Deciphering the impact of aging on splenic endothelial cell heterogeneity and immunosenescence through single-cell RNA sequencing analysis.

BACKGROUND: Aging is associated with significant structural and functional changes in the spleen, leading to immunosenescence, yet the detailed effects on splenic vascular endothelial cells (ECs) and their immunomodulatory roles are not fully understood. In this study, a single-cell RNA (scRNA) atlas of EC transcriptomes from young and aged mouse spleens was constructed to reveal age-related molecular changes, including increased inflammation and reduced vascular development and also the potential interaction between splenic endothelial cells and immune cells. RESULTS: Ten clusters of splenic endothelial cells were identified. DEGs analysis across different EC clusters revealed the molecular changes with aging, showing the increase in the overall inflammatory microenvironment and the loss in vascular development function of aged ECs. Notably, four EC clusters with immunological functions were identified, suggesting an Endothelial-to-Immune-like Cell Transition (EndICLT) potentially driven by aging. Pseudotime analysis of the Immunology4 cluster further indicated a possible aging-induced transitional state, potentially initiated by Ctss gene activation. Finally, the effects of aging on cell signaling communication between different EC clusters and immune cells were analyzed. CONCLUSIONS: This comprehensive atlas elucidates the complex interplay between ECs and immune cells in the aging spleen, offering new insights into endothelial heterogeneity, reprogramming, and the mechanisms of immunosenescence.

Surgical Outcomes of Standardized Endoscopical Deep Medial Orbital Decompression in Dysthyroid Optic Neuropathy.

INTRODUCTION: The aim of the study was to standardize the endoscopic deep medial orbital decompression surgery for better relief of optic nerve compression in dysthyroid optic neuropathy (DON). METHODS: A total of 128 eyes from patients received the standardized endoscopic deep medial orbital decompression surgery were recruited in this study. The efficacy of the procedure was assessed at a 1-month follow-up by the best-corrected visual acuity (VA), visual field (VF), and visual evoked potential (VEP). Clinical data were collected to explore the factors that affected visual recovery. Oxygen saturation of retinal blood vessels, retinal thickness, and vessel density were measured to demonstrate the potential recovery mechanisms. RESULTS: After surgery, the ratio of extraocular muscle volume in the orbital apex to orbital apex volume significantly decreased from 44.32 ± 22.31% to 36.82 ± 12.02% (p < 0.001). 96.87% of eyes' final VA improved; average VA improved from 0.93 ± 0.73 to 0.50 ± 0.60 at 1 week (p < 0.001) and 0.40 ± 0.53 at 1 month (p < 0.001). Postoperatively, VF and VEP also improved, the oxygen saturation of retinal arteries increased, and the retinal thickness was reduced. Preoperative VA, visual impairment duration, and clinical activity score evaluation were associated with visual recovery. CONCLUSION: In this study, we standardized the endoscopic deep medial orbital decompression, of which key point was to relieve pressure in the orbital apex and achieved satisfactory visual recovery in DON patients.

Modified Conjoint Fascial Sheath and Levator Muscle Complex Suspension for the Correction of Simple Severe Congenital Ptosis in Pediatrics and the Effect on Refractive Status.

PURPOSE: To evaluate the outcomes of modified combined fascia sheath and levator muscle complex suspension to correct severe congenital ptosis in pediatrics and the effect on refractive status. METHODS: This prospective, case series study enrolled patients (aged ≤18 years) with simple severe congenital ptosis at Zhongshan Ophthalmic Center. All patients were treated with combined fascia sheath + levator muscle suspension and followed up for 3 months. Preoperative and postoperative cycloplegic refraction and the best-corrected visual acuity were performed. The types of astigmatism include with-the-rule, against-the-rule, and oblique. RESULTS: Thirty-six patients (50 eyes) were enrolled. The mean age was 7.11 ± 3.72 years. The surgery success rate was 90.0%. Following surgery, the eyelid contour of all eyes exhibited natural symmetry and satisfactory curvature. The eyelid height difference in OUs was ≤1 mm for 42 eyes. For 47 eyes, the eyelid crease was symmetry. Two eyes had conjunctival prolapse, and 1 eye developed trichiasis. After surgery, cylinder power changed from mean -1.14 ± 1.27 D to -1.54 ± 1.25 D ( p < 0.001) and best-corrected visual acuity improved from mean 0.205 ± 0.217 logarithm of the minimum angle of resolution to 0.168 ± 0.176 logarithm of the minimum angle of resolution ( p = 0.048). The quantities of with-the-rule increased from 35 eyes to 41 eyes, oblique from 4 eyes to 6 eyes, while against-the-rule decreased from 11 eyes to 3 eyes ( p = 0.01). CONCLUSIONS: Combined fascia sheath + levator muscle suspension under general anesthesia is effective and safe for severe congenital ptosis in pediatrics. However, astigmatism increased and the types of astigmatism changed after surgery.

Dry eye and decreased tear film stability in primary acquired nasolacrimal duct obstruction patients.

PURPOSE: Exploring the prevalence of dry eye (DE) and the changes of tear film stability in patients with primary acquired obstruction of the nasolacrimal duct (PANDO). METHODS: In this cross-sectional, observational study, 370 eyes in 223 patients with PANDO were assessed. The ocular surface disease index (OSDI) was used to evaluate ocular surface symptoms, and the Keratograph 5M non-invasive ocular surface analyser was used to assess ocular surface parameters. According to the TFOS DEWS II criteria, patients with OSDI ≥ 13 and NIKBUT < 10 s were diagnosed with DE. RESULTS: Of the 223 PANDO patients, 65 (29.1%) met the diagnostic criteria for DE. Compared with patients without DE, PANDO patients with DE were significantly older (p < 0.001), had a longer duration of epiphora (p = 0.023), and more likely to have a positive regurgitation on pressure over the lacrimal sac (ROPLAS) sign (p = 0.003). Multifactorial analysis showed that older age, positive ROPLAS and hypertension were significant independent predictors of DE (p < 0.05). Among the 147 unilateral PANDO patients without DE, the TMH, NIKBUT-first, NIKBUT-average and bulbar erythema scores were significantly higher in the PANDO sides. CONCLUSIONS: This study illustrated the prevalence of DE in PANDO patients was 29.1% and DE is more likely to occur in those who are older, have hypertension and are positive for ROPLAS. In addition, in patients with unilateral nasolacrimal duct obstruction, a decrease in tear film stability was observed in the healthy eye.

Controlled Synthesis of MOF-Derived Nano-Microstructure toward Lightweight and Wideband Microwave Absorption.

Correlating metal-organic framework (MOF) synthesis processes and microwave absorption (MA) enhancement mechanisms is a pioneer project. Nevertheless, the correlation process still relies mainly on empirical doctrine, which hardly corresponds to the specific mechanism of the effect on the dielectric properties. Hereby, after the strategy of modulation of protonation engineering and solvothermal temperature in the synthesis route, the obtained sheet-like self-assembled nanoflowers were constructed. Porous structures with multiple heterointerfaces, abundant defects, and vacancies are obtained by controlled design of the synthesis procedure. The rearrangement of charges and enhanced polarization can be promoted. The designed electromagnetic properties and special nano-microstructures of functional materials have significant impact on their electromagnetic wave energy conversion effects. As a consequence, the MA performance of the samples has been enhanced toward broadband absorption (6.07 GHz), low thickness (2.0 mm), low filling (20%), and efficient loss (-25 dB), as well as being suitable for practical environmental applications. This work establishes the connection between the MOF-derived materials synthesis process and the MA enhancement mechanism, which provides insight into various microscopic microwave loss mechanisms.

Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation.

BACKGROUND: Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. METHODS: Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. RESULTS: We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. CONCLUSIONS: Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression.

Critical role of transcriptome-wide m6A methylation in the aqueous humor of patients with pseudoexfoliation glaucoma.

N6-methyladenosine (m6A) modification is one of the most common types of methylation modifications in eukaryotic mRNA. However, its role in the pathogenesis of pseudoexfoliation glaucoma (PXG) has not yet been reported. To enhance understanding in this regard, we assessed the m6A methylome in the aqueous humor of patients with PXG. MeRIP-Seq and RNA-Seq analyses were performed to compare the m6A methylomes and gene expression profiles of the aqueous humor of patients with PXG with those of patients with age-related cataract (ARC). Colorimetric m6A quantification was performed to detect global m6A levels. Quantitative reverse transcription PCR confirmed the expression of m6A-related enzymes and mRNAs in both groups. Results showed significantly higher aqueous humor m6A levels in the PXG group than in the ARC group. Five m6A-related enzymes, including METTL3, YTHDC2, HNRNPA2B1, HNRNPC, and LRPPRC, were significantly up-regulated in PXG specimens. We also observed 9728 m6A-modified peaks related to 6126 gene transcripts in the PXG group, with more than 250 genes containing one m6A peak (hypomethylated or hypermethylated). The distribution of the m6A peaks was enriched in coding sequences and 3'-untranslated regions for both groups. GGAC motif structures were also significantly enriched. Bioinformatics analysis further revealed that m6A plays a critical role in extracellular matrix formation and histone deacetylation. Additionally, MMP14, ADAMTSL1, FN1, and HDAC1 showed significant changes in m6A methylation and mRNA expression in the PXG group. Therefore, m6A methylation may regulate extracellular matrix composition in PXG and METTL3 may be a pivotal regulator of this process. In the future, it would be necessary to investigate MMP14, ADAMTSL1, FN1, and HDAC1, which are potential target genes.

Application effect of an artificial intelligence-based fundus screening system: evaluation in a clinical setting and population screening.

BACKGROUND: To investigate the application effect of artificial intelligence (AI)-based fundus screening system in real-world clinical environment. METHODS: A total of 637 color fundus images were included in the analysis of the application of the AI-based fundus screening system in the clinical environment and 20,355 images were analyzed in the population screening. RESULTS: The AI-based fundus screening system demonstrated superior diagnostic effectiveness for diabetic retinopathy (DR), retinal vein occlusion (RVO) and pathological myopia (PM) according to gold standard referral. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of three fundus abnormalities were greater (all > 80%) than those for age-related macular degeneration (ARMD), referable glaucoma and other abnormalities. The percentages of different diagnostic conditions were similar in both the clinical environment and the population screening. CONCLUSIONS: In a real-world setting, our AI-based fundus screening system could detect 7 conditions, with better performance for DR, RVO and PM. Testing in the clinical environment and through population screening demonstrated the clinical utility of our AI-based fundus screening system in the early detection of ocular fundus abnormalities and the prevention of blindness.

An SCD1-dependent mechanoresponsive pathway promotes HCC invasion and metastasis through lipid metabolic reprogramming.

Matrix stiffness promotes hepatocellular carcinoma (HCC) metastasis. This study examined the contribution of lipid metabolic reprogramming to matrix stiffness-induced HCC metastasis. HCC cells were cultured on mechanically tunable polyacrylamide gels and subjected to lipidomic analysis. The key enzyme that responded to matrix stiffness and regulated lipid metabolism was identified. The comparative lipidomic screening revealed that stearoyl-CoA desaturase 1 (SCD1) is a mechanoresponsive enzyme that reprogrammed HCC cell lipid metabolism. The genetic and pharmacological inhibition of SCD1 expression/activity altered the cellular lipid composition, which in turn impaired plasma membrane fluidity and inhibited in vitro invasive motility of HCC cells in response to high matrix stiffness. Knockdown of SCD1 suppressed HCC invasion and metastasis in vivo. Conversely, the overexpression of SCD1 or exogenous administration of its product oleic acid augmented plasma membrane fluidity and rescued in vitro invasive migration in HCC cells cultured on soft substrates, mimicking the effects imposed by high matrix stiffness. In human HCC tissues, collagen content, a marker of increasing matrix stiffness, and increased expression of SCD1 together predicted poor survival of HCC patients. An SCD1-dependent mechanoresponsive pathway that responds to increasing matrix stiffness in the tumor microenvironment promotes HCC invasion and metastasis through lipid metabolic reprogramming.

Polyester 5-0 suture for porous implant placement after retinoblastoma enucleation: analysis of 120 sockets.

BACKGROUND: Techniques used to suture the rectus muscle to the implant can influence the implant-related complications which is still a major problem following retinoblastoma enucleation. The goals of this work were to report the efficacy among patients with retinoblastoma who underwent enucleation followed by porous implant placement with the rectus muscles sutured with 5-0 polyester suture. METHODS: This was a retrospective study of consecutive patients with retinoblastoma who underwent primary enucleation and porous implant placement with the rectus muscles tagged and sutured to the implant with polyester 5-0 suture. All the patients were followed up for a minimum of 2 years. The main outcome measure was implant exposure. The secondary efficacy measures were other implant-related complications. RESULTS: Between May 2016 and December 2018, a total of 120 patients (120 eyes) underwent primary enucleation and porous implant placement were included. Postoperatively, 10/120 (8.3%) eyes developed exposure or conjunctival granuloma. Exposure was the most common postoperative complication (7/10, 70.0%). There were no cases of implant extrusion, migration, or infection. CONCLUSIONS: Polyester 5-0 sutures are successful in patients with retinoblastoma who underwent enucleation followed by porous implant placement. Complications are minimal. Polyester 5-0 sutures were not associated with unacceptable complications in this pediatric population.

Efficacy and safety of super pulse CO2 laser-assisted punctoplasty with canalicular curettage in primary canaliculitis.

The objective of this study was to evaluate the efficacy and safety of super pulse CO2 laser-assisted punctoplasty with canalicular curettage in primary canaliculitis. In this retrospective serial case study, the clinical data of 26 patients who underwent super pulse CO2 laser-assisted punctoplasty for the treatment of canaliculitis were collected from January 2020 to May 2022. The clinical presentation, intraoperative and microbiologic findings, surgical pain severity, postoperative outcome, and complications were studied. Of the 26 patients, most were females (female:male 20:6), with a mean age of 60.1 ± 16.1 years (range, 19-93). Mucopurulent discharge (96.2%), eyelid redness and swelling (53.8%), and epiphora (38.5%) were the most common presentations. During the surgery, concretions were present in 73.1% (19/26) of the patients. The surgical pain severity scores ranged from 1 to 5, according to the visual analog scale, with a mean score of 3.2 ± 0.8. This procedure resulted in complete resolution in 22 (84.6%) patients and significant improvement in 2 (7.7%) patients, and 2 (7.7%) patients required additional lacrimal surgery with a mean follow-up time of 10.9 ± 3.7 months. The surgical procedure of super pulse CO2 laser-assisted punctoplasty followed by curettage appears to be a safe, effective, minimally invasive, and well-tolerated treatment for primary canaliculitis.

A simple and efficient technique for suturing and knotting during endoscopic dacryocystorhinostomy.

PURPOSE: This study evaluated the long-term outcomes of endoscopic suturing and knotting-dacryocystorhinostomy (eSK-DCR) without the use of a stent or mitomycin C. METHODS: A prospective interventional case series was performed on patients with nasolacrimal duct obstruction (NLDO) who underwent eSK-DCR at Zhongshan Ophthalmic Center from October 2019 to December 2019. The surgeon sutured the lacrimal sac mucosa with the nasal mucosa by tying knots under endoscopic DCR. Subject demographics, preoperative data and postoperative data were collected, including clinical presentation, Munk score for epiphora, surgical indications, operation time, duration of knotting, number of knots, endoscopic ostium size, complications, and anatomical and functional success. Anatomic success was defined as patent ostium on lacrimal irrigation, and functional success was defined as subjective improvement in symptoms. Statistical analysis was performed by IBM SPSS software (Version 20.0; SPSS Inc., Chicago, IL, USA). RESULTS: A total of 60 patients (71 eyes) underwent pure eSK-DCR. Of these, 95.0% (57/60) were females. The mean age of the patients was 54.7 years. The mean surgical time was 37.60 min, and the average time for each knotting was 2.86 min. Endoscopic evidence found that all patients showed patent ostium and normal healing of the flaps after 4 weeks. The Munk scores dropped significantly at 6 months postoperatively compared to preoperative scores (P < 0.0001). Although 4 patients (7 eyes) were lost to follow-up at the end of the 2-year period, the anatomical and functional success remained stable during the 2-year follow-up period (anatomical, 100%; functional, 87.5%). No serious complications were detected during the follow-up period. CONCLUSION: Pure eSK-DCR is a simple and reliable therapeutic method for the management of NLDO. The surgical outcomes were good and remained stable beyond 6 months postoperatively.

Microbial distributions in the conjunctiva and lacrimal sacs of patients with chronic dacryocystitis in a tertiary hospital.

BACKGROUND: The aim was to clarify the distributions of bacteria in the conjunctival sac and lacrimal sac in patients with chronic dacryocystitis. METHODS: In total, 297 (322 eyes) chronic dacryocystitis patients who underwent nasal endoscopic dacryocystorhinostomy (EN-DCR) were included. Conjunctival sac secretions from the affected eye were collected preoperatively, and lacrimal sac retention fluid from the affected side in the same patient was collected intraoperatively. Bacterial culture and drug sensitivity testing were performed to determine bacterial distributions. RESULTS: In total, 127 bacterial isolates (49 species) were detected in 123 eyes in the conjunctival group, with a positivity rate of 38.2% (123/322); 85 bacterial isolates (30 species) were detected in 85 eyes in the lacrimal sac group, with a positivity rate of 26.4% (85/322). The positivity rates were significantly different (P = 0.001) between two groups. The gram-negative bacilli proportion in the lacrimal sac group (36/85, 42.4%) was significantly higher than that in the conjunctival sac group (37/127, 29.2%) ( P = 0.047). Positive conjunctival sac secretion culture (123/322) was significantly associated with increased ocular secretion (281/322, 87.3%) (P = 0.002). Among the culture-positive bacteria in the conjunctival sac group and the lacrimal sac group, 30/127, 23.6% and 43/127, 26.7% and 21/85, 24.7% and 20/85, 23.5% were resistant to levofloxacin and tobramycin, respectively. CONCLUSIONS: This study illustrated differences in bacterial distributions between conjunctival sac secretions and retained lacrimal sac fluid in chronic dacryocystitis patients, with a higher proportion of gram-negative bacilli in lacrimal sac secretions. The ocular surface flora in chronic dacryocystitis patients is partially resistant to levofloxacin and tobramycin, which need to be considered by ophthalmologists.

lncRNA-AC079061.1/VIPR1 axis may suppress the development of hepatocellular carcinoma: a bioinformatics analysis and experimental validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable. METHODS: Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC. RESULTS: lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells. CONCLUSION: The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.

On the knowledge of solitary juvenile xanthogranuloma of the eyelid: a case series and literature review.

PURPOSE: Solitary eyelid juvenile xanthogranuloma (JXG) is extremely rare, and there is limited literature on its clinical features and treatment outcomes. Here, we present a case series and comprehensive review of the literature on patients with isolated eyelid JXG. METHODS: We systematically extracted data from our institution's records of isolated eyelid JXG cases and conducted a search for additional cases from the literature utilising the PubMed, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases. Patients with JXG were analysed with respect to age, sex, clinical presentation, therapy, and outcome. Group comparisons were performed. RESULTS: Thirty-two patients (including 13 at our institution and 19 from prior publications) were identified. The median age at first presentation was higher in current patients than in the patients from the published cases (median 9 years, range 1.2 to 47.0 years; median 2 years, range 0.5 months to 46.0 years, respectively, P = 0.014). Of the patients who had known characteristics, no significant differences were observed between the two groups in terms of sex, affected eye, eyelid site, type of cutaneous involvement, or duration of symptoms (each P > 0.05). Seventeen (54.8%) patients were male. The most common lesion location was the upper eyelid (n = 10, 62.5%). Twenty-four (75.0%) cutaneous lesions had full-thickness skin involvement; 8 (25.0%) subcutaneous masses had a chalazion-like appearance. Histologically, the JXG masses were characterised by Touton giant cells with inflammatory cells. Additionally, there was no significant difference in treatment modalities between the two groups (P = 0.072), and 24 (75.0%) patients underwent surgical excision. The overall recurrence-free survival was 3.6 to 52.8 (median 27.0) months in the current patients. For published cases with available follow-up information, there was no recurrence in 10 cases and improvement in 1 case, with a median follow-up of 9.5 months. CONCLUSION: Solitary eyelid JXG is a rare clinical entity and should be included in the differential diagnosis of eyelid mass lesions in patients of all age groups. Surgical excision is often selected for efficient treatment and to obtain an excisional biopsy.

Disulfiram Exerts Antifibrotic and Anti-Inflammatory Therapeutic Effects on Perimysial Orbital Fibroblasts in Graves' Orbitopathy.

Fibrosis of extraocular muscles (EOMs) is a marker of end-stage in Graves' orbitopathy (GO). To determine the antifibrotic and anti-inflammatory therapeutic effects and the underlying molecular mechanisms of disulfiram (DSF) on perimysial orbital fibroblasts (pOFs) in a GO model in vitro, primary cultures of pOFs from eight patients with GO and six subjects without GO (NG) were established. CCK-8 and EdU assays, IF, qPCR, WB, three-dimensional collagen gel contraction assays, cell scratch experiments, and ELISAs were performed. After TGF-ß1 stimulation of pOFs, the proliferation rate of the GO group but not the NG group increased significantly. DSF dose-dependently inhibited the proliferation, contraction, and migration of pOFs in the GO group. Additionally, DSF dose-dependently inhibited fibrosis and extracellular matrix production markers (FN1, COL1A1, α-SMA, CTGF) at the mRNA and protein levels. Furthermore, DSF mediates antifibrotic effects on GO pOFs partially through the ERK-Snail signaling pathway. In addition, DSF attenuated HA production and suppressed inflammatory chemokine molecule expression induced by TGF-ß1 in GO pOFs. In this in vitro study, we demonstrate the inhibitory effect of DSF on pOFs fibrosis in GO, HA production, and inflammation. DSF may be a potential drug candidate for preventing and treating tissue fibrosis in GO.

Lateral and Normal Capillary Force Evolution of a Reciprocating Liquid Bridge.

Capillary forces of a shearing liquid bridge can significantly affect the friction and adhesion of interacting surfaces, but the underlying mechanisms remain unclear. We custom built a surface force apparatus (SFA, ±2 µN) equipped with in situ optical microscopy and performed normal and lateral force measurements on a reciprocating water bridge formed between two flat plates. A modified wedge method was developed to correct the unique force measurement errors caused by the changing bridge geometry and position. The results found (1) strong linear relations among the bridge shear displacement, the cosine difference between the left and right contact angles, and the lateral adhesion force and (2) the normal adhesion force increased monotonically up to 13% as the bridge geometry approached its axisymmetric state. Quasi-static force analyses based on a newly developed decahedral model showed good agreement with the experiments and improved accuracy compared with that of cylindrical or rectangular column models previously proposed in the literature. Although limited in certain aspects, this study may (1) prove helpful to the design and analysis of liquid bridge force experiments on platforms similar to the SFA used in this study and (2) help to bridge the gap between friction and liquid bridge physics in the literature.

Low initial trough concentration of rituximab is associated with unsatisfactory response of first-line R-CHOP treatment in patients with follicular lymphoma with grade 1/2.

For follicular lymphoma (FL) with grade 1/2, the complete response (CR) rate of the first-line R-CHOP treatment was significantly low. In this study, we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses. Thus, we conducted a prospective pharmacokinetic (PK) study in 68 FL patients with grades 1-3 treated with R-CHOP at 21-day intervals. Plasma rituximab concentrations were quantified using ELISA and the population PK modeling was established with Phoenix® NLMETM. The first cycle trough concentration (C1-trough) of rituximab was a significant independent risk factor for achieving CR in matched-pair logistic regression analysis, rather than the concentrations in later cycles; the recommendatory minimum optimal C1-trough was 13.60 µg/mL. Patients with grade 1/2 had significantly lower C1-trough compared with grade 3 (12.21 µg/mL vs. 23.45 µg/mL, P < 0.001), only 30% patients with grade 1/2 could reach 13.60 µg/mL, compared with 91.67% in patients with grade 3, which was in accord with its unsatisfactory CR rates (43.33% vs. 76.32%). The stage indicating the tumor burden (the target) was a crucial influence factor for C1-trough, accounting for 40.70% of its variability, 70% patients with grade 1/2 were stage IV in this study, since the systemic therapy only started at the disseminated disease stage. The initial dose of 1800 mg was recommended by Monte Carlo simulation for patients with grade 1/2. In summary, low C1-trough accounted for low-grade FL's unsatisfactory CR rate, designing the first dosage of rituximab should be a very important component of individualized therapy for FL.

Albumin-to-alkaline phosphatase ratio as a predictor of tumor recurrence and prognosis in patients with early-stage hepatocellular carcinoma undergoing radiofrequency ablation as initial therapy.

OBJECTIVE: Albumin-to-alkaline phosphatase ratio (AAPR), a newly developed blood biomarker, has been reported to have prognostic value in several types of cancer. This study aimed to investigate the predictive value of AAPR in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) as initial therapy. METHODS: This retrospective study analyzed 445 patients with newly diagnosed HCC undergoing RFA as initial therapy. A series of survival analyses were performed to evaluate the prognostic value of AAPR. Univariate and multivariate analyses were performed to identify independent prognostic factors. An AAPR-based nomogram was constructed, and its predictive performance was validated. RESULTS: Patients with a low AAPR had a significantly reduced recurrence-free survival (RFS) and overall survival (OS) compared with those with a high AAPR. AAPR was found to be an independent prognostic indicator and showed superior discrimination efficacy than other liver function indices. The AAPR-based nomogram had a concordance index value of 0.72 (95% confidence interval [CI]: 0.65-0.79) in the training cohort and 0.72 (95% CI: 0.63-0.81) in the validation cohort, which significantly outperformed other existing staging systems. CONCLUSIONS: AAPR serves as a promising indicator of prognosis in patients with early-stage HCC undergoing RFA. The AAPR-based nomogram might contribute to individualized prognosis prediction and clinical decision making.