Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes.

BACKGROUND: Liver injury is common in severe acute pancreatitis (SAP). Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes, which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis. Our previous study found that milk fat globule epidermal growth factor 8 (MFG-E8) alleviates acinar cell damage during SAP via binding to αvß3/5 integrins. MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy. AIM: To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux. METHODS: SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50 µg/kg cerulein plus lipopolysaccharide. mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAP-induced liver injury. Cilengitide, a specific αvß3/5 integrin inhibitor, was used to investigate the possible mechanism of MFG-E8. RESULTS: The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice, enhanced autophagy flux in hepatocyte, and worsened the degree of ferroptosis. Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner. Mechanistically, MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells. Cilengitide abolished MFG-E8's beneficial effects in SAP-induced liver injury. CONCLUSION: MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury. MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrin αVß3/5.

Liver transplantation using magnetic anastomosis in pigs.

Magnetic anastomosis substantially shortens the duration of vascular anastomosis. We aimed to apply magnetic anastomosis technology (MAT) to donor liver implantations in pig orthotopic liver transplantation (OLT). Twenty healthy adult pigs were randomly divided into donors and recipients, and major vascular anastomosis was performed using MAT during OLT. Recipient liver and kidney function was measured pre-surgery and 12, 24 and 72 h post-surgery. Vascular anastomoses examinations were performed using ultrasound or angiography weekly post-surgery, and pathological examinations of vascular anastomoses were performed during autopsy after animal euthanasia. All recipients survived 24 h after surgery, which is considered as successful transplantation. Anhepatic duration was only 13 min, and no anastomotic obstruction or stenosis, magnetic displacement and anastomotic angulation, or distortion was found upon postoperative examinations of major liver vasculature. Aspartate aminotransferase, alanine aminotransferase, and total bilirubin serum levels increased considerably postoperatively. The follow-up period for this study was 1 year, and the median survival time of all recipients was 115 d (interquartile range = 11-180 d). The main causes of death were liver failure, immune rejection, infection, and arterial anastomotic bleeding. Moreover, vascular anastomoses healed well with a survival time of more than two weeks. We developed a novel magnetic device to create a fast and safe technique to perform major vascular anastomoses in pig liver transplantations. Additionally, the liver graft implantation using MAT considerably shortened the recipient warm ischemia time, which will reduce the extent of ischemia-reperfusion injury. We conclude that MAT is an effective method for donor liver fast implantation in OLT in pigs.

The m6A reader YTHDF1 attenuates fulminant hepatitis via MFG-E8 translation in an m6A dependent manner.

Background and Aims: N6-methyladenosine (m6A) is the most common post-transcriptional modification of RNA in eukaryotes, which has been demonstrated to play important roles in various biological processes. However, its roles in fulminant hepatitis remain largely unknown. In the current study, YTHDF1 expression was found to be significantly downregulated in the livers among patients, as well as murine models with fulminant hepatitis versus normal controls. Thus, we hypothesized that YTHDF1 protects against fulminant hepatitis and investigated the underlying molecular mechanisms. Methods: Fulminant hepatitis was induced by D-GalN/LPS in conventional YTHDF1 knockout (YTHDF1-/-) mice, hepatocyte-specific YTHDF1 overexpression (AAV8- YTHDF1) mice, and corresponding control mice. Primary hepatocytes were cultured and subjected to LPS insult in vitro. Hepatic histology, cell death, oxidative stress and mitochondrial function were examined to assess liver damage. The molecular mechanisms of YTHDF1 function were explored using multi-omics analysis. Results: Ablation of YTHDF1 exacerbated hepatic apoptosis and reactive oxygen species (ROS) production and increased the number of aberrant mitochondria, while YTHDF1 overexpression resulted in the opposite effects. Multiomics analysis identified MFG-E8 as the direct target of YTHDF1. YTHDF1 augmented the translation of MFG-E8 in an m6A-dependent manner without effect on its mRNA expression, thereby restoring mitochondrial function. Additionally, administration of MFG-E8 almost completely reversed the YTHDF1 deficiency-mediated exacerbation of liver injury. Conclusions: The current study suggested that the m6A reader YTHDF1 alleviates cell death, enhances antioxidant capacity and restores mitochondrial function in fulminant hepatitis by promoting MFG-E8 protein translation in an m6A-dependent manner.

Magnetic-assisted laparoscopic liver transplantation in swine.

BACKGROUND: Although laparoscopic technology has achieved rapid development in the surgical field, it has not been applied to liver transplantation, primarily because of difficulties associated with laparoscopic vascular anastomosis. In this study, we introduced a new magnetic-assisted vascular anastomosis technique and explored its application in laparoscopic liver transplantation in pigs. METHODS: Two sets of magnetic vascular anastomosis rings (MVARs) with different diameters were developed. One set was used for anastomosis of the suprahepatic vena cava (SHVC) and the other set was used for anastomosis of the infrahepatic vena cava (IHVC) and portal vein (PV). Six laparoscopic orthotopic liver transplantations were performed in pigs. Donor liver was obtained via open surgery. Hepatectomy was performed in the recipients through laparoscopic surgery. Anastomosis of the SHVC was performed using hand-assisted magnetic anastomosis, and the anastomosis of the IHVC and PV was performed by magnetic anastomosis with or without hand assistance. RESULTS: Liver transplants were successfully performed in five of the six cases. Postoperative ultrasonographic examination showed that the portal inflow was smooth. However, PV bending and blood flow obstruction occurred in one case because the MVARs were attached to each other. The durations of loading of MVAR in the laparoscope group and manual assistance group for IHVC and PV were 13 ± 5 vs. 5 ± 1 min (P < 0.01) and 10 ± 2 vs. 4 ± 1 min (P < 0.05), respectively. The durations of MVAR anastomosis in the laparoscope group and manual assistance group for IHVC and PV were 5 ± 1 vs. 1 ± 1 min (P < 0.01), and 5 ± 1 vs. 1 ± 1 min (P < 0.01), respectively. The anhepatic phase was 43 ± 4 min in the laparoscope group and 23 ± 2 min in the manual assistance group (P < 0.01). CONCLUSIONS: Our study showed that magnetic-assisted laparoscopic liver transplantation can be successfully carried out in pigs.

Liver fibrosis promotes immune escape in hepatocellular carcinoma via GOLM1-mediated PD-L1 upregulation.

Immune checkpoint blockade is considered a breakthrough in cancer treatment. However, with the low response rates and therapeutic resistance of patients with hepatocellular carcinoma (HCC), the challenges facing the application of this treatment are tremendous. Liver fibrosis is a key driver of tumor immune escape, the underlying mechanism has never been clarified. This study sought to explore the role of liver fibrosis in regulating tumor-infiltrating lymphocytes (TILs) and inducing tumor immunosuppression. Ninety-nine fixed HCC tissue samples were used to analyze the association between liver fibrosis and immune escape using immunohistochemistry. In HCC patients, low FIB-4 values and high CD8+ T cell infiltration were correlated with prolonged survival. Elevated expression of immune checkpoints and attenuated antitumor immunity were observed in CCl4-induced mice liver fibrosis models and human fibrotic livers compared to control group. GOLM1 levels were increased in livers of patients with fibrosis and mice in response to CCl4-induced liver fibrosis. CD8+ T cell infiltrations were significantly decreased and PD-L1 expression was significantly increased in tumor tissues from hepatocyte-specific GOLM1 transgenic mice (Alb/GOLM1 mice) inducing chemical carcinogenesis compared to their corresponding control WT mice. GOLM1 induced PD-L1 expression via EGFR pathway activation. EGFR inhibitors, especially together with anti-PD-L1 therapy, improved the efficacy of immunotherapy in HCC. These findings illustrate the importance of liver fibrosis-induced immunosuppression as a tumor-promoting mechanism. GOLM1, which is highly upregulated in the fibrotic liver, regulates tumor microenvironmental immune escape via the EGFR/PD-L1 signaling pathway. EGFR blockade may bolster the efficacy of immune checkpoint inhibitors for HCC treatment.

T-tube vs no T-tube for biliary tract reconstruction in adult orthotopic liver transplantation: An updated systematic review and meta-analysis.

BACKGROUND: Whether to use a T-tube for biliary anastomosis during orthotopic liver transplantation (OLT) remains a debatable question. Some surgeons chose to use a T-tube because they believed that it reduces the incidence of biliary strictures. Advances in surgical techniques during the last decades have significantly decreased the overall incidence of postoperative biliary complications. Whether using a T-tube during OLT is still associated with the reduced incidence of biliary strictures needs to be re-evaluated. AIM: To provide an updated systematic review and meta-analysis on using a T-tube during adult OLT. METHODS: In the electronic databases MEDLINE, PubMed, Scopus, ClinicalTrials.gov, the Cochrane Library, the Cochrane Hepato-Biliary Group Controlled Trails Register, and the Cochrane Central Register of Controlled Trials, we identified 17 studies (eight randomized controlled trials and nine comparative studies) from January 1995 to October 2020. The data of the studies before and after 2010 were separately extracted. We chose the overall biliary complications, bile leaks or fistulas, biliary strictures (anastomotic or non-anastomotic), and cholangitis as outcomes. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to describe the results of the outcomes. Furthermore, the test for overall effect (Z) was used to test the difference between OR and 1, where P ≤ 0.05 indicated a significant difference between OR value and 1. RESULTS: A total of 1053 subjects before 2010 and 1346 subjects after 2010 were included in this meta-analysis. The pooled results showed that using a T-tube reduced the incidence of postoperative biliary strictures in studies before 2010 (P = 0.012, OR = 0.62, 95%CI: 0.42-0.90), while the same benefit was not seen in studies after 2010 (P = 0.60, OR = 0.76, 95%CI: 0.27-2.12). No significant difference in the incidence of overall biliary complications (P = 0.37, OR = 1.41, 95%CI: 0.66-2.98), bile leaks (P = 0.89, OR = 1.04, 95%CI: 0.63-1.70), and cholangitis (P = 0.27, OR = 2.00, 95%CI: 0.59-6.84) was observed between using and not using a T-tube before 2010. However, using a T-tube appeared to increase the incidence of overall biliary complications (P = 0.049, OR = 1.49, 95%CI: 1.00-2.22), bile leaks (P = 0.048, OR = 1.91, 95%CI: 1.01-3.64), and cholangitis (P = 0.02, OR = 7.21, 95%CI: 1.37-38.00) after 2010. A random-effects model was used in biliary strictures (after 2010), overall biliary complications (before 2010), and cholangitis (before 2010) due to their heterogeneity (I 2 = 62.3%, 85.4%, and 53.6%, respectively). In the sensitivity analysis (only RCTs included), bile leak (P = 0.66) lost the significance after 2010 and a random-effects model was used in overall biliary complications (before 2010), cholangitis (before 2010), bile leaks (after 2010), and biliary strictures (after 2010) because of their heterogeneity (I 2 = 92.2%, 65.6%, 50.9%, and 80.3%, respectively). CONCLUSION: In conclusion, the evidence gathered in our updated meta-analysis showed that the studies published in the last decade did not provide enough evidence to support the routine use of T-tube in adults during OLT.

CXCL12 promotes spinal nerve regeneration and functional recovery after spinal cord injury.

Spinal cord injury (SCI) leads to permanent loss of motor and sensory function due to the complex mechanisms of the external microenvironment and internal neurobiochemistry that restrict neuronal plasticity and axonal regeneration. Chemokine CXCL12 was verified in regulating the development of central nervous system (CNS) and repairing of CNS disease. In the present study, CXCL12 was downregulated in the spinal cord after SCI. SCI also induced gliosis and loss of synapse. Intrathecal treatment of CXCL12 promoted the functional recovery of SCI by inducing the formation of neuronal connections and suppressing glia scar. To confirm whether CXCL12 promoted synapse formation and functional neuronal connections, the primary cortical neurons were treated with CXCL12 peptide, the synapse was examined using Immunofluorescence staining and the function of synapse was tested using a whole-cell patch clamp. The results indicated that CXCL12 peptide promoted axonal elongation, branche formation, dendrite generation and synaptogenesis. The electrophysiological results showed that CXCL12 peptide increased functional connections among neurons. Taken together, the present study illustrated an underlying mechanism of the development of SCI and indicated a potential approach to facilitate functional recovery of spinal cord after SCI.

Fedora-type magnetic compression anastomosis device for intestinal anastomosis.

BACKGROUND: Although previous studies have confirmed the feasibility of magnetic compression anastomosis (MCA), there is still a risk of long-term anastomotic stenosis. For traditional MCA devices, a large device is associated with great pressure, and eventually increased leakage. AIM: To develop a novel MCA device to simultaneously meet the requirements of pressure and size. METHODS: Traditional nummular MCA devices of all possible sizes were used to conduct ileac anastomosis in rats. The mean (± SD) circumference of the ileum was 13.34 ± 0.12 mm. Based on short- and long-term follow-up results, we determined the appropriate pressure range and minimum size. Thereafter, we introduced a novel "fedora-type" MCA device, which entailed the use of a nummular magnet with a larger sheet metal. RESULTS: With traditional MCA devices, the anastomoses experienced stenosis and even closure during the long-term follow-up when the anastomat was smaller than Φ5 mm. However, the risk of leakage increased when it was larger than Φ4 mm. On comparison of the different designs, it was found that the "fedora-type" MCA device should be composed of a Φ4-mm nummular magnet with a Φ6-mm sheet metal. CONCLUSION: The diameter of the MCA device should be greater than 120% of the enteric diameter. The novel "fedora-type" MCA device controls the pressure and optimizes the size.

Author Correction: End-to-end vascular anastomosis using a novel magnetic compression device in rabbits: a preliminary study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Neutrophil-to-lymphocyte ratio predicts acute kidney injury occurrence after gastrointestinal and hepatobiliary surgery.

BACKGROUND: Postoperative acute kidney injury (AKI) is a complex pathological process involved intrarenal and systemic inflammation caused by renal hypoperfusion, nephrotoxic drugs and urinary obstruction. Neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation reflecting the progress of many diseases. However, whether NLR at admission can predict the occurrence of AKI after surgery in the intensive care unit (ICU) remains unknown. AIM: To clarify the relationship between NLR and the occurrence of AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU. METHODS: A retrospective analysis of 282 patients receiving surgical ICU care after gastrointestinal and hepatobiliary surgery in our hospital from December 2014 to December 2018 was performed. RESULTS: Postoperative AKI occurred in 84 patients (29.79%) in this cohort. NLR by the multivariate analysis was an independent risk factor for occurrence of postoperative AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU. In this cohort, receiver operating characteristic curves of AKI occurrence showed that the optimal cut-off value of NLR was 8.380. NLR was found to be significantly correlated with the white blood cell count, neutrophil count, lymphocyte count, arterial lactate and dialysis (P < 0.05). Additionally, NLR value at admission was higher in AKI patients compared with the non-AKI patients and increased with the severity of AKI. Patients with NLR ≥ 8.380 exhibited significantly higher incidences of postoperative AKI and severe AKI than patients with NLR < 8.380 (AKI: 38.12% vs 14.85%, P < 0.001; severe AKI: 14.36% vs 1.98%, P = 0.001). CONCLUSION: NLR at admission is a predictor of AKI occurrence in patients with gastrointestinal and hepatobiliary surgery in ICU. NLR should be included in the routine assessment of AKI occurrence.

Overexpression of Platelet-Derived Growth Factor Receptor Α D842V Mutants Prevents Liver Regeneration and Chemically Induced Hepatocarcinogenesis via Inhibition of MET and EGFR.

Platelet-derived growth receptor α (PDGFRα) is a key factor in many pathophysiological processes. The expression level of PDGFRα is significantly elevated in the early stage of liver development and maintained at a lower level in adult normal livers. In this study, we constructed a liver-specific PDGFRαD842 mutant transgenic (TG) mice model to explore the effect of continuous activation of PDGFRα on liver regeneration and hepatocarcinogenesis. 14-day-old TG and wild-type (WT) mice were intraperitoneally injected with diethylnitrosamine (DEN) at a dose of 25 µg/g body weight. Two-month-old male TG and WT mice were subjected to partial hepatectomy (PH). The liver tissues were collected for further analysis at different time points. Overexpression of PDGFRα D842V and its target genes, Akt, c-myc and cyclin D1 in hepatocytes with no overt phenotype versus WT mice were compared. Unexpectedly, a dramatic decrease in hepatocyte proliferation was noted after PH in TG versus WT mice, possibly due to the downregulation of hepatocyte growth factor receptor (MET) and epidermal growth factor receptor (EGFR). No TG mice developed HCC spontaneously after 14 months follow-up. However, TG mice were more resistant to DEN-induced hapatocarcinogenesis at 6, 10, and 12 months of age, showing delayed hepatocyte proliferation and apoptosis, lower tumor incidence, smaller size and fewer number, compared with age-matched WTs, partially through downregulation of MET and EGFR. In conclusion, continuous activation of PDGFRα signaling by expression of PDGFRα D842V does not promote, but inhibit hepatic regeneration and hepatocarcinogenesis, possibly through compensatory downregulation of MET and EGFR.

End-to-end vascular anastomosis using a novel magnetic compression device in rabbits: a preliminary study.

Magnetic compression anastomosis (MCA) has been appreciated as an innovative alternative to manual suturing in vascular reconstruction. However, magnetic devices have limitations in their applications. The present study aimed to introduce a newly developed magnetic device for end-to-end vascular anastomosis. Twenty male New Zealand rabbits were randomly assigned to receive end-to-end postcaval vein anastomosis using either a newly designed MCA device (Group MCA) or continuous-interrupted suturing (Group CIS). The anastomotic patency was evaluated by Doppler or venography immediately, 1 week, and 12 weeks after surgery. Anastomotic quality was evaluated gross and microscopic histological study 12 weeks after surgery. The procedure was successfully performed and all animals survived until sacrifice. The duration of surgery and anastomosis time in Group MCA were significantly shorter compared to Group CIS (all p < 0.001), and the incidence of anastomotic patency and postoperative morbidity were comparable between the two groups (all p > 0.05). Hematoxylin-eosin staining showed that anastomotic intima from Group MCA was much smoother with more regularly arranged endothelial cells than from compared to the Group CIS. A novel MCA device was successfully applied in rabbit vascular anastomosis. We demonstrated the reliability and effectiveness of this newly developed MCA in this study.

Irisin attenuates intestinal injury, oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is often associated with intestinal injury, which in turn exaggerates the progression of AP. Our recent study has shown that a low level of serum irisin, a novel exercise-induced hormone, is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP. However, the role of irisin in intestinal injury in AP has not been evaluated. AIM: To investigate the effect of irisin administration on intestinal injury in experimental AP. METHODS: AP was induced in male adult mice by two hourly intraperitoneal injections of L-arginine. At 2 h after the last injection of L-arginine, irisin (50 or 250 µg/kg body weight) or 1 mL normal saline (vehicle) was administered through intraperitoneal injection. The animals were sacrificed at 72 h after the induction of AP. Intestinal injury, apoptosis, oxidative and endoplasmic reticulum (ER) stress were evaluated. RESULTS: Administration of irisin significantly mitigated intestinal damage, reduced apoptosis, and attenuated oxidative and ER stress in AP mice. In addition, irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas, liver and lung of AP mice. CONCLUSION: Irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP. Irisin has a great potential to be further developed as an effective treatment for patients with AP.

Novel magnetic compression technique for establishment of a canine model of tracheoesophageal fistula.

BACKGROUND: Clinically, tracheoesophageal fistula (TEF) is lack of effective surgical strategies. One reason is due to the lack of appropriate animal models of acquired TEF, which is usually complex and difficult. Recently, the magnetic compression technique has been applied for digestive tract anastomosis or vascular anastomosis in animals. In this study, an animal model of TEF in dogs was developed by using the magnetic compression technique, hoping to provide a new method for mimicking TEF. AIM: To establish a TEF model in dogs by using the magnetic compression technique. METHODS: Six male beagles were used as models with two Nd-Fe-B permanent magnets for TEF. The parent magnet and the daughter magnet were placed in the cervical esophagus and trachea, respectively. The anterior wall of the esophagus and the posterior wall of the trachea were compressed when the two magnets coupled. After 4-6 d, the necrotic tissue between the two magnets fell off and the parent and daughter magnets disengaged from the target location, leaving a fistula. Gastroscopy/bronchoscopy, upper gastrointestinal contrast study, and histological analysis were performed. RESULTS: The establishment of the TEF model in all six beagles was successful. The average time of magnet placement was 4.33 ± 1.11 min (range, 3-7 min). Mean time for the magnets to disengage from the target location was 4.67 ± 0.75 d (range, 4-6 d). TEFs were observed by gastroscopy/bronchoscopy and esophageal angiography. The gross anatomical structure of the esophagus and the trachea was in good condition. There was no esophageal mucosa or pseudostratified ciliated columnar epithelium at the site of the fistula according to histological analysis. CONCLUSION: It is simple, feasible, and minimally invasive to use the magnetic compression technique for the establishment of the TEF model in dogs.

Effect of low-dose aspirin administration on long-term survival of cirrhotic patients after splenectomy: A retrospective single-center study.

BACKGROUND: Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown. AIM: The main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and long-term survival of cirrhotic patients after splenectomy. METHODS: The clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed. RESULTS: During follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative long-term low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P = 0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR) = 6.211, 95% confidence interval (CI): 1.142-27.324, P = 0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P = 0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049-0.960, P = 0.044]. CONCLUSION: In patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.

Effects of Different 980-nm Diode Laser Parameters in Hepatectomy.

BACKGROUND AND OBJECTIVE: Despite the successful application of laser in animal experiments and clinics, the adjustment of laser parameters during surgery is still unclear. This study aimed to investigate the effect of different 980-nm diode laser parameters in hepatectomy. This could provide a clear protocol for using 980-nm diode laser in hepatectomy. STUDY DESIGN/MATERIALS AND METHODS: In total, 48 Sprague-Dawley rats were used to explore the effects of different 980-nm diode laser parameters in hepatectomy, by setting different parameter combinations. The rats were randomly divided into eight groups, including the continuous wave group and quasi-continuous wave group. The effects were assessed in terms of liver resection speed, extent of intraoperative bleeding, and thermal damage. RESULTS: In the quasi-continuous wave group, there was a significant difference in resection speed at the different laser parameters (P < 0.001); however, there was no significant difference in intraoperative bleeding and thermal damage. In the continuous wave group, there was a significant difference in resection speed, intraoperative bleeding, and thermal damage at different parameters. CONCLUSION: The study showed that the average power determined hemostasis efficiency and thermal damage, and peak power determined the liver resection speed, whereas the pulse width and repetition frequency are not independent factors. When using 980-nm diode laser in hepatectomy, the average power should be decreased to prove hemostasis efficiency in delicate operations, and the peak power should be decreased to accelerate the procedure without worsening thermal damage. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Value of pretransplant albumin-bilirubin score in predicting outcomes after liver transplantation.

BACKGROUND: Due to the significant shortage of organs and the increasing number of candidates on the transplant waiting list, there is an urgent need to identify patients who are most likely to benefit from liver transplantation. The albumin-bilirubin (ALBI) grading system was recently developed to identify patients at risk for adverse outcomes after hepatectomy. However, the value of the pretransplant ALBI score in predicting outcomes after liver transplantation has not been assessed. AIM: To retrospectively investigate the value of the pretransplant ALBI score in predicting outcomes after liver transplantation. METHODS: The clinical data of 272 consecutive adult patients who received donation after cardiac death and underwent liver transplantation at our centre from March 2012 to March 2017 were analysed in the cohort study. After the exclusion of patients who met any of the exclusion criteria, 258 patients remained. The performance of the ALBI score in predicting overall survival and postoperative complications after liver transplantation was evaluated. The optimal cut-off value of preoperative ALBI was calculated according to long-term survival status. The outcomes after liver transplantation, including postoperative complications and survival analysis, were measured. RESULTS: The remaining 258 consecutive patients were included in the analysis. The median follow-up time was 17.30 (interquartile range: 8.90-28.98) mo. Death occurred in 35 patients during follow-up. The overall survival rate was 81.0%. The preoperative ALBI score had a significant positive correlation with the overall survival rate after liver transplantation. The calculated cut-off for ALBI scores to predict postoperative survival was -1.48. Patients with an ALBI score > -1.48 had a significantly lower survival rate than those with an ALBI score ≤ -1.48 (73.7% vs 87.6%, P < 0.05), and there were no statistically significant differences in survival rates between patients with a model for end stage liver disease score ≥ 10 and < 10 and different Child-Pugh grades. In terms of the specific complications, a high ALBI score was associated with an increased incidence of biliary complications, intraabdominal bleeding, septicaemia, and acute kidney injury after liver transplantation (P < 0.05 for all). CONCLUSION: The ALBI score predicts overall survival and postoperative complications after liver transplantation. The ALBI grading system may be useful in risk-stratifying patients on the liver transplant waiting list.

Current Technologies of Synthetic Biosensors for Disease Detection: Design, Classification and Future Perspectives.

Synthetic biology aims to endow living cells with new functions by incorporating functional gene networks into them. By overexpressing, blocking and rewiring native gene pathways, synthetic biologists have harnessed this promising technology to reprogram cells to perform diverse tasks such as drug discovery, biopharmaceutical manufacturing, gene therapy and tissue engineering, etc. In this review, we focus on current technologies of synthetic biosensors for disease detection. We start with the design principle of synthetic biosensors. Then we move towards the characteristics of simple synthetic biosensors, which can respond to a single input signal, and complex synthetic biosensors including Boolean gate biosensors, cascade biosensors, time-delay biosensors, oscillator biosensors and hysteretic biosensors, which can respond to more than two input signals and perform complex tasks. Synthetic biosensor has showed great potential in disease detection, but it is still in its infancy stage. More efforts should be made in identifying and constructing clinically relevant regulation systems. Computational tools are also needed in the design process in order to guarantee the precision of the synthetic biosensor. The ultimate goal of a synthetic biosensor is to act as a therapeutic sensor-effector device that connects diagnostic input with therapeutic output and therefore provides all-in-one diagnostic and therapeutic solutions for future gene- and cell-based therapies.

Miniature magnetically anchored and controlled camera system for trocar-less laparoscopy.

AIM: To design a miniature magnetically anchored and controlled camera system to reduce the number of trocars which are required for laparoscopy. METHODS: The system consists of a miniature magnetically anchored camera with a 30° downward angle, an external magnetically anchored unit, and a vision output device. The camera weighs 12 g, measures Φ10.5 mm × 55 mm and has two magnets, a vision model, a light source, and a metal hexagonal nut. To test the prototype, the camera was inserted through a 12-mm conventional trocar in an ex vivo real liver laparoscopic training system. A trocar-less laparoscopic cholecystectomy was performed 6 times using a 12-mm and a 5-mm conventional trocar. In addition, the same procedure was performed in four canine models. RESULTS: Both procedures were successfully performed using only two conventional laparoscopic trocars. The cholecystectomy was completed without any major complication in 42 min (38-45 min) in vitro and in 50 min (45-53 min) using an animal model. This camera was anchored and controlled by an external unit magnetically anchored on the abdominal wall. The camera could generate excellent image. with no instrument collisions. CONCLUSION: The camera system we designed provides excellent optics and can be easily maneuvered. The number of conventional trocars is reduced without adding technical difficulties.