Background Lead exposure induces microglial cell death, of which the mechanism is unclear. Ferroptosis is a new death form and its role in microglia death has not been reported. Objective To investigate the role of ferroptosis in microglia following lead exposure in order to provide a theoretical basis for the mechanism of lead neurotoxicity. Methods Microglial cell line BV-2 cells were co-cultured with 0, 10, 20 and 40 μmol·L⁻¹ lead acetate for 24 h. The 40 μmol·L⁻¹ lead acetate group with iron chelator (DFO) was named the 40+DFO group. Changes in BV-2 cell morphology after lead exposure were observed under an inverted microscope; tissue iron kit and glutathione kit were used to detect intracellular iron and glutathione (GSH) respectively; flow cytometry was applied to detect lipid reactive oxygen species (lipid ROS) immunofluorescence intensity. Western blotting and qPCR were adopted to detect the expressions of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), transferrin receptor 1 (TFR-1), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1) protein and mRNA. Results Compared with the control group, the number of BV-2 cells decreased with increasing doses of lead and the cells showed a large, round amoeboid shape. The intracellular levels of iron of BV-2 cells were (1.08±0.04), (1.29±0.03), and (1.72±0.10) mg·g⁻¹ (calculated by protein, thereafter) in the 10, 20, and 40 μmol·L⁻¹ lead acetate groups, respectively, significantly higher than that in the control group (P<0.05), and the intracellular level of iron in the 40+DFO group, (1.34±0.10) mg·g⁻¹, was lower than that in the 40 μmol·L⁻¹ lead acetate group, (1.72±0.03) mg·g⁻¹ (P<0.05). Compared with the control group, the TFR-1 and DMT1 protein and mRNA expressions were increased in BV-2 cells in the 10, 20, 40 μmol·L⁻¹ lead acetate groups (P<0.05), especially in the 40 μmol·L⁻¹ lead acetate group; the FPN1 protein expression did not change significantly, but the FPN1 mRNA expressions in BV-2 cells in the 10, 20, 40 μmol·L⁻¹ lead acetate groups were significantly decreased (P<0.05). Compared with the control group, the intracellular GSH level decreased and the lipid ROS content increased in all three lead acetate groups; compared with the 40 μmol·L⁻¹ lead acetate group, the GSH level increased by 12.30% and the lipid ROS content decreased by 13.00% in the 40+DFO group (P<0.05). The expressions of GPX4 protein were reduced to 50.00%, 35.00%, and 17.00% of that of the control group in the 10, 20, and 40 μmol·L⁻¹ lead acetate groups respectively, while the expressions of GPX4 mRNA were also significantly reduced; the expressions of SLC7A11 protein and mRNA in the 20 and 40 μmol·L⁻¹ lead acetate groups were lower than that in the control group, with the most significant decrease in the 40 μmol·L⁻¹ lead acetate group (P<0.05). Conclusion Lead exposure could induce ferroptosis in BV-2 cells, in which iron transport imbalance and oxidative damage might be involved.

Objective To evaluate the therapeutic effects of liver transplantation (LT) for cholangiocarcinoma(CC)and analyze the prognostic factors.Methods From December 2001 to December 2006,234 patients receiving LT for hepatic carcinoma in our institute were enrolled as a basis of comparative study for 6 CC patients undergoing LT during the same period.Results These 6 patients were followed-up from 1 to 56 months.Five patients died and one recurred.The 0.5-,1-and 2-year patient cumulative survival rates were 4/6,3/6 and 1/6,respectively.The 0.5-,1-and 2-year tumor-free survival rates were 3/6,2/6 and 1/6,respectively.The average patient or tumor-free survival time were both(14±4) months.Conclusion The prognosis of cholangioearcinoma patients after LT iS poor.

Objective To summarize the clinical experience in liver retransplantation. Methods The clinical data of 24 patients receiving liver retransplantation 28 times in this hospital were retrospectively analyzed and discussed with relevant literature. Results Among the 880 consecutive liver transplantations, 28(3.18%) had liver retransplantation. The causes of liver retransplantation were biliary complications ( 16 cases, 57. 1%), carcinoma recurrece (6 cases, 21. 4%), hepatic artery thrombosis (4 cases, 14. 3%), chronic rejection (1 case, 3. 6%), primary nonfunction (1 case, 3.6%). Thirteen patients among the 24 were discharged healthy and were followed up for 51days to 67months. Eleven patients died. Three of them died of hemorrhagic shock, 2 of septic shock, 2 of hepatocellular carcinoma recurrence, 2 of cardiovascular system complication, 1of nervous system complication, and 1 of hepatic artery thrombosis. Conclusion Liver retransplantation can effectively save patients with graft failure. Proper indication, optimal operating time, improvement of operative skills,and appropriate treatment during the perioperative period are very important for promoting the rate of successful liver retransplantation.

Objective To investigate the surgical options for the management of portal vein thrombosis (PVT) during liver transplantation and its impact on the outcome of patients. Methods 773 cases of liver transplantation were analyzed retrospectively. PVT occurred in 107 patients, inclu-ding 59 of grade Ⅰ ,33 of grade Ⅱ, 12 of grade Ⅲ and 3 of grade Ⅳ. Simple thrombectomy or thrombus-extraction was performed in grade Ⅰ and Ⅱ. 12 patients with grade Ⅲ received thrombus-extraction or using the donor iliac vein to act as a bridge between the donor portal vein and host superior mesenteric vein. Two cases of grade Ⅳ received a modified cavo-portal hemitransposition and one case received portal-vena coronaria varication anastomosis. Results Liver function had a good recover and the perio-perative mortality is 4. 3% in grade Ⅰ and Ⅱ. In grade Ⅲ , 5 cases received thrombus-extraction had a normal liver function after transplantation and had no died. 2 cases among the other 7 cases using por-tal vein reconstruction had bad liver function and died. The liver function recovered well after trans-plantation and there was no died in grade Ⅳ. Conclusions PVT is not a contraindication for liver transplantation. Good results can be obtained by applying reasonable operative procedures individually.

Objective To investigate some improvements in the surgical techniques of adult-to-adult living donor liver transplantation( A-A LDLT) without the middle hepatic vein(MHV) for hepat-ic vein reconstruction. Methods The retrospective analysis was made on the clinical data of 11 recipi-ents who underwent the operation in A-A LDLT including the hepatic vein reconstructed in right liver lobe without MHV from June 2007 to January 2008. The key techniques included reconstructing out-flow of graft on shaping the tips of vena cava and right hepatic veins, cadaveric vein allografts stored in 4℃ UW solution within 7d being used for significant-sized hepatic vein reconstruction such as tributa-ries of the middle hepatic vein from V5, V8 and right inferior hepatic vein. Results 10 cases success-fully underwent reconstruction of outflow of graft on shaping the tips of vena cava and right hepatic veins and the outflow reconstruction ratio of V5, V8 and right inferior hepatic vein was 81. 8% (9/11), 7 one-vein reconstruction, 1 two-vein reconstruction and 1 three-vein reconstruction. 1 recipient died of renal failure and pulmonary infection 14 days after operation without venous outflow obstruc-tion. Doppler ultrasonography showed no thrombosis and the blood flowed smoothly in the right he-patic vein of other 8 recipients during the 9th to 15th mouth of follow-up. The cumulative patency rates of these 8 survivals for interposition vein grafts were 100% (11/11), 72. 7 %(8/11), 54. 5%(6/11) and 36. 5%(4/11) in 1, 3, 6 and 9 mouths, respectively. The regeneration of paramedian sectors was equivalent. Conclusion Shaping the tips of vena cava and right hepatic veins and using cadaveric vein allografts in adult-to-adult right lobe living donor liver transplantation for hepatic vein reconstruc-tion are both safe,simple and effective methods.This approach can be recommended.

The clinical data of 67 patients underwent orthotopic liver transplantation, including 4 cases of early intra abdominal hemorrhage after orthotopic liver transplantation, were analyzed retrospectively.Anastomotic liver artery hemorrhage was found in 2 cases, hemorrhage of IVC in 1 case and hemorrhage of right adrenal gland in 1 case. All the 4 patients were correctly dignosed and successfully treated by operation in time. It suggests that the early intra abdominal hemorrhage after orthotopic liver transplantation is mostly due to surgical technique. The improvement of surgical technique,correct diagnosis and timely operation are very important for the treatment of intra abdominal hemorrhage.

Objective:To investigate the effect of nano lead oxide (nano-PbO) exposure on learning and memory as well as spatial exploration ability in the mice, and the role of leukocyte infiltration of brain tissue in neurobehavioral damage caused by nano-PbO exposure.Methods:A total of 60 male SPF grade Kunming mice were divided into control group, low-dose nano-PbO group, medium-dose nano-PbO group and high-dose nano-PbO group according to body mass matching method, with 15 mice in each group.Mice in low, medium and high dose groups of nano-PbO were intraperitoneally injected with 5 mg·kg -1, 10 mg·kg -1, 20 mg·kg -1 nano-PbO, respectively. And mice in the control group were intraperitoneally injected with the same volume of 0.9% normal saline.The frequency of intervention was once a day for 28 days.Morris water maze test and open field test were used to detect the ability of learning and memory and spatial exploration of mice. Western blot was used to detect the protein expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in hippocampus of mice, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in mouse microvessels and lymphocyte function-associated antigen-1 (LAF-1) in mouse blood leukocyte. The proportion of leukocytes in mouse brain was detected by flow cytometry. All statistical analyses were performed by SPSS 20.0. Morris water maze data were analyzed by repeated measures ANOVA, the other data among multiple groups were compared by one-way ANOVA, and Tukey's test was used for further pairwise comparison.Pearson correlation analysis was performed to evaluate the correlation between neurobehavioral indexes and the proportion of white blood cells, TNF-α and IL-1β in brain tissue. Results:Morris water maze results showed that the escape latency of the four groups of mice had a significant interaction between group and time( F=3.21, P<0.05). The escape latencies of mice in middle and high dose groups of nano-PbO were higher than that in the control group (both P<0.05), and the numbers of crossing the platform of the two groups were lower than that in the control group (both P<0.05). The results of open field test showed that there was a statistically significant difference in the residence time of the mice in the four groups ( F=119.10, P<0.01). The total standing times of mice in the middle group and high dose group of nano-PbO were lower than that in the control group (both P<0.01). The results of Western blot showed that the levels of TNF-α and IL-1β in hippocampus tissue of mice were significant differences among the four groups ( F=7.21, 9.89, both P<0.05). The levels of TNF-α and IL-1β in the hippocampus of mice in the high-dose nano-PbO group were higher than those in the control group (TNF-α: (0.35±0.10), (1.03±0.30), P<0.05; IL-1β: (0.32±0.10), (0.50±0.15), P<0.05). The results of flow cytometry analysis showed that the proportions of leukocytes in the brain tissue of mice in the low, medium and high dose groups of nano-PbO were (9.99±1.09)%, (13.03±0.94)% and (16.51±3.89)%, respectively. Among them, the proportions of leukocytes in the middle and high dose groups of nano-PbO were significantly higher than that in the control group((8.13±1.29)%) (both P<0.05). The results of correlation analysis showed that the proportion of leukocytes, levels of TNF-α, IL-1β protein of hippocampus in the medium, high dose groups of nano-PbO were negatively correlated with the behavioral indexes ( r=-0.815, -0.744, -0.578, all P<0.01; r=-0.771, -0.836, -0.704, all P<0.05; r=-0.823, -0.876, -0.695, all P<0.05). The results of Western blot showed that the levels of ICAM-1 and VCAM-1 in cerebral microvessels of mice in the four groups were significantly different ( F=5.51, 16.19, both P<0.05). The levels of ICAM-1 and VCAM-1 in the middle and high dose groups of nano-PbO were higher than those in the control group(ICAM-1: (1.07±0.16), (1.21±0.35), (0.59±0.19), all P<0.05; VCAM-1: (0.68±0.12), (1.92±0.23), (0.23±0.05), both P<0.05). In addition, there was a significant difference in the level of LFA-1 protein in blood leukocytes of mice in the four groups ( F=41.80, P<0.05). The levels of LFA-1 in the middle and high dose groups of nano-PbO were higher than that in the control group((0.33±0.06), (0.89±0.23), (0.05±0.01), both P<0.05). Conclusion:The nano-PbO exposure can lead to cognitive impairment and increased inflammatory factors in the hippocampus of mice, which may be related to the increase of ICAM-1 and VCAM-1 in vascular endothelial cells, which promotes leukocyte infiltration into brain tissue.

Objective:To observe the clinical effects of intraperitoneal perfusion of bevacizumab combined with albumin paclitaxel and carboplatin in the treatment of malignant peritoneal adhesion caused by ovarian cancer.Methods:From January 2016 to December 2020, 54 patients treated in our hospital with malignant peritoneal adhesions caused by ovarian cancer were enrolled in this study. They were randomly divided into experimental group ( n=27) and control group ( n=27) according to the random number table method. The treatment regimen of the experimental group was intravenous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin and bevacizumab. The treatment regimen of the control group was intra-venous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin. The treatment was repeated every 21 days, and the therapeutic effect was evaluated every two cycles. The treatment lasted for six cycles. The efficacy and incidence of adverse reactions were compared between the two groups. Results:The remission rate of incomplete malignant bowel obstruction of the experimental group was higher than that of the control group [85.19% (23/27) vs. 59.26% (16/27)], the total effective rate of the experimental group was higher than that of the control group [74.07% (20/27) vs. 44.44% (12/27)], and there were statistically significant differences ( χ2=4.523, P=0.033; χ2=4.909, P=0.027). After treatment, the levels of vascular endothelial growth factor (VEGF) in ascites of the experimental group and the control group were significantly lower than those before treatment [(80.33±1.41) pg/ml vs. (310.45±3.35) pg/ml, t=449.884, P<0.001; (135.68±1.60) pg/ml vs. (310.46±3.09) pg/ml, t=499.281, P<0.001], and after treatment, the VEGF level in the experimental group decreased more significantly than that in the control group ( t=-134.907, P<0.001). Patients in the experimental group and the control group tolerated the treatment well, and there were no significant differences in the incidences of adverse reactions such as hypertension (11.11% vs. 3.70%, χ2=0.270, P=0.603), neutropenia (14.81% vs. 11.11%, χ2<0.001, P>0.999), peripheral neuropathy (3.70% vs. 0, χ2<0.001, P>0.999), diarrhea (7.41% vs. 3.70%, χ2<0.001, P>0.999), nausea (3.70% vs. 0, χ2<0.001, P>0.999), epistaxis (7.41% vs. 0, χ2=0.519, P=0.471) or albuminuria (3.70% vs. 0, χ2<0.001, P>0.999) between the two groups. Conclusion:Intraperitoneal perfusion of bevacizumab combined with chemotherapy is superior to simple chemotherapy in the treatment of malignant peritoneal adhesion caused by ovarian cancer.

Objective To summarize our experience in the diagnosis and treatment of hepatic epithelioid angiomyolipoma (HEAML),with the aim to reduce the future misdiagnosis rate.Methods The PubMed,Medline,China Science Periodical Database (CSPD),and VIP Databases were searched from January 2000 to March 2018 on all reports on HEAML.Results There were 409 cases of HEAML in 97 reports.The ratio of men to women was 1∶4.84.The age ranged from 12 to 80 years and the median age was 44 years.61.9％ of patients (205/331) were asymptomatic,while 34.7％ (115/331) had upper or right upper quadrant abdominal discomfort.Some patients presented with abdominal mass,gastrointestinal reaction,low grade fever or weight loss.The clinical symptoms in 78 patients were not mentioned in the reports.The misdiagnostic rate of HEAML was as high as 40.3％ (165/409).The imaging findings of HEAML were nonspecific.Ultrasound,CT and MRI scan usually showed contrast enhancement in the arterial phase.Most lesions were accompanied by central vessels with early drainage veins.The enhanced scans showed varied characteristics.The ratios of fast wash-in and fast wash-out,to fast wash-in and slow wash-out,and to delayed enhancement were roughly 4∶ 5∶ 1.A definitive diagnosis of HEAML is based on the pathological findings of epithelioid cells in the lesions and the expressions of HMB45,SMA,Melan-A and Actin on immunohistochemical staining.HEAML had a relatively low malignant rate of 3.9％.Surgical resection was the main treatment for HEAML.Conclusion HEAML was a rare and easily misdiagnosed disease.,which could be diagnosed by taking into account the clinical course,imaging,pathological and immunohistochemical findings.HEAML.