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Abstract In clinical practice, the effect of a high vault on corneal endothelial cells after implantable collamer lens (ICL) implantation remains unclear. Many clinicians theoretically assume that a high postoperative vault leads to rapid endothelial damage, but no study has yet proven this hypothesis. We conducted a paired-eye study to compare changes in corneal endothelial cell density (ECD) between high and low postoperative vault groups. This retrospective study included 150 eyes of 75 patients with bilateral postoperative vault levels differing by more than 200 μm after ICL implantation. Patients were followed up for 7 years with ECD measurements, and changes in ECD were assessed between 6 months and 7 years post-surgery. Over the 7-year follow-up period, the percentage of ECD loss was 15.04% and 14.45% in the high- and low-vault groups, respectively. The bilateral paired-eye comparison revealed a significant reduction in ECD in the high-vault group at 3, 5, and 7 years postoperatively (P-value

Recent clinical outcomes of multi-regimen chemotherapy in patients with cholangiocarcinoma (CCC) have shown benefits in terms of overall survival. However, repeated endoscopic biliary drainage (EBD) and serious adverse events negatively affect prolongation of the survival period. The aim of this study was to investigate the prevalence of massive hemobilia and the outcomes of its management with fully covered self-expandable metal stents (FC-SEMSs) in patients with hilum-involving CCC receiving multi-regimen chemotherapy. The methods and effects of FC-SEMS placement were retrospectively investigated following the occurrence of massive hemobilia during EBD. A total of 356 patients with CCC received multi-regimen chemotherapy. Among them, 181 patients had hilar invasion, and seven patients (3.9%) developed massive hemobilia during repeated EBD using removable stents. In all cases, the tumor encased the right hepatic artery. In six patients (85.7%), hemostasis was immediately and completely achieved by inserting one or two FC-SEMSs proximal to the hilar invasion area. Therefore, if the tumor encases the right hepatic artery, massive hemobilia is likely to occur during multi-regimen chemotherapy. Thus, prompt placement of a FC-SEMS would be an effective treatment option for massive hemobilia in patients with hilum-involving CCC.

Abstract With the severity of chronic kidney disease worldwide, strategies to recover renal function via tissue regeneration provide alternatives to kidney replacement therapy. To exclude side effects from direct cell transplantation, extracellular vesicles (EVs) are great substitutes representing paracrine cell signaling. To build three-dimensional structures for implantation into the 5/6 nephrectomy model by incorporating bioactive materials, including multifunctional EVs (mEVs), porous PMEZE/mEV scaffolds were developed in combination with edaravone (EDV; E) and mEV based on PMEZ scaffolds with PLGA (P), MH-RA (M), ECM (E), ZnO-ALA (Z). The oxygen free radical scavenger EDV was incorporated to induce tubular regeneration. mEVs were engineered to serve regenerative activities with a combination of two EVs from SDF-1α overexpressed tonsil-derived mesenchymal stem cells (sEVs) and intermediate mesoderm (IM) cells during differentiation into kidney progenitor cells (dEVs). mEVs displayed beneficial effects on regeneration by facilitating migration and inducing differentiation of surrounding stem cells, and EDV improved kidney function by regulating the GDNF/RET pathway and their downstream genes. The promotion of MSC recruitment was confirmed with sEV particles number dependently, and the regulation of the GDNF/RET pathway by the effect of EDV and its enhanced effect by mEVs were elucidated using in vitro analysis. The regeneration of tubules was additionally demonstrated through the increased expression of aquaporin-1 (AQP-1) and cadherin-16 (CDH16) for proximal tubules, and calbindin and PAX2 for distal tubules in the renal defect model. With these, structural regeneration and functional recovery were achieved with kidney regeneration in the 5/6 nephrectomy mice model. Graphical abstract

Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options. This underscores the growing need for novel therapeutic strategies to complement existing treatments and improve patient outcomes. In recent years, pentacyclic triterpenoids, a group of natural compounds, have emerged as promising candidates for cancer therapy due to their anticancer properties. Pentacyclic triterpenoids, such as lupeol, betulinic acid, betulin, oleanolic acid, ursolic acid, glycyrrhetinic acid, glycyrrhizin, and asiatic acid, have demonstrated the ability to inhibit cell proliferation and angiogenesis, induce apoptosis, suppress metastasis, and modulate inflammatory and immune pathways in NSCLC cell line models. These compounds exert their effects by modulating important signaling pathways such as NF-κB, PI3K/Akt, and MAPK. Furthermore, advances in drug delivery technologies such as nanocarriers and targeted delivery systems have improved the bioavailability and therapeutic efficacy of triterpenoids. However, despite promising preclinical data, rigorous clinical trials are needed to verify their safety and efficacy. This review explores the role of triterpenoids in NSCLC and therapeutic potential in preclinical models, focusing on their molecular mechanisms of action.

Abstract Introduction The neutrophil-to-lymphocyte ratio (NLR) has been found to be useful in the prognostication of immune-mediated neurological disorders because it roughly reflects the systemic innate immune response compared to the adaptive immune response. However, studies on the validity of NLR in demyelinating disorders of the central nervous system have shown conflicting results. Therefore, we aimed to investigate NLR in the idiopathic transverse myelitis (ITM) cohort. Methods We retrospectively analyzed the cohort data of patients with ITM between January 2006 and February 2020. The medical data of all patients with myelitis were reviewed to exclude patients with disease-associated myelopathy according to predefined exclusion criteria. The relationship between the natural log-transformed NLR (lnNLR) and the clinical, paraclinical, and imaging data was evaluated. Factors associated with neurological disability were analyzed using a linear mixed-effects model. Predictive factors for moderate-to-severe neurological disability (Expanded Disability Status Scale [EDSS] score ≥ 4) were investigated. Results A total of 124 participants were included in the analysis. The lnNLR correlated with EDSS and lesion length. Linear mixed-effects analysis showed that age, lesion length, and lnNLR were independently associated with neurological disabilities. Multivariable logistic regression revealed that lnNLR (odds ratio [OR] = 4.266, 95% confidence interval [CI] = 1.220–14.912, p = 0.023) and lesion length (OR = 1.848, 95% CI = 1.249–2.734, p = 0.002) were independent predictive factors of the worst neurological disability. Conclusion NLR may be used as an independent prognostic factor for predicting poor neurological outcomes in patients with ITM.

BackgroundWhile studies have suggested an association between periodontal disease and an increased risk of cardiovascular disease, the strength of this association and its specific links to various types of cardiovascular disease have not been thoroughly investigated. This study aimed to examine how gingivitis and tooth loss affect cardiovascular diseases, probing their individual impacts.MethodsA retrospective cohort study was conducted, encompassing 3,779,490 individuals with no history of cardiovascular disease, utilizing data from the National Health Examination and the Korean National Health Insurance database from 2006 to 2019. Cox proportional hazards models were applied to estimate the association between tooth loss, gingivitis, and cardiovascular disease.ResultsFollowing a median follow-up of 10.38 years, 17,942 new cardiovascular disease cases were identified, comprising 10,224 cases of angina pectoris, 6,182 cases of acute myocardial infarction, and 9,536 cases of stroke. It was observed that the risk of stroke was significantly higher in the tooth loss group compared to the control group (adjusted hazard ratio [aHR]: 1.09, 95% confidence interval [CI]: 1.04-1.15). In the group with gingivitis and tooth loss, the risk of stroke and cardiovascular disease was significantly higher than in the control group (aHR: 1.12, 95% CI: 1.04-1.20; aHR: 1.08, 95% CI: 1.03-1.14). The gingivitis group exhibited a higher risk associated with stroke (aHR: 1.05, 95% CI: 1.01-1.10) among individuals aged 50 and above. However, statistically significant associations between periodontal disease and angina pectoris were not observed, nor between periodontal disease and acute myocardial infarction except among those aged above 50. Furthermore, the association between periodontal disease and cardiovascular disease was found to be stronger among individuals over the age of 50, males, those with obesity, and smokers compared to the control group.ConclusionsOur results emphasize the association of tooth loss and gingivitis with cardiovascular disease, specifically stroke, underlining the critical need for preventive oral healthcare. Tailored interventions are necessary to reduce the heightened risk of cardiovascular disease events, especially stroke, among older, obese individuals and smokers.

Abstract Purpose Mesenchymal stem cells (MSCs) react dynamically with the surrounding microenvironment to promote tissue‐specific differentiation and hence increase targeted regenerative capacity. Extracellular matrix (ECM) would be the first microenvironment to interact with MSCs injected into the tissue lesion. However, degenerative tissues would have different characteristics of ECM in comparison with healthy tissues. Therefore, the influence of degenerative ECM on tissue‐specific differentiation of MSCs and the formation of matrix composition need to be considered for the sophisticated therapeutic application of stem cells for tissue regeneration. Methods Human degenerative tendon tissues were obtained from patients undergoing rotator cuff repair and finely minced into 2 ~ 3 mm fragments. Different amounts of tendon matrix (0.005 g, 0.01 g, 0.025 g, 0.05 g, 0.1 g, 0.25 g, 0.5 g, 1 g, and 2 g) were co‐cultured with bone marrow MSCs (BM MSCs) for 7 days. Six tendon‐related markers, scleraxis, tenomodulin, collagen type I and III, decorin, and tenascin‐C, osteogenic marker, alkaline phosphatase (ALP), and chondrogenic marker, aggrecan (ACAN), were analyzed by qRT‐PCR. Cell viability and senescence‐associated beta‐galactosidase assays were performed. The connective tissue growth factor was used as a positive control. Results The expressions of six tendon‐related markers were significantly upregulated until the amount of tendon matrix exceeded 0.5 g, the point where the mRNA expressions of all six genes analyzed started to decrease. The tendon matrix exerted an inhibitory effect on ACAN expression but had a negligible effect on ALP expression. Cell viability did not change significantly over the culture period. The amount of tendon matrix exceeding 0.01 g significantly increased the SA‐βgal activity of BM MSCs. Conclusion This study successfully demonstrated tendon ECM‐stimulated tenogenesis of BM MSCs through an indirect co‐culture system without the use of exogenous growth factors and the alteration of cellular viability. In contrast to the initial hypothesis, the tenogenesis of BM MSCs induced with the degenerative tendon matrix accompanied cellular senescence.

Reconstruction of patient-specific scaffolds to repair uniquely shaped bone defects remains a major clinical challenge in tissue engineering. Recently, three-dimensional (3D) printed scaffolds have received considerable attention as a promising technology for the rapid generation of custom shapes. However, synthetic polymers commonly used for 3D printing, such as polycaprolactone (PCL), lack the biological capacity to mimic native extracellular matrix functions to support cell growth and differentiation into desired tissues. We described the preparation and characterization of a 3D hybrid model for bone tissue engineering that comprises an extracellular matrix (ECM)-enriched hydrogel embedded in a PCL scaffold. The human bone marrow-derived mesenchymal stem cell–derived matrisome (BMTS) was utilized as a source of ECM-enriched biomacromolecules, and scaffold biocompatibility was evaluated in vitro using human bone marrow-derived mesenchymal stem cells (BM-MSCs). The 3D hybrid model exhibited excellent BM-MSC viability and osteogenic activity in vitro in both two-dimensional (2D) and 3D cultures. Furthermore, bone remodeling was evaluated by in vivo through a rat calvarial defect model; notably, the fabricated 3D hybrid model effectively enhanced vascularized bone regeneration. Therefore, this promising BMTS-based 3D hybrid model might serve as an excellent bone tissue-engineered scaffold for use in orthopedic applications.

The purpose of this study was to explore the mothering experiences of children with disabilities. The theory of ambiguous loss was applied to interpret the meanings that mothers give to the process of caregiving and the ways they stay proactive in the midst of challenges. Eleven mothers of children ages 6 to 35 with various disabilities participated in in-depth interviews to talk about their child’s educational history, their family’s routine, and the rewards and challenges of raising a child with disabilities. Findings illustrate that the mothers faced different experiences of ambiguity depending on the visible or invisible nature of their child’s disabilities. However, regardless of the nature of the disabilities, the mothers had learned to live with ambiguity in the face of new and continuous challenges. They did this by redefining their lives through maintaining valued identities as mothers and redefining the meaning of family. Findings also imply that the scope of ambiguous loss needs to be expanded.

The liver plays important roles in drug metabolism and homeostasis. The metabolism and biotransformation can not only affect the efficacy of drugs but also result in hepatotoxicity and drug-induced liver injury. Understanding the complex physiology of the liver and the pathogenetic mechanisms of liver diseases is essential for drug development. Conventional in vitro models have limitations in the ability to predict drug effects, due to the lack of physiological relevance. Recently, the liver-on-a-chip platform has been developed to reproduce the microarchitecture and in vivo environment of the liver. These efforts have improved the physiological relevance of the liver tissue used in the platform and have demonstrated its applicability to drug screening and disease models. In this review, we summarize the recent development of liver-on-a-chip models that closely mimic the in vivo liver environments and liver diseases.

Cartilage is a connective tissue that constitutes the structure of the body and consists of chondrocytes that produce considerable collagenous extracellular matrix and plentiful ground substances, such as proteoglycan and elastin fibers. Self-repair is difficult when the cartilage is damaged because of insufficient blood supply, low cellularity, and limited progenitor cell numbers. Therefore, three-dimensional (3D) culture systems, including pellet culture, hanging droplets, liquid overlays, self-injury, and spinner culture, have attracted attention. In particular, 3D spheroid culture strategies can enhance the yield of exosome production of mesenchymal stem cells (MSCs) when compared to two-dimensional culture, and can improve cellular restorative function by enhancing the paracrine effects of MSCs. Exosomes are membrane-bound extracellular vesicles, which are intercellular communication systems that carry RNAs and proteins. Information transfer affects the phenotype of recipient cells. MSC-derived exosomes can facilitate cartilage repair by promoting chondrogenic differentiation and proliferation. In this article, we reviewed recent major advances in the application of 3D culture techniques, cartilage regeneration with stem cells using 3D spheroid culture system, the effect of exosomes on chondrogenic differentiation, and chondrogenic-specific markers related to stem cell derived exosomes. Furthermore, the utilization of MSC-derived exosomes to enhance chondrogenic differentiation for osteoarthritis is discussed. If more mechanistic studies at the molecular level are conducted, MSC-spheroid-derived exosomes will supply a better therapeutic option to improve osteoarthritis.

Glioblastomas may develop de novo or through progression from low-grade or anaplastic astrocytomas. The term ‘primary glioblastoma’ refers to a glioblastoma that lacks a precursor lesion and has a clinical history of less than three months. On the other hand, the term ‘secondary glioblastoma’ indicates that the glioblastoma has progressed from a low-grade tumor after a long latency period and often manifests in younger patients. These subtypes of glioblastoma develop via different genetic pathways, and they differ in prognosis and response to therapy. Thus, differential diagnosis of these subtypes and prediction of the factors that affect the progression from low-grade diffuse astrocytoma to secondary glioblastoma would be clinically very important. We present a rare case of secondary glioblastoma, which developed only three months after the follow up imaging evaluations, with a history of low grade glioma, and present the factors that cause rapid progression.

Fibrous hamartoma of infancy (FHI) is a rare, benign subcutaneous tumor occurring mainly before the age of 2 years. The most commonly reported locations of FHI are the extremities such as the shoulder or axilla. However, FHI arising in the genital area is extremely rare and has not been reported with correlated radiologic findings. In this case report, we present a case of 5-month-old male child diagnosed with FHI in the scrotum, with a focus on the correlation between the radiologic and pathologic findings.

ABSTRACT Objective: To investigate the safety and efficacy of allogeneic platelet-rich plasma (PRP) in rotator cuff repair . Methods: Seventeen patients with a full-thickness rotator cuff tear were included. Ten patients underwent arthroscopic rotator cuff repair with allogeneic, and seven patients with autologous PRP. Three PRP gels in a volume 3 ml each were applied between the torn end and the greater tuberosity. Clinical outcomes were assessed preoperatively and at a minimum of 2 years after surgery. Structural outcomes were evaluated with the presence of retear and the change of the cross-sectional area (ACT) of the supraspinatus . Results: Allogeneic PRP did not cause any adverse events during the follow-up period. There was no significant difference in the clinical outcome measures between the two groups (all p > 0.05). The retear rate was 33.3% and 25.0% in the allogeneic group and autologous group, respectively (p = 0.764). The change between the one-year postoperative and immediately postoperative ACT was not also significantly different between the two groups (p = 0.373) . Conclusion: Allogeneic PRP in arthroscopic rotator cuff did not cause any local or general complications and that has the efficacy comparable to autologous PRP with respect to the clinical and structural outcomes. Level of Evidence III, Retrospective Comparative Study.

Chondroblastomas are rare benign cartilaginous neoplasms found in young patients. These tumors typically arise in the epiphysis or apophysis of a long bone. Chondroblastomas arising in the skull and facial bones are extremely rare. We describe a rare case of a patient presenting with chondroblastoma with secondary aneurysmal bone cyst in the sphenoid sinus that mimicked invasive sinusitis or malignant bone tumor.

Polycystic ovary syndrome (PCOS) is an endocrinal disorder that afflicts mainly women of childbearing age. The symptoms of PCOS are irregular menstrual cycles, weight gain, subfertility and infertility. However, because the etiology is unclear, management and treatment methods for PCOS are not well established. Recently, natural substances have been used for PCOS therapy. Ecklonia cava (E. cava) is a well-known natural substance that attenuates the effects of inflammation, allergies, and cancer. In this study, we investigated the effects of E. cava extract in rats with PCOS. When rats with letrozole-induced PCOS were exposed to the E. cava extract, the regular estrus cycle was restored, similar to that in placebo rats. Hormone levels, including the levels of testosterone, estrogen, luteinizing hormone (LH), follicle stimulating hormone (FSH), and anti-Müllerian hormone (AMH), were restored to their normal states. Histological analysis revealed that the polycystic ovary symptoms were significantly decreased in the E. cava-treated rats and were comparable to those of normal ovaries. At the transcriptional and translational levels, Ar, and Esr2 levels were markedly increased in the E. cava-treated rats with PCOS compared with the rats with letrozole-induced PCOS. These results suggest that the E. cava extract inhibits the symptoms of PCOS by restoring imbalanced hormonal levels and irregular ovarian cycles in letrozole-induced female rats.

In 2015, programmatic accreditation by the Commission on Accreditation of Allied Health Education Programs (CAAHEP) was initiated for art therapy education. The study examined art therapy faculty's perception of the CAAHEP accreditation process through a nation-wide online survey research. The mixed-method analysis supports the complexity of the current art therapy programmatic accreditation as perceived by faculty. Three main themes were identified: (1) accreditation as accountability, (2) additional burden and time-consuming, and (3) limited support and skill mismatch. The findings suggest that programmatic accreditation brings both benefits and challenges while also supporting the development of quality accreditation procedures for art therapy education.

This pilot study examined the effectiveness of a 4-month clinic-based dietary intervention emphasizing the intake of deep yellow and dark green vegetables versus usual care on improving diet quality in postpartum women. The intervention group (n = 31) received 1 face-to-face nutrition education session with a registered dietitian, 2 follow-up phone calls, and 3 pamphlets distributed by mail. The usual care group (n = 25) received handouts with guidelines on healthy eating. Dietary outcomes were assessed from 3-day food recalls and evaluated using paired and independent t tests. Intervention women exhibited a significant increase in total vegetable intake ( P < .001) and in dark green and deep yellow vegetables ( P < .001). In comparison, the control group increased the intake of total vegetables ( P < .001), but did not increase the consumption of dark green and deep yellow vegetables. When comparing the change in intake between study groups for both types of vegetables, the difference was not significant. Furthermore, 61% of the intervention women met the goals for total vegetable intake compared with 12% for the usual care group ( P < .001). The intervention group also had a greater percentage of women (25.8%) that met the goal for deep yellow and dark green vegetable intake when compared with the usual care group (8%; P < .08). These results suggest that postpartum women are receptive to nutrition education and that nutrition education can influence vegetable intake.

Background/aims Age-related macular degeneration (AMD) and cancer may share similar risk factors, indicating possible common pathogenic pathways. We aimed to describe the site-specific cancer risk based on the relationship of AMD with visual disability (VD) status. Methods This was a population-based cohort study using data from the Korean National Health Insurance Service database (2009-2019) including patients who participated in a national health screening programme in 2009. The subjects were categorised based on the presence of AMD and VD. The occurrence of cancer was identified using principal diagnosis according to the International Classification of Disease, 10th revision codes in claims data. The Cox regression hazard model was used to compare HRs of site-specific cancer. Results Among 4 088 814 participants, 51 596 had AMD of which 3683 subjects had VD. The mean follow-up period was 9.6 years. The overall cancer risk was generally null, but the risk of hypervascular cancer such as thyroid cancer (adjusted HR (aHR) 1.10, 95% CI 1.00 to 1.20) and renal cancer (aHR 1.16, 95% CI 1.00 to 1.33) was higher and the risk of stomach cancer (aHR 0.89, 95% CI 0.84 to 0.94) was lower in the AMD group than in the non-AMD group. Conclusion This study demonstrated a possible association between AMD and several cancers. Increased renal and thyroid cancer risk among patients with AMD could indicate that AMD is associated with hypervascular cancer. Further studies in which additional databases are used and the underlying detailed mechanisms evaluated are needed to validate our Results. [ABSTRACT FROM AUTHOR]