Donor Safety and Risk Factors of Pure Laparoscopic Living Donor Right Hepatectomy: A Korean Multicenter Study.

OBJECTIVE: The aim of this study was to identify safety and risk factors of living donor after pure laparoscopic donor right hepatectomy in a Korean multicenter cohort study. BACKGROUND: Pure laparoscopic donor right hepatectomy is not yet a standardized surgical procedure due to lack of data. METHODS: This retrospective study included 543 patients undergoing PLRDH between 2010 and 2018 in 5 Korean transplantation centers. Complication rates were assessed and multivariate logistic regression analyses were performed to identify risk factors of open conversion, overall complications, major complications, and biliary complications. RESULTS: Regarding open conversion, the incidence was 1.7% and the risk factor was body mass index >30 kg/m 2 [ P =0.001, odds ratio (OR)=22.72, 95% CI=3.56-146.39]. Rates of overall, major (Clavien-Dindo classification III-IV), and biliary complications were 9.2%, 4.4%, and 3.5%, respectively. For overall complications, risk factors were graft weight >700 g ( P =0.007, OR=2.66, 95% CI=1.31-5.41), estimated blood loss ( P <0.001, OR=4.84, 95% CI=2.50-9.38), and operation time >400 minutes ( P =0.01, OR=2.46, 95% CI=1.25-4.88). For major complications, risk factors were graft weight >700 g ( P =0.002, OR=4.01, 95% CI=1.67-9.62) and operation time >400 minutes ( P =0.003, OR=3.84, 95% CI=1.60-9.21). For biliary complications, risk factors were graft weight >700 g ( P =0.01, OR=4.34, 95% CI=1.40-13.45) and operation time >400 minutes ( P =0.01, OR=4.16, 95% CI=1.34-12.88). CONCLUSION: Careful donor selection for PLRDH considering body mass index, graft weight, estimated blood loss, and operation time combined with skilled procedure can improve donor safety.

Pure Laparoscopic Donor Hepatectomy: A Multicenter Experience.

According to recent international consensus conferences, pure laparoscopic donor hepatectomy (PLDH), particularly right and left hepatectomies, is not yet considered a standard practice because studies remain limited. Thus, we present the outcomes of more than 500 PLDH patients, mostly receiving a right hepatectomy. To our knowledge, this is the largest study to date on PLDH. Data from all living liver donors who underwent PLDH at 5 centers in Korea until June 2018 were retrospectively analyzed. The outcomes of both donors and recipients were included. Pearson correlation analysis was used to explore the relationship between the duration of surgery and cumulative experience at each center, which reflects the learning curve. Overall, 545 PLDH cases were analyzed, including 481 right hepatectomies, 25 left hepatectomies, and 39 left lateral sectionectomies (LLS). The open conversion was necessary for 10 (1.8%) donors, and none of the donors died or experienced irreversible disability. Notably, there were 25 (4.6%) patients with major complications (higher than Clavien-Dindo grade 3). All centers except one showed a significant decrease in surgery duration as the number of cases accumulated. Regarding recipient outcomes, there were 110 cases (20.2%) of early major complications and 177 cases (32.5%) of late major complications. This study shows the early and late postoperative outcomes of 545 donors and corresponding recipients, including 481 right hepatectomies and 25 left hepatectomies, from 5 experienced centers. Although the results are comparable to those of previously reported open donor hepatectomy series, further studies are needed to consider PLDH a new standard practice.

Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma.

Exosomal noncoding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance of circulating exosomal ncRNAs in the prognosis of hepatocellular carcinoma (HCC) remains to be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) for human HCC. This prospective study enrolled 79 HCC patients between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome Precipitation Solution. To validate the isolation of the exosomes from serum, immunoblotting for exosome markers and characterization of nanoparticle using NanoSight were performed. NcRNAs were isolated from exosomes using the miRNeasy serum/plasma micro kit. Both circulating exosomal miRNA-21 and lncRNA-ATB were related to TNM stage and other prognostic factors, including the T stage and portal vein thrombosis. Multivariate analysis using the Cox regression test identified that both higher miRNA-21 and higher lncRNA-ATB were independent predictors of mortality and disease progression, along with larger tumor size and higher C-reactive protein (all p < 0.05). The overall survival and progression-free survival were significantly lower in patients with higher circulating levels of exosomal miRNA-21 (≥0.09) and lncRNA-ATB (≥0.0016) (log-rank test: p < 0.05). In conclusion, our study has provided strong evidence that circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) are novel prognostic markers and therapeutic targets for HCC.

Simplified one-orifice venoplasty for middle hepatic vein reconstruction in adult living donor liver transplantation using right lobe grafts.

Middle hepatic vein (MHV) reconstruction is often essential to avoid hepatic congestion and serious graft dysfunction in living donor liver transplantation (LDLT). The aim of this report was to introduce evolution of our MHV reconstruction technique and excellent outcomes of simplified one-orifice venoplasty. We compared clinical outcomes with two reconstruction techniques through retrospective review of 95 recipients who underwent LDLT using right lobe grafts at our institution from January 2008 to April 2012; group 1 received separate outflow reconstruction and group 2 received new one-orifice technique. The early patency rates of MHV in group 2 were higher than those in group 1; 98.4% vs. 88.2% on postoperative day 7 (p = 0.054) and 96.7% vs. 82.4% on postoperative day 14, respectively (p = 0.023). Right hepatic vein (RHV) stenosis developed in three cases in group 1, but no RHV stenosis developed because we adopted one-orifice technique (p = 0.043). The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in group 2 were significantly lower than those in group 1 during the early post-transplant period. In conclusion, our simplified one-orifice venoplasty technique could secure venous outflow and improve graft function during right lobe LDLT.

Variability in Paralytic Shellfish Toxin Profiles and Dinoflagellate Diversity in Mussels and Seawater Collected during Spring in Korean Coastal Seawater.

Paralytic shellfish toxins (PSTs) are potent neurotoxins produced by certain microalgae, particularly dinoflagellates, and they can accumulate in shellfish in coastal seawater and thus pose significant health risks to humans. To explore the relationship between toxicity and PST profiles in seawater and mussels, the spatiotemporal variations in PST concentrations and profiles were investigated along the southern coast of Korea under peak PST levels during spring. Seawater and mussel samples were collected biweekly from multiple stations, and the toxin concentrations in the samples were measured. Moreover, the dinoflagellate community composition was analyzed using next-generation sequencing to identify potential PST-producing species. The PST concentrations and toxin profiles showed substantial spatiotemporal variability, with GTX1 and GTX4 representing the dominant toxins in both samples, and C1/2 tending to be higher in seawater. Alexandrium species were identified as the primary sources of PSTs. Environmental factors such as water temperature and salinity influenced PST production. This study demonstrates that variability in the amount and composition of PSTs is due to intricate ecological interactions. To mitigate shellfish poisoning, continuous monitoring must be conducted to gain a deeper understanding of these interactions.

Detectable depth of unexposed parathyroid glands using near-infrared autofluorescence imaging in thyroid surgery.

Background: Near-infrared light can penetrate the fat or connective tissues overlying the parathyroid gland (PG), enabling early localization of the PG by near-infrared autofluorescence (NIRAF) imaging. However, the depth at which the PG can be detected has not been reported. In this study, we investigated the detectable depth of unexposed PGs using NIRAF during thyroidectomy. Materials and methods: Fifty-one unexposed PGs from 30 consecutive thyroidectomy patients, mapped by an experienced surgeon (K.D. Lee) with the use of NIRAF imaging, were included. For NIRAF detection of PGs, a lab-built camera imaging system was used. Detectable depths of the unexposed PGs were measured using a Vernier caliper. The NIRAF images were classified as faint or bright depending on whether a novice could successfully interpret the image as showing the PG. Data on variables that may affect detectable depth and NIRAF intensity were collected. Results: Detectable depth ranged between 0.35 and 3.05 mm, with a mean of 1.23 ± 0.73 mm. The average NIRAF intensity of unexposed PGs was 3.13 au. After dissection of the overlying tissue, the intensity of the exposed PG increased to 4.88 au (p < 0.001). No difference in NIRAF intensity between fat-covered (3.27 ± 0.90 au) and connective tissue-covered PGs (3.00 ± 1.23 au) was observed (p = 0.369). PGs covered by fat tissue (depth: 1.77 ± 0.67 mm) were found at deeper locations than those covered by connective tissue (depth: 0.70 ± 0.21 mm) (p < 0.001). The brightness of images of the faint group (2.14 ± 0.48 au) was on average 1.24 au lower than that of the bright group (3.38 ± 1.04 au) (p = 0.001). A novice successfully localized 80.4% of the unexposed PGs. Other variables did not significantly affect detectable depth. Conclusion: Unexposed PGs could be mapped using NIRAF imaging at a maximum depth of 3.05 mm and an average depth of 1.23 mm. A novice was able to localize the PGs before they were visible to the naked eye at a high rate. These results can be used as reference data for localization of unexposed PGs in thyroid surgery.

Oxidative Stress and DNA Damage in Pagrus major by the Dinoflagellate Karenia mikimotoi.

Karenia mikimotoi is a common species of red tide dinoflagellate that causes the mass mortality of marine fauna in coastal waters of Republic of Korea. Despite continuous studies on the ecophysiology and toxicity of K. mikimotoi, the underlying molecular mechanisms remain poorly understood. Red sea bream, Pagrus major, is a high-value aquaculture fish species, and the coastal aquaculture industry of red sea bream has been increasingly affected by red tides. To investigate the potential oxidative effects of K. mikimotoi on P. major and the molecular mechanisms involved, we exposed the fish to varying concentrations of K. mikimotoi and evaluated its toxicity. Our results showed that exposure to K. mikimotoi led to an accumulation of reactive oxygen species (ROS) and oxidative DNA damage in the gill tissue of P. major. Furthermore, we found that K. mikimotoi induced the activation of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, in the gill tissue of P. major, with a significant increase in activity at concentrations above 5000 cells/mL. However, the activity of glutathione S-transferase did not significantly increase at the equivalent concentration. Our study confirms that oxidative stress and DNA damage is induced by acute exposure to K. mikimotoi, as it produces ROS and hypoxic conditions in P. major. In addition, it was confirmed that gill and blood samples can be used as biomarkers to detect the degree of oxidative stress in fish. These findings have important implications for the aquaculture of red sea bream, particularly in the face of red tide disasters.

Surgical Outcomes of Laparoscopic versus Open Hepatectomy for Left Hepatocellular Carcinoma: Propensity Score Analyses Using Retrospective Japanese and Korean Individual Patient Data.

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC). Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups. Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group. Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

Chronic exposure to sublethal concentrations of saxitoxin reduces antioxidant activity and immunity in zebrafish but does not affect reproductive parameters.

Saxitoxin produced by dinoflagellates and cyanobacteria can be transferred to humans through intoxicated organisms such as fish, but limited research has addressed the adverse effects of this toxin on aquatic organisms. In this study, we measured the potential effects of a 90-day exposure to saxitoxin (0.1 or 1 µg·L - 1) on body weight and length, antioxidant defense system, immunity, sex hormones, and genes involved in associated key metabolic pathways in zebrafish (Danio rerio). Significant impairments in body weight and length were observed in response to 1 µg·L - 1 saxitoxin in both male and female zebrafish. A significant increase in the levels of malondialdehyde, together with decreased enzymatic activities of catalase and superoxide dismutase, was observed in fish of both sexes exposed to 1 µg·L - 1 saxitoxin, indicating the occurrence of lipid peroxidation and oxidative stress. Immune parameters such as alternative complement activity, lysozyme activity, and immunoglobulin content were also significantly reduced. However, exposure of male and female zebrafish to saxitoxin for 90 days did not significantly affect reproductive parameters such as the gonadosomatic index and plasma concentrations of vitellogenin, estradiol, and 11-keto testosterone. Transcriptional responses showed similar trends to those of the biochemical parameters, as genes involved in the antioxidant defense system and immunity were downregulated, whereas the transcription of genes related to reproductive metabolism showed no significant change upon treatment with 1 µg·L - 1 saxitoxin. Our findings indicate that long-term exposure to a sublethal concentration of saxitoxin can inhibit growth through induction of oxidative stress and immunosuppression, while the reproductive parameters of zebrafish are not a main target of this toxin at sublethal concentrations.

What makes acute cholecystitis recur after removing the percutaneous cholecystostomy tube?

ABSTRACT: Percutaneous transhepatic gallbladder drainage (PTGBD) is an alternative treatment option for acute cholecystitis. However, the disease may recur after PTGBD catheter removal. This study aimed to evaluate the role of endoscopic sphincterotomy and other risk factors in reducing the recurrence of cholecystitis.We retrospectively analyzed data from 1088 patients who underwent PTGBD for cholecystitis at Kyungpook National University Hospital, Republic of Korea, between January 2011 and April 2018.A total of 115 patients were enrolled in the study. The recurrence rate of cholecystitis was 17.4% (n = 20) during a median follow-up period of 1159 (range, 369-2774) days. Endoscopic biliary sphincterotomy did not significantly affect the recurrence rate of cholecystitis (P = .561). In multivariable analysis, cystic duct stones (P = .013) and PTGBD catheter migration before the prescheduled removal time (P = .002) were identified as independent risk factors for cholecystitis recurrence after PTGBD.To reduce post-PTGBD recurrence in cholecystitis, caution must be exercised to avoid inadvertent dislodging of the PTGBD catheter. In cases of cholecystitis with cystic duct stones, cholecystectomy should be considered only after careful assessment of postoperative risks. Instead, transluminal endoscopic gallbladder drainage could represent a promising option for the prevention of recurrent cholecystitis.

A Case of Hepatic Immunoglobulin G4-Related Disease Presenting as an Inflammatory Pseudotumor and Sclerosing Cholangitis.

An inflammatory pseudotumor is a benign disease characterized by tumor-like lesions consisting of inflammatory cells including plasma cells and fibrous tissue. Recently, some inflammatory pseudotumor cases proved to be a form of Immunoglobulin G4-related disease (IgG4-RD). This novel clinical entity, recognized as a fibroinflammatory condition, is characterized by lymphoplasmacytic infiltration with a predominance of IgG4-positive plasma cells, storiform fibrosis, and often elevated serum IgG4 concentrations. We report a case of IgG4-RD in the form of an inflammatory pseudotumor in the liver with combined sclerosing cholangitis. We recommend that for diagnosing IgG4-RD accurately, it is important to obtain adequate tissue samples and follow-up the lesion in clinical practice.

A tissue attached to self-expandable metal stents for biliary stricture could be useful to find malignancy.

Biliary strictures can have several benign or malignant causes. We attempted to determine the usefulness of establishing a diagnosis using self-expandable metal stents (SEMS) in a prospective series of patients with suspected malignant biliary obstruction. Data of patients who underwent SEMS removal from August 2016 to December 2019 were collected. During this period, 55 patients underwent endobiliary biopsy and SEMS insertion and removal. Fifty-five consecutive patients (mean age, 69 years; range 53-90 years) were enrolled, and of these, 37 were male and 18 were female. A final diagnosis was established using biopsy specimens in 37 cases (67.3%) and surgical specimens in 6 cases (10.9%), with 12 cases (21.8%) diagnosed on radiological follow-up. The final diagnoses included malignancy in 34 cases (61.8%) and benign stricture in 21 cases (38.2%). Endobiliary biopsy had a sensitivity and specificity of 44.1% and 95.2%, whereas SEMS cytology had a sensitivity and specificity of 52.9% and 100%, respectively. Combining endobiliary biopsy and/or SEMS cytology yielded a sensitivity and specificity of 73.5% and 95.2%, respectively. (1) The use of biopsy results alone as a diagnostic tool yielded an area under the receiver operating characteristic curve (AUC) of 0.70 (0.60-0.79). (2) The addition of SEMS to the biopsy results yielded an AUC of 0.86 (0.78-0.94). (3) The addition of CA 19-9 levels to the biopsy results yielded an AUC of 0.81 (0.71-0.94). (4) Combining the endobiliary biopsy results, SEMS tissues, and CA 19-9 levels yielded the best diagnostic accuracy, with an AUC of 0.90 (0.83-0.98). Detection of biliary obstruction using the combination strategy was better than the diagnostic results based on biopsy alone according to recent 3-year data. Our study suggested that SEMS removal could help establish a diagnosis of suspected malignant biliary obstruction.

Circular Noncoding RNA hsa_circ_0003570 as a Prognostic Biomarker for Hepatocellular Carcinoma.

Circular RNAs (circRNAs) are potential biomarkers owing to their stability, tissue specificity, and abundance. This study aimed to evaluate the clinical significance of hsa_circ_0003570 expression and to investigate its potential as a biomarker in hepatocellular carcinoma (HCC). We evaluated hsa_circ_0003570 expression in 121 HCC tissue samples, its association with clinicopathological characteristics, and overall and progression-free survival. Hsa_circ_0003570 expression was downregulated in HCC tissues. Low hsa_circ_0003570 expression was more common in tumors larger than 5 cm (odds ratio (OR), 6.369; 95% confidence interval (CI), 2.725−14.706; p < 0.001), vessel invasion (OR, 5.128; 95% CI, 2.288−11.494; p < 0.001); advanced tumor-node metastasis stage (III/IV; OR, 4.082; 95% CI, 1.866−8.929; p < 0.001); higher Barcelona Clinic Liver Cancer stage (B/C; OR, 3.215; 95% CI, 1.475−6.993; p = 0.003); and higher AFP (>200 ng/mL; OR, 2.475; 95% CI, 1.159−5.291; p = 0.018). High hsa_circ_0003570 expression was an independent prognostic factor for overall survival (hazard ratio (HR), 0.541; 95% confidence interval (CI), 0.327−0.894; p = 0.017) and progression-free survival (HR, 0.633; 95% CI, 0.402−0.997; p = 0.048). Hsa_circ_0003570 is a potential prognostic biomarker in patients with HCC, and further validation of hsa_circ_0003570 is needed.

Long interspersed nuclear element-1 hypomethylation is associated with poor outcomes via the activation of ST18 in human hepatocellular carcinoma.

ABSTRACT: The level of long interspersed nuclear element-1 (LINE-1) methylation, representing the global deoxyribonucleic acid methylation level, could contribute to the prognosis of cancer via the activation of oncogenes. This study was performed to evaluate the prognostic implications of LINE-1 hypomethylation in patients with hepatocellular carcinoma (HCC) and the possible mechanisms related to oncogene activation.Seventy-seven HCC patients between October 2014 and September 2015 were enrolled in this prospective study. Quantitative pyrosequencing was performed to assess the LINE-1 methylation level of HCC and matched non-HCC tissue samples. The expression of suppression of tumorigenicity 18 was measured by immunohistochemistry and its correlation with LINE-1 methylation levels was examined.LINE-1 was significantly hypomethylated in the HCC tissue compared with the matched nontumor tissue (64.0 ± 11.6% vs 75.6 ±â€Š4.0%, P < .001). LINE-1 hypomethylation was an independent risk factor for overall survival (hazard ratio = 27.291, P = .032) and disease progression (hazard ratio = 5.298, P = .005). The expression of suppression of tumorigenicity 18 was higher in the hypomethylated LINE-1 HCC tissue than the hypermethylated LINE-1 tumor tissue (P = .030).LINE-1 hypomethylation may serve as a potential prognostic marker for patients with HCC.

The Anti-Oxidative and Anti-Neuroinflammatory Effects of Sargassum horneri by Heme Oxygenase-1 Induction in BV2 and HT22 Cells.

Sargassum horneri is used as a traditional medicinal agent and exhibits various pharmacological effects. In this study, we found that the 70% EtOH extract contained 34.37 ± 0.75 µg/mg fucosterol. We tested the antioxidant activities of the 70% EtOH extracts and their fractions. The CH2Cl2-soluble fraction showed the strongest DPPH and ABTS radical scavenging activities. Next, we evaluated the anti-neuroinflammatory effects of S. horneri on lipopolysaccharide (LPS)-stimulated BV2 cells. Pretreatment with the extract and fractions suppressed LPS-induced production of nitric oxide (NO) in BV2 cells. The 70% EtOH, CH2Cl2-soluble fraction, and water-soluble fraction inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, as well as markedly blocking LPS-induced expression of inducible NO synthase and cyclooxygenase-2 via inactivation of the nuclear factor-kappa B pathway. In addition, the CH2Cl2-soluble fraction showed the most remarkable heme oxygenase (HO)-1 expression effects and increased nuclear erythroid 2-related factor translocation in the nucleus. In HT22 cells, the CH2Cl2-soluble fraction inhibited cell damage and ROS production caused by glutamate via the regulation of HO-1. Therefore, CH2Cl2-soluble fractions of S. horneri can attenuate oxidative action and neuroinflammatory responses via HO-1 induction, demonstrating their potential in the treatment of neuroinflammatory diseases.

Synchronous gallbladder metastasis of renal cell carcinoma presenting as a gallbladder polyp: A case report.

RATIONALE: Gallbladder polyps are common in the general population, but gallbladder metastasis of renal cell carcinoma (RCC) is very rare. In a patient with RCC diagnosed with a small gallbladder polyp that does not meet the traditional size criteria, the surgeon faces a dilemma of whether cholecystectomy should be performed given the possibility of metastasis. PATIENT CONCERNS: A 55-year-old man who had received a left nephrectomy for RCC presented with a gallbladder polyp that was noted at the time of the nephrectomy. Imaging showed the maximum diameter of the polyp had increased from 5 mm to 24 mm in the 40 months after the initial diagnosis. DIAGNOSIS: Pathological and immunohistology findings confirmed the gallbladder polyp as a metastasis of clear-cell RCC. INTERVENTIONS: : We performed a laparoscopic cholecystectomy. OUTCOMES: Even though the synchronous solitary gallbladder metastasis was left untreated and a cholecystectomy was not performed over the 40 months, no metastasis occurred in other sites. The patient is free from disease 10 months after the cholecystectomy. LESSONS: Solitary gallbladder metastasis of RCC may have more favorable outcomes than typical metastases. Although gallbladder metastasis of RCC occur rarely, it can occur, and any changes in gallbladder polyps in RCC patients should be managed under a strong suspicion of metastasis.

Circular noncoding RNA hsa_circ_0005986 as a prognostic biomarker for hepatocellular carcinoma.

Circular RNAs (circRNAs) represent potential biomarkers because of their highly stable structure and robust expression pattern in clinical samples. The aim of this study was to evaluate the expression of a recently identified circRNA, hsa_circ_0005986; determine its clinical significance; and evaluate its potential as a biomarker of hepatocellular carcinoma (HCC). We evaluated hsa_circ_0005986 expression in 123 HCC tissue samples, its clinical significance, and its association with patients' clinicopathological characteristics and survival. Hsa_circ_0005986 expression was downregulated in HCC tissues. Low hsa_circ_0005986 expression was more common in tumors larger than 5 cm [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.51-6.76; p = 0.002], advanced TNM stage (III/IV; OR, 2.39; 95% CI, 1.16-4.95; p = 0.018), and higher BCLC stage (B/C; OR, 2.71; 95% CI, 1.30-5.65; p = 0.007). High hsa_circ_0005986 expression was associated with improved survival and was an independent prognostic factor for overall [hazard ratio (HR), 0.572; 95% CI, 0.339-0.966; p = 0.037] and progression-free (HR, 0.573; 95% CI, 0.362-0.906; p = 0.017) survival. Moreover, the circRNA-miRNA-mRNA network was constructed using RNA-seq/miRNA-seq data and clinical information from TCGA-LIHC dataset. Our findings indicate a promising role for hsa_circ_0005986 as a prognostic biomarker in patients with HCC.

UVB protective effects of Sargassum horneri through the regulation of Nrf2 mediated antioxidant mechanism.

The present study aimed to evaluate the protective effect of a methanol extract of Sargassum horneri (SHM), which contains 6-hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydrobenzofuran-2(4H)-one (HTT) and apo-9'-fucoxanthinone, against ultraviolet B (UVB)-induced cellular damage in human keratinocytes and its underlying mechanism. SHM significantly improved cell viability of UVB-exposed human keratinocytes by reducing the generation of intracellular reactive oxygen species (ROS). Moreover, SHM inhibited UVB exposure-induced apoptosis by reducing the formation of apoptotic bodies and the populations of the sub-G1 hypodiploid cells and the early apoptotic cells by modulating the expression of the anti- and pro-apoptotic molecules, Bcl-2 and Bax, respectively. Furthermore, SHM inhibited NF-κB p65 activation by inducing the activation of Nrf2/HO-1 signaling. The cytoprotective and antiapoptotic activities of SHM are abolished by the inhibition of HO-1 signaling. In further study, SHM restored the skin dryness and skin barrier disruption in UVB-exposed human keratinocytes. Based to these results, our study suggests that SHM protects the cells against UVB-induced cellular damages through the Nrf2/HO-1/NF-κB p65 signaling pathway and may be potentially useful for the prevention of UVB-induced skin damage.

Efficacy and safety of a switch from twice-daily tacrolimus to once-daily generic tacrolimus in stable liver transplant patients.

Background: Once-daily tacrolimus reduces non-compliance relative to twice-daily tacrolimus. However, little is known about the safety and efficacy of conversion from twice-daily tacrolimus to generic once-daily tacrolimus in liver transplantation (LT). Herein, we investigated the efficacy and safety of a switch from twice-daily tacrolimus to generic once-daily tacrolimus in patients with stable liver graft function. Methods: This prospective, multicenter, open-label, single-arm study was conducted in 17 medical centers for 1 year from July 2019 to July 2020 (NCT04069065). Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR) for 24 weeks after conversion. Secondary endpoints were graft failure, patient death, and adverse events (AEs). Results: Of 151 screened LT patients, 144 patients were enrolled. BPAR, graft failure, and patient death did not occur in this patient population. There were no statistical differences in blood tests, liver function tests, or biochemical tests between visits in any of the patients. Median tacrolimus trough level decreased abruptly from 4.7 ng/mL to 3.2 ng/mL after generic once-daily tacrolimus conversion, but median tacrolimus dose increased due to low tacrolimus trough level. Ninety-two adverse events occurred in 54 patients. Liver enzyme levels increased in seven patients (4.9%) after the switch to generic once-daily tacrolimus, but the liver function tests of these patients normalized thereafter. There were three cases of severe AEs not related to investigational drug. Conclusions: Present study suggests that conversion from twice-daily tacrolimus to generic once-daily tacrolimus is effective and safe in stable LT patients.

Natural soluble human leukocyte antigen class I in donor serum neutralizes donor-specific HLA alloantibodies in recipient serum.

BACKGROUND: Human leukocyte antigen (HLA) molecules are cell-bound but can be identified in a soluble form. These soluble HLA (sHLA) molecules have an immunomodulatory function. We investigated whether natural sHLA in donor serum can neutralize donor-specific HLA alloantibodies (DSAs) in recipient serum. METHODS: Neutralizing effects of donor serum on DSAs in recipient serum were measured using inhibition assay principle of flow cytometric crossmatch (FCXM), performed using sera from 143 kidney transplant recipients and their donors. The adding of donor serum to recipient serum yielded lower mean fluorescence intensity (MFI) ratios (test/control) than when diluent was added [Roswell Park Memorial Institute (RPMI) or third-party serum], which was presumed to be caused by the neutralizing effects of sHLA. RESULTS: In the recipient group with class I DSAs alone (N=14), donor serum addition to recipient serum resulted in lower T cell MFI ratios [2.25 (1.31‒32.51)] than those observed on RPMI addition [3.04 (1.33‒125.39), P <0.05]. In the recipient group with class II DSAs alone (N=27), donor serum addition showed no significant difference in B cell MFI ratios [5.03 (1.41‒103.53)] compared to diluent addition: RPMI [4.50 (1.34‒145.98)] or third-party serum [5.08 (1.44‒138.47)], P >0.05 for both. CONCLUSION: Using inhibition FCXM, we verified that natural sHLA class I in donor serum neutralizes DSAs in recipient serum. However, no neutralizing effects of sHLA class II were revealed in this study. These potentially beneficial effects of sHLA infused via blood-derived products should be considered when desensitizing highly HLA-sensitized patients.