Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt:Mechanistic and clinical implications

In this article,we provide commentary on the recent article by Zhao et al.We focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and treatment.By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy group.The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies.Furthermore,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated PH.Despite these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal models.In conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

Dynamics of glutamine synthetase expression in hepatic ischemiareperfusion injury: Implications for therapeutic interventions

BACKGROUND Hepatic ischemia-reperfusion injury(IRI)poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses.The changes in glutamine synthetase(GS)expression during hepatic IRI remain unclear.AIM To investigate the dynamic expression of GS during hepatic IRI.METHODS Following hepatic ischemia for 1 h and reperfusion,liver tissue samples were collected at 0.5,6,and 24 hours postreperfusion for fixation,embedding,section-ing.Hematoxylin and eosin staining and GS staining were performed.RESULTS GS expression rapidly decreases in hepatocytes around the central vein after IRI,reaching its lowest point at 6 hours postreperfusion,and then gradually recovers.CONCLUSION GS is highly sensitive to IRI,highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.

Laparoscopic cholecystectomy with communicating accessory hepatic duct injury and management: A case report

BACKGROUND Laparoscopic cholecystectomy is considered the gold standard for the treatment of patients with gallstones.However,bile duct injury is one of the most serious complications of this surgery,with an incidence rate of 0.3%-0.7%.Variations in anatomical structures are one of the main reasons for such injuries.CASE SUMMARY We report a 26-year-old male patient who presented with repeated upper abdominal pain for 1 year.Ultrasound examination and blood tests indicated gallstones accompanied by chronic cholecystitis.The patient underwent laparo-scopic cholecystectomy.During the surgery,a communicating bile duct connec-ting the gallbladder neck and the right hepatic duct was discovered and injured.Meticulous dissection identified it as a communicating accessory hepatic duct,which was then definitively ligated.Postoperatively,the patient recovered well,magnetic resonance imaging and magnetic resonance cholangiopancreatography showed no intrahepatic or extrahepatic bile duct strictures.The pathology report showed chronic cholecystitis with gallstones.CONCLUSION Carefully manage communicating accessory bile ducts in cholecystectomy using cholangiography or meticulous separation,followed by ligation is effective.

Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

miR-30b inhibits autophagy to alleviate hepatic ischemiareperfusion injury via decreasing the Atg12-Atg5 conjugate

AIM: To explore the role and potential mechanism of miR-30 b regulation of autophagy in hepatic ischemiareperfusion injury(IRI).METHODS: An animal model of hepatic IRI was generated in C57BL/6 mice. For in vitro studies, AML12 cells were immersed in mineral oil for 1 h and then cultured in complete Dulbecco's Modified Eagle's Medium(DMEM)/F12 to simulate IRI. Mice and cells were transfected with miR-30 b agomir/mimics or antagomir/inhibitor to examine the effect of miR-30 b on autophagy to promote hepatic IRI. The expression of miR-30 b was measured by real-time polymerase chain reaction. Apoptotic cells were detected by terminal uridine nickend labeling(TUNEL) staining, and cell viability was detected by methylthiazole tetrazolium assay. The expression of light chain 3, autophagy-related gene(Atg)12, Atg5, P62, and caspase-3 were detected by western blotting analysis.RESULTS: miR-30 b levels were significantly downregulated after hepatic IRI, and the numbers of autophagosomes were increased in response to IRI both in vivo and in vitro. These findings demonstrate that low levels of miR-30 b could promote hepatic IRI. Furthermore, we found that miR-30 b interacted with Atg12-Atg5 conjugate by binding to Atg12. Overexpression of miR-30 b diminished Atg12 and Atg12-Atg5 conjugate levels, which promoted autophagy in response to IR. In contrast, downregulation of miR-30 b was associated with increased Atg12-Atg5 conjugate levels and increased autophagy.CONCLUSION: miR-30 b inhibited autophagy to alleviate hepatic ischemia-reperfusion injury via decreasing the Atg12-Atg5 conjugate.

Role of P-selectin and anti-P-selectin monoclonal antibody in apoptosis during hepatic/renal ischemia-reperfusion injury

AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expression and cell apoptosiswere detected in rat model of hepatic/ renalischemia-reperfusion injury.ELISA,immunohist-ochemistry and TUNEL were used.Someischemia-reperfusion rats were treated with anti-P-selectin mAb.RESULTS Hepatic/renal function insuffic-iency,up-regulated expression of P-selectin inplasma and hepatic/renal tissue,hepatic/renalhistopathological damages and cell apoptosiswere found in rats with hepatic/renal ischemia-reperfusion injury,while these changes becameless conspicuous in animals treated with anti-P-selectin mAb.CONCLUSION P-selectin might mediateneutrophil infiltration and cell apoptosis andcontribute to hepatic/renal ischemia-reperfusioninjury,anti-P-selectin mAb might be an efficientapproach for the prevention and treatment ofhepatic/renal ischemia-reperfusion injury.

Molecular therapy for hepatic injury and fibrosis:Where are we?

Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.

Hepatic recompensation according to Baveno VII criteria via transjugular intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunt is a therapeutic modality done through interventional radiology.It is aimed to decrease portal pressure in special situations for patients with decompensated liver disease with portal hypertension.It represents a potential addition to the therapeutic modalities that could achieve hepatic recompensation in those patients based on Baveno VII criteria.

Ex vivo-expanded bone marrow stem cells home to the liver and ameliorate functional recovery in a mouse model of acute hepatic injury

BACKGROUND:Stem cell transplantation provides a theoretical approach for liver regeneration medicine;it may promote liver regeneration and self-repair.However,the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated.This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl 4 injury.METHODS:Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation,characterized by cytoflow immunofluorescence,and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl 4.The integration of bone marrow cells into the liver was examined microscopically,and plasma hepatic enzymes were determined biochemically.RESULTS:Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells.Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl 4 -treated mice.Densitometry showed increased in situ cell proliferation (50±14 vs 20±3 cells/high-power field,P<0.05) and albumin expression (149±25 vs 20±5 cells/high-power field,P<0.05) in the liver,as well as reduced serum aminotransferase levels (P<0.05) and better survival rates (P<0.05) in animals receiving cultured bone marrow cells relative to controls.CONCLUSIONS:Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically- injured liver.Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.

什么是近肝静脉损伤（Juxtrahepatic venous injury，JHVI）？

解答：近肝静脉损伤是指肝静脉与肝后下腔静脉的损伤。由于解剖结构特殊，近肝静脉损伤后出血量大，易发生卒气栓寒，死亡率高，是肝破裂治疗中的棘手问题；如术中常规的Pringle手法阻断肝十二指肠韧带止血无效，则应考虑存在JHVI的可能，除补充循环血容量维持生命体征等治疗措施外，尽快手术修补损伤的血管最为关键。可切除部分肝组织充分暴露肝静脉或下腔静脉肝控制大血符裂口，予以修补，亦可采用房腔分流法进行修补。

Curcumin protects against acetaminophen-induced apoptosis in hepatic injury

AIM:To explore the effects of curcumin(CMN)on hepatic injury induced by acetaminophen(APAP)in vivo.METHODS:Male mice were randomly divided into three groups:groupⅠ(control)mice received the equivalent volumes of phosphate-buffered saline(PBS)intraperitoneally(ip);GroupⅡ[APAP+carboxymethylcellulose(CMC)]mice received 1%CMC(vehicle)2h before APAP injection;GroupⅢ(APAP+CMN)mice received curcumin(10 or 20 mg/kg,ip)2 h before before or after APAP challenge.In GroupsⅡandⅢ,APAP was dissolved in pyrogen-free PBS and injected at a single dose of 300 mg/kg.CMN was dissolved in 1%CMC.Mice were sacrificed 16 h after the APAP injection to determine alanine aminotransferase(ALT)levels in serum and malondialdehyde(MDA)accumulation,superoxide dismutase(SOD)activity and hepatocyte apoptosis in liver tissues.RESULTS:Both pre-and post-treatment with curcumin resulted in a significant decrease in serum ALT compared with APAP treatment group(10 mg/kg:801.46±661.34 U/L;20 mg/kg:99.68±86.48 U/L vs 5406.80±1785.75 U/L,P<0.001,respectively).The incidence of liver necrosis was significantly lowered in CMN treated animals.MDA contents were significantly reduced in 20 mg/kg CMN pretreatment group,but increased in APAP treated group(10.96±0.87 nmol/mg protein vs 16.03±2.58 nmol/mg protein,P<0.05).The decrease of SOD activity in APAP treatment group and the increase of SOD in 20 mg/kg CMN pretreatment group were also detected(24.54±4.95 U/mg protein vs 50.21±1.93 U/mg protein,P<0.05).Furthermore,CMN treatment efficiently protected against APAPinduced apoptosis via increasing Bcl-2/Bax ratio.CONCLUSION:CMN has significant therapeutic potential in both APAP-induced hepatotoxicity and other types of liver diseases.

Naringenin protects against isoniazid- and rifampicininduced apoptosis in hepatic injury

AIM To explore the protective effects and mechanisms of naringenin(NRG) on hepatic injury induced by isoniazid(INH) and rifampicin(RIF).METHODS Male mice were randomly divided into four groups and treated for 14 d as follows: normal control group was administered intragastrically with normal saline solution alone; model group was administered intragastrically with INH(100 mg/kg) and RIF(100 mg/kg); lowand high-dosage NRG pretreatment groups were administered intragastrically with different doses of NRG(50 or 100 mg/kg) 2 h before INH and RIF challenge. Mice were killed 16 h after the last dose of drug treatment to determine activity of serum transaminases. Oxidative stress was evaluated by measuring hepatic glutathione(GSH) and superoxide dismutase(SOD) and malondialdehyde(MDA) levels. Histopathological changes in hepatic tissue were observed under the optical microscope. Hepatocyte apoptosis was measured by TUNEL assay and caspase-3 activation. Expression of Bcl-2 and Bax in liver was determined by western blot.RESULTS Both low- and high-dosage NRG pretreatment obviously alleviated serum levels of alanine aminotransferase and aspartate aminotransferase, liver index, hepatic MDA content, and increased hepatic GSH content and SOD activity compared with the INH and RIF-treated group(44.71 ± 8.15 U/L, 38.22 ± 6.64 U/L vs 58.15 ± 10.54 U/L; 98.36 ± 14.78 U/L, 92.41 ± 13.59 U/L vs 133.05 ± 19.36 U/L; 5.34% ± 0.26%, 4.93% ± 0.25% vs 5.71% ± 0.28%; 2.76 ± 0.67 nmol/mgprot, 2.64 ± 0.64 nmol/mgprot vs 4.49 ± 1.12 nmol/mgprot; 5.91 ± 1.31 mg/gprot, 6.42 ± 1.42 mg/gprot vs 3.11 ± 0.73 mg/gprot; 137.31 ± 24.62 U/mgprot, 148.83 ± 26.75 U/mgprot vs 102.34 ± 19.22 U/mgprot; all P < 0.01 or 0.05). Histopathological evaluation showed obvious necrosis and inflammatory cell infiltration in liver of mice administered INH and RIF; however, mice pretreated with NRG showed minor hepatic injury. In addition, INH and RIF resulted in hepatocyte apoptosis, and NRG pretreatment dramatically suppressed INHand RIF-induced hepatocytes apoptosis. Furthermore, NRG-mediated anti-apoptotic effects seemed to be in connection with its regulation of Bax and Bcl-2 protein expression in hepatic tissue.CONCLUSION NRG might attenuate INH- and RIF-induced hepatic injury via suppression of oxidative stress and hepatocyte apoptosis.

Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50μg/kg pcDNA3-ALR DNA.The effect of intravenous injection of recombinant pcDNA3ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid,the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P＜0.01).CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level ofAST and ALT in CCl4-intoxicated rats.

Study on protecting effects of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis

AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes.RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.

Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis

BACKGROUND Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury,and finally leads to liver cirrhosis or even hepatocellular carcinoma.The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells(HSCs),which can transdiffer-entiate into myofibroblasts to produce an excess of the extracellular matrix(ECM).Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis.Therefore,activated hepatic stellate cells(aHSCs),the principal ECM producing cells in the injured liver,are a promising therapeutic target for the treatment of hepatic fibrosis.AIM To explore the effect of taurine on aHSC proliferation and the mechanisms involved.METHODS Human HSCs(LX-2)were randomly divided into five groups:Normal control group,platelet-derived growth factor-BB(PDGF-BB)(20 ng/mL)treated group,mmol/L,respectively)with PDGF-BB(20 ng/mL)treated group.Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs.Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species(ROS),malondialdehyde,glutathione,and iron concen-tration.Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs.Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression ofα-SMA,Collagen I,Fibronectin 1,LC3B,ATG5,Beclin 1,PTGS2,SLC7A11,and p62.RESULTS Taurine promoted the death of aHSCs and reduced the deposition of the ECM.Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation,by decreasing autophagosome formation,downregulating LC3B and Beclin 1 protein expression,and upregulating p62 protein expression.Meanwhile,treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload,lipid ROS accumu-lation,glutathione depletion,and lipid peroxidation.Furthermore,bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4,exhibiting the best average binding affinity of-20.99 kcal/mol.CONCLUSION Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.

New progress in roles of nitric oxide during hepatic ischemia reperfusion injury

Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1 alpha-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.

Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury

Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis （SAP） in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death, lts complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR （oxygen free radical）, endotoxin, etc. may play important roles in its progression.

Two clinically relevant pressures of carbon dioxide pneumoperitoneum cause hepatic injury in a rabbit model

AIM:To observe the hepatic injury induced by carbon dioxide pneumoperitoneum(CDP) in rabbits,compare the eects olow-and high-pressure pneumoperitoneum,and to determine the degree o hepatic injury induced by these two clinically relevant CDP pressures.METHODS:Thirty healthy male New Zealand rabbits weighing 3.0 to 3.5 kg were randomly divided into three groups(n = 10 for each group) and subjected to the ollowing to CDP pressures:no gas control,10 mmHg,or 15 mmHg.Histological changes in liver tissues were observed with hematoxylin and eosin staining and transmission electron microscopy.Liver unction was evaluated using an automatic biochemical analyzer.Adenine nucleotide translocator(ANT) activity in liver tissue was detected with the atractyloside-inhibitor stop technique.Bax and Bcl-2 expression levels were detected bywestern blotting.RESULTS:Liver Functions in the 10 mmHg and 15 mmHg experimental groups were significantly disturbed compared with the control group.After CDP,the levels or alanine transaminase and aspartate transaminase were 77.3 ± 14.5 IU/L and 60.1 ± 11.4 IU/L,respectively,in the 10 mmHg experimental group and 165.1 ± 19.4 IU/L and 103.8 ± 12.3 IU/L,respectively,in the 15 mmHg experimental group,which were all higher than those of the control group(p < 0.05).There was no difference in pre-albumin concentration between the 10 mmHg experimental group and the control group,but the prealbumin level of the 15 mmHg experimental group was significantly lower than that of the control group(p < 0.05).No significant differences were observed in the levels of total bilirubin or albumin among the three groups.After 30 and 60 min of CDP,pH was reduced(p < 0.05) and fa CO2 was elevated(p < 0.05) in the 10 mmHg group compared with controls,and these changes were more pronounced in the 15 mmHg group.Hematoxylin and eosin staining showed no significant change in liver morphology,except for mild hyperemia in the two experimental groups.Transmission electron microscopy showed mild mitochondrial swelling in hepatocytes of the 10 mmHg group,and this was more pronounced in the 15 mmHg group.No significant difference in ANT levels was found between the control and 10 mmHg groups.However,ANT concentration was significantly lower in the 15 mmHg group compared with the control group.The expression of hepatic Bax was significantly increased in the two experimental groups compared with the controls,but there were no differences in Bcl-2 levels among the three groups.Twelve hours after CDP induction,the expression of hepatic Bax was more significant in the 15 mmHg group than in the 10 mmHg group.CONCLUSION:A CDP pressure of 15 mmHg caused more substantial hepatic injury,such as increased levels of acidosis,mitochondrial damage,and apoptosis;therefore,10 mmHg CDP is preferable for laparoscopic operations.