The role of exosomes in hepatitis, liver cirrhosis and hepatocellular carcinoma.

Exosomes are small vesicles that were initially thought to be a mechanism for discarding unneeded membrane proteins from reticulocytes. Their mediation of intercellular communication appears to be associated with several biological functions. Current studies have shown that most mammalian cells undergo the process of exosome formation and utilize exosome-mediated cell communication. Exosomes contain various microRNAs, mRNAs and proteins. They have been reported to mediate multiple functions, such as antigen presentation, immune escape and tumour progression. This concise review highlights the findings regarding the roles of exosomes in liver diseases, particularly hepatitis B, hepatitis C, liver cirrhosis and hepatocellular carcinoma. However, further elucidation of the contributions of exosomes to intercellular information transmission is needed. The potential medical applications of exosomes in liver diseases seem practical and will depend on the ingenuity of future investigators and their insights into exosome-mediated biological processes.

The ALPPS in the Treatment of Hepatitis B-Related Hepatocellular Carcinoma With Cirrhosis: A Single-Center Study and Literature Review.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been reported to be a new treatment strategy for patients with predicted small volumes of future liver remnant (FLR). ALPPS is associated with rapid hypertrophy of FLR but it has a high postoperative mortality and morbidity. Up to now, it is controversial to apply ALPPS in hepatocellular carcinoma, especially for patients with liver cirrhosis. METHODS: Between May 2014 and June 2015, consecutive patients who underwent ALPPS with hepatitis B-related hepatocellular carcinoma with cirrhosis carried out in our center were included into the study. Demographic characteristics, surgical outcomes, and pathological results were evaluated. Subsequently, follow-up was still in progress. RESULTS: The median operating time of the first (n = 12) and the second procedures (n = 10) were 285.0 and 212.5 minutes, respectively. The median blood loss were 200 and 800 mL for 2 stages of operations. The severe complication (≥IIIB) rates for the first and the second operations were 25.0% versus 40.0%, respectively. Six patients with too small future live remnant died of postoperative hepatic failure. On a median follow-up of 16 months of the 6 patients discharged, 4 patients were still alive and of 2 were disease-free. CONCLUSION: In terms of the feasibility and safety, this study showed that ALPPS in the treatment of hepatocellular carcinoma with insufficient future liver remnant might be a double-edged sword, and careful patients selected was proposed. Too small of FLR/SLV, less than 30%, is not recommended for ALPPS in liver with cirrhosis.

Laparoscopic liver resection and the learning curve: a 14-year, single-center experience.

BACKGROUND: Laparoscopic liver resection has not been widely used because of intraoperative bleeding. This problem should be solved with instruments and techniques that require a short learning curve. MATERIALS AND METHODS: The aim of this work was to present the technique used in our center to perform laparoscopic liver resection using the 'curettage and aspiration' technique with laparoscopic Peng's multifunctional operational dissectors and regional occlusion of inflow and outflow. We retrospectively analyzed patients who underwent a laparoscopic liver resection from August 1998 to August 2012, and collected the conversion rate, operating time, blood loss, hospitalization, bile leakage rate, bleeding rate, and other complications on a yearly basis and in total. We used SPSS software to analyze whether there was a significant difference, and summarized the learning curve of laparoscopic liver resection with various procedures. RESULTS: We performed 365 cases of laparoscopic liver resection, including left hemihepatectomy, left lateral lobectomy, segmental hepatectomy, non-anatomic liver resection, right hemihepatectomy, and caudate lobectomy. The diseases included liver cancer, hepatolithiasis, liver hemangioma, focal nodular hyperplasia, liver abscess, and metastatic hepatic carcinoma. In total, 63 cases (17.20 %) were converted to open surgery because of severe adhesions, bleeding, or anatomical limitation. Mean blood loss was 370.6 ± 404.0 ml; mean operating time was 150.8 ± 73.0 min; and mean postoperation hospitalization was 9.2 ± 5.3 days. There were four cases (1.32 %) with the complication of bile leakage and two cases of hemorrhage (0.66 %). No intraoperative or postoperative deaths occurred. After finishing 15-30, 43, 35, and 28 cases of laparoscopic left hemihepatectomy, left lateral hepatectomy, non-anatomic liver resection, and segmentectomy, respectively, the average operating time, blood loss, and hospitalization were almost the same as the overall mean results. CONCLUSION: The technique used in our center is a safe, fast, and effective approach to laparoscopic liver resection. Our 14 years of experience demonstrates that this technique can prevent postoperative bleeding and bile leakage. A surgeon can master the skill of laparoscopic left hemihepatectomy, left lateral hepatectomy, non-anatomic liver resection, and segmentectomy after ∼15-30, 43, 35, and 28 case procedures, respectively.

Design and analysis of self-priming extension DNA hairpin probe for miRNA detection based on a unified dynamic programming framework.

MicroRNAs (miRNAs) are potential biomarkers for cancer diagnosis and prognosis, methods for detecting miRNAs with high sensitivity, selectivity, and stability are urgently needed. Various nucleic acid probes that have traditionally been for this purpose suffer several drawbacks, including inefficient signal-to-noise ratios and intensities, high cost, and time-consuming method establishment. Computing tools used for investigating the thermodynamics of DNA hybridization reactions can accurately predict the secondary structure of DNA and the interactions between DNA molecules. Herein, NUPACK was used to design a series of nucleic acid probes and develop a phosphorothioated-terminal hairpin formation and self-priming extension (PS-THSP) signal amplification strategy, which enabled the ultrasensitive detection of miR-200a in serum samples. The free and binding energies of the DNA detection probes calculated using NUPACK, as well as the biological experimental results, were considered synthetically to select the best sequence and experimental conditions. A unified dynamic programming framework, NUPACK analysis and the experimental data, were complementary and improved the designed model in all respects. Our study demonstrates the feasibility of using computer technology such as NUPACK to simplify the experimental process and provide intuitive results.

Hepatocyte-specific loss of DDB1 attenuates hepatic steatosis but aggravates liver inflammation and fibrosis in MASH.

BACKGROUND: MASH is a common clinical disease that can lead to advanced liver conditions, but no approved pharmacotherapies are available due to an incomplete understanding of its pathogenesis. Damaged DNA binding protein 1 (DDB1) participates in lipid metabolism. Nevertheless, the function of DDB1 in MASH is unclear. METHODS: Clinical liver samples were obtained from patients with MASH and control individuals by liver biopsy. Hepatocyte-specific Ddb1-knockout mice and liver Hmgb1 knockdown mice were fed with a methionine-and choline-deficient diet to induce MASH. RESULTS: We found that the expression of DDB1 in the liver was significantly decreased in MASH models. Hepatocyte-specific ablation of DDB1 markedly alleviated methionine-and choline-deficient diet-induced liver steatosis but unexpectedly exacerbated inflammation and fibrosis. Mechanistically, DDB1 deficiency attenuated hepatic steatosis by downregulating the expression of lipid synthesis and uptake genes. We identified high-mobility group box 1 as a key candidate target for DDB1-mediated liver injury. DDB1 deficiency upregulated the expression and extracellular release of high-mobility group box 1, which further increased macrophage infiltration and activated HSCs, ultimately leading to the exacerbation of liver inflammation and fibrosis. CONCLUSIONS: These data demonstrate the independent regulation of hepatic steatosis and injury in MASH. These findings have considerable clinical implications for the development of therapeutic strategies for MASH.

[Efficacy of postoperative continuous wound infiltration with local anesthesia after open hepatectomy].

OBJECTIVE: To evaluate the efficacy of continuous wound infusion of ropivacaine for postoperative pain relief after open hepatectomy. METHODS: From May 2011 to December 2012, 60 patients undergoing open hepatectomy were randomized into normal saline continuous infusion group (n = 30) and 0.3% ropivacaine continuous infusion group (n = 30). The following variables were recorded for the 48 hours postoperatively: pain scores at rest and sedation score every 8 hours, total sufentanil consumption, first postoperative bowel movement, length of hospitalization, nausea and vomiting score, liver function change and other adverse events were also recorded. RESULTS: Pain scores at rest were lower for the ropivacaine group and reached significance after 8 h (all P < 0.05). The values of sufentanil consumption ((43.8 ± 21.8) vs (78.2 ± 35.2) µg, P < 0.01), time to bowel recovery ((1.2 ± 0.4) vs (1.5 ± 0.5) days, P < 0.01) and mean length of hospitalization ((6.1 ± 2.6) vs (7.6 ± 2.9) days, P < 0.05) decreased significantly. Sedation score and liver function recovery were better in ropivacaine group. No surgical wound infection occurred in either group. CONCLUSION: Surgical wound infusion with ropivacaine is safe and effective. And it improves postoperative pain relief and accelerates patients recovery and discharge with less damage to liver function.

Comparison of short-term outcomes between robotic and laparoscopic distal gastrectomy performed by the same surgical team during the same period.

Objective: To evaluate the short-term outcomes of laparoscopic distal gastrectomy and robotic distal gastrectomy performed during the same period. Methods: This study enrolled 46 cases of laparoscopic distal gastrectomy and 67 cases of robotic distal gastrectomy that were performed by a single surgeon between April 2020 to October 2021. Baseline characteristics and short-term outcomes of these two groups were then compared. Moreover, the robotic distal gastrectomy group was further divided into two subgroups according to the learning curve. Finally, the baseline characteristics and short-term outcomes of both subgroups were compared with the laparoscopic group, respectively. Results: The baseline characteristics and short-term outcomes of the LDG group and RDG group were comparable. In contrast, the operation time in the laparoscopic group was significantly shorter than that in the early experience robotic group (191.3 ± 37.6 VS 225.1 ± 49, P=0.001). However, the operation time (191.3 ± 37.6 VS 185.3 ± 25.3, P=0.434) was comparable between the laparoscopic group and the late experience robotic group. Likewise, the bleeding volume was comparable between the laparoscopic and early experience robotic groups. However, bleeding volume was significantly lower in the late experience robotic group compared to that in the laparoscopic group (37.5 ± 18.8 VS 49.2 ± 29.0, P=0.049). Conclusions: With surgeons stepping into the stable stage of the robotic learning curve, RDG showed a comparable operation time and lower volume of blood loss compared with LDG. Collectively, our study supports the application of robotic distal gastrectomy in patients diagnosed with gastric cancer.

Review on Rice Husk Biochar as an Adsorbent for Soil and Water Remediation.

Rice husk biochar (RHB) is a low-cost and renewable resource that has been found to be highly effective for the remediation of water and soil environments. Its yield, structure, composition, and physicochemical properties can be modified by changing the parameters of the preparation process, such as the heating rate, pyrolysis temperature, and carrier gas flow rate. Additionally, its specific surface area and functional groups can be modified through physical, chemical, and biological means. Compared to biochar from other feedstocks, RHB performs poorly in solutions with coexisting metal, but can be modified for improved adsorption. In contaminated soils, RHB has been found to be effective in adsorbing heavy metals and organic matter, as well as reducing pollutant availability and enhancing crop growth by regulating soil properties and releasing beneficial elements. However, its effectiveness in complex environments remains uncertain, and further research is needed to fully understand its mechanisms and effectiveness in environmental remediation.

Microbial Removal of Petroleum Hydrocarbons from Contaminated Soil under Arsenic Stress.

The contamination of soils with petroleum and its derivatives is a longstanding, widespread, and worsening environmental issue. However, efforts to remediate petroleum hydrocarbon-polluted soils often neglect or overlook the interference of heavy metals that often co-contaminate these soils and occur in petroleum itself. Here, we identified Acinetobacter baumannii strain JYZ-03 according to its Gram staining, oxidase reaction, biochemical tests, and FAME and 16S rDNA gene sequence analyses and determined that it has the ability to degrade petroleum hydrocarbons. It was isolated from soil contaminated by both heavy metals and petroleum hydrocarbons. Strain JYZ-03 utilized diesel oil, long-chain n-alkanes, branched alkanes, and polycyclic aromatic hydrocarbons (PAHs) as its sole carbon sources. It degraded 93.29% of the diesel oil burden in 7 days. It also had a high tolerance to heavy metal stress caused by arsenic (As). Its petroleum hydrocarbon degradation efficiency remained constant over the 0-300 mg/L As(V) range. Its optimal growth conditions were pH 7.0 and 25-30 °C, respectively, and its growth was not inhibited even by 3.0% (w/v) NaCl. Strain JYZ-03 effectively bioremediates petroleum hydrocarbon-contaminated soil in the presence of As stress. Therefore, strain JYZ-03 may be of high value in petroleum- and heavy-metal-contaminated site bioremediation.

Effect of Pyrolysis Temperature on the Sorption of Cd(II) and Se(IV) by Rice Husk Biochar.

This study investigated the removal of metal cations (Cd(II)) and metalloid anions (Se(IV)) from their aqueous solution by using agricultural waste (rice husk biochar). Rice husk biochar samples were prepared under 300, 500, and 700 °C pyrolysis conditions and their physicochemical properties were characterized. Aqueous Cd(II) and Se(IV) sorption kinetics and isotherms of rice husk biochar were studied. The results showed that the yield of rice husk biochar decreased from 41.6% to 33.3%, the pH increased from 7.5 to 9.9, and the surface area increased from 64.8 m2/g to 330.0 m2/g as the pyrolysis temperature increased from 300 °C to 700 °C. Under the experimental conditions, at increasing preparation temperatures of rice husk biochar, the sorption performance of Cd(II) and Se(IV) was enhanced. The sorption capability and sorption rate were considerably higher and faster for Cd(II) ions than for Se(IV) ions. Cd(II) sorption was found to reach equilibrium faster, within 150 min, while Se(IV) sorption was slower and reached equilibrium within 750 min. The maximum sorption capacities of cadmium and selenium by rice husk biochar were 67.7 mg/g and 0.024 mg/g, respectively, according to Langmuir model fitting.

Simultaneous Kinetics of Selenite Oxidation and Sorption on δ-MnO2 in Stirred-Flow Reactors.

Selenium (Se) is an essential and crucial micronutrient for humans and animals, but excessive Se brings negativity and toxicity. The adsorption and oxidation of Se(IV) on Mn-oxide surfaces are important processes for understanding the geochemical fate of Se and developing engineered remediation strategies. In this study, the characterization of simultaneous adsorption, oxidation, and desorption of Se(IV) on δ-MnO2 mineral was carried out using stirred-flow reactors. About 9.5% to 25.3% of Se(IV) was oxidized to Se(VI) in the stirred-flow system in a continuous and slow process, with the kinetic rate constant k of 0.032 h-1, which was significantly higher than the apparent rate constant of 0.0014 h-1 obtained by the quasi-level kinetic fit of the batch method. The oxidation reaction was driven by proton concentration, and its rate also depended on the Se(IV) influent concentration, flow rate, and δ-MnO2 dosage. During the reaction of Se(IV) and δ-MnO2, Mn(II) was produced and adsorbed strongly on Mn oxide surfaces, which was evidenced by the total reflectance Fourier transform infrared (ATR-FTIR) results. The X-ray photoelectron spectroscopy (XPS) data indicated that the reaction of Se(VI) on δ-MnO2 produced Mn(III) as the main product. These results contribute to a deeper understanding of the interface chemical process of Se(IV) with δ-MnO2 in the environment.

Combined passivators regulate the heavy metal accumulation and antioxidant response of Brassica chinensis grown in multi-metal contaminated soils.

Passivation of heavy metals is one of the most efficient techniques to remediate soil pollution. However, passivators with single component are usually unsatisfactory in the case of multi-metal contaminated soils. To resolve this problem, a series of combined passivators containing different ratios of Fe-Mn ore, Fe powder, zeolite, bentonite, etc. were designed and used to study their effects on the growth, heavy metal accumulation, and the antioxidant response of Chinese cabbage (Brassica chinensis L.) as well as the soil available forms of heavy metals in a copper refinery's multi-metal (As, Cd, Pb, Cu) contaminated yellow-brown soil and an artificially contaminated (As, Cd, Pb, Cu) calcareous alluvial soil. The results showed that compared with the control, the addition of combined passivators significantly promoted cabbage growth, with the biomass increase up to 1.77 and 3.54 times in yellow-brown soil and calcareous alluvial soil, respectively. The activity of antioxidant enzymes (SOD, CAT, POD) and the content of malondialdehyde (MDA) and glutathione (GSH) decreased, while the chlorophyll content increased significantly, as compared with no passivators. In addition, passivator application decreased As, Cd, Pb, and Cu contents in shoots and roots by 34.8%, 45.6%, 34.9%, and 11.1% and 49.2%, 63.8%, 38.6%, and 46.4% in yellow-brown soil and by 29.8%, 27.3%, 26.8%, and 25.5% and 45.8%, 55.2%, 61.8%, and 5.7% in calcareous alluvial soil, respectively. Besides, the content of soil available heavy metals was reduced by 8.0-17.1% in yellow-brown soil and 3.3-19.1% in calcareous alluvial soil after the application of passivators. The results indicated that the combined passivators formulated in this experiment could efficiently reduce the content of the multi-metals in cabbage and relieve the oxidant stress and could be used as a way to remediate multi-metal polluted soils.

Mitochondrial dysfunction attenuates rapid regeneration in livers with toxin-induced fibrosis.

BACKGROUND: The mechanism of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)-induced rapid liver regeneration remains poorly documented, especially in patients with fibrosis. Therefore, this study aims to investigate the underlying mechanism of ALPPS-induced accelerated regeneration in toxin-induced fibrosis models. METHODS: The ALPPS-induced regeneration model was established in livers with thioacetamide (TAA)-induced fibrosis to determine the regenerative pathways involved in rapid regeneration. Confirmatory experiments were performed in transforming growth factor beta 1 (TGFß1)-treated AML12 cells and mice with carbon tetrachloride (CCl4)-induced fibrosis. Finally, mitochondrial dysfunction was validated in fibrotic/non-fibrotic patients. RESULTS: In TAA-induced fibrotic mice, ALPPS-induced regeneration was significantly inferior to that of the control group (P=0.027 at day 2 and P<0.001 at day 7). Furthermore, mitochondria-associated genes were significantly downregulated in TAA-challenged mice. Accordingly, the reduced production of ATP and elevated levels of malondialdehyde indicated disturbances in intracellular energy metabolism during the ALPPS-induced regenerative process after TAA treatment. Further investigations were performed in TGF-ß1-treated AML12 cells and CCl4-treated mice, which indicated that mitochondrial dysfunction attenuated the capacity for rapid regeneration after ALPPS. CONCLUSIONS: In summary, this study revealed that mitochondrial dysfunction led to inferior regeneration in livers with toxin-induced fibrosis and identified new therapeutic targets to improve the feasibility and safety of the ALPPS procedure. Further studies in human patients are required in the future.

Robotic versus Open Pancreatoduodenectomy for Pancreatic and Periampullary Tumors (PORTAL): a study protocol for a multicenter phase III non-inferiority randomized controlled trial.

BACKGROUND: Pancreatoduodenectomy is a complex and challenging procedure that requires meticulous tissue dissection and proficient suturing skills. Minimally invasive surgery with the utilization of robotic platforms has demonstrated advantages in perioperative patient outcomes in retrospective studies. The development of robotic pancreatoduodenectomy (RPD) in specific has progressed significantly, since first reported in 2003, and high-volume centers in pancreatic surgery are reporting large patient series with improved pain management and reduced length of stay. However, prospective studies to assess objectively the feasibility and safety of RPD compared to open pancreatoduodenectomy (OPD) are currently lacking. METHODS/DESIGN: The PORTAL trial is a multicenter randomized controlled, patient-blinded, parallel-group, phase III non-inferiority trial performed in seven high-volume centers for pancreatic and robotic surgery in China (> 20 RPD and > 100 OPD annually in each participating center). The trial is designed to enroll and randomly assign 244 patients with an indication for elective pancreatoduodenectomy for malignant periampullary and pancreatic lesions, as well as premalignant and symptomatic benign periampullary and pancreatic disease. The primary outcome is time to functional recovery postoperatively, measured in days. Secondary outcomes include postoperative morbidity and mortality, as well as perioperative costs. A sub-cohort of 128 patients with pancreatic adenocarcinoma (PDAC) will also be compared to assess the percentage of patients who undergo postoperative adjuvant chemotherapy within 8 weeks, in each arm. Secondary outcomes in this cohort will include patterns of disease recurrence, recurrence-free survival, and overall survival. DISCUSSION: The PORTAL trial is designed to assess the feasibility and safety of RPD compared to OPD, in terms of functional recovery as described previously. Additionally, this trial will explore whether RPD allows increased access to postoperative adjuvant chemotherapy, in a sub-cohort of patients with PDAC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04400357 . Registered on May 22, 2020.

C1GALT1C1/COSMC is a novel prognostic biomarker for hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this study is to explore the effects of COSMC on the prognosis of hepatocellular carcinoma (HCC), and establish a novel model with improved predictive capacity. METHODS: Ninety-two patients diagnosed with HCC from 2006 to 2010 in our hospital were recruited to analyze the correlation between COSMC expression and prognosis. Cellular experiments were performed to verify the anti-tumor effects of COSMC. A predictive model was established based on the risk factors from multiple COX regression analysis. After validation, the novel model was compared with the conventional model in terms of capacity of predicting the prognosis. RESULTS: The expression of COSMC was lower in tumor tissues than in normal tissues and inhibited HCC migration in cells. Besides the expression of COSMC was significantly negatively correlated with overall survival (OS) in HCC, regression analysis showed that COSMC expression, vascular invasion, and TNM stage were prognostic risk factors. Our novel model comprising these three elements was established and validated. Besides the good fit of the calibration curves, a higher concordance index (C-index) for OS (P=0.011) as well as better decision curve analysis (DCA) and survival curves for both disease-free survival (DFS) and OS suggested the superiority of this novel model compared with conventional TNM staging in predicting the prognosis of HCC patients. CONCLUSIONS: We established a novel model by integrating the expression of COSMC, vascular invasion, and TNM stage, and found that it was better able to predict survival in patients with HCC compared with conventional TNM staging.

Activation of TGR5 alleviates inflammation in rheumatoid arthritis peripheral blood mononuclear cells and in mice with collagen II­induced arthritis.

Rheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis resulting in progressive joint destruction. Persistent synovial inflammation is induced by activation of various inflammatory cells. G­protein­coupled bile acid receptor 1 (TGR5) is a G­protein­coupled receptor activated by various bile acids, which has been reported to act as a key adaptor in regulating various signaling pathways involved in inflammatory responses and a diverse array of physiological processes, including bile acid synthesis, lipid and carbohydrate metabolism, carcinogenesis, immunity and inflammation. In the present study, TGR5 expression was detected in RA peripheral blood mononuclear cells (PBMCs), and its association with clinical disease activity, histological synovitis severity and radiological joint destruction was analyzed. Subsequently, the role and potential underlying mechanisms of TGR5 in the PBMCs of patients with RA and mice with collagen II­induced arthritis (CIA) were investigated. PBMCs were obtained from 50 patients with RA and 40 healthy controls (HCs). The mRNA and protein expression levels of TGR5 were detected in PBMCs via reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and immunofluorescence staining, respectively. Additionally, the levels of proinflammatory cytokines were analyzed by RT­qPCR and enzyme­linked immunosorbent assay (ELISA). The activation of nuclear factor­κB (NF­κB) and IκB kinase a was determined via western blot analysis. The anti­arthritic and anti­inflammatory effects of LCA on mice with CIA were then investigated. The arthritis score was assessed, and the protein levels of proinflammatory cytokines in the plasma of mice were detected via ELISA. TGR5 mRNA expression was significantly downregulated in the PBMCs of patients with RA compared with in those of the HCs (0.53±0.58 for patients vs. 1.49±0.83 for HCs; P<0.001); similar findings were observed at the protein level. The mRNA expression levels of TGR5 in the PBMCs of patients with RA with a high 28­Joint Disease Activity Score (DAS28) were significantly decreased compared with in patients with a low DAS28 (0.81±0.65 for low score vs. 0.35±0.46 for high score; P=0.002). Furthermore, TGR5 expression was significantly correlated with the levels of C­reactive protein (r=­0.429; P=0.002) and the DAS28 (r=­0.383; P=0.006). RT­qPCR and ELISA analyses indicated that lithocholic acid (LCA, 10 mg/kg/day) attenuated lipopolysaccharide­induced proinflammatory cytokine production via inhibition of NF­κB activity in the PBMCs of patients with RA. In addition, the arthritis score was significantly decreased in LCA­treated CIA mice compared with in non­treated CIA mice. The increased production of tumor necrosis factor­α, interleukin (IL)­1ß, IL­6 and IL­8 was significantly reduced in the plasma of LCA­treated CIA mice compared with the control. In conclusion, TGR5 may contribute to the inflammation of PBMCs in patients with RA and mice with CIA.

A novel scoring system for conversion and complication in laparoscopic liver resection.

BACKGROUND: Although laparoscopic liver resection (LLR) has been increasingly popular worldwide, there is lack of predictive model to evaluate the feasibility and safety of LLR. The aim of this study was to establish a scoring system for predicting the possibility of conversion and complication, which could facilitate the patient selection for clinicians and communication with patients and their relatives during the informed consent process. METHODS: Consecutively 696 patients between August 1998 and December 2016 underwent LLR were recruited. The entire cohort was divided randomly into development and validation cohorts. The scoring system for conversion and complication were established according to risk factors identified from multiple logistic analysis. Subgroup analysis was performed to assess the clinical application. And the C-index and decision curve analysis (DCA) were conducted to evaluate the discrimination in comparison with other predictive models. RESULTS: Six hundred and ninety-six patients were enrolled eventually. The rate of conversion in the development and validation cohorts was 8.3% and 10.3%, respectively. Compared with 12.6% complication rate in the development cohort, 12.9% was concluded in the validation cohort. Upon on the identified risk factors, the risk stratification model was established and validated. Subsequent subgroup analysis indicated low risk patients presented superior surgical outcomes compared with high risk patients. Besides, the C-index and DCA implied our models had better capacities of predicting conversion and complication in comparison with previous scoring systems. CONCLUSIONS: This novel scoring system presents the remarkable capacities of predicting conversion, complication in LLR. And thereby, it could be a useful instrument to facilitate the patient selection for clinicians and communication with patients and their relatives during the informed consent process.

Nitric oxide induces rice tolerance to excessive nickel by regulating nickel uptake, reactive oxygen species detoxification and defense-related gene expression.

Soil contamination with nickel (Ni) is a persistent threat to crop production worldwide. The present study examined the putative roles of nitric oxide (NO) in improving Ni-tolerance in rice. Our findings showed that application of exogenous sodium nitroprusside (SNP), a NO donor, significantly improved the growth performance of rice seedlings when grown under excessive Ni. The enhanced Ni-tolerance of rice prompted by SNP could be ascribed to its ability to regulate Ni uptake, decrease Ni-induced oxidative stress as evidenced by reduced levels of hydrogen peroxide, malondialdehyde, and electrolyte leakage in Ni-stressed plants. The positive roles of NO against Ni-toxicity also reflected through its protective effects on photosynthetic pigments, soluble proteins and proline. SNP also boosted antioxidant capacity in Ni-stressed plants by maintaining increased levels of ascorbate, enhanced activities of ROS-detoxifying enzymes, particularly peroxidase (POD) and catalase (CAT) in both roots and shoots compared with Ni-stressed alone plants. Moreover, SNP treatment also upregulated the transcript levels of CAT, POD, ascorbate peroxidase, glutathione reductase and superoxide dismutase genes in shoots under Ni-stress. Using different sulfide compounds and NO scavenger cPTIO, we also provided evidence that NO, rather than other byproducts of SNP, contributed to the improved performance of rice seedlings under Ni-stress. Collectively, our results conclude that exogenous SNP-mediated modulation of endogenous NO enhanced rice tolerance to Ni-stress by restricting Ni accumulation, maintaining photosynthetic performance and reducing oxidative damage through improved antioxidant system, thereby suggesting NO as an effective stress regulator in mitigating Ni-toxicity in economically important rice, and perhaps in other crop plants.

Prognostic significance of cytokeratin 19 expression in pancreatic neuroendocrine tumor: A meta-analysis.

BACKGROUND: Pancreatic neuroendocrine tumor (PNET) comprises 1-2% of all pancreatic tumors, but its incidence is increasing. Although many studies have investigated the correlation between cytokeratin 19 (CK-19) and PNET, the prognostic significance of CK-19 expression in PNET is inconclusive. METHODS: Eligible studies were retrieved from Pubmed, Elsevier, Embase, Cochrane Library and Web of Science databases. All relevant data were extracted to analyze the relationship between CK-19 and PNET. We utilized a fixed or random effects model to calculate the pooled odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Pooled data indicated CK-19 expression was significantly associated with poor 3- and 5-year overall survival (OS) for PNET, but not for 1-year overall survival. Additionally, positive CK-19 expression was correlated with large tumor size, advanced differentiation grade in World Health Organization-2010 (WHO-2010) and WHO-2004, vascular invasion, lymph node metastasis and liver metastasis. CONCLUSIONS: Positive CK-19 expression can be used as a predictor of poor prognosis of PNET.

Postoperative adjuvant TACE for patients of hepatocellular carcinoma in AJCC stage I: friend or foe? a propensity score analysis.

BACKGROUND: Although the transcatheter arterial chemoembolization (TACE) was demonstrated to be an alternative treatment of hepatocellular carcinoma with favorable oncological effect, the benefit of postoperative adjuvant TACE was still controversial. The aim of this study was to evaluate the effect of postoperative TACE in hepatocellular carcinoma. RESULTS: The 1, 3, and 5-year overall and disease-free survival rates were comparable between Surgery+TACE and Surgery groups. In subgroup analysis, tumor size (≥ 5 cm) was detrimental to disease-free survival (p = 0.028) and an inferior tendency of overall survival was presented. Besides, repeated TACE for patients contributed to a poor disease-free survival (p = 0.005). While, postoperative adjuvant TACE improved the overall survival in patients with high preoperative alpha-fetoprotein or positive pathologically (p = 0.039 and p = 0.045). MATERIALS AND METHODS: The data were collected from consecutive patients between January 2010 and September 2014. After propensity score matching, baseline characteristics, overall and disease-free survival were compared between two groups. Subsequently, univariate and subgroup analysis were carried on. CONCLUSIONS: Our study indicated that single postoperative adjuvant TACE was beneficial for selected patients of stage I with tumor less than 5 cm, or high preoperative alpha-fetoprotein in serum or positive of alpha-fetoprotein pathologically.