Management of anastomotic biliary stricture through utilizing percutaneous transhepatic cholangioscopy.

AIM: Occurrence of anastomotic biliary stricture (AS) remains an essential issue following hepatobiliary surgeries, and percutaneous transhepatic cholangioscopy (PTCS) has great therapeutic significance in handling refractory AS for patients with altered gastrointestinal anatomy after cholangio-jejunostomy. This present study aimed to investigate feasibility of PTCS procedures in AS patients for therapeutic indications. MATERIALS AND METHODS: This study was a single-center, retrospective cohort study with a total number of 124 consecutive patients who received therapeutic PTCS due to AS. Clinical success rate, required number, and adverse events of therapeutic PTCS procedures as well as patients survival state were reviewed. RESULTS: These 124 patients previously underwent choledochojejunostomy or hepatico-jejunostomy, and there was post-surgical altered gastrointestinal anatomy. Overall, 366 therapeutic PTCS procedures were performed for these patients through applying rigid choledochoscope, and the median time of PTCS procedures was 3 (1-11). Among these patients, there were 34 cases (27.32%) accompanied by biliary strictures and 100 cases (80.65%) were also combined with biliary calculi. After therapeutic PTCS, most patients presented with relieved clinical manifestations and improved liver functions. The median time of follow-up was 26 months (2-86 months), and AS was successfully managed through PTCS procedures in 104 patients (83.87%). During the follow-up period, adverse events occurred in 81 cases (65.32%), most of which were tackled through supportive treatment. CONCLUSION: PTCS was a feasible, safe and effective therapeutic modality for refractory AS, which may be a promising alternative approach in clinical cases where the gastrointestinal anatomy was changed after cholangio-jejunostomy.

IL-33/ST2 Signaling and its Correlation with Macrophage Heterogeneity and Clinicopathologic Features in Human Intrahepatic Cholangiocarcinoma.

BACKGROUND: IL-33/ST2 signaling plays crucial roles in the development and progression of various human malignancies. However, its significance in intrahepatic cholangiocarcinoma (ICC) still remains unclear. OBJECTIVE: This study aimed to investigate the expression of IL-33/ST2 signaling and its correlations with macrophage heterogeneity and ICC patients' clinicopathologic features. METHODS: The expression of different phenotype macrophage markers and IL-33/ST2 signalingrelated markers was detected. The correlation between L-33/ST2 signaling and different phenotype macrophage markers as well as ICC patients' clinicopathologic data was evaluated. RESULTS: Massive heterogeneous cancer cells and PAS-positive cells were observed in tumor tissues. CD68-positive cells accumulated in tumor tissues and expression of both M1 phenotype markers and M2 phenotype macrophage markers was higher in tumor samples than para-carcinoma samples. However, M2 phenotype macrophages represented the dominant macrophage population in ICC tissues. Plasma levels of IL-33, ST2, and MIF were evidently enhanced in ICC patients compared to healthy controls. IL-33/ST2 signaling-related markers exhibited a massive increase in tumor samples than para-carcinoma samples. IL-33 and ST2 expression in ICC tissues was positively associated with M1 and M2 phenotype macrophages. Plasma levels of IL-33, ST2, and MIF were correlated with the diameter of tumor lesions, lymph node metastasis, TNM stage, and tumor differentiation degree. Multivariate analysis demonstrated IL-33 expression to exhibit a correlation with the diameter of tumor lesions, lymph node metastasis, and TNM stage. Additionally, there was a relationship observed between ST2, MIF expression, and diameter of tumor lesions plus TNM stage. CONCLUSION: IL-33/ST2 signaling exhibited a positive relationship with macrophage heterogeneity in ICC tissues, and upregulated levels of IL-33, ST2, and MIF were associated with aggressive clinicopathologic characteristics. These findings may provide promising diagnostic biomarkers and potential therapeutic strategies for ICC patients targeting IL-33/ST2 signaling.

Exosomes derived from TGF-ß1-pretreated mesenchymal stem cells alleviate biliary ischemia-reperfusion injury through Jagged1/Notch1/SOX9 pathway.

BACKGROUND: This study aimed to evaluate the efficacy of exosomes (EXO) derived from TGF-ß1-pretreated mesenchymal stem cells (MSCs) on biliary ischemia reperfusion injury (IRI) and further reveal the possible mechanisms. METHODS: Bone marrow-derived MSCs were treated with exogenous TGF-ß1, Jagged1/Notch1/SOX9 pathway inhibitor LY450139, or their combination. Then, EXO were isolated from the culture supernatants and further characterized. After establishing IRI model of biliary epithelial cells (EpiCs), EXO derived from differently-treated MSCs were applied to detect their protective effects on EpiCs, and LY450139 was applied in EpiCs to detect the possible mechanisms after treatment with MSCs-EXO. EXO derived from differently-treated MSCs were further injected into the hepatic artery immediately after establishment of intrahepatic biliary IRI for animal studies. RESULTS: Pretreatment with TGF-ß1 significantly enhanced MSCs-EXO production and elevated the levels of massive miRNAs associated with anti-apoptosis and tissue repair, which were evidently decreased after TGF-ß1 plus LY450139 cotreatment. Notable improvement was observed in EpiCs after MSCs-EXO treatment, evidenced by reduced cellular apoptosis, increased cellular proliferation and declined oxidative stress, which were more evident in EpiCs that were treated with EXO derived from TGF-ß1-pretreated MSCs. However, application of EXO derived from TGF-ß1 plus LY450139-cotreated MSCs reversely enhanced cellular apoptosis, decreased cellular proliferation and anti-oxidants production. Interestingly, LY450139 application in EpiCs after treatment with MSCs-EXO also reversed the declined cellular apoptosis and enhanced oxidative stress induced by TGF-ß1 pretreatment. In animal studies, administration of EXO derived from TGF-ß1-pretreated MSCs more effectively attenuated biliary IRI through reducing oxidative stress, apoptosis, inflammation and enhancing the expression levels of TGF-ß1 and Jagged1/Notch1/SOX9 pathway-related markers, which were reversed after administration of EXO derived from TGF-ß1 plus LY450139-cotreated MSCs. CONCLUSION: Our results provided a vital insight that TGF-ß1 pretreatment endowed MSCs-EXO with stronger protective effects to improve biliary IRI via Jagged1/Notch1/SOX9 pathway.

Efficiency of percutaneous transhepatic cholangioscopy in the treatment of biliary complications after liver transplantation.

BACKGROUND: Percutaneous transhepatic cholangioscopy (PTCS) has provided an alternative therapeutic option for handling refractory biliary complications in liver transplanted recipients. This study aimed to evaluate short-term PTCS efficiency in the management of biliary complications following liver transplantation. METHODS: Clinical data of 25 patients who received therapeutic PTCS due to biliary complications after liver transplantation were retrospectively analyzed. RESULTS: Therapeutic PTCS was successfully performed in 25 patients. Biliary complications were anastomotic strictures in seven cases, intrahepatic cholangiolithiasis in four cases, extra-and intrahepatic cholangiolithiasis in three cases, choledocholithiasis complicated with anastomotic strictures in four cases, intrahepatic cholangiolithiasis complicated with non-anastomotic strictures in one case, intrahepatic cholangiolithiasis complicated with anastomotic strictures in five cases, intrahepatic cholangiolithiasis complicated with anastomotic strictures and ischemic cholangitis in one case. The median time between liver transplantation and first PTCS was 24 months, and median times of PTCS was 2.6. Clinical manifestations were significantly improved in most patients after PTCS, and biliary complications were successfully managed through PTCS in 15 cases, which were partially effective in eight cases and ineffective in two cases. PTCS was more effective in tackling anastomotic strictures and cholangiolithiasis. CONCLUSION: PTCS was an effective therapeutic modality for treating refractory biliary complications following liver transplantation.

Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus multilocularis Infection.

Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an "immunosuppressive" microenvironment are poorly understood. Here, we profiled 83,921 CD45+ lymphocytes isolated from the peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue of four advanced-stage AE patients using single-cell RNA and T-cell receptor (TCR) sequencing technology. We identified 23 large clusters, and the distributions and transcriptomes of these cell clusters in the liver and periphery were different. The cellular proportions of exhausted CD8+ T cells and group 2 innate lymphoid cells (ILC2s) were notably higher in PL tissue, and the expression features of these cell subsets were related to neoplasm metastasis and immune response suppression. In the 5 CD8+ T-cell populations, only CD8+ mucosa-associated invariant T (MAIT) cells were enriched in PL samples and the TRAV1-2_TRAJ33_TRAC TCR was clonally expanded. In the 11 subsets of CD4+ T cells, Th17 cells and induced regulatory T cells (iTregs) were preferentially enriched in PL samples, and their highly expressed genes were related to cell invasion, tumor metastasis, and inhibition of the inflammatory immune response. Exhaustion-specific genes (TIGIT, PD-1, and CTLA4) were upregulated in Tregs. Interestingly, there was a close contact between CD8+ T cells and iTregs or Th17 cells, especially for genes related to immunosuppression, such as PDCD1-FAM3C, which were highly expressed in PL tissue. This transcriptional data set provides valuable insights and a rich resource for deeply understanding the immune microenvironment in AE, which could provide potential target signatures for AE diagnosis and immunotherapies.

Roles of immune cells in the concurrence of Echinococcus granulosus sensu lato infection and hepatocellular carcinoma.

Immune cells are pivotal players in the immune responses against both parasitic infection and malignancies. Substantial evidence demonstrated that there may exist possible relationship between echinococcus granulus sensu lato (E. granulosus s.l.) infection and hepatocellular carcinoma (HCC) development. Thus, this study aimed to observe crucial roles of immune cells in the formation of subcutaneous lesions after transplanting HepG2 cell lines with or without E. granulosus s.l. protoscoleces (PSCs). HepG2 cell lines were subcutaneously injected into nude mice in the control group. In the co-transplantation group, HepG2 cells were subcutaneously co-injected with high dosage of E. granulosus s.l. PSCs. From the 25th day of transplantation, volume of subcutaneous lesions was measured every four days, which were removed at the 37th day for further studies. Basic pathological and functional changes were observed. Moreover, expression of Ki67, Bcl-2, Caspase3, α-smooth muscle actin (α-SMA), T cell markers (CD3, CD4, CD8), PD1/PD-L1, nature killer (NK) cell markers (CD16, CD56) were further detected by immunohistochemical staining and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Subcutaneous lesions were gradually increased in volume and there occurred pathologically heterogeneous tumor cells, which were more significant in the co-transplantation group. Compared to the control group, expression of proliferation markers Ki67 and Bcl-2 was at higher levels in the co-transplantation group. Reversely, apoptotic marker Caspase3 was highly detected in the control group, suggesting promoting effects of E. granulosus s.l. PSCs on HCC development. Interestingly, subcutaneous lesions of the co-transplantation group were more functional in synthesizing and storing glycogen. Collagen and α-SMA+ cells were also at higher levels in the co-transplantation group than those in the control group. Most importantly, co-transplantation of HepG2 cells with E. granulosus s.l. PSCs led to significant increase in the expression of T cell markers, PD1/PD-L1 and NK cells markers. E. granulosus s.l. may have promoting effects on HCC development, which was closely associated with the immune responses of T cells and NK cells.

Long-term postoperative outcomes of Roux-en-Y cholangiojejunostomy in patients with benign biliary stricture.

BACKGROUND: Although there are common postoperative complications, Roux-en-Y cholangiojejunostomy is still broadly used as a standard surgical procedure for patients with biliary stricture. This study aimed to explore long-term risk factors of cholangiojejunostomy in patients with biliary stricture who underwent revisional cholangiojejunostomy. METHODS: Clinical data of 61 patients with biliary stricture undergoing revisional cholangiojejunostomy were retrospectively analyzed. These patients were classified into two groups (patients with traumatic biliary stricture and non-traumatic biliary stricture). Postoperative complications and survival time were successfully followed up. RESULTS: Among the patients, 34 underwent revisional cholangiojejunostomy due to traumatic biliary stricture, and 27 underwent revisional cholangiojejunostomy due to non-traumatic biliary surgery. Although there was no statistical difference in most clinical data between two groups, biliary dilation or not during the first surgery, cholelithiasis or not during the first surgery, long-term complications after first surgery, cholelithiasis or not during the second surgery, identifying abnormalities during the second surgery and long-term complications after second surgery were significantly different. All patients were successfully followed up and average follow-up time for patients with traumatic and non-traumatic biliary stricture was (88.44 ± 35.67) months and (69.48 ± 36.61) months respectively. Survival analysis indicated that there was no statistical difference in overall survival between two groups. Additionally, cox proportional hazard analysis demonstrated that first preoperative bilirubin level, short-term complication after first surgery and identifying abnormalities during the second surgery were independent risk factors that may have significant effects on patients' overall survival and long-term prognosis after cholangiojejunostomy. Among the intraoperative abnormal findings, residual lesions after the first operation had significant effects on the patients overall survival in the earlier stage. Relatively, anastomotic stoma stricture and biliary output loop problems had obvious effects on patients' overall survival at later stages. CONCLUSION: First preoperative bilirubin level, short-term complication after first surgery and abnormal findings during the second surgery were independent risk factors of revisional cholangiojejunostomy, which may affect patients' long-term survival. Therefore, surgeons should minimize incidence of postoperative complications through fully evaluating optimal operative time and standardizing surgical procedures.

Single-Cell RNA Sequencing Reveals the Heterogeneity of Infiltrating Immune Cell Profiles in the Hepatic Cystic Echinococcosis Microenvironment.

Human cystic echinococcosis, caused by the larval stage of Echinococcus granulosus sensu lato, has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce a lesion microenvironment; however, cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironments are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, perilesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between perilesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of type 2 innate lymphoid cells (ILC2s) and plasmacytoid dendritic cells (pDCs) were higher in perilesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was upregulated in these cells. Seven subsets of CD4+ T cell populations were found, and there were more regulatory-CD4+ T cells (Treg-CD4+) and Th2-CD4+ T cells in perilesion tissue than in adjacent normal tissue. There was close contact between CD4+ T cells and ILC2s and pDCs, which caused upregulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A/HLA-E, was obviously higher in perilesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the cystic echinococcosis (CE) lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironments at a single-cell level and provides potential target signatures for diagnosis and immunotherapies.

Quantitative evaluation of range and metabolic activity of hepatic alveolar echinococcosis lesion microenvironment using PET/CT and multi-site sampling method.

BACKGROUND: Alveolar echinococcosis (AE) lesion microenvironment (LME) is crucial site where parasite-host interactions happen and of great significance during surgery and obtaining liver samples for basic research. However, little is known about quantification of LME range and its' metabolic activity regarding different lesion characteristics. METHODS: A prospective and retrospective analysis of LME from surgical AE patients was performed. Patients (n = 75) received abdominal computed tomography (CT) and position emission tomography/computed tomography using 18F-fluodeoxyglucose (18F-FDG-PET/CT) within 1 week prior to surgery. Semiquantitatively, calcification was clustered with 0%, < 50% and ≥ 50% degrees at lesion periphery; liquefaction was clustered with 0%, < 50%, 50 ~ 75%, ≥75% degrees at lesion center using volumetric ratio. Tumor to background ratio (TBR) of 18F-FDG standard uptake value (SUV, n = 75) was calculated, and range of 18F-FDG uptake area was measured; Multi-site sampling method (MSS, n = 35) was introduced to obtain histological slides to evaluate immune cell infiltrative ranges. RESULTS: Altogether six major lesion groups have been identified (A: 0% calcified, 0% liquefied; B: ≥50% calcified, 0% liquefied; C: < 50% calcified, < 50% liquefied; D: ≥50% calcified, < 50% liquefied; E: < 50% calcified, 50 ~ 75% liquefied; F: ≥50% calcified, ≥75% liquefied). Statistically, TBR values respectively were 5.1 ± 1.9, 2.7 ± 1.2, 4.2 ± 1.2, 2.7 ± 0.7, 4.6 ± 1.2, 2.9 ± 1.1 in groups A ~ F, and comparisons showed A > B, A > D, A > F, E > B, E > D, E > F, C > B, C > D, C > F (P < 0.05); LME ranges indicated by PET/CT respectively were 14.9 ± 3.9, 10.6 ± 1.5, 12.3 ± 1.1, 7.8 ± 1.6, 11.1 ± 2.3, 7.0 ± 0.4 mm in groups A ~ F, and comparisons showed A > B, A > D, A > F, A > E, C > B, C > D, C > F, E > D, E > F, B > D, B > F (P < 0.05); LME ranges indicated by MSS respectively were 17.9 ± 4.9, 13.0 ± 2.7, 11.9 ± 2.6, 6.0 ± 2.2, 11.0 ± 4.1, 6.0 ± 2.2 mm in groups A ~ F, and comparisons showed A > C, A > D, A > F, B > D, B > F, C > D, C > F (P < 0.05). Generally, less calcifications indicated higher TBR values and wider LME ranges; and, severer liquefactions indicated smaller LME ranges. Additionally, patients with previous medication history had lower TBR values. CONCLUSIONS: PET/CT and MSS method showed distinct TBRs and LME ranges for different calcifications and liquefactions. This study would be able to provide references for both surgical resections of lesions and more accurate sample acquisitions for basic research targeted to immunology.

Identification of infiltrating immune cell subsets and heterogeneous macrophages in the lesion microenvironment of hepatic cystic echinococcosis patients with different cyst viability.

Human cystic echinococcosis (CE) is characterized by lesion microenvironment formation through gathering various immune cells, including macrophages. However, immune cell subsets and heterogeneous macrophages in CE lesion microenvironment are poorly defined. Massive infiltrating immune cells formed lesion microenvironment, among which CD4+T cells and CD19+B cells were predominant and CD68+ macrophages were more evident in patients with active cysts. Different degrees of liver fibrosis was observed in Peri-Lesion (PL) liver samples, which was more evident in patients with active cysts. Expression of both M1 and M2 macrophage markers was significantly increased in PL liver samples. Importantly, elevation of M1 macrophage markers was more obvious in patients with inactive cysts, whereas M2 macrophage markers represented dominant macrophage phenotype in patients with active cysts. Additionally, macrophage-derived MIF, TGF-ß1 and ECM1 were also expressed at higher level in CE lesion microenvironment of patients with active cysts. Moreover, MIF was evidently enhanced in the serum of hepatic CE patients, which was also predominant in patients with active cysts. Correlation analysis demonstrated positive correlation between expression of macrophage-derived cytokines and liver fibrosis degree. Heterogeneous macrophages may play significant roles in liver fibrosis of CE lesion microenvironment through producing pro-fibrogenic cytokines.

Th1/Th2/Th17 cytokine profile in hepatic cystic Echinococcosis patients with different cyst stages.

AIMS: The study aimed to investigate possible correlation between expression level of Th1/Th2/Th17-type profile and cyst viability in the systemic and local immunity of hepatic cystic Echinococcosis (CE) patients. METHODS AND RESULTS: Expression of Th1-type interleukin (IL)-2, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, Th2-type IL-4, IL-6, IL-10 and Th17-type IL-17A was examined in the serum and liver samples of hepatic CE patients with different cyst stages. Compared with healthy controls, Th1/Th2/Th17-type cytokines were significantly increased in the serum of hepatic CE patients. Moreover, expression of these cytokines was also at higher level in the inflammatory cell band of peri-lesion liver (PL) tissues than that in the adjacent normal (AN) liver tissues. Interestingly, elevation of Th1-type and Th17-type cytokines was more evident in PL tissues of patients with inactive cysts. Relatively, Th2-type cytokines were predominant in PL tissues of patients with active cysts. CONCLUSION: Our findings provide new insights that Th1/Th2/Th2-type cytokine profile was associated with cyst stages. In hepatic CE patients with inactive cysts, Th1 and Th17-type cytokines were predominant. Comparatively, Th2-type cytokines were more evident in hepatic CE patients with active cysts, which may provide basis for the immune response diversity in hepatic CE patients with different cyst stages.

Echinococcus granulosus protoscoleces promotes proliferation and invasion of hepatocellular carcinoma cells.

There may exist a connection between Echinococcus granulosus infection and cancer development. Here, it is aimed to investigate specific effects of E. granulosus protoscoleces (PSCs) on the proliferation and invasion capacities of hepatocellular carcinoma (HCC) cells in vitro and ex vitro. HepG2 cells were cultured with different quantities of E. granulosus PSCs in vitro. MTT analysis was used to evaluate effects of E. granulosus PSCs on the proliferation of HepG2 cells. Besides, scratch and transwell assays were respectively used for the detection of HepG2 cells migration and invasion capacities after co-culture with E. granulosus PSCs. Then, HepG2 cells were subcutaneously transplanted into nude mice with or without E. granulosus PSCs. From the 25th day of transplantation, the volume of subcutaneous lesions was measured every four days. At the 37th day, subcutaneous lesions were removed and their weight was evaluated. H&E staining was used for detecting basic pathological changes. HepG2 cells grew well without obvious morphological changes. Proliferation rate and migration capacity of HepG2 cells were higher in the co-culture group than the control group, which was closely associated with quantities of E. granulosus PSCs and co-culture time length. Moreover, HepG2 cells co-cultured with E. granulosus PSCs had stronger invasion ability than the control HepG2 cells. Importantly, there existed significant differences in the volume and weight of subcutaneous lesions after transplanting HepG2 cells with E. granulosus PSCs than the control group. HepG2 cells were also more pathologically heterogeneous in morphology after transplantation with E. granulosus PSCs. Thus, E. granulosus PSCs may promote proliferation and invasion of HCC cells.

Feasibility of Retrohepatic Inferior Vena Cava Resection Without Reconstruction for Hepatic Alveolar Echinococcosis.

This study evaluates the feasibility of retrohepatic inferior vena cava (RHIVC) resection without reconstruction in patients with end-stage hepatic alveolar echinococcosis (AE). Four hundred and fifty-seven patients diagnosed with hepatic AE and who underwent surgical resections between January 2010 and October 2018 were retrospectively analyzed. Nine patients receiving RHIVC resection without reconstruction were included in this study. Among the patients, 5 were male and 4 female. Mean follow-up time was 64.4 months (18-95). In this series, adequate collateral circulation was formed before operation in all patients, and 7 cases underwent ex vivo liver resection and autotransplantation (ELRA) and 2 cases underwent extended right hemi-hepatectomy. Average standard liver volume, graft volume, surgical time, and anhepatic phase in ELRA group patients was 1144 ± 127 cm3, 740 ± 235 cm3, 16.8 ± 4.1 hours, and 337.4 ± 108.65 minutes respectively. Average hospital stay time for all patients was 45 ± 36.4 days. There were no intraoperative deaths. The 30-day mortality rate was 11.1%, and total mortality rate was 22.2%. Postoperative complications occurred in 4 patients. During follow-up, no relapsed AE lesions were found. RHIVC resection without reconstruction is a feasible way for hepatic AE patients with adequate collateral circulation. Careful protection of collateral venous is the key factor for successful operation.

Direct effects of transforming growth factor-ß1 signaling on the differentiation fate of fetal hepatic progenitor cells.

Aim: To investigate direct roles of TGF-ß1 signaling in the differentiation process of fetal hepatic progenitor cells (HPCs). Materials & methods: Exogenous TGF-ß1 and SB431542 were added into fetal HPCs. Then, SB431542 was intraperitoneally injected into pregnant mice for 8 days. Results: Fetal HPCs treated with TGF-ß1 differentiated into cholangiocytes. However, hepatocyte marker was highly expressed after inhibiting TGF-ß1 signaling. In vivo, hematopoietic cells were gradually replaced with liver cells and TGF-ß1 expression was evidently decreased as fetal liver developed. Inhibition of TGF-ß1 signaling caused increase of ALB+ cells, but CK19 expression was more obvious in control mice livers. Conclusion: TGF-ß1 signaling may play decisive roles in fetal HPCs differentiation into functional hepatocytes or cholangiocytes.

Co-existence of hepatocellular carcinoma and cystic echinococcosis.

PURPOSE: Co-existence of hepatocellular carcinoma (HCC) and cystic echinococcus (CE) is extremely rare. Echinococcus granulosus may exhibit a protective effect against cancer. Herein, this study aimed to evaluate the possible effects of echinococcal infection on HCC patients. METHODS: Three thousand three hundred hepatic CE patients and 815 HCC patients were retrospectively reviewed between January 2010 and December 2018 in Xinjiang, China, and these patients were 1:5 matched according to their sex, age and tumor TMN stage, and only 13 patients coexisted both CE and HCC. Preoperative ultrasonography (US), computed tomography (CT), liver magnetic resonance imaging (MRI) and dot immune-gold filtration assay (DIGFA) were used for preoperative identification and intraoperative specimens from liver resections were pathologically examined for further confirmation. Survival time was analyzed through Cox proportional hazard model analysis. RESULTS: The co-existing incidence rate of two diseases was 0.39%. For these concurrent cases, HCC was all at the advanced stage and CE lesions were inactive. Median survival time for HCC patients was 6 month (1-17). However, it was 8 month (3-90) for the co-existing cases and was much longer than the median survival time of HCC patients (P<0.05), which was closely associated with tumor size, location, TMN stage and hydatid size, location, classification. Four of the patients underwent surgical intervention and their median survival time was 17 month (3-68). CONCLUSIONS: Echinococcus granulosus may elicit a protective effect against the development and progression of HCC, while more basic and clinical researches are needed.

Progress and applications of single-cell sequencing techniques.

Single-cell sequencing (SCS) is a next-generation sequencing method that is mainly used to analyze differences in genetic and protein information between cells, to obtain genetic information on microorganisms that are difficult to cultivate at a single-cell level and to better understand their specific roles in the microenvironment. By sequencing the whole genome, transcriptome and epigenome of a single cell, the complex heterogeneous mechanisms involved in disease occurrence and progression can be revealed, further improving disease diagnosis, prognosis prediction and monitoring of the therapeutic effects of drugs. In this study, we mainly summarized the methods and application fields of SCS, which may provide potential references for its future clinical applications, including the analysis of embryonic and organ development, the immune system, cancer progression, and parasitic and infectious diseases as well as stem cell research, antibody screening, and therapeutic research and development.

Liver metastasis and local recurrence of meningeal hemangiopericytoma: a case report.

This report describes the clinical features, diagnostic and treatment modalities of a 62-year-old female patient with liver metastasis and local recurrence of meningeal hemangiopericytoma (HPC), who presented with the clinical manifestations of memory deterioration, visual reduction and abdominal mass for one month. Skull and abdominal computed tomography (CT), magnetic resonance imaging (MRI) and 18FFluorodeoxyglucose positron emission tomography (FDG-PET)-CT were used for pre-surgery identification. Lesions without FDG uptake and less tumoral viability was observed through FDG-PET-CT, which was characteristic features of HPC before operation. The intraoperative specimens from the liver resection and the calvarium were pathologically examined for further confirming the diagnosis. The patient underwent liver resection and bilateral frontal cerebral convex and parafalx resection as well as intracranial pressure sensor implantation for liver metastasis and local recurrence of HPC respectively. The patient recovered well and no recurrence or distant metastasis was found after 2-year follow-up. Early diagnosis and long-term follow-up are crucial for patients with hepatic metastasis or local recurrence of HPC, and FDG-PET-CT is recommended as an ideal imaging tool. Radical resection of HPC lesions is considered as an optimal treating approach.

Role of TGF-β1 in hepatic fibrosis induced by echinococcus multilocular infection / 医学研究生学报

ObjectiveTo investigate the role of transforming growth factor (TGF-β1) in hepatic fibrosis induced by echinococcus multilocular infection and its possible mechanisms in this process.Methods Forty-five C57BL/6 mice were randomly divided into the model group（30）and the control group (15). Protoscolece suspension of echinococcus multilocular was infused through portal vein in the model group (4000/each). Mice in the control group was injected the same volume of normal saline solution. Six mice in the model group and 3 mice in the control group were sacrificed at 1, 2, 4, 8 and 12 weeks after infection. The liver tissues were observed the histopathological changes by using hematoxylin-eosin (H&E) staining. The fibrosis degree and glycogen synthesis function of liver tissue were observed by Sirius-red staining and Periodic acid schiff (PAS), respectively. The expression levels of TGF-β1 and a-smooth muscle actin (α-SMA) were measured by immunohistochemical staining.ResultsThe obvious abnormal changes were not observed in 1 week after model setup. The diffuse distribution of multiple white spots began to appear at 2 weeks, but the amount of white plaques decreased after 8 weeks. Meanwhile, forming small lesions were not obviously observed the boundary with the surrounding normal liver tissue. Clear echinococcal vesicles were seen at week 12. H&E staining showed that hepatic tissue structure of control group was normal. In the model group, the number of lesions with worms decreased gradually and amount of granulomas were increased. The inflammatory lesions did not change significantly. Sirius-red staining demonstrated that collagen deposition in the control group was mainly around the bile duct and blood vessels. However, the deposition in the model group was mainly around the lesion and the degree of fibrosis became more serious with time. PAS staining displayed that the content of glycogen in the liver tissues of the control group was rich, evenly distributed and stained uniformly. However, the glycogen staining positive area decreased with the time of infection and the staining became lighter in the model group. Immunohistochemical staining indicated that the positive expression of α-SMA and TGF- β1 in the control group were mainly found in the bile ducts and perivascular areas. The positive areas in the model group were mostly granulomatous areas around the metacercariae and fibroblasts. Expression of α-SMA and TGF- β1 increased over time after infection with the expression peak at 12 weeks(16.80±2.09、4.10±2.14).ConclusionThe degree of fibrosis in liver tissues at different time points was consistent with the expression trend of TGF- β1 and α-SMA. TGF-β1 may promote collagen deposition and lead to fibrosis by activating hepatic stellate cells.