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 FCSEMS 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.

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 FCSEMS 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.

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 FCSEMS 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.

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 FCSEMS 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.

Background: Recently, deep learning techniques have been used in medical imaging studies. We present an algorithm that measures radiologic parameters of distal radius fractures using a deep learning technique and compares the predicted parameters with those measured by an orthopedic hand surgeon. Methods: We collected anteroposterior (AP) and lateral X-ray images of 634 wrists in 624 patients with distal radius fractures treated conservatively with a follow-up of at least 2 months. We allocated 507 AP and 507 lateral images to the training set (80% of the images were used to train the model, and 20% were utilized for validation) and 127 AP and 127 lateral images to the test set. The margins of the radius and ulna were annotated for ground truth, and the scaphoid in the lateral views was annotated in the box configuration to determine the volar side of the images. Radius segmentation was performed using attention U-Net, and the volar/dorsal side was identified using a detection and classification model based on RetinaNet. The proposed algorithm measures the radial inclination, dorsal or volar tilt, and radial height by index axes and points from the segmented radius and ulna. Results: The segmentation model for the radius exhibited an accuracy of 99.98% and a Dice similarity coefficient (DSC) of 98.07% for AP images, and an accuracy of 99.75% and a DSC of 94.84% for lateral images. The segmentation model for the ulna showed an accuracy of 99.84% and a DSC of 96.48%. Based on the comparison of the radial inclinations measured by the algorithm and the manual method, the Pearson correlation coefficient was 0.952, and the intraclass correlation coefficient was 0.975. For dorsal/ volar tilt, the correlation coefficient was 0.940, and the intraclass correlation coefficient was 0.968. For radial height, it was 0.768 and 0.868, respectively. Conclusions The deep learning-based algorithm demonstrated excellent segmentation of the distal radius and ulna in AP and lateral radiographs of the wrist with distal radius fractures and afforded automatic measurements of radiologic parameters.

Background/Aims: This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. Methods: The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. Results: The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. Conclusions This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Gua Sha is a traditional Asian medicine with different names in many Asian countries. It is a treatment to scrape the petechiae of the skin with ointment. It has generally been administered to patients with upper respiratory infections, heat syndrome, and pain. Herein, we report the case of a 31-year-old Cambodian man who was found dead at a farm accommodation. During the autopsy, multiple linear intradermal hemorrhages without subcutaneous damage were observed in the upper chest and both shoulders. The cause of death was sudden unexpected nocturnal death syndrome because he was a young Asian man who died while sleeping without specific findings. Since it is an unfamiliar traditional medicine in Korea compared to other Asian countries, forensic officers without background knowledge about Gua Sha initially suspected that he was severely assaulted or pressed against a particular object enough to cause crush asphyxia. Because of the difficulty of going to the hospital during the coronavirus disease 2019 pandemic, Gua Sha was used to treat headaches and mild fever. Therefore, this case shows that understanding the culture of other countries could be helpful for investigations especially with the increase of multicultural families in Korea.

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.

Objective: Glucagon in mammals and its homolog (adipokinetic hormone [AKH] in Drosophila melanogaster) are peptide hormones which regulate lipid metabolism by breaking down triglycerides. Although regulatory mechanisms of glucagon and Akh expression have been widely studied, post-transcriptional gene expression of glucagon has not been investigated thoroughly. In this study, we aimed to profile proteins binding with Gcg messenger RNA (mRNA) in mouse and Akh mRNA in Drosophila. Methods: Drosophila Schneider 2 (S2) and mouse 3T3-L1 cell lysates were utilized for affinity pull down of Akh and Gcg mRNA respectively using biotinylated anti-sense DNA oligoes against target mRNAs. Mass spectrometry and computational network analysis revealed mRNA-interacting proteins residing in functional proximity. Results: We observed that 1) 91 proteins interact with Akh mRNA from S2 cell lysates, 2) 34 proteins interact with Gcg mRNA from 3T3-L1 cell lysates. 3) Akh mRNA interactome revealed clusters of ribosomes and known RNA-binding proteins (RBPs). 4) Gcg mRNA interactome revealed mRNA-binding proteins including Plekha7, zinc finger protein, carboxylase, lipase, histone proteins and a cytochrome, Cyp2c44. 5) Levels of Gcg mRNA and its interacting proteins are elevated in skeletal muscles isolated from old mice compared to ones from young mice. Conclusion Akh mRNA in S2 cells are under active translation in a complex of RBPs and ribosomes. Gcg mRNA in mouse precursor adipocyte is in a condition distinct from Akh mRNA due to biochemical interactions with a subset of RBPs and histones. We anticipate that our study contributes to investigating regulatory mechanisms of Gcg and Akh mRNA decay, translation, and localization.