The proliferation and migration of vascular smooth muscle cells (VSMCs) are key contributors to the development of atherosclerosis and restenosis. We investigated the impact of rosuvastatin (RSV) on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, with a focus on the Akt/mTORautophagy signaling pathways. The cytotoxicity of RSV was assessed using MTT and annexin V staining, while the proliferation and migration capabilities of PDGF-BBinduced VSMCs were evaluated using MTT and cell migration assays. Confocal microscopy was employed to examine autophagic cell images, and protein expressions were analyzed via Western blotting. Our key findings revealed that RSV inhibited PDGF-BB-induced proliferation and migration of VSMCs, significantly reducing the expression of proliferating cell nuclear antigen and matrix metalloproteinase-2, which are crucial for these processes. RSV also enhanced autophagy in PDGF-BBstimulated cells by inducing the maturation of microtubule-associated protein light chain 3 and increasing the expression of Beclin-1, autophagy related (Atg)3, Atg5, and Atg7. The regulatory effects of RSV on PDGF-BB-induced autophagy, proliferation, and migration were associated with the suppression of the Akt/mTOR signaling pathway. These findings suggest that RSV may have potential therapeutic benefits in preventing and treating vascular diseases by targeting the Akt/mTOR pathway and inducing autophagy.

BACKGROUND: Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture. METHODS: This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DWMSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts. RESULTS: Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring. CONCLUSION Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.

Objective: This study aims to objectively evaluate turning gait parameters in Parkinson’s disease (PD) patients using 2D-RGB video-based analysis and explore their relationships with imbalance. Methods: We prospectively enrolled PD patients for clinical assessment, balance analysis and gait with 180º turning. Spatiotemporal gait parameters during turning were derived using video-based analysis and correlated with modified Hoehn and Yahr (mHY) stages and center of pressure (COP) oscillations. Results: A total of 64 PD patients were enrolled. The PD patients with higher mHY stages (≥2.5) had significantly longer turning times, greater numbers of steps, wider step bases and less variability in step length during turns. COP oscillations were positively correlated with the mean turning time on both the anterior-posterior and right-left axes. Conclusion Spatiotemporal gait parameter during turning, derived from video-based gait analysis, may represent apromising biomarker for monitoring postural instability in PD patients.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

The application area of biportal endoscopic spine surgery (BESS) is gradually expanding. Compared with conventional fusion surgery, transforaminal interbody fusion (TLIF) using BESS (BESS-TLIF) has the advantages of less bleeding, minimal postoperative pain, and faster recovery. This technical note highlights its application in managing complex conditions such as scar tissue adhesion, altered anatomy, and implant removal, common in reoperations. The method focuses on precise dissection, endoscopic visualization, and careful tissue handling to ensure effective decompression and stabilization. Three representative cases, including reoperations for recurrent disc herniation, adjacent segment disease (ASD) following prior fusion, and ASD with nonunion of the prior fusion site requiring fusion extension, were described. All three cases exhibited clinical improvement following surgery. BESS is an effective and safe method for spinal revision surgery not only in simple decompression surgery but also in cases that required fusion surgery. As BESS is advancing, its role in complex spinal surgeries is expected to expand, potentially setting new standards in minimally invasive spine surgery.

This study introduces a novel biportal endoscopic foraminal decompression technique that minimizes bone removal while ensuring safe and effective nerve root decompression. Leveraging the accessory process as a key surgical landmark, this technique enables precise navigation and controlled turn-down of the ligamentum flavum (LF). A key advantage of this technique is its reduced requirement for bone resection, differing from traditional microscopic or uniportal endoscopic surgeries that often necessitate resection of the lateral isthmus or superior articular process. This technique is particularly beneficial for foraminal and extraforaminal herniated nucleus pulposus cases, where bony decompression needs are relatively lower compared to foraminal stenosis. Using the accessory process as a landmark also enhances surgical precision and reduces the risk of nerve root injury, providing a valuable advantage for less experienced surgeons. Despite these advantages, challenges exist, particularly at the L5–S1 level, where the less prominent accessory process and limited workspace due to anatomical constraints can pose difficulties. In cases of severe bony compression, additional bone removal may be necessary to achieve adequate decompression. In conclusion, the Non-facetectomy LF turn-down technique (non-facetectomy foraminal decompression) offers a safe and effective minimally invasive alternative for treating various foraminal pathologies.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Purpose: Lupus nephritis (LN) can be caused by the complement activation. This study aimed to investigate the differences and clinical implications of the activation pattern of the complement system for pediatric and adult LN patients. Methods: We retrospectively reviewed the medical records of 40 patients (14 pediatric and 26 adult patients) diagnosed with LN through kidney biopsy. Results: The mean ages at diagnosis of pediatric and adult patients were 11.7±2.92 and 37.3±13.5 years, respectively. At the first LN diagnosis, compared with adult patients, pediatric patients had a higher estimated glomerular filtration rate and milder proteinuria; however, there was no statistical significance. The age-adjusted mean serum complement 3 value was significantly lower in the pediatric group (33.0±11.3 mg/dL) than in the adult group (50.8±25.2 mg/dL) (P<0.01). Based on the findings of kidney biopsy, no significant differences were observed in the severity of pathologic classification and the positive rate of complements between adults and children. However, the chronicity index score of adult patients was significantly higher than that of pediatric patients and in the case of complement 4d, despite a similar positive rate, the intensity was significantly stronger for adults (2.35±0.83 vs. 1.54±0.52, (P=0.04). Conclusions The activation pattern of the complement system in LN differs clinicopathologically between pediatric and adult patients and these differences might play an important role in the age-dependent prognosis of LN.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.