Development and validation of a nomogram for predicting the need for concomitant endoscopic septoplasty during endonasal endoscopic dacryocystorhinostomy.

Background: Simultaneous endoscopic septoplasty is often required during endonasal endoscopic dacryocystorhinostomy (En-DCR) to improve access to the lacrimal sac and potentially optimize surgical success rates. In current practice, the decision to proceed to concomitant endoscopic septoplasty during En-DCR in patients with primary acquired nasolacrimal duct obstruction (PANDO) is determined by anterior rhinoscopy and nasal endoscopic examination. However, none of these methods can be used to quantitatively assess the severity of septal deviation to determine the need for concomitant endoscopic septoplasty during En-DCR. This study was thus conducted to develop and validate a radiological prediction model based on computed tomography (CT) to predict the necessity of concomitant endoscopic septoplasty during En-DCR. Methods: Data from 225 patients with PANDO and nasal septal deviation (NSD) who had undergone unilateral En-DCR in a single center from January 2022 to June 2023 were retrospectively analyzed. Least absolute shrinkage and selection operator (LASSO) was used to select predictors for concomitant endoscopic septoplasty during En-DCR. The ultimate model was developed through the application of multivariable logistic regression and subsequently confirmed through assessment with an internal validation cohort. The final model was then visually represented using a nomogram and an online calculator. Results: In this retrospective study of 225 eyes from 225 patients with PANDO and NSD, the training cohort included 157 eyes, and the validation cohort included 68 eyes. CT imaging characteristics including NSD angle [odds ratio (OR) 1.54; 95% confidence interval (CI): 1.32-1.87], NSD location (OR 4.49; 95% CI: 1.25-18.77), NSD direction (OR 5.38; 95% CI: 1.48-24.52), and middle nasal passage width (MNPW) at the surgical side (OR 0.61; 95% CI: 0.43-0.82) were identified as independent predictors for concomitant endoscopic septoplasty during En-DCR. A novel nomogram constructed from these CT signs showed high predictive performance. The area under the curves (AUCs) of the training set and internal validation set were 0.913 and 0.909, respectively. Conclusions: A CT-based radiological prediction model was created to help surgeons determine if concomitant endoscopic septoplasty is needed during En-DCR in patients with PANDO and NSD.

Cation Vacancy Strategy Activated Layered Double Hydroxides: Enhanced Electrochemical Performance and Longevity.

The defect design strategy has been extensively employed to enhance the reaction kinetics of layered double hydroxide (LDH) electrode materials. Furthermore, it is anticipated to improve the cyclic stability of LDHs through this approach, serving a dual purpose. However, the potential mechanisms of cation vacancies' impact on the electrochemical performance of electrodes at the atomic scale still need further clarification. In this study, a typical aluminum-vacancy LDH material via a simple alkaline etching method was demonstrated. Electrochemical in situ Raman spectroscopy, ex situ X-ray diffraction (XRD), and first-principles calculations were utilized to elucidate the mechanism of Faradaic reactions. The findings indicate that this cation vacancy strategy not only enhances the electrochemical reaction kinetics of the electrodes but also effectively reduces the energy barrier for the α to γ phase transition of LDHs during the charge-discharge processes, thereby enhancing its longevity. To further validate the practical application of this defect design, an asymmetric solid-state supercapacitor was formed, which maintains 93.9% capacity after 20 000 charge-discharge cycles. This research offers technical guidance for the development of a new generation of high-performance and long-life LDH electrode materials based on a cation vacancy strategy.

An L-type calcium channel blocker nimodipine exerts anti-fibrotic effects by attenuating TGF-ß1 induced calcium response in an in vitro model of thyroid eye disease.

BACKGROUND: Thyroid eye disease (TED) is a vision-threatening autoimmune disorder. Orbital tissue fibrosis leading to intractable complications remains a troublesome issue in TED management. Exploration of novel therapeutic targets and agents to ameliorate tissue fibrosis is crucial for TED. Recent work suggests that Ca2+ signaling participates in tissue fibrosis. However, whether an alteration of Ca2+ signaling has a role in fibrogenesis during TED remains unclear. In this study, we aimed to investigate the role of Ca2+ signaling in the fibrogenesis process during TED and the potential therapeutic effects of a highly selective inhibitor of the L-type calcium channel (LTCC), nimodipine, through a TGF-ß1 induced in vitro TED model. METHODS: Primary culture of orbital fibroblasts (OFs) were established from orbital adipose connective tissues of patients with TED and healthy control donors. Real-time quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing were used to assess the genes expression associated with LTCC in OFs. Flow cytometry, RT-qPCR, 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay, wound healing assay and Western blot (WB) were used to assess the intracellular Ca2+ response on TGF-ß1 stimulation, and to evaluate the potential therapeutic effects of nimodipine in the TGF-ß1 induced in vitro TED model. The roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and signal transducer and activator of transcription 1 (STAT1) in fibrogenesis during TED were determined by immunohistochemistry, WB, flow cytometry and co-immunoprecipitation assay. Selective inhibitors were used to explore the downstream signaling pathways. RESULTS: LTCC inhibitor nimodipine blocked the TGF-ß1 induced intracellular Ca2+ response and further reduced the expression of alpha-smooth muscle actin (α-SMA), collagen type I alpha 1 (Col1A1) and collagen type I alpha 2 (Col1A2) in OFs. Besides, nimodipine inhibited cell proliferation and migration of OFs. Moreover, our results provided evidence that activation of the CaMKII/STAT1 signaling pathway was involved in fibrogenesis during TED, and nimodipine inhibited the pro-fibrotic functions of OFs by down-regulating the CaMKII/STAT1 signaling pathway. CONCLUSIONS: TGF-ß1 induces an LTCC-mediated Ca2+ response, followed by activation of CaMKII/STAT1 signaling pathway, which promotes the pro-fibrotic functions of OFs and participates in fibrogenesis during TED. Nimodipine exerts potent anti-fibrotic benefits in vitro by suppressing the CaMKII/STAT1 signaling pathway. Our work deepens our understanding of the fibrogenesis process during TED and provides potential therapeutic targets and alternative candidate for TED.

Experimental Study of Ultra-Pulsed CO 2 Fractional Laser Combined With Recombinant Human Epidermal Growth Factor Gel in the Treatment of Eyelid Keloid.

OBJECTIVE: Keloid (KD) and hypertrophic scars are prevalent and result from excessive growth of dermal tissue after skin damage. This review focused on the clinical application of the ultra-pulsed CO 2 fractional laser combined with recombinant human epidermal growth factor (rHEGF) gel in patients with eyelid KD. METHODS: Patients (N = 98) with KD who underwent surgery were randomly divided into a study group (ultra-pulsed CO 2 fractional laser combined with rHEGF gel therapy, N = 49) and a control group (ultra-pulsed CO 2 fractional laser therapy, N = 49). Besides, 5 cases dropped out of the study, including 2 cases in the study group and 3 cases in the control group. Finally, 47 cases of the study group and 46 cases of the study group were included in the analysis. The clinical baseline data such as sex, age, body mass index, scar area, etiology, Vancouver Scar Scale score, Patient and Observer Scar Assessment Scale score, four-item itch questionnaire score, serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α level expression were recorded in the study group (N = 47) and the control group (N = 46). RESULTS: There was no significant difference in gender, age, body mass index, scar area, etiology, Vancouver Scar Scale score, Patient and Observer Scar Assessment Scale score, 4-item itch questionnaire score, IL-6, IL-10, and tumor necrosis factor-α levels between the patients treated with ultra-pulse CO 2 fractional laser + rHEGF gel and those only treated with ultra-pulse CO 2 fractional laser ( p > 0.05). Vancouver Scar Scale scores, Patient and Observer Scar Assessment Scale scores, and four-item itch questionnaire scores of patients with eyelid KD decreased to a greater extent than those treated with ultra-pulsed CO 2 fractional laser combined with rHEGF gel ( p <0.01). Compared with ultra-pulsed CO 2 fractional laser treatment, ultra-pulsed CO 2 fractional laser combined with rHEGF gel was more efficacious in treating patients with eyelid KD, with a lower incidence of adverse effects and a 1-year recurrence rate. CONCLUSIONS: Ultra-pulsed CO 2 fractional laser combined with rHEGF gel can significantly improve the scar status and scar itching in patients with eyelid KD, with an obvious therapeutic effect, a low incidence of adverse effects, a 1-year recurrence rate, and high safety, which is worthy of popularization and application.

Nasolacrimal duct rhinostomy for low-level nasolacrimal duct obstruction:long-term outcomes and surgical selection paradigm.

PROPOSE: This study aims to present long-term outcomes in a specific patient population experiencing epiphora due to low-level nasolacrimal duct obstruction (NLDO) following endonasal endoscopic nasolacrimal duct rhinostomy, and to propose a surgical selection paradigm for varying locations of NLDO. METHODS: Between September 1, 2017 and February 28, 2023, a retrospective analysis was conducted on 26 patients diagnosed with primary acquired nasolacrimal duct obstruction (PANDO) who underwent endonasal endoscopic nasolacrimal duct rhinostomy for low-level NLDO (defined as obstruction below the plane of the superior border of the inferior turbinate attachment). The study assessed surgical success through objective measures of anatomical patency and subjective measures of functional patency during a postoperative follow-up period of at least six months. Additionally, any complications that arose during this follow-up period were documented. RESULTS: The study included a cohort of 26 patients, consisting of 24 women and 2 men, with a mean age of 47.58 ± 3.09 years (range: 8-75). All patients underwent endoscopic nasolacrimal duct rhinostomy, with 10 eyes having previously undergone tear duct recanalization procedures. Anatomical patency was achieved in 88.5% (23/26) of cases, while functional patency was achieved in 80.8% (21/26) after an average follow-up period of 41.9 ± 22.1 months. No significant complications were observed in any of the patients during the follow-up period. CONCLUSION: Endonasal endoscopic nasolacrimal duct rhinostomy is effective in treating epiphora in over 80% of cases with low-level NLDO. Tailoring the surgery to the location of the obstruction can improve outcomes and minimize damage.

An Oxidative Stress-Related Prognostic Signature Predicts Treatment Response and Outcomes for Hepatocellular Carcinoma After Transarterial Chemoembolization.

Purpose: Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored. Methods: We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis. Results: The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival. Conclusion: The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.

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.

DDR2/STAT3 Positive Feedback Loop Mediates the Immunosuppressive Microenvironment by Upregulating PD-L1 and Recruiting MDSCs in Oxaliplatin-Resistant HCC.

BACKGROUND AND AIMS: Transcriptome sequencing revealed high expression of DDR2 in oxaliplatin-resistant hepatocellular carcinoma (HCC). This study aimed to explore the role of DDR2 in oxaliplatin resistance and immune evasion in HCC. METHODS: Oxaliplatin-resistant HCC cell lines were established. The interaction between DDR2 and STAT3 was investigated, along with the mechanisms involved in DDR2/STAT3-mediated PD-L1 upregulation and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) accumulation both in vitro and in vivo. RESULTS: DDR2 was found to induce the phosphorylation of STAT3, leading to its nuclear translocation. Conversely, the activation of STAT3 enhanced DDR2 expression. A positive feedback loop involving DDR2/STAT3 was identified in oxaliplatin-resistant HCC, which was associated with PD-L1 upregulation and PMN-MDSCs accumulation. Knockdown of DDR2 and STAT3 sensitized oxaliplatin-resistant HCC cells to oxaliplatin and resulted in decreased PMN-MDSCs and increased CD8+ T cells in the tumor microenvironment. Enzyme-linked immunosorbent array and MDSC transwell migration assays indicated that oxaliplatin-resistant HCC cells recruited PMN-MDSCs through CCL20. Dual luciferase reporter assays demonstrated that STAT3 can directly enhance the transcription of PD-L1 and CCL20. Furthermore, treatment with a PD-L1 antibody in combination with CCL20 blockade had significant antitumor effects on oxaliplatin-resistant HCC. CONCLUSIONS: Our findings revealed a positive feedback mechanism involving DDR2 and STAT3 that mediates the immunosuppressive microenvironment and promotes oxaliplatin resistance and immune evasion via PD-L1 upregulation and PMN-MDSC recruitment. Targeting the DDR2/STAT3 pathway may be a promising therapeutic strategy to overcome immune escape and chemoresistance in HCC.

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.

Clinical utility of digital radiography dacryocystography for preoperative assessment in nasolacrimal duct obstruction prior to endoscopic dacryocystorhinostomy.

Purpose: To evaluate the clinical usefulness of digital radiography dacryocystography in patients with primary acquired nasolacrimal duct obstruction prior to endoscopic dacryocystorhinostomy. Methods: All dacryocystography images from 129 patients with primary acquired nasolacrimal duct obstruction were analyzed. Each group was assessed for postoperative epiphora severity using Munk's score via telephone follow-up three years post-surgery. Receiver operating characteristic (ROC) curve was plotted to obtain a suitable cutoff value of the transverse diameter of the lacrimal sac (LS), used to categorize LS size into small (≤4.350 mm) and large (>4.350 mm). Results: Analysis of the transverse diameter of the LS among 129 patients showed a negative correlation between it and Munk's score (r = -0.282, p = 0.001). There was a statistical difference between the surgical outcomes and the sizes of the LS (p = 0.041). The ROC curve analysis showed that the transverse diameter of the LS at 4.350 mm was the ideal cutoff value for the outcome of endoscopic dacryocystorhinostomy, with a sensitivity of 42.2 %, and specificity of 92.3 %. After adjusting for the age and sex, the small LS was associated with an increased risk of postoperative failed outcome (adjusted odds ratio [95 % CI]: 8.628 [1.074, 69.335]). Conclusion: The small LS was independently associated with the failed surgical outcome. Furthermore, the preoperative measurement of the LS transverse diameter serves as one of the reliable predictors for postoperative epiphora severity.

Radiotherapy enhances efficacy of PD-1 inhibitors in advanced hepatocellular carcinoma: A propensity-matched real-world study.

BACKGROUND: To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma (HCC), combination with radiotherapy (RT) has emerged as a promising strategy. In preclinical studies, irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy. Hence, we investigated whether RT enhances the efficacy of anti-programmed death receptor-1 (PD-1) inhibitors in advanced HCC in real-world practice. METHODS: Between August 2018 and June 2021, 172 patients with advanced primary HCC were enrolled in the tertiary center (Zhongshan Hospital of Fudan University); 95 were treated with a combination of RT and the inhibitor of PD-1 (RT-PD1 cohort), and 77 were administered anti-PD-1 therapy (PD1 cohort). The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT. Propensity score matching for bias reduction was used to evaluate the clinical outcomes. RESULTS: Among 71 propensity-matched pairs, median progression-free survival was 5.7 months in the RT-PD1 cohort vs. 2.9 months in the PD1 cohort ( P  <0.001). Median overall survival was 20.9 months in the RT-PD1 cohort vs. 11.2 months in the PD1 cohort ( P  = 0.018). Compared with patients in the PD1 cohort, patients in the RT-PD1 cohort had significantly higher objective response rates (40.8%, 29/71 vs. 19.7%, 14/71, P  = 0.006) and disease control rates (62.0%, 44/71 vs. 31.0%, 22/71, P  <0.001). The incidences of toxic effects were not significantly different between the two cohorts. CONCLUSIONS: RT plus anti-PD-1 therapy is well tolerated. RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.

Localized light chain amyloidosis involving the lacrimal sac: A case report.

Amyloidosis involving the lacrimal sac is extremely rare. In this study, we demonstrated a rare case of localized light chain amyloidosis in the lacrimal sac region. The lacrimal sac lesion presented as infiltrative with bony erosion. Given the slow growth of the lesion and the absence of a blood flow signal inside, we concluded that the lesion was less likely to be malignant. Complete removal of the lacrimal sac lesion combined with simultaneous lacrimal passage reconstruction was performed. The diagnosis of light chain amyloidosis was confirmed by histology. The surgical results were favorable, and no recurrence was observed over one-year follow-up. Our case report enriches the understanding of amyloid deposition in the ocular adnexa.

Development and Validation of a Nomogram for Patients Undergoing Transarterial Chemoembolization for Recurrent Hepatocellular Carcinoma After Hepatectomy.

Purpose: This study aims to establish a prognostic nomogram for patients who underwent transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after hepatectomy. Patients and Methods: Patients who underwent TACE for recurrent early- and middle-stage HCC after hepatectomy between 2009.01 and 2015.12 were included. Enrolled patients were randomly divided into training (n=345) and validation (n=173) cohorts according to a computer-generated randomized number. Independent factors for overall survival (OS) were determined and included in the nomogram based on the univariate and multivariate analyses of the training group. The nomogram was validated and compared to other prognostic models. Discriminative ability and predictive accuracy were determined using the Harrell C index (C-index), area under the receiver operating characteristic curve (AUROC), and calibration curve. Results: The final nomogram was established based on four parameters including resection-to-TACE time interval, recurrent tumor diameter, recurrent tumor number, and AFP level. The C-indexes of the nomogram for predicting OS were 0.67 (95% CI 0.63-0.70) and 0.71 (95% CI 0.68-0.74) in the training and validation cohort respectively. The AUROCs for predicting the 1-year, 2-year and 3-year OS based on the nomogram were also superior to those of the other models. The calibration curve for 3-year survival showed a high congruence between the predicted and actual survival probabilities. According to the scores calculated by the nomogram, patients were stratified into three subgroups: high-risk (scoring ≥53 points), middle-risk (scoring ≥26 and <53 points), and low-risk (scoring <26 points) subgroups with a median OS of 10.1 (95% CI 0.63-0.70), 20.3 (95% CI 17.5-22.5) and 47.0 (95% CI 34.2-59.8) months, respectively. Conclusion: The proposed nomogram served as a new tool to predict individual survival in patients who underwent TACE for recurrent HCC after hepatectomy, with favorable performance and discrimination. For high-risk patients, treatment should be optimized beyond TACE alone based on the nomogram.

Real-world study of hepatic artery infusion chemotherapy combined with anti-PD-1 immunotherapy for hepatocellular carcinoma patients with portal vein tumor thrombus.

Background: Patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) present a poor prognosis. Current systemic therapies offer limited benefits. Hepatic artery infusion chemotherapy (HAIC) is a local regional treatment for advanced HCC, particularly in selected patients such as patients with PVTT or high intrahepatic tumor burden. Objectives: The purpose of this study is to retrospectively evaluate the efficacy and safety of HAIC combined with anti-PD-1 immunotherapy for HCC patients with PVTT, and explore factors related to survival prognosis, providing clues for treatment decisions for HCC patients. Design: This is a single-center retrospective study conducted over 2 years on consecutive PVTT patients receiving HAIC combined anti-PD-1 antibodies. Methods: The primary endpoint was overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors affecting OS. Treatment-associated adverse events were evaluated as well. Results: A total of 119 patients were analyzed. The median OS and PFS were 14.9 months and 6.9 months. A total of 31.1% of grade 3-4 adverse events were reported, with elevated transaminase and total bilirubin being the most common. The independent variables correlated with survival include treatment-related alpha-fetoprotein (AFP) response, the presence of extrahepatic organ metastasis, absolute value of platelet (PLT), neutrophil-to-lymphocyte ratio, and combined usage of tyrosine kinase inhibitors (TKIs). Conclusion: In HCC patients with PVTT, combination therapy with HAIC and anti-PD-1 antibodies might be a promising therapy. The efficacy and safety of this combination protocol on patients with HCC complicated by PVTT warrants further investigation prospectively, especially in combination with TKIs.

CT-Measured Angulation Between the Frontal Bone and Bony Nasolacrimal Duct: Variations in Obstructed and Healthy Lacrimal Ducts.

PURPOSE: The aim of this study was to analyze the characteristics of CT-measured intersection angle (FB-BNLD) between the frontal bone and bony nasolacrimal duct and to provide suggestions for treating primary acquired nasolacrimal duct obstruction (PANDO) patients in West China. METHODS: Three hundred and nine participants' CT were, respectively, evaluated with RadiAnt DICOM Viewer. We defined the FB-BNLD angle >0° as the anterior type and the FB-BNLD angle ≤0° as the posterior type. RESULTS: The mean FB-BNLD was -2.52° (95% CI, -3.16° to -1.88°) across all participants, of whom 37.2% were of the anterior type and 62.8% of the posterior type. Approximately 65.0% of the female patients had a posterior FB-BNLD type, and 54.2% of the male patients had an anterior FB-BNLD type (p = .002). Posterior FB-BNLD was the dominant type in the PANDO and control groups (p = .011), and the angle of FB-BNLD was statistically different in both groups (PANDO group, -2.54° to -0.71°; control group, -4.42° to -2.67°; p < .001). Among the male participants, the type of FB-BNLD differed between the two groups (p = .036), with differences in the angle of FB-BNLD (PANDO group, 0.59° to 5.13°; control group, -4.08° to 1.89°; p = .034). There was no difference in the type of FB-BNLD in female participants between the two groups (p = .051). CONCLUSION: The present study revealed individual differences in the type of FB-BNLD, with anterior-type majority in males and posterior-type dominance in females. Evaluating the FB-BNLD type on CT can provide a fast method for knowing the nasolacrimal duct condition during planning for lacrimal manipulation.

Development and Preliminary Validation of a Novel Convolutional Neural Network Model for Predicting Treatment Response in Patients with Unresectable Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy.

The goal of this study was to evaluate the performance of a convolutional neural network (CNN) with preoperative MRI and clinical factors in predicting the treatment response of unresectable hepatocellular carcinoma (HCC) patients receiving hepatic arterial infusion chemotherapy (HAIC). A total of 191 patients with unresectable HCC who underwent HAIC in our hospital between May 2019 and March 2022 were retrospectively recruited. We selected InceptionV4 from three representative CNN models, AlexNet, ResNet, and InceptionV4, according to the cross-entropy loss (CEL). We subsequently developed InceptionV4 to fuse the information from qualified pretreatment MRI data and patient clinical factors. Radiomic information was evaluated based on several constant sequences, including enhanced T1-weighted sequences (with arterial, portal, and delayed phases), T2 FSE sequences, and dual-echo sequences. The performance of InceptionV4 was cross-validated in the training cohort (n = 127) and internally validated in an independent cohort (n = 64), with comparisons against single important clinical factors and radiologists in terms of receiver operating characteristic (ROC) curves. Class activation mapping was used to visualize the InceptionV4 model. The InceptionV4 model achieved an AUC of 0.871 (95% confidence interval [CI] 0.761-0.981) in the cross-validation cohort and an AUC of 0.826 (95% CI 0.682-0.970) in the internal validation cohort; these two models performed better than did the other methods (AUC ranges 0.783-0.873 and 0.708-0.806 for cross- and internal validations, respectively; P < 0.01). The present InceptionV4 model, which integrates radiomic information and clinical factors, helps predict the treatment response of unresectable HCC patients receiving HAIC treatment.

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.

Corneal Morphological and Biomechanical Changes in Thyroid-Associated Ophthalmopathy.

PURPOSE: This study aimed to evaluate corneal morphological and biomechanical changes in patients with thyroid-associated ophthalmopathy (TAO) and their correlations with activity and severity. METHODS: Patients diagnosed with TAO were recruited and divided into groups by activity and severity. All subjects underwent a complete ophthalmic examination, including magnetic resonance imaging. Corneal topography was measured using a Pentacam device, and biomechanical parameters were obtained using a CorVis ST tonometer. Correlations among the corneal parameters, clinical activity score, and NOSPECS score were analyzed. Areas under the receiver operating characteristic curves were calculated to evaluate the diagnostic accuracy of corneal changes for active and severe TAO. RESULTS: Fifty-three eyes with TAO and 16 healthy eyes were enrolled in our study. The back elevation, CorVis biomechanical index, tomographic and biomechanical index, stiffness parameter at the first applanation, deviation from normality in back elevation, relational thickness, and overall deviation from normality were significantly increased in patients with TAO (all P <0.05), whereas the smallest corneal thickness, maximum Ambrósio relational thickness, and deformation amplitude (DA) ratio were significantly decreased (all P <0.05). The clinical activity score was strongly positively correlated with back elevation (γ = 0.515, P <0.001). The NOSPECS score was strongly positively correlated with relational thickness and tomographic and biomechanical index (γ = 0.429 and 0.515, P <0.001) and negatively correlated with maximum Ambrósio relational thickness (γ = -0.53, P <0.001). Moreover, maximum Ambrósio relational thickness and the Ambrósio relational thickness through the horizontal meridian showed desirable diagnostic capacity in distinguishing mild TAO from moderate-severe TAO (areas under the receiver operating characteristic curve, 0.799 and 0.769). CONCLUSIONS: Corneal morphological and biomechanical changes were found in patients with TAO, which might be related to the presence of inflammation. Measurements of corneal morphological and biomechanical parameters could serve as references in evaluating TAO.

A synergistic regulation works in matrix stiffness-driven invadopodia formation in HCC.

Growing evidence has suggested that increased matrix stiffness can significantly strengthen the malignant characteristics of hepatocellular carcinoma (HCC) cells. However, whether and how increased matrix stiffness regulates the formation of invadopodia in HCC cells remain largely unknown. In the study, we developed different experimental systems in vitro and in vivo to explore the effects of matrix stiffness on the formation of invadopodia and its relevant molecular mechanism. Our results demonstrated that increased matrix stiffness remarkably augmented the migration and invasion abilities of HCC cells, upregulated the expressions of invadopodia-associated genes and enhanced the number of invadopodia. Two regulatory pathways contribute to matrix stiffness-driven invadopodia formation together in HCC cells, including direct triggering invadopodia formation through activating integrin ß1 or Piezo1/ FAK/Src/Arg/cortactin pathway, and indirect stimulating invadopodia formation through improving EGF production to activate EGFR/Src/Arg/cortactin pathway. Src was identified as the common hub molecule of two synergistic regulatory pathways. Simultaneously, activation of integrin ß1/RhoA/ROCK1/MLC2 and Piezo1/Ca2+/MLCK/MLC2 pathways mediate matrix stiffness-reinforced cell migration. This study uncovers a new mechanism by which mechanosensory pathway and biochemical signal pathway synergistically regulate the formation of invadopodia in HCC cells.

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.