Comparison of various excimer laser (EL) combination therapies for vitiligo: a systematic review and network meta-analysis.

AIM: This study aimed to compare the efficacy and safety of excimer laser (EL)-based combination regimens in improving repigmentation. METHODS: A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, and Embase on July 1, 2023, to include randomized controlled trials of EL combination treatments for vitiligo that met the criteria. The primary outcome measure was a repigmentation rate ≥ 75%, and the secondary outcome measures were a repigmentation rate of ≤ 25% and adverse events. RESULTS: Eleven studies involving 348 patients were included. Network Meta-Analysis showed that EL combined with antioxidants (SUCRA = 98.8%), EL combined with calcipotriol (SUCRA = 59.8%) and EL combined with tacalcitol (SUCRA = 59.6%) were the three optimal interventions achieving repigmentation rates ≥ 75%. EL alone (SUCRA = 77.6%), EL combined with tacalcitol (SUCRA = 61.7%) and EL combined with antioxidants (SUCRA = 57.2%) were the three interventions with the highest rates of treatment failure. Adverse events in all groups mainly included erythema, burning sensation and hyperpigmentation. Based on the results of the current study, EL combination therapies were safe with mild adverse events. CONCLUSION: EL combined with antioxidants was the preferred regimen for vitiligo, whereas EL alone was the regimen with the highest rate of treatment failure in vitiligo.

Systematic Review and Meta-analysis: Macrolide in the Treatment of Chronic Rhinosinusitis After Endoscopic Sinus Surgery.

OBJECTIVES: To evaluate the efficacy and safety of macrolide antibiotics therapy in patients with chronic rhinosinusitis (CRS) receiving endoscopic sinus surgery. DATA SOURCES: PubMed, Web of Science, Embase, and Cochrane Library. REVIEW METHODS: The electronic databases were comprehensively searched on June 2, 2022, for randomized controlled trials on macrolide antibiotics in the treatment of patients undergoing CRS endoscopic surgery. The primary outcome measures were the sinonasal outcome test (SNOT) score and the visual analog scale (VAS) score. The secondary outcome measures were the nasal endoscopy score (NES), the sinus computed tomography score, and adverse events. RESULTS: A total of 8 studies were included, involving 606 patients who used macrolide for a long time. Meta-analysis showed that no significant difference was observed in SNOT (standardized mean difference [SMD] = -0.13; 95% confidence interval [CI]: -0.38 to 0.13, I2 = 0%) and VAS (SMD = -0.10; 95% CI, -0.88 to 0.68, I2 = 81%) between the macrolide and placebo groups. However, macrolide outperformed the placebo in improving NES (SMD = -0.32; 95% CI, -0.62 to -0.03, I2 = 21%). The use of macrolide did not increase the incidence of adverse events. CONCLUSION: Long-term use of macrolide after CRS surgery may not significantly improve the quality of life and disease severity of the patients but may play a role in improving postoperative NES in patients with CRS. There is still no sufficient evidence to determine whether the disease phenotype of CRS or the patient's race will affect the efficacy of long-term use of macrolide after CRS.

Krüppel-like factor 5 -mediated Sirtuin6 promotes osteogenic differentiation and inhibits inflammatory injury of lipopolysaccharide-induced periodontal membrane stem cells by inhibiting nuclear factor kappa-B pathway.

Periodontitis is a chronic infectious disease that causes inflammation and immune response and has an ultimate impact on the health of the whole body. Sirtuin6 (SIRT6) and Krüppel-like factor 5 (KLF5) have been reported to regulate the inflammatory response and play an important role in the development of periodontitis. LPS was adopted to induce periodontal ligament stem cells (PDLSCs) to construct a periodontitis cell model. SIRT6 expression was assayed through RT-qPCR and Western blot. Subsequently, after SIRT6 was overexpressed, CCK8 was to appraise cell viability. ELISA analysis was used to estimate inflammatory response. ALP staining, ARS staining, and Western blot were used to detect osteogenic differentiation. The JASPAR website then predicts the binding of transcription factor KLF5 to SIRT6 promoter. The interaction between KLF5 and SIRT6 was verified by a luciferase reporter and ChIP assays. Additionally, the osteogenic differentiation and inflammation in LPS-induced PDLSCs transfected with Ov-SIRT6 and si-KIF5 were also explored. Finally, the protein levels of the nuclear factor kappa-B (NF-κB) pathway-related factors were detected by Western blot to further explore the mechanism. There was a marked decrease in SIRT6 expression in LPS-induced PDLSCs. SITR6 overexpression prevented LPS-induced cell viability loss and inflammation, while promoting osteogenic differentiation. In addition, KLF5 could transcriptionally activate SIRT6. Further, KLF5 knockdown reversed the impacts of SIRT6 on the proliferation, inflammation, and osteogenic differentiation of LPS-induced PDLSCs via mediating NF-κB pathway. Overall, KLF5-mediated SIRT6 promoted the viability and osteogenic differentiation, while inhibiting the inflammatory response of LPS-induced PDLSCs by inhibiting NF-κB pathway.

Association Between Chronic Periodontal Disease and Erectile Dysfunction: A Case-Control Study.

Erectile dysfunction (ED) and chronic periodontal disease (CPD) share mutual risk factors, and the incidence of ED is increasing among young adults. The relation of CPD and ED remains obscure due to inconsistent clinical evidence. This study aimed to further assess the relationship between CPD and ED using the Community Periodontal Index of Treatment Need (CPITN) and the International Index of Erectile Function (IIEF). Totally, 202 adult men were included, with 100 subjects with ED in the case group and 102 subjects without ED undergoing routine dental examinations in the control group. The IIEF questionnaire was used to assess the severity of ED, and CPD was assessed through the Community Periodontal Index (CPI) score. Periodontal assessments were performed by one single calibrated examiner. Logistic regression analysis was performed for the association between CPD and ED. After adjustment for age, smoking status, tooth brushing time, education level, monthly income, tooth brushing frequency, and gum bleeding, higher CPI score was identified to be associated with a greater risk of ED (odds ratio [OR] = 2.755, 95% confidence interval [CI] = [1.400, 5.423], p = .003), suggesting that CPD was positively associated with the odds of ED. CPD was getting more severe with the progress of ED (p < .05). Men with ED could be encouraged to receive routine dental examinations and appropriate preventive dental measures to maintain oral and periodontal health.

Increased risk of periodontitis occurrence in patients with rheumatoid arthritis and its association with the levels of IL-1ß and TNF-α in gingival crevicular fluid.

BACKGROUND: Periodontitis (PD) is a chronic inflammatory disease caused by infection of the periodontal supporting tissues. Clinical studies have reported that rheumatoid arthritis (RA) patients have a higher prevalence of PD. This study aimed to explore the correlation between RA and PD. METHODS: A total of 307 RA patients (RA group) and 324 healthy individuals (control group) who received physical examinations during the same period were recruited to this study. The incidence of PD in the two groups was analyzed, and the periodontal disease index (PDI) and bleeding on probing (BOP) were recorded. Then, 42 RA patients with PD and 56 control group patients with PD were selected for further analysis. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the gingival crevicular fluid (GCF) of the two groups. For patients with both RA and PD, the level of serum C-reactive protein (CRP) and the duration of morning stiffness were also recorded. RESULTS: The prevalence of PD in the RA group (51.5%) was significantly higher than that in the control group (31.2%), and the prevalence of PD also increased notably with the increase of age and the duration of the disease in RA patients. The levels of TNF-α and IL-1ß in the PDI and the GCF in the concurrent RA and PD group were significantly higher than those in the PD group (P<0.05). Partial correlation analysis showed that TNF-α in the GCF positively correlated with the BOP of patients with RA and PD. Multiple linear regression analysis showed that the level of TNF-α in the GCF and serum CRP were independent influencing factors of the level of IL-1ß in the GCF (the r values were 1.074 and 3.851, respectively; P<0.01). CONCLUSIONS: The presence of RA can increase risk of PD occurrence and is positively correlated with the levels of IL-1ß and TNF-α in the GCF.

Long non-coding RNA TUG1 participates in LPS-induced periodontitis by regulating miR-498/RORA pathway.

AIM: This study was aimed to investigate the role of TUG1 in LPS-stimulated hPDLCs and to evaluate the potential functions of TUG1 in the pathogenesis of periodontitis. METHODS: LPS-stimulated hPDLCs were established as the cell model. CCK-8 assay was performed to assess cell proliferation ability. Flow cytometry was performed to detect cell cycle distribution, and quantitative RT-PCR and Western blotting were conducted to measure gene expressions. ELISA kits were used to evaluate the production of inflammatory cytokines. The putative binding site between TUG1 and miR-498 was verified using luciferase reporter and RNA immunoprecipitation assays. RESULTS: TUG1 was downregulated upon LPS stimulation in hPDLCs. TUG1 overexpression promoted cell proliferation through regulating the cell cycle distribution, along with the decreased expression of p21 and increased expression of CDK2 and cyclin D1. Besides, TUG1 overexpression decreased the production of inflammatory cytokines. The effects were opposite upon TUG1 knockdown. TUG1 negatively regulated its target miR-498, and influenced the expression of RORA, the direct target of miR-498. Simultaneous TUG1 overexpression and miR-498 reversed the effect of TUG1 overexpression alone on alleviating LPS-induced cell injury and inhibition of Wnt/ß-catenin signaling, which was further changeover after co-overexpression with RORA. CONCLUSION: Therefore, TUG1 could protect against periodontitis via regulating miR-498/RORA mediated Wnt/ß-catenin signaling.

Identification of associations between genotypes and longitudinal phenotypes via temporally-constrained group sparse canonical correlation analysis.

MOTIVATION: Neuroimaging genetics identifies the relationships between genetic variants (i.e., the single nucleotide polymorphisms) and brain imaging data to reveal the associations from genotypes to phenotypes. So far, most existing machine-learning approaches are widely used to detect the effective associations between genetic variants and brain imaging data at one time-point. However, those associations are based on static phenotypes and ignore the temporal dynamics of the phenotypical changes. The phenotypes across multiple time-points may exhibit temporal patterns that can be used to facilitate the understanding of the degenerative process. In this article, we propose a novel temporally constrained group sparse canonical correlation analysis (TGSCCA) framework to identify genetic associations with longitudinal phenotypic markers. RESULTS: The proposed TGSCCA method is able to capture the temporal changes in brain from longitudinal phenotypes by incorporating the fused penalty, which requires that the differences between two consecutive canonical weight vectors from adjacent time-points should be small. A new efficient optimization algorithm is designed to solve the objective function. Furthermore, we demonstrate the effectiveness of our algorithm on both synthetic and real data (i.e., the Alzheimer's Disease Neuroimaging Initiative cohort, including progressive mild cognitive impairment, stable MCI and Normal Control participants). In comparison with conventional SCCA, our proposed method can achieve strong associations and discover phenotypic biomarkers across multiple time-points to guide disease-progressive interpretation. AVAILABILITY AND IMPLEMENTATION: The Matlab code is available at https://sourceforge.net/projects/ibrain-cn/files/ . CONTACT: dqzhang@nuaa.edu.cn or shenli@iu.edu.

Mining Outcome-relevant Brain Imaging Genetic Associations via Three-way Sparse Canonical Correlation Analysis in Alzheimer's Disease.

Neuroimaging genetics is an emerging field that aims to identify the associations between genetic variants (e.g., single nucleotide polymorphisms (SNPs)) and quantitative traits (QTs) such as brain imaging phenotypes. In recent studies, in order to detect complex multi-SNP-multi-QT associations, bi-multivariate techniques such as various structured sparse canonical correlation analysis (SCCA) algorithms have been proposed and used in imaging genetics studies. However, associations between genetic markers and imaging QTs identified by existing bi-multivariate methods may not be all disease specific. To bridge this gap, we propose an analytical framework, based on three-way sparse canonical correlation analysis (T-SCCA), to explore the intrinsic associations among genetic markers, imaging QTs, and clinical scores of interest. We perform an empirical study using the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to discover the relationships among SNPs from AD risk gene APOE, imaging QTs extracted from structural magnetic resonance imaging scans, and cognitive and diagnostic outcomes. The proposed T-SCCA model not only outperforms the traditional SCCA method in terms of identifying strong associations, but also discovers robust outcome-relevant imaging genetic patterns, demonstrating its promise for improving disease-related mechanistic understanding.