ß-blocker eye drops affect ocular surface through ß2 adrenoceptor of corneal limbal stem cells.

BACKGROUND: Topical application of ß-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of ß-blocker eye drops on corneal epithelial wound healing. METHODS: Corneal epithelial wound healing models were constructed by epithelial scraping including in the limbal region and unceasingly received eye drops containing 5 mg/mL ß-blocker levobunolol, ß1-adrenoceptor (ß1AR)-specific antagonist atenolol or ß2-adrenoceptor (ß2AR)-specific antagonist ICI 118, 551. For the migration assay, the murine corneal epithelial stem/progenitor cells (TKE2) were wounded and subsequently incubated with levobunolol, atenolol, or ICI 118, 551. The proliferation and colony formation abilities of TKE2 cells treated with levobunolol, atenolol, or ICI 118, 551 were investigated by CCK-8 kit and crystal violet staining. The differentiation marker Cytokeratin 3 (CK3), the stem cell markers-Cytokeratin 14 (CK14) and Cytokeratin 19 (CK19), and corneal epithelium regeneration-related signaling including in Ki67 and the phosphorylated epithelial growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were assessed by immunofluorescence staining. RESULTS: Levobunolol and ICI 118, 551 impaired corneal wound healing, decreased the expressions of CK3, CK14, and CK19 after limbal region scraping in vivo and reduced the migration and proliferation of TKE2 in vitro, whereas atenolol had no significant effect. Moreover, levobunolol and ICI 118, 551 inhibited corneal wound healing by mediating the expression of Ki67, and the phosphorylation of EGFR and ERK1/2 in the limbal and regenerated corneal epithelium. CONCLUSION: ß-blocker eye drops impaired corneal wound healing by inhibiting the ß2AR of limbal stem cells, which decreased corneal epithelial regeneration-related signaling. Therefore, a selective ß1AR antagonist might be a good choice for glaucoma treatment to avoid ocular surface damage.

Coronal subluxation of the tibiofemoral joint before and after anterior cruciate ligament reconstruction.

BACKGROUND: Studies have shown that medial subluxation of the tibia occurs after anterior cruciate ligament (ACL) rupture. However, it is unclear whether anterior cruciate ligament reconstruction (ACLR) can correct tibial coronal subluxation. PURPOSE: To determine whether the tibia is medially subluxated after ACL rupture, and whether ACLR can correct medial subluxation of the tibia. STUDY DESIGN: Case series; Level of evidence, 4, Retrospective clinical study. METHODS: The distance of tibial coronal subluxation before and after ACLR surgery was measured in 48 patients with ACL rupture and meniscus injury. Tibiofemoral subluxation was defined as the perpendicular distance between the long axis of the tibia and a second parallel line originating at the most proximal aspect of the femoral intercondylar notch. To determine the long axis of the tibia, two circles separated by 5 cm were centered on the proximal tibia. The proximal circle is 5 cm from the tibial plateau, and the distal circle is 5 cm from the proximal circle. The line passing through the center of the two circles was considered the long axis of the proximal tibia. Care was taken to ensure that each patient lied on the back with their patellae facing upward, to minimize rotational variation among the radiographs. At the same time, 30 patients with simple meniscus injury who underwent arthroscopy during the same period were selected to determine the degree of tibiofemoral coronal subluxation as the baseline value. The changes before and after operation were compared, as well as the differences with the baseline data. RESULT: The average follow-up period was 21.2 ± 5.8 months. The average distance of tibial coronal subluxation before ACLR was 5.5 ± 2.1 mm, which was significantly different from that of baseline group (7.3 ± 2.1 mm) (P < 0.001). The tibial subluxation after ACLR was 7.7 ± 2.6 mm, which was significantly different from that before operation (P < 0.001). There was no significant difference in the distance between postoperative tibial subluxation and baseline group (P = 0.472). CONCLUSION: The tibia was coronally medially subluxated after ACL rupture. ACLR can correct the medial subluxation of tibia. This finding is helpful in the diagnosis of ACL rupture, and can be used to assess the imaging status of the tibiofemoral joint on the coronal plane during or after ACLR.

A decreased ratio of height of lateral femoral condyle to anteroposterior diameter is a risk factor for anterior cruciate ligament rupture.

BACKGROUND: Studies have shown that the spherical shape of the lateral femoral condyle has a clear relationship with the relative axial movement of tibiofemoral joint and the anterior cruciate ligament (ACL) rupture. The purpose of this study was to describe the distal curvature of the lateral femoral condyle by ratio of height of lateral femoral condyle to anteroposterior diameter (HAPR), and evaluate its correlation with ACL rupture. METHODS: A retrospective case-control study of 64 patients was conducted. Two age-and sex-matched cohorts (each n = 32) were analyzed: primary ACL ruptures, and a control group consisting of isolated meniscal tears. On the radiograph, the distance from the intersection of the axis of the distal femur and the anteriorly diameter of the lateral femoral condyle to the lower point of the lateral femoral condyle divided by the anteriorly diameter of the lateral femoral condyle is HAPR. The HAPR was measured by digital radiograph imaging systems (DR) to quantify femoral sphericity. Cutoff values were defined; and diagnostic performance of the risk factors was assessed. Meanwhile, we measured the posterior tibial slope (PTS) on radiograph and compared the two methods to evaluate the significance of HAPR in predicting ACL rupture. RESULTS: A total of sixty-four patients who met the inclusion criteria were included in the final analysis (32 with primary ACL rupture, 32 controls). The HAPR was smaller in the knees with primary ACL rupture (0.31 ± 0.02) than that of the control group (0.33 ± 0.02) (p < 0.01). The PTS was bigger in the knees with primary ACL rupture (8.18 ± 2.77) than that of the control group (6.61 ± 2.85) (p = 0.036). The AUC of HAPR was bigger (0.825; 95% CI, 0.72-0.93) than that of PTS (0.675; 95%CI, 0.85-0.81). The calculated cutoff of HAPR of 0.32 (Youden index, 0.56) was associated with an increased risk for ACL rupture, with sensitivity of 75% and specificity of 81% to predict an ACL rupture. CONCLUSIONS: This study showed that a decreased HAPR is associated with an ACL rupture, and the decrease of HAPR was more significant in predicting ACL ruptures than the PTS. This helps clinicians identify susceptible individuals who may benefit from targeted ACL rupture prevention counseling and intervention.

Global burden of rheumatoid arthritis among adolescents and young adults aged 10-24 years: A trend analysis study from 1990 to 2019.

BACKGROUND: In recent decades, there has been a global increase in the burden of rheumatoid arthritis (RA) among adolescents and young adults (AYAs), making it a significant public health issue. However, our understanding of the disease burden, harm, and influencing factors of RA in this population remains insufficient. This study aimed to assess the trends in RA burden among AYAs aged 10-24 years from 1990 to 2019 at the global, regional, and national levels. METHODS: Incidence, prevalence, and disability-adjusted life years (DALYs) rate per 100,000 population, as well as average annual percentage changes (AAPCs), of RA among individuals aged 10-24 years were reported globally, regionally, and nationally based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). These global trends were further analyzed by age, sex, and Sociodemographic index (SDI). Joinpoint regression analysis was used to determine the year in which the most significant changes in global trends occurred. RESULTS: Globally, the incidence of RA among AYAs increased from 4.98 per 100,000 population in 1990 to 5.41 per 100,000 population in 2019, with an AAPCs of 0.29 (95%CI: 0.26, 0.32, p < 0.001). The most significant increase occurred in 2000, while the most significant decrease occurred in 2014. The prevalence increased from 34.11 per 100,000 population in 1990 to 36.34 per 100,000 population in 2019, with an AAPCs of 0.22 (95%CI: 0.19, 0.24, p<0.001); The most significant increase was observed in 2000, and the most significant decrease occurred in 2014. DALYs rate with RA were 5.96 per 100,000 population in 1990 and 5.79 per 100,000 population in 2019 for AYAs, with an average decrease of 0.1 years per year (AAPCs = -0.1, 95%CI: -0.2, -0.01, p = 0.04). In terms of gender, the incidence, prevalence, and DALYs rate were higher for females compared to males during the same period. Regarding age, the incidence, prevalence, and DALYs rate increased with increasing age. Based on the SDI quintile, the incidence, prevalence, and DALYs rate of RA were highest in countries with high SDI and lowest in countries with low SDI from 1990 to 2019. However, the relationship between incidence and SDI is non-linear. In terms of regions, Tropical Latin America exhibited the highest incidence, prevalence, and DALYs rate, while Andean Latin America experienced the most rapid increase in incidence and prevalence. Southern Latin America saw the fastest growth in DALYs rate, whereas Southern Sub-Saharan Africa witnessed the most significant decline. CONCLUSION: In conclusion, the study revealed an overall increase in the incidence and prevalence of RA among adolescents and young adults (AYAs) over the past three decades, while DALYs rate remained relatively stable. Furthermore, the incidence, prevalence, and DALYs rate of RA were found to increase with age. Fortunately, recent proactive preventive measures and treatment methods have shown promising results. Moving forward, it is crucial to prioritize the female population and AYAs patients in order to further alleviate the global burden of RA.

Analysis of adverse drug reactions of Denosumab (Prolia) in osteoporosis based on FDA adverse event reporting system (FAERS).

Objective: To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy. Methods: Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals. Results: Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the "primary suspected (PS)" ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation. Conclusion: Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).

Bibliometric and visualized analysis of elite controllers based on CiteSpace: landscapes, hotspots, and frontiers.

Background: A unique subset of people living with HIV, known as elite controllers, possess spontaneous and consistent control over viral replication and disease progression in the absence of antiviral intervention. In-depth research on elite controllers is conducive to designing better treatment strategies for HIV. However, comprehensive and illuminating bibliometric reports on elite controllers are rare. Methods: Articles on elite controllers were retrieved from the Web of Science Core Collection. A visualized analysis of this domain was conducted by CiteSpace software. Taking count, betweenness centrality, and burst value as criteria, we interpreted the visualization results and predicted future new directions and emerging trends. Results: By December 31, 2022, 843 articles related to elite controllers had been published. The largest contributors in terms of country, institution, and author were the United States (485), Univ Calif San Francisco (87), and Walker B.D. (65), respectively. Migueles S.A. (325) and Journal of Virology (770) were the most cocited author and journal, respectively. Additionally, by summarizing the results of our CiteSpace software analysis on references and keywords, we considered that the research hotspots and frontiers on elite controllers mainly focus on three aspects: deciphering the mechanisms of durable control, delineating the implications for the development of treatments for HIV infection, and highlighting the clinical risks faced by elite controllers and coping strategies. Conclusion: This study performed a bibliometric and visual analysis of elite controllers, identified the main characteristics and emerging trends, and provided insightful references for further development of this rapidly evolving and complex field.