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Purpose: This study aimed to describe adult living donor liver transplantation (LDLT) for acute liver failure and evaluate its clinical significance by comparing its surgical and survival outcomes with those of deceased donor liver transplantation (DDLT)., Methods: We retrospectively reviewed the medical records of 267 consecutive patients (161 LDLT recipients and 106 DDLT recipients) aged 18 years or older who underwent liver transplantation between January 2006 and December 2020., Results: The mean periods from hepatic encephalopathy to liver transplantation were 5.85 days and 8.35 days for LDLT and DDLT, respectively (P = 0.091). Among these patients, 121 (45.3%) had grade III or IV hepatic encephalopathy (living, 34.8% vs. deceased, 61.3%; P < 0.001), and 38 (14.2%) had brain edema (living, 16.1% vs. deceased, 11.3%; P = 0.269) before liver transplantation. There were no significant differences in in-hospital mortality (living, 11.8% vs. deceased, 15.1%; P = 0.435), 10-year overall survival (living, 90.8% vs. deceased, 84.0%; P = 0.096), and graft survival (living, 83.5% vs. deceased, 71.3%; P = 0.051). However, postoperatively, the mean intensive care unit stay was shorter in the LDLT group (5.0 days vs. 9.5 days, P < 0.001). In-hospital mortality was associated with vasopressor use (odds ratio [OR], 3.40; 95% confidence interval [CI], 1.45-7.96; P = 0.005) and brain edema (OR, 2.75; 95% CI, 1.16-6.52; P = 0.022) of recipient at the time of transplantation. However, LDLT (OR, 1.26; 95% CI, 0.59-2.66; P = 0.553) was not independently associated with in-hospital mortality., Conclusion: LDLT is feasible for acute liver failure when organs from deceased donors are not available., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Canola meal, a by-product of processing canola into oil, reportedly contains high amounts of phenolic compounds and proteins. However, as canola meal is primarily used as feed for livestock, advances in multiple research fields are required to broaden its potential applications. Photoaging is caused by continuous exposure to ultraviolet (UV) radiation from sunlight. UV radiation generates reactive oxygen species and destroys collagen in the skin, thickening the epidermis, reducing elasticity, and causing wrinkles. We hypothesized that canola meal extract (CME) can mitigate the damage to skin associated with wrinkles induced by exposure to UVB radiation. To evaluate the anti-wrinkle effect, we administered CME orally to 40 female Hos:HR-1 hairless mice divided into 5 groups: (1) control mice, (2) a UVB group, and (3-5) CME-treated groups (CME-250, 500, and 1000 mg/kg body weight/day, respectively). All groups except the controls were irradiated with UVB 3 times a week to create wrinkles due to photoaging. CME administration inhibited the increase of the number, mean length, and mean depth of wrinkles induced by UVB radiation as assessed using a skin replica. Histopathological image analysis revealed that CME administration resulted in a decrease in epidermal thickness and an increase in collagen content, while increasing catalase activity and hydroxyproline content in skin tissues. CME administration inhibited the phosphorylation of mitogen-activated protein kinase and decreased the production of collagenase and gelatinase. These results suggest that CME, an upcycled material, has the potential to develop into a healthful and functional food ingredient with anti-wrinkling effects., Competing Interests: Author declarations None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: This study assessed whether or not the ABO blood type affects the incidence of HCC recurrence after living donor liver transplantation (LDLT)., Methods: This retrospective observational study included 856 patients with hepatocellular carcinoma (HCC) who underwent LDLT between January 2006 and December 2016 at the Asan Medical Center., Results: This study included 324 patients (37.9%) with blood type A, 215 (25.1%) with blood type B, 210 (24.5%) with blood type O, and 107 (12.5%) with blood type AB. ABO-incompatible LT was performed in 136 (15.9%) patients. The independent risk factors for the disease-free survival (DFS) were maximal tumor diameter, microvascular invasion, and Milan criteria. The only independent risk factor for the overall survival (OS) was microvascular invasion. The ABO blood group did not affect the DFS (P = 0.978) or OS (P = 0.261). The DFS according to the ABO blood group did not differ significantly between the ABO-compatible (p = 0.701) and ABO-incompatible LDLT recipients (p = 0.147). The DFS according to the ABO blood group did not differ significantly between patients within the Milan criteria (p = 0.934) and beyond the Milan criteria (p = 0.525). The DFS did not differ significantly between recipients with and without type A blood (p = 0.941)., Conclusions: This study demonstrated that the ABO blood group system had no prognostic impact on the oncological outcomes of patients undergoing LT for HCC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Hepatic artery thrombosis (HAT) is a common cause of graft loss in living-donor liver transplantation, occurring in ~2.5%-8% of patients. Some right lobe grafts have 2 hepatic arteries (HAs), and the optimal reconstruction technique remains controversial. This study aimed to identify risk factors for HAT and to evaluate the efficacy of reconstructing 2 HAs in right lobe grafts. This retrospective, single-center study analyzed 1601 living-donor liver transplantation recipients with a right liver graft and divided them into 1 HA (n = 1524) and 2 HA (n = 77) groups. The reconstruction of all HAs was performed using a microscope with an interrupted suture. The primary outcome was any HAT event. Of the 1601 patients, 37.8% had a history of transcatheter arterial chemoembolization, and 130 underwent pretransplant hepatectomy. Extra-anatomical arterial reconstruction was performed in 38 cases (2.4%). HAT occurred in 1.2% of patients (20/1601) who underwent surgical revascularization. In the multivariate analysis, undergoing pretransplant hepatectomy ( p = 0.008), having a female donor ( p = 0.02), having a smaller graft-to-recipient weight ratio ( p = 0.002), and undergoing extra-anatomical reconstruction ( p = 0.001) were identified as risk factors for HAT. However, having 2 HA openings in right liver grafts was not a risk factor for HAT in our series. Kaplan-Meier survival analysis showed no significant difference in graft survival and patient survival rates between the 1 HA and 2 HA groups ( p = 0.09, p = 0.97). In our series, although the smaller HA in the 2 HA group should increase the risk of HAT, HAT did not occur in this group. Therefore, reconstructing both HAs when possible may be a reasonable approach in living-donor liver transplantation using a right liver graft with 2 HA openings., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss., Methods: In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020. Overall, 1040 right-lobe donors were included, with 150 and 890 donors in the weight loss and control (non-steatosis) groups, respectively., Results: We performed 1:1 individual matching using the greedy matching method, by which 124 patients were included in each group. The median period from the date of the first visit to donation was 113 (interquartile range: 78-184) days in the weight loss group. As body weight changed from 82.8 ± 13.7 kg to 70.8 ± 11.8 kg (p < 0.0001), body mass index also improved from 27.8 ± 3.9 kg/m 2 to 23.8 ± 3.1 kg/m 2 (p < 0.0001). No significant between-group differences existed in the postoperative laboratory data for living donors and recipients. The incidence of postoperative complications in donors was comparable between the groups (control group, 9.7%; weight loss group, 13.7%; p = 0.3185). The graft and recipient survival rates were comparable between the groups (p = 1.000)., Conclusion: Weight loss through diet and exercise significantly could improve hepatic steatosis in living donor candidates for liver transplantation, with the surgical outcomes in recipients and donors being equivalent to those in recipients and non-steatotic donors., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background: Mild cognitive impairment (MCI) is an intermediary condition between typical cognitive decline that occurs owing to aging and dementia. It is necessary to implement an intervention to slow the progression from MCI to Alzheimer's disease. This manuscript reports the protocol for a clinical trial on the effect of acupuncture in patients with MCI., Methods: The trial will be a randomized, prospective, parallel-arm, active-controlled trial. Sixty-four patients with MCI will be randomized to the Rehacom or acupuncture group ( n  = 32 each). The participants in the acupuncture group will receive electroacupuncture at GV24 (Shenting) and GV20 (Baihui) and acupuncture at EX-HN1 (Sishencong) once (30 min) a day, twice per week for 12 weeks. The patients in the Rehacom group will receive computerized cognitive rehabilitation using RehaCom software once (30 min) daily, twice weekly for 12 weeks. The primary outcome measure is the change in the Montreal Cognitive Assessment Scale score. The secondary outcome measures are the Geriatric Depression Scale, Alzheimer's Disease Assessment Scale-Korean version-cognitive subscale-3 scores, and European Quality of Life Five Dimensions Five Level Scale. The safety outcomes will include the incidence of adverse events, blood pressure, blood chemistry parameters, and pulse rate. The efficacy outcome will be assessed at baseline and at six weeks, 13 weeks, and 24 weeks after baseline., Discussion: The findings of this protocol will provide information regarding the effects of acupuncture on MCI., Clinical Trial Registration: https://cris.nih.go.kr/cris/search/detailSearch.do?search&#95;lang=E&focus=reset&#95;12&search&#95;page=M&pageSize=10&page=undefined&seq=25579&status=5&seq&#95;group=25579, KCT0008861., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Shin, Kim, Seo, Park, Kang and Lee.)

BACKGROUND The effects of a low graft-to-recipient weight ratio (GRWR) on the prognosis of patients with hepatocellular carcinoma (HCC) are unclear. The present study examined whether the GRWR had an impact on the rate of HCC recurrence following living donor liver transplantation (LDLT). MATERIAL AND METHODS This retrospective observational single-center study included 856 patients who underwent LDLT for HCC between January 2006 and December 2016 at Asan Medical Center and evaluated the association between GRWR and post-transplant tumor recurrence. RESULTS Of the 856 patients who underwent LDLT for HCC, 54 (6.3%), 272 (31.8%), 274 (32.0%), and 256 (29.9%) had GRWR <0.8%, 0.8-0.99%, 1.0-1.19%, and ≥1.2%, respectively. Analysis of all patients revealed that the disease-free survival (DFS; P=0.545) and overall survival (OS; P=0.313) rates were not different in these 4 groups. Subgroups analyses also showed that GRWR did not influence survival rates in patients within (DFS: P=0.398; OS: P=0.676) and beyond (DFS: P=0.602; OS: P=0.649) the Milan criteria, or in patients with alpha-fetoprotein-des-γ-carboxyprothrombin-tumor volume scores <5log (DFS: P=0.633; OS: p=0.285) and ≥5log (DFS: P=0.674; OS: P=0.906). CONCLUSIONS GRWR less than 0.8% did not demonstrate a noteworthy prognostic influence on the oncological results among patients who had undergone LDLT for HCC. High-volume multi-center studies are necessary to validate these findings.

Rationale: The surge of severe liver damage underscores the necessity for identifying new targets and therapeutic agents. Endoplasmic reticulum (ER) stress induces ferroptosis with Gα 12 overexpression. NF-κB essential modulator (NEMO) is a regulator of inflammation and necroptosis. Nonetheless, the regulatory basis of NEMO de novo synthesis and its impact on hepatocyte ferroptosis need to be established. This study investigated whether Nrf2 transcriptionally induces IKBKG (the NEMO gene) for ferroptosis inhibition and, if so, how NEMO induction protects hepatocytes against ER stress-induced ferroptosis. Methods: Experiments were conducted using human liver tissues, hepatocytes, and injury models, incorporating NEMO overexpression and Gα 12 gene modulations. RNA sequencing, immunoblotting, immunohistochemistry, reporter assays, and mutation analyses were done. Results: NEMO downregulation connects closely to ER and oxidative stress, worsening liver damage via hepatocyte ferroptosis. NEMO overexpression protects hepatocytes from ferroptosis by promoting glutathione peroxidase 4 (GPX4) expression. This protective role extends to oxidative and ER stress. Similar shifts occur in nuclear factor erythroid-2-related factor-2 (Nrf2) expression alongside NEMO changes. Nrf2 is newly identified as an IKBKG (NEMO gene) transactivator. Gα 12 changes, apart from Nrf2, impact NEMO expression, pointing to post-transcriptional control. Gα 12 reduction lowers miR-125a, an inhibitor of NEMO, while overexpression has the opposite effect. NEMO also counters ER stress, which triggers Gα 12 overexpression. Gα 12 's significance in NEMO-dependent hepatocyte survival is confirmed via ROCK1 inhibition, a Gα 12 downstream kinase, and miR-125a. The verified alterations or associations within the targeted entities are validated in human liver specimens and datasets originating from livers subjected to exposure to other injurious agents. Conclusions: Hepatic injury prompted by ER stress leads to the suppression of NEMO, thereby facilitating ferroptosis through the inhibition of GPX4. IKBKG is transactivated by Nrf2 against Gα 12 overexpression responsible for the increase of miR-125a, an unprecedented NEMO inhibitor, resulting in GPX4 induction. Accordingly, the induction of NEMO mitigates ferroptotic liver injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The COVID-19 pandemic has had a major impact on liver transplantation (LT) and living donor programs globally., Purpose: In this study, we aimed to present the principles and strategies of our LT program during the pandemic period and describe its achievements., Basic Procedures: We retrospectively reviewed the outcomes of 1417 LTs performed at Asan Medical Center, Seoul, Korea, from 2020 to 2022. Of these, 216 recipients who received transplants from deceased donors were excluded, and 1201 recipients who received transplants from 1268 live donors were included in the study, including 38 children <18 years old., Main Findings: Among the 1201 living donor LT (LDLT) recipients, the most common indication for LT was unresectable hepatocellular carcinoma (315/1163, 27.1%) in adults and biliary atresia (29/38, 76.3%) in pediatric recipients. Emergency LDLT was performed in 40 patients (3.3%). The median model of end-stage liver disease and pediatric end-stage liver disease scores were 13.9 ± 7.2 and 13.8 ± 7.1, respectively. In-hospital mortality of recipients was higher than usual at 2.2%, but the cause of death was not related to COVID-19 infection. Of the 1268 live donors who underwent hepatectomy for liver donation, 660 (52.1%) underwent hepatectomy using a minimally invasive approach. Although 17 (1.3%) live donors experienced major complications, there were no serious life-threatening complications and no mortality., Conclusion: Even in a pandemic era, a team with well-established infection control protocols, patient-tailored surgical strategies, and thorough perioperative care can maintain LDLT at a similar quantitative and qualitative level as in a non-pandemic era., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Portal vein (PV) interposition can induce various PV-related complications, making more reliable techniques necessary. The present study describes the development of a modified patch venoplasty technique, combining the native PV wall and a vein homograft conduit, called modified patch-conduit venoplasty (MPCV)., Methods: The surgical technique for MPCV was optimized by simulation and applied to seven pediatric patients undergoing liver transplantation (LT) for biliary atresia combined with PV hypoplasia., Results: The simulation study revealed that inserting the whole-length native PV wall as a longitudinal rectangular patch was more effective in preventing PV conduit stenosis than the conventional technique using triangular partial insertion. These findings were used to develop the MPCV technique, in which the native PV wall was converted into a long rectangular patch, acting as a backbone for PV reconstruction. A longitudinal incision on the vein conduit converted the cylindrical vein into a large vein patch. The wall of the native PV was fully preserved as the posterior wall of the PV conduit, thus preventing longitudinal redundancy and unwanted rotation of the reconstructed PV. This technique was applied to seven patients with biliary atresia undergoing living-donor and deceased-donor split LT. None of these patients has experienced PV complications for up to 12 months after transplantation., Conclusions: This newly devised MCPV technique can replace conventional PV interposition. MCPV may be a surgical option for reliable PV reconstruction using fresh or cryopreserved vein homografts during pediatric LT.

Background: Mesenchymal stem cells (MSCs) are widely used in regenerative medicine and cell-based transplantations. However, an in-depth comparison of the different MSC origins is lacking. This study aimed to compare the expression of adipose-derived (AMSCs), bone marrow-derived (BMSCs), and tonsil-derived (TMSCs) and evaluate whether TMSCs are good alternatives for AMSCs or BMSCs., Methods: We analyzed the expression levels of 47,000 transcripts in AMSCs (n = 4), BMSCs (n = 4), and TMSCs (n = 4) using GeneChip. Microarray data were analyzed using the LIMMA package to compare the TMSCs, AMSCs, and BMSCs. Hub genes were analyzed using STRING and Cytoscape. To ascertain the functional roles of AURKA and AURKB, small interfering RNA (siRNA) molecules specifically targeting AURKA and AURKB mRNA were synthesized and employed to induce knockdown of AURKA and AURKB in TMSC and AMSC. We analyzed the expression level of OCT4, SOX-2, and NANOG genes in TMSC and AMSCs by cell culture and real-time PCR., Results: We identified commonly increased 256 and decreased 160 genes in TMSCs from the differentially expressed genes (DEGs) between the TMSCs, AMSCs, and BMSCs. In the DEG-based protein-protein interaction and gene set enrichment analysis, hub genes (AURKA, AURKB, CDC20, and BUB1) highly expressed in TMSCs were enriched for development- and progression-related oocyte meiosis, the cell cycle, and ubiquitin-mediated proteolysis. In vitro analysis demonstrated that cells with downregulated expression of AURKA and AURKB exhibited a significant reduction in proliferation compared to control cells. However, silencing of the genes did not affect the differentiation capacity in TMSCs and AMSCs., Conclusion: Our study compared MSCs of different origins to better understand the similarities and differences among these cell types., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B 1 exacerbated allogeneic immune responses in vitro and in vivo , and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs.

Background: Shoulder arthroplasty (SA), including hemiarthroplasty, reverse and anatomical total SA (TSA), improves quality of life by reducing shoulder pain and restoring function in patients not only with irreparable rotator cuff tears and/or cuff tear arthropathy but also with osteoarthritis posttraumatic arthritis, proximal humeral fractures, etc. Given the rapid developments in artificial joints and improvements in postoperative outcomes, the number of SA surgeries is increasing worldwide. Therefore, we investigated changes in trends over time in Korea., Methods: We analyzed the longitudinal changes in the incidence of SA including anatomic and reverse TSA, hemiarthroplasty, and shoulder revision arthroplasty (SRA) by changes in the Korean age profile, surgical facilities, and geographical regions using the Korean Health Insurance Review and Assessment Service database from 2010 to 2020. Data were also collected from the National Health Insurance Service and the Korean Statistical Information Service., Results: From 2010 to 2020, the TSA rate per 1,000,000 person-years increased from 10.571 to 101.372 (time trend = 1.252; 95% CI 1.233-1.271, P < .001). The shoulder hemiarthroplasty (SH) rate per 1,000,000 person-years decreased from 6.414 to 3.685 (time trend = 0.933; 95% CI 0.907-0.960, P < .001). The SRA rate per 1,000,000 person-years increased from 0.792 to 2.315; the increase was significant (time trend = 1.133; 95% CI 1.101-1.166, P < .001)., Discussion: Overall, TSA and SRA are increasing and SH is decreasing. For both total TSA and SRA, steep increases are evident in the numbers of patients in their 70s and older than 80 years. The SH trend is decreasing regardless of differences in age groups, surgical facilities, and geographical regions. SRA is preferentially performed in Seoul., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Acetaminophen (APAP) may cause acute liver injury with therapeutic doses in high-risk conditions such as chronic alcohol consumption or malnutrition. In acute hepatitis A (AHA), however, the safety of APAP has not been fully established. This study examined the potential association between APAP use and clinical outcomes of AHA in a nationwide and hospital-based cohort., Methods: Adult patients with AHA were identified from claims data of South Korean national healthcare insurance between 2008 and 2016 (n = 43,500). Logistic regression models were used to compare the risk of adverse outcomes (renal replacement therapy, hepatic encephalopathy and/or brain edema, mechanical ventilation, and liver transplantation) in patients exposed to APAP against control and patients exposed to NSAIDs. A propensity score (PS)-matched hospital-based AHA cohort (n = 146) was assessed for biochemical profiles after exposure to APAP or NSAIDs., Results: AHA patients were exposed to APAP or NSAIDs in 26.4% and 11.5% of cases, respectively. Compared to NSAID treatment, APAP exposure was associated with a higher incidence of hospitalization (98.8% vs. 92.4%; p < 0.0001). APAP exposure was independently associated with increased adverse outcomes (odds ratio [OR] = 5.66, p < 0.0001 against control; OR =1.67, p = 0.0015 against NSAIDs). PS-matched hospital cohort showed higher peak serum bilirubin levels (7.0 vs. 5.3 mg/dL; p = 0.03) and a longer time to recovery of jaundice after APAP use than with NSAID use., Conclusion: APAP exposure was associated with increased adverse outcomes in a nationwide AHA cohort., Competing Interests: Declaration of Competing Interest The authors do not have any disclosures to report., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center., Methods: This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%)., Results: Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374)., Conclusion: Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2023, the Korean Surgical Society.)

Objective: The aim of this study was to measure the ability of radiomics analysis to diagnose different stages of sialadenitis, compare the diagnostic accuracy of computed tomography (CT) and ultrasonography (US), and suggest radiomics features selected through 3 machine learning algorithms that would be helpful in discriminating between stages of sialadenitis with both imaging systems., Study Design: Wistar rats were treated to induce acute and chronic sialadenitis in the left and right submandibular glands, respectively. Contrast-enhanced CT and US of the glands were performed, followed by extirpation and histopathologic confirmation. Radiomics feature values of the glands were obtained from all images. Based on 3 feature selection methods, an optimal feature set was defined after a comparison of the receiver operating characteristic area under the curve (AUC) of each combination of 3 deep learning algorithms and 3 classification models., Results: The attribute features for the CT model were 2 gray-level run length matrices and 2 gray-level zone length matrices. In the US model, there were 2 gray-level co-occurrence matrices and 2 gray-level zone length matrices. The most accurate diagnostic models of CT and US yielded outstanding (AUC = 1.000) and excellent (AUC = 0.879) discrimination, respectively., Conclusions: The radiomics diagnostic model using gray-level zone length matrices-based features conferred clinically outstanding discriminating ability among stages of sialadenitis using CT and excellent discrimination with US in almost all combinations of machine learning feature selections and classification models., Competing Interests: Declarations of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Canola meal, a by-product of canola oil processing, is a source of bioactive compounds that show antioxidant and skin anti-aging effects through upcycling (i.e., creative reuse). Here we describe the antioxidant and skin anti-aging effects of canola meal extract (CME) obtained by upcycling canola meal. The antioxidant capacity of CME is due in part to its antioxidative phenolics. Seven phenolics, including sinapine and sinapic acid, in CME were identified using ultra-high-performance liquid chromatography-Orbitrap mass spectrometry. Addition of CME (1000 μg/mL) to human dermal fibroblast neonatal cells  significantly ( p  < 0.05) reduced matrix metalloproteinase-12 production and increased pro-collagen Ι alpha 1 content in response to ultraviolet B-induced oxidative stress compared with cells without CME. These results suggest that CME can serve as a functional food ingredient with antioxidant capacity and anti-aging effects on the skin., Competing Interests: Conflict of interestThe authors declare no conflict of interests., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: This study aimed to investigate prognostic factors of recurrence and survival associated with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT)., Patients and Methods: This retrospective study included 161 patients with HCC with PVTT who underwent hepatectomy between January 2003 and January 2014 at the Asan Medical Center. Regression analyses were conducted to identify favorable predictive factors for overall survival (OS) and recurrence-free survival (RFS)., Results: The median follow-up was 15.9 months, while 1-, 3-, and 5-year OS was 65.0%, 38.4%, and 36.0%, respectively, and 1-year RFS was 25.5%. There were no significant differences in OS and RFS between the patients with portal vein invasion (Vp) 1-2 and Vp3-4 PVTT. Patients with intrahepatic recurrence had significantly better overall survival than patients with extrahepatic recurrence. Transcatheter arterial chemoembolization and radiofrequency ablation were the most effective treatments for intrahepatic metastasis, and surgery was the most effective treatment for extrahepatic metastasis. On multivariate analysis, absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection were favorable prognostic factors for OS and R0 resection, and absence of microvascular invasion was a favorable prognostic factor for RFS., Conclusion: The long-term outcome of patients with HCC with PVTT can be improved under consideration of favorable prognostic factors including absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection, R0 resection, and absence of microvascular invasion. In addition, recurrent HCC required aggressive management to prolong overall survival., (© 2023. Society of Surgical Oncology.)

Background: This study aimed to present our surgical technique and the long-term outcomes of living donor liver transplantations with renoportal anastomosis for patients with complete portal venous occlusion. Renoportal anastomosis (RPA) is a promising technique for portal flow reconstruction during liver transplantation in patients with complete occlusion of the portal vein and extensive splanchnic vein thrombosis. However, reports demonstrating living donor liver transplantations (LDLT) with renoportal anastomosis are rarer than those demonstrating deceased donor liver transplantation., Materials and Methods: In this single-centre retrospective cohort study, the authors analyzed the medical records of patients who underwent portal flow reconstruction via RPA with end-to-end anastomosis between the interposition graft and LRV-connected inferior vena cava (VC) cuff. The outcomes included postoperative RPA-related morbidity and patient and allograft survival for patients who underwent LDLT with RPA., Results: Fifteen patients underwent LDLT with portal flow reconstruction via RPA from January 2005 to December 2019. The median follow-up period was 80.7 months (range: 27 days-195.2 months). RPA evolved from end-to-end anastomosis in 1 (6.7%) patient to end-to-side anastomoses in the next 6 (40%) patients and finally, to end-to-end anastomoses between the inferior VC cuff connected to the left renal vein and interposing vascular grafts in 8 (53.3%) patients. After standardization of the RPA technique from the eighth case in 2011, the incidence rate of RPA-related complications significantly decreased from 42.9% (3/7) to 12.5% (1/8). At the last follow-up, all 11 surviving patients had normal liver function, and 10 patients had patent anastomoses on imaging examination., Conclusions: This standardized RPA technique using an inferior VC cuff connected to the left renal vein creates a safe end-to-end RPA., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The aim of this study is to validate the prognostic impact of ADV score (α-fetoprotein [AFP]-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score) for predicting prognosis of hepatocellular carcinoma (HCC) following liver transplantation (LT)., Background: ADV score has been reported as a prognostic surrogate biomarker of HCC following LT and hepatectomy., Methods: The study patients were 1599 LT recipients selected from the Korean Organ Transplantation Registry database., Results: Deceased-donor and living-donor LTs were performed in 143 and 1456 cases, respectively. Weak correlation was present among AFP, DCP, and TV. The viable HCC group showed ADV score-dependent disease-free survival (DFS) and overall patient survival (OS) rates from 1log to 10log (p<0.001). Prognosis of complete pathological response group was comparable to that of ADV score <1log (p≥0.099). ADV score cutoff of 5log (ADV-5log) for DFS and OS was obtained through receiver operating characteristic curve analysis with area under the curve ≥0.705. Both ADV-5log and Milan criteria were independent risk factors for DFS and OS, and their prognostic impacts were comparable to each other. Combination of these two factors resulted in further prognostic stratification, showing hazard ratios for DFS and OS as 2.98 and 2.26 respectively for one risk factor and 7.92 and 8.19 respectively for two risk factors (p<0.001). ABO-incompatible recipients with ADV score ≥8log or two risk factors showed higher recurrence rates., Conclusions: This validation study revealed that ADV score is a reliable surrogate biomarker for posttransplant HCC prognosis, which can be used for selecting LT candidates and guiding risk-based posttransplant follow-up surveillance., (© 2023. The Society for Surgery of the Alimentary Tract.)

Wavelength tunable lasers with narrow dynamic linewidths are essential in many applications, such as optical coherence tomography and LiDAR. In this letter, we present a 2D mirror design that provides large optical bandwidth and high reflection while being stiffer than 1D mirrors. Specifically, we investigate the effect of rounded corners of rectangles as they are transferred from the CAD to the wafer by lithography and etching.

The mechanism underlying xerostomia after menopause has not yet been fully elucidated. This study aimed to investigate the mechanism of xerostomia and the effect of the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (FER) on salivary gland dysfunction in a postmenopausal animal model. Twenty-four female Sprague-Dawley rats were randomly divided into four groups: a SHAM group ( n = 6, sham-operated rats), an OVX group ( n = 6, ovariectomized rats), an FER group ( n = 6, ovariectomized rats injected intraperitoneally with FER), and a DFO group ( n = 6, ovariectomized rats injected intraperitoneally with DFO). GPX4 activity, iron accumulation, lipid peroxidation, inflammation, fibrosis, and salivary gland function were analyzed. Recovery of GPX4 activity and a decrease in iron accumulation and cytosolic MDA + HAE were observed in the DFO group. In addition, collagen I, collagen III, TGF-β, IL-6, TNF-α, and TGF-β levels were decreased in the DFO group compared to the OVX group. Recovery of GPX4 activity and the morphology of mitochondria, and reduction of cytosolic MDA + HAE were also observed in the FER group. In addition, decreased expression of inflammatory cytokines and fibrosis markers and increased expression of AQP5 were observed in both the DFO and FER groups. Postmenopausal salivary gland dysfunction is associated with ferroptosis, and DFO and FER may reverse the postmenopausal salivary gland dysfunction after menopause. DFO and FER are hence considered promising treatments for postmenopausal xerostomia.

Delayed gastric emptying (DGE) is a common complication of liver transplantation. This study aimed to clarify the efficacy and safety of the application of an adhesion barrier for preventing DGE in living-donor liver transplantation. This retrospective study included 453 patients who underwent living-donor liver transplantation using a right lobe graft between January 2018 and August 2019, and the incidence of postoperative DGE and complications was compared between patients in whom adhesion barrier was used (n=179 patients) and those in whom adhesion barrier was not used (n=274 patients). We performed 1:1 propensity score matching between the 2 groups, and 179 patients were included in each group. DGE was defined according to the International Study Group for Pancreatic Surgery classification. The use of adhesion barrier was significantly associated with a lower overall incidence of postoperative DGE in liver transplantation (30.7 vs. 17.9%; p =0.002), including grades A (16.8 vs. 9.5%; p =0.03), B (7.3 vs. 3.4%; p =0.08), and C (6.6 vs. 5.5%; p =0.50). After propensity score matching, similar results were observed for the overall incidence of DGE (29.6 vs. 17.9%; p =0.009), including grades A (16.8 vs. 9.5%; p =0.04), B (6.7 vs. 3.4%; p =0.15), and C (6.1 vs. 5.0%; p =0.65). Univariate and multivariate analyses showed a significant correlation between the use of adhesion barrier and a low incidence of DGE. There were no statistically significant differences in postoperative complications between the 2 groups. The application of an adhesion barrier could be a safe and feasible method to reduce the incidence of postoperative DGE in living-donor liver transplantation., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: We aim to obtain clinical trial data regarding the safety, efficacy, and usefulness of invasive laser acupuncture (ILA) for non-specific chronic low back pain (NSCLBP) through a randomized placebo-controlled trial., Methods: Our clinical trial will be an assessor- and patient-blinded, prospective, parallel-arm, multi-center, randomized placebo-controlled clinical trial. One hundred and six participants with NSCLBP will be allocated evenly to the 650 ILA or control group. All participants will receive education on exercise and self-management. The 650 ILA group will undergo 650 nm ILA for 10 min, and the control group will undergo sham ILA for 10 min per visit, twice a week for 4 weeks, at bilateral GB30, BL23, BL24, and BL25. The primary outcome will be the proportion of responders (≥30% reduction in pain visual analogue scale [VAS] without increased use of painkillers) at 3 days after the intervention ends. The secondary outcomes will include changes in the scores of the VAS, European Quality of Life Five Dimension Five Level scale, and Korean version of the Oswestry Disability Index at 3 days after the intervention ends and 8 weeks after the intervention ends., Discussions: The results of our study will provide clinical evidence concerning the safety and efficacy of 650 nm ILA for the management of NSCLBP., Clinical Trial Registration: https://cris.nih.go.kr/cris/search/detailSearch.do?search&#95;lang=E&focus=reset&#95;12&search&#95;page=M&pageSize=10&page=undefined&seq=21591&status=5&seq&#95;group=21591, identifier KCT0007167., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Yang, Yoo, Park, Kang, Kim, Kim, Nam and Hong.)

Backgrounds: The anatomy of the left hepatic vein (LHV) is variable; thus, it should be considered for graft hepatic vein (GHV) venoplasty for left lateral section (LLS) and left liver grafts. This study assessed the incidence of superficial LHV (sLHV) branches according to LHV anatomy and its usability for GHV venoplasty in pediatric liver transplantation (LT)., Methods: This study consisted of three parts: (1) anatomical classification of LHV variations and the incidence of sLHV branches; (2) morphometric simulative analysis of GHV reconstruction and (3) clinical application based on LHV anatomy., Results: The LHV anatomy of 248 potential LLS graft donors was classified into four types according to the number and location of GHV openings: one single opening (type 1; n = 186 [75.0%]), two large openings (type 2; n = 35 [14.1%]), one large and one small adjacent opening (type 3; n = 14 [5.6%]), and two large widely-separated openings (type 4; n = 13 [5.2%]). An sLHV branch was identified in 87 of 248 (35.1%) donor livers. Morphometric analysis of simulative GHV venoplasty with an sLHV branch increased GHV diameters by 30% in type 1 LLS grafts and 20% in type 2/3 LLS grafts. An analysis of 50 consecutive patients who underwent pediatric LT showed that the 2-year rates of GHV obstruction were 2.0% with LLS grafts and 0% with left liver grafts., Conclusions: The GHV orifice can be enlarged through LHV anatomy-based unification venoplasty. Unification venoplasty with an sLHV branch provided sufficient enlargement of the GHV orifice., (© 2022 Wiley Periodicals LLC.)

Introduction: Lenvatinib is approved for the treatment of patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, clinical outcomes of lenvatinib therapy in patients with post-liver transplantation (LT) HCC recurrence remain unclear. We investigated the efficacy and safety of lenvatinib in patients with post-LT HCC recurrence., Methods: This multinational, multicenter, retrospective study included 45 patients with recurrent HCC after LT who received lenvatinib at six institutions in three countries (Korea, Italy, and Hong Kong) from June 2017 to October 2021., Results: At the time of lenvatinib initiation, 95.6% (n = 43) of patients had Child-Pugh A status, and 35 (77.8%) and 10 (22.2%) participants were classified as having albumin-bilirubin (ALBI) grades 1 and 2, respectively. The objective response rate was 20.0%. With a median follow-up duration of 12.9 months (95% confidence interval [CI]: 11.2-14.7), the median progression-free survival and overall survival (OS) were 7.6 (95% CI: 5.3-9.8) months, and 14.5 (95% CI: 0.8-28.2) months, respectively. Patients with ALBI grade 1 showed significantly better OS (52.3 months, [95% CI: not assessable]) than patients with ALBI grade 2 (11.1 months [95% CI: 0.0-30.4 months], p = 0.003). The most common adverse events were hypertension (n = 25, 55.6%), fatigue (n = 17, 37.8%), and anorexia (n = 14, 31.1%)., Conclusion: Lenvatinib showed consistent efficacy and toxicity profiles in patients with post-LT HCC recurrence that were comparable to those reported from previous studies among non-LT HCC patients. The baseline ALBI grade correlated with better OS in post-LT lenvatinib-treated patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Controlling the contact properties of a copper (Cu) electrode is an important process for improving the performance of an amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistor (TFT) for high-speed applications, owing to the low resistance-capacitance product constant of Cu. One of the many challenges in Cu application to a-IGZO is inhibiting high diffusivity, which causes degradation in the performance of a-IGZO TFT by forming electron trap states. A self-assembled monolayer (SAM) can perfectly act as a Cu diffusion barrier (DB) and passivation layer that prevents moisture and oxygen, which can deteriorate the TFT on-off performance. However, traditional SAM materials have high contact resistance and low mechanical-adhesion properties. In this study, we demonstrate that tailoring the SAM using the chemical coupling method can enhance the electrical and mechanical properties of a-IGZO TFTs. The doping effects from the dipole moment of the tailored SAMs enhance the electrical properties of a-IGZO TFTs, resulting in a field-effect mobility of 13.87 cm 2 /V·s, an on-off ratio above 10 7 , and a low contact resistance of 612 Ω. Because of the high electrical performance of tailored SAMs, they function as a Cu DB and a passivation layer. Moreover, a selectively tailored functional group can improve the adhesion properties between Cu and a-IGZO. These multifunctionally tailored SAMs can be a promising candidate for a very thin Cu DB in future electronic technology.

In the liver, reactive oxygen species (ROS) are constantly released during cellular metabolic processes, and excess ROS production can cause redox stress. The redox stress is both beneficial for and harmful to the survival of cells since it modulates the cellular redox control system. The redox control system is a series of cellular responses that are responsible for maintaining a balanced oxidation-reduction status. Many cellular processes including growth, proliferation, and senescence are sensitively regulated by the redox control system. Imbalance of redox induces redox stress and damages DNA, proteins, and lipids in cells, and further contributes to the pathogenesis of severe diseases and disorders like cancer. However, the cellular redox control system also utilizes redox stress-responsive pathways and increases antioxidant enzymes to aid cell survival. Therefore, a deeper understanding of the connection between the redox control system and liver disease is likely to pave the way for the future development of new therapeutic strategies. This review will examine the redox control systems in liver with responsive regulating molecules, current knowledge of the redox control system and liver disease, and suggest potential therapeutic targets for liver diseases., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Backgrounds/aims: Although body surface area (BSA)-based standard liver volume (SLV) formulae have been used for living donor liver transplantation and hepatic resection, hemi-liver volume (HLV) is needed more frequently. HLV can be assessed using right or left portal vein diameter (RPVD or LPVD). The aim of this study was to validate the reliability of using portal vein diameter ratio (PVDR) for assessing HLV in living liver donors., Methods: This study included 92 living liver donors (59 males and 33 females) who underwent surgery between January 2020 and December 2020. Computed tomography (CT) images were used for measurements., Results: Mean age of donors was 35.5 ± 7.2 years. CT volumetry-measured total liver volume (TLV), right HLV, left HLV, and percentage of right HLV in TLV were 1,442.9 ± 314.2 mL, 931.5 ± 206.4 mL, 551.4 ± 126.5 mL, and 64.6% ± 3.6%, respectively. RPVD, LPVD, and main portal vein diameter were 12.2 ± 1.5 mm, 10.0 ± 1.3 mm, and 15.3 ± 1.7 mm, respectively (corresponding square values: 149.9 ± 36.9 mm 2 , 101.5 ± 25.2 mm 2 , and 237.2 ± 52.2 mm 2 , respectively). The sum of RPVD 2 and LPVD 2 was 251.1 ± 56.9 mm 2 . BSA-based SLV was 1,279.5 ± 188.7 mL (error rate: 9.1% ± 14.4%). SLV formula- and PVDR-based right HLV was 760.0 ± 130.7 mL (error rate: 16.2% ± 13.3%)., Conclusions: Combining BSA-based SLV and PVDR appears to be a simple method to predict right or left HLV in living donors or split liver transplantation.

Post-menopausal dry mouth or xerostomia is caused by reduced salivary secretion. This study aimed to investigate the efficacy of echinochrome A (Ech A) in alleviating submandibular gland dysfunctions in ovariectomized rats that mimic menopause. Female rats that were eight-weeks-old were randomly divided into SHAM-6, -12; OVX-6, -12; and ECH-6, -12 groups (consisting of 6- and 12-weeks post-sham-operated, ovariectomized, and Ech A-treated ovariectomized rats, respectively). The ECH groups had lower body weight than OVX but similar food intake and estradiol or estrogen receptor β expression. However, the ECH groups had lower mRNA expression of sterol-regulatory element binding protein-1c ( Srebp-1c ), acetyl-CoA carboxylase ( Acc ), fatty acid synthase ( Fasn ), cluster of differentiation 36 ( Cd36 ), and lipid vacuole deposition than OVX mice. Moreover, reactive oxygen species (ROS), malondialdehyde (MDA), and iron accumulation were lower in the ECH than in the OVX groups. Fibrosis markers, transforming growth factor β ( Tgf-βI and Tgf-βII mRNA ) increased in the OVX than SHAM groups but decreased in the ECH groups. Aquaporin ( Aqp-1 and Aqp-5 mRNA ) and mucin expressions were downregulated in the OVX groups but improved with Ech A. In addition, Ech A prevented post-menopausal salivary gland dysfunction by inhibiting lipogenesis and ferroptosis. These findings suggest Ech A as an effective remedy for treating menopausal dry mouth.

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the host cells depends on the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). We investigated the distribution of ACE2- and TMPRSS2-expressing cells in various oral tissues to identify the underlying mechanism of oral manifestations in patients with coronavirus disease 2019., Subjects: We analyzed the expression patterns of ACE2 and TMPRSS2 in the oral mucosa (tongue, palate, and buccal mucosa), trigeminal ganglion, vessels, and salivary glands of 9 Sprague-Dawley rats using immunohistochemistry and immunofluorescence., Results: ACE2 and TMPRSS2 were strongly expressed in the intermediate layer of the squamous epithelia of tongue papillae and buccal mucosa. ACE2- and TMPRSS2-positive cells were observed in the taste buds of the tongue. Additionally, ACE2 and TMPRSS2 were co-expressed in the ductal epithelium and acinar cells of salivary glands. Furthermore, both ACE2 and TMPRSS2 were stained in the neuronal cell body of trigeminal ganglia, but not in Schwann cells. Moreover, ACE2 and TMPRSS2 were expressed in capillaries, but not in venules/arterioles., Conclusions: SARS-CoV-2 can spread the suprabasal area of squamous epithelia of the oral mucosa, invades taste bud, trigeminal nerve, parotid gland, and microvessel, resulting in oral manifestations., (© 2022 Wiley Periodicals LLC.)

Complete pathological response (CPR) is achieved with various pretransplant locoregional treatments for hepatocellular carcinoma (HCC). This study aimed to investigate pretransplant expression of HCC tumor markers in liver transplantation (LT) recipients showing CPR. For the CPR group, 166 patients were selected from a single-institution LT database. Two control groups of 332 patients without HCC and 184 patients with partial pathological response (PPR) were also selected. The model for end-stage liver disease score in the CPR group was 11.5 ± 7.7. The number of transcatheter arterial chemoembolization sessions before LT was one in 68 patients (14.0%), two in 38 patients (22.9%), and three or more in 60 patients (36.1%). A solitary non-viable tumor was identified in 120 (86.4%) of the explant livers and the largest tumor size was 2.4 ± 1.3 cm. Living-donor and deceased-donor LTs were performed in 152 (91.6%) and 14 (8.4%) patients, respectively. The median levels of α-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) measured within two weeks before LT were 4.2 ng/mL and 20 mAU/mL, respectively. These tumor marker levels were comparable to those in the no-HCC control group, but much lower than those in the PPR group (p < 0.001). Receiver operating characteristic curve analysis of AFP and PIVKA-II showed no definite cutoff values for CPR in the cohort of CPR and no-HCC patients, but significant cutoffs of 6.5 ng/mL for AFP and 29 mAU/mL for PIVKA-II were obtained in the cohort of CPR and PPR patients. The 1-, 3- and 5-year HCC recurrence and overall patient survival rates of the CPR group were 5.1% and 93.3%, 7.6% and 89.6%, and 7.6% and 89.6%, respectively. These tumor recurrence rates were much lower than those in the PPR group (p < 0.001). In conclusion, the present study results suggest that normalizing AFP and PIVKA-II after locoregional treatment is indicative of CPR. However, some CPR patients showed high expression of tumor markers; thus, pretransplant values of HCC tumor markers should be interpreted with caution.

Background: It is important to develop effective treatments to prevent the progress of mild cognitive impairment to Alzheimer's disease. Cheonwangbosimdan has been widely prescribed for palpitation, anxiety, insomnia, and memory decline. We aimed to obtain clinical trial data concerning the safety and efficacy of Cheonwangbosimdan for mild cognitive impairment., Methods: This clinical trial would be a single-center, double-blinded, parallel-arm, prospective, randomized controlled trial. Forty-eight participants with mild cognitive impairment would be randomly allocated evenly to the placebo or Cheonwangbosimdan groups. Participants will be educated on self-management and exercise at baseline and will receive the trial medication (Cheonwangbosimdan group, Cheonwangbosimdan; placebo group, placebo) once daily for 24 weeks. Primary outcome would include the changes in the Montreal Cognitive Assessment scale scores at the end of the intervention. Secondary outcomes would include the changes in the Montreal Cognitive Assessment scale scores at 12 weeks following the first intervention and changes in the scores of the Alzheimer's Disease Assessment Scale-cognitive subscale-3, the European Quality of Life Five Dimension Five Level scale, Korean Instrumental Activities of Daily Living, Korean Activities of Daily Living, and Geriatric Depression Scale at 12 and 24 weeks following the first intervention., Discussion: The results of our trial would provide clinical trial data concerning the usefulness, safety, and efficacy of Cheonwangbosimdan in the management of mild cognitive impairment., Trial Registration: Clinical Research Information Service (Date: November 26, 2021; Registration No. KCT0006787; https://cris.nih.go.kr/cris/search/detailSearch.do?search&#95;lang=E&search&#95;page=M&pageSize=10&page=undefined&seq=20869&status=5&seq&#95;group=20869).

When timely access to deceased-donor livers is not feasible, living-donor liver transplantation (LDLT) is an attractive option for patients with hepatorenal syndrome (HRS). This study's primary objective was to describe outcomes after LDLT among HRS recipients, and the secondary objective was to determine predictors of poor renal recovery after LDLT. This single-center, retrospective study included 2185 LDLT recipients divided into HRS (n = 126, 5.8%) and non-HRS (n = 2059, 94.2%) groups. The study outcomes were survival and post-LT renal recovery. The HRS group had a higher death rate than the non-HRS group (17.5% vs. 8.6%, p < 0.001). In the HRS group, post-LT renal recovery occurred in 69.0%, and the death rate was significantly lower in association with HRS recovery compared with non-recovery (5.7% vs. 43.6%, p < 0.001). Multivariable analysis indicated that post-LT sepsis (p < 0.001) and non-recovery of HRS (p < 0.001) were independent negative prognostic factors for survival. Diabetes mellitus (p = 0.01), pre-LT peak serum creatinine ≥3.2 mg/dl (p = 0.002), time interval from HRS diagnosis to LDLT ≥38 days (p = 0.01), and post-LT sepsis (p = 0.03) were important negative prognostic factors for renal recovery after LDLT. In conclusion, post-LT renal recovery was important for survival, and the interval from HRS to LDLT was significantly associated with post-LT renal recovery., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

BACKGROUND This retrospective study from a single center aimed to evaluate the long-term patency of all-in-one sleeve venoplasty (ASV) in 16 patients who underwent living donor liver transplantation (LDLT) with a right liver graft (RLG) between 2009 and 2019. ASV unifies the right hepatic vein (RHV), short hepatic vein (SHV), and middle hepatic vein (MHV) of an RLG. ASV enables wide side-to-side anastomosis to the recipient inferior vena cava (IVC). MATERIAL AND METHODS Of 2875 patients who underwent LDLT with an RLG from August 2009 to July 2019, 16 (0.5%) patients underwent ASV. We analyzed the ASV techniques applied to these patients, as well as patient long-term outcomes. RESULTS Type 1 ASV unified 1 RHV, 1 IRHV, and 1 MHV conduit (n=12 [75.0%]). Type 2 ASV unified 1 RHV, multiple IRHVs, and 1 MHV conduit (n=4 [25.0%]). All patients are currently alive, with a mean follow-up period of 70.1±41.9 months. No patient underwent retransplantation. Follow-up computed tomography showed SHV occlusion in 1 (6.3%) patient at 4 months, resulting in 1-, 3-, and 5-year SHV patency rates of 93.8% each. MHV occlusion was identified in 6 (37.5%) patients, with 1-, 3-, and 5-year MHV patency rates of 81.3%, 68.8%, and 68.8%, respectively (P=0.037). No patient underwent endovascular stenting of the SHV or MHV. Patency rates were significantly higher for SHV than MHV (P=0.037). CONCLUSIONS ASV using various vascular patches is a useful technique enabling secure reconstruction of an RLG in grafts with complex hepatic vein anatomy or recipients with poor IVC condition.

Background: With the recent rapid increase in the prevalence of obesity, the number of obese patients requiring liver resection, including laparoscopy, has increased. Accordingly, evaluating the outcome of laparoscopic liver resection in obese patients is increasingly important. This study aimed to compare the safety and feasibility of laparoscopic major liver resection (LMR) and open major liver resection (OMR) in patients with a high body mass index (BMI > 25.0 kg/m 2 )., Methods: We reviewed 521 patients with high BMI (> 25.0 kg/m 2 ) who underwent major liver resection for various indications between January 2009 and November 2018 at Asan Medical Center. We performed 1:1 propensity score matching of the LMR and OMR groups, with 120 patients subsequently included in each group., Results: LMR was associated with lower blood loss and shorter postoperative hospital stays (p < 0.001). Although there was no significant difference in overall complications (p = 0.080), non-liver-specific complications were observed less frequently after LMR (p = 0.025). American Society of Anesthesiologists class > II, BMI > 30 kg/m 2 , and malignancy were independent predictors of morbidity. In a subgroup analysis of patients with hepatocellular carcinoma, there was no significant difference between the two groups in overall survival (hazard ratio 0.225; 95% confidence interval 0.049-1.047; p = 0.057) and recurrence-free survival (hazard ratio 0.761; 95% confidence interval 0.394-1.417; p = 0.417)., Conclusions: Obesity should not be considered a contraindication for major liver resection using a laparoscopic approach; however, when applying this approach for resecting malignancies in patients with a BMI > 30 kg/m 2 and comorbid diseases, special attention should be paid to the possibility of complications., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Human tonsil-derived mesenchymal stem cells (TMSCs) have a superior proliferation rate and differentiation potential compared to adipose-tissue-derived MSCs (AMSCs) or bone-marrow-derived MSCs (BMSCs). TMSCs exhibit a significantly higher expression of the tensin3 gene ( TNS3 ) than AMSCs or BMSCs. TNS is involved in cell adhesion and migration by binding to integrin beta-1 (ITG β1) in focal adhesion. Here, we investigated the roles of four TNS isoforms, including TNS3 and their relationship with integrin in various biological processes of TMSCs. Suppressing TNS1 and TNS3 significantly decreased the cell count. The knockdown of TNS1 and TNS3 increased the gene and protein expression levels of p16, p19, and p21. TNS1 and TNS3 also have a significant effect on cell migration. Transfecting with siRNA TNS3 significantly reduced Oct4, Nanog, and Sox-2 levels. Conversely, when TNS4 was silenced, Oct4 and Sox-2 levels significantly increase. TNS1 and TNS3 promote osteogenic and adipogenic differentiation, whereas TNS4 inhibits adipogenic differentiation of TMSCs. TNS3 is involved in the control of focal adhesions by regulating integrin. Thus, TNS enables TMSCs to possess a higher proliferative capacity and differentiation potential than other MSCs. Notably, TNS3 plays a vital role in TMSC biology by regulating ITGβ1 activity., Competing Interests: The authors indicated no potential conflict of interest.

We propose an active optical Fano switch (OFS) based on an embedded dielectric metasurface (EDM) including dual-layer graphene (DLG). An EDM is a dielectric grating overlapped by two cladding layers, and it excites a Fano resonance. DLG is positioned inside the upper cladding layer to maximize light-graphene interaction. Thus, with a small change of the chemical potential (µ c ) of graphene, a resonance wavelength is tuned to switch the OFS on and off. First, a red-parity asymmetric Fano resonance is realized, and a sharp asymmetric lineshape is achieved by controlling the structural parameters of the EDM and the interaction between the Fano resonance and additional weak Fabry-Perot interference for efficient switching. The distance of a peak-to-dip wavelength (Δλ p-d ) and the change of chemical potential (Δµ c ) for switching is analyzed by varying the duty cycle (DC) and grating thickness (t g ) of the EDM. Furthermore, switching contrast as a figure of merit (FoM) is analyzed. With DC of 0.5 and t g of 70 nm, the OFS requires Δλ p-d of 7.3 nm and Δµ c of 0.25 eV. The FoM of 0.97 is achieved. By adjusting the two parameters, the switching condition is tuned. In the case of a blue parity, the effect of the two parameters exhibits a similar trend to that of the red parity. The FoM, however, is lower due to the reversed parity.

Living donor liver transplantation (LDLT) is a significant advancement for the treatment of children with end-stage liver disease given the shortage of deceased donors. The ultimate goal of pediatric LDLT is to achieve complete donor safety and zero recipient mortality. We conducted a retrospective, single-center assessment of the outcomes as well as the clinical factors that may influence graft and patient survival after primary LDLTs performed between 1994 and 2020. A Cox proportional hazards model was used for multivariate analyses. The trends for independent prognostic factors were analyzed according to the following treatment eras: 1, 1994 to 2002; 2, 2003 to 2011; and 3, 2012 to 2020. Primary LDLTs were performed on 287 children during the study period. Biliary atresia (BA; 52%), acute liver failure (ALF; 26%), and monogenic liver disease (11%) were the leading indications. There were 45 graft losses (16%) and 27 patient deaths (7%) in this population during the study period. During era 1 (n = 81), the cumulative survival rates at 1 and 5 years after LDLT were 90.1% and 81.5% for patients and 86.4% and 77.8% for grafts, respectively. During era 2 (n = 113), the corresponding rates were 92.9% and 92% for patients and 89.4% and 86.7% for grafts, respectively. During era 3 (n = 93), the corresponding rates were 100% and 98.6% for patients and 98.9% and 95.4% for grafts, respectively. In the multivariate analyses, primary diagnosis ALF, bloodstream infection, posttransplant lymphoproliferative disease, and chronic rejection were found to be negative prognostic indicators for patient survival. Based on generalized care guidelines and center-oriented experiences, comprehensive advances in appropriate donor selection, refinement of surgical techniques, and meticulous medical management may eventually realize a zero-mortality rate in pediatric LDLT., (Copyright © 2021 American Association for the Study of Liver Diseases.)

This study aimed to provide preliminary evidence for the efficacy of invasive laser acupuncture (ILA) for chronic non-specific low back pain (CNLBP). This was a single-center, randomized, patient and assessor-blinded, placebo-controlled, parallel-arm, clinical trial with a 1:1:1 allocation ratio that included a full analysis set. Forty-five participants with CNLBP were randomly assigned to the control group (sham laser), 650 group (650 nm-wavelength ILA), or 830 group (830 nm-wavelength ILA) (n = 15/group). All participants received ILA for 10 min, followed by electroacupuncture for 10 min on the same day. The treatment was performed once per day, twice per week for 4 weeks at bilateral BL23, BL24, BL25, and GB30. The primary outcome was the among-group difference of changes in the visual analog scale (VAS) scores at intervention endpoint (week 4). The secondary outcomes were the among-group difference of changes in VAS at 4 weeks after intervention completion (week 8), those in the Korean version of the Oswestry Disability Index (ODI) and the European Quality of Life Five-Dimension- Five-Level (EQ-5D-5L) at intervention endpoint (week 4) and 4 weeks after intervention completion (week 8). The VAS scores of the 650 group decreased significantly compared with those of the control group (p = 0.047; week 4 vs. week 0). The ODI scores of the 650 group (p = 0.018, week 4 vs. week 0; p = 0.006, week 8 vs. week 0) and 830 group (p = 0.014, week 4 vs. week 0) decreased significantly compared with those of the control group. There was no adverse event related to ILA and no significant difference in changes in vital signs among the three groups. The 650 group showed significant improvements in pain intensity and functional disability. The 830 group showed significant improvements in functional disability. Therefore, ILA therapy at 650 nm and 830 nm wavelengths can be used to treat CNLBP., Competing Interests: The authors have declared that no competing interests exist.

Backgrounds/aims: Anatomical resection has superior oncologic outcomes over non-anatomical resection in hepatocellular carcinoma, and left lateral sectionectomy is the simplest and easiest perform anatomical resection procedure among liver resections. The purpose of this study was to find out the safety and feasibility of pure laparoscopic left lateral sectionectomy (PLLLS) for hepatocellular carcinoma., Methods: Patients who underwent left lateral sectionectomy at a tertiary referral hospital, from August 2007 to April 2019 were enrolled in this retrospective study. After matching the 1 : 3 propensity score, 17 open and 51 pure laparoscopic cases were selected out of 102 cases of total left lateral resection for hepatocellular carcinoma. The group was analyzed in terms of patient demographics, preoperative data, and postoperative outcomes., Results: During the study period, there was no open conversion case. The mean operative time and complication were not statistically significant different between the two groups. There was no statistically significant difference in disease-free survival and overall survival had no statistical between the two groups. There were no mortality cases, and postoperative hospital stay was significantly shorter in the PLLLS group than in the open left lateral sectionectomy (OLLS) group., Conclusions: The oncologic outcomes and complication rate were the same in the PLLLS and OLLS groups. However, the hospital stay was shorter in the PLLLS group than in the OLLS group. The present study findings demonstrate that the PLLLS is a safe and feasible procedure for hepatocellular carcinoma.

Thyroid dysfunction has been reported to be an extrapulmonary symptom of COVID-19. It is important to identify the tissue subset that expresses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are essential for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to understand the viral pathogenesis of COVID-19-related thyroid dysfunction. We investigated the expression and distribution of ACE2- and TMPRSS2-expressing cells in the thyroid gland. RT-PCR and Western blotting were performed on human thyroid follicular cells (Nthy-ori3-1) and rat thyroid tissues to detect the expression levels of ACE and TMPRSS2 mRNA and proteins. We also analyzed the expression patterns of ACE2 and TMPRSS2 in 9 Sprague-Dawley rats and 15 human thyroid tissues, including 5 normal, 5 with Hashimoto's thyroiditis, and 5 with Graves' disease, by immunohistochemistry (IHC) and immunofluorescence. Both ACE2 and TMPRSS2 mRNAs and proteins were detected in the thyroid tissue. However, ACE2 and TMPRSS2 proteins were not expressed in thyroid follicular cells. In IHC, ACE2 and TMPRSS2 were not stained in the follicular cells. No cells co-expressed ACE2 and TMPRSS2. ACE2 was expressed in pericytes between follicles, and TMPRSS2 was mainly stained in the colloid inside the follicle. There was no difference in expression between the normal thyroid, Hashimoto's thyroiditis, and Graves' disease. SARS-CoV-2 does not directly invade the thyroid follicular cells. Whether SARS-CoV-2 infection of pericytes can affect COVID-19-related thyroid dysfunction warrants further study.

Background: The outcomes of liver transplantation (LT) have improved, but actual 20-year survival data have rarely been presented., Methods: Longitudinal follow-up data of 20-year LT survivors were retrospectively analyzed. The LT database of our institution was searched to identify patients who underwent primary LT from January 2000 to December 2001. The study cohort of 251 patients was divided into three groups 207 adults who underwent living donor LT (LDLT), 22 adults who underwent deceased donor LT (DDLT), and 22 pediatric patients who underwent LT., Results: Hepatitis B virus-associated liver cirrhosis and biliary atresia were the most common indications for adult and pediatric LT, respectively. Seven patients required retransplantation, including six who underwent DDLT and one who underwent LDLT. Twenty-two patients died within 3 months after LT and 69 died at later intervals. The overall survival rates at 1, 3, 5, 10, and 20 years were 86.4%, 79.6%, 77.7%, 72.8%, and 62.6%, respectively, in the adult LDLT group; 86.4%, 72.7%, 72.7%, 72.7%, and 68.2%, respectively, in the adult DDLT group; and 86.4%, 86.4%, 81.8%, 81.8%, and 77.3%, respectively, in the pediatric LT group (P=0.545). Common immunosuppressive regimens at 20 years included tacrolimus monotherapy, tacrolimus-mycophenolate dual therapy, cyclosporine monotherapy, and mycophenolate monotherapy., Conclusions: The present study is the first report of actual 20-year survival data from a Korean high-volume LT center. The graft and patient survival outcomes reflected the early experiences of LT in our institution, with long-term outcomes being similar regardless of graft type and patient age., (Copyright © 2022 The Korean Society for Transplantation.)

Background: Bloodstream infection (BSI) is one of the most significantly adverse events that can occur after liver transplantation (LT) in children., Aim: To analyze the profile of BSI according to the postoperative periods and assess the risk factors after pediatric LT., Methods: Clinical data, collected from medical charts of children ( n = 378) who underwent primary LT, were retrospectively reviewed. The primary outcome considered was BSI in the first year after LT. Univariate and multivariate analyses were performed to identify risk factors for BSI and respective odds ratios (ORs)., Results: Of the examined patients, 106 (28%) experienced 162 episodes of pathogen-confirmed BSI during the first year after LT. There were 1.53 ± 0.95 episodes per children (mean ± SD) among BSI-complicated patients with a median onset of 0.4 mo post-LT. The most common pathogenic organisms identified were Coagulase-negative staphylococci , followed by Enterococcus spp. and Streptococcus spp. About half (53%) of the BSIs were of unknown origin. Multivariate analysis demonstrated that young age (≤ 1.3 year; OR = 2.1, P = 0.011), growth failure (OR = 2.1, P = 0.045), liver support system (OR = 4.2, P = 0.008), and hospital stay of > 44 d (OR = 2.3, P = 0.002) were independently associated with BSI in the year after LT., Conclusion: BSI was frequently observed in patients after pediatric LT, affecting survival outcomes. The profile of BSI may inform clinical treatment and management in high-risk children after LT., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Dry mouth that occurs after menopause significantly reduces the quality of life of the elderly. The extracellular vesicles derived from mesenchymal stem cells are being studied for application in various pathological conditions in the field of tissue regenerative medicine. This study is to investigate the therapeutic effect on salivary gland dysfunction occurring after ovariectomy using tonsil mesenchymal stem cells (T-MSCs)-derived extracellular vesicles. The rats were divided into the following groups: sham-operated rats (SHAM), rats that underwent ovariectomy (OVX), and rats that underwent OVX surgery and were simultaneously injected with T-MSC-derived extracellular vesicles (OVX+EV). The rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in the OVX group compared with those in the SHAM group. Extracellular vesicles had no effect on estradiol levels or estrogen receptor β expression. The evaluation of pro-inflammatory cytokines, TNF-α and IL-6, increased in the OVX group and decreased in the OVX+EV group. The expressions of collagen I and TGFβI increased in the OVX group but decreased in the OVX+EV group. Moreover, to examine submandibular gland function, AQP5 and α-amylase expressions were downregulated in the OVX group, but improved upon exosome injection. In conclusion, T-MSC-derived extracellular vesicles are useful for the prevented submandibular gland dysfunction that occurs after menopause.

Rationale: Liver injury must be further characterized to identify novel therapeutic approaches. Endoplasmic reticulum (ER) stress may cause hepatocyte death. Gα 12 affects cell viability and its expression varies depending on physiological conditions. This study investigated whether hepatocyte-specific Gα 12 overexpression affects acute liver injury, and if so, what the underlying mechanisms and treatment strategies are. Methods: All experiments were performed using human liver, hepatocytes, and toxicant injury models with Gna12 KO and/or hepatocyte-specific Gα 12 overexpression. RNA-sequencing, immunoblotting, immunohistochemistry, reporter assays, and mutation assays were conducted. Results: Hepatic Gα 12 was overexpressed in mice challenged with acetaminophen or other ER stress inducers or in patients with acute liver injury or fibrosis/cirrhosis. Several Gα 12 and ER-associated pathways were identified using transcriptomic analysis. Acetaminophen intoxication was characterized by lipid peroxide-induced ferroptosis and was less severe in Gα 12 -deficient animals and cells. Conversely, Gα 12 overexpression in wild-type or Gna12 KO hepatocytes increased hepatotoxicity, promoting lipid peroxidation, inflammation, and ferroptosis. IRE1α-dependent Xbp1 transactivated Gna12 . Moreover, Gα 12 overexpression enhanced the ability of acetaminophen to induce ALOX12, while downregulating GPX4. The level of miR-15a, herein identified as an ALOX12 inhibitor, was decreased. siRNA knockdown or pharmacological inhibition of ROCK1 prevented dysregulation of ALOX12 and GPX4, rescuing animals from toxicant-induced ferroptosis. These changes or correlations among the targets were confirmed in human liver specimens and datasets of livers exposed to other injurious medications. Conclusions: Gα 12 overexpression by ER stress facilitates hepatocyte ferroptosis through ROCK1-mediated dysregulation of ALOX12, and miR-15a, supporting the concept that inhibition of Gα 12 overexpression and/or ROCK1 axis may constitute a promising strategy for acute liver injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)