Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Biolimus-coated versus paclitaxel-coated balloons for coronary in-stent restenosis (BIO ASCEND ISR): a randomised, non-inferiority trial.

BACKGROUND: The treatment of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains challenging in current clinical practice. AIMS: The study was conducted to investigate a novel biolimus-coated balloon (BCB) for the treatment of coronary DES-ISR compared with the best-investigated paclitaxel-coated balloon (PCB). METHODS: This was a prospective, multicentre, randomised, non-inferiority trial comparing a novel BCB with a clinically proven PCB for coronary DES-ISR. The primary endpoint was in-segment late lumen loss (LLL) at 9 months assessed by an independent core laboratory. Baseline and follow-up optical coherence tomography were performed in a prespecified subgroup of patients. RESULTS: A total of 280 patients at 17 centres were randomised to treatment with a BCB (n=140) versus a PCB (n=140). At 9 months, LLL in the BCB group was 0.23±0.37 mm compared to 0.25±0.35 mm in the PCB group; the mean difference between the groups was -0.02 (95% confidence interval [CI]: -0.12 to 0.07) mm; p-value for non-inferiority<0.0001. Similar clinical outcomes were also observed for both groups at 12 months. In the optical coherence tomography substudy, the neointimal area at 9 months was 2.32±1.04 mm2 in the BCB group compared to 2.37±0.93 mm2 in the PCB group; the mean difference between the groups was -0.09 (95% CI: -0.94 to 0.76) mm2; p=non-significant. CONCLUSIONS: This head-to-head comparison of a novel BCB shows similar angiographic outcomes in the treatment of coronary DES-ISR compared with a clinically proven PCB. (ClinicalTrials.gov: NCT04733443).

Pyridine-Based Covalent Organic Frameworks with Pyridyl-Imine Structures for Boosting Photocatalytic H2O2 Production via One-Step 2e- Oxygen Reduction.

Bipyridine-based covalent organic frameworks (COFs) have emerged as promising contenders for the photocatalytic generation of hydrogen peroxide (H2O2). However, the presence of imine nitrogen alters the mode of H2O2 generation from an efficient one-step two-electron (2e-) route to a two-step 2e- oxygen reduction pathway. In this work, we introduce 3,3'-bipyridine units into imine-based COF skeletons, creating a pyridyl-imine structure with two adjacent nitrogen atoms between the pyridine ring and imine linkage. This unique bipyridine-like architecture can effectively suppress the two-step 2e- ORR process at the single imine-nitrogen site, facilitating a more efficient one-step 2e- pathway. Consequently, the optimized pyridyl-imine COF (PyIm-COF) exhibits a remarkable H2O2 production rate of up to 5850 µmol h-1 g-1, nearly double that of pristine bipyridine COFs. This work provides valuable insight into the rational design of functionalized COFs for enhanced H2O2 production in photocatalysis.

3D monitoring of the microphase separations inside the intraocular lens.

Glistenings often occur after implanting the intraocular lens (IOL) due to the formation of numerous microvacuoles (MVs) and may lead to deterioration of vision quality. Previous studies showed the formation of MVs was associated with the hydrophobicity of IOL materials. Yet, the mechanism remains an open question due to the complexity of IOL polymer networks. In this study, two commercialized IOLs with similar hydrophobicity are found distinct in the formation of MVs. The 3D growth kinetics of MVs during cooling processes are captured for the first time by digital holographic microscopy (DHM) and the components of MVs are measured by DHM and Raman spectroscopy. The results reveal that the growth of MVs stems from the microphase separation of water and surrounding IOL polymers. A polymer swelling model is thus proposed to describe the microphase separation process which is found dependent on the elasticity of IOL polymer networks. The total volume of MVs is determined by the IOL hydrophobicity, while the elastic force of IOL polymer networks determines the number density and size of MVs. This study demonstrates an approach for characterizing the phase separation of crosslinked polymeric materials in biosystems and sheds lights on the refinement of IOL materials. STATEMENT OF SIGNIFICANCE: Glistenings due to the formation of numerous microvacuoles (MVs) in intraocular lens (IOL) can occur after IOL implantation, which may induce poor quality of vision. However, the underlying mechanism of MVs formation is still an open question. This study establishes an in-situ 3D imaging platform to monitor growth kinetics of the MVs in IOLs, which allows to uncover the mechanism of glistenings formation resulting from the microphase separation. The findings imply the material hydrophobicity influences the total volume of MVs, while the local elasticity of IOL polymer networks determines the number density and the size of MVs. This study offers a new approach for characterizing phase separation in crosslinking biosystems and sheds lights on the refinement of IOL materials.

Smurf1 Modulates Smad Signaling Pathway in Fibrotic Cataract Formation.

Purpose: TGF-ß/BMP signaling pathway plays a significant role in fibrotic cataract. Smurf1, a ubiquitin protein ligase, regulates the TGF-ß/BMP signaling pathway through the ubiquitin-proteasome system (UPS). This study aims to investigate the role of Smurf1 in the progression of fibrotic cataract and its underlying mechanism. Methods: We used a mouse model of injury-induced anterior subcapsular cataract (ASC) and administered the Smurf1 inhibitor A01 for in vivo investigations. RNA sequencing was performed to examine global gene expression changes. Protein levels were assessed by Simple Western analysis. The volume of subcapsular opacity was determined using whole-mount immunofluorescence of lens anterior capsules. Lentivirus was utilized to establish cell lines with Smurf1 knockdown or overexpression in SRA01/04. Lens epithelial cell (LEC) proliferation was evaluated by CCK8 and EdU assays. Cell cycle profile was determined by flow cytometry. LEC migration was measured using Transwell and wound healing assays. Results: The mRNA levels of genes associated with cell proliferation, migration, epithelial-mesenchymal transition (EMT), TGF-ß/BMP pathway, and UPS were upregulated in mouse ASC model. Smurf1 mRNA and protein levels were upregulated in lens capsules of patients and mice with ASC. Anterior chamber injection of A01 inhibited ASC formation and EMT. In vitro, Smurf1 knockdown reduced proliferation, migration and TGF-ß2-induced EMT of LECs, concomitant with the upregulation of Smad1, Smad5, and pSmad1/5. Conversely, overexpression of Smurf1 showed opposite phenotypes. Conclusions: Smurf1 regulates fibrotic cataract progression by influencing LEC proliferation, migration, and EMT through the modulation of the Smad signaling pathway, offering a novel target for the fibrotic cataract treatment.

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS).

BACKGROUND: Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. METHODS: The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. CONCLUSIONS: The MOYAOMICS project represents a significant step toward comprehending MMD's molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry.

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Association of refractive outcome with postoperative anterior chamber depth measured with 3 optical biometers.

PURPOSE: This study evaluated the relationship between refractive outcomes and postoperative anterior chamber depth (ACD, measured from corneal epithelium to lens) measured by swept-source optical coherence tomography (SS-OCT), optical low-coherence reflectometry (OLCR), and Scheimpflug devices under the undilated pupil. METHODS: Patients undergoing cataract phacoemulsification with intraocular lens (IOL) implantation in a hospital setting were enrolled. Postoperative ACD (postACD) was performed with an SS-OCT device, an OLCR device, and a Scheimpflug device at least 1 month after cataract surgery. After adjusting the mean predicted error to 0, differences in refractive outcomes were calculated with the Olsen formula using actual postACD measured from 3 devices and predicted value. RESULTS: Overall, this comparative case study included 69 eyes of 69 patients, and postACD measurements were successfully taken using all 3 devices. The postACD measured with the SS-OCT, OLCR, and Scheimpflug devices was 4.59 ± 0.30, 4.50 ± 0.30, and 4.54 ± 0.32 mm, respectively. Statistically significant differences in postACD were found among 3 devices (P < 0.001), with intraclass correlation coefficients (ICCs) and Bland-Altman showing good agreement. No significant difference in median absolute error was found with the Olsen formula using actual postACD obtained with 3 devices. Percentage prediction errors were within ± 0.50 D in 65% (OLCR), 70% (Scheimpflug), and 67% (SS-OCT) calculated by actual postACD versus 64% by predicted value. CONCLUSION: Substantial agreement was found in postACD measurements obtained from the SS-OCT, OLCR, and Scheimpflug devices, with a trend toward comparable refractive outcomes in the Olsen formula. Meanwhile, postACD measurements may be potentially superior for the additional enhancement of refractive outcomes.

Primary study on the effects and mechanisms of separate and combined decoctions of Scutellaria baicalensis Georgi - Coptis chinensis Franch extracts in relieving acute alcoholic liver injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (SBG) and Coptis chinensis Franch (CCF) are traditional herbal medicine pairs used for clearing heat and eliminating dampness, stopping diarrhea, and detoxification. Traditionally, these two herbs are combined and decocted together, but the modern preparation procedures separate them to avoid the large amount of precipitation generated from co-decoction. Thus, a conflict lies between the traditional and modern extraction processes of Scutellaria baicalensis Georgi - Coptis chinensis Franch (SBG-CCF). AIM OF STUDY: There is a conflict between traditional medical practices of SBG-CCF and the modern formulation industry. In this study, we investigated the differences in the effects and mechanisms of SBG-CCF extracted by decocting separately and combining decoctions, as well as the scientific effectiveness of traditional and modern treatment methods on both. Acute alcoholic liver injury (ALI) rats were used as the pathological model. MATERIALS AND METHODS: SD rats were divided into 8 groups, including blank group, model group, low, medium, and high dose groups of SBG-CCF separated decoction, low, medium, and high dose groups of SBG-CCF combined decoction. Acute alcoholic liver injury model was induced in rats by gradually increasing the dose of alcohol through gavage everyday using white wine with an alcohol content 52%. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) were used as indicators to assess the intervention effect of SBG-CCF. And the potential active ingredients of SBG-CCF and the targets related to ALI were screened using network pharmacology, and the prediction results of network pharmacology were verified by quantitative real-time fluorescence PCR (qRT-PCR). RESULTS: SBG-CCF decoction alone and six combinations of decoctions have different degrees of improvement on alcoholic liver injury, with significant efficacy in the middle-dose group, and the combined decoction was superior to the individual decoction. SBG-CCF gavage can reduce the activity of AST, ALT, TC, TG, LDH, and MDA in the serum and liver of ALI rats, while increasing the levels of SOD and GSH. Network pharmacological analysis identified 39 active components, mainly flavonoids and alkaloids. Enrichment analysis suggested that SBG-CCF may treat ALI through the regulation of tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), interleukin-17 (IL-17), apoptosis, and the Toll-like receptor signaling pathways. The key targets in the Disease-Signaling Pathway-Target Network were MAPK8, IKBKB, MAPK10, MAPK3, MAPK1, and AKT1. qRT-PCR results indicated that targets regulating inflammation and lipid metabolism are MAPK8, MAPK10, MAPK3, and AKT1. CONCLUSION: SBG-CCF separately extracts and combines decoction can alleviate acute alcoholic liver injury, and the effect of combined decoction is more significant than separate decoction, implying that the precipitate produced by the combination of the two is also an active substance. The resistance mechanism of SBG-CCF ALI may be related to the modulation of lipid metabolism, inhibition of lipid peroxidation, and oxidative stress. SBG-CCF has the characteristics of multi-component, multi-pathway, and multi-target resistance to ALI.

Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

Comparative Clinical Implications of Calcified versus Non-Calcified Tissue Protrusion After Coronary Stent Implantation.

Purpose: The prognostic implications of calcified versus non-calcified tissue protrusions (TPs) following stent implantation remain undetermined. This study aimed to evaluate the differential clinical outcomes associated with calcified and non-calcified TP morphologies. Patients and Methods: Employing intravascular ultrasound (IVUS), we identified calcified TPs as calcium fragment extrusions permeating the stent struts, while non-calcified TPs were characterized as plaque and/or thrombus extensions through the stent into the arterial lumen. The primary endpoint encompassed target lesion failure (TLF), comprising cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization (TLR), or stent thrombosis, assessed in patients with a follow-up period exceeding one year. Results: Of 1033 patients subjected to pre- and post-intervention IVUS, 62 exhibited calcified TPs (6.0%), and 279 presented non-calcified TPs (27.0%), forming the basis of this analysis. Multivariable linear regression indicated calcified nodules as a significant predictor of calcified TP [Odds Ratio (OR) 2.47; 95% Confidence Interval (CI) 2.33 to 2.62; P <0.001], with ST-segment elevation myocardial infarction emerging as an inverse correlate [OR 0.82; 95% CI 0.73 to 0.93; P = 0.004]. Two-year data revealed a higher incidence of TLF in patients with calcified TPs versus their non-calcified counterparts (11.3% vs 2.2%, P <0.001), and a marked increase in clinically driven TLR (9.7% vs 1.4%, P <0.001). Calcified TPs were independently correlated with increased TLF risk in the adjusted model [Hazard Ratio (HR) 2.47; 95% CI 1.17 to 5.16; P = 0.027]. Conclusion: After drug-eluting stent implantation, IVUS-identified calcified TPs correlate with adverse clinical outcomes compared to non-calcified TP formations.

Comparison of clinical outcomes of Ibutilide-guided cardioversion and direct current synchronized cardioversion after radiofrequency ablation of persistent atrial fibrillation.

Backgroup: Ibutilide has already been used for cardioversion of persistent atrial fibrillation (PsAF) after radiofrequency catheter ablation (RFCA). The purpose of this study was to determine the effect of Ibutilide-guided cardioversion on clinical outcomes after individualized ablation of PsAF. Methods: From October 2020 to September 2021, consecutive patients with PsAF accepted for RFCA were prospectively enrolled. After individualized ablation including pulmonary vein isolation plus left atrial roof line ablation and personalized linear ablation based on left atrial low-voltage zones, patients were divided into the spontaneous conversion (SCV) group, direct current synchronized cardioversion (DCC) group and Ibutilide group according to different cardioversion types during ablation. The rates of freedom from atrial tachyarrhythmia (ATT) among the three groups were evaluated after follow-up. Results: In this study, 110 patients were enrolled, including 12 patients with SCV, 50 patients receiving DCC and 48 patients receiving Ibutilide cardioversion after individualized ablation. Among the three groups, the SCV group had shorter AF duration {12 months [interquartile range (IQR) 12-16], P = 0.042} and smaller left atrial diameter (LAD) [35 mm (IQR: 33-42), P = 0.023]. A 12-month freedom from ATT rate was 83.3% in SCV group, 69.4% in DCC group, and 79.2% in Ibutilide group, respectively (Log-rank, P = 0.745). During the follow-up [17 months (IQR: 15-19)], the rate of freedom from ATT of SCV group (83.3%), and Ibutilide group (72.9%) were both higher than that of DCC group (53.1%, P = 0.042). Moreover, Kaplan-Meier analysis showed a significantly higher sinus rhythm (SR) maintenance in Ibutilide group than in DCC group (Log-rank, P = 0.041). After adjusting for risk factors of AF recurrence, the hazard ratio for AF recurrence of the DCC group with reference to the Ibutilide group was 4.10 [95% confidence interval (CI) (1.87-8.98), P < 0.001]. Furthermore, subgroup analysis showed that freedom from ATT rate in effective Ibutilide subgroup was significantly higher than noneffective Ibutilide subgroup (Log-rank, P < 0.001). Conclusion: For the treatment of the patients with PsAF, Ibutilide-guided cardioversion after individualized RFCA may be benefit for maintenance of SR compared to conventional DCC, especially for the patients who are effective for administration of Ibutilide.

Antegrade versus Retrograde Approach for Recanalization of Ostial or Stumpless Coronary Chronic Total Occlusion.

Purpose: This research aimed to evaluate the procedural and in-hospital clinical outcomes of percutaneous coronary intervention (PCI) for ostial or stumpless chronic total occlusion (CTO) utilizing both the antegrade-only and retrograde approaches. Methods: A comprehensive retrospective examination was conducted on the procedural and in-hospital clinical outcomes of 89 consecutive patients subjected to ostial or stumpless CTO PCI at our institution between April 2015 and October 2022. Results: The antegrade-only technique demonstrated a superior technical success rate (92.0% vs 71.9%, p = 0.041) and procedural success rate (92.0% vs 68.8%, p = 0.022) in comparison to the retrograde approach (RA). The RA group presented a notably elevated Japanese-CTO (J-CTO) score relative to the antegrade-only approach group (2.45±0.73 vs 1.64±0.70, p < 0.001). The antegrade-only approach group manifested an increased frequency of microchannels at the proximal stump relative to the RA group (56.0% vs 10.9%, p < 0.001). In-hospital major adverse cardiac events (MACE) and in-hospital myocardial infarction (MI) were observed more prevalently in the RA group (18.8% vs 0, p = 0.003; 15.6% vs 0, p = 0.008; respectively). A J-CTO score below 2 and the manifestation of microchannels at the proximal stump were identified as predictors for successful antegrade-only approach PCI for ostial or stumpless CTO (OR: 2.79 [95% CI: 1.92-5.03, P =0.003]; OR: 2.89 [95% CI: 1.32-6.03, P =0.001]; respectively). Conclusion: Relative to RA PCI for ostial or stumpless CTO, the antegrade-only approach is utilized for less complex CTO lesions and is associated with a diminished probability of in-hospital MACE.

Endoscopy-assisted purely total outer wall excision for pediatric Sylvian arachnoid cysts.

BACKGROUND: To present a novel endoscopy-assisted surgical strategy of Sylvian arachnoid cysts (ACs). CASE PRESENTATION: Endoscopy-assisted surgery was performed on 9 children (May 2019-December 2021). All patients were evaluated with CT and/or MRI and had regular follow-up examinations. The procedure consisted of performing a small temporal craniotomy (2 cm) behind the hairline. After dural opening, the surgery was performed with the assistance of a rigid 30-degree transcranial endoscope, self-irrigating bipolar forceps, and other standard endoscopic instruments. Steps included total excision of the AC outer wall and dissection of arachnoid adhesion around the cystic edge to communicate the residual cyst cavity with subdural space. Compared with the microscopical procedure, a 30-degree transcranial endoscope provides a wider view, especially for the lateral part exposure of the outer wall. The average age of the patients was 27.7 months (range 13-44 months). The Sylvian AC was in the right hemisphere in three patients and six in the left, respectively. 1 patient suffered transient postoperative epilepsy. There was no mortality or additional postoperative neurological deficit in this series. All of the patients achieved significant clinical improvement after surgery. Radiological examination after the operation showed a significant reduction in all cases (100%, 9/9) and disappearance in one case (11.1%, 1/9). Postoperative subdural fluid collection occurred in six cases and completely resolved spontaneously in 9 months. CONCLUSION: The study demonstrated the minimally invasive, safety, and effectivity of the endoscopy-assisted purely total outer wall excision.

Construction and integrated analysis of the ceRNA network hsa_circ_0000672/miR-516a-5p/TRAF6 and its potential function in atrial fibrillation.

Atrial fibrosis is a crucial contributor to initiation and perpetuation of atrial fibrillation (AF). This study aimed to identify a circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network related to atrial fibrosis in AF, especially to validate hsa_circ_0000672/hsa_miR-516a-5p/TRAF6 ceRNA axis in AF preliminarily. The circRNA-miRNA-mRNA ceRNA network associated with AF fibrosis was constructed using bioinformatic tools and literature reviews. Left atrium (LA) low voltage was used to represent LA fibrosis by using LA voltage matrix mapping. Ten controls with sinus rhythm (SR), and 20 patients with persistent AF including 12 patients with LA low voltage and 8 patients with LA normal voltage were enrolled in this study. The ceRNA regulatory network associated with atrial fibrosis was successfully constructed, which included up-regulated hsa_circ_0000672 and hsa_circ_0003916, down-regulated miR-516a-5p and five up-regulated hub genes (KRAS, SMAD2, TRAF6, MAPK11 and SMURF1). In addition, according to the results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, these hub genes were clustered in TGF-beta and MAPK signaling pathway. In the patients with persistent AF, hsa_circ_0000672 expression in peripheral blood monocytes was significantly higher than those in controls with SR by quantitative real-time polymerase chain reaction (p-value < 0.001). Furthermore, hsa_circ_0000672 expression was higher in peripheral blood monocytes of persistent AF patients with LA low voltage than those with LA normal voltage (p-value = 0.002). The dual-luciferase activity assay confirmed that hsa_circ_0000672 exerted biological functions as a sponge of miR-516a-5p to regulate expression of its target gene TRAF6. Hsa_circ_0000672 expression in peripheral blood monocytes may be associated with atrial fibrosis. The hsa_circ_0000672 may be involved in atrial fibrosis by indirectly regulating TRAF6 as a ceRNA by sponging miR-516a-5p.

Targeted long-term noninvasive treatment of choroidal neovascularization by biodegradable nanoparticles.

Choroidal neovascularization (CNV) is the main cause of vision loss in patients with wet age-related macular degeneration (AMD). Currently, treatment of these conditions requires repeated intravitreal injections, which may lead to complications such as infection and hemorrhage. So, we have developed a noninvasive method for treating CNV with nanoparticles, namely, Angiopoietin1-anti CD105-PLGA nanoparticles (AAP NPs), which targets the CNV to enhance drug accumulation at the site. These nanoparticles, with PLGA as a carrier, can slowly release encapsulated Angiopoietin 1 (Ang 1) and target the choroidal neovascularization marker CD105 to enhance drug accumulation, increases vascular endothelial cadherin (VE-cadherin) expression between vascular endothelial cells, effectively reduce neovascularization leakage and inhibit Angiopoietin 2(Ang 2) secretion by endothelial cells. In a rat model of laser-induced CNV, intravenous injection of AAP NPs exerted a good therapeutic effect in reducing CNV leakage and area. In short, these synthetic AAP NPs provide an effective alternative treatment for AMD and meet the urgent need for noninvasive treatment in neovascular ophthalmopathy. STATEMENT OF SIGNIFICANCE: This work describes the synthesis, injection-mediated delivery, in vitro and in vivo efficacy of targeted nanoparticles with encapsulated Ang1; via these nanoparticles, the drug can be targeted to choroidal neovascularization lesions for continuous treatment. The release of Ang1 can effectively reduce neovascularization leakage, maintain vascular stability, and inhibit Ang2 secretion and inflammation. This study provides a new approach for the treatment of wet age-related macular degeneration.

BMP-4 and BMP-7 Inhibit EMT in a Model of Anterior Subcapsular Cataract in Part by Regulating the Notch Signaling Pathway.

Purpose: The proliferation, migration, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) are believed to be the pathological mechanisms underlying anterior subcapsular cataract (ASC). Bone morphogenetic proteins (BMPs) inhibit transforming growth factor-beta (TGF-ß)-induced fibrosis in the lens. Herein, we aimed to further clarify the roles of BMP-4/BMP-7 in the progression and the underlying mechanisms of fibrotic cataract. Methods: BMP-4/BMP-7, TGF-ß2, jagged-1 peptide, or DAPT were applied in a mouse injury-induced ASC model and in the human LEC cell line SRA01/04. The volume of opacity was examined by a slit lamp and determined by lens anterior capsule whole-mount immunofluorescence. Global gene expression changes were assessed by RNA sequencing, and the levels of individual mRNAs were validated by real-time PCR. Protein expression was determined by the Simple Western sample dilution buffer. Cell proliferation was examined by CCK8 and EdU assays, and cell migration was measured by Transwell and wound healing assays. Results: Anterior chamber injection of BMP-4/BMP-7 significantly suppressed subcapsular opacification formation. RNA sequencing of the mouse ASC model identified the Notch pathway as a potential mechanism involved in BMP-mediated inhibition of ASC. Consistently, BMP-4/BMP-7 selectively suppressed Notch1 and Notch3 and their downstream genes, including Hes and Hey. BMP-4/BMP-7 or DAPT suppressed cell proliferation by inducing G1 cell cycle arrest. BMP-4/BMP-7 also inhibited TGF-ß2-induced cell migration and EMT by modulating the Notch pathway. Conclusions: BMP-4/BMP-7 attenuated ASC by inhibiting proliferation, migration, and EMT of LECs via modulation of the Notch pathway, thereby providing a new avenue for ASC treatment.

A case report of interstitial keratitis and secondary glaucoma after cataract surgery that may be related to late congenital syphilis.

BACKGROUND: The destruction of blood eye barrier and the administration of corticosteroid eyedrops after phacoemulsification surgery can lead to the replication of the local potential pathogens. With the rapid increase and popularization of cataract surgery, all kinds of rare postoperative complications have appeared. Here, we report a case of interstitial keratitis and secondary glaucoma after cataract surgery, which may be related to late congenital syphilis, which eventually led to blindness in the right eye. We hope that the timely report of this case will enable doctors to pay more attention to the possibility of potential pathogen replication after cataract surgery, and enable more patients to receive reasonable and effective treatment. CASE PRESENTATION: A 63-year-old female was referred to our clinic for investigation with a 1-week history of moderate pain in the right eye and ipsilateral headache in January 2020. She had cataract surgery on her right eye two years ago and on her left eye one year ago. The intraocular pressure (IOP) in the right eye was 43.2 mmHg and that in the left eye was 28.5 mmHg. Her right eye underwent medication, trabeculectomy and finally was subjected to ciliary body photocoagulation to control the IOP. The IOP of the left eye was well controlled by regular use of eye drops. In addition to the elevated IOP, the inflammation of the anterior segment and corneal stroma was found. Before cataract surgery, bilateral corneal opacities was revealed, but after cataract surgery, interstitial keratitis in both eyes was gradually aggravated, during the follow-up period from 2019 to 2021. She informed us that she had suffered from decreased vision in both eyes and was diagnosed with bilateral keratitis and congenital syphilis at the age of 20. In 2018, the serologic test for syphilis was positive in blood (Chemiluminescence analysis (CLIA): + ; Toluidine red unheated serum test (TRUST): + , titer was 1:1). However, four tests for TRUST were negative in 2019 and 2020, so she was not treated for syphilis. CONCLUSION: This case of glaucoma and interstitial keratitis might be secondary to ocular inflammation caused by late congenital syphilis. The ocular inflammation and the activation of syphilis may be related to cataract surgery.

Clinical characteristics and prognosis differences between isolated right and left ventricular myocardial infarction in the Chinese population: a retrospective study.

Background and aims: Acute myocardial infarction (AMI) is divided into left ventricular myocardial infarction (LVMI) and right ventricular myocardial infarction (RVMI) according to the regions of myocardial ischemic necrosis. Clinical characteristics, treatment strategies, and prognosis differences between isolated RVMI and LVMI have not been well characterized. This study aimed to explore this difference of patients with isolated RVMI and LVMI. Methods: This retrospective cohort study included 3,506 patients hospitalized with coronary angiography diagnosed type 1 myocardial infarction (MI). Characteristics of admission and treatment strategies were compared in patients with isolated RVMI and LVMI. COX proportional hazards models with and without inverse probability of treatment weighting (IPTW) adjustment were performed to estimate the difference in all-cause and cardiovascular mortality between the two groups. Results: In this retrospective study, we found the frequency of isolated RVMI was significantly lower in the population than that of isolated LVMI (406 (11.6%) vs 3,100 (88.4%)). Patients with isolated RVMI have similar age, sex, and comorbidities to the patients with isolated LVMI. However, patients with isolated RVMI have lower heart rate and blood pressure, but higher rates of cardiogenic shock and atrioventricular block. It is noteworthy that patients with isolated RVMI are more likely to be complicated with the multivessel lesion. Patients with isolated RVMI have lower risk of all-cause mortality (HR 0.36; 95% CI [0.24-0.54], p < 0.001) and cardiovascular mortality (HR 0.37; 95% CI [0.22-0.62], p < 0.001) than patients with isolated LVMI. Conclusions: This study showed that patients with isolated RVMI and LVMI have similar baseline characteristics. However, the clinical manifestations were different in the isolated RVMI and LVMI patients. This study revealed a better prognosis of isolated RVMI patients compared to isolated LVMI, which indicates the ischemic region could be considered in AMI risk stratification models for better assessment of risk for adverse clinical events.