Magnesium isoglycyrrhizinate inhibits inflammatory response through STAT3 pathway to protect remnant liver function

AIM: To investigate the protective effect of magnesium isoglycyrrhizinate(Mg IG) on excessive hepatectomy animal model and its possible mechanism.METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond's method,in which the left,middle,right upper,and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups,and were injected intraperitoneally with 3 m L saline(control group),30 mg/kg(low-dose group) and 60 mg/kg(high-dose group) of Mg IG,respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl endopeptidase,total bilirubin(TBil),direct bilirubin(DBil),total protein,albumin,blood glucose(Glu),hyper-sensitivity C-reactive protein,prothrombin time(PT),and thrombin time(TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines(IL-1,IL-6,IL-10,and i NOS) was analyzed by ELISA. STAT3 protein and m RNA were analyzed by Western blot and quantitative reversetranscription PCR,respectively.RESULTS: The high-dose group demonstrated a significantly prolonged survival time,compared with both the control and the low-dose groups(22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h,P = 0.018). There were significant differences among the groups in ALT,Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the Mg IG treated groups than in the control group. Both Glu and PT levels were significantly higher in the Mg IG treated groups than in the control group. At 12 h,ALT,AST,TBil,DBil and TT levels showed significant differences between the Mg IG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group,the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10,and a decrease in IL-6. Both STAT3 protein and m RNA levels were significantly lower in the Mg IG treated groups than in the control group at 6 h,12 h,and 18 h after surgery.CONCLUSION: High-dose Mg IG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflam-matory response through inhibition of the STAT3 pathway.

Three-dimensional printing: review of application in medicine and hepatic surgery

Three-dimensional(3D) printing(3DP) is a rapid prototyping technology that has gained increasing recognition in many different fields. Inherent accuracy and low-cost property enable applicability of 3DP in many areas, such as manufacturing, aerospace,medical, and industrial design. Recently, 3DP has gained considerable attention in the medical field. The image data can be quickly turned into physical objects by using 3DP technology. These objects are being used across a variety of surgical specialties. The shortage of cadaver specimens is a major problem in medical education. However, this concern has been solved with the emergence of 3DP model. Custom-made items can be produced by using 3DP technology. This innovation allows 3DP use in preoperative planning and surgical training. Learning is difficult among medical students because of the complex anatomical structures of the liver. Thus, 3D visualization is a useful tool in anatomy teaching and hepatic surgical training. However,conventional models do not capture haptic qualities. 3DP can produce highly accurate and complex physical models. Many types of human or animal differentiated cells can be printed successfully with the development of 3D bio-printing technology. This progress represents a valuable breakthrough that exhibits many potential uses, such as research on drug metabolism or liver disease mechanism. This technology can also be used to solve shortage of organs for transplant in the future.

The response of Golgi protein 73 to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma may relate to the influence of certain chemotherapeutics

BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma

BACKGROUND Gallbladder carcinoma(GBC)carries a poor prognosis and requires a prediction method.Gamma-glutamyl transferase–to–platelet ratio(GPR)is a recently reported cancer prognostic factor.Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear,studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases.AIM To assess the prognostic value of GPR and to design a prognostic nomogram for GBC.METHODS The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017.The patients were stratified into a high-or low-GPR group.The predictive ability of GPR was evaluated by Kaplan–Meier analysis and a Cox regression model.We developed a nomogram based on GPR,which we verified using calibration curves.The nomogram and other prognosis prediction models were compared using timedependent receiver operating characteristic curves and the concordance index.RESULTS Patients in the high-GPR group had a higher risk of jaundice,were older,and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes.Univariate analysis revealed that GPR,age,body mass index,tumor–node–metastasis(TNM)stage,jaundice,cancer cell differentiation degree,and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival(OS).Multivariate analysis confirmed that GPR,body mass index,age,and TNM stage were independent predictors of poor OS.Calibration curves were highly consistent with actual observations.Comparisons of timedependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging.CONCLUSION GPR is an independent predictor of GBC prognosis,and nomogram-integrated GPR is a promising predictive model for OS in GBC.

Advances in preoperative assessment of liver function

BACKGROUND： Postoperative liver failure remains a lifethreatening complication. Preoperative evaluation of liver function is essential in reducing the complications after hepatectomy. However, it is difficult to accurately evaluate liver function before surgery because of the limitations of the liver function tests available. Recent advances in liver function tests improved the ability to assess liver function. The present review was to analyze these methods and their advantages.DATA SOURCES： MEDLINE was searched using the terms of ＂liver function test＂, ＂liver function evaluation＂ and ＂galactosyl serum albumin＂. Relevant articles published in English and Chinese from 1961 to 2014 were reviewed.RESULTS： Although serological tests are used frequently in practice, they reflect the degree of total liver damage or function, not the remnant of liver function. Child-Pugh score and model for end-stage liver disease（MELD） score assess whole liver function, and are particularly useful in determining whether patients with hepatocellular carcinoma and cirrhosis are candidates for resection or transplantation, but cannot determine the safe extent or removal. The indocyanine green and other metabolic quantitative liver function tests can evaluate functional hepatocytes, making them more accurate in predicting liver function. Computed tomography（CT）volumetry can provide anatomic information on the remnant liver volume but not on functional volume. 99mTc-galactosyl serum albumin scintigraphy, combined with single photon emission computed tomography, CT and three-dimensional reconstruction, may be a better quantitative measure of liver function, especially of remnant liver function.CONCLUSIONS： Tests used to evaluate liver functional reserve and to predict surgical risk have limitations. 99mTc-galactosylserum albumin scintigraphy, which can more accurately evaluate the whole and regional liver function, may be promising in predicting resection margins and risks of liver failure.

Diagnosis and Treatment of Cholangiocarcinoma: A Consensus from Surgical Specialists of China

Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.

Combination of tumor-associated regulatory T cell deletion and PD-1/PD-L1 blockade: A promising immunotherapy for hepatocellular carcinoma?

During the past decades,the treatment of hepatocellular carcinoma(HCC)has been limited to surgical resection and liver transplantation,but the prognosis is still poor.Recently,tumor immunotherapy,particularly immune checkpoints programmed cell death-1/programmed cell death ligand-1(PD-1/PD-L1)blockade,brings a breakthrough for HCC[1,2].However,anti-PD-1/PD-L1 immunotherapy is not satisfactory and the response rates were between 20%and 30%[3].How to improve the efficacy of PD-1/PD-L1blockade is the main issue.

Potential application of neogalactosylalbumin in positron emission tomography evaluation of liver function

AIM To investigate the evaluation of neogalactosylalbumin (NGA) for liver function assessment based on positron emission tomography technology. METHODS Female Kunming mice were assigned randomly to two groups: fibrosis group and normal control group. A murine hepatic fibrosis model was generated by intraperitoneal injection of 10% carbon tetrachloride (CCl4) at 0.4 ml every 48 h for 42 d. F-18-labeled NGA ([F-18] FNGA) was synthesized and administered at a dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice. Distribution of [F-18] FNGA amongst organs was examined, and dynamic scanning was performed. Parameters were set up to compare the uptake of tracers by fibrotic liver and healthy liver. Serologic tests for liver function were also performed. RESULTS The liver function of the fibrosis model mice was significantly impaired by the use of CCl4. In the fibrosis model mice, hepatic fibrosis was verified by naked eye assessment and pathological analysis. [F-18] FNGA was found to predominantly accumulate in liver and kidneys in both control group (n = 21) and fibrosis group (n = 23). The liver uptake ability (LUA), peak time (T-p), and uptake rate (LUR) of [F-18] FNGA between healthy liver (n = 8) and fibrosis liver (n = 10) were significantly different (P < 0.05, < 0.01, and < 0.05, respectively). LUA was significantly correlated with total serum protein level (TP) (P < 0.05). T-p was significantly correlated with both TP and glucose (Glu) concentration (P < 0.05 both), and LUR was significantly correlated with both total bile acid and Glu concentration (P < 0.01 and < 0.05, respectively). CONCLUSION [F-18] FNGA mainly accumulated in liver and remained for sufficient time. Functionally-impaired liver showed a significant different uptake pattern of [F-18] FNGA compared to the controls.

Research progress and prospects of circulating tumor cells in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most common cancers and is the second leading cause of cancer-related deaths worldwide[1,2].The main therapies for HCC include surgical re-section,local ablation,or liver transplantation,which are only applied to early-stage HCC.However,most patients at the time of initial HCC diagnosis have already progressed to an advanced stage,and survival can only be prolonged finitely via palliative therapies,such as transarterial chemoembolization,systemic ther-apy with tyrosine kinase inhibitors,and selective internal radiation therapy[3,4].Moreover,as HCC has a high recurrence rate,the treatment efficacy is not satisfactory[5].Currently,the diagnosis and monitoring of HCC primarily depend on serum biomarker de-tection,pathological examination,and imaging analysis.Common serum markers display poor diagnostic performance,and imaging and pathological examinations have limitations in diagnostic accu-racy and sensitivity[6,7].Therefore,we urgently require better ap-proaches for the diagnosis and monitoring of HCC.

Liver injury in COVID-19:What do we know now?

Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has become a global pandemic.Several large cohort studies have reported liver injury in COVID-19 patients.Here,we reviewed the manifestations and causes of liver injury in COVID-19 patients and the effects of liver injury on the clinical outcomes based on the published literature.

Novel 3D preclinical model systems with primary human liver cells: Recent progresses, applications and future prospects

Liver plays a central role in various physiological functions,including metabolism,biliary secretion,production of plasma proteins,regulation of hormones as well as detoxication.Because of its multidimensional functions,liver diseases such as viral hepatitis,non-alcoholic fatty liver disease,non-alcoholic steato-hepatitis,fibrosis and liver cancer may lead to serious consequences.

Transarterial radioembolization with Yttrium-90:current status and future prospects

In recent years,transarterial radioembolization(TARE)with Yttrium-90(Y90)has emerged as a technique for treating malignant neoplasms in the liver.Compared with other locoregional therapies,such as transarterial chemoembolization(TACE),patients who underwent TARE with Y90 have higher tumor response rates and better outcomes.Moreover,no significant treatment-related complications or treatment-related deaths have been reported[1].We here review the clinical application of TARE and its associated issues.