The role of ectopic P granules protein 5 homolog (EPG5) in DHPG-induced pain sensitization in mice.

Nociplastic pain is a severe health problem, while its mechanisms are still unclear. (R, S)-3,5-Dihydroxyphenylglycine (DHPG) is a group I metabotropic glutamate receptor (mGluR) agonist that can cause central sensitization, which plays a role in nociplastic pain. In this study, after intrathecal injection of 25 nmol DHPG for three consecutive days, whole proteins were extracted from the L4~6 lumbar spinal cord of mice 2 h after intrathecal administration on the third day for proteomics analysis. Based on the results, 15 down-regulated and 20 up-regulated proteins were identified in mice. Real-time quantitative PCR (RT-qPCR) and western blotting (WB) revealed that the expression of ectopic P granules protein 5 homolog (EPG5) mRNA and protein were significantly up-regulated compared with the control group, which was consistent with the proteomics results. Originally identified in the genetic screening of Caenorhabditis elegans, EPG5 is mainly involved in regulating autophagy in the body, and in our study, it was mainly expressed in spinal neurons, as revealed by immunohistochemistry staining. After the intrathecal injection of 8 µL adeno-associated virus (AAV)-EPG5 short hairpin RNA (shRNA) to knock down spinal EPG5, the hyperalgesia caused by DHPG was relieved. Altogether, these results suggest that EPG5 plays an important role in DHPG-induced pain sensitization in mice.

Epstein-Barr virus-derived circular RNA LMP2A induces stemness in EBV-associated gastric cancer.

Cancer stem cells (CSCs) are cancer-initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5-fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU-4th, which displays properties of CSCs and mainly consists of CD44+ CD24- cells. In SNU-4th cells, an EBV-encoded circRNA, ebv-circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR-3908/TRIM59/p53 axis. Additionally, high expression of ebv-circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv-circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.

Fragile X mental retardation protein-regulated proinflammatory cytokine expression in the spinal cord contributes to the pathogenesis of inflammatory pain induced by complete Freund's adjuvant.

Studies have verified that Fragile X mental retardation protein (FMRP), an RNA-binding protein, plays a potential role in the pathogenesis of formalin- and (RS)-3,5-dihydroxyphenylglycine-induced abnormal pain sensations. However, the role of FMRP in inflammatory pain has not been reported. Here, we showed an increase in FMRP expression in the spinal dorsal horn (SDH) in a rat model of inflammatory pain induced by complete Freund's adjuvant (CFA). Double immunofluorescence staining revealed that FMRP was mainly expressed in spinal neurons and colocalized with proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)]. After consecutive intrathecal injection of fragile X mental retardation 1 small interfering RNA for 3 days post-CFA injection, FMRP expression in the SDH was reduced, and CFA-induced hyperalgesia was decreased. In addition, the CFA-induced increase in spinal TNF-α and IL-6 production was significantly suppressed by intrathecal administration of fragile X mental retardation 1 small interfering RNA. Together, these results suggest that FMRP regulates TNF-α and IL-6 levels in the SDH and plays an important role in inflammatory pain.

Promotion of Proton Conductivity by Encapsulation of Metal-Organic Polyhedra in Metal-Organic Frameworks.

A Zr-based metal-organic polyhedron (MOP) was self-assembled in a porous MOF host, DUT-68, successfully to synthesize MOP-1@DUT-68. The MOP guest (MOP-1) has a diameter of about 20 Å, larger than that of the square windows (pore sizes of ∼14 Å) of DUT-68 but smaller than that of the rhombicuboctahedral cage (27.7 Å), which means that the migration and leaching of MOP-1 could be effectively prohibited if MOP-1 is encapsulated in the MOF's cavities. The proton conductivity of MOP-1@DUT-68 is 1.14×10-3  S cm-1 (at 80 °C under 98 % relative humidity), which is three orders of magnitude higher than that of DUT-68. Compared with MOP-1⊂DUT-68, which was synthesized by impregnation, MOP-1@DUT-68 is more prone to form faster proton-conduction pathways and thus provides higher proton conductivity.

Role of fragile X mental retardation protein in chronic pain.

Chronic pain has detrimental effects on one's quality of life. However, its treatment options are very limited, and its underlying pathogenesis remains unclear. Recent research has suggested that fragile X mental retardation protein is involved in the development of chronic pain, making it a potential target for prevention and treatment. The current review of literature will examine the function of fragile X mental retardation protein and its associated pathways, through which we hope to gain insight into how fragile X mental retardation protein may contribute to nociceptive sensitization and chronic pain.

WeChat app-based reinforced education improves the quality of opioid titration treatment of cancer-related pain in outpatients: a randomized control study.

BACKGROUND: As inadequate pain communication contributes to difficulties in optimizing outcomes of outpatients, we investigated the effect of reinforced education using WeChat App to the opioid titration treatment of cancer-related pain in the outpatient setting. METHODS: We conducted a prospective study to compare reinforced education using Wechat with care as usual from February to December 2019. Patients in the reinforced education group received reinforced education via Wechat, while those in the control group received care as usual. Effect measurements for both groups are carried out with questionnaires at the baseline and 3 days later. Questionnaires include pain intensity (NRS), treatment-related adverse events, cancer-related quality of life (QOL), sleep (PSQI), satisfaction, anxiety (GAD-7) and depression (PHQ-9). Number of patients whose NRS reduced to less than three points in 24 h was the primary outcomes. Secondary outcomes included treatment-related adverse events, cancer-related quality of life, sleep, satisfaction, anxiety and depression. RESULTS: Although there was no significant difference regarding pain intensity (NRS) between the two groups at 72 h, the rate of NRS that reduced to less than three points in 24 h was significantly higher in the Wechat group than in the control group. Patients' satisfaction was significantly higher in the Wechat group than in the control group. There was no significant difference between the two groups regarding the other findings at 72 h, including pain intensity (NRS), cancer-related quality of life (QOL), anxiety (GAD-7), depression (PHQ-9), and sleep (PSQI). However, no significant difference was found between the two groups for constipation, nausea, vomiting, dizziness, somnolence, pruritus, loss of consciousness, and death. CONCLUSIONS: Our results indicated that receiving instructions delivered by Wechat resulted an increased number of patients with good pain control and better satisfaction. The study provided insight into the effectiveness of the reinforced education using a Wechat app delivered by a doctor to outpatients in the titration treatment of cancer-related pain. TRIAL REGISTRATION: This study was registered at chictr.org (Registration number: ChiCTR1900021150 , Date of Registration: January 30, 2019).

[Studies on chemical constituents of stems of Herpetospermum pedunculosum].

This project is to study chemical compositions from the stems of Herpetospermum pedunculosum. Twenty-two compounds were isolated from the 70% acetone extract of the stems of H. pedunculosum by column chromatography on Sephadex LH-20, semi-preparative HPLC and preparative TLC. Their structures were elucidated by their physicochemical properties and spectroscopic data as N-benzyltyramine(1), α-spinasterol(2),(2S)-1-O-heptatriacontanoyl glycerol(3), 5,7-dihydroxychromanone(4), methyl 2ß,3ß-dihydroxy-D:C-friedoolean-8-en-29-oate(5), p-hydroxy benzyl alcohol(6), p-hydroxybenzoate(7), p-hydroxy cinnamic acid(8), 1H-indol-3-carboxylic acid(9), rhodiocyanoside B(10), rhodiolgin(11), rhodiosin(12), 9,12,13-trihydroxy-10(E)-octadecenoic acid(13), cylo-(Tyr-Leu)(14), matteflavoside A(15), loliolide(16), 1H-indol-3-carboxaldehyde(17),(+)-dehydrovomifoliol(18), 3-hydroxy-5α,6α-epoxy-ß-ionone(19), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy-1-propen-1-yl)-2-methoxyphenoxy]-1-propanone(20), 7-en-nonadecanoic acid monoglyceride(21), vanillic acid(22). Compound 1 is a new natural product, while compounds 3-15 were isolated from this plant for the first time.

IFI16 is involved in HBV-associated acute-on-chronic liver failure inflammation.

BACKGROUND: Hepatitis B virus (HBV) is a hepatotropic DNA virus, and its DNA may be a potent inflammatory molecule. Interferon-inducible protein 16 (IFI16), a newly discovered DNA sensor, plays an important role in the process of inflammation in viral infections. Our study sought to identify a correlation between IFI16 expression and inflammation in patients with chronic hepatitis B (CHB) and HBV-associated acute-on-chronic liver failure (HBV-ACLF). METHODS: We performed flow cytometry to measure IFI16 levels in peripheral blood mononuclear cells (PBMC) and used immunohistochemistry and western blotting to measure IFI16 protein levels in liver tissues. The cellular source of IFI16 was detected using double immunofluorescence. All datum were analyzed using SPSS 13.0 and GraphPad Prism 6. RESULTS: The number of IFI16+ cells was significantly associated with the degree of inflammation. In detail, the number of IFI16+ cells was higher in livers but lower in PBMCs in HBV-ACLF patients than those in CHB patients and healthy controls. There was no significant difference between CHB patients and healthy controls in numbers of IFI6+ cells in livers and PBMCs. There was no significant relationship between IFI16 expression levels and HBV parameters. Furthermore, IFI16 was expressed in the nucleus of Kupffer cells (KCs), endothelial cells, natural killer cells, dendritic cells, and hepatic stellate cells in healthy donors and CHB patients, but only in the cytoplasm of KCs in the livers of HBV-ACLF patients. CONCLUSIONS: IFI16 was closely related to the degree of inflammation in CHB and HBV-ACLF patients and may serve as a vital contributor to the pathogeneses of liver damage in HBV-ACLF.

The analgesic efficacy of subcostal transversus abdominis plane block with Mercedes incision.

BACKGROUND: Conventional perioperative analgesic modalities (e.g. opioids, epidural analgesia) have their own drawbacks, which limit their clinical application. This study investigated the opioid-sparing effectsof the oblique subcostal transversus abdominis plane (OSTAP) blockade with ropivacaine for the patients undergoing open liver resection with a Mercedes incision. METHODS: 126 patients who were scheduled for open liver resection were enrolled in this study. Patients were randomly assigned to receive bilateral ultrasound-guided OSTAPblocks with either 0.375% ropivacaine (groupT) or 0.9% isotonic saline (group C). Both groups also received intravenous patient-controlled analgesia and intravenous 40 mg parecoxib every 12 h for a total of 3 days. Preoperative and intraoperative parameters, plus intraoperative and postoperative cumulative sufentanil consumption, were recorded. RESULTS: 70 patients were enrolled in the study finally. There were no significant differences between the two groups with respect to preoperative parameters, and surgical and anesthetic characteristics. The intraoperative sufentanil use, cumulative sufentanil consumption at 5 min after extubation, 2 h, 4 h,12 h and 24 h after operation in group T was significantly less than that in group C (P = 0.001, 0.001, 0.000, 0.000, 0.001 and 0.044, respectively). Compared with group C, postoperative NRS pain scores at rest were significantly lower at 2 h and 4 h postoperatively in group T (P = 0.04and 0.02, respectively); NRS scores at the time of coughing were also significantly lower in group T than in group C at all time points except 5 min after extubation (all P < 0.001). Furthermore, compared with group C, the number of intraoperative vasodilator use, the extubation time and the incidence of nausea was reduced in group T. CONCLUSION: Ultrasound-guided OSTAP block with ropivacaine can significantly decrease the perioperative cumulative dosage of analgesics and improve analgesic effect without obvious side effects for the patients who underwent an open liver resection with Mercedes incision when compared tothe ultrasound-guided OSTAP block with saline. TRIAL REGISTRATION: The study protocol was registered at http://www.chictr.org.cn (ChiCTR-TRC- 14004827) on February 19, 2014.

Prospective investigation of intravenous patient-controlled analgesia with hydromorphone or sufentanil: impact on mood, opioid adverse effects, and recovery.

BACKGROUND: Radical surgery for colorectal cancer, associated with moderate to severe postoperative pain, needs multimodal analgesia with opioid for analgesia. Despite considerable advancements, the psychological implications and other side effects with opioid remain substantially unresolved. This study aimed to investigate the impact on mood, side effects relative to opioid, and recovery of the patients with hydromorphone or sufentanil intravenous patient-controlled analgesia (IV-PCA) in a multimodal perioperative analgesia regimen undergoing radical surgery for colorectal cancer. METHODS: Eighty patients undergoing elective laparoscopic or open radical surgery for colorectal cancer under general anesthesia were randomized to receive postoperative IV-PCA with either sufentanil (group S) or hydromorphone (group H). All patients received additionally flurbiprofen axetil 50 mg 30 min before the end of surgery and wound infiltration with 10 ml of 0.75% ropivacaine at the end of surgery. The primary endpoint was mood changes at 48 and 96 h after surgery. The secondary endpoints were the incidence of opioid-related adverse effects, recovery results and patient satisfaction after surgery. RESULTS: Seventy-two patients completed the study finally. There were no significant differences between the two groups with respect to preoperative parameters, surgical and anesthetic characteristics (P > 0.05). No obvious significant differences were observed in VAS score (at rest and during mobilization) and rescue analgesics use (P > 0.05). Compared with group S, the anger scores in the group H at 48 h and 96 h after surgery were significantly lower (P = 0.012 and 0.005; respectively), but the incidences of pruritus and nausea were higher (P = 0.028 and 0.008; respectively). There were no significant differences in the incidences of vomiting, respiratory depression, dizziness, Ramsay score, and hemodynamic changes between the two groups (P > 0.05). Moreover, there were no significant differences in the time to gastrointestinal recovery, time to drainage tube removal, time to walk, hospital stay after surgery and patient satisfaction between the two groups (P > 0.05). CONCLUSIONS: Under the similar analgesia effect with different opoiods postoperatively, hydromorphone IV-PCA resulted in an improved mood, however, a higher occurrence of pruritus and nausea while compared to sufentanil IV-PCA in a multimodal perioperative analgesia regimen. Both regimens of opioid with IV-PCA may serve as promising candidates for good postoperative pain management, and provide with similar postoperative recovery for the patients undergoing radical surgery for colorectal cancer. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry on September 20, 2015 (URL: http://www.chictr.org.cn . Registry number: ChiCTR-IPR-15007112).

Novel multimodal analgesia regimen improves post-TACE pain in patients with hepatocellular carcinoma.

BACKGROUD: Transarterial chemoembolization (TACE) is the primary palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it is often accompanied by postoperative pain which hinder patient recovery. This study was to examine whether preemptive parecoxib and sufentanil-based patient controlled analgesia (PCA) could improve the pain management in patients receiving TACE for inoperable HCC. METHODS: From June to December 2016, 84 HCC patients undergoing TACE procedure were enrolled. Because of the willingness of the individuals, it is difficult to randomize the patients to different groups. We matched the patients' age, gender and pain scores, and divided the patients into the multimodal group (n = 42) and control group (n = 42). Patients in the multimodal group received 40 mg of parecoxib, 30 min before TACE, followed by 48 h of sufentanil-based PCA. Patients in the control group received a routine analgesic regimen, i.e., 5 mg of dezocine during operation, and 100 mg of tramadol or equivalent intravenous opioid according to patient's complaints and pain intensity. Postoperative pain intensity, percentage of patients as per the pain category, adverse reaction, duration of hospital stay, cost-effectiveness, and patient's satisfaction were all taken into consideration when evaluated. RESULTS: Compared to the control group, the visual analogue scale scores for pain intensity was significantly lower at 2, 4, 6, and 12 h (all P < 0.05) in the multimodal group and a noticeably lower prevalence of post-operative nausea and vomiting in the multimodal group (31.0% vs. 59.5%). Patient's satisfaction in the multimodal group was also significantly higher than that in the control group (95.2% vs. 69.0%). No significant difference was observed in the duration of hospital stay between the two groups. CONCLUSION: Preemptive parecoxib and sufentanil-based multimodal analgesia regime is a safe, efficient and cost-effective regimen for postoperative pain control in HCC patients undergoing TACE.

The overexpression of Rabl3 is associated with pathogenesis and clinicopathologic variables in hepatocellular carcinoma.

Overexpression of Rabl3 is associated with some malignancies. However, their relationship with hepatocellular carcinoma remains unclear. In this study, the expression of Rabl3 in hepatocellular carcinoma cell lines, and four pairs of matched hepatocellular carcinoma tissues and their adjacent normal hepatic tissues were detected by quantitative reverse transcription polymerase chain reaction and western blot. In addition, the protein expression of Rabl3 was examined in 162 cases of hepatocellular carcinoma by immunohistochemistry. Rabl3 in hepatocellular carcinoma cell lines was elevated at both messenger RNA and protein levels, and the Rabl3 protein was significantly upregulated by upto 3.3-fold in hepatocellular carcinoma compared with the paired normal hepatic tissues. Immunohistochemical analysis revealed that overexpressions of Rabl3 were 80.2% in hepatocellular carcinoma. Rabl3 is expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissue (p < 0.01). Statistical analysis suggested the upregulation of Rabl3 was significantly associated with lymph node metastasis, tumor thrombus of the portal vein, and advanced clinical stage (p < 0.05). Furthermore, we found that overexpression of Rabl3 in hepatocellular carcinoma cells could significantly enhance cell proliferation and growth ability. Conversely, silencing Rabl3 by small hairpin RNA interference caused an inhibition of cell proliferation and growth. Our studies suggest that the Rabl3 is a valuable marker of hepatocellular carcinoma progression and that the overexpression of Rabl3 plays an important role in the development and pathogenesis of hepatocellular carcinoma.

Sonic hedgehog signalling pathway regulates apoptosis through Smo protein in human umbilical vein endothelial cells.

OBJECTIVE: The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells. METHODS: The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined. RESULTS: We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2-8 µmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD (P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group (P < 0.05). CONCLUSION: The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner.

A role of microRNA-370 in hepatic ischaemia-reperfusion injury by targeting transforming growth factor-ß receptor II.

BACKGROUND & AIMS: MicroRNAs (miRNAs) are a group of small non-coding RNAs with modulator activity of gene expression. The role of miRNAs in hepatic ischaemia-reperfusion (IR) injury is currently largely unknown. The aim of this study was to investigate the potential role of miR-370 in hepatic IR injury. METHODS: The expression levels of hepatic miR-370 in male C57BL/6 mice subjected to hepatic IR injury or ischaemia preconditioning were assessed by quantitative real-time PCR. The effect of miR-370 on hepatic IR injury was investigated by serum enzyme analysis and histological examination of liver following treatment of mice with antagomir-370 or control. The levels of proinflammatory cytokines and apoptosis- and proliferation-related genes were also determined by quantitative real-time PCR. Furthermore, the potential targets of miR-370 in this injury were studied by bioinformatics analysis, luciferase assays, quantitative real-time PCR and Western blot. RESULTS: The results showed that miR-370 expression was significantly upregulated in the mice subjected to hepatic IR injury as compared with the sham-operated mice. Inhibition of miR-370 led to the downregulation of serum aminotransferase and proinflammatory cytokines, as well as the improvement of hepatic histological damage. Reporter assays confirmed that miR-370 directly targeted the 3' untranslated region of transforming growth factor-ß receptor II (TßRII). Inhibition of miR-370 was sufficient to reinstate the expression of TßRII and its downstream target phosphorylated Smad3. CONCLUSION: Our data suggest that miR-370 acting via TßRII might play a potential role in hepatic IR injury, and inhibition of miR-370 efficiently attenuated the damage to the liver.

Lack of Sex Difference in Minimum Local Analgesic Concentration of Ropivacaine for Ultrasound-Guided Supraclavicular Brachial Plexus Block.

BACKGROUND: Sex differences, which may be an important variable for determining anesthetic requirements, have not been well investigated in the aspect of local anesthetic. This investigation aimed to compare the minimum local analgesic concentration (MLAC) of ropivacaine for ultrasound-guided supraclavicular brachial plexus block (US-SCB) between men and women. MATERIAL AND METHODS: Patients aged 18-45 years undergoing elective forearm, wrist, or hand surgeries under US-SCB were divided into 2 groups according to sex. The initial concentration was 0.375% ropivacaine 20 mL and the concentration for the next patient was determined by the up-down technique at 0.025% intervals. Success was defined as the absence of any pain in response to a pinprick in the region of all 4 terminal nerves and the skin incision within 45 min. The primary outcome was the MLAC of ropivacaine, which was estimated by the Dixon and Massey method. The analgesia duration, which was defined as the time from the end of the US-SCB injection to the time of feeling discomfort and need for additional analgesics, was observed for each patient. RESULTS: The MLAC of ropivacaine 20 mL for US-SCB was 0.2675% (95% confidence interval [CI], 0.2512-0.2838%) in men and 0.2675% (95% CI, 0.2524-0.2826%) in women. There was no significant difference in MLAC or the analgesia duration between the 2 groups (P>0.05). CONCLUSIONS: We found no significant sex-related differences in MLAC or analgesia duration of ropivacaine for US-SCB.

Inferior thyroid artery pseudoaneurysm associated with internal jugular vein puncture: a case report.

BACKGROUND: Central venous catheter placement is an important aspect of patient care for the administration of fluids and medications and for monitoring purposes. However, it is still associated with significant morbidity and mortality. CASE PRESENTATION: We report a case of iatrogenic inferior thyroid artery pseudoaneurysm during the central line placement due to internal jugular vein puncture. This is a rare complication of central venous cannulation. Fortunately the pseudoaneurysm was monitored closely, diagnosed promptly and obliterated by using radiological intervention. We discuss the risk factors and management of the unintended artery puncture. CONCLUSION: The pathway of the management post arterial puncture depends on the size of the needle or catheter, which is direct related to the consequence of arterial injuries. Identifying risk factors is very important to avoid the complications. However, the use of ultrasound guided venipuncture is the most important method to avoid mechanical complications.

The expression of Survivin and NF-κB associated with prognostically worse clinicopathologic variables in hepatocellular carcinoma.

Expressions of Survivin and nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) are associated with a poor prognosis in many malignancies. However, their relationship in hepatocellular carcinoma remains unclear. To investigate the protein expression of Survivin and NF-κB, determine their role in the pathogenesis of hepatocellular carcinoma, and correlate expression with patient survival outcome, immunohistochemistry was used to detect the protein expression of Survivin and NF-κB in 305 cases of hepatocellular carcinoma. Statistical analysis was performed to determine the relationship between the protein expression of Survivin and NF-κB and clinicopathological parameters, survival time, and prognosis. Survivin was expressed predominantly in the cytoplasm, and NF-κB was expressed mostly in the nucleolus. Survivin and NF-κB are expressed at significantly higher rates in hepatocellular carcinoma compared with benign tissue (75.7 vs 13.4 %, P < 0.01 and 79.0 vs 17.1 %, P < 0.01, respectively). Both Survivin and NF-κB expression levels are associated with poor prognostic factors, including tumor size, capsular invasion, tumor thrombus of the portal vein, metastasis of the lymph node, and clinical staging. There was an obvious positive correlation between the expression of Survivin and NF-κB in hepatocellular carcinoma (r = 0.23, P < 0.01). Patients expressing Survivin and NF-κB had significantly shorter survival compared with patients negative for protein expression (P < 0.01). The overexpressions of both Survivin and NF-κB are associated with worse survival outcome in patients with hepatocellular carcinoma. Thus, these proteins could be used as negative prognostic indicators.

Ischemic preconditioning improves liver tolerance to congestion-reperfusion injury in mice.

BACKGROUND: Congestion-reperfusion injury (CRI) is a common complication after living donor liver transplantation, which has not been fully understood. It causes more severe inflammatory response as compared with ischemia-reperfusion injury (IRI). Ischemic preconditioning (IPC) has been endowed with powerful protective properties toward IRI. This study aimed to investigate whether IPC also has a protective effect against CRI and potential underlying mechanisms. MATERIALS AND METHODS: Mice were randomly divided into sham operation, CRI, IPC-CRI, and congestion precondition (CPC-CRI) group. The hepatic vein of the left anterior hepatic lobe was occluded for 75 min followed by reperfusion in the CRI group. The blood inflow was previously clamped for 10 min followed by 10 min of reperfusion just before occluding the hepatic vein in the IPC-CRI group. To imitating IPC in the CPC-CRI group, 10 min of congestion followed by 10 min of reperfusion just before CRI was performed. The animals were sacrificed at 2, 6, 24, 48 h, and 7 d after reperfusion. The blood and liver samples were collected for hepatic function assay, histology, terminal deoxynucleotidyl transferase dUTP nick end labeling, myeloperoxidase, and real-time polymerase chain reaction analysis. RESULTS: Mice in the CRI, IPC-CRI, and CPC-CRI group demonstrated elevated liver enzymes, histologic damage, cellular apoptosis, and inflammatory response compared with those in the sham operation group. Compared with the CRI group, mice in the IPC-CRI group expressed lower alanine transaminase activities (2 h: 839.2 ± 132.5 versus 384.2 ± 94.8, P < 0.01; and 6 h: 680 ± 142.4 versus 342.3 ± 99.7, P < 0.01) and lower myeloperoxidase levels (2 h: 7.1 ± 4.0 U/g versus 3.8 ± 1.6 U/g, P < 0.05; and 6 h: 8.1 ± 1.3 U/g versus 5.2 ± 3.0 U/g, P < 0.05). However, the alanine transaminase level in the CPC-CRI group was notably higher at 2 h (839.2 ± 132.5 versus 1087.5 ± 192.5, P < 0.05). Livers from mice in the IPC-CRI group showed better tissue integrity, diminished hepatocellular injury, and apoptosis at 2 and 6 h. The messenger RNA transcriptions of interleukin 1 and interleukin 6 were significantly lower after 2-24 h of reperfusion, whereas tumor necrosis factor α and monocyte chemoattractant protein 1 were significantly lower after 24 h of reperfusion in the IPC-CRI group. CONCLUSIONS: IPC can significantly improve liver tolerance to CRI by attenuating neutrophil infiltration, proinflammatory cytokine formation, and hepatocytes apoptosis. This pretreatment strategy holds greater prospect of being translated into clinical use in living donor liver transplantation.