BACKGROUND: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. METHODS: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. RESULTS: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-b1-stimulation in Smad2 phosphorylation and RhoA upregulation. CONCLUSION These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

Objective: This study investigated the current work status of emergency medical services (EMS) personnel and the differences in perception between EMS personnel and medical directors (MD) regarding on-line medical oversight in a province. Methods: A total of 1,781 EMS personnel and 51 medical directors were surveyed. The questionnaire consisted of the basic demographic data, work status, perception of on-line medical oversight, and the upcoming national pilot project of the expanding firefighter EMS personnel’s clinical scope. The survey was conducted from May 17 to 27, 2019. Results: The response rates for EMS personnel and MD were 73.7% and 65.3%, respectively. Of the local EMS personnel, 86.8% were male. The average age and field career was 33.5±6.2 years and 50 months, respectively. The proportion of nurse and 1st-grade emergency medical technicians were 30.6% and 35.7%. The EMS personnel and MD answered ‘on-scene basic life support’ and ‘patient’s refusal of transport’, respectively, as the most unnecessary medical oversight. Both responded to the main problem of current medical oversight as ‘request for unnecessary medical oversight.’ EMS personnel responded that all items in the national pilot project of expanding firefighter EMS personnel’s clinical scope would be helpful, while MD reported that only ‘use of epinephrine in anaphylactic patient’ and ‘use of pre-hospital 12 lead electrocardiogram in chest pain patient’ would helpful (P<0.01). Conclusion There was a certain difference in perception of the most unnecessary medical oversight and the upcoming national pilot project of expanding the clinical scope of firefighter EMS personnel between EMS personnel and MD.

Objective: This study investigated the current work status of emergency medical services (EMS) personnel and the differences in perception between EMS personnel and medical directors (MD) regarding on-line medical oversight in a province. Methods: A total of 1,781 EMS personnel and 51 medical directors were surveyed. The questionnaire consisted of the basic demographic data, work status, perception of on-line medical oversight, and the upcoming national pilot project of the expanding firefighter EMS personnel’s clinical scope. The survey was conducted from May 17 to 27, 2019. Results: The response rates for EMS personnel and MD were 73.7% and 65.3%, respectively. Of the local EMS personnel, 86.8% were male. The average age and field career was 33.5±6.2 years and 50 months, respectively. The proportion of nurse and 1st-grade emergency medical technicians were 30.6% and 35.7%. The EMS personnel and MD answered ‘on-scene basic life support’ and ‘patient’s refusal of transport’, respectively, as the most unnecessary medical oversight. Both responded to the main problem of current medical oversight as ‘request for unnecessary medical oversight.’ EMS personnel responded that all items in the national pilot project of expanding firefighter EMS personnel’s clinical scope would be helpful, while MD reported that only ‘use of epinephrine in anaphylactic patient’ and ‘use of pre-hospital 12 lead electrocardiogram in chest pain patient’ would helpful (P<0.01). Conclusion There was a certain difference in perception of the most unnecessary medical oversight and the upcoming national pilot project of expanding the clinical scope of firefighter EMS personnel between EMS personnel and MD.

BACKGROUND: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. METHODS: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. RESULTS: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-b1-stimulation in Smad2 phosphorylation and RhoA upregulation. CONCLUSION These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

Objective: This study aimed to investigate the perception of emergency medical service (EMS) providers and medical directors toward the field skill proficiency of EMS providers. We further examined differences in perception according to the certification and hospital career of individuals. Methods: This survey was conducted enrolling all active EMS providers in Busan, Ulsan, and Gyeongnam, as well as emergency physicians who participated in direct medical direction. Pre-developed questionnaires were sent as text messages to individual EMS providers and emergency physicians using an internet-based survey tool (Google Forms).Questionnaires were composed of 25 items in 7 categories: “airway management”, “ventilatory support”, “circulatory support”, “field assessment and management of trauma patients”, “field assessment and management of patients with chest pain”, “field assessment and management of patients with neurologic symptoms”, and “other items”. The response was based on a five-point Likert scale, where 0 score indicated no experience at all. Results: The questionnaire was distributed to 1,781 EMS providers and 52 medical directors; of these, 1,314 (73.7%) EMS providers and 34 (65.3%) medical directors completed the survey. EMS providers rated themselves as above average (3 points) for most of the questions. However, the majority responded that they had no experience or low proficiency in endotracheal intubation and prehospital delivery (median 2; interquartile range [IQR], 0-3). Conversely, medical directors assessed the EMS provider’s proficiency as above average in use of I-gel, recognition of hypoglycemia, field management of trauma patients, use of oropharyngeal and nasopharyngeal airway, use of laryngeal mask airway, and optimal oxygen supply (median, 4; IQR, 3-4), but responded with low scores for most other questions. Based on the EMS provider certification, nurses scored themselves more proficient than level-1 emergency medical technicians (EMTs) for intravenous access (P<0.001), whereas level-1 EMTs recognized themselves more proficient than nurses for endotracheal intubation (P<0.001), use of Magill forceps (P=0.004), and pediatric cardiopulmonary resuscitation (P<0.001). Conclusion This study recognized the discrepancies in the perception of EMS provider’s field skill proficiency, as perceived by EMS providers and medical directors, and between level-1 EMTs and nurses. We propose that regional EMS authorities need to make persistent efforts to narrow these perception gaps through effective educational programs for EMS providers and medical directors.

Background: s/Aims: Rebleeding of gastric varices (GVs) after endoscopic variceal obturation (EVO) can be fatal. This study was performed to evaluate the usefulness of computed tomography (CT) for the prediction of rebleeding after EVO GV bleeding. Methods: Patients who were treated with EVO for GV bleeding and underwent CT before and after EVO were included. CT images of the portal phase showing pretreatment GVs and feeding vessels, and nonenhanced images showing posttreatment cyanoacrylate impaction were reviewed. Results: Fifty-three patients were included. Their mean age was 60.6±11.6 years, and 40 patients (75.5%) were men. Alcoholic liver disease was the most frequent underlying liver disease (45.3%). Complete impaction of cyanoacrylate in GVs and feeding vessels were achieved in 40 (75.5%) and 24 (45.3%) of patients, respectively. During the follow-up, GV rebleeding occurred in nine patients, and the cumulative incidences of GV rebleeding at 3, 6, and 12 months were 11.8%, 18.9%, and 18.9%, respectively. The GV rebleeding rate did not differ significantly according to the complete cyanoacrylate impaction in the GV, while it differed significantly according to complete cyanoacrylate impaction in the feeding vessels. The cumulative incidences of GV rebleeding at 3, 6, and 12 months were 22.3%, 35.2%, and 35.2%, respectively, in patients with incomplete impaction in feeding vessels, and there was no rebleeding during the follow-up period in patients with complete impaction in the feeding vessels (p=0.002). Conclusions Abdominal CT is useful in the evaluation of the treatment response after EVO for GV bleeding. Incomplete cyanoacrylate impaction in feeding vessels is a risk factor for GV rebleeding.

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1