimmune disease (AD) and is characterized by a complex etiology, high morbidity, and high rate of blindness. AU remission has been observed in pregnant female patients. However, the effects of progesterone (PRG), a critical hormone for reproduction, on the treatment of AU and the regulatory mechanisms remain unclear. METHODS: To this end, we established experimental autoimmune uveitis (EAU) animal models and constructed a high-dimensional immune atlas of EAU-model mice undergoing PRG treatment to explore the underlying therapeutic mechanisms of PRG using single-cell RNA sequencing. RESULTS: We found that PRG ameliorated retinal lesions and inflammatory infiltration in EAU-model mice. Further single-cell analysis indicated that PRG reversed the EAU-induced expression of inflammatory genes (AP-1 family, S100a family, and Cxcr4) and pathological processes related to inflammatory cell migration, activation, and differentiation. Notably, PRG was found to regulate the Th17/Treg imbalance by increasing the reduced regulatory functional mediators of Tregs and diminishing the overactivation of pathological Th17 cells. Moreover, the Id2/Pim1 axis, IL-23/Th17/GM-CSF signaling, and enhanced Th17 pathogenicity during EAU were reversed by PRG treatment, resulting in the alleviation of EAU inflammation and treatment of AD. CONCLUSIONS: Our study provides a comprehensive single-cell map of the immunomodulatory effects of PRG therapy on EAU and elaborates on the possible therapeutic mechanisms, providing novel insights into its application for treating autoimmune diseases.

Single-Cell Profiling Reveals Sustained Immune Infiltration, Surveillance, and Tumor Heterogeneity in Infiltrative Basal Cell Carcinoma.

Infiltrative basal cell carcinoma (iBCC) is a particularly aggressive subtype of basal cell carcinoma that tends to progress and recur after surgery, and its malignancy is closely related to the tumor microenvironment. In this study, we performed a comprehensive single-cell RNA analysis to profile 29,334 cells from iBCC and adjacent normal skin. We found active immune collaborations enriched in iBCC. Specifically, SPP1+CXCL9/10high macrophage 1 had strong BAFF signaling with plasma cells, and T follicular helper-like cells highly expressed the B-cell chemokine CXCL13. Heterogeneous proinflammatory SPP1+CXCL9/10high macrophage 1 and angiogenesis-related SPP1+CCL2high macrophage 1 were identified within the tumor microenvironment. Interestingly, we found an upregulation of major histocompatibility complex I molecules in fibroblasts in iBCC compared with those in adjacent normal skin. Moreover, MDK signals derived from malignant basal cells were markedly increased, and their expression was an independent factor in predicting the infiltration depth of iBCC, emphasizing its role in driving malignancy and remodeling the tumor microenvironment. In addition, we identified differentiation-associated SOSTDC1+IGFBP5+CTSV+ malignant basal subtype 1 and epithelial-mesenchymal transition-associated TNC+SFRP1+CHGA+ malignant basal subtype 2 cells. The high expression of malignant basal 2 cell markers was associated with the invasion and recurrence of iBCC. Altogether, our study helps to elucidate the cellular heterogeneity in iBCC and provides potential therapeutic targets for clinical research.

Sleep loss potentiates Th17-cell pathogenicity and promotes autoimmune uveitis.

BACKGROUND: Sleep loss (SL) is a health issue associated with the higher risk of autoimmune and inflammatory disorders. However, the connection between SL, the immune system, and autoimmune diseases remains unknown. METHODS: We conducted mass cytometry, single-cell RNA sequencing, and flow cytometry to analyze how SL influences immune system and autoimmune disease development. Peripheral blood mononuclear cells from six healthy subjects before and after SL were collected and analyzed by mass cytometry experiments and subsequent bioinformatic analysis to identify the effects of SL on human immune system. Sleep deprivation and experimental autoimmune uveitis (EAU) mice model were constructed, and scRNA-seq data from mice cervical draining lymph nodes were generated to explore how SL influences EAU development and related autoimmune responses. RESULTS: We found compositional and functional changes in human and mouse immune cells after SL, especially in effector CD4+ T and myeloid cells. SL upregulated serum GM-CSF levels in healthy individuals and in patients with SL-induced recurrent uveitis. Experiments in mice undergoing SL or EAU demonstrated that SL could aggravate autoimmune disorders by inducing pathological immune cell activation, upregulating inflammatory pathways, and promoting intercellular communication. Furthermore, we found that SL promoted Th17 differentiation, pathogenicity, and myeloid cells activation through the IL-23Th17GM-CSF feedback mechanism, thus promoting EAU development. Lastly, an anti-GM-CSF treatment rescued SL-induced EAU aggravation and pathological immune response. CONCLUSIONS: SL promoted Th17 cells pathogenicity and autoimmune uveitis development, especially through the interaction between Th17 and myeloid cells involving GM-CSF signaling, providing possible therapeutic targets for the SL-related pathological disorders.

Optimized design of surgical steps in pars plana vitrectomy for macular hole retinal detachment in pathological myopia decreases rate of iatrogenic retinal break and shortens length of operation.

BACKGROUND: To investigate the effect of surgical steps optimization in pars plana vitrectomy (PPV) with internal limiting membrane (ILM) flap for macular hole retinal detachment (MHRD) in pathological myopia. METHODS: A retrospective, consecutive, nonrandomized comparative study. High myopic eyes diagnosed with MHRD receiving PPV with ILM flap from March 2019 to June 2020 in Department of Ophthalmology, Xiangya Hospital, Central South University were included in the study. Patients were included into two groups based on different design of surgical steps. In the routine group, extension of posterior vitreous detachment (PVD) towards periphery was performed right after induction of PVD. In the experiment group, the retina was reattached with drainage of subretinal fluid through macular hole before peripheral vitreous was dealt with. Complete ophthalmic examinations were performed before and after surgery. The follow-up time was at least 6 months. The rate of iatrogenic retinal break and length of operation were compared between the two groups. RESULTS: Thirty-one eyes from 31 patients were included in the study with 15 in the experiment group and 16 in the routine group. Demographics showed no statistically significant difference between the two groups. Post-op BCVA, rate of macular hole closure and rate of retinal reattachment were similar in the two groups. The rate of iatrogenic retinal break in the experiment group was significantly lower than that in the routine group (6.7% vs. 37.5%, P < 0.05). The average length of operation was 78.6 ± 18.8 min in the routine group and 64.0 ± 12.1 min in the experiment group (P < 0.05). CONCLUSIONS: Optimized design of surgical steps in PPV for MHRD could effectively decrease the rate of iatrogenic retinal tear and shorten the length of operation.

Risk of Cardiovascular Disease Death in Older Malignant Melanoma Patients: A Population-Based Study.

Noncancer deaths account for a large proportion of deaths in patients with malignant melanoma (MM), but the risk of cardiovascular disease (CVD) death in older MM patients remains unclear. This study aimed to estimate the risk of CVD death in older MM patients. Data on older MM patients were obtained in the Surveillance, Epidemiology, and End Results database. Risk of CVD death was calculated by standardized mortality rates (SMRs), cumulative mortality and proportion of different causes of death. MM patients had a higher risk of CVD death than general populations (SMR = 1.98; 95% CI 1.93−2.03, p < 0.001). CVD death was more common in MM patients who were diagnosed at age 85 or older, had a localized stage, were white, had surgical treatment, had a primary head/neck/upper limb site and had a low-grade and superficial spreading/lentigo malignant pathologic type. Cumulative CVD mortality was more common than primary cancer in all older age groups, male or female, and patients with localized-stage disease. Other than primary cancer, CVD was the main cause of death in older patients diagnosed with MM. Our findings highlight CVD death is an important competing event of deaths in older MM patients, and more attention should be paid to reducing CVD death to improve survival.

Bioinformatic profiling identifies the glutaminase to be a potential novel cuproptosis-related biomarker for glioma.

Glioma is the most common tumour of the central nervous system, with a poor prognosis and an increasing trend of incidence in recent years; it is also beginning to affect younger age groups more. Added to this, cuproptosis is a new form of cell death. Indeed, when a certain amount of copper accumulates in a cell, it affects specific mitochondrial metabolic enzymes in that cell and leads to cell death-a phenomenon known as cuproptosis. In this study, we applied bioinformatics analysis, and, according to the results of the study analysis and Gene Ontology (GO), as well as the Kyoto Encyclopedia of Genes and Genomes KyotoEncyclopediaofGenesandGenomes, the glutaminase (GLS) genes affect the prognosis and tumour mutation of glioma patients through cuproptosis. Interestingly, however, GLS is not involved in the immune escape of glioma. Glutaminase genes are a class of glucose metabolism-related genes that are involved in the tricarboxylic acid cycle of cells. At the same time, the expression of the glutaminase gene was positively correlated with the degree of immune cell infiltration and the expression of various immune cell markers, and thus affected the prognosis of glioma patients. Therefore, we believe that the cuproptosis-related glutaminase gene can be an important factor in determining the prognosis of glioma patients.

Identification of a prognostic model using cuproptosis-related genes in uveal melanoma.

The most common intraocular malignancy in adults remains uveal melanoma (UVM), and those with metastatic disease have a poor outlook. Proliferation, angiogenesis, and metastasis of tumor cells can be triggered by cuproptosis, affecting the survival of cancer patients. Nonetheless, cuproptosis-related genes (CRGs) have not been identified in UVM. In this study, we analyzed 10 CRGs in 80 patients with UVM in the Cancer Genome Atlas (TCGA) database regarding the alterations of the genes including copy number variation and methylation. We further constructed a prognostic gene model using these CRGs and built the risk score formula. Univariate and multivariate Cox regression was applied to validate the risk score as an independent prognostic factor. The prognostic model was validated using 63 UVM samples from the GSE22138 cohort, an independent validation data set. Based on the risk scores for 80 patients with UVM from TCGA, we categorized the patients into high- and low-risk groups. Differentially expressed genes (DEGs) between groups were enriched in allograft rejection, hypoxia, glycolysis, TNFα signaling via NF-κB, and interferon-γ responses via Gene set enrichment analysis (GSEA). CD8 T cells and exhausted T cells were notably enriched in the high-risk group. In conclusion, the alteration of CRGs is related to patients with UVM, and the constructed CRG-related model may be helpful to predict the prognosis of such patients.

Single-cell RNA sequencing depicts the local cell landscape in thyroid-associated ophthalmopathy.

There is a specific reactivity and characteristic remodeling of the periocular tissue in thyroid-associated ophthalmopathy (TAO). However, local cell changes responsible for these pathological processes have not been sufficiently identified. Here, single-cell RNA sequencing is performed to characterize the transcriptional changes of cellular components in the orbital connective tissue in individuals with TAO. Our study shows that lipofibroblasts with RASD1 expression are highly involved in inflammation and adipogenesis during TAO. ACKR1+ endothelial cells and adipose tissue macrophages may engage in TAO pathogenesis. We find CD8+CD57+ cytotoxic T lymphocytes with the terminal differentiation phenotype to be another source of interferon-γ, a molecule actively engaging in TAO pathogenesis. Cell-cell communication analysis reveals increased activity of CXCL8/ACKR1 and TNFSF4/TNFRSF4 interactions in TAO. This study provides a comprehensive local cell landscape of TAO and may be valuable for future therapy investigation.

Inverted multi-layer internal limiting membrane flap for macular hole retinal detachment in high myopia.

To investigate the surgical outcomes of pars plana vitrectomy (PPV) combined with inverted multi-layer internal limiting membrane (ILM) flap for the treatment of macular hole retinal detachment in high myopia. We retrospectively analysed the medical records of macular hole retinal detachment (MHRD) patients with high myopia. The patients were divided into two groups with different surgical procedure: inverted multi-layer ILM flap group (group 1, 27 eyes) and the ILM peeling group (group 2, 29 eyes). Retinal reattachment rate, macular hole closure rate at last follow-up and BCVA at 6 months post-operation were compared between the two groups. After primary PPV and silicone oil removal, the retinal reattachment rate was 96.3% in group 1 and 93.1% in group 2 respectively at last follow-up, showing no statistically significant difference (odds ratio = 0.525, P = 1.000). All eyes in group 1 had type I macular closure (100%, 27/27), while only 7 eyes (24.1%, 7/29) in group 2 have type I macular hole closure. The difference was statistically significant (odds ratio = 0, P < 0.05). The mean logMAR BCVA both improved significantly at 6 months post-operation compared with pre-operation (t = 4.181, P < 0.001; t = 3.217, P < 0.001), however the difference of post-operation BCVA between the two groups was not statistically significant (t = 0.906, P > 0.05). PPV combined with inverted multi-layer ILM flap could achieve better anatomical outcomes than ILM peeling technique with no significant advantage in functional outcomes.

Machine learning to predict metabolic drug interactions related to cytochrome P450 isozymes.

Drug-drug interaction (DDI) often causes serious adverse reactions and thus results in inestimable economic and social loss. Currently, comprehensive DDI evaluation has become a major challenge in pharmaceutical research due to the time-consuming and costly process of the experimental assessment and it is of high necessity to develop effective in silico methods to predict and evaluate DDIs accurately and efficiently. In this study, based on a large number of substrates and inhibitors related to five important CYP450 isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4), a series of high-performance predictive models for metabolic DDIs were constructed by two machine learning methods (random forest and XGBoost) and 4 different types of descriptors (MOE_2D, CATS, ECFP4 and MACCS). To reduce the uncertainty of individual models, the consensus method was applied to yield more reliable predictions. A series of evaluations illustrated that the consensus models were more reliable and robust for the DDI predictions of new drug combination. For the internal validation, the whole prediction accuracy and AUC value of the DDI models were around 0.8 and 0.9, respectively. When it was applied to the external datasets, the model accuracy was 0.793 and 0.795 for multi-level validation and external validation, respectively. Furthermore, we also compared our model with some recently published tools and then applied the final model to predict FDA-approved drugs and proposed 54,013 possible drug pairs with potential DDIs. In summary, we developed a powerful DDI predictive model from the perspective of the CYP450 enzyme family and it will help a lot in the future drug development and clinical pharmacy research.

Prediction of Tacrolimus Dose/Weight-Adjusted Trough Concentration in Pediatric Refractory Nephrotic Syndrome: A Machine Learning Approach.

PURPOSE: Tacrolimus (TAC) is a first-line immunosuppressant for patients with refractory nephrotic syndrome (NS). However, there is a high inter-patient variability of TAC pharmacokinetics, thus therapeutic drug monitoring (TDM) is required. In this study, we aimed to employ machine learning algorithms to investigate the impact of clinical and genetic variables on the TAC dose/weight-adjusted trough concentration (C0/D) in Chinese children with refractory NS, and then develop and validate the TAC C0/D prediction models. PATIENTS AND METHODS: The association of 82 clinical variables and 244 single nucleotide polymorphisms (SNPs) with TAC C0/D in the third month since TAC treatment was examined in 171 children with refractory NS. Extremely randomized trees (ET), gradient boosting decision tree (GBDT), random forest (RF), extreme gradient boosting (XGBoost), and Lasso regression were carried out to establish and validate prediction models, respectively. The best prediction models were validated on a cohort of 30 refractory NS patients. RESULTS: GBDT algorithm performed best in the whole group (R2=0.444, MSE=591.032, MAE=20.782, MedAE=18.980) and CYP3A5 nonexpresser group (R2=0.264, MSE=477.948, MAE=18.119, MedAE=18.771), while ET algorithm performed best in the CYP3A5 expresser group (R2=0.380, MSE=1839.459, MAE=31.257, MedAE=19.399). These prediction models included 3 clinical variables (ALB0, AGE0, and gender) and 10 SNPs (ACTN4 rs3745859, ACTN4 rs56113315, ACTN4 rs62121818, CTLA4 rs4553808, CYP3A5 rs776746, IL2RA rs12722489, INF2 rs1128880, MAP3K11 rs7946115, MYH9 rs2239781, and MYH9 rs4821478). CONCLUSION: The association between the clinical and genetic variables and TAC C0/D was described, and three TAC C0/D prediction models integrating clinical and genetic variables were developed and validated using machine learning, which may support individualized TAC dosing.

Corrigendum: TNF-α in Uveitis: From Bench to Clinic.

[This corrects the article DOI: 10.3389/fphar.2021.740057.].

Tanshinone IIA from Salvia miltiorrhiza exerts anti-fibrotic effects on cardiac fibroblasts and rat heart tissues by suppressing the levels of pro-fibrotic factors: The key role of miR-618.

Tanshinone IIA (TAN) is widely employed for handling cardiovascular disorders. The current study explored the potential role of miRs in the antifibrotic effect of TAN on heart. Fibrotic features were induced in cardiac fibroblasts (CFs) and in rat hearts, and then handled with TAN. MicroRNAs (miRs) responding to TAN were determined using a microarray assay. The selected miR was modulated to verify its role in antifibrotic effects of TAN. TAN suppressed the viability and the production of α-SMA in CFs, which was associated with 101 miR being upregulated and 223 miR being downregulated. MiR-618 was selected as the potential target of TAN. Ang II inhibited miR-618 level and resulted in the upregulation of pro-fibrosis factors, which was reversed by TAN. The antifibrotic effect of TAN was weakened by miR-618 inhibition. TAN inhibits hypertrophy and collagen deposition in heart tissues, which is associated with the increased level of miR-618. PRACTICAL APPLICATIONS: The findings outlined in the current study show that the antifibrotic function of TAN is closely related to the function of miRs: the induction of miR-618 is indispensable for the function of TAN against the fibrotic process after heart injury, which will promote the application of TAN as an adjuvant therapy for improving heart function.

The application of medical scale in the treatment of plantar warts: analysis and prospect.

Plantar warts are common cutaneous diseases on the sole caused by the human papillomavirus, with a high annual incidence rate of 14%. It often causes pain, which impairs quality of life of patients. Numerous therapeutic options for plantar warts exist with variable success. However, all of them, including first-line treatment, have different adverse reactions or high recurrence rates. There is no one effective method for all patients. The choice of treatment method puzzles doctors. With the help of medical scales, we can analyze the patients' condition, so as to guide the choice of treatment methods, which is of great significance for the individualized treatment of patients with plantar warts. This review takes cryotherapy, intralesional injection of bleomycin and photodynamic therapy as examples to discuss the application of medical scales in the treatment of plantar warts, summarizes the scales that can be used to evaluate the status of plantar wart, adverse reactions, prognosis and patient's financial situation, and discusses their clinical and scientific value. We hope to use scales to consider the severity of plantar warts and economic level, help different patients to choose different treatment options, and make suggestions on the evaluation of the adverse reactions and treatment effect.

Socioeconomic Determinants of Melanoma-Related Health Literacy and Attitudes Among College Students in China: A Population-Based Cross-Sectional Study.

Objectives: To investigate the association of gender, ethnicity, living region, and socioeconomic status (SES) with health literacy and attitudes toward nevi and melanoma in Chinese adolescents and to examine whether health literacy mediates the association of SES with attitudes. Study Design: A multicenter cross-sectional study was conducted among newly enrolled college students. First-year students were recruited from five universities in different regions of China in 2018 using the cluster sampling method. The observers were blinded to the participants. Methods: Health literacy and attitudes were measured using a previously validated tool (Nevus and Melanoma Health Literacy and attitudes Test). SES was measured by annual family income and parental highest educational level. Nonparametric test was used to examine the association of participants' characteristics with health literacy and attitudes. Two-level generalized linear model with logarithm link function and Gamma distribution was used individually for SES. The mediation effect model was used to examine the mediation effect of health literacy. Results: A total of 21,086 questionnaires were completed by college students with a mean age of 18.0 ± 0.8 years. The mean scores of health literacy and attitudes were 9.83 ± 7.46 (maximum score: 28) and 16.98 ± 2.92 (maximum score: 20), respectively. Female, Han nationality, annual family income, and parental educational levels were positively associated with health literacy and attitudes. Regional differences showed different effects on health literacy and attitudes. A mediation model showed that literacy mediated the association of SES with attitudes toward nevi and melanoma. Health literacy mediated ~30-50% of the association of SES with attitudes. Conclusions: Melanoma-related health literacy among Chinese college students is generally insufficient and needs to be improved. Targeted and personalized health education for improving health literacy related to nevi and melanoma may improve the general population's attitudes and further promote health-related behavior to prevent and identify early-stage melanoma.

Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity.

Purpose: The purpose of this study was to elucidate the effects of interleukin (IL)-38 on experimental autoimmune uveitis (EAU) and its underlying mechanisms. Methods: Mice with EAU were treated with IL-38, and the retinas and cervical draining lymph nodes (CDLNs) were analyzed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was conducted to analyze the immune cell profiles of CDLNs from normal, EAU, and IL-38-treated mice. Results: Administration of IL-38 attenuated EAU symptoms and reduced the proportion of T helper 17 (Th17) and T helper 1 (Th1) cells in the retinas and CDLNs. In scRNA-seq analysis, IL-38 downregulated the IL-17 signaling pathway and reduced the expression of Th17 cell pathogenicity-related genes (Csf2 and Il23r), findings which were also confirmed by flow cytometry. In vitro, IL-38 reduced the granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation function of IL-23 and inhibited IL-23R expression in Th17 cells. Moreover, when co-cultured with Th17 cells, IL-38 prevented IL-23 production in antigen-presenting cells (APCs). Conclusions: Our data demonstrate the therapeutic effect of IL-38 on EAU, and suggest that the effect of IL-38 may be caused by dampening of the GM-CSF/IL-23R/IL-23 feedback loop between Th17 cells and APCs.

TNF-α in Uveitis: From Bench to Clinic.

Uveitis is an inflammation of the iris, ciliary body, vitreous, retina, or choroid, which has been shown to be the first manifestation of numerous systemic diseases. Studies about the immunopathogenesis and treatment of uveitis are helpful to comprehend systemic autoimmune diseases, and delay the progression of systemic autoimmune diseases, respectively. Tumor necrosis factor-alpha (TNF-α), a pleiotropic cytokine, plays a pivotal role in intraocular inflammation based on experimental and clinical data. Evidence of the feasibility of using anti-TNF-α agents for uveitis management has increased. Although there are numerous studies on TNF-α in various autoimmune diseases, the pathological mechanism and research progress of TNF-α in uveitis have not been reviewed. Therefore, the objective of this review is to provide a background on the role of TNF-α in the immunopathogenesis of uveitis, as well as from bench to clinical research progress, to better guide TNF-α-based therapeutics for uveitis.

First Human Results With the 256 Channel Intelligent Micro Implant Eye (IMIE 256).

Purpose: To report on the safety and efficacy of the 256-channel Intelligent Micro Implant Eye epiretinal prosthesis system (IMIE 256). Methods: The IMIE 256 implants were implanted in the right eyes of five subjects with end-stage retinitis pigmentosa. Following implantation, the subjects underwent visual rehabilitation training for 90 days, and their visual performance was evaluated using the grating visual acuity test, Tumbling E visual acuity test, direction of motion, square localization, and orientation and mobility test. To evaluate the safety of the IMIE 256, all adverse events were recorded. Results: Subjects performed significantly better on all evaluations with the IMIE 256 system on as compared with the performance at baseline or with the system off. There was a steady improvement in performance at each observation interval, indicating that the training and/or practice helped the subjects use the IMIE 256. There were two serious adverse events-electrode array movement and low intraocular pressure in one subject, which resolved with surgery. There were no other adverse events observed except those expected in the course of postoperative healing. Conclusions: These results show an improved safety and efficacy profile compared with that of the Argus II implant. Further clinical trials are needed to confirm these results in a larger number of subjects and over longer durations. Translational Relevance: To our knowledge, this study reports the first in-human data from a high-density (256 electrodes) epiretinal implant to restore sight to a subset of blind patients.