Supplementary Material for: Iris chafing syndrome secondary to iridociliary adhesions in a patient with a single-piece acrylic intraocular lens

Introduction: We present a unique case of iris chafing syndrome in a patient with a complex ophthalmologic history after the successful placement of a single-piece in-the-bag intraocular lens (IOL) in an eye with healthy zonular support. Case presentation: A patient with a previous history of multiple retinal surgeries presented with pain and elevated intraocular pressure (IOP) secondary to retained viscoelastic in the anterior chamber. Following removal of the viscoelastic material in clinic, the patient underwent a combined cataract and glaucoma surgery. Subsequently, the patient developed signs and symptoms of iris chafing syndrome. Anterior segment imaging revealed the cause to be iridociliary adhesion causing an elimination of the sulcus space. Iris chafing syndrome was suspected when the patient presented post-operatively with changes in vision and anterior chamber inflammation. New iris transillumination defects present at the edge of the optic and haptic of the 1-piece lens helped confirm the diagnosis of UGH. Upon further investigation with gonioscopy, ultrasound biomicroscopy and anterior segment optical coherence tomography, it was determined that the patient had iridociliary adhesions. These adhesions eliminated the sulcus space which resulted in iris chafing. The patient opted for conservative medical management. Best corrected distance visual acuity remained stable at 20/100 and IOP remained well-controlled. Conclusion: A complex ocular history of multiple retinal surgeries and retained viscoelastic in the anterior chamber resulted in adhesions of the ciliary processes to the iris, leading to UGH syndrome in a patient with an otherwise unremarkable placement of a single-piece in-the-bag IOL

Supplementary Material for: Prognostic Value of miR-375 for Survival Outcomes in Various Cancers: A Systematic Review and Meta-Analysis

<div>Background: miR-375 plays a role in tumor progression; however, its potential as a prognostic factor in cancer remains unclear. This meta-analysis assessed the value of miR-375 as a global prognostic biomarker in human cancer. Methods: A systematic literature review was performed to retrieve publications with relevant survival </div><div>data. Pooled hazard ratios (HRs) were calculated for low miR-375 expression. Publication bias was examined. Results: Data were extracted from 11 studies of 1,797 patients (low expression in 769 cases; high in 1,028 cases). The pooled HR for overall/cumulative survival (OS/CS) was 1.90 (95% confidence interval (CI) 1.57–2.29) and the pooled HR for disease-free, recurrence-free or progression-free survival (DFS/RFS/PFS) was 1.93 (95% CI 1.39–2.67), indicating low miR-375 expression was associated with significantly poorer outcomes compared to normal/high miR-375 expression. Subgroup analysis revealed miR-375 might be a good prognostic factor in cancer, regardless of population, sample type, and cancer type. The prognostic value of miR-375 in non-Chinese patients was particularly high (pooled HR > 2). Conclusion: Low miR-375 expression could represent a valuable prognostic marker in various cancers. Circulating miR-375 Levels may provide a useful non-invasive, practical prognostic </div><div>biomarker. However, the prognostic value of miR-375 in specific cancer types remains unclear; further studies are warranted.</div

Supplementary Material for: Body mass index and all-cause mortality in elderly patients with percutaneous coronary intervention: A meta-analysis

Background: The ‘obesity paradox’ in elderly patients suffering from percutaneous coronary intervention (PCI) remains a source of controversy. The present meta-analysis focused on exploring the real existence of ‘obesity paradox’ in these patients. Methods: As of November 2022, PubMed, Cochrane and Embase databases were comprehensively searched to identify articles reporting all-cause mortality according to diverse body mass index (BMI) categories after PCI among the old cases developing coronary artery disease (CAD). Summary estimates of risk ratios (RRs) were assigned four BMI groups, including underweight, normal weight, overweight, and obesity groups. Results: There were altogether nine articles involving 25,798 cases selected for further analysis. Relative to normal weight group, overweight and obesity groups had decreased all-cause mortality (RR 0.86, 95%CI 0.77-0.95 for overweight group; RR 0.57,95%CI 0.40-0.80 for obesity group), while underweight group had elevated all-cause mortality (RR 1.52, 95%CI 1.01-2.29). Conclusions: Our study revealed an ‘obesity paradox’ relation of BMI with all-cause mortality in elderly cases receiving PCI. In comparison with normal weight group, overweight and obesity groups had decreased all-cause mortality, while underweight group had increased all-cause mortality

Supplementary Material for: Ureteroscopic Lithotripsy versus Laparoscopic Ureterolithotomy or Percutaneous Nephrolithotomy in the Management of Large Proximal Ureteral Stones: A Systematic Review and Meta-Analysis

<p><b><i>Objectives:</i></b> To provide a systematic review and meta-analysis of studies comparing ureterolithotripsy (URS) with percutaneous nephrolithotripsy (PCNL) or laparoscopic ureterolithotomy (LU) techniques for the management of large proximal ureteral stones (diameter greater than 10 mm). <b><i>Methods:</i></b> A literature search was performed using PubMed, EMBASE, EBSCO, Web of Science, and Cochrane Library to identify suitable studies until November 2016. We used weighted mean difference to measure operative time and hospital stay, OR to measure stone free rate (SFR), and complication rate. Subgroup analyses were assessed for heterogeneity. <b><i>Results:</i></b> Fourteen publications strictly met our eligibility criteria of which 7 were randomized control studies (RCTs) and 7 non-RCTs. Meta-analysis of extractable data showed that LU and PCNL had higher SFR than URS. URS led to a similar hospital stay like that of LU. However, it had a shorter operative time and lower complication rate than LU. When we compared URS with PCNL, we found a shorter hospital stay in the URS group. However, there was no significant difference in terms of the operative time and complication rate between URS and PCNL. <b><i>Conclusion:</i></b> URS should be considered standard therapy for treating large proximal ureteral stones.</p

Supplementary Material for: Development of a Genetic and Clinical Data-Based (GC) Risk Score for Predicting Survival of Hepatocellular Carcinoma Patients After Tumor Resection

<b><i>Background/Aims:</i></b> Carnitine palmitoyltransferase 1A (CPT1A) is a rate-limiting enzyme in the transport of long-chain fatty acids for β-oxidation. Increasing evidence has indicated that CPT1A plays an important role in carcinogenesis. However, the expression and prognostic value of CPT1A in hepatocellular carcinoma (HCC) have not been extensively studied. <b><i>Methods:</i></b> Here, we collected 66 post-operative liver cancer tissue samples. Gene profile expression was tested by RT-PCR. Receiver operating characteristic (ROC) analysis was performed and multivariate analysis with Cox’s Proportional Hazard Model was used for confirming the selected markers’ predictive efficiency for HCC patients’ survival. A simple risk scoring system was created based on Cox’s regression modeling and bootstrap internal validation. <b><i>Results:</i></b> Cox multivariate regression analysis demonstrated that CPT1A, tumor size, intrahepatic metastasis, TNM stage and histological grade were independent risk factors for the prognosis of HCC patients after surgery. Our genetic and clinical data-based (GC) risk scoring system revealed that HCC patients whose total score≥3 are more likely to relapse and die than patients whose total score < 3. Finally, the good discriminatory power of our risk scoring model was validated by bootstrap internal validation. <b><i>Conclusions:</i></b> The genetic and clinical data-based risk scoring model can be a promising predictive tool for liver cancer patients’ prognosis after operation

Supplementary Material for: Activin B Promotes Initiation and Development of Hair Follicles in Mice

Activin B has been reported to promote the regeneration of hair follicles during wound healing. However, its role in the development and life cycle of hair follicles has not been elucidated.<b> </b>In our study, the effect of activin B on mouse hair follicles of cultured and neonatal mouse skin was investigated. In these models, PBS or activin B (5, 10 or 50 ng/ml) was applied, and hair follicle development was monitored. Hair follicle initiation and development was examined using hematoxylin and eosin staining, alkaline phosphatase activity staining, Oil Red O+ staining, and the detection of TdT-mediated dUTP-biotin nick end-labeling cell apoptosis. Activin B was found to efficiently induce the initiation of hair follicles in the skin of both cultured and neonatal mice and to promote the development of hair follicles in neonatal mouse skin. Moreover, activin-B-treated hair follicles were observed to enter the anagen stage from the telogen stage and to remain in the anagen stage. These results demonstrate that activin B promotes the initiation and development of hair follicles in mice

Supplementary Material for: CD4+ T Lymphocytes, Especially Th2 Cells, Contribute to the Progress of Renal Fibrosis

<b><i>Background:</i></b> Renal tubulointerstitial fibrosis is the final common stage of renal failure. CD4+ T lymphocyte recruitment and activation after injury could be the very important early event that mediates the onset of renal fibrogenesis. But the role of CD4+ T lymphocytes in renal fibrosis is controversial and its cellular mechanism needs to be further investigated. <b><i>Methods:</i></b> Biopsy specimens were from patients with minimal-change or IgA nephropathy. Mouse renal fibrosis was induced by unilateral ureteral obstruction (UUO). CD4+ T lymphocytes of wild BALB/c mice were depleted with anti-CD4 antibody. BALB/c Nu/Nu mice were reconstituted with polarized Th1 or Th2 cells by tail vein injection. <b><i>Results:</i></b> Our study demonstrated that massive CD4+ T lymphocytes infiltrated fibrotic kidneys of patients. The depletion of CD4+ T lymphocytes inhibited UUO-induced mouse renal fibrosis. In the process of UUO-induced renal fibrosis, the ratios of Th2/Th1 increased with time. Results have also shown that Th2-reconstituted mice developed renal fibrosis more easily than Th1-reconstituted mice, which manifested by interstitial expansion and collagen deposition, higher expression of α-SMA and vimentin and increased expression of fibronectin, TGF-β and collagen I. We also found that CD4+ T cells from Th1-reconstitued mice tended to secrete IL-4 and IL-13 Th2-like cytokines. <b><i>Conclusion:</i></b> In conclusion, our study demonstrated the importance of CD4+ T lymphocytes in renal fibrosis and gave the first direct evidence that Th2 cells play a pivotal role in UUO-induced renal fibrosis. Inhibition of CD4+ T lymphocyte differentiation to Th2 would be a potential therapeutic intervention to prevent renal fibrosis

Supplementary Material for: Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

<b><i>Background/Aims:</i></b> Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. <b><i>Methods:</i></b> Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed <i>in vitro</i> by flow cytometry analysis and western blotting. The concentration and function of LY in rat-tail disc-degeneration models were also assessed by HPLC (High Performance Liquid Chromatography) quantification and histological analysis. <b><i>Results:</i></b> In CEP cells, Interleukin (IL)-1β upregulated the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is critical for the degradation of cartilage extracellular matrix. Interestingly, LY suppressed the expression of these enzymes via the inhibition of nuclear factor-κB (NFκB) signalling and thus prevented IL-1β-induced endplate cell degeneration <i>in vitro</i>. More importantly, LY also reduced the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on matrix-degrading protease expression, LY treatment also reduced positive regulators of proinflammatory cytokines, such as MIF, which can be secreted by CEP cells and subsequently target NP cells. <b><i>Conclusion:</i></b> LY could serve as a potential drug for treating IVD disease

Supplementary Material for: Pilot Study Using Proteomics to Identify Predictive Biomarkers of Necrotizing Enterocolitis from Buccal Swabs in Very Low Birth Weight Infants

<b><i>Background:</i></b> Necrotizing enterocolitis (NEC) is a major cause of death and morbidity in very low birth weight infants. <b><i>Objective:</i></b> To identify biomarker(s) that would predict NEC using buccal swab samples utilizing a proteomic approach. <b><i>Methods:</i></b> Cumulative buccal swab samples derived from very low birth weight preterm infants (<32 weeks' gestational age and <1,250 g) at 1, 2 and 3 weeks prior to the development of NEC and matched controls were subjected to two-dimensional difference gel electrophoresis and LC-MS/MS analysis for proteomic protein discovery. After identification of 21 altered proteins, we chose 3 candidate proteins using a broad systems biologic analysis approach that suggested several altered cellular processes that could be associated with NEC. <b><i>Results:</i></b> Preliminary validation studies using Western blots on these samples and 10 additional NEC and 10 matched control buccal samples collected within 2 or 3 weeks before NEC diagnosis analysis showed lower interleukin-1 receptor antagonist. <b><i>Conclusion:</i></b> Our results suggest that interleukin-1 receptor antagonist is worthy of further studies to determine its utility in helping predict NEC

Supplementary Material for: Inhibition of Rac1 Signaling Downregulates Inflammasome Activation and Attenuates Lung Injury in Neonatal Rats Exposed to Hyperoxia

<p><b><i>Background:</i></b> Inflammatory injury, particularly the production of active interleukin (IL)-1β plays a major role in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. The release of active IL-1β is controlled by posttranscriptional modifications of its proform (pro-IL-1β) through the inflammasome. Rac1 is a member of the Rho family of GTPases that regulate the inflammatory process. <b><i>Objective:</i></b> This study tested the hypothesis that Rac1 signaling increases inflammasome activation that results in damaging inflammation, and that the inhibition of Rac1 signaling prevents lung injury, by inhibiting inflammasome activation in a newborn rat model of BPD induced by hyperoxia. <b><i>Methods:</i></b> Newborn rat pups were exposed to room air or hyperoxia (85% O₂) and received daily intraperitoneal injections of placebo (normal saline) or NSC23766, a specific Rac1 inhibitor, for 10 days. The effects on lung inflammation, alveolarization, vascular development, vascular remodeling, right ventricular systolic pressure, and right ventricular hypertrophy (RVH) were then assessed. <b><i>Results:</i></b> Hyperoxia exposure upregulated Rac1 and increased the production of active IL-1β, which was accompanied by increasing expression of the inflammasome. In addition, hyperoxia induced the pathological hallmarks of BPD. However, treatment with NSC23766 significantly decreased inflammasome activation and macrophage infiltration, improved alveolar and vascular development, and reduced pulmonary vascular remodeling and RVH. <b><i>Conclusion:</i></b> These results indicate that Rac1 signaling regulates the expression of the inflammasome and plays a pivotal role in the pathogenesis of hyperoxia-induced neonatal lung injury. Therefore, targeting Rac1 signaling may provide a novel strategy to prevent and treat BPD in preterm infants.</p