The role of PI3k/AKT signaling pathway in attenuating liver fibrosis: a comprehensive review.

Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as liver fibrosis. Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), autoimmune issues, and viral hepatitis cause chronic liver injury. Exploring potential therapeutic targets and understanding the molecular mechanisms involved in liver fibrosis are essential for the development of effective interventions. The goal of this comprehensive review is to explain how the PI3K/AKT signaling pathway contributes to the reduction of liver fibrosis. The potential of this pathway as a therapeutic target is investigated through a summary of results from in vivo and in vitro studies. Studies focusing on PI3K/AKT activation have shown a significant decrease in fibrosis markers and a significant improvement in liver function. The review emphasizes how this pathway may prevent ECM synthesis and hepatic stellate cell (HSC) activation, ultimately reducing the fibrotic response. The specific mechanisms and downstream effectors of the PI3K/AKT pathway in liver fibrosis constitute a rapidly developing field of study. In conclusion, the PI3K/AKT signaling pathway plays a significant role in attenuating liver fibrosis. Its complex role in regulating HSC activation and ECM production, demonstrated both in vitro and in vivo, underscores its potential as a effective therapeutic approach for managing liver fibrosis and slowing disease progression. A comprehensive review of this field provides valuable insights into its future developments and implications for clinical applications.

Effect of echinacoside intervention on liver and pancreas injury in rats with acute pancreatitis and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the effect and mechanism of echinacoside （ECH） in improving liver injury in rats with acute pancreatitis by establishing a rat model of acute pancreatitis and liver injury. MethodsA total of 24 Sprague-Dawley rats were randomly divided into blank group （Con group）， control group （Con+ECH group）， acute pancreatitis group （AP group）， and acute pancreatitis+ECH intervention （AP+ECH group）. The rats were given intraperitoneal injection of 10 mg/kg ECH on day 7 before the establishment of the model of acute pancreatitis； at 24 hours after the last administration of cerulein， blood samples were collected via the abdominal aorta， and serum was separated for biochemical analysis including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， lactate dehydrogenase （LDH）， gamma-glutamyl transpeptidase （GGT）， alkaline phosphatase （ALP）， albumin （Alb）， total bilirubin （TBil）， cholinesterase， blood amylase （Amy）， and lipase （LPS）. HE staining was used to observe the histopathological changes of the pancreas and the liver； transmission electron microscopy （TEM） was used to observe the microstructural changes of pancreas and liver tissue； ELISA was used to measure the levels of interleukin-1β （IL-1β）， interleukin-16 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） in liver tissue homogenate； immunohistochemistry was used to measure the levels of TNF-α and p-p65 NF-κB in pancreas and liver tissue； Western blot was used to measure the expression levels of NF-κB pathway proteins in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the SNK test or the Dunnett’s T3 method was used for further comparison between two groups. ResultsCompared with the Con group， the AP group had significant increases in ALT， AST， GGT， LDH， ALP， TBil， Amy， and LPS （all P<0.01）， as well as significant increases in the levels of IL-1β， IL-6， IL-10， and TNF-α in liver tissue homogenate （all P<0.01）. ECH intervention reduced the levels of ALT， AST， GGT， LDH， ALP， TBil， AMY， and LPS and inhibited the secretion of IL-1β， IL-6， and TNF-α in rats with acute pancreatitis. HE staining showed that ECH intervention alleviated the vacuolar degeneration of acinar cells， inflammatory cell infiltration in pancreatic tissue， and the necrosis of hepatocytes compared with the AP group. TEM showed that compared with the AP group， there was a reduction in the degree of mitochondrial swelling in liver and pancreatic cells after ECH intervention. ECH intervention partially reversed the elevated expression levels of p-p65 NF-κB and TNF-α in liver and pancreatic tissue. In addition， the expression levels of MyD88， p-IκBα， p-IKKα， and p-p65 were upregulated in liver tissue of rats with acute pancreatitis， which could be partially reversed after ECH intervention. ConclusionEchinacoside can alleviate liver and pancreatic injury induced by acute pancreatitis by inhibiting the TLR4/MyD88/NF-κB pathway.

Expression of neutrophil extracellular traps and phagocytic functions among patients with hepatic alveolar echinococcosis / 中国血吸虫病防治杂志

Objective To investigate the expression of neutrophil extracellular traps (NETs) and phagocytic function in the peripheral blood of patients with hepatic alveolar echinococcosis (HAE), and to examine their correlations with clinical inflamma tory indicators and liver functions. Methods A total of 50 patients with HAE admitted to Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qinghai University from August 2022 to June 2023 were enrolled, while 50 age- and gender-matched healthy individuals from the Centre for Healthy Examinations of the hospital during the same period served as controls. The levels of NETs markers neutrophil myeloperoxidase (MPO) and neutrophil elastase (NE) were measured using enzyme-linked immunosorbent assay (ELISA). Peripheral blood neutrophils were isolated using density gradient centrifugation, stimulated in vitro using phorbol 12-myristate 13 acetate (PMA), and the levels of MPO and citrullination histone H3 (CitH3) released by neutrophils were quantified using flow cytometry. The phagocytic functions of neutrophils were examined using flow cytometry. In addition, the correlations of MPO and NE levels with clinical inflammatory indicators and liver biochemical indicators were examined using Spearman correlation analysis among HAE patients. Results The peripheral blood plasma MPO［(417.15 ± 76.08) ng/mL vs. (255.70 ± 80.84) ng/mL; t = 10.28, P < 0.05］, NE［(23.16 ± 6.75) ng/mL vs. (11.92 ± 3.17) ng/mL; t = 10.65, P < 0.05］and CitH3 levels［(33.93 ± 18.93) ng/mL vs. (19.52 ± 13.89) ng/mL; t = 4.34, P < 0.05］were all significantly higher among HAE patients than among healthy controls, and a lower phagocytosis rate of neutrophils was detected among HAE patients than among healthy controls［(70.85 ± 7.32)% vs. (94.04 ± 3.90)%; t = 20.18, P < 0.05］, and the ability to produce NETs by neutrophils was higher among HAE patients than among healthy controls following in vitro PMA stimulation. Pearson correlation analysis showed that the phagocytosis rate of neutrophils correlated negatively with platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6) level and C-reactive protein (CRP) level (rs = −0.515 to −0.392, all P values < 0.05), and the MPO and NE levels positively correlated with inflammatory markers NLR, PLR, CRP and IL-6 (rs = 0.333 to 0.445, all P values < 0.05) and clinical liver biochemical indicators aspartic transaminase, alanine aminotransferase, direct bilirubin and total bilirubin among HAE patients (rs = 0.290 to 0.628, all P values < 0.001). Conclusions Excessive formation of NETs is found among HAE patients, which affects the phagocytic ability of neutrophils and results in elevated levels of inflammatory indicators. NETs markers may be promising novel biomarkers for early diagnosis, monitoring, and severity assessment of liver disease.

Progress in diagnosis and treatment of hepatic alveolar echinococcosis / 器官移植

Hepatic echinococcosis is a chronic parasitic disease, which is caused by the larvae of Echinococcus multilocularis. It has a high risk of disability and mortality, which is also known as "parasite cancer". In clinical practice, hepatic echinococcosis can be divided into hepatic alveolar echinococcosis and hepatic cystic echinococcosis. Hepatic echinococcosis is widely prevalent worldwide. It mainly occurs in the populations residing agricultural and pastoral areas in western China, posing significant threats to the quality of life of local residents. At present, surgery is the main treatment for hepatic echinococcosis in clinical settings. With rapid development of surgical diagnosis and treatment technology and deepening understanding of hepatic echinococcosis, diagnosis and treatment regimens have also been constantly improved. In this article, research progresses on the diagnosis and treatment of hepatic alveolar echinococcosis were reviewed, aiming to provide reference for clinicians, deliver early diagnosis and treatment, mitigate adverse effects of this disease upon patients and improve clinical prognosis.

Research progress on the formation mechanism of hepatocellular carcinoma with portal vein tumor thrombus / 中华肝胆外科杂志

Hepatocellular carcinoma is a common malignant disease in clinical practice, and portal vein tumor thrombosis (PVTT) is one of the important factors affecting the prognosis of hepatocellular carcinoma. PVTT has strong oncologic characteristics and is highly susceptible to extrahepatic metastasis, complicating portal hypertension, leading to gastrointestinal bleeding or liver failure and causing death. In this paper, we review the formation mechanism of hepatocellular carcinoma combined with PVTT in terms of local anatomy, hemodynamics, molecular biology and tumor microenvironment to provide effective reference for clinical treatment.

Research advances in immunotherapy for hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

Traditional Chinese medicine for treatment of echinococcosis: a review / 中国血吸虫病防治杂志

Echinococcosis is a zoonotic parasitic disease caused by infection with Echinococcus species. As the drug of first choice for treatment of echinococcosis, albendazole suffers from problems of large doses and remarkable adverse reactions in clinical therapy. Development of novel drugs against echinococcosis is of urgent need. Recently, great advances have been achieved in the research on traditional Chinese medicine for treatment of echinococcosis. This review summarizes the progress of researches on traditional Chinese medicine for treatment of echinococcosis, aiming to provide insights into development of anti-echinococcosis drugs.

Advances in the application of three-dimensional visualization technique in hepatic alveolar echinococcosis / 临床肝胆病杂志

Hepatic alveolar echinococcosis (HAE) is a parasitic disease caused by Echinococcus multilocularis infection and has wide distribution and great harm in China. At present, ultrasound, CT, and MRI are the main radiological examination methods for HAE, with certain limitations in preoperative diagnosis and evaluation. This article introduces the guiding effect of three-dimensional visualization technique and its derivative technologies in the accurate diagnosis and preoperative evaluation of HAE, so as to provide help for the clinical diagnosis and treatment of HAE in the future.

Role of type 2 innate lymphoid cells in helminth infections: a review / 中国血吸虫病防治杂志

Helminth infections may trigger host innate and adaptive immune responses. Group 2 innate lymphoid cells (ILC2) are an important factor involved in type 2 immune responses, and produce a large number of T helper 2 cell (Th2) cytokines following stimulation by interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), which play a critical role in parasite clearance and tissue repair. Following helminth infections, autocrine factors, mast cells, enteric nervous system and Th2 cells have been recently found to be involved in regulation of ILC2. Unraveling the role of ILC2 in immune response against helminth infections is of great value for basic research and drug development. This review summarizes the research progress on ILC2 and its role in helminth infections.

Effect of exosomes derived from Echinococcus multilocularis on macrophage polarization: A preliminary study / 临床肝胆病杂志

Objective To investigate the effect of exosomes derived from Echinococcus multilocularis on macrophage polarization after treatment for different durations and concentrations. Methods A total of 60 BALB/c mice were used for modeling, among which 4 mice were selected to observe the growth of abdominal lesions on 7.0T MRI. The mice for modeling were dissected, and the protoscoleces was taken from the abdominal lesion and cultured in vitro ; ultracentrifugation was used to extract the exosomes from the supernatant, and transmission electron microscopy and Western blotting were used for the characterization of exosomes. The macrophages without exosome treatment were established as control group, and the macrophages co-cultured with different concentrations of exosomes derived from Echinococcus multilocularis were established as experimental group (10 μg/mL group and 50 μg/mL group) and were cultured for 48 and 72 hours. The morphological changes of macrophages were observed under a microscope, and flow cytometry and ELISA were used to observe polarization state. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results The results of 7.0T MRI showed the formation of diffuse lesions with different sizes in the abdominal cavity of mice, and the exosomes derived from Echinococcus multilocularis were approximately 100 nm in diameter and were cup-shaped or saucer-shaped, with the positive expression of the surface markers CD9, TSG101, and CD63. After co-culture, most of the cells in the experimental group were elongated with an irregular and polygonal shape. Flow cytometry showed that after 48 hours of co-culture, the positive rates of CD16/32, CD206, and CD369 in the control group were 99.53%±0.06%, 90.27%±0.21%, and 2.40%±0.20%, respectively; compared with the control group, except that the 10 μg/mL exosome group had a significant reduction in the positive rate of CD369 (0.80%±0.00%) ( P < 0.05), all the other groups had a significant increase in the positive rates of CD16/32, CD206, and CD369 (all P < 0.000 1); after 72 hours of co-culture, the positive rates of CD16/32, CD206, and CD369 in the control group were 99.67%±0.06%, 85.47%±0.55%, and 6.60%±0.20%, respectively, and compared with the control group, the experimental group had significant increases in the positive rates of CD16/32, CD206, and CD369 (all P < 0.05). ELISA showed that after 48 hours of co-culture, the levels of IL-6 and TNFα in the control group were 58.53±15.52 pg/mL and 320.70±5.30 pg/mL, respectively, and when the exosome concentration was 50 μg/mL, the level of IL-6 in the experimental group was 98.81±15.55 pg/mL, which was higher than that in the control group ( P < 0.05); after 72 hours of co-culture, the levels of IL-6 and TNFα in the control group were 76.22±9.68 pg/mL and 323.90±87.37 pg/mL, respectively, and when the exosome concentration was 10 μg/mL, the level of TNFα was 164.20±14.17 pg/mL, which was significantly lower than that in the control group ( P < 0.05); when the exosome concentration was 50 μg/mL, the level of IL-6 was 99.52±8.35 pg/mL, which was significantly higher than that in the control group ( P < 0.05). Conclusion Exosomes derived from Echinococcus multilocularis can regulate macrophage polarization and induce M2-like polarization of macrophages after co-culture at a concentration of 10 μg /mL for 72 hours, and further studies are needed to clarify the specific method.

Correlation between systemic immune inflammatory index and prognosis of patients with hepatic alveolar hydatid disease and establishment of a nomogram prediction model.

Background: To explore the evaluation value of systemic immune inflammation index (SII) in the prognosis of patients with alveolar hydatid disease, and establish a nomogram prediction model. Methods: Collect the clinical data of 351 patients undergoing hepatic alveolar hydatid surgery admitted to the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qinghai University from January 2015 to December 2020, calculate the SII value, and use the receiver operating characteristic curve (ROC curve) to determine According to the optimal clinical cut-off value of SII, patients were divided into two groups with high SII and low SII, and the relationship between SII and clinicopathological factors and prognosis of patients with alveolar echinococcosis was analyzed. Establish a nomogram prediction model based on independent risk factors for patient prognosis, and evaluate the prediction accuracy and discrimination ability of the nomogram through the consistency index (C-index) and calibration curve. The result is through the use of bootstrapping validation with 1,000 re-sampling Method for internal verification. Results: The ROC curve was used to determine the optimal cut-off value of SII before operation 761.192, and patients were divided into low SII group (n = 184) cases and high SII group (n = 167) cases. The 1, 3, and 5-year survival rates of patients with hepatic alveolar hydatid in the low SII group and the high SII group were 98.90%, 96.90%, 86.50% and 98.20%, 72.50%, 40.30%, respectively. The survival rate of worm disease patients was significantly better than that of the high SII group, and the overall survival rate difference between the two groups was statistically significant (P < 0.001). Multivariate Cox regression model analysis results showed that intraoperative blood loss (HR = 1.810, 95%CI: 1.227-2.668, P = 0.003), SII (HR = 5.011, 95%CI: 3.052-8.228, P < 0.001), Complications (HR = 1.720, 95%CI: 1.162-2.545, P = 0.007) are independent risk factors for the prognosis of patients with alveolar hydatid disease. Draw a nomogram and include statistically significant factors in the multivariate Cox regression model to predict the overall survival rate of patients with alveolar hydatid disease at 1, 3, and 5 years. The survival probability calibration curve is displayed. The nomogram is compared with The actual results have a high degree of agreement. The concordance index (C-index) of the nomogram model in the modeling sample is 0.777, and the C-index in the verification sample is 0.797, indicating that the nomogram model of this study has good accuracy and discrimination. Conclusions: SII has a clear correlation to the prognosis of patients with alveolar echinococcosis. The nomogram prediction model constructed on this basis is beneficial to the clinically individualized analysis of the patient's prognosis.

Advances in the treatment of hepatocellular carcinoma combined with hepatic vein tumor thrombus / 中华肝胆外科杂志

Hepatocellular carcinoma is one of the common malignant tumors in China, which seriously threatens the life and health of the nation. Hepatic vein tumor thrombosis (HVTT) is one of the common clinical manifestations. The prognosis of hepatocellular carcinoma combined with HVTT is extremely poor, and there is no unanimous opinion on its treatment in China and abroad. Currently, Asian guidelines recommend multidisciplinary treatment for patients with vascular invasion. This article reviewed the current progress in the treatment of hepatocellular carcinoma combined with HVTT.

Clinical efficacy and safety of ex-vivo liver resection and liver auto-transplantation: a bayesian single-arm Meta-analysis / 中华肝胆外科杂志

Objective:To evaluate the clinical efficacy and safety of ex vivo liver resection and autotransplantation (ELRA) by using a Bayesian single-arm Meta-analysis.Methods:Databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang were searched from January 1, 1990 to December 30, 2021 on ELRA studies. The Bayesian one-arm Meta-analysis was performed by using the statistical software of R (V4.1.2) and the Markov chain-Monte Carlo method was used to simulate the posterior distribution. The mortality rate within 30 days after operation, 1-year survival rate, major postoperative complications, R 0 resection rate and other related indexes were analyzed. Results:A total of 20 studies with 436 patients were included. Bayesian single-arm Meta-analysis showed that the 1-year survival rate after ELRA was 83.24% [95% highest posterior density ( HPD): 72.40%-92.05%]. The 1-year survival rates after surgery were 88.66% (95% HPD: 81.52%-94.50%) for patients with hepatic alveolar echinococcosis and 61.29% (95% HPD: 38.53%-93.68%) for patients with hepatic malignancies, respectively. The mortality rate within 30 d after surgery, the incidence of significant postoperative complications, and the R 0 resection rate were 6.96% (95% HPD: 4.47%-10.15%), 27.91% (95% HPD: 19.00%-38.30%), and 99.84% (95% HPD: 37.61%-100.00%), respectively. Renal failure was the most frequent cause of death after ELRA. Conclusion:ELRA is indicated for hepatic malignancies and hepatic alveolar echinococcosis when intrahepatic resection cannot be accomplished in vivo. The greatest benefit is observed in patients with hepatic alveolar echinococcosis, while only some patients with hepatic malignancies can benefit. The indications for ELRA for hepatic malignancies need to be further studied to define the subgroup of patients who can benefit from this operation.

Effect of Echinococcus multilocularis secreted antigen on the phenotype and function of mouse bone marrow - derived dendritic cells induced by lipopolysaccharide / 临床肝胆病杂志

Objective To investigate the effect of different concentrations of Echinococcus multilocularis secretion antigen (Em-sAg) on the phenotype and function of mouse bone marrow-derived dendritic cells (BMDCs) induced by lipopolysaccharide (LPS). Methods The bone marrow precursor cells isolated from the mouse bone marrow cavity were stimulated by mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to form BMDCs, and then cell morphology was observed under an inverted microscope. After the purity of BMDCs was identified by flow cytometry, BMDCs were divided into control group, positive control group (LPS 1 μg/ml), LPS+3 mg/ml Em-sAg group, LPS+1.5 mg/ml Em-sAg group, LPS+0.75 mg/ml Em-sAg group, and LPS+0.375 mg/ml Em-sAg group. Flow cytometry was used to measure the expression of BMDC surface molecules (CD80, CD86, and MHC-Ⅱ molecules) in each group, and ELISA was used to measure the expression level of the cytokine IL-12p70. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Observation under an inverted microscope showed that after 8-10 days of culture, the cells had burr-like protrusions and were in a state of complete suspension. Flow cytometry showed that the positive rate of CD11c was above 70% and most of the cultured cells were identified as BMDCs based on this. Flow cytometry further showed that compared with the control group, the LPS group had significant increases in the cell molecules CD80, CD86, and MHC-Ⅱ on surface (all P 0.05). ELISA showed that there was a significant difference in the level of IL-12 p70 between groups ( F =73.140, P < 0.05); compared with the control group, the LPS group had a significant increase in the expression level of IL-12p70 after stimulation ( P < 0.05); compared with the positive control group, the LPS+3 mg/ml Em-sAg group, the LPS+1.5 mg/ml Em-sAg group, the LPS+0.75 mg/ml Em-sAg group, and the LPS+0.375 mg/ml Em-sAg group had a significant reduction in the expression level of IL-12p70 ( P < 0.05), and the degree of reduction in the pro-inflammatory factor IL-12p70 increased with the increase in the concentration of Em-sAg. Conclusion Different concentrations of Em-sAg can inhibit LPS-induced maturity of BMDCs and the expression of the pro-inflammatory cytokine IL-12p70.

Correlation between systemic immune-inflammation index and prognosis in patients with hepatic alveolar echinococcosis / 临床肝胆病杂志

ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P＜0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII ＞758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of ＞50% and a mean survival time of 55.584 months (95% confidence interval［CI］: 53550-57.617), while the high SII group had a cumulative survival rate of ＜50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P＜005). The univariate analysis showed that SII ＞758.92 (hazard ratio ［HR］=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.

Screening and a preliminary study of specific microRNA for hepatic alveolar echinococcosis / 临床肝胆病杂志

ObjectiveTo investigate new biomarkers for hepatic alveolar echinococcosis by screening out differentially expressed microRNAs (miRNAs) in the tissues and plasma of patients with hepatic alveolar echinococcosis, since hepatic alveolar echinococcosis is caused by the infection of multilocular hydatid cyst. MethodsPatients with hepatic alveolar echinococcosis diagnosed in Qinghai University Affilrated Hospital from June 2016 to May 2018 were in cluded. Two marginal tissue samples and three adjacent normal tissue samples were collected from patients with hepatic alveolar echinococcosis, and plasma samples were collected from three patients with hepatic alveolar echinococcosis and three healthy controls. Agilent Human miRNA microarray was used to obtain the miRNA expression profile in tissue and plasma, and differentially expressed miRNAs were screened out based on fold change (FC＞1.2) and P value (P＜0.05). Plasma miRNAs and tissue miRNAs associated with liver diseases were selected based on target gene prediction of differentially expressed miRNAs and literature reports, and quantitative real-time PCR (qRT-PCR) was used for validation. The t-test was used for comparison of continuous data between two groups. A spearman analysis was used to investigate correlcction. ResultsThere was a significant difference in microRNA expression profile between the patients with hepatic alveolar echinococcosis and the health individuals, and qRT-PCR found that three miRNAs (hsa-miR-4644, hsa-miR-136-5p, hsa-miR-483-3p) were significantly differentially expressed in patients with hepatic alveolar echinococcosis (P＜0.05), among which hsa-miR-4644 and hsa-miR-483-3p were significantly upregulated (P＜0.05) and hsa-miR-136-5p was significantly downregulated (P＜0.05) in patients with hepatic alveolar echinococcosis. Target gene prediction was performed for miRNAs based on TargetScan, PITA, and microRNAorg databases, and the intersection of the target genes predicted by these three databases showed that 137 genes were targeted with miRNAs. The differentially expressed miRNA hsa-miR-483-3p was involved in the target regulation of the genes (IL17A, IL5, CD40LG, TAP2, and TNF) associated with immune response and liver diseases. Gene ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that the target genes of hsa-miR-483-3p played an important role in the primary immunodeficiency signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway. ConclusionHepatic alveolar echinococcosis has a unique microRNA expression profile, among which hsa-miR-483-3p can be used as a new biomarker for hepatic alveolar echinococcosis, and the target genes regulated by this miRNA are mainly involved in the primary immunodeficiency signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway. However, further studies are needed to verify the regulatory relationship between these miRNAs and hepatic alveolar echinococcosis.

Influence of endoplasmic reticulum stress on the secretion of some inflammatory mediators in hepatic alveolar echinococcosis / 临床肝胆病杂志

ObjectiveTo investigate the influence of endoplasmic reticulum stress (ERS) on some inflammatory mediators during the progression of hepatic alveolar echinococcosis (HAE) and its clinical significance. MethodsA total of 15 patients with HAE who underwent partial liver resection in Qinghai University Affiliated Hospital from June 2018 to September 2019 were enrolled, and the marginal zone of HAE lesion was resected as AE group; 15 normal liver tissue samples collected during the same period of time were selected as control group. Western blot and qRT-PCR were used to measure the protein and mRNA expression of protein kinase R-like ER kinase (PERK), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and glucose-regulated protein-78 (GRP-78), and q-PCR was used to measure the mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF). The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the t-test was used for comparison of normally distributed continuous data between two groups; a Pearson correlation analysis was performed to investigate the correlation between two variables. ResultsCompared with the control group, the AE group had significantly higher protein expression levels of PERK, CHOP, caspase-12, and GRP78 (U=4.165, 3.461, 2.577, and 3.344, all P＜0.001) and their mRNA expression levels (t= 34003, 4.461, 53.573, and 55.224, all P＜0.001). The AE group had significantly higher mRNA expression levels of IL-1β, IL-6, and TNF than the control group (t=6.090, 12.578, and 53.573, all P＜0.001). The protein expression levels of PERK, CHOP, caspase-12, and GRP-78 were positively correlated with the mRNA expression levels of IL-1β, IL-6, and TNF (all r＞0.700, all P≤0.05). ConclusionPositive correlation is observed between the activation of ERS and inflammatory mediators in HAE, and excessive activation of ERS can change the secretion of several inflammatory mediators to exacerbate liver injury, while further studies are needed to clarify the specific mechanism.

Diagnosis and treatment of hepatic alveolar echinococcosis with intraperitoneal implantable metastasis / 中华消化外科杂志

Hepatic alveolar echinococcosis is a zoonotic parasitic disease caused by echinococcus multilocularis infection. The growth pattern of the lesions of hepatic alveolar echinococcosis is similar to that of liver malignant tumor showing invasive growth. Hepatic alveolar echinococcosis can not only directly invade the adjacent tissue structure, but also metastasize through the lymphatic tracts and blood vessels. Hepatic alveolar echinococcosis with intraperitoneal implantable metastasis is extremely rare. The authors introduce the diagnosis and treatment of 1 patient who had hepatic alveolar echinococcosis with intraperitoneal implantable metastasis.

Current status of research on elastography combined with serology in the diagnosis of chronic hepatitis B liver fibrosis / 临床肝胆病杂志

Liver biopsy is the gold standard for the diagnosis of liver fibrosis stage in patients with chronic hepatitis B, but it has certain limitations due to its invasiveness. At present, elastography and serological examination have the advantages of convenience, good repeatability, and dynamic testing and are thus widely used in clinical practice. The accuracy of testing has been supported by a large number of studies, and they have been gradually recommended by various guidelines and expert consensus. However, the diagnostic accuracy of the two methods is affected by factors such as inflammation, obesity, ascites, eating, and intercostal space stenosis, and elastography combined with serological examination can greatly improve the accuracy, sensitivity, and specificity of liver fibrosis staging. With reference to related articles in China and globally, this article reviews the problems of the two methods in the staging of chronic hepatitis B liver fibrosis.

Association between serum macrophage polarization-related factors and liver fibrosis in echinococcosis multilocularis / 临床肝胆病杂志

Objective To investigate the association between serum macrophage polarization-related factors and liver fibrosis in patients with alveolar echinococcosis (AE). Methods A total of 120 patients with AE who attended Department of Hepatobiliary and Pancreatic Surgery in The Affiliated Hospital of Qinghai University from September 2018 to October 2020 were enrolled as AE group, and 33 healthy controls were enrolled as normal control group. The two groups and the patients with varying degrees of liver fibrosis were compared in terms of the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Comparison of normally distributed continuous data between two groups was made by the independent samples t -test, while comparison of non-normally distributed continuous data was made by the Mann-Whitney U test or Kruskal-Wallis H test. Comparison of categorical data between groups was made by the chi-square test. Univariate and multivariate logistic regression analyses were used to investigate the association between serum macrophage polarization-related factors and liver fibrosis in patients with AE, and the receiver operating characteristic (ROC) curve was used to analyze the value of serological examination in the diagnosis of liver fibrosis in patients with AE. A Spearman correlation analysis was used to analyze the correlation of each index with HAI score and Metavir score. Results Compared with the normal control group, the AE group had significant increases in the serum levels of IL-6 [13.97 (9.64-23.62) pg/mL vs 1.30 (0.35-2.71) pg/mL, Z =-5.980, P < 0.001], TNF-α [2.26 (1.65-4.13) pg/mL vs 1.40 (1.04-2.10) pg/mL, Z =-3.114, P < 0.01], and TGF-β1 [3.64(2.71-5.72) pg/mL vs 2.91(2.20-3.35) pg/mL, Z =-2.594, P < 0.05], and increases in the serum levels of IL-6 (hazard ratio [ HR ]=2.721, 95% confidence interval [ CI ]: 1.730-4.280, P < 0.05) and TNF-α( HR =3.527, 95% CI : 1.158-10.747, P < 0.05) were independent risk factors for the onset of liver fibrosis in AE patients. The ROC curve analysis showed that hydatid IgG combined with the serum levels of IL-6 and TNF-α had a sensitivity of 88.4%, a specificity of 95.8%, and an area under the ROC curve of 0.951(95% CI : 0.937-0.964) in the diagnosis of liver fibrosis, which were significantly higher than those of IL-6, TNF-α, or hydatid IgG alone ( Z =-3.458, -4.011, and 2.379, all P < 0.05). The Spearman analysis showed that the serum levels of IL-6, TNF-α, and TGF-β1 were positively correlated with HAI score ( r =0.560, 0.644, and 0.465, all P < 0.001) and Metavir fibrosis score ( r =0.530, 0.758, and 0.567, all P < 0.001), and the serum level of IL-10 was negatively correlated with HAI score ( r =-0.232, P =0.011) and Metavir fibrosis score ( r =-0.288, P =0.001). Conclusion Macrophage polarization is often observed in patients with hepatic AE, and the levels of the macrophage polarization-related factors IL-6, TNF-α, and TGF-β1 are associated with the development and progression of liver fibrosis, which can provide certain reference information for predicting the onset of liver fibrosis.