BACKGROUND: Skeletal muscles play many important roles in the human body and any malfunction or disorder of the skeletal muscles can lead to a reduced quality of life. Some skeletal dysfunctions are acquired, such as sarcopenia but others are congenital. Duchenne muscular dystrophy (DMD) is one of the most common forms of hereditary muscular dystrophy and is caused by a deficiency of the protein, Dystrophin. Currently, there is no clear treatment for DMD, there are only methods that can alleviate the symptoms of the disease. Mesenchymal stem cells, including tonsil-derived mesenchymal stem cells (TMSCs) have been shown to differentiate into skeletal muscle cells (TMSC-myocyte) and can be one of the resources for the treatment of DMD. Skeletal muscle cell characteristics of TMSC-myocytes have been confirmed through changes in morphology and expression of skeletal muscle markers such as Myogenin, Myf6, and MYH families after differentiation.MEOTHDS: Based on these characteristics, TMSC-myocytes have been transplanted into mdx mice, a mouse model of DMD, to investigate whether they can help improve the symptoms of DMD. The red fluorescent protein gene was transduced into TMSC (TMSC-R) for tracking transplanted cells. RESULTS: Prior to transplantation (TP), it was confirmed whether TMSC-R-myocytes had the same differentiation potential as TMSC-myocytes. Increased expression of dystrophin and autophagy markers in the TP group compared with the sham group was confirmed in the gastrocnemius muscle 12 weeks after TP. CONCLUSION These results demonstrate muscle regeneration and functional recovery of mdx via autophagy activation following TMSC-myocyte TP.

Since sarcomatoid carcinoma in the common bile duct (CBD) is rarely reported, the clinical course and prognosis after surgery are unclear. We report a case of a patient who died within 1 month after surgery due to rapid tumor progression. A 65-year-old woman had abdominal pain with jaundice. She was diagnosed with CBD cancer and underwent pancreatoduodenectomy. Pathologic examination revealed sarcomatoid carcinoma. There was no postoperative complication, but multiple liver metastasis was diagnosed on computed tomography at 7 days after surgery. Also, the patient complained of abdominal pain and had jaundice with elevated liver enzyme on the 14th postoperative day. Her general condition was getting worse and she died of hepatic failure 23 days after surgery. We report a case of sarcomatoid carcinoma of the CBD that progressed very rapidly. Further research and case reports are needed to establish proper diagnostic and treatment tools.
Abdominal Pain ; Aged ; Carcinosarcoma ; Common Bile Duct ; Female ; Humans ; Jaundice ; Liver ; Liver Failure ; Neoplasm Metastasis ; Pancreaticoduodenectomy ; Postoperative Complications ; Prognosis

Background: The pathogenesis and development of autoimmune diseases are associated with alteration of hormone levels. The effects of menopausal hormone therapy (MHT) on Behcet’s disease (BD) are unclear. Objective: We hypothesized that MHT would increase the risk of BD in postmenopausal women due to the central role of immunomodulation of estrogen and other sex hormones in autoimmune diseases. Methods: We analyzed data from the Korean National Health Insurance Service database and investigated the relationship between MHT and the risk of BD in postmenopausal women with BD. The study included 220,663 patients who received MHT and 1,170,566 who did not. The hazard ratio (HR) of BD was measured in all subjects.Statistical analyses were utilized with adjustments for possible confounding factors such as age, body mass index, smoking, alcohol consumption, physical activity, income, diabetes, hypertension, dyslipidemia, age at menarche (group), age at menopause (group), parity, breastfeeding, and oral contraceptive use. Results: After adjusting for confounding factors, the participants with a history of MHT had a higher risk of BD (MHT＜2 years, HR=1.459, 95% confidence interval [95% CI]=1.29∼1.649; MHT＞2 and ＜5 years, HR=1.512, 95% CI=1.265∼1.808; MHT≥5 years, HR=2.045, 95% CI=1.708∼2.447). Conclusion The findings demonstrate that MHT is associated with an increased risk of BD in postmenopausal women, indicating that estrogen plays an important role in the disease activity of BD. However, additional studies are needed to confirm these findings.

Background: The pathogenesis and development of autoimmune diseases are associated with alteration of hormone levels. The effects of menopausal hormone therapy (MHT) on Behcet’s disease (BD) are unclear. Objective: We hypothesized that MHT would increase the risk of BD in postmenopausal women due to the central role of immunomodulation of estrogen and other sex hormones in autoimmune diseases. Methods: We analyzed data from the Korean National Health Insurance Service database and investigated the relationship between MHT and the risk of BD in postmenopausal women with BD. The study included 220,663 patients who received MHT and 1,170,566 who did not. The hazard ratio (HR) of BD was measured in all subjects.Statistical analyses were utilized with adjustments for possible confounding factors such as age, body mass index, smoking, alcohol consumption, physical activity, income, diabetes, hypertension, dyslipidemia, age at menarche (group), age at menopause (group), parity, breastfeeding, and oral contraceptive use. Results: After adjusting for confounding factors, the participants with a history of MHT had a higher risk of BD (MHT＜2 years, HR=1.459, 95% confidence interval [95% CI]=1.29∼1.649; MHT＞2 and ＜5 years, HR=1.512, 95% CI=1.265∼1.808; MHT≥5 years, HR=2.045, 95% CI=1.708∼2.447). Conclusion The findings demonstrate that MHT is associated with an increased risk of BD in postmenopausal women, indicating that estrogen plays an important role in the disease activity of BD. However, additional studies are needed to confirm these findings.

Background: The pathogenesis and development of autoimmune diseases are associated with alteration of hormone levels. The effects of menopausal hormone therapy (MHT) on Behcet’s disease (BD) are unclear. Objective: We hypothesized that MHT would increase the risk of BD in postmenopausal women due to the central role of immunomodulation of estrogen and other sex hormones in autoimmune diseases. Methods: We analyzed data from the Korean National Health Insurance Service database and investigated the relationship between MHT and the risk of BD in postmenopausal women with BD. The study included 220,663 patients who received MHT and 1,170,566 who did not. The hazard ratio (HR) of BD was measured in all subjects.Statistical analyses were utilized with adjustments for possible confounding factors such as age, body mass index, smoking, alcohol consumption, physical activity, income, diabetes, hypertension, dyslipidemia, age at menarche (group), age at menopause (group), parity, breastfeeding, and oral contraceptive use. Results: After adjusting for confounding factors, the participants with a history of MHT had a higher risk of BD (MHT＜2 years, HR=1.459, 95% confidence interval [95% CI]=1.29∼1.649; MHT＞2 and ＜5 years, HR=1.512, 95% CI=1.265∼1.808; MHT≥5 years, HR=2.045, 95% CI=1.708∼2.447). Conclusion The findings demonstrate that MHT is associated with an increased risk of BD in postmenopausal women, indicating that estrogen plays an important role in the disease activity of BD. However, additional studies are needed to confirm these findings.

Background: The pathogenesis and development of autoimmune diseases are associated with alteration of hormone levels. The effects of menopausal hormone therapy (MHT) on Behcet’s disease (BD) are unclear. Objective: We hypothesized that MHT would increase the risk of BD in postmenopausal women due to the central role of immunomodulation of estrogen and other sex hormones in autoimmune diseases. Methods: We analyzed data from the Korean National Health Insurance Service database and investigated the relationship between MHT and the risk of BD in postmenopausal women with BD. The study included 220,663 patients who received MHT and 1,170,566 who did not. The hazard ratio (HR) of BD was measured in all subjects.Statistical analyses were utilized with adjustments for possible confounding factors such as age, body mass index, smoking, alcohol consumption, physical activity, income, diabetes, hypertension, dyslipidemia, age at menarche (group), age at menopause (group), parity, breastfeeding, and oral contraceptive use. Results: After adjusting for confounding factors, the participants with a history of MHT had a higher risk of BD (MHT＜2 years, HR=1.459, 95% confidence interval [95% CI]=1.29∼1.649; MHT＞2 and ＜5 years, HR=1.512, 95% CI=1.265∼1.808; MHT≥5 years, HR=2.045, 95% CI=1.708∼2.447). Conclusion The findings demonstrate that MHT is associated with an increased risk of BD in postmenopausal women, indicating that estrogen plays an important role in the disease activity of BD. However, additional studies are needed to confirm these findings.

The Pfizer-BioNTech COVID-19 vaccine has shown excellent clinical effectiveness; however, adverse events of the vaccine remain a concern in Korea. We surveyed adverse events in 2498 healthcare workers vaccinated with the Pfizer-BioNTech COVID-19 vaccine at a university hospital. The survey was conducted using a diary card for 7 days following each injection. The questionnaire response rate was 75.1% (1876/2498) for the first dose and 73.8% (1840/2493) for the second dose. Among local reactions, pain was the most commonly reported (84.9% after the first dose and 90.4% after the second dose). After the second dose, two people visited the emergency room due to severe local pain, but no hospitalization or skin necrosis occurred. Among systemic reactions, fatigue was most frequently reported (52.8% after the first dose and 77.0% after the second dose), followed by myalgia (49.0% and 76.1%), headache (28.7% and 59.2%), chills (16.7% and 54.0%), and arthralgia (11.4% and 39.2%). One or more critical adverse events occurred in 0.2% and 0.7% of the vaccinees. Except for urticaria, more adverse events were reported after the second dose than after the first dose. In the future, adverse events should be investigated in older adults, and a future study with a longer observation period should be conducted.

BACKGROUND: The aim of this study was to assess the feasibility of targeted ultrasound imaging on apoptosis with annexin A5 microbubbles (A5MB) in acute doxorubicin-induced cardiotoxicity. METHODS: Avidinated and octafluoropropan-filled phospholipid microbubbles were conjugated with biotinylated annexin A5. To confirm the specific binding of A5MB, flow cytometry was performed with hydrogen peroxide induced apoptosis in rat aorta smooth muscle cells incubated with fluorescein-5-isothiocyanate (FITC) labeled annexin A5 and A5MB. Adult male rats were injected intraperitoneally with 5 mg/kg doxorubicin weekly for 3 weeks (n = 5). Control rats were injected with normal saline (n = 5). At 24 hours after the final treatment, triggering imaging was performed 15 min after an intravenous bolus injection of A5MB for washout of freely circulating microbubbles. After echocardiography, the heart was isolated for histological detection of apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. RESULTS: In the in vitro tests, fluorescence intensity was low for healthy cells and high for apoptotic cells when incubated with FITC-labeled annexin A5 and A5MB. Rats treated with doxorubicin showed significant contrast opacification of the myocardium on contrast echocardiography using A5MB. However, no opacification was observed in control rats. Apoptosis was confirmed by TUNEL assay in doxorubicin treated rats. CONCLUSION: Acute doxorubicin-induced cardiomyopathy based on early apoptosis can be assessed and imaged with targeted ultrasound imaging using A5MB in rats.
Adult ; Animals ; Annexin A5 ; Aorta ; Apoptosis ; Avidin ; Cardiomyopathies ; Doxorubicin ; Echocardiography ; Flow Cytometry ; Fluorescein-5-isothiocyanate ; Fluorescence ; Heart ; Humans ; Hydrogen Peroxide ; In Situ Nick-End Labeling ; Male ; Microbubbles ; Myocardium ; Myocytes, Smooth Muscle ; Rats

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. METHODS: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. RESULTS: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. CONCLUSIONS: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.
Biomarkers ; Classification ; Humans ; Immunohistochemistry ; Keratin-19* ; Multivariate Analysis ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Pancreas ; Prognosis ; Survival Rate ; World Health Organization

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. METHODS: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival. RESULTS: PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses. CONCLUSIONS: Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.
Carcinogenesis* ; Classification ; Disease-Free Survival ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Pancreas ; Pancreatic Neoplasms ; Progesterone* ; Prognosis ; Receptors, Progesterone* ; Survival Rate ; Telomere ; World Health Organization