[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective To analyze the progress and current status of ethical research in the field of organ donation and transplantation in China by bibliometric analysis.Methods Literature review was conducted from CNKI between January 2000 to December 2023.The number of published articles,the cooperation network of core authors,the cooperation network of publication institutions,the co-occurrence of keywords,the emergent keywords and the clustering of keywords were analyzed by CiteSpace 6.2.6.Results A total of 399 valid articles were obtained.The three peaks in the trend of published articles were affected by current policy events and the development of transplantation technology.From 2000 to 2014,the number of published articles showed an upward trend.At this stage,these studies focused on ethical speculation in the field of organ donation and transplantation.From 2015 to 2023,the number of published articles showed a fluctuating trend.During this stage,these researches highlighted the work system of donation and transplantation and ethical issues in medical practice.Organ donation and ethical review after citizen death became the research frontiers.The co-occurrence knowledge map of authors reflected that the authors mainly served as single nodes,lacking of communication among authors.Twenty-five core authors were identified.Diverse publication institutions were searched including medical departments from colleges and universities,ethics research institutions,organ transplantation departments from hospitals,ethics committees from hospitals and human Organ Procurement Organization(OPO),etc.The First Hospital of Kunming published the largest number of articles.A total of 252 keywords and 13 emergent words were extracted.The keywords with the highest degree of emergency consisted of brain death,organ donation,legislation and ethical review.A total of 14 keyword clusters were generated,including organ transplantation,organ donation,organ donation after citizen's death,ethics,ethical review and medical staff.Conclusions The cooperation among authors and institutions is insufficient in the field of organ donation and transplantation ethics.Multi-center research and cooperation among authors should be strengthened.Extensive efforts should be made to strengthen the exploration and empirical research of ethical issues based on current work system and medical practice,aiming to provide ethical basis and defense for the reform and practice of organ donation and transplantation.

Objective To observe the anesthetic effect of laryngeal mask general anesthesia combined with abdominal"loop anesthesia"block in laparoscopic resection of colon cancer.Methods A total of 60 patients who underwent laparoscopic resection of colon cancer in the Third Hospital of Xiamen from January 2022 to March 2023 were selected.According to random number table method,they were divided into L group(laryngeal mask general anesthesia,30 cases)and U group(laryngeal mask general anesthesia combined with abdominal"loop anesthesia"block,30 cases).The dosage of propofol and remifentanil for anesthesia maintenance,time to completion of surgery,visual analogue scale(VAS)score after consciousness and sufentanil dosage were recorded and compared between two groups.The satisfaction of analgesia 12h after surgery was compared between two groups.Results There were no significant differences in gender,age,body mass,height and operation time between two groups(P>0.05).The total dosage of remifentanil and propofol in U group was significantly lower than that in L group(P<0.001).The VAS score in the anesthesia recovery room of U group was significantly lower than that of L group,and the dosage of sufentanil was significantly lower than that of L group(P<0.001).The satisfaction of analgesia in U group was significantly higher than that in L group(χ2=6.772,P=0.031).Conclusion Compared with laryngeal mask general anesthesia,laryngeal mask general anesthesia combined with abdominal"loop anesthesia"block can reduce the amount of anesthesia maintenance drugs in laparoscopic colon cancer resection,reduce the amount of sufentanil in the anesthesia recovery room,and improve the satisfaction of postoperative analgesia.

Objective:To study the different factors affecting platelet production post transplantation of hematopoietic stem cells (HSCs) isolated from different sources in order to explore novel options for treating platelet depletion following HSCs transplantation.Methods:HSCs and their downstream derivatives including myeloid and lymphoid cells (i.e., collective of mononuclear cells (MNCs)), were isolated from E14.5 fetal liver (FL) and bone marrow (BM) of 8-week-old mice by Ficoll separation technique. These cells were subsequently transplanted into the tibia bone marrow cavity of recipient mice post lethal myeloablative treatment in order to construct the FL-MNCs and BM-MNCs transplantation mouse model. Routine blood indices were examined in these recipient mice. The chimeric rate of donor cells in recipient peripheral blood cells were determined by flow cytometry. Different groups of cells involved in platelet reconstruction were analyzed. CD41 +megakaryocytes were sorted from fetal liver or bone marrow using magnetic beads, which were then induced to differentiate into platelets in an in vitro assay . Quantitative RT-PCR was used to detect the expression of platelet-related genes in CD41 +megakaryocytes from the two sources. Results:Both the FL-MNCs and the BM-MNCs transplantation groups resumed normal hematopoiesis at the 4th week after transplantation, and the blood cells of the recipient mice were largely replaced by the donor cells. Compared with the mice transplanted with BM-MNCs, the platelet level of mice transplanted with FL-MNCs recovered faster and were maintained at a higher level. At week 4, the PLT level of the FL-MNCs group was (1.45±0.37)×10 12/L, and of the BM-MNCs group was (1.22±0.24)×10 12/L, P<0.05. The FL-MNCs contain a higher proportion of hematopoietic stem cells (Lin -Sca-1 +c-Kit +)(7.60%±1.40%) compared to the BM-MNCs (1.10%±0.46%), P<0.01; the proportion of the megakaryocyte progenitor cells (Lin -Sca-1 -c-Kit +CD41 +CD150 +) and mature megakaryocyte cells (CD41 +CD42b +), also differ significantly between the FL-MNCs (3.05%±0.22%, 1.60%±0.06%, respectively) and the BM-MNCs (0.15%±0.02%, 0.87%±0.11%, respectively) groups, both P<0.01. In vitro functional studies showed that FL-MNCs-CD41 +megakaryocytes could produce proplatelet-like cells more quickly after induction, with proplatelet-like cells formation on day 3 and significant platelet-like particle formation on day 5, in contrast to bone marrow-derived BM-MNCs-CD41 +megakaryocytes that failed to form proplatelet-like cell on day 5. In addition, FL-MNCs-CD41 +cells expressed higher levels of platelet-related genes, Mpl (3.25-fold), Fog1 (3-fold), and Gata1 (1.5-fold) ( P<0.05). Conclusion:Compared with the BM-MNCs group, the FL-MNCs transplantation group appears to have a more efficient platelet implantation effect in the HSCs transplantation recipient in vivo , as well as a higher platelet differentiation rate in vitro. This might be related to a higher proportion of megakaryocytes and higher expression levels of genes such as Mpl, Fog1, and Gata1 that could be important for platelet formation in FL-MNCs-CD41 +cells. Further exploration of the specific functions of these genes and the characteristics of the different proportions of the donor cells will provide valuable clues for the future treatment of platelets reconstitution after HSCs transplantation clinically.

Objective To establish a porcine model of liver failure after different percent hepatectomy.Methods The porcine models of liver failure 75%,85%,95% hepatectomy were developed and the living conditions and survival time were recorded.The blood samples of pre-surgery,post-hepatectomy d1,d3,d5 and post-hepatectomy 1 week,2 weeks,and 3 weeks were collected for hepatic function analysis.Histological examination of liver tissues was performed using HE staining.Liver injury histology was interpreted and scored in the terminal samples.Results The average survival time of pigs with post-hepatectomy liver failure after 75%,85%,95% hepatectomy was 19.0±5.6 days,17.3±5.5 days,1.3±1.5 days,respectively.Their pathological scores were 5.67±0.52,8.17±0.82 and 8.50±0.71,respectively.With the increase of percent hepatic resection,the incidence of hepatic failure was increasing.ALT,AST,ALP,LDH and TBA were dramatically increased in the pigs after 85% hepatectomy.Conclusions The pig model of acute liver failure by 85% hepatectomy is successfully established,which can cause typical acute liver failure in Bama miniature pigs.

Objective To study the synergetic effect and possible mechanism of transplanting mesenchymal stem cells (MSCs) in combination with interleukin-1 receptor antagonist (IL-1Ra) on acute liver failure (ALF).Methods MSCs transplantation combined with IL-1Ra was used for a swine model of ALF induced by 85％ total hepatectomy.The living conditions,blood samples and survival time were recorded or collected for analysis of hepatic function.Liver injury histology was analyzed.Hepatic cell regeneration and apoptosis were studied by immunohistochemistry staining of Ki67 and TUNELassays respectively.The expression levels of AKT and NF-κB were analyzed by Western blotting.Results The difference on the survival time between the model group and combined therapy group was statistically significant (P ＜ 0.05).Combined therapy displayed improvement not only in the serum biochemical conditions but also in the serum inflammatory cytokines.Furthermore,the observed hepatic histopathological score was significantly less compared to model group.In addition,the combined therapy group significantly inhibited the liver cell apoptosis and increased hepatic cell regeneration.Finally,a significant increase in AKT expression and decrease of NF-κB expression (P ＜ 0.05) were observed,which was consistent with their important roles in liver regeneration.Conclusion The combined therapy displayed a synergistic effect on liver regeneration,by promoting restoration and reconstruction of ALF,through regulation of inflammation and apoptosis signaling network.

ABSTRACT:Objective To investigate changes in the neutrophils in rats with D-galactosamine (D-GalN)-induced acute liver failure (ALF)and to explore the therapeutic effect of interventions treatment of neutrophils on ALF.Methods Liver function,the expressions of inflammatory cytokines TNF-αand IL-1β,and the changes of neutrophils in the peripheral blood and the liver were observed in rats with D-GalN (intraperitoneal injection)-induced ALF.SD rats were randomly divided into three groups when treated with intervention of neutrophils:control group,ALF group (intraperitoneal injection of D-GalN),and treatment group (intravenous injection of anti-PMN serum via tail vein 24 h before modeling).Biochemical analysis was used to detect serum ALT,AST, TBIL and blood ammonia.Hematology analyzer was applied to analyze the number and percentage of peripheral blood neutrophils.The number of neutrophils in the liver was evaluated by immunohistochemistry.Liver RT-PCR was adopted to detect the mRNA expression of inflammatory cytokines TNF-αand IL-1β.Results We found that 6 h after D-GalN injection,serum ALT,AST,TBIL and blood ammonia in ALF rats were significantly increased (P <0.05).The mRNA expression levels of inflammatory cytokines TNF-αand IL-1βin the liver reached the peak at 6 h after modeling (P <0.001),and it was still notably higher at 24 h than before modeling (P <0.001 ).The number and percentage of peripheral blood neutrophils and the number of neutrophils in the liver were all markedly increased 12 h after modeling (P <0.001 ),and the increase continued at least until 24 h (P <0.001 ).24 h after intravenous injection of anti-PMN serum via tail vein,ALF rats had a distinct decrease in the number of peripheral blood neutrophils and neutrophils in the liver 24 h after modeling (P <0.001).Meanwhile,serum ALT,AST,TBIL and blood ammonia were all greatly decreased compared with those in ALF group (P <0.05);a significant reduction of hepatocyte apoptosis was observed.Also,the expressions of TNF-α and IL-1β in the liver were remarkably decreased after treatment (P <0.05).Conclusion Neutrophils accumulated in peripheral blood and liver of rats with D-GalN-induced ALF.The treatment of anti-PMN serum may have a therapeutic effect on liver function and immune microenvironment in ALF rats.

Objective To investigate the therapeutic effect of bone marrow mesenchymal stromal cell (BMSC) transplantation on D-galactosamine-induced acute liver failure in Sprague-Dawley (SD) rats,as well as the mechanism of neutrophils in this process.Methods A total of 39 male SD rats were divided into control group (8 rats,intraperitoneal injection of isotonic saline),model group (10 rats,intraperitoneal injection of D-galactosamine),solvent group (9 rats,tail vein injection of isotonic saline at 2 hours after intraperitoneal injection of D-galactosamine),and treatment group (12 rats,tail vein injection of MSCs at 2 hours after intraperitoneal injection of D-galactosamine).The rats were sacrificed at 24 hours after the model of D-galactosamine-induced acute liver failure was established,and the blood and liver tissue were harvested.The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TBil) were measured,and blood analysis was performed to measure the number and percentage of neutrophils in peripheral blood.Immunofluorescence assay was used to measure the expression of the neutrophil marker Ly6g in the liver,the myeloperoxidase (MPO) kit was used to measure the activity of MPO in liver,and RT-PCR was used to measure the mRNA expression of inflammatory cytokines and chemokines in the liver,i.e.,tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),interferon-γ (IFN-γ),interleukin-10 (IL-10),CXC chemokine ligand 1 (CXCL1),and CXC chemokine ligand 2 (CXCL2).Another 64 male SD rats were randomly divided into groups,and the survival rates of rats in each group were observed for 7 days.The independent samples t-test was used for comparison between any two groups (Levene homogeneity test of variance,and the corrected t-test was used for a P value of ＜ 0.05),and the log-rank test was used for comparison of survival rates between any two groups.Results At 24 hours after acute liver failure was induced by D-galactosamine in the SD rats,there were significant increases in the liver function parameters (ALT:2884.1±541.0 U/L vs 45.4±11.0 U/L,P ＜ 0.001;AST:3634.9±755.9 U/L vs 143.9±23.7 U/L,P ＜ 0.001;TBil:44.4±8.4 μmmol/L vs 0.9±0.2 μmmol/L,P ＜ 0.001) and the number and percentage of peripheral blood neutrophils [number:(4.7±1.1)×109 vs (1.4±0.4)× 109,P ＜0.001;percentage:44.9％±8.0％ vs 18.3％±4.4％,P ＜ 0.001].A large number of neutrophils aggregated in the liver tissue,and there were significant increases in the MPO activity (4.72±1.09 U/g vs 1.13±0.24 U/g,P ＜ 0.001),inflammatory cytokines,and chemokines.Compared with the model group,the treatment group showed significant improvements in liver function (ALT:1 823.9a389.2 U/L vs 2 884.1±541.0 U/L,P ＜ 0.001;AST:2173.0±567.3U/L vs 3634.9±755.9 U/L,P ＜ 0.001;TBil:30.9±6.5 μmmol/L vs 44.4±8.4 μmmol/L,P ＜ 0.001) and survival rate (50％ vs 12.5％,P=0.023).Meanwhile,the treatment group also showed significant reductions in the number and percentage of peripheral blood neutrophils [number:(3.5±1.0)× 109 vs (4.7±1.1)×109,P =0.012;percentage:35.9％±8.9％ vs 44.9％±8.0％,P =0.021],number of neutrophils in the liver,and MPO activity (3.52±1.03 U/g vs 4.72±1.09 U/g,P =0.040),as well as significantly inhibited expression of inflammatory cytokines and chemokines (TNF-α:2.458±0.762 vs 3.778±1.046,P =0.005;IL-1β:2.498±0.547 vs 4.065 ± 0.953,P =0.002;IFN-γ:3.977±1.039 vs 5.418±1.255,P =0.025;IL-10:6.056±1.542 vs 3.368±0.952,P=0.001;CXCL1:7.988±1.911 vs 10.366±1.239,P =0.010;CXCL2:3.441±1.005 vs 4.847±1.113,P=0.019).Conclusion BMSC transplantation has a therapeutic effect on D-galactosamine-induced acute liver failure in rats,and this process is accompanied by reduced aggregation and activity of neutrophils in peripheral blood and liver.Inflammatory cytokines and chemokines may be involved in the mechanism of regulation of these two aspects.

A novel amplifier system was proposed for low-noise recording of pico-ampere current in nanopore experiment (<100 pA). As an example, the amplifier system was applied in α-hemolysin based nanopore detection of DNA-PEG-DNA conjugate to record the signals of translocation and bumping events in buffer solution (1 mol/L KCl, 10 mmol/L Tris--HCl, 1 mmol/L EDTA and pH=8. 0). The amplified current signal was filtered by a 3 kHz Bessel filter and sampled by a 100 kHz analog-digital convertor. As a result, the presented amplifier system could lower the noise in recording the current. The current blockages (<10 pA) of single molecules with low amplitude were recovered due to the high signal-to-noise ratio.