We aimed to evaluate the tolerance of preoperative chord mu (angle kappa) after cataract or clear lens exchange surgery and implantation of AcrySof IQ PanOptix and PanOptix Toric in a Chinese cohort. This prospective observational study consecutively enrolled patients undergoing PanOptix/PanOptix Toric implantation at Peking Union Medical College Hospital. Eyes were analyzed by chord mu (< 0.3 mm vs. ≥ 0.3 mm), lens opacity (clear lens or cataract), and intraocular lens (PanOptix or PanOptix Toric). Visual acuity was assessed at 1 and 3 months. Patient-reported outcomes were assessed at 3 months using the IOLSAT and the QUVID. A total of 122 eyes from 62 patients were analyzed. Seventy-nine eyes received PanOptix Toric lenses, and 43 eyes received non-toric PanOptix lenses. The κ ≥ 0.3 mm group had less myopic spherical equivalent (P = 0.004) than the κ < 0.3 mm group. At 1 and 3 months, the uncorrected and corrected distance, intermediate, and near visual acuity outcomes were excellent and did not differ significantly between κ groups in the overall cohort (all P > 0.05). In the toric subgroup,1-m UNVA was better in eyes with κ < 0.3 mm (P < 0.001, adj. P = 0.024) than in those with κ ≥ 0.3 mm. Overall spectacle independence was 90

A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

IgG4-related disease (IgG4-RD) is an immune-mediated condition with diagnostic challenges in clinical practice. Sensitive biomarkers are needed for diagnosis, disease activity and disease progression assessment. This study aimed to identify and validate novel serum protein biomarkers of IgG4-RD to improve clinical management. Using Olink proteomics, we analyzed the expression of 92 serum immuno-oncology-related proteins in 11 treatment-naïve IgG4-RD patients and 11 healthy controls (HCs). Candidate biomarkers capable of distinguishing IgG4-RD patients from HC were subsequently validated by enzyme-linked immunosorbent assay in a large independent cohort (n = 220). Diagnostic performance was assessed via 5-fold cross-validation. Correlations between biomarkers and clinical characteristics were also investigated, as well as predictive value for disease relapse. Olink proteomic analysis identified 27 differentially expressed proteins between IgG4-RD and HCs. Through longitudinal follow-up, serum PD1, OX40, CCL19, and MMP12 were significantly upregulated in IgG4-RD patients and closely associated with disease progression, serum IgG4 levels and inflammatory indicators. A comprehensive diagnostic model incorporating the four biomarkers was developed and showed high discriminatory capacity. Elevated baseline PD1 level served as an independent risk factor to predict clinical relapse of IgG4-RD patients. This study identifies four novel serum biomarkers that effectively assist diagnosis, assess disease activity, and one capable for clinical relapse prediction. These findings provide a practical approach for large-scale clinical screening and monitoring of IgG4-RD patients. Furthermore, the identified proteins may offer new insights into disease pathogenesis and represent potential therapeutic targets for this challenging condition.

Background: The chronic inflammatory state of COPD can lead to an imbalance in immune cell subsets, specifically manifested as an increase in regulatory T cells (Tregs), which may promote tumor immune escape. However, few studies have reported the correlation between polymorphisms of Treg-related FOXP3, IL2, and TGFB1 genes and the risk of lung cancer in COPD patients. Methods: Six SNPs in FOXP3, IL2, and TGFB1 were genotyped in 582 patients with COPD combined with lung cancer (the study group) and 603 patients with simple COPD (the control group) using a MassARRAY platform. Results: By comparing the allele frequencies of the study group and the control group, three SNPs were found to be associated with the risk of lung cancer in patients with COPD, including FOXP3-rs3761547, IL2-rs2069762 and TGFB1-rs4803455 (p < 0.0001). Genotype frequencies analysis revealed that FOXP3-rs3761547-TC/CC, IL2-rs2069762-AC/CC and TGFB1-rs4803455-CA/AA genotypes were associated with increased risk of lung cancer in COPD patients (p < 0.0001). Moreover, genetic model analysis results showed that FOXP3-rs3761547 had the highest risk of causing lung cancer in COPD patients in the recessive model, at 2.68 times (p < 0.0001). IL2-rs2069762 and TGFB1-rs4803455 had the highest pathogenic risks in the dominant model, at 2.11 and 3.27 times respectively (p < 0.0001). Additionally, stratified analyses showed that the three SNPs were significantly associated with the risk of lung cancer in both smoking and non-smoking COPD patients (p < 0.0001), and the risk of lung squamous cell carcinoma and lung adenocarcinoma in COPD patients (p < 0.001). Conclusion: Our results suggest that Treg-related genes polymorphisms may serve as susceptibility markers for lung cancer in the COPD population.

Background: Management of pituitary neuroendocrine tumors (pitNETs) during pregnancy is challenging. Involvement of the multidisciplinary team (MDT) may benefit the collaborative decision-making. However, this aspect has not been well documented. We provided cases with pitNETs during pregnancy and summarized our experience on the MDT-guided management. Methods: We performed a retrospective study enrolling all pregnant patients with pitNETs treated at our institute between March 1995 and July 2024. Results: During the indexed period, 121 patients with pitNETs consulted our institute during pregnancy, with 111 of them being treated conservatively and 10 undergoing surgery due to progressive visual defect and other symptoms. The age of the included surgical cases was 33 years, and the gestational session at surgery ranged from 13 to 36 weeks (1 in the first trimester, 4 in the second, and 5 in the third). Of the resected tumors, six were nonfunctioning and the other four were functioning (1 lactotroph, 1 somatotroph, and 1 thyrotroph). All surgical cases received MDT-guided management by physicians from neurosurgery, endocrinology, ophthalmology, obstetrics, pediatrics, and anesthesiology, leading to gross total tumor resection, improved visual acuity, and successful delivery in all patients. Conclusion: MDT guided management is essential for pitNETs during pregnancy. Surgical tumor resection is necessary for patients whose symptoms deteriorate rapidly. Transsphenoidal operation under general anesthesia is safe for pregnant patients with pitNETs.

Background: For non-small-cell lung cancer (NSCLC) patients who progressed after first-line chemotherapy, immunotherapy targeting programmed cell death (ligand) 1 has shown promising activity. However, the activity is relatively limited in patients harboring epidermal growth factor receptor (EGFR) mutations. Objectives: This study aimed to evaluate the efficacy and safety of camrelizumab plus famitinib in previously treated patients with locally advanced and metastatic NSCLC. Design: A single-center, single-arm, phase II study. Methods: Previously treated patients with locally advanced and metastatic NSCLC were enrolled to receive camrelizumab (200 mg, administered intravenously every 3 weeks) and famitinib (20 mg, administered orally once daily). Patients harboring EGFR mutation genes had received at least one EGFR tyrosine kinase inhibitor and no more than two lines of chemotherapy regimen before the enrollment. The other patients had progressed on first-line chemotherapy with or without immunotherapy before the enrollment. The primary endpoint was the objective response rate (ORR) per RECIST v1.1 by the investigator. Results: Our study encompassed 23 NSCLC patients between October 2019 and October 2022. For all patients, the confirmed ORR was 30.4%, and the disease control rate was 95.7%. The median progression-free survival (PFS) was 6.9 months (95% CI: 4.9 months–not reached). The median overall survival (OS) was not reached. 1- and 2-year OS rates were 85.6% (95% CI: 71.8%–100.0%) and 56.8% (95% CI: 37.7%–85.7%). Especially, for the 6 patients with EGFR genetic aberrations, the confirmed ORR was 33.3%, the median PFS was 10.3 months (95% CI: 1.8–18.8 months), and the median OS was 20.3 months (95% CI: 0.8–39.8 months). The most common grade 3 and above treatment-related adverse events were platelet count decreased, white blood cell count decreased, and hypertension. No unexpected adverse events were reported. Conclusion: Camrelizumab plus famitinib demonstrated encouraging clinical activity with a manageable safety profile in previously treated patients with locally advanced and metastatic NSCLC. The results warranted further validation. Trial registration: Chinese Clinical Trial Registry identifier: ChiCTR1900026641.

Purpose:Glaucoma, characterized by progressive retinal ganglion cell (RGC) degeneration and optic nerve atrophy, remains a leading global cause of irreversible blindness, despite advancements in clinical management. While current therapies predominantly focus on lowering intraocular pressure (IOP), neuroprotective strategies to preserve visual function remain an unmet clinical need. Stem cells exhibit high proliferative capacity and multilineage differentiation potential, demonstrating notable efficacy in glaucoma treatment. Emerging preclinical evidence further highlights dual neuroprotective mechanisms (i.e., paracrine neurotrophic support and cellular replacement) of stem cell-based interventions. Accordingly, this systematic review and meta-analysis evaluated the therapeutic efficacy and safety of stem cell transplantation in experimental glaucoma models, with a focus on functional outcomes (IOP modulation), structural preservation (RGC survival, and nerve fiber layer integrity), and neuroprotective efficacy. Methods:A systematic literature retrieval from multiple online databases (e.g., PubMed, Web of Science, Embase, Cochrane Library, Scopus, CNKI, WFSD, VIP, and CBM) was conducted through 3 January 2025, to identify relevant animal experimental studies. After the assessment of the risk of bias in the listed articles, this study further computed effect sizes of stem cell transplantation on indices such as IOP, RGC count. Statistical analyses were completed using RevMan 5.3. Results:In the meta-analysis involving 19 studies, the stem cell transplantation group had significantly lower IOP (MD = -1.55,95% CI = -2.62 to -0.47) at weeks 3 and 4, higher RGC count at weeks 2, 3, and 4 (MD = 23.06,95%CI = 18.22-27.89), and greater nerve fiber layer thickness (MD = 10.69, 95%CI = 9.44-11.94) compared to the control group. Meanwhile, the stem cell transplantation group also had higher retinal BDNF expression at weeks 2 and 4 (MD = 0.75,95%CI = 0.67-0.83), GDNF expression at weeks 1, 2, 3, and 4, and IGF-1 expression (MD = 0.49,95%CI = 0.39-0.58). None of these studies reported any adverse systemic events. Conclusion:This meta-analysis provides preclinical evidence supporting stem cell transplantation as a multimodal therapeutic strategy for glaucoma, demonstrating significant efficacy in IOP modulation, neurostructural preservation, and neurotrophic factor expression. Given the severity of glaucoma-induced ocular structural damage, it underscores the significance of stem cell transplantation as a secure and promising therapeutic option with notable neuroprotective potential, despite existing translational challenges regarding optimal cell sources, delivery routes, and long-term safety profiles. Systematic Review Registration:www.inplasy.com, identifier 202520023.

PURPOSE:To evaluate the 5-year visual outcomes, refractive stability, IOL centration, patient satisfaction, and complications following trifocal intraocular lens (IOL) implantation in a Chinese cohort. DESIGN:Retrospective study. SUBJECTS:This study included 33 patients (66 eyes) with bilateral implantation of the AT LISA 839MP trifocal IOL. METHODS:Postoperative assessments at 5 years included uncorrected and corrected distance, intermediate and near visual acuity, refractive outcomes, contrast sensitivity (CS), defocus curves, reading speed, and patient-reported outcomes (VFQ-25 questionnaire). IOL tilt/decentration and aberrometry were analyzed using anterior segment optical coherence tomography (AS-OCT) and iTrace visual function analyzer. MAIN OUTCOME MEASURES:Postoperative outcomes at 5 years: uncorrected and corrected visual acuity (distance, intermediate, near), refractive results, and IOL centration. RESULTS:At 5 years, mean UDVA, UIVA, and UNVA were 0.06 ± 0.16, 0.10 ± 0.14, and 0.09 ± 0.12 logMAR, respectively. 92.4% of eyes achieved a postoperative spherical equivalent within ±1.0D. Over 87.9% of patients achieved spectacle independence. Mean IOL tilt was 4.19 ± 1.46° and mean IOL decentration was 0.21 ± 0.11 mm. Contrast sensitivity declined under glare, particularly at mesopic conditions. Moderate-to-severe halos were reported by 21.2% of patients, correlating significantly with IOL tilt. Posterior capsule opacification necessitated Nd:YAG capsulotomy in 63.6% of eyes (mean intervention time: 22.0 ± 9.9 months), with no complications post-procedure. Patient satisfaction remained high (VFQ-25 score: 93.9 ± 13.7), despite persistent dysphotopsias. CONCLUSION:Trifocal IOLs provided long-term efficacy in visual acuity, refractive stability, and exceptional patient satisfaction among Chinese populations. However, PCO remains a prevalent late complication, requiring timely Nd:YAG intervention. IOL tilt significantly influences halo severity.

BACKGROUND:Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thinning are used as markers of subclinical retinal degeneration to evaluate the effect of disease-modifying therapies (DMTs) on disease progression in clinical trials of multiple sclerosis (MS). This study aimed to assess the available evidence regarding the effects of DMTs on retinal thinning in people with MS. METHODS:Databases were searched for studies reporting longitudinal optical coherence tomography (OCT)-derived annualized RNFL and GCIPL thinning in patients receiving DMTs treatment. The standardized mean differences (Hedges g) of RNFL and GCIPL thickness between the baseline and follow-up were used as the primary effect size measure. DMTs were divided into moderate (M-DMTs) and high (H-DMTs) efficacy therapies. RESULTS:Twenty-one studies including 2158 patients and 3685 eyes were included. Overall, significant annualized RNFL (g = -0.6715, p = 0.0077) and GCIPL (g = -0.31, p < 0.0001) thinning was observed at follow-up compared with baseline. Annualized RNFL thinning was only significant in the M-DMTs group (g = -0.6992, p = 0.0243). Annualized GCIPL thinning was significant in both M-DMTs (g = -0.38, p = 0.0006) and H-DMTs group (g = -0.19, p < 0.0001) but was significantly greater in the M-DMTs group compared with the H-DMTs group (g = -0.20, p = 0.0017). There was no difference in annualized GCIPL or RNFL thinning between RRMS and PMS, or between RRMS with and without ON history. CONCLUSIONS:High-DMTs are more effective in reducing longitudinal thinning of RNFL and GCIPL compared with M-DMTs. GCIPL thinning could serve as a sensitive predictor for the surveillance of optic nerve degeneration and the assessment of DMT efficacy for both RRMS and PMS.

Purpose To investigate the difference in choroidal structure between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients with or without optic neuritis (ON) attacks using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods This prospective case-control study included 30 eyes of MS, 32 eyes of NMOSD, and the same number of eyes from healthy controls. All participants underwent EDI-OCT examination. The choroidal thickness (CT) was evaluated at the subfoveal and eight sites around the subfoveal. Total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) were calculated by binarizing EDI-OCT images. Results There were 6 and 12 eyes with histories of ON in MS and NMOSD patients, respectively. Compared with MS patients, NMOSD patients had significantly thinner CTs at most sites and smaller TCA and LA regardless of ON attacks (p < 0.05). There was no significant difference in the CVI between MS and NMOSD patients with ON (p = 0.723) or without ON (p = 0.383). Among patients with ON attacks, compared with healthy controls, MS patients showed a trend toward larger choroidal parameters, whereas NMOSD patients exhibited a trend toward smaller values, although these differences were not statistically significant (all p > 0.05). Conclusions NMOSD patients exhibited a trend toward reduced ocular vascular perfusion compared to MS patients, irrespective of ON attack history. However, the lack of statistical significance compared with healthy controls suggests that these differences may be largely attributable to baseline imbalances, such as age. Further studies are warranted to verify the trend of the difference.

Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by demyelination, with failed remyelination leading to progressive axon loss in chronic stages. Oligodendrocyte precursor cells (OPCs) are critical for remyelination. Recent studies suggest that both hypoxia and ferroptosis play crucial roles in the dysfunctional differentiation of OPCs. This research seeks to identify key genes linked to hypoxia and ferroptosis and immune infiltration characteristics in OPCs derived from induced pluripotent stem cells (iPSCs) of MS patients and to construct a diagnostic model centered on these pivotal genes. We analyzed gene expression data from the GSE196575 and GSE147315 datasets and compared MS patients with healthy individuals. Using weighted gene coexpression network analysis (WGCNA), we pinpointed primary module genes and essential genes associated with hypoxia, ferroptosis, and MS. The ferroptosis Z score and the hypoxia Z score calculated via gene set variation analysis (GSVA) were greater in the iPSC-derived OPCs of MS patients than those of the control group. The implicated genes are predominantly linked to the PI3K/Akt/mTOR pathway, as identified through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network of crucial genes revealed 10 central hub genes (COL4A1, COL4A2, ITGB5, ITGB1, ITGB8, ITGAV, VIM, FLNA, VCL, and SPARC). The robust expression of ITGB1, ITGB8, and VIM was validated in the GSE151306 dataset, supporting their role as key hub genes. Additionally, an interaction network between transcription factors (TFs) and hub genes was established via Transcriptional Regulatory Relationships Unraveled by Sentence-based Text (TRRUST), which identified five key TFs. The results of this study could help elucidatenovel biomarkers or therapeutic targets for MS.

To evaluate the predictive value of the preoperative orientation and offset of angle alpha(chord alpha) and angle kappa(chord mu) for visual outcomes in patients who underwent trifocal intraocular lens (IOL) implantation. Patient records of eyes that underwent AT LISA tri 839MP implantation were retrospectively collected and grouped according to the preoperative offset and orientations of chord alpha and chord mu. The two-dimensional location of each angle was described by the interaction of the orientation and offset. Multiple regression models and likelihood ratio tests were established to determine their predictive value for postoperative visual outcomes, National Eye Institute Visual Function Questionnaire (NEI-VFQ) and Quality of Vision Questionnaire (QoV) scores. One hundred and two patients (184 eyes) were included. The orientation of chord alpha had a significant overall prediction to postoperative visual outcomes (p = 0.014). A superior chord alpha was an independent predictor of better postoperative uncorrected distance visual acuity (UDVA, p < 0.001) and a larger modulation transfer function (MTF) curve average height (p = 0.041). However, the offsets of chords alpha and chord mu and the orientation of chord mu did not significantly predict UDVA, uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), MTF, total ocular aberration (TOA), or high-order aberration (HOA).Better patient reported general vision was correlated with a nasal chord alpha (p = 0.012), whereas better near vision was correlated with a smaller kappa offset (p = 0.022) and nasal chord alpha (p = 0.019). The absence of postoperative halos was independently associated with the location of nasal chord alpha(p = 0.039), while starbursts were independently correlated with a larger chord mu offset (p = 0.007). A superior chord alpha was an independent predictor of better postoperative visual outcomes after trifocal IOL implantation. The predictive value of either the orientation or offset of chord mu for the VA, TOA and HOA was insignificant. Not applicable. What is known What this paper adds

OBJECTIVE:The aim of this study was to explore the optimal method of induction of labor in women with gestational diabetes mellitus and its impact on delivery outcomes. METHODS:This retrospective cohort study was conducted among nulliparous women with gestational diabetes mellitus delivering at the First Affiliated Hospital of Fujian Medical University and the First People's Hospital of Yunnan Province from 2018 to 2023. Data were extracted from electronic medical records. RESULTS:A total of 600 patients who delivered met the inclusion criteria: the double-balloon group (Group B, n=198), the misoprostol vaginal insert group (Group M, n=200), and the Misoprostol combined with artificial membrane stripping group (Group MA, n=202). Group MA showed higher induction of labor success rates (93.5%) compared to Group M (86.0%) and Group B (81.5%, p=0.002). The time to labor onset was shortest in Group MA (32.5±6.5 h), followed by Group M (35.8±2.5 h) and Group B (45.8±4.5 h, p<0.001). Vaginal delivery time was also significantly shorter in Group MA (47.4±4.3 h) compared to Group M (49.1±7.4 h) and Group B (57.1±5.7 h, p<0.001). Chorioamnionitis rates were lower in Group MA (2.5%) and Group M (3.0%) compared to Group B (8.5%, p=0.007). No significant differences were observed between groups for cesarean rates, fetal distress, abnormal labor, or neonatal outcomes (p>0.05). CONCLUSION:The combination of misoprostol vaginal insert and artificial membrane stripping effectively enhances cervical ripening and improves vaginal delivery success in gestational diabetes mellitus patients, providing a promising strategy for labor induction.

PURPOSE:To assess the retinal structural and microvascular change in aquaporin-4 antibody (AQP4) positive neuromyelitis optica spectrum disorder (NMOSD) patients and the correlation with clinical features.METHODS:A cross-sectional study was performed with optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to measure retinal structure and microvascular parameters in AQP4 positive NMOSD patients.RESULTS:Sixty-two NMOSD patients (44 eyes with ON, NMOSD+ON; 77 eyes without ON, NMOSD-ON) and 62 healthy controls (HC, 124 eyes) were included. BCVA was worse in NMOSD patients compared to HC (p<0.001). Peripapillary retinal nerve fiber layer (pRNFL, p<0.001) and ganglion cell complex (GCC, p<0.001) was thinner in NMOSD+ON eyes compared to NMOSD-ON eyes and HC. Compared to HC, pRNFL (p = 0.002) and GCC (p = 0.001) was thinner in NMOSD-ON eyes. The vessel density (VD) in superficial capillary plexus (SCP, NMOSD+ON vs HC p<0.001, NMOSD-ON vs HC p = 0.002) and radial peripapillary capillary (RPC, NMOSD+ON vs HC p<0.001, NMOSD-ON vs HC p = 0.001) were also lower in NMOSD patients than HC independent of the history of ON. ON frequency and BCVA were correlated with the thickness of pRNFL and GCC, and VD in SCP and RPC (all p<0.001). EDSS was correlated with thickness of GCC (p = 0.008), and VD in SCP (p = 0.013), DCP (p<0.001) and RPC (p = 0.009).CONCLUSIONS:Subclinical degradation of retinal structure and microvasculature was found in NMOSD patients before the occurrence of ON, and was correlated with clinical disability. Retinal parameter might be a tool to estimate the disease progression and investigate the pathogenesis of NMOSD.

Purpose: To examine the effects of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) on choroidal structures with different blood glucose levels in patients with diabetes mellitus (DM) with acromegaly without diabetic retinopathy. Methods: Eighty-eight eyes of 44 patients with acromegaly were divided into a nondiabetic group (23 patients, 46 eyes) and a diabetic group (21 patients, 42 eyes). Forty-four age- and sex-matched healthy controls and 21 patients with type 2 DM without diabetic retinopathy were also included. Linear regression models with a simple slope analysis were used to identify the correlation and interaction between endocrine parameters and choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascular index (CVI). Results: Our study revealed significant increases in the ChT, LA, SA, and TCA in patients with acromegaly compared with healthy controls, with no difference in the CVI. Comparatively, patients with DM with acromegaly had greater ChT than matched patients with type 2 DM, with no significant differences in other choroidal parameters. The enhancement of SA, LA and TCA caused by an acromegalic status disappeared in patients with diabetic status, whereas ChT and CVI were not affected by the interaction. In the diabetic acromegaly, higher IGF-1 (P = 0.006) and GH levels (P = 0.049), longer DM duration (P = 0.007), lower blood glucose (P = 0.001), and the interaction between GH and blood glucose were associated independently with thicker ChT. Higher GH levels (P = 0.016, 0.004 and 0.007), longer DM duration (P = 0.022, 0.013 and 0.013), lower blood glucose (P = 0.034, 0.011 and 0.01), and the interaction of IGF-1 and blood glucose were associated independently with larger SA, LA, and TCA. As blood glucose levels increased, the positive correlation between serum GH level and ChT diminished, and became insignificant when blood glucose was more than 7.35 mM/L. The associations between serum IGF-1 levels and LA, SA, and TCA became increasingly negative, with LA, becoming signif- icantly and negatively associated to the GH levels only when blood glucose levels were more than 8.59 mM/L. Conclusions: Acromegaly-related choroidal enhancements diminish in the presence of DM. In diabetic acromegaly, blood glucose levels are linked negatively with changes in choroidal metrics and their association with GH and IGF-1. Translational Relevance: We revealed the potential beneficial impacts of IGF-1 and GH on structural measures of the choroid in patients with DM at relatively well-controlled blood glucose level, which could provide a potential treatment target for diabetic retinopathy.

Abstract Background Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. Methods The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. Results 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p < 0.05). High-order aberrations decreased significantly (p < 0.05). Despite the high incidence of posterior capsule opacification (83.2%), managed with early Nd: YAG capsulotomy, no other severe complications were reported. Patient-reported outcomes indicated high satisfaction, with an average VF-14 score of 94.3 ± 10.2 and 93.5% achieving complete spectacle independence. Halo (66.2%) was the most commonly reported optical phenomena, followed by glare (18.2%), and starburst (7.8%) after surgery. Conclusions Bilateral RLE with trifocal IOLs in presbyopic patients without cataracts significantly improves visual acuity and reduces ocular aberrations in presbyopic patients. The procedure offers high patient satisfaction and spectacle independence, though it requires careful patient selection and management of expectations regarding potential photic phenomena.

This study aimed to screen differentially expressed genes (DEGs) involved in the influence of antiangiogenic therapy on myeloid-derived suppressor cell (MDSC) infiltration and investigate their mechanisms of action. Data on DEGs after the action of antiangiogenic drugs in a pan-cancer context were obtained from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the clusterProfiler package in R software. Single-sample gene set enrichment analysis was performed using the gene set variation analysis package to evaluate the levels of immune cells and the activity of immune-related pathways. The relationships of DEGs with the infiltration levels of MDSCs and specific immune cell subpopulations were investigated via gene module analysis. The top 10 key genes were subsequently obtained from PPI network analysis using the cytoHubba plugin of the Cytoscape platform. When the DEGs of the four datasets were intersected, a DEG in the intersection of three datasets and 12 DEGs in the intersection of two datasets were upregulated, and 28 DEGs in the intersection of two datasets were downregulated. GO and KEGG pathway enrichment analyses revealed that the DEGs were associated with multiple important signaling pathways closely related to tumor onset and development, including cell differentiation, cell proliferation, the cell cycle, and immune responses. Most downregulated genes in lung adenocarcinoma (LUAD) were positively correlated with MDSC expression. Only MGP was negatively correlated; the correlation between CACNG6 and MDSC expression was statistically insignificant. In lung squamous cell carcinoma (LUSC), the relationships of PMEPA1, PCDH7, NEURL1B, and CACNG6 with MDSC expression were statistically insignificant; MGP was negatively correlated with MDSC expression. The top 10 key genes with the highest degree scores obtained using the cytoHubba plugin of Cytoscape were AURKB, RRM2, BUB1, NUSAP1, PRC1, TOP2A, NCAPH, CENPA, KIF2C, and CCNA2. Most of these genes were upregulated in LUAD and associated with immune cell infiltration and prognosis in tumors. An analysis of the relationships between DEGs and infiltration by other specific immune cells revealed the presence of consistent patterns in the downregulated genes, which exhibited positive correlations with the levels of Th2 cells, γδ T cells, and CD56dim NK cells, and negative correlations with other infiltrating immune cells. Antiangiogenic therapy may regulate MDSC infiltration through multiple important signaling pathways closely associated with tumor onset and development, such as cell differentiation, cell proliferation, the cell cycle, and immune responses. Antiangiogenic drugs may exert effects by affecting various types of infiltrating cells associated with immune suppression.

Objective: To investigate the clinical features, molecular subtypes, and factors influencing metastasis in patients with breast cancer chest wall metastasis. Methods: We collected the clinical data of patients who developed isolated chest wall metastasis following radical surgery for breast cancer. The molecular subtypes of the primary lesions and secondary biopsy lesions in patients with chest wall metastasis were analyzed and summarized. The disease-free survival (DFS) after breast cancer surgery and its influencing factors were also documented. Results: Of the 99 cases of isolated chest wall recurrence included in our study, DFS varied from 1 to 264 months, with a median DFS of 36 months. The 3-year disease-free survival rate was 44.6%, while the 5-year rate was 24.2%. Molecular subtype changes occurred in a total of 28 cases before and after metastasis, accounting for 34% of the cases. COX multivariate analysis revealed that pathological type, surgical staging, postoperative expression status of ER (estrogen receptor), PR (progesterone receptor), Ki-67, HER-2 (human epidermal growth factor receptor-2), and the receipt of adjuvant chemotherapy after surgery were independent factors affecting chest wall recurrence and metastasis. Conclusion: Local recurrence after breast cancer surgery increases the risk of distant metastasis. Identifying high-risk factors for recurrence enables the tailoring of individualized comprehensive treatment plans based on the patient's condition, thus reducing the risk of local recurrence and improving survival outcomes.

Abstract Background IOL fixation without capsular support presents challenges for surgeons. Although innovative techniques were developed to address subluxated IOLs, adjustable IOL fixation methods are seldom reported. We introduce a novel two-way adjustable double-knots intrascleral fixation combined with single sclerotomy looping technique for fixing intraocular lenses (IOL) or IOL-capsular bags. Methods A bent 30-gauge needle threaded with 8 − 0 polypropylene was introduced into the eye. A gripping forceps assisted the haptic looping. Two overhand knots were made with 8 − 0 polypropylene thread. The knots were incarcerated into a scleral tunnel made by a 30-gauge needle, with two ends of the thread left at each side of the tunnel. The IOL was adjusted to the premium position with adequate tension by pulling either end of the threads. The study included 19 eyes with aphakia, subluxated IOL-capsular bags, or subluxated crystalline lenses. The mean followed up period was 18.9 ± 7.1 months with evaluations of uncorrected visual acuity (UCVA), intraocular pressure, slit-lamp examination, and swept-source optical coherence tomography of the anterior segment. Results UCVA increased from 1.28 ± 0.74 at baseline to 0.44 ± 0.51 (logMAR) at final visit (P < 0.001). All IOLs were fixed well-centered. The mean IOL tilt was 3.5°±1.1°. Postoperative complications included transient IOP elevation (15.8%), hypotony (10.5%), and cystoid edema (5.3%) which resolved within 4 weeks. Conclusions We presented a novel adjustable technique for IOL fixation, which stabilize IOLs by using an intrascleral double-knots structure. This technique minimized surgical manipulations by using a single sclerotomy looping technique without large conjunctival dissection and scleral flap creation. The technique offers a reliable and optimal IOL positioning and improved visual outcomes in patients undergoing scleral fixed IOL implantation.

Objective Oncogenic alternation in RET is one of the important targets of non-small cell lung cancer (NSCLC). Pralsetinib has shown great efficacy in RET fusion-positive NSCLC, but a series of adverse reactions will inevitably occur in the meantime. We aimed to explore the clinical characteristics of patients with pneumonia and recognition it in early stage, so patients could longer benefit from pralsetinib. Methods This is a multicenter, retrospective study. RET fusion-positive advanced NSCLC patients who developed pneumonia during pralsetinib treatment from January 2020 to December 2022 were included. Clinical data, time to onset of pneumonia, methods of pneumonia diagnosis, treatment with pneumonia, prognosis of pneumonia, and the effect of pneumonia on the efficacy of pralsetinib. Results A total of 8 patients with pneumonia were included in the study, most of which were non-smoking female patients and the main fusion gene was KIF5B (87.5%), which was consistent with the general characteristics of RET fusion population. The median occurrence time of pralsetinib-associated pneumonia was 2.15 (range 1.1–6.63) months. All patients were infected by opportunistic pathogens, and the most common pathogen was human herpesviruses and pneumospora yerbii. Fever was always the first symptom, and timely anti-infective treatment including antibiotics, antiviral drugs, and antifungal drugs was effective. Until February 28, 2023, the median follow-up time was 18.7 months, the mean PFS of patients was 17.4 months, and the median PFS was not reached. Fortunately, patients who restarted pralsetinib after infection control continued to benefit. Conclusions Opportunistic infection may be a unique adverse effect of pralsetinib. During the treatment of pralsetinib, we should be vigilant about the occurrence of pneumonia and achieve early recognition and timely treatment.