Staining Score Research Articles

Non-invasive assessment of IgA nephropathy severity with [18F] AlF-NOTA-FAPI-04 PET/CT imaging

Abstract Background Renal biopsy plays a crucial role in diagnosing and assessing the severity of IgA nephropathy (IgAN), despite being an invasive procedure with potential risk of failure. Our study focused on evaluating the capability of [18F] AlF-NOTA-FAPI-04 PET/CT in identifying the extent of pathological alterations in IgAN. Methods Twenty patients (13 males and 7 females; mean age, 44 ± 16 years) with newly diagnosed primary IgAN and 10 patients (7 males and 3 females; mean age, 51 ± 4 years) without known renal disease underwent [18F] AlF-NOTA-FAPI-04 PET/CT imaging. Kidney tissues from biopsies were stained with various techniques and examined using immunofluorescence. The Oxford classification was used to evaluate pathological indicators. Immunohistochemical staining was conducted to assess α-smooth muscle actin (αSMA) and FAP expression. Renal FAPI uptake measured by PET/CT (SUVmax and SUVmean) was correlated with histological findings. Results The renal parenchymal FAPI uptake was significantly higher in IgAN patients compared to control patients (SUVmax = 3.9 ± 1.3 vs 1.9 ± 0.4, SUVmean = 3.6 ± 1.2 vs 1.5 ± 0.4; all P < 0.001). We identified a significant difference in renal parenchymal FAPI uptake among the various categories of the Oxford classification. Correlation analysis revealed a positive association between SUVmax and interstitial fibrosis and tubular atrophy (IF/TA), as well as tubulointerstitial inflammation (TII) scores in scarred cortex and non-scarred cortex (r = 0.637, 0.593, and 0.491, all P < 0.05), Similar associations were observed between SUVmean and these scores (r = 0.641, 0.592, and 0.479, all P < 0.05). Furthermore, significant positive correlations were observed between SUVmax or SUVmean and the staining scores for glomerular αSMA and FAP, as well as for tubulointerstitial αSMA and FAP (all P < 0.01). Conclusion [18F] AlF-NOTA-FAPI-04 PET/CT imaging offers IgAN patients a non-invasive and reproducible auxiliary modality to monitor disease progression.

CILP-2 expression in the intervertebral discs of patients with lumbar radiculopathy

BackgroundIntervertebral disc (IVD) degeneration (IVDD) is one of the main causes of low back pain. One of the most important features of IVDD is the loss of extracellular matrix (ECM) with its structural components. Cartilage intermediate layer proteins (CILPs), minor glycoproteins residing in ECM, have been found to be increased in IVD as degeneration and aging progresses. The aim of the present study was to evaluate the expression of CILP-2 in the IVD of patients with lumbar radiculopathy.MethodsThe IVD samples were collected from 25 patients during spinal surgery (interlaminectomy, herniated disc removal). The control IVD samples were obtained from nine patients who underwent lateral corpectomies in the thoracic region. CILP-2 expression was detected by immunohistochemistry. The patients were divided into two groups – aged under or over 50 years. A standardized clinical examination with assessment of radicular signs and deficits was performed. Subjective disability and pain were assessed using the visual analogue scale and Oswestry Disability Index (ODI). The pre-operative MRI was graded for the degree of IVD degeneration by Pfirrmann grading system. IVD samples obtained during operations were subjected to the standardized histopathological analysis applying modified Boos classification. The data were analysed by t-test, Mann-Whitney U-test, and Spearman correlation test.ResultsBoth histopathology scores and Pfirrmann grades did not differ between patients’ groups. Also, no correlations were found between histopathology and Pfirrmann grades, neither were any differences seen when correlating both grades to ODI, back pain or leg pain scores. CILP-2 staining was noted in all studied samples, notably strong staining was seen around large cell clusters. However, no differences in CILP-2 staining were seen between the age groups of patients. No correlations were found between CILP-2 staining and Pfirrmann grades. Grading of CILP-2 immunostaining in nine control patient samples resulted in significantly lower values. The difference is statistically significant (P = 0.002) compared to CILP-2 staining scores of all 25 patients’ samples.ConclusionIn this study, we detected increased CILP-2 expression in the human IVD as compared to the control group patients. CILP-2 can be a possible IVDD marker; however, as knowledge about the role of CILP-2 is limited, further studies are required.

Perfluorohexyloctane ophthalmic solution for dry eye disease: pooled analysis of two phase 3 clinical trials

BackgroundDry eye disease (DED) is commonly caused by excessive tear film evaporation due to Meibomian gland dysfunction (MGD). There is a need for DED treatment options that address tear evaporation and benefit patients across a broad range of demographic and disease characteristics. This study evaluated treatment effects of perfluorohexyloctane ophthalmic drop (formerly NOV03) in the pooled dataset from 2 pivotal clinical trials in patients with DED associated with MGD, both in the overall population and in patient subgroups based on sex, age, and baseline severity of eye dryness.MethodsPooled data from 2 similarly designed, phase 3, randomized controlled trials (GOBI, MOJAVE) were analyzed. Patients aged ≥18 years with DED administered perfluorohexyloctane (n=614) or hypotonic (0.6% solution) saline control (n=603) four times daily for 8 weeks. Primary endpoints were total corneal fluorescein staining (tCFS) score (National Eye Institute scale, 0-15) and eye dryness visual analog scale (VAS) score (0-100). Efficacy was evaluated using analysis of covariance among patient subgroups (male and female, older [≥65 years] and younger [18 to <65 years], tCFS score <7 and ≥7, VAS eye dryness score <70 and ≥70, MGD score <7 and ≥7, Schirmer I test <10 mm and ≥10 mm).ResultsReductions in tCFS and VAS eye dryness scores were greater for perfluorohexyloctane versus control. In the overall patient population, least-squares mean treatment difference was −1.1 (95% CI: −1.41 to −0.79; p<0.0001) for tCFS and −9.0 (95% CI: −11.90 to −6.00; p<0.0001) for VAS eye dryness. Treatment favored perfluorohexyloctane over control in all patient subgroup analyses of tCFS and VAS eye dryness. Overall, the most common adverse event with perfluorohexyloctane was blurred vision (2.1% of patients), which was mild and transient.ConclusionsCompared with a hypotonic saline control, perfluorohexyloctane improved both the signs and symptoms of DED, including in patients with greater self-reported severity of eye dryness.Clinical trial registrationThis study represents an integrated analysis of 2 previous clinical trials: GOBI (ClinicalTrials.gov, NCT04139798) and MOJAVE (ClinicalTrials.gov, NCT04567329).

Short-term variability in ocular biometry and the impact of preoperative dry eye.

This study aimed to investigate the short-term variability of ocular biometric measurements and to analyze the factors associated with high variability of biometric values in patients with cataract. This retrospective study included 60 eyes of 60 patients who underwent ocular biometry twice with the IOLMaster 700 (March to November 2023). Ocular surface parameters included tear film break-up time (TBUT), corneal and conjunctival staining scores (CSS/ConSS). Refractive surprise was defined as a mean absolute error exceeding 0.5 diopter (D). Participants included 22 men and 38 women with a mean age of 70.6 ± 8.4 years. The variability of mean keratometric (K) values and astigmatism showed notable variability compared to axial length (mean K: 0.18 ± 0.17D, astigmatism: 0.21 ± 0.26D, axial length: 0.01 ± 0.01mm). A decreased TBUT and increased CSS were significantly associated with high variability (≥ 0.25D) of mean K (p = 0.040/0.008). The high K variability group (≥ 0.25D) revealed a significantly higher incidence of refractive surprise (> 0.5D) compared with the low K variability group (< 0.25D) (45.5%/17.9%, p = 0.037). Preoperative lower TBUT and higher CSS influenced the variability of K values in ocular biometry and may be related with postoperative refractive surprise due to erroneous K values.

Development of a nomogram for predicting postoperative recurrence of cervical intraepithelial neoplasia using immunohistochemical and clinical parameters

ABSTRACT Background We aimed to develop a nomogram to predict abnormal follow-up results of co-testing for cytology and human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) patients after conization. Research design and methods Two hundred sixty-three patients initially diagnosed as CIN2+ were recruited. Data on immunohistochemical (IHC) staining scores, along with demographic and clinical information were collected. Using least absolute shrinkage and selection operator (LASSO) regression analysis, variables were identified for inclusion. A predict model and nomogram were developed through multi-factor logistic regression. The goodness-of-fit test was applied across different cohorts to construct the calibration curve of the model, and the predictive effect was evaluated by the receiver operating characteristic curve. Decision curve analysis was performed to determine the net benefit. Results Five predictor variables, including protein expression score, vaginal infection, HPV coinfection, and cone height were screened and plotted as a nomogram. The calibration curves showed a good fit. The area under the curve of the model was 0.835 for the training cohort and 0.728 for the internal test cohort. The decision curve analysis indicated that the nomogram provides significant net advantages for clinical use. Conclusion A practical nomogram predict model was developed to predict abnormal follow-up outcomes in CINs after conization.

Effects of Rebamipide for Dry Eye on Optical Quality and Efficacy: A Systematic Review and Meta-Analysis.

Purpose: To evaluate the effects of rebamipide ophthalmic suspension on optical quality and efficacy of patients with dry eye under different conditions. Methods: A comprehensive search across five databases (PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wan Fang) was conducted for studies published through May 13, 2024, focusing on rebamipide for dry eye treatment. Results: A total of 11 studies including 334 patients with dry eye were included. Tear breakup time (TBUT) values of patients with dry eye increased significantly after 2 weeks (standardized mean difference [SMD] =1.07, 95% confidence interval [CI] = [0.05, 2.09]), 4 weeks (SMD = 1.26, 95% CI = [0.77, 1.75]), and 12 weeks (SMD = 1.04, 95% CI = [0.37, 1.71]) of rebamipide treatment. Subgroup analysis revealed that patients with dry eye wearing soft contact lens (SCL) exhibited higher TBUT values after 4 weeks of rebamipide treatment compared with those who received rebamipide alone. In addition, rebamipide significantly improved fluorescein staining score of patients with dry eye after 4 weeks of treatment (SMD = -0.34, 95% CI = [-0.63, -0.06]). However, 4 weeks of rebamipide treatment showed no significant effect on Schirmer I test values (SMD = -0.04, 95%, CI = [-0.43, 0.35]) and higher-order aberrations (SMD = -0.73, 95% CI = [-1.77, 0.30]). Conclusions: These results indicate a significant improvement in the efficacy of rebamipide treatment for patients with dry eye, particularly for those wearing SCL. The effect of rebamipide on visual quality was found to correlate with the underlying dry eye status.

Preliminary investigation on the establishment of a new meibomian gland obstruction model and gene expression

Meibomian gland dysfunction is a chronic ocular surface disease with a complex pathogenesis, whose main clinical manifestations are meibomian gland obstruction or/and lipid abnormalities. To explore the mechanism of MGD due to meibomian gland obstruction (MGO), we established a rat model of MGO by cauterizing the meibomian gland orifice. The morphology of the lid margins and meibomian gland orifices were visualized by slit lamp. The tear production of rats was measured by phenol red cotton thread, the tear film breakup time and corneal fluorescein staining scores of rats were detected under cobalt blue light of slit lamp. Changes in the histological structure of the meibomian gland (MG) were observed by HE staining, Oil Red O staining and immunofluorescence staining (collagen IV). RNA sequencing was used to detect differentially expressed genes in MGO and normal rats, which were validated by qPCR. In the MGO group after 4, 8, and 16 weeks, the meibomian gland orifices were closed, tear film break-up time decreased and corneal fluorescein staining score increased (p < 0.05). MG acini was smaller at 8-week and 16-week MGO rats in HE staining. Oil Red O staining showed less condensed staining in the 8- and 16-week MGO groups, while more condensed staining in the 4-week MGO group. Additionally, the basement membrane was destroyed in 16-week MGO group by immunofluorescence staining of collagen IV. Meanwhile, RNA sequencing and qPCR showed that lipid peroxidation (LPO), transient receptor potential vanilloid-3 (TRPV3) and genes in PPAR signaling pathway were differentially expressed in 16-week meibomian gland obstructive rats (p < 0.05). Consequently, meibomian gland obstruction model rats were established successfully with corneal damage and lower tear film stability. Meibomian gland obstruction is a causative factor of MGD, which led to abnormal histological structure in MG, differential expression of PPAR signaling pathway and TRPV3.

Should test for dry eyes be done before age-related cataract surgery?

Objectives: This study aimed to determine if tests for dry eyes should be done routinely before age-related cataract surgery. Materials and Methods: This was a hospital-based observational prospective study. Patients 50 years and above with age-related cataracts that met the inclusion criteria scheduled for manual small incision cataract surgery (MSICS) were assessed for dry eye disease (DED) before and after surgery. Numerical variables were described using the mean and standard deviation (SD) with a 95% confidence interval and P &lt; 0.05. Results: A total of 81 patients were studied: 60.5% (49) males and 39.5% (32) females. The mean pre-operative Schirmer’s test value was 14.09 mm (SD = 10.7 mm). Post-operative schirmer’s test values were 18.12mm (SD = 11.81mm) at 1 week, 14.98mm (SD = 11.26mm) at 4 weeks and 16.20 mm (SD = 11.06 mm) at 6 weeks. Pre-operative mean tear break-up time (TBUT) was 10.05 (SD = 5.13 s), 9.46 s (SD = 4.18 s) at 1 week, 10.13 s (SD = 4.29 s) at 4 weeks and 9.80 s (SD = 4.33 s) at 6 weeks postoperatively. Lissamine green staining score (LGSS) Grade 0 was 80% at 1 week post-operative, Grade 0 increased to 85%, 90% at 4 weeks and 91% at post-operative 6 weeks. Conclusion: This study showed that DED is not associated with MSICS, and it is not associated with objective worsening of previously diagnosed DED. Testing for DED preoperatively plays a significant role in the pre-operative evaluation of patients and symptomatic expectations, but its testing before MSICS might not always be necessary.

The Proportion of Ocular Involvement and Characteristics of Dry Eye Parameters in Primary Sjögren's Syndrome Referred from the Rheumatology Department.

To report the proportion of ocular involvement in primary Sjögren's syndrome (pSS) and to analyze various dry eye indexes and serum titers of markers depending on whether ocular involvement has occurred or not. This retrospective study considered 214 patients referred from the rheumatology department for pSS workup. Symptom questionnaires, ocular surface stain score (OSS), Schirmer test, tear break-up time (TBUT), meibomian gland (MG) dropout, meibum quality, meibum expressibility, lid margin abnormalities, and lipid layer thickness were evaluated. Anti-Ro Ab, anti-La Ab, ANA, RF, ESR, and CRP were included as systemic serum titers of markers. Patients with (Group 1) and without (Group 2) ocular involvement were compared. We conducted a further subgroup analysis of group 1 by dividing it into two groups based on whether or not the cases met all the ocular criteria for pSS diagnosis. Among the 214 referred patients, 118 were diagnosed as pSS: 87 out of 118 (74%) in group 1 and 31 (25%) in group 2. Group 1 showed higher meibum quality scores (p=0.016), meibum expressibility (p=0.01), and lid margin abnormalities on the lower lid (p=0.029) and lower TBUT (p=0.016) than group 2. Among the serum titers of markers, anti-Ro Ab negatively correlated with TBUT (r=-0.211, p=0.028). OSS, TBUT, and the schirmer test statistically differed between the patients who satisfied both ocular criteria (N=46) and those who satisfied only one criterion (N=41) (p=<0.001, 0.041, 0043, respectively). There were no statistical differences in serum titers of markers between the two groups. About half of patients referred from the rheumatology department for diagnosis of pSS were diagnosed with pSS. The proportion of ocular involvement in the pSS patients was 74%, and half of these patients met both ocular criteria. Only anti-Ro Ab negatively correlated with TBUT. Also, OSS, TBUT, and schirmer test were statistically different between the two subgroups.

A Preservative-Free Combination of Sodium Hyaluronate and Trehalose Improves Dry Eye Signs and Symptoms and Increases Patient Satisfaction in Real-Life Settings: The TEARS Study.

Dry eye disease (DED) is a frequently observed condition characterized by ocular discomfort and visual disturbance. It is highly prevalent and impairs patients' quality of life (QoL). This study assessed the benefit of a preservative-free bioprotectant eye drop formulation containing sodium hyaluronate and trehalose (SH-trehalose) with regards to DED, as well as patient satisfaction, through a large-scale real-life survey. In a multi-center, international, prospective observational study, subjects with DED received SH-trehalose for 84 days. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire-5 items (DEQ-5), and patient satisfaction were assessed at baseline, day 28, and day 84, and clinical evaluations included ocular surface staining, Schirmer test, tear film break-up time (TBUT), and conjunctival hyperemia at baseline and day 84. A total of 312 patients were evaluated, of whom 82.4% were women. The mean age was 57.9±15.2 years. The mean OSDI score at baseline was 41.7 ± 20.6. After 84 days, the mean OSDI score was 27.3 ± 19.8 (p < 0.001). The percentage of patients with a severe OSDI score decreased from 60.3 to 34.5%. The DEQ-5 score significantly (p < 0.001) improved after 28 and 84 days, as did patient satisfaction. Ocular surface staining, Schirmer test, TBUT, and conjunctival hyperemia scores improved significantly (all p < 0.001) for both eyes with SH-trehalose between baseline and day 84. Tolerance of SH-trehalose was good. SH-trehalose significantly improved the clinical signs and symptoms of DED after 84 days. Moreover, it significantly increased patient satisfaction and was well tolerated. NCT04803240.

A Selective Melatonin 2 Receptor Agonist, IIK7, Relieves Blue Light-Induced Corneal Damage by Modulating the Process of Autophagy and Apoptosis

This study aims to investigate the effect of the selective MT2 receptor agonist, IIK7, on corneal autophagy and apoptosis, aiming to reduce corneal epithelial damage and inflammation from blue light exposure in mice. Eight-week-old C57BL/6 mice were divided into BL-exposed (BL) and BL-exposed with IIK7 treatment (BL + IIK7 group). Mice underwent blue light exposure (410 nm, 100 J) twice daily with assessments at baseline and on days 3, 7, and 14. Corneal samples were analyzed for MT2 receptor expression, autophagy markers (LC3-II and p62), and apoptosis indicators (BAX expression and TUNEL assay). Then, mice were assigned to normal control, BL, and BL + IIK7. Ocular surface parameters, including corneal fluorescein staining scores, tear volume, and tear film break-up time, were evaluated on days 7 and 14. On day 14, reactive oxygen species (ROS) levels and CD4+ IFN-γ+ T cells percentages were measured. The BL group exhibited higher LC3-II and p62 expression, while the BL + IIK7 group showed reduced expression (p &lt; 0.05). The TUNEL assay showed reduced apoptosis in the BL + IIK7 group compared to the BL group. ROS levels were lower in the BL + IIK7 group. The BL + IIK7 group showed improved ocular surface parameters, including decreased corneal fluorescein staining and increased tear volume. The percentages of CD4+ IFN-γ+ T cells indicated reduced inflammatory responses in the BL + IIK7 group. The MT2 receptor agonist IIK7 regulates corneal autophagy and apoptosis, reducing corneal epithelial damage and inflammation from blue light exposure.

Serial intravitreal injections in age-related macular degeneration patients from the dry eye disease perspective: a cross-sectional study

BackgroundTo evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD).MethodsPatients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI.ResultsForty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6–22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047).ConclusionThe results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements.

Concurrent Limbal Stem Cell Deficiency and Mild Neurotrophic Keratopathy in Graft-Vs-Host Disease

Purpose: The purpose of this study was to delineate the concurrence of limbal stem cell deficiency (LSCD) and neurotrophic keratopathy in patients with ocular graft-vs-host disease (oGVHD). Methods: Medical records of patients with oGVHD were reviewed. Parameters collected included corneal sensitivity measured by using a noncontact esthesiometer, corneal fluorescein staining score (National Eye Institute grading scale), tear volume (Schirmer I test), and subbasal nerve density and limbal structure assessed by in vivo confocal microscopy. Results: Twenty-eight patients (mean age: 60.8 ± 10.4 years) with oGVHD were included; 50% (n = 14) had partial LSCD (P-LSCD), and 32% (n = 9) had complete LSCD (C-LSCD). Patients with C-LSCD showed significantly reduced total nerve density and branch nerve density compared with those with P-LSCD (P &lt; 0.02, P &lt; 0.04) and no LSCD (P &lt; 0.01, P = 0.02). Dendritic cell density was significantly higher in the C-LSCD group compared with the no LSCD group (P &lt; 0.05). Corneal sensitivity was significantly reduced in patients with C-LSCD compared with those with P-LSCD (P = 0.01) and no LSCD (P &lt; 0.02). Patients with C-LCSD had higher corneal fluorescein staining scores than patients with P-LSCD (P &lt; 0.01) and no LSCD (P = 0.02). Conclusions: This study highlights a significant concurrence of LSCD and neurotrophic keratopathy in patients with oGVHD, underscoring the link between inflammation, neurodegeneration, and loss of stem cell function.

Efficacy of Topical Cyclosporine Combined with Punctal Plugs in Treating Dry Eye Disease and Inflammation

Purpose To evaluate the effect of punctal plugs combined with cyclosporine eye drops on dry eye disease (DED) and ocular surface inflammation. Methods In a clinical trial, 73 patients were randomly allocated into three groups: punctal plug group, combination therapy group, and cyclosporine group. At the baseline and four weeks after treatment, the Schirmer I test score, fluorescein tear film break-up time (FBUT), ocular surface staining score and dry eye symptoms were assessed. Tear samples were collected to detect the level of inflammatory factors (interleukins, matrix metalloproteinase 9 (MMP-9) and tumor necrosis factor alpha (TNF-α)). In an animal experiment, a New Zealand rabbit dry eye model was induced. The rabbits were randomly divided into control group, punctal plug group, and combination therapy group (n = 6). Conjunctival goblet cell density, protein level of MMP-9 in conjunctiva and mRNA levels of inflammatory factors in conjunctiva and cornea were measured before and after treatment. Results In combination therapy group of the clinical trial, the following results were observed: significant improvement in Schirmer I test scores and FBUT compared to the cyclosporine group and punctal plug group, respectively; a decrease in the tear levels of IL-6, IL-1, and MMP-9 compared to the punctal plug group; and a decrease in the tear levels of IL-1α, IL-6, and IL-17 compared to the baseline (all p < 0.05). In the animal experiment, rabbits in combination therapy group had a higher goblet cell density (p < 0.01) and lower mRNA levels of IL-16 (p < 0.05), IL-17 (p < 0.05), and MMP-9 (p < 0.01) in conjunctiva and that of MMP-9 (p < 0.01) in cornea compared to punctal plug group. Conclusion Cyclosporine eye drops combined with degradable punctal plugs is a more optimized clinical treatment strategy for DED compared with degradable punctal plugs or cyclosporine eye drops alone, considering the influence of comprehensive clinical efficacy and ocular surface inflammation.

Comparative Evaluation of Efficacy of Chitosan and Chlorhexidine Mouthwash in Plaque Control and Gingivitis: An Observational Study.

Mouth rinse is a highly effective chemical solution for managing plaque and gingivitis. This study evaluated and compared the efficacy of chitosan (CH)-rich mouthwash with standard chlorhexidine (CHX) mouthwash in reducing gingivitis, plaque, halitosis, and stains. This retrospective, observational study was conducted on the clinical case records of 60 patients who were treated with CH mouthwash (formulated and dispensed from the department) as group 1 and CHX mouthwashas group 2 for at least three months. Indices such as the plaque index (PI), gingival index (GI), stain index (SI), and halitosis index (HI) were obtained at baseline (T0) and the end of three months of mouthwash use (T1) from the case records. The data were subjected to statistical analysis. Both groups effectively reduced all indices from T0 to T1; however, group 1 was more effective than group 2 in reducing gingival, plaque, and stain scores. The results were statistically significant (p<0.05) for all indices, and both groups were equally effective in reducing halitosis. Male sex showed a significant positive correlation with PI, GI, and SI, whereas female sex showed a positive correlation with PI and HI. Based on the findings of the present study, it was concluded that the CH mouthwash was more effective in reducing plaque, gingival, and staining scores than the CHX mouthwash. Both types of mouthwash were equally effective in reducing halitosis scores.

Assessing the therapeutic role of trehalose and hyaluronic acid: implications for patient care.

This Systematic review aims to assess the efficacy of trehalose and hyaluronic acid in enhancing ocular recovery post-cataract surgery, focusing on their impact on tear film stability, ocular surface integrity, and patient-reported outcomes. A comprehensive search was conducted across MEDLINE, PubMed, and Cochrane Library databases to identify randomized controlled trials investigating the efficacy of trehalose, hyaluronic acid, or their combination in post-cataract surgery care. The inclusion criteria focused on peer-reviewed studies in English, detailing outcomes relevant to ocular recovery such as tear film stability, ocular surface integrity, patient-reported discomfort, or visual acuity (VA). The quality of the included studies was assessed using the Cochrane Risk of Bias Tool and synthesized the data qualitatively. Four qualitative investigations met the inclusion criteria. The studies collectively assessed the efficacy of a 3% trehalose and 0.15% hyaluronic acid eye drop solution in reducing postoperative eye symptoms compared to various control solutions. Parameters measured included tear break-up time (TBUT), Fluorescein staining, tear production (Schirmer test), and Ocular Surface Disease Index (OSDI) scores. The results indicated significant improvements in tear film stability and ocular surface health for the treatment groups compared to controls, with a notable decrease in patient-reported discomfort. The study showed an improvement of - 18 (± 14.6) in the treatment group compared to - 7 (± 8.0) in the control group for OSDI. For TBUT, the treatment group improved by 3 (± 1.2) s, whereas the control group improved by 0.3 (± 0.71) s. VA, measured on a scale of 0-100, increased to 17 (± 0.7) in the treatment group compared to 15 (± 1.1) in the control group. Trehalose and hyaluronic acid may be beneficial in the postoperative period by enhancing tear film stability and ocular surface health. While the results are promising, further research is needed to confirm these findings, understand the mechanisms of action, and explore broader applications.

Predictors of Discordance Between Dry Eye Symptoms and Signs: Insights From the Sjögren's International Collaborative Clinical Alliance.

The diagnosis and management of dry eye disease (DED) could be complicated by the discordance between DED-related symptoms and signs. We performed a cross-sectional study to investigate the factors of and develop predictive models for the discrepancy in DED symptomatology. We used data from 3455 participants, 21 to 89 years old, from the Sjögren's International Collaborative Clinical Alliance study. We performed a multivariable stepwise linear regression model with backward elimination and Bayesian information criteria to select predictors for the discordance in DES symptomatology, which was defined as the difference between the rank score of Ocular Surface Disease Index 6 (OSDI-6) and the rank score of ocular staining score (OSS). Ten predictors, such as "vitality," "immunomodulating drugs," sensory symptoms," and "ethnicity," remained in the final models, achieving an adjusted R2 (aR2) of 0.35 (95% confidence interval [CI], 0.32-0.39). Specifically, medication use explained 19% (95% CI, 0.17-0.22) of the variance in the outcome, followed by medical history (aR2 = 0.18; 95% CI, 0.15-0.21). Health-related quality of life contributed 16% to the variance in the outcome (95% CI, 0.13-0.19), and, last, demographics contributed 11% (95% CI, 0.09-0.13). Our results suggest that individuals of Asian descent and those using immunomodulating medications often present with severe ocular signs that necessitate regular ophthalmological evaluations, even in the absence of proportionate ocular symptoms. Additionally, ocular symptoms, when accompanied by abnormal sensations in other parts of the body, could indicate systemic conditions that require further investigation and medical care.

Discovery of a novel thiophene carboxamide analogue as a highly potent and selective sphingomyelin synthase 2 inhibitor for dry eye disease therapy

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC50, SMS2 = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t1/2, cornea = 1.11 h; t1/2, meibomian glands = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Expression in High-Risk Human Papilloma Virus-Induced Cervical Carcinoma and Its Correlation With p16INK4A Protein.

Introduction Recently, the expression of metallophosphoesterase-domain-containing protein 2 (MPPED2) was identified in cervical cancer. However, its precise role and correlation with other tumor suppressor proteins, such as p16INK4A, is not well studied in high-risk human papillomavirus (HPV) integrated human cervical carcinoma. Hence, in the present study, we try to see the expression of MPPED2 in human cervical carcinoma and its correlation with age and p16INK4A protein expression level. Methods The prospective study consists of 200 samples of 150 known cervical carcinoma and 50 controls. Histopathological evaluation, immunohistochemical staining, and semi-quantitative scoring of the intensity of proteins were performed. Statistical analysis was performed with the Shapiro-Wilk test, Spearman's rho correlation sig. (two-tailed), and Student's t-test. Results The data show that among the 150 cases, 136 (68.0%) cervical carcinoma tissues express the presence of high-risk HPV viral genome integration in the host cell. The expression of p16INK4A protein is higher in those tissues identified with high-risk HPV viral genomes. In contrast, the expression of MPPED2 protein is lesser or absent in those cervical tissues that have the higher expression of p16INK4A protein and vice versa. There is a significant correlation (p=0.000) between age and p16INK4A protein expression but not with MPPED2. A significant linear correlation (p=0.000) is found between the p16INK4A and MPPED2 proteins. Conclusion It may support the therapeutic application of MPPED2 protein to prevent cervical carcinoma progression in the near future.

IL-37 Inhibits Inflammation of Lacrimal Gland in Dry Eye Mice via the IL-37-PTEN-NFκB Signaling Pathway

ABSTRACT Purpose This study aims to investigate the role of Interleukin-37 (IL-37) in mouse models of dry eye. Methods Two murine models of dry eye were employed in this investigation. The evaluation of the anti-inflammatory impact of IL-37 (200 μl, 10 μg/ml) on dry eye mice involved intraperitoneal injections administered once daily for 7 days. Additionally, intraperitoneal injection of VO-Ohpic trihydrate (VO, 0.25 mg/kg) in dry eye mice was performed to investigate the role of PTEN in the IL-37 anti-inflammatory signaling pathway. Tear production was assessed using phenol red cotton thread, while corneal damage was examined through sodium fluorescein staining using a slit lamp. Histological alterations in the lacrimal gland were observed through H&E staining. PAS staining was used to assess conjunctival goblet cells. The levels of NFκB-P65, p-NFκB-P65, IL-1β, IL-6, TNF-α, CD3, AQP5, α-SMA and PTEN proteins were determined via Western blotting or immunofluorescence. Results Following IL-37 treatment, both dry eye models exhibited reduced corneal fluorescence staining scores and enhanced tear production. In lacrimal gland, the expression of p-NFκB-P65, IL-1β, IL-6, CD3 and TNF-α was diminished, while PTEN, AQP5, α-SMA expression increased after IL-37 treatment in both dry eye mice. However, the intraperitoneal injection of VO significantly attenuated the anti-inflammatory effect of IL-37 on dry eye mice. Conclusion IL-37 emerges as an anti-inflammatory mediator within the lacrimal gland of dry eye mice, exerting its effects through the IL-37-PTEN-NFκB signaling pathway.