Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Lipomas, the most common soft-tissue mesenchymal neoplasms in adults, are characterized by the proliferation of mature white adipocytes without cytologic atypia. Lipomas are rarely observed in the head and neck region. We present a case of resection and orthognathic surgical removal of an intramuscular lipoma of the mandible with involvement of the mandibular ramus and condylar head and neck. An 18-year-old female patient was referred to our hospital for orthognathic surgery for the management of facial asymmetry and mandibular prognathism. The patient did not present with facial swelling, pain, or temporomandibular dysfunction; however, on radiographic examination, including cone-beam computed tomography and magnetic resonance imaging, an infiltrative fatty lesion was observed in the masticator space inside the right mandible, and the adjacent mandible exhibited bone thinning and deformity. Resection of the lipoma was performed along with orthognathic surgery, including a Le Fort I osteotomy for the maxilla and bilateral sagittal split ramus osteotomy (BSSRO). In this case, because the ramus was split using BSSRO, accessing the lipoma intraorally was easy.Consequently, aesthetic scarring was avoided, and no complications, such as unfavorable splitting or pathologic fracture, occurred. Although recurrence has not been observed about 1 year, long-term follow-up should be performed.

BACKGROUND: Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes. CDNs exhibit structural, physical, and biological properties similar to exosomes, containing intracellular protein and genetic components encapsulated by the cell plasma membrane. These characteristics allow CDNs to be used as regenerative medicine and therapeutics on their own, or as a drug delivery system. METHODS: The paper reviews diverse methods for CDN synthesis, current analysis techniques, and presents engineering strategies to improve lesion targeting efficiency and/or therapeutic efficacy. RESULTS: CDNs, with their properties similar to those of exosomes, offer a cost-effective and highly productive alternative due to their non-living biomaterial nature, nano-size, and readiness for use, allowing them to overcome several limitations of conventional cell therapy methods. CONCLUSION Ongoing research and enhancement of CDNs engineering, along with comprehensive safety assessments and stability analysis, exhibit vast potential to advance regenerative medicine by enabling the development of efficient therapeutic interventions.

Patellofemoral joint problems refer to a spectrum of conditions affecting the patellofemoral joint, which is the joint between the patella and femur. These conditions can cause pain and instability in the knee and affect an individual’s ability to perform daily activities. Patellofemoral joint problems commonly cause knee pain, particularly among young athletes and physically active individuals. This review article discusses current patellofemoral joint problems, including their epidemiology, pathophysiology, diagnosis, and management.Current Concepts: Patellofemoral joint problems are presented as clinical symptoms of pain and instability. Dividing the diagnostic criteria into anterior knee pain, patella instability, and patellofemoral arthritis is useful. Anterior knee pain is diagnosed after excluding possible causes. Patellar instability is classified into recurrent dislocation, habitual dislocation (extension and flexion types), and permanent dislocation. Moreover, patellar instability can progress to the final stage of patellofemoral arthritis. Thus, patellar instability should be treated according to the Dejour criterion, and patellofemoral arthritis treatment requires artificial joint replacement surgery.Discussion and Conclusion: The pathological mechanism of patellofemoral joint problems still needs to be properly established, and multifactorial causes make it difficult to treat patellofemoral joint problems. Accurate diagnosis is considered an essential factor for successful treatment.

Background: Many people with a longer second toe or lesser toes experience symptoms such as corns, hammertoe, and numerous others, especially when wearing open-toe shoes. Proximal interphalangeal joint arthrodesis using intraosseous loop wiring performed through a hidden side incision is a useful method to shorten the lesser toes aesthetically. Methods: Aesthetic toe-shortening procedures were performed in 30 patients. All patients were evaluated by a physical examination and X-rays, and they underwent proximal interphalangeal joint arthrodesis using intraosseous loop wiring through a medial incision. Demographic characteristics, including foot morphology, were analyzed. The number of resected toes and resection amounts of each toe were measured. Patients’ satisfaction was determined through a questionnaire administered at each follow-up. Results: In total, 91 toe-shortening procedures were performed in 30 patients who were followed up for an average of 24 months (range, 6–48 months). Sixteen patients had Greek-type feet (53.3%) and 14 had square-type feet (46.7%). Twelve patients had hammer toe deformity (40.0%) and 13 had corns (43.3%). The average length of the resected second and third toes was 9.66±2.79 mm (range, 5–15 mm) and 7.78±2.51 mm (range, 5–12 mm), respectively. The vast majority of patients were satisfied with the final results. No significant complications such as nonunion occurred. Only one case of mild angulation of the second toe was noted. Conclusions Aesthetic toe-shortening using the procedure described here can prevent the development of lessor toe deformities and provide permanent, aesthetically pleasing results with a short recovery time.

Atopic dermatitis (AD) is one of the most prevalent inflammatory skin diseases that is characterized by eczematous rashes, intense itching, dry skin, and sensitive skin. Although AD significantly impacts the quality of life and the number of patients keeps increasing, its pathological mechanism is still unknown because of its complexity. The importance of developing new in vitro three-dimensional (3D) models has been underlined in order to understand the mechanisms for the development of therapeutics since the limitations of 2D models or animal models have been repeatedly reported. Thus, the new in vitro AD models should not only be created in 3D structure, but also reflect the pathological characteristics of AD, which are known to be associated with Th2-mediated inflammatory responses, epidermal barrier disruption, increased dermal T-cell infiltration, filaggrin down-regulation, or microbial imbalance. In this review, we introduce various types of in vitro skin models including 3D culture methods, skin-on-a-chips, and skin organoids, as well as their applications to AD modeling for drug screening and mechanistic studies.

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive muta-tions initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resis-tance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunc-tion, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

Background: Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas. Methods: This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis. Results: In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively). Conclusions There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.

Mitotane is an adrenolytic drug that exhibits therapeutic effects within a narrow target range (14–20 μg/dL). Various complications develop if the upper limit is exceeded. We present the case of a 5-year-old girl with breast development, acne, and pubic hair who was diagnosed with an adrenal mass that was subsequently excised. The pathological finding was adrenocortical carcinoma with a high risk of malignancy, and adjuvant therapy (combined mitotane and radiation therapy) was recommended. Mitotane was initiated at a low dose to allow monitoring of the therapeutic drug level, and high-dose hydrocortisone was also administered. However, the patient exhibited elevated adrenocorticotropic hormone levels and vague symptoms such as general weakness and difficulty concentrating. It was important to determine if these symptoms were signs of the neurological complications that develop when mitotane level is elevated. Encephalopathy progression and pubertal signs appeared 6 months after diagnosis, induced by high mitotane level. The mitotane decreased to subtherapeutic level several months after its discontinuation, at which time endocrinopathy (central hypothyroidism, hypercholesterolemia, and secondary central precocious puberty) developed. The case shows that low-dose mitotane can trigger neurological and endocrinological complications in a pediatric patient, indicating that the drug dose should be individualized with frequent monitoring of the therapeutic level.

BACKGROUND/OBJECTIVES: Hydrolyzed formula is often fed to infants with gastrointestinal or immune issues, such as malabsorption or cow's milk allergy, because enzymatic treatment has rendered it more digestible and less allergenic than standard cow's milk formula (SF). Partially hydrolyzed formula (PHF) should be considered for those infants who are intolerant to extensively hydrolyzed formula. However, there are concerns about the nutritional insufficiencies of PHF. We aimed to evaluate the effects of PHF on the growth and health indicators in infants who were at high-risk of allergic disease and potential candidates for consuming PHF. SUBJECTS/METHODS: A total of 83 infants aged 0–2 mon with a family history of allergies were assigned to consume either PHF or SF until 24 weeks of age. Anthropometric measures were obtained at baseline, 12 weeks, and 24 weeks; blood samples were drawn and evaluated at the end of the study. RESULTS: No significant differences were observed in weight, height, and weight-for-height at any time point in each sex between the PHF and SF groups. At 24 weeks of age, the weightfor-age and height-for-age z-scores of the SF group were higher than those of the PHF group, but there was no significant difference in the weight-for-height z-score. There were no significant differences in levels of white blood cells, hemoglobin, ferritin, protein, albumin, aspartate aminotransferase, alanine aminotransferase, eosinophil cationic protein, and immunoglobulin E. CONCLUSIONS In this study, there were no differences in growth and blood panels between the infants consuming PHF or SF. Therefore, infants who are unable to tolerate SF can be fed PHF without nutritional concerns about growth.