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.

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.

Systematic comparison of ligand-based and structure-based virtual screening methods on poly (ADP-ribose) polymerase-1 inhibitors.

The poly (ADP-ribose) polymerase-1 (PARP1) has been regarded as a vital target in recent years and PARP1 inhibitors can be used for ovarian and breast cancer therapies. However, it has been realized that most of PARP1 inhibitors have disadvantages of low solubility and permeability. Therefore, by discovering more molecules with novel frameworks, it would have greater opportunities to apply it into broader clinical fields and have a more profound significance. In the present study, multiple virtual screening (VS) methods had been employed to evaluate the screening efficiency of ligand-based, structure-based and data fusion methods on PARP1 target. The VS methods include 2D similarity screening, structure-activity relationship (SAR) models, docking and complex-based pharmacophore screening. Moreover, the sum rank, sum score and reciprocal rank were also adopted for data fusion methods. The evaluation results show that the similarity searching based on Torsion fingerprint, six SAR models, Glide docking and pharmacophore screening using Phase have excellent screening performance. The best data fusion method is the reciprocal rank, but the sum score also performs well in framework enrichment. In general, the ligand-based VS methods show better performance on PARP1 inhibitor screening. These findings confirmed that adding ligand-based methods to the early screening stage will greatly improve the screening efficiency, and be able to enrich more highly active PARP1 inhibitors with diverse structures.

Single-Cell Analysis Reveals the Heterogeneity of Monocyte-Derived and Peripheral Type-2 Conventional Dendritic Cells.

Dendritic cells (DCs) are critical for pathogen recognition and Ag processing/presentation. Human monocyte-derived DCs (moDCs) have been extensively used in experimental studies and DC-based immunotherapy approaches. However, the extent of human moDC and peripheral DCs heterogeneity and their interrelationship remain elusive. In this study, we performed single-cell RNA sequencing of human moDCs and blood DCs. We identified seven subtypes within moDCs: five corresponded to type 2 conventional DCs (cDC2s), and the other two were CLEC10A+CD127+ cells with no resemblance to any peripheral DC subpopulations characterized to date. Moreover, we defined five similar subtypes in human cDC2s, revealed the potential differentiation trajectory among them, and unveiled the transcriptomic differences between moDCs and cDC2s. We further studied the transcriptomic changes of each moDC subtype during maturation, demonstrating SLAMF7 and IL15RA as maturation markers and CLEC10A and SIGLEC10 as markers for immature DCs. These findings will enable more accurate functional/developmental analyses of human cDC2s and moDCs.

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.

Photoelectrochemical assay for the detection of circulating tumor cells based on aptamer-Ag2S nanocrystals for signal amplification.

In this work, we developed a photoelectrochemical assay for circulating tumor cells (CTCs) detection based on hexagonal carbon-nitrogen tubes (HCNT) as visible light-sensitive materials. The MCF-7 cell was selected as the model CTC and was captured through specific recognition between epithelial cell adhesion molecules (EpCAM) on the cell surface and anti-EpCAM antibodies. Anti-EpCAM antibody-modified magnetic nanoparticles were used to enrich and separate MCF-7 cells from samples. The detection signal was amplified by Ag2S nanocrystals, which can compete with HCNTs for absorbing visible light, leading to a decrease of photocurrent intensity. The linear range of the assay for MCF-7 cells is from 10 to 5000 cells mL-1, with a detection limit of 3 cells mL-1 (S/D = 3). The assay has good selectivity for MCF-7 detection over HeLa cells. The assay was successfully applied for the detection of MCF-7 in human whole blood, which indicates the potential for clinical application.

Sensitive colorimetric assay for the determination of alkaline phosphatase activity utilizing nanozyme based on copper nanoparticle-modified Prussian blue.

Nanozyme based on Prussian blue nanocubes (PB NCs) loaded with copper nanoparticles (Cu@PB NCs) was synthesized. The peroxidase (POD)-like activity of Cu@PB NCs was studied and utilized for detecting the activity of alkaline phosphatase (ALP). The Cu@PB NCs possess higher POD-like activity compared with PB NCs and natural horseradish peroxidase (HRP) due to the loading of copper nanoparticles. 3,3',5,5'-Tetramethylbenzidine (TMB) can be oxidized to oxTMB in the presence of Cu@PB NCs and H2O2, generating blue-colored compound, while introduction of pyrophosphate (PPi) leads to the POD-like activity of Cu@PB NCs decreased obviously. In the presence of ALP, PPi was hydrolyzed and then the POD-like activity of Cu@PB NCs was restored. So, according to the change of the POD-like activity of Cu@PB NCs, a sensitive colorimetric assay for ALP activity was reported. The limit of detection of the assay is 0.08 mU/mL, with linear range from 0.1 to 50 mU/mL. In addition, the assay was also applied for screening the inhibitors of ALP. Nanozyme based on Prussian blue nanocube (PB NCs) loaded with copper nanoparticles was synthesized and utilized for detecting the activity of alkaline phosphatase (ALP).

Posterior pole retinotomy for treatment of recurrent macular hole retinal detachment in highly myopic eyes: a pilot study.

BACKGROUND: To investigate the feasibility and efficacy of posterior pole retinotomy to treat recurrent macular hole retinal detachment (MHRD) in highly myopic patients. METHODS: We performed a retrospective study and reviewed the medical records in our hospital between January 1, 2016 and December 31, 2018. Highly myopic patients who received posterior pole retinotomy with silicone oil tamponade for their recurrent MHRD after pars plana vitrectomy were included in the analysis. Postoperative retinal reattachment, best-corrected visual acuity (BCVA), macular hole closure, and complications were evaluated. RESULTS: There were 11 patients (11 eyes) included in this study. All retinas were reattached. Silicone oil was successfully removed from all eyes 1.5-3 months after the surgery. Macular holes were completely closed in three eyes and remained flat open in eight eyes. The BCVA of all eyes improved significantly at 12 months after surgery (logarithm of the minimal angle of resolution, pre vs. postoperatively, 1.87 ± 0.44 vs. 1.15 ± 0.24, P < 0.05). None of the patients had complications such as endophthalmitis, fundus hemorrhage, retinal redetachment, and proliferative vitreoretinopathy. CONCLUSION: Posterior pole retinotomy is a safe and effective surgery to treat recurrent MHRD after pars plana vitrectomy in highly myopic patients.

The Classification of Six Common Skin Diseases Based on Xiangya-Derm: Development of a Chinese Database for Artificial Intelligence.

BACKGROUND: Skin and subcutaneous disease is the fourth-leading cause of the nonfatal disease burden worldwide and constitutes one of the most common burdens in primary care. However, there is a severe lack of dermatologists, particularly in rural Chinese areas. Furthermore, although artificial intelligence (AI) tools can assist in diagnosing skin disorders from images, the database for the Chinese population is limited. OBJECTIVE: This study aims to establish a database for AI based on the Chinese population and presents an initial study on six common skin diseases. METHODS: Each image was captured with either a digital camera or a smartphone, verified by at least three experienced dermatologists and corresponding pathology information, and finally added to the Xiangya-Derm database. Based on this database, we conducted AI-assisted classification research on six common skin diseases and then proposed a network called Xy-SkinNet. Xy-SkinNet applies a two-step strategy to identify skin diseases. First, given an input image, we segmented the regions of the skin lesion. Second, we introduced an information fusion block to combine the output of all segmented regions. We compared the performance with 31 dermatologists of varied experiences. RESULTS: Xiangya-Derm, as a new database that consists of over 150,000 clinical images of 571 different skin diseases in the Chinese population, is the largest and most diverse dermatological data set of the Chinese population. The AI-based six-category classification achieved a top 3 accuracy of 84.77%, which exceeded the average accuracy of dermatologists (78.15%). CONCLUSIONS: Xiangya-Derm, the largest database for the Chinese population, was created. The classification of six common skin conditions was conducted based on Xiangya-Derm to lay a foundation for product research.

Identification of G-Quadruplex-Binding Protein from the Exploration of RGG Motif/G-Quadruplex Interactions.

The arginine/glycine-rich region termed the RGG domain is usually found in G-quadruplex (G4)-binding proteins and is important in G4-protein interactions. Studies on the binding mechanism of RGG domains found that small segments (RGG motif) inside the domain contribute greatly to the G4 binding affinity. However, unlike the entire RGG domains that have been broadly explored, the role of the RGG motif remains obscure, with very limited study. Herein, to clarify the role of the RGG motif in G4-protein interactions, we systematically investigated the binding affinity and mode between RGG-motif peptides and G4s. The internal arrangement of RGG repeats and gap amino acids played a more crucial role in the G4-binding mechanism than a critical number of RGG repeats. Arginines and phenylalanines at the exact position of the RGG motif might enable additional hydrogen bonding and π-stacking interaction with nucleobases and strengthen the binding of G4. Impressively, proceeding from a G4-binding RGG peptide, 12, discovered above, we identified the cold-inducible RNA-binding protein (CIRBP) as a new G4 DNA-binding protein both in vitro and in cells. In addition, we found that the key amino acids for G4 binding in peptide 12 and CIRBP were highly similar, and peptide 12 clearly played a key role in the G4 binding of CIRBP. This report is the first in which a G4-binding protein was identified from exploration of the G4-binding RGG motif. Our findings suggest a novel strategy for discovering new G4-binding proteins by exploring key peptide segments.

Subconjunctival orbital fat prolapse: an unsuspecting rare lesion.

PURPOSE: Subconjunctival orbital fat prolapse has been rarely described in the literature, often leading to misdiagnosis. In this article, we present the clinical features and treatment of patients with subconjunctival orbital fat prolapse as experienced in our clinic. SUBJECTS AND METHODS: Cases of subconjunctival orbital fat prolapse were evaluated retrospectively from the records of the Zhongshan Ophthalmic Center at Sun Yat-sen University for the period of January 1, 1991 to December 31, 2010. RESULTS: A total of 46 patients (33 males and 13 females) with subconjunctival orbital fat prolapse were identified. Their ages ranged from 44.0 to 82.0 years (mean age, 65.8 y). The right eye was involved in 16 cases, the left eye was involved in 11 cases, and both eyes were involved in 19 cases. Subconjunctival fat prolapse appeared as a soft, mobile yellowish mass, quite different from conjunctival dermolipoma, which presents as a congenital soft or firm pinkish-white or pinkish-yellow mass with hairs on the surface. The conjunctival fat prolapse was located in the superotemporal quadrant in 45 patients and in the superonasal quadrant in the remaining patient with no history of trauma or previous eye surgery in all the patients. Forty patients underwent surgical excision of the prolapsed fat and fixation of Tenon's capsule to the sclera. There were no recurrences of orbital fat prolapse or surgical complications in these patients with a mean follow-up of 2.4 years. CONCLUSIONS: Subconjunctival orbital fat prolapse is a rare benign entity and can be easily diagnosed when this condition is considered. The surgical management usually has an excellent therapeutic outcome.

Concomitant multiple cavernous hemangiomas and venous angioma of the orbit.

PURPOSE: The coexistence of multiple cavernous hemangiomas and venous malformation is an extremely rare clinical condition. In this report, we describe a patient showing initial multiple cavernous hemangiomas followed years later by a recurrence of multiple cavernous hemangiomas along with the appearance of venous angioma coexisting in the same orbit. METHODS: A 52-year-old woman was referred with a gradually progressive proptosis and upward displacement of her left eye that were present for 10 years. The clinical features, computed tomography and ultrasonography examination, surgery, and histopathologic findings from this patient with multiple cavernous hemangiomas coexisting with venous angioma in the same orbit are presented. RESULTS: Color Doppler ultrasonography and computed tomography scan displayed more than 10 well-defined homogenous masses in the left orbit measuring 0.5 × 0.5 to 1.0 × 0.8 cm with no blood flow. Anterior orbitotomy of the left eye was performed. Fifteen accessible, distinct, red-purple, round masses were excised with tumors measuring 0.5 × 0.5 × 0.6 to 1.0 × 1.0 × 1.0 cm. Histopathologic analysis confirmed the diagnosis of multiple cavernous hemangiomas. Eight years later, she again developed left proptosis. Color Doppler ultrasonography and computed tomography disclosed multiple smoothly outlined homogeneous masses in the left orbit ranging in size from 5 × 4 to 28 × 16 mm, along with some scattered, high-density, vein-stone shadows within the mass. An anterior orbitotomy was again performed. At surgery, 4 violaceous, well-defined, and cone-shaped masses were removed with minimal bleeding. Histopathologic examination confirmed the diagnosis of multiple cavernous hemangiomas with coexisting venous angioma. There was no recurrence of orbital hemangioma at 2 years after the second surgery. CONCLUSIONS: Orbital cavernous hemangioma and venous angioma may share a yet-to-be-described common link.

A bibliometric and visualization analysis of global research status and frontiers on autophagy in cardiomyopathies from 2004 to 2023.

BACKGROUND: Autophagy is intimately associated with the development of cardiomyopathy, and has received widespread attention in recent years. However, no relevant bibliometric analysis is reported at present. In order to summarize the research status of autophagy in cardiomyopathy and provide direction for future research, we conducted a comprehensive, detailed, and multidimensional bibliometric analysis of the literature published in this field from 2004 to 2023. METHODS: All literatures related autophagy in cardiomyopathy from 2004 to 2023 were collected from the Web of Science Core Collection (WOSCC), and annual papers, global publication trends and proportion charts were analyzed and plotted using Graphpad price v8.0.2. In addition, CtieSpace (6.2.4R (64 bit) Advanced Edition) and VOSviewer (1.6.18 Edition) were used to analyze and visualize these data. RESULTS: 2279 papers about autophagy in cardiomyopathy were accessed in the WoSCC over the last 20 years, comprising literatures from 70 countries and regions, 2208 institutions, and 10,810 authors. China contributes 56.32% of the total publications, substantially surpassing other countries, while the U.S. is ranked first in frequency of citations. Among the top 10 authors, 6 are from China and 4 are from the United States. Air Force Military Medical University was the institution with the highest number of publications; while journal of molecular and cellular cardiology (62 articles, 2.71% of the total) was the journal with the highest number of papers published in the field. Clustering of co-cited references and temporal clustering analysis showed that ferroptosis, hydrogen sulfide mitophagy, lipid peroxidation, oxidative stress, and SIRT-1 are hot topics and trends in the field. The principal keywords are oxidative stress, heart and heart-failure. CONCLUSION: The research on autophagy in cardiomyopathy is in the developmental stage. This represents the first bibliometric analysis of autophagy in cardiomyopathy , revealing the current research hotspots and future research directions in this field.

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.

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.

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.

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.

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.

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.