Over the years of exploration and development, the surgical techniques and prognosis of liver transplantation in China have been significantly improved, resulting in a notable decrease in the prevalence of postoperative complications. However, ischemic-type biliary lesion remain a non-negligible issue. The Third Affiliated Hospital of Sun Yat-sen University formulated and published the "Expert Consensus on the Diagnosis and Treatment of Ischemic-Type Biliary Lesions after Liver Transplantation in Mainland China" in 2015, which has now been updated into a guideline based on current conditions and literature reports. This guideline elaborates in detail on the definition, incidence, pathogenesis, diagnosis, prevention of high-risk factors, and treatment of ischemic-type biliary lesion, aiming to provide standardized and normative guidance for the diagnosis and treatment of ischemic-type biliary lesion after liver transplantation, thereby reducing the rate of re-transplantation and fatality, and to improve the overall quality of life of liver transplant recipients.

Objective To evaluate the protective effect and the underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) on radiation-induced liver injury and liver cell line injury in mouse models. Methods C57BL/6 mice were randomly divided into the blank group, model group and MSC-EV treatment group (treatment group), with 9 mice in each group. AML12 cells were randomly divided into the control group, irradiation group and MSC-EV intervention group (intervention group). Animal and cell models with radiation-induced injury were established by one-time 15 Gy and 6 Gy X-ray irradiation, respectively. At 48 h after irradiation, liver tissues and serum samples of mice were collected and prepared for subsequent experiments. At 15 h post-irradiation, cell experiment was carried out. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and content of malondialdehyde (MDA) in liver tissues and cells were measured. The relative expression levels of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and CXC chemokine ligand (CXCL)10 messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Liver tissues were prepared for hematoxylin-eosin (HE) staining to calculate liver pathological injury score. The apoptosis of liver tissues and cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidiumiodide (PI) staining, respectively. The expression levels of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins were detected by Western blot. The production level of reactive oxygen species (ROS) was detected by dihydroethidine (DHE) staining. The fluorescence intensity of mitochondrial permeability transition pore (mPTP) was determined. Results Compared with the blank group, serum levels of AST and ALT were up-regulated, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the mouse liver tissues were up-regulated, and MDA content was increased, liver injury score was elevated, cell apoptosis rate was increased, intracellular ROS level was elevated, and the relative expression levels of GPX4 and FSP1 proteins in the mouse liver tissues were down-regulated in the model group, and the differences were statistically significant (all P<0.05). Compared with the model group, serum levels of AST and ALT were decreased, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the liver tissues of mice were down-regulated, MDA content was declined, liver injury score was declined, cell apoptosis rate was decreased, intracellular ROS level was decreased, and the relative expression levels of GPX4 and FSP1 proteins in the liver tissues of mice were up-regulated in the treatment group, and the differences were statistically significant (all P<0.05). Compared with the control group, cell apoptosis rate was increased, intracellular ROS level was elevated, the fluorescence intensity of mPTP was weakened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were up-regulated, MDA content was increased, and the relative expression levels of GPX4 and FSP1 proteins were down-regulated in the irradiation group, and the differences were statistically significant (all P<0.05). Compared with the irradiation group, cell apoptosis rate was declined, intracellular ROS level was decreased, the fluorescence intensity of mPTP was strengthened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were down-regulated, MDA content was decreased and the relative expression levels of GPX4 and FSP1 proteins were up-regulated in the intervention group, and the differences were statistically significant (all P<0.05). Conclusions MSC-EV may effectively alleviate radiation-induced liver injury by reducing ferroptosis of liver cells, enhancing antioxidant level and decreasing the production of lipid peroxide, thereby effectively alleviating radiation-induced liver injury.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective To establish a detection system of ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for everolimus concentration in whole blood of liver transplant recipients. Methods The proteins of samples were precipitated with methanol and zinc sulfate, and everolimus-D4 was used as the internal standard. Phenomenex Kinetex PFP column was used. The mobile phase A was water (containing 2 mmol/Lammonium formate and 0.1% formic acid), and the mobile phase B was methanol (containing 2 mmol/L ammonium formate and 0.1% formic acid). The gradient elution was performed with the flow rate of 1 mL/min, the column temperature of 50 ℃ and the injection volume of 1 μL. The multi-reaction monitoring mode was used to quantitatively analyze with electrospray positive ionization. The UPLC-MS/MS detection system required only 100 μL of whole blood, and could achieve a sufficient lower limit of quantification without complicated sample preparation. The total running time was within 4.5 min. Linear regression (1/x²) analysis was performed using peak area of everolimus / peak area of everolimus-D4 (y) and concentration of everolimus/concentration of everolimus-D4 (x) to calculate the calibration function and analyze its accuracy and linear relationship. UPLC-MS/MS was used to detect the trough blood concentration of everolimus in blood samples of 5 recipients after liver transplantation. Results The accuracy of quality control was within 15%, and the linear relationship of everolimus was good in the blood concentration range of 1-100 ng /mL(R² > 0.990). Trough blood concentration of everolimus measured in blood samples of 5 liver transplant recipients ranged from 3.77 to 9.27 ng/mL. Conclusions The detection system of UPLC-MS/MS in this study is suitable for monitoring the concentration of everolimus in whole blood of liver transplant recipients because of its high accuracy, simple sample processing method and short detection time.

Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.

Purpose: Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy,which is associated with the progression of carcinoma. Yet, it is still unclear whetherLC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aimto explore the predictive value of LC3B on prognosis of ICC, and to establish a novel andavailable nomogram to predict relapse-free survival (RFS) and overall survival (OS) for thesepatients after curative-intent hepatectomy. Materials and Methods: From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the ThirdAffiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolledpatients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry. Results: The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariateCox regression analysis, independent risk factors for 5-year OS were cancer antigen 125,microvascular invasion, LC3B expression and lymph node metastasis. Except for the above4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factorsfor 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and0.747, respectively. Conclusion The nomograms based on LC3B can be considered as effective models to predict postoperativesurvival for ICC patients.

Objective To evaluate the safety and efficacy of individualized treatment of splenorenal shunt during liver transplantation. Methods Clinical data of 2 recipients who underwent orthotopic liver transplantation and splenorenal shunt intraoperatively were retrospectively analyzed. According to the perfusion status after splenorenal shunt and donor liver reflow, the left renal vein ligation and splenorenal shunt vessel ligation were performed in two recipients during liver transplantation. The general postoperative conditions of the recipients were observed, including surgical related complications, peak portal blood flow velocity, liver and renal function indexs. The postoperative conditions of the recipients were monitored by abdominal ultrasound. Results No intraoperative or postoperative complications occurred in two recipients. The changes of peak portal blood flow velocity before and after splenorenal shunt in two recipients were 22.9-35.1 cm/s and 24.3-58.8 cm/s respectively. No delayed recovery of alanine aminotransferase (ALT) level was observed in two patients after operation. Case 1 experienced a transient increase in the serum creatinine (Scr), which was recovered to normal at postoperative 13 d. During the postoperative follow-up, ultrasound examination demonstrated that the direction and velocity of portal blood flow were normal and liver perfusion was excellent. Conclusions It is safe and effective to selectively ligate the left renal vein or splenorenal shunt vessels of the recipients with severe splenorenal shunt during liver transplantation.

Objective To study the feasibility of diffusion tensor imaging(DTI) in assessment of lumbosacral neuropathy. Methods Eighteen patients with lumbosacral neuropathy (experimental group) and 20 healthy volunteers (control group) were enrolled prospectively in the neurological department by clinical symptoms and neuroelectrophysiology. The experimental group were divided into experimental subgroup A(demyelination group, 6 cases),subgroup B(axonal injury with demyelination group, 12 cases) based on electrophysiology.All of L4-SN nerves of the experiment group and the control group received DTI examination."Sowing points"as ROIs were placed in the proximal, middle and distal of bilateral L4-SN nerves by two experienced physicians.The average of the DTI parameters of 3 ROIs at each nerve were used as its final DTI parameters.Independent sample t test was used to evaluate the difference of the L4-SN DTI parameters between the experimental group and the control group.The differences of DTI parameters among the control group, the experimental subgroup A and the experimental subgroup B were compared by the nonparametric independent samples Kruskal-Wallis H test and the Nemenyi test. The ROC analysis was performed on the FA values and λ⊥values of the control and experimental groups.Results (1)The L4-SN FA values in the experimental group was significantly lower than those in the control group (t range from 4.11 to 6.36, P<0.05). The L4 and S1-SN ADC values of the experimental group were significantly higher than those of the control group (t range from - 4.77 to - 1.17, P<0.05). The L4-SN λ ⊥ values in the experimental group were significantly higher than those in the control group (t range from -5.30 to -2.57，P< 0.05). (2) L4-SN FA values (H values ranged from 18.5 to 30.6, P<0.05), λ⊥ values (H values ranged from 6.8 to 29.2, P<0.05) and L4, S1-SN ADC values (H values ranged from 6.8 to 19.6, P<0.05) were significantly different among control group, experimental subgroup A and experimental subgroup B. Nemenyi test showed there were significant differences in FA values (H values ranged from 18.4 to 30.1,P<0.05) and λ⊥ values (H values ranged from 6.2 to 29.0, P<0.05)) of L4-SN and in ADC values (H values ranged from 6.4 to 19.54, P<0.05) of L4，S1-SN between control group and experimental subgroup B. (3) The analysis of ROC of the experimental group and control group showed the AUC values of L4-SN FA values were 0.834, 0.745, 0.860, 0.772, 0.811 respectively, the sensitivity were 66.7%, 72.2%, 77.8%, 83.3% and 66.7% respectively, and the specificity were 91.7%,69.4%,80.6%,61.1% and 88.9% respectively. The AUC values of L4-SN λ⊥ values were 0.796, 0.656, 0.791, 0.701, 0.843 respectively, and the sensitivity were 55.6%, 50.0%, 66.7%, 97.2% and 88.9% respectively,and the specificity were 91.7% , 77.85% , 86.1% , 36.1% and 66.7% respectively. Conclusion DTI has the feasibility to evaluate lumbosacral neuropathy and it can identify patients with axonal injury with demyelination and healthy subjects.

Objective To explore the image quality of 3.0 T Magnetic Resonance foot and ankle array coil on Achilles tendon ab-normalities for the clinical application.Methods 26 patients (with Achilles tendon symptoms)and 5 volunteers underwent MR exam-ination.The scanning sequences were used:T1 WI、PDWI、T2 WI-FS and STIR.Image diagnoses and clinical data of all patients were obtained and analyzed.Subjective scores on image quality were used.Degrees of comfort in coil were evaluated.Results 10 patients had Achilles tendon inj ury,6 patients with Achilles tendonitis,3 patients with part Achilles tendon rupture,1 patient with tendon xanthoma,and 6 patients were normal.Image scores in patients with T1 WI、PDWI and T2 WI-FS sequences were higher,the anatom-ic structures,lesions of whole Achilles tendon were clear.On the contrary,the lower scores were in STIR sequences.In the heel, images were distorted,the level of organization was disappeared and signal intensity was increased.The volunteers felt a slight dis-comfort at the coil entrance and support point of the heel.Conclusion Patients using 3.0T foot and ankle array coil for the Achilles tendon scanning could get high image quality and degrees of comfort.

Rectal diverticulum is rarely seen in clinical practice.Perforation or rupture of rectal diverticulum with symptoms and signs of acute diffuse peritonitis makes it easily be misdiagnosed as appendicitis,rectal neoplasms,intestinal obstruction and other abdominal diseases.In this article,a retrospective analysis of the clinical data of one patient with extraperitoneal pneumatosis caused by perforation of rectal diverticulum was performed to investigate the diagnosis and treatment of the disease.