丁苯酞软胶囊对中重度脑白质疏松患者血浆尿酸表达及脑白质病变的影响

目的 探究丁苯酞软胶囊对中重度脑白质疏松患者血浆尿酸表达及脑白质病变的影响。方法 选取江苏省海安市人民医院神经内科2021年5月至2022年11月收治的中重度脑白质疏松患者,按随机数字表法分为研究组和对照组。对照组采用常规基础治疗,研究组在对照组的基础上加用丁苯酞软胶囊。比较两组患者治疗前后简易智力状态检查(MMSE)评分、蒙特利尔认知评估量表(MoCA)评分、Hachinski缺血评分量表(HIS)、全面衰退量表(GDS)、血浆因子[同型半胱氨酸(Hcy)、总胆固醇(TC)、中枢神经特异蛋白(S100β)、尿酸(UA)]水平以及脑白质病变改善情况[大动脉血流速度收缩期峰流速(Vs)、舒张期末峰流速(Vd)以及平均峰流速(Vm)]。结果 共纳入60例脑白质疏松患者,研究组和对照组各30例。两组治疗前MMSE、MoCA、HIS、GDS评分、Hcy、TC、S100β、UA水平及两侧Vs、Vd、Vm比较差异均无统计学意义(P> 0.05),治疗后MMSE、MoCA评分、两侧Vs、Vd、Vm均较治疗前升高(P <0.05),且研究组较对照组高(P <0.05);HIS、GDS评分、Hcy、TC、S100β、UA水平明显较治疗前降低(P <0.05),且研究组较对照组低(P<0.05)。结论 丁苯酞软胶囊可用于中重度脑白质疏松的治疗,可有效降低患者认知障碍,恢复认知功能,降低血浆因子水平,提高脑血流量,改善脑白质病变情况。

Exosome is involved in liver graft protection after remote ischemia reperfusion conditioning

Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in rats.Methods:Twenty-five rats(including 10 donors)were randomly divided into five groups(n=5 each group):five rats were used as sham-operated controls(Sham),ten rats were for orthotopic liver transplantation(OLT,5 donors and 5 recipients)and ten rats were for OLT+RIPerC(5 donors and 5 recipients).Liver architecture and function were evaluated.Results:Compared to the OLT group,the OLT+RIPerC group exhibited significantly improved liver graft histopathology and liver function(P<0.05).Furthermore,the number of exosomes and the level of P-Akt were increased in the OLT+RIPerC group.Conclusions:RIPerC effectively improves graft architecture and function,and this protective effect may be related to the increased number of exosomes.The upregulation of P-Akt may be involved in underlying mechanisms.

Remote ischemic perconditioning prevents liver transplantation-induced ischemia/reperfusion injury in rats: Role of ROS/RNS and e NOS

AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning(RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation(OLT), ischemic postconditioning(IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine(Cr) and creatinine kinase-myocardial band(CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species(ROS), H2O2, mitochondrial membrane potential(ΔΨm) and total nitric oxide(NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase(e NOS) was analyzed by reverse transcription-polymerase chain reaction(RTPCR) and western blotting, and peroxynitrite was semiquantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions(P < 0.05). ROS(P < 0.001) including H2O2(P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC(P < 0.05) reversed this trend. The collapse of ΔΨm induced by OLT ischemia/reperfusion(I/R) injury was significantly attenuated in the RIPerC group(P < 0.001). A marked increase of NO content and phosphoserine eN OS, both in protein and mR NA levels, was observed in liver graft of the RIPer C group as compared with the OLT group(P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group(P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group(P < 0.01).CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up-regulation of the PI3K/Akt/e NOS/NO pathway.

Influence of perfusate on liver viability during hypothermic machine perfusion

AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best(vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001).CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.

Management hepatolithiasis with operative choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy

BACKGROUND: Hepatolithiasis is very common in East Asia. It is benign in nature, but has a high recurrence rate. It is likely to lead to biliary cirrhosis and increase the risk of cholangiocarcinoma. Hence, the treatment of hepatolithiasis is difficult but vital. In this report, we present a novel approach to manage hepatolithiasis using the choledochoscopic Frequency-Doubled Double pulse Nd:YAG (FREDDY) laser lithotripsy combined with or without hepatectomy. METHODS: Between July 2009 and October 2012, 45 patients underwent choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy (laser lithotripsy group). Fortyeight patients underwent a traditional operation (traditional method group) from January 2009 to June 2009. Comparative analysis was made of demographic and clinical characteristics of the two groups. RESULTS: The final stone clearance rate of the laser lithotripsy group was 93.3%, whereas that of the traditional method group was 85.4% (P=0.22). In the laser lithotripsy group, 2 patients experienced hemobilia and 3 patients had acute cholangitis. In the traditional method group, 3 patients had intraoperative hemorrhage, 1 patient had bile leakage, 6 patients had acute cholangitis, and 1 patient died of liver failure. Moreover, the operative time in the traditional method group was significantly longer than that in the laser lithotripsy group (P=0.01). The mean hospital stay of the patients in the traditional method group was longer than that in the laser lithotripsy group (9.8 vs8.2 days, P=0.17). Recurrent intrahepatic bile duct stones were not found during the follow-up period in the two groups. CONCLUSION: Operative choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy may be an effective and safe treatment for hepatolithiasis.

Optimal immunosuppressor induces stable gut microbiota after liver transplantation

AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosuppression,normal graft function and stable gut microbiota following LT in rats.The stable gut microbiota presented increased probiotics and decreased potential pathogenic endotoxin-producing bacteria.These findings provide a novel strategy based on gut microbiota for immunosuppressive dosage assessment for recipients following LT.

Retinoblastoma binding protein 4 up-regulation is correlated with hepatic metastasis and poor prognosis in colon cancer patients

Background: Retinoblastoma binding protein 4 (RBBP4) plays an essential role in the development of multiple cancers. However, its relationship with prognosis in colon cancer and colon cancer hepatic metastasis has not been elucidated. The aim of this study was to explore the relationship between RBBP4 expression and prognosis of colon cancer patients and to evaluate RBBP4 as a new prognostic marker in these patients. Methods: Eighty colon cancer patients underwent surgical resection of the colon were enrolled. Among them, forty colon cancer patients suffered with hepatic metastasis. The colon cancer tissues, para-colon cancer tissues, and hepatic metastatic cancer tissues were collected from the pathological department for further analysis. The expression of RBBP4 proteins was examined by immunohistochemistry and correlated with clinicopathological parameters. The Cancer Genome Atlas (TCGA) database was used to validate the expression and explore its relationship with clinical characteristics. Results: RBBP4 was up-regulated in the colon cancer tissues compared with the para-colon cancer tissues. The analysis of TCGA database verified the upregulation of RBBP4 in the colon cancer tissues and RBBP4 overexpression was correlated with nerve invasion and poor outcomes of chemotherapy. Moreover, the positive rate of RBBP4 expression in 40 colon cancer patients with hepatic metastasis was higher in the hepatic metastatic cancer tissues (39/40, 97.5%) than in the colon cancer tissues (26/40, 65.0%). Our clinicopathological analysis showed that RBBP4 expression was significantly correlated with vascular invasion, hepatic metastasis, and lymph node involvement (all P < 0.05). Additionally, the survival analysis demonstrated that RBBP4 over-expression was correlated with poor prognosis. Conclusions: RBBP4 was upregulated in the colon cancer. RBBP4 may be a novel predictor for poor prognosis of colon cancer and colon cancer hepatic metastasis.

Hangzhou criteria as downstaging criteria in hepatocellular ca

Background:The downstaging of hepatocellular carcinoma(HCC)has been confirmed to benefit liver transplantation(LT)patients whose tumors are beyond the transplantation criteria.Milan criteria(MC),a tumor size and number-based assessment,is currently used as the endpoint in these patients.However,many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy.Hence,this study aimed to explore the feasibility of Hangzhou criteria(HC),which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number,as an endpoint of downstaging.Methods:We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy(LRT)as downstaging/bridge treatment prior to LT in three centers of China.Results:Recipients were divided into four groups:failed downstaging to the HC(group A,n=46),successful downstaging to the HC(group B,n=30),remained within the HC all the time(group C,n=113),and tumor progressed(group D,n=17).The 3-year HCC recurrence probabilities of groups B and C were not significantly different(10.3%vs.11.6%,P=0.87).The HCC recurrent rate was significantly higher in group A(52.3%)compared with that in group B/C(P<0.05).Seven patients(7/76,9.2%)whose tumor exceeded the the HC were successfully downstaged to the MC,and 39.5%(30/76)to the the HC.In group B,23 patients remained beyond the MC and their survivals were as well as those of patients within the MC.Conclusions:Compared to the MC,HC downstaging criteria can give more HCC patients access to LT and furthermore,the outcome of these patients is the same as those matching MC downstaging criteria.Hangzhou downstaging criteria therefore is applicable in clinical practice.

Chronic bile duct hyperplasia is a chronic graft dysfunction following liver transplantation

AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal group (n = 12): normal BN rats without any drug or operation; (2) SGT group (syngeneic transplant of BN-BN, n = 12): both donors and recipients were BN rats; and (3) AGT group (allogeneic transplant of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one d after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora. RESULTS: During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (aP < 0.01, bP < 0.001, respectively). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both aP < 0.01, bP < 0.05, respectively). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87± 0.13) were remarkably reduced (both aP < 0.01, bP < 0.05, respectively). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups. CONCLUSION: Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.

Human hepatocytes loaded in 3D bioprinting generate mini-liver

BACKGROUND: Because of an increasing discrepancy be-tween the number of potential liver graft recipients and the number of organs available, scientists are trying to create artiifcial liver to mimic normal liver function and therefore, to support the patient’s liver when in dysfunction. 3D printing technique meets this purpose. The present study was to test the feasibility of 3D hydrogel scaffolds for liver engineering. METHODS: We fabricated 3D hydrogel scaffolds with a bioprinter. The biocompatibility of 3D hydrogel scaffolds was tested. Sixty nude mice were randomly divided into four groups, with 15 mice in each group: control, hydrogel, hydro-gel with L02 (cell line HL-7702), and hydrogel with hepatocyte growth factor (HGF). Cells were cultured and deposited in scaffolds which were subsequently engrafted into livers after partial hepatectomy and radiation-induced liver damage (RILD). The engrafted tissues were examined after two weeks. The levels of alanine aminotransferase (ALT), aspartate amino-transferase (AST), albumin, total bilirubin, CYP1A2, CYP2C9, glutathione S-transferase (a-GST), and UDP-glucuronosyl transferase (UGT-2) were compared among the groups. He-matoxylin-eosin (HE) staining and immunohistochemistry of cKit and cytokeratin 18 (CK18) of engrafted tissues were evalu-ated. The survival time of the mice was also compared among the four groups. RESULTS: 3D hydrogel scaffolds did not impact the viability of cells. The levels of ALT, AST, albumin, total bilirubin, CY-P1A2, CYP2C9, a-GST and UGT-2 were signiifcantly improved in mice engrafted with 3D scaffold loaded with L02 compared with those in control and scaffold only (P<0.05). HE staining showed clear liver tissue and immunohistochemistry of cKit&nbsp;and CK18 were positive in the engrafted tissue. Mice treated with 3D scaffold+L02 cells had longer survival time compared with those in control and scaffold only (P<0.05). CONCLUSION: 3D scaffold has the potential of recreating liver tissue and partial liver functions and can be used in the reconstruction of liver tissues.

Mitofusin-2 mediated mitochondrial Ca2+ uptake 1/2 induced liver injury in rat remote ischemic perconditioning liver transplantation and alpha mouse liver-12 hypoxia cell line models

AIM To investigate the protective mechanism of mitofusin-2(Mfn2) in rat remote ischemic perconditioning(RIC) models and revalidate it in alpha mouse liver-12(AML-12) hypoxia cell lines.METHODS Sprague-Dawley rats were divided into three groups(n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting(WB) and quantitative real-time(q RT)-PCR. AML-12 cell lines were then subjected to normal culture, anoxic incubator tank culture(hypoxia) and anoxic incubator tank culture with Mfn2 knockdown(hypoxia + Si), and data of q RT-PCR, WB, mitochondrial membrane potential(ΔΨm), apoptosis, endoplasmic reticulum Ca2+ concentrations and mitochondrial Ca2+ concentrations were collected.RESULTS Both sham and normal culture groups showed no injury during the experiment. The RIC group showed amelioration of liver function compared with the orthotopic liver transplantation group(P < 0.05). q RTPCR and WB confirmed that Mfn2-mitochondrial Ca2+ uptake 1/2(MICUs) axis was changed(P < 0.005). In AML-12 cell lines, compared with the hypoxia group, the hypoxia + Si group attenuated the collapse of ΔΨm and apoptosis(P < 0.005). The endoplasmic reticulum Ca2+ decrease and mitochondrial Ca2+ overloading observed in the hypoxia group were also attenuated in the hypoxia + Si group(P < 0.005). Finally, q RT-PCR and WB confirmed the Mfn2-MICUs axis change in all the groups(P < 0.005).CONCLUSION Mfn2 participates in liver injury in rat RIC models and AML-12 hypoxia cell lines by regulating the MICUs pathway.

Central pancreatectomy for pancreatic schwannoma: A case report and literature review

Schwannomas are mesenchymal tumors originating from Schwann cells in peripheral nerve sheaths. Although the tumor can be located in any part of the human body, the most common locations are the head, neck, trunk and extremities. Pancreaticschwannomas are rare. To our knowledge, only 64 cases of pancreatic schwannoma have been reported in the English literature over the past 40 years. In this paper, we present a pancreatic schwannoma in a 59-year-old female. Ultrasound, computed tomography and magnetic resonance imaging revealed the tumor located in the pancreatic body; however, accurate diagnosis was hard to obtain preoperatively and a pancreatic cystadenoma was preliminarily considered. During laparotomy, the mass was found in the body of the pancreas. An enlarged gallbladder with multiple stones was also observed. We performed central pancreatectomy, end-to-side pancreaticojejunostomy and cholecystectomy. Notably, central pancreatectomy has been reported in only one case prior to this report. The gross specimen showed a mass with a thin capsule, 1.6 cm × 1.1 cm × 1.1 cm in size. Microscopic examination showed that the tumor was mainly composed of spindle-shaped cells with palisading arrangement and no atypia, which is consistent with a benign tumor. Both hypercellular and hypocellular areas were visible. Immunohistochemical staining revealed strongly positive results for protein S-100. Finally, the tumor was diagnosed as a schwannoma of the pancreatic body. Postoperatively, the patient recovered well and left the hospital 6 d later. During the 53-mo follow-up period, the patient remained well and free of complications.

C–C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

Background:Liver cirrhosis results from many forms of chronic damage,characterized by accumulation of extracellular matrix.The present study aimed to explore a potential non-invasive biomarker and its mechanism in the progression of liver cirrhosis.Methods:Gene Expression Omnibus(GEO)dataset(GSE15654,n=216)was analyzed to screen genes associated with progression of liver cirrhosis.A total of 181 plasma samples,including healthy control(HC,n=20),chronic hepatitis B(CHB,n=77)and HBV-related liver cirrhosis(LC,n=84),were enrolled for validation.In vitro and in vivo experiments were employed for the mechanistic investigation.Results:GEO dataset analysis showed that relatively low mRNA-expression of C–C motif chemokine ligand 16(CCL16)was associated with elevated Child-Pugh score(P=0.034)and worse prognosis(P=0.025).Plasma CCL16 level decreased in a stepwise pattern,with a median concentration of 10.29,6.57 and 4.47 ng/mL in the HC,CHB and LC groups,respectively(P<0.001).Low plasma CCL16 was significantly related to hepatic dysfunction both in the CHB and LC groups(P<0.05).Combination of CCL16 and ALT showed improved distinguishing capability for LC compared to either alone.In vitro,CCL16 expression was downregulated by lipopolysaccharide and hypoxia.Overexpression of CCL16 from human normal liver cell line(LO2)reduced the extracellular matrix associated proteins(Col1 and Col4)in human hepatic stellate cell line(LX-2).In vivo,the pathological feature of cirrhosis was alleviated by the hepatocytespecific expression of CCL16.Conclusions:CCL16 could be a feasible plasma marker to predict the occurrence and progression of liver cirrhosis.CCL16 might impact liver cirrhosis through inactivating hepatic stellate cells.

Survival comparison between primary hepatic neuroendocrine neoplasms and primary pancreatic neuroendocrine neoplasms and the analysis on prognosis-related factors

Background:Primary hepatic neuroendocrine neoplasms(PHNENs)are extremely rare and few articles have compared the prognosis of PHNENs with other neuroendocrine neoplasms(NENs).This study aimed to investigate the different prognosis between PHNENs and pancreatic NEN(Pan NENs)and evaluate the relevant prognosis-related factors.Methods:From January 2012 to October 2016,a total of 44 NENs patients were enrolled and divided into two groups according to the primary tumor location which were named group PHNENs(liver;n=12)and group Pan NENs(pancreas;n=32).Demographic,clinical characteristics and survival data were compared between the two groups with Kaplan-Meier method and log-rank tests.Prognostic factors were analyzed using the Cox regression model.Results:The overall survival of group PHNENs and group Pan NENs were 25.4±6.7 months and 39.8±3.7 months,respectively(P=0.037).The cumulative survival of group Pan NENs was significantly higher than that of group PHNENs(P=0.029).Univariate analysis revealed that sex,albumin,total bilirubin,total bile acid,aspartate aminotransferase,alkaline phosphatase,α-fetoprotein and carbohydrate antigen 19-9,histological types,treatments and primary tumor site were the prognostic factors.Further multivariate analysis indicated that albumin(P=0.008),histological types NEC(P=0.035)and treatments(P=0.005)were the independent prognostic factors.Based on the histological types,the cumulative survival of patients with well-differentiated neuroendocrine tumor was significant higher than that of patients with poorly differentiated neuroendocrine carcinoma in group PHNENs(P=0.022),but not in group Pan NENs(P>0.05).According to the different treatments,patients who received surgery had significantly higher cumulative survival than those with conservative treatment in both groups(P<0.05).Conclusions:PHNENs have lower survival compared to Pan NENs.Histological types and treatments affect the prognosis.Surgical resection still remains the first line of treatment for resectable lesions and can significantly improve the survival.

Oncogenic role of microRNA-423-5p in hepatocellular carcinoma

BACKGROUND： It has been found that microRNA-423-5p （miR423-Sp） is an oncogenic factor and frequently upregulated in gastric carcinoma. However, the involvement of miR423- 5p in hepatocellular carcinoma （HCC） has been rarely reported. The aim of this study was to assess whether miR423-Sp is aberrantly expressed in HCC tissues, and to characterize its roles in the cancerous biology of HCC.

A good prognostic predictor for liver transplantation recipients with benign end-stage liver cirrhosis

BACKGROUND： Post-transplant model for predicting mortality（PMPM, calculated as-5.359＋1.988×ln（serum creatinine [mg/d L]）＋1.089×ln（total bilirubin [mg/d L]）） score has been proved to be a simple and accurate model for predicting the prognosis after liver transplantation（LT） in a single center study. Here we aim to verify this model in a large cohort of patients.METHODS： A total of 2727 patients undergoing LT with endstage liver cirrhosis from January 2003 to December 2010 were included in this retrospective study. Data were collected from the China Liver Transplant Registry（CLTR）. PMPM score was calculated at 24-h and 7-d following LT. According to the PMPM score at 24-h, all patients were divided into the low-risk group（PMPM score ≤-1.4, n=2509） and the high-risk group（PMPM score 〉-1.4, n=218）. The area under receiver operator characteristic curve（AUROC） was calculated for evaluating the prognostic accuracy.RESULTS： The 1-, 3-, and 5-year patient survival rates in the low-risk group were significantly higher than those in the high-risk group（90.23%, 88.01%, and 86.03% vs 63.16%, 59.62%, and 56.43%, respectively, P〈0.001）. In the high-risk group, 131 patients had a decreased PMPM score（≤-1.4） at 7-d, and their cumulative survival rate was significantly higher than the other 87 patients with sustained high PMPM score（〉-1.4）（P〈0.001）. For predicting 3-month mortality, PMPM score showed a much higher AUROC than post-transplant MELD score（P〈0.05）.CONCLUSION： PMPM score is a simple and effective tool to predict short-term mortality after liver transplantation in patients with benign liver diseases, and an indicator for prompt salvaging treatment as well.

Lack of association between genetic polymorphisms in cytokine genes and tumor recurrence in patients with hepatocellular carcinoma undergoing transplantation

BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after liver transplantation(LT) remains one of the most common causes of poor long-term survival.However,the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated.The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC.METHODS:Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes,i.e.,the IL-1 family(IL-1α and IL-1β),IL-6,IL-8,IL-10,TNF-α,and TGF-β1,were genotyped in 93 HCC patients treated with LT using DNA sequencing.The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables.RESULTS:The genotype frequency of IL-10-1082 A/G in patients with and without recurrence of HCC was AA 83.3%,GA 16.7% and AA 97.6%,GA 2.4%,respectively.The association between IL-10-1082 GA and recurrence was significant(P=0.033).No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence.Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients(23.5 vs 5.7 months,P=0.001).However,multivariate analysis failed to reveal that the GA genotype of IL-10-1082 A/G was an independent indicator of recurrence.CONCLUSIONS:This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population.The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.

CADM1 regulates the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma

BACKGROUND： Increasing evidence indicates that down- regulation of cell adhesion molecule 1 （CADM1） contributes to tumorigenesis in various cancers. The present study was undertaken to investigate the CADM1 expression pattern in human hepatocellular carcinoma （HCC）, and to elucidate the mechanism underlying CADMl-mediated tumor suppression.

The effect of SphK1/S1P signaling pathway on hepatic sinus microcirculation in rats with hepatic ischemia-reperfusion injury

To the Editor:Hepatic ischemia-reperfusion(I/R)injury is the component of liver injury related to liver transplantation and liver surgery[1-3].The hepatic sinus microcirculation injury is a central part of hep-atic I/R injury,which eventually leads to hepatocyte injury.This process is closely associated with the participation of liver non-parenchymal cells such as Kuffer cells,hepatic stellate cells,liver sinusoidal endothelial cells(LSECs),and cytokines.

Schwannoma in the hepatoduodenal ligament: A case report and literature review

Schwannomas are mesenchymal neoplasms with low malignant potential that arise from Schwann cells. They can occur almost anywhere, although the most common locations are the head, neck and extremities. Primary benign schwannoma of the hepatoduodenal ligament is rare. To date, only three cases have been reported in the English literature. In the present study, we report a case of hepatoduodenal ligament schwannoma in a 43-year-old male, who was admitted to our hospital because of a abdominal mass found by physical examination. It was hard to determine the definitive location and diagnosis of the mass using ultrasound, computed tomography and magnetic resonance cholangiopancreatography. During laparotomy, the mass was found in the hepatoduodenal ligament and close to the cholecystic duct, so we resected the gallbladder and cholecystic duct along with the mass. The gross specimen revealed an 8.5 cm × 5.5 cm × 3.0 cm localized tumor. Microscopic examination showed that the tumor was mainly composed of spindle-shaped cells. Immunohistochemical staining showed a strong positive S-100 protein reaction. Finally, the lesion was diagnosed as a benign schwannoma in the hepatoduodenal ligament. However, one month later, the patient was readmitted to our hospital because of skin and sclera jaundice caused by common bile duct stenosis without common bile duct stone or tumor. The patient recovered well after implantation of a common bile duct stent under endoscopic retrograde cholangiopancreatography. He was followed up for a period of 17 mo, during which he was well with no complications.