Rotator cuff tears are common shoulder injuries, particularly in older adults. Arthroscopic rotator cuff repair (ARCR) is the preferred treatment due to its successful outcomes, but complications like suture knot impingement may arise.Knot impingement, although rare, can lead to subacromial bone erosion and persistent pain. The condition remains under-reported, and direct evidence linking knot impingement to subacromial erosion is scarce. A 63-year-old woman presented with progressively worsening shoulder pain and restricted range of motion, 10 years after undergoing ARCR. Clinical assessment indicated subacromial impingement with positive Neer, Hawkins test results and reduced shoulder mobility. Arthroscopic evaluation revealed suture knots embedded in the subacromial bone, directly causing erosion. This is the first case to confirm through arthroscopy that subacromial bone erosion resulted from knot impingement. This case emphasizes the importance of follow-up and highlights the need to consider alternative suture techniques to avoid complications like knot impingement. Surgeons should be vigilant in minimizing risks associated with suture materials and techniques to improve long-term outcomes for patients undergoing ARCR.

Purpose: Precise control of proliferation and differentiation of Leydig cells is important for gonadal androgenesis and spermatogenesis. Though cyclin-dependent kinase inhibitors are crucial for cell proliferation and differentiation, their role in the development of early adult Leydig cells (ALCs) remained unanswered. To understand mechanism for ALC development, functional expression of p57KIP2 (cdkn1c) was investigated in the stem Leydig cells (SLCs) and progenitor Leydig cells (PLCs) in mice. Materials and Methods: The roles of p57KIP2 in the proliferation, differentiation, apoptosis, and steroidogenesis in SLCs and PLCs were investigated by antibodies and bromodeoxyuridine (BrdU) labeling in the early neonatal testes and p57kip2 siRNA in the isolated SLCs and PLCs. Steroidogenic differentiation of PLCs was examined by progesterone and testosterone production in cell culture. Results: From postnatal day (PND) 1 to 14, p57KIP2(+) spindle-shaped cells in the testis interstitium were α-smooth muscle actin (αSMA)(-), a peritubular myoid cells marker, suggesting that they are SLCs and PLCs. Besides, p57KIP2 was also expressed in HSD3β(+) fetal Leydig cells. From PND1 to 14, BrdU(+)/αSMA(-), Ki67(+)/p57KIP2(+), and BrdU(+)/p57KIP2(+) spindle-shaped cells were gradually decreased. From PND1 to 14, p57KIP in the αSMA(-)/p57KIP2(+) cells was peaked at PND7 and decreased thereafter. In THY1(+) isolated SLCs, p57kip2 siRNA significantly increased ki67 and pcna mRNA and pdgfrα mRNA, a differentiation marker and decreased nestin mRNA, a SLC marker. No significant difference in apoptosis related genes mRNA was found after p57kip2 siRNA treatment. In HSD3β(+) PLCs, p57kip2 siRNA increased proapoptotic genes mRNA, annexin V(+) early-apoptotic cells. Importantly, p57kip2 siRNA significantly decreased hsd3β6 and cyp17a1 mRNA and progesterone production. Conclusions p57KIP2 may suppress proliferation and support stemness of SLCs. In PLCs, p57KIP2 may suppress apoptosis and potentiate the steroidogenic differentiation.

Background: This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management. Methods: Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline. Results: Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%). Conclusion Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.

Background: s/Aims: In hepatocellular carcinoma (HCC), which exhibits high mortality and recurrence rates globally, the traits of cancer stem cells (CSCs) that significantly influence recurrence and metastasis are not well understood. CSCs are self-renewing cell types identified in most liquid and solid cancers, contributing to tumor initiation, growth, resistance, recurrence, and metastasis following chemo-radiotherapy or trans-arterial chemoembolization therapy. Methods: CSCs are classified based on the expression of cell surface markers such as CD133, which varies depending on the tumor type. Proteomic analysis of liver cancer cell lines with cancer stem cell potential and HCC cancer cell lines lacking stem cell propensity was conducted to compare and analyze specific expression patterns. Results: Proteomic profiling and enrichment analysis revealed higher expression of the calcium-binding protein S100 family in CD133+ Huh7 cells than in CD133- or wild-type cells. Furthermore, elevated expression of S100 family members was confirmed in an actual CD133+ liver cancer cell line via protein-protein network analysis and quantitative polymerase chain reaction (qPCR). Conclusion The S100 family members are not only new markers of cancer stem cells but will also assist in identifying new treatment strategies for CSC metastasis and tumor advancement.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Background/Aims: Rectal hyposensitivity (RH), as defined by the London Classification, has been linked to sensory dysfunction caused by diabetes mellitus and Parkinson’s disease (PD); however, its clinical interpretation has not been sufficiently validated. In this study, we aim to explore the correlations between rectal sensory thresholds and the clinical characteristics of patients with functional defecatory disorders. Methods: We reviewed data from patients who underwent high-resolution anorectal manometry and acquired their clinical characteristics using a standardized questionnaire. The associations between RH based on either 1 (borderline RH) or 2 (RH) abnormal rectal sensory thresholds and patients’ clinical and demographic characteristics were analyzed using linear and logistic regression models in the overall sex-stratified populations. Results: We enrolled 2540 patients, of whom 1046 (41.2%) were men. Overall, 150 (5.9%) patients were diagnosed with RH, whereas 422 (16.6%) had borderline RH. Multivariate linear regression analysis revealed that the Cleveland Clinic Constipation Score (CCCS) increased linearly with the increase in the number of abnormal rectal sensory thresholds (effect per threshold: 0.900 [standard deviation: 0.188]). Upon stratification by sex, borderline RH was positively associated with diabetes mellitus, PD, and CCCS (adjusted odds ratio [aOR] = 2.11, 95% confidence interval [1.08, 4.15]; aOR = 1.49 [1.03, 2.14]; aOR = 1.03 [1.01, 1.05], respectively) in women. However, RH was positively associated with only the CCCS. Conclusions Defining RH based on 1 or more abnormal sensory thresholds showed better clinical correlation with patient characteristics. However, further prospective studies are needed to validate these findings before proposing revisions to the current London classification criteria.

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.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

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: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.