Background/Aims: Biliary complications are a leading cause of morbidity after liver transplantation, but can be reduced using real-time assessment of the biliary tree. This study described a novel technique for performing ex vivo cholangioscopy during cold static storage and normothermic machine perfusion (NMP) to assess the biliary tree before liver transplantation. Methods: Human donor livers, which were considered unsuitable for transplantation, were perfused at 36ºC using a modified commercial ex vivo perfusion system. Ex vivo cholangioscopy was performed using a SpyGlass Discover system. Cholangioscopy was performed during cold static storage and after 12 hours in NMP. Bile duct biopsies and confocal microscopy were performed. Results: Ex vivo cholangioscopy was performed on eight grafts. During cold static storage, luminal debris was visualized throughout the biliary tree. After 12 hours of reperfusion, the bile ducts appeared hyperemic, heterogeneous, and mottled. Confocal microscopy confirmed perfusion of biliary microvasculature. Conclusions We describe the first use of ex vivo cholangioscopy to assess the biliary tree before liver transplantation. This real-time technique can be used to assess biliary trees during cold static storage and NMP. In addition, cholangioscopy-based interventions can be used to better assess intrahepatic bile ducts.

Background/Aims: Biliary complications are a leading cause of morbidity after liver transplantation, but can be reduced using real-time assessment of the biliary tree. This study described a novel technique for performing ex vivo cholangioscopy during cold static storage and normothermic machine perfusion (NMP) to assess the biliary tree before liver transplantation. Methods: Human donor livers, which were considered unsuitable for transplantation, were perfused at 36ºC using a modified commercial ex vivo perfusion system. Ex vivo cholangioscopy was performed using a SpyGlass Discover system. Cholangioscopy was performed during cold static storage and after 12 hours in NMP. Bile duct biopsies and confocal microscopy were performed. Results: Ex vivo cholangioscopy was performed on eight grafts. During cold static storage, luminal debris was visualized throughout the biliary tree. After 12 hours of reperfusion, the bile ducts appeared hyperemic, heterogeneous, and mottled. Confocal microscopy confirmed perfusion of biliary microvasculature. Conclusions We describe the first use of ex vivo cholangioscopy to assess the biliary tree before liver transplantation. This real-time technique can be used to assess biliary trees during cold static storage and NMP. In addition, cholangioscopy-based interventions can be used to better assess intrahepatic bile ducts.

Background/Aims: Biliary complications are a leading cause of morbidity after liver transplantation, but can be reduced using real-time assessment of the biliary tree. This study described a novel technique for performing ex vivo cholangioscopy during cold static storage and normothermic machine perfusion (NMP) to assess the biliary tree before liver transplantation. Methods: Human donor livers, which were considered unsuitable for transplantation, were perfused at 36ºC using a modified commercial ex vivo perfusion system. Ex vivo cholangioscopy was performed using a SpyGlass Discover system. Cholangioscopy was performed during cold static storage and after 12 hours in NMP. Bile duct biopsies and confocal microscopy were performed. Results: Ex vivo cholangioscopy was performed on eight grafts. During cold static storage, luminal debris was visualized throughout the biliary tree. After 12 hours of reperfusion, the bile ducts appeared hyperemic, heterogeneous, and mottled. Confocal microscopy confirmed perfusion of biliary microvasculature. Conclusions We describe the first use of ex vivo cholangioscopy to assess the biliary tree before liver transplantation. This real-time technique can be used to assess biliary trees during cold static storage and NMP. In addition, cholangioscopy-based interventions can be used to better assess intrahepatic bile ducts.

Background: s/Aims: While patients with borderline resectable pancreatic cancer (BRPC) are a target population for neoadjuvant chemotherapy (NAC), formal guidelines for neoadjuvant therapy are lacking. We assessed the perioperative and oncological outcomes in patients with BRPC undergoing NAC with FOLFIRINOX for patients undergoing upfront surgery (US). Methods: The AHPBA criteria for borderline resectability and/or a CA19-9 level > 100 µ/mL defined borderline resectable tumors retrieved from a prospectively populated institutional registry from 2007 to 2020. The primary outcome was overall survival (OS) at 1 and 3 years. A Cox Proportional Hazard model based on intention to treat was used. A receiver–operator characteristics (ROC) curve was constructed to assess the discriminatory capability of the use of CA19-9 > 100 µ/mL to predict resectability and mortality. Results: Forty BRPC patients underwent NAC, while 46 underwent US. The median OS with NAC was 19.8 months (interquartile range [IQR], 10.3−44.24) vs. 10.6 months (IQR, 6.37−17.6) with US. At 1 year, 70% of the NAC group and 41.3% of the US group survived (p = 0.008). At 3 years, 42.5 % of the NAC group and 10.9% of the US group survived (p = 0.001). NAC significantly reduced the hazard of death (adjusted hazard ratio, 0.20; 95% confidence interval, 0.07−0.54; p = 0.001). CA19-9 > 100 µ/mL showed poor discrimination in predicting mortality, but was a moderate predictor of resectability. Conclusions We found a survival benefit of NAC with FOLFIRINOX for BRPC. Greater pre-treatment of CA19-9 and multivessel involvement on initial imaging were associated with progression of the disease following NAC.

OBJECTIVE: To study the effects of total ginsenosides (TG) extract from Panax ginseng on neural stem cell (NSC) proliferation and differentiation and their underlying mechanisms. METHODS: The migration of NSCs after treatment with various concentrations of TG extract (50, 100, or 200 µ g/mL) were monitored. The proliferation of NSCs was examined by a combination of cell counting kit-8 and neurosphere assays. NSC differentiation mediated by TG extract was evaluated by Western blotting and immunofluorescence staining to monitor the expression of nestin and microtubule associated protein 2 (MAP2). The GSK-3β/β-catenin pathway in TG-treated NSCs was examined by Western blot assay. The NSCs with constitutively active GSK-3β mutant were made by adenovirus-mediated gene transfection, then the proliferation and differentiation of NSCs mediated by TG were further verified. RESULTS: TG treatment significantly enhanced NSC migration (P<0.01 or P<0.05) and increased the proliferation of NSCs (P<0.01 or P<0.05). TG mediation also significantly upregulated MAP2 expression but downregulated nestin expression (P<0.01 or P<0.05). TG extract also significantly induced GSK-3β phosphorylation at Ser9, leading to GSK-3β inactivation and, consequently, the activation of the GSK-3β/β-catenin pathway (P<0.01 or P<0.05). In addition, constitutive activation of GSK-3β in NSCs by the transfection of GSK-3β S9A mutant was found to significantly suppress TG-mediated NSC proliferation and differentiation (P<0.01 or P<0.05). CONCLUSION TG promoted NSC proliferation and neuronal differentiation by inactivating GSK-3β.
Animals ; Cell Differentiation ; Cell Proliferation ; Ginsenosides/pharmacology* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Neural Stem Cells/metabolism* ; Panax ; Plant Extracts/pharmacology* ; Rats ; beta Catenin/metabolism*

Background/Aims: We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients. Methods: The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals. Results: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57). Conclusions We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

Objective:To investigate the short term clinical efficacy of intra-gastric balloon (IGB) on obesity patients with different body mass index (BMI).Methods:The retrospective and descriptive study was conducted. The clinical data of 62 obesity patients with different BMI who were admitted to three medical centers, including 56 cases in the Hurstville Private Hospital, 4 cases in the St George Private Hospital of University of New South Wales and 2 cases in the East Sydney Private Hospital, from January 2017 to December 2021 were collected. There were 15 males and 47 females, aged 45.1(range, 18.0 to 67.0)years, with the BMI of 35.1(range, 27.8 to 48.4)kg/m 2. Of the 62 patients, there were 33 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 29 cases with BMI≥35 kg/m 2. Observation indicators: (1) first operation and postoperative complications; (2) follow-up after first IGB; (3) recurrent IGB and postoperative complications; (4) follow up after recurrent IGB. Follow-up was conducted using outpatient examinations to detect postoperative complications and weight loss effects. Patients were followed up at postoperative 1, 3, 6 month. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers. Results:(1) First opera-tion and postoperative complications. All 62 obesity patients underwent the first IGB successfully. Of the 62 patients, 45 cases had postoperative complications, including 38 cases with gastroesophageal reflux, 12 cases with dysphagia or burping, 9 cases with epigastric pain and 4 cases with nausea. One patient may have multiple complications. Cases with above complications in the 33 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 29 cases with BMI≥35 kg/m 2 were 21, 8, 7, 2 and 17, 4, 2, 2, respectively. (2) Follow-up after first IGB. Of the 62 obesity patients, there were 52, 46 and 38 cases completing followed up at postoperative 1, 3 and 6 month, respectively, including 30, 25,20 cases in patients with 27 kg/m 2≤BMI<35 kg/m 2 and 22, 21, 18 cases in patients with BMI≥35 kg/m 2. Of the 62 obesity patients, there were 15 cases requiring early balloon extraction due to intractable symptoms, inclu-ding 7 cases with ongoing dysphagia or burping, 6 cases with complaining of ineffective weight loss, 1 case with acute right-sided abdominal pain and 1 case with a serendipitous discovery of pregnant. The cumulative weight loss of the 30 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 22 cases with BMI≥35 kg/m 2 at postoperative 1 month was (4.8±3.0)kg and (6.6±2.8)kg, respectively. The above indicator was (6.7±4.4)kg and (10.6±4.8)kg at postoperative 3 month for the 25 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 21 cases with BMI≥35 kg/m 2, and (8.5±4.8)kg and (9.8±3.9)kg at postoperative 6 month for the 20 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 18 cases with BMI≥35 kg/m 2. The percentage of excess weight loss was 53%±26% and 29%±15% at postoperative 6 month and the percentage of total weight loss was 14%±5% and 10%±5% at postoperative 6 month for the 20 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 18 cases with BMI≥35 kg/m 2, respectively. (3) Recurrent IGB and postoperative complications. Of the 38 cases completing the postoperative 6 month followed up after the first IGB, 9 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 7 cases with BMI≥35 kg/m 2 choosing a second IGB immediately after the removal of the first balloon. Cases with postoperative compli-cations, including gastroesophageal reflux, dysphagia or burping, epigastric pain, nausea were 4, 3, 0, 0 in patients with 27 kg/m 2≤BMI<35 kg/m 2 and 4, 0, 2, 1 in patients with BMI≥35 kg/m 2. (4) Follow up after recurrent IGB. All the 16 patients who chosen a second IGB completed the postoperative 6 month followed up, with the cumulative weight loss of (8.8±8.5)kg and (18.9±9.7)kg and the percentage of excess weight loss of 44%±38% and 41%±15% in the 9 cases with 27 kg/m 2≤BMI<35 kg/m 2 and 7 cases with BMI≥35 kg/m 2, respectively. Conclusions:IGB can achieve a good short-term weight loss effects in obesity patients with BMI≥27 kg/m 2. Gastroesophageal reflux, dysphagia or burping, epigastric pain and nausea are common postoperative complications.

Objective:To analyze the research hotspot and frontier of severe coronavirus disease 2019 (COVID-19) in China and abroad.Methods:The CiteSpace software was used to visually analyze the relevant research of severe COVID-19 published by CNKI and Web of Science databases from January 30th to April 20th in 2020. The analysis content included the author of the literature, the publishing institutions, and high-frequency keywords.Results:There were 389 Chinese literatures and 59 English literatures included. Analysis using CiteSpace software showed that there were four large teams in China currently concerning about the research on severe COVID-19. The co-authoring of each team was relatively close, but the teams were lack of cooperation. The main issuing institutions were affiliated hospitals of colleges and universities, but colleges and enterprises had less participation. The authors of English-language publications mainly had five research teams, some of whom had co-authored relationships. The country with the most enormous volume of English-language publications was China, followed by the United States and Canada. The Chinese keyword co-occurrence, clustering and highlighted words analysis showed that the main research areas of severe COVID-19 included clinical features, traditional Chinese medicine treatment, medical imaging, integrated traditional Chinese and Western medicine treatment and so on; nucleic acid detection, clinical features and diagnosis, plague theory and etiology mechanism, traditional Chinese medicine and integrated Chinese and Western medicine treatment, severe COVID-19 combined with diabetes and prognosis research will become future research trends; keyword cluster analysis showed that severe COVID-19, combined chronic underlying diseases, CT imaging characteristics will also become new trends in the field of research. Co-occurrence analysis of keywords in English literatures showed that the main research areas of severe COVID-19 included the names of novel coronavirus, pandemic diseases, infectious diseases, medical supplies distribution, and indicators related to myocardial damage.Conclusions:Researchers in China and abroad have different concerns about severe COVID-19. Domestic research focuses on the diagnosis and treatment of severe cases, while foreign countries attach importance to epidemic response and prevention.

Objective: To discuss the misdiagnosis of pyriform sinus fistula and to better understand this kind of illness. Methods: The analysis was based on twenty-eight patients with congenital pyriform sinus fistula aged from 11 months to 14 years, with the median age of 5 years, and who were surgically treated from January 2013 to January 2017 in Kunming Children′s Hospital.Twenty patients were misdiagnosed in other hospital.After the routine examination of neck ultrasound and enhanced CT, internal fistula was found by self-retaining laryngoscope, traced by methylene blue, and excised by high ligation. Results: Twenty patients were misdiagnosed.The misdiagnosis time ranged from 6 months to 3 years.Under self-retaining laryngoscope, piriform fossa fistula were found in all patients.Nineteen fistula were found in the left and 1 in the right.The fistula in patients was unilateral.Seven cases were misdiagnosed as suppurative lymphadensitis, undergone abscess incisional drainage many times.Three cases were misdiagnosed as thyroglossal duct cyst and performed excision of thyroglossal duct cyst.One case was treated by extended Sistruck operation again because the doctor considered that excision of middle segment of hyoid bone was not enough and the fistula was not ligated completely.One case was misdiagnosed as second branchial cleft fistula on the right side of the neck.Nine cases were misdiagnosed as hyroid-associated diseases including 2 cases suppurative thyroiditis, 2 cases subacute thyroiditis and 5 cases thyroid neoplasms.Among them, 2 cases underwent partial thyroidectomy.All the patients were treated with high ligation of fistula under general anesthesia.The operation was smooth, and no hoarseness, bucking and pharyngeal fistula occurred after the operation.Postoperative follow-up time ranged from 12 months to 4 years and the median follow-up was 18 months without recurrence.The diagnosis was confirmed pathologically. Conclusions Pyriform sinus fistula in children was uncommon and easily misdiagnosed in clinic.The majority of physician including some otolaryngologists were lack of understanding of the disease.It should be regarded as one of the important differential diagnosis of neck mass in children.Children with recurrent left neck infection and/or abscess should be highly suspected.Self-retaining laryngoscopic examination can make a definite diagnosis and high ligation of the fistula through the external neck approach can achieve good therapeutic effect.