Single-Cell RNA-Seq Analysis Reveals Microenvironmental Infiltration of Plasma Cells and Hepatocytic Prognostic Markers in HCC With Cirrhosis.

The occurrence of hepatocellular carcinoma (HCC) related to liver cirrhosis is mostly accompanied by extensive immune infiltration. To reveal the infiltration immune cells landscape, single-cell RNA sequencing data from the healthy donor (HD), patients with liver cirrhosis (LC) and HCC were collected for analysis. By drawing a cell map and calculating the proportion of each cell type, total B cells were identified with a significant higher proportion in HCC (24.26%) than in LC (5.41%) and HD (5.82%), in which plasma cells account for 97.1% in HCC. While in HCC, TCGA datasets were taken for further investigation, and it was found that patients with lower proportion of plasma cells showed better prognosis. The pseudotime cell trajectory analysis of B cell population found that humoral immunity continuously changes during HD, LC and HCC, and humoral immune-related genes are highly expressed in the HCC stage. This suggests humoral immunity may play a key role in the development of LC-associated HCC. At the same time, single cell data of hepatocytes identified differentially expressed genes in HD/LC and LC/HCC groups, and a prognostic model constructed with six of the differential genes (FTCD, MARCKSL1, CXCL3, RGS5, KNG1, and S100A16) could classify HCC patients to two distinct risk groups (median survival time 2.46 years vs. 6.73 years, p < 0.001). Our study demonstrated the power of single-cell data analysis in dissecting tissues into infiltration and main body cells, it revealed the pivotal roles of humoral immunity infiltration in the landscape of HCC associated with cirrhosis, and the key tumor prognostic genes in hepatocytes themselves. These brought novel insights into studying microenvironment and tumor cells parallelly in cancer research. The interaction of both, rather than factors from one side may have caused tumorigenesis and progression.

What are the Particularities of Oesophageal Surgery in Cirrhotic Patients.

The aim of this paper was to review the entire literature on esophageal surgery to best define the surgical indications and the specifics of their management. The bibliographic research was carried out on Pubmed between January 1995 and June 2015, using French and English as publication languages.

What are the Particularities of Gastric and Bariatric Surgery in the Cirrhotic Patient.

The objective of this work was to review the entire literature on gastric and bariatric surgery in order to best define the surgical indications and the specifics of their management. A literature review from 1995 to August 2015 was conducted in Pubmed and Google Scholar, using French and English as publication languages. 21 studies were included (level 3 and 4) over 128 identified. In total, if the cirrhotic patients, candidates for gastric surgery, are appropriately selected, long-term survival seems relatively good. No risk factors for long-term survival have been reported. The literature data are insufficient to be able to make recommendations concerning bariatric surgery in the cirrhotic patient.

Laparoscopic Cholecystectomy in Cirrhotic Patients.

Laparoscopic cholecystectomy is the gold standard procedure in patients with cirrhosis and symptomatic gallbladder disease or acute cholecystitis. In this retrospective study we evaluated laparoscopic cholecystectomy in patients with cirrhosis based on Child-Pugh score as a predictor of morbidity. In the First Surgical Clinic of Iasi, from 01 jan 2010 to 31 jan 2020, we performed 111 laparoscopic cholecystectomies in Child-Pugh A, B, and C cirrhotic patients. Intraoperative difficulty (grade 3 Cuschieri) was experienced in 32 patients (28.8%). Highly vascular sub hepatic adherences have been reported in a quarter of all patients. Intraoperative incidents were more frequent 27 (24.3%) compared to laparoscopic cholecystectomy performed in other patient groups. The conversion rate to open cholecystectomy was 6.3% (7 cases). Mean operative time was 84 min. Mean duration of hospitalization stay was 4.7 days. The morbidity rate was 16.2% of patients and included bleeding, intraabdominal fluid collections and wound complications more common in patients with Child-Pugh Cirrhosis B and C. The results are dependent of the perioperative management of the liver function.

ThepredictiveanalysisofspectralCTportalveinimagingforesophagealGgastricvaricealbleeding / 实用放射学杂志

Objective ToinvestigatethevalueoftheoptimalCNR monoenergeticimagesofportalveininpredictingesophagealGgastric varicealbleeding(EVB).Methods FortypatientswithlivercirrhosisandportalhypertensionunderwentcontrastGenhancedspectral CTscan.TheoptimalCNR monoenergeticimagesand70keV monoenergeticimagesoftheportalveinphasewereselectedtocompare theimagingquality.TheconsistencyoftheoptimalCNR monoenergeticimageswithendoscopyforesophagealGgastricvaricealwas analyzed by Kappa test.A ccording to the E V B history ,the patients w ere divided into bleeding group and nonGbleeding group.T he ROCcurveswerecalculatedtoassessthevaluesofthemainportalvein(MPV)anditstributariesdiameterstopredictingEVB.Results TheCNRandobjectivescoreoftheoptimalCNR monoenergeticimagesweresignificantlyhigherthanthoseofthe70keVimages(P＜0.05).TheoptimalCNR monoenergeticimageshadgoodconsistency withgastroscopeintheclassificationofesophagealGgastric variceal(k＝0.769).ThereweresignificantdifferencesofthediametersofMPV,intrahepaticleftbranchofportalvein(LPV),splenic vein(SV)andleftgastricvein (LGV)betweenthebleedinggroupandnonGbleedinggroup (P＜0.05).ROCcurveanalysisshowed thattheincidenceofEVBwashighestwithasensitivityof76.92%andaspecificityof85.71%,whentheLGVwasgreaterthan6.1mm. Conclusion TheoptimalCNR monoenergeticimagesofportalveincouldimprovetheimagingquality,andLGVdiametershouldbe ariskindicatorforpredictingEVBinlivercirrhosis.

The Outcome of Colorectal Surgery in Cirrhotic Patients: A Case Match Report.

Background: Colorectal surgery in cirrhotic patients has had limited indications, but as the study aims to show, careful evaluation of risk factors can extend boundaries. Methods: From January 2011 to January 2016, using a case match cohort, 68 patients with colorectal malignancy and cirrhosis were compared against 136 persons with no liver disease. Significant risk criteria, morbidity and mortality were evaluated. Results: When analyzing specific risk factors age, etiology and severity of liver disease (MELD, Child-Pugh score, ascites and hypoalbuminemia) were found to be significant to surgical outcome. Approach and type of intervention as well as emergency status reflected upon reintervention rates with 10.2% in the cirrhotic population vs 5.1% in the non-cirrhotic one (p=0.3). Postoperative morbidity was higher in the chronic liver disease patients - 47.1% vs 27.9% in the case-match group (p=0.035). Mortality rate in the cirrhotic population was 5.9% while in the non-cirrhotic one was 2.2% (p=0.2). Child C patients had a morbidity and a mortality rate of 75% and 50% respectively. CONCLUSION: Child A patients can be treated no different than the general population; Child B group needs proper assessment and care while in Child C population surgery should at all costs be avoided.

The correlation between liver fibrosis inflammatory infiltration and postoperative cholangitis after Kasai operation for children with biliary atresia / 天津医药

@# To analyze the relationship between the degree of hepatic fibrosis, the inflammatory cell infiltrationandthepostoperativecholangitisafterKasaioperationinchildrenwithbiliaryatresia(BA).Methods Atotalof 92childrendiagnosedasBAinourhospitalfromJanuary2015toDecember2016wereselectedinthisstudy.Patientswere dividedintohepaticfibrosisgradeⅠgroup(n=8),hepaticfibrosisgradeⅡgroup(n=31),hepaticfibrosisgradeⅢgroup(n= 35)andhepaticfibrosisgradeⅣgroup(n=18),accordingtoJapan’sOhkuma’shepaticfibrosisgradingcriteria.Combined with Kasai age, the relationship between hepatic fibrosis and surgical age was analyzed. Samples of liver tissues were evaluatedbyhematoxylin/eosin(HE)andMassonstaining.Theexpressionsofspecificinflammatorycellmarkerantibody LCA,CD4,CD8andCD68inliverwereobservedbyIHCstaining.Combinedwiththepostoperativefollow-updataofKasai, the relationship between the degree of inflammatory infiltration of liver tissue, the degree of hepatic fibrosis and the postoperative cholangitis of Kasai in BA children was analyzed. Results Routine pathological staining showed that lymphocytesinfiltratedmainlyinlivertissue.TheexpressionlevelsofLCAandCD4werehigheringroupⅠandgroupⅣ comparedwiththoseofgroupⅡandgroupⅢ.TherewasnosignificantdifferenceintheCD8expressionbetweenfour groups.All92childrenwithBAwerefollowedup.Itwasfoundthatcholangitisoccurredin 50cases,earlycholangitis occurredin38cases,andfrequentcholangitisoccurredin23cases.Theincidenceofcholangitis,earlycholangitis,and frequentcholangitisafterKasaisurgerywasstatisticallysignificantinBApatientswithdifferentgradesofhepaticfibrosis (P＜0.05). The incidence of cholangitis was higher in the groupⅠand group Ⅳ than that in groupⅡand group Ⅲ. Conclusion TheoccurrenceofcholangitisafterKasaioperationinchildrenwithBAiscorrelatedwiththehepaticfibrosis andliverinflammatorycells,especiallyTlymphocytesubgroups.

Study on effect and mechanism of Shenshaoruangan Decoction on liver fibrosis in rats / 重庆医学

Objective To study the effect and mechanism of Shenshaoruangan Decoction on liver fibrosis in rats.Methods Seventy-two male Wistar rats were selected and normally fed for 1 week.Then they divided into the control group(n=12) and model constructing group(n=60).The model constructing group was subcutaneously and intraperitoneally injected by 40％ CCl4 olive oil for constructing fibrosis rat model.After successfully constructing model,which was divided into the model group(equivalent normal saline gavage),positive control group(colchicines 0.154 mg · kg-1 · d-1),low-dose group(2 mL per 100 g body mass,containing Shenshaoruangan Decoction crude drug 0.23 g/mL),medium-dose group(2 mL per 100 g body mass,containing Shenshaoruangan Decoction crude drug 0.46 g/mL) and high-dose group(100 g/2 mL,containing Shenshaoruangan Decoction crude drug 0.69 g/mL),12 cases in each group.The differences of related indicators rat hepatic fibrosis after 8-weeks treatment were observed.Results The control group was the stage 0 standard,the liver fibrosis degree in the positive control group was significantly better than that in the model group(P＜0.05);the liver fibrosis degree in the low-dose group,medium-dose group and high-dose group was gradually alleviated;the liver fibrosis degree in the high-dose group was significantly slighter than that in the model group and-dose group(P＜0.05).The detection values of PC-Ⅲ,LN,Ⅳ-C and HA in the model group were significantly higher than those in the control group(P＜0.05),and the detection values of PC-Ⅲ,LN,Ⅳ-C and HA in the positive control group,lowdose group,medium-dose group and high-dose group were significantly lower than those in the model group(P＜0.05).Serum SOD detection value of the model group was significantly lower than that in the control group(P＜0.05),the serum MDA level in the model group was significantly higher than that in the control group(P＜0.05);serum SOD level in the positive control group,low dose group,medium-dose group and high-dose group was significantly higher than that in the model group(P＜0.05),while serum MDA level in those group was significantly lower than that in the model group(P＜0.05).Conclusion Shenshaoruangan Decoction can effectively alleviate the liver fibrosis degree,and its mechanism is to reduce the levels of liver fibrosis indicators,inhibit the prodmotion of peroxides and alleviate the damage of free radicals on liver cells.

Differences of T helper 17 cells and transforming growth factor-β1 between early and late primary biliary cirrhosis / 中华风湿病学杂志

Objective To explore the differences of Th17 population and serum transforming growth factor (TGF)-β1 levels between early-and late-stage primary biliary cirrhosis (PBC) and their roles in pathogenesis.Methods Peripheral Th17 counts were analyzed by flow cytometry.The expression of IL-17A in peripheral blood mononuclear cells and TGF-β1 were measured by real-time quantitative polymerase chain reaction.Serum concentration of TGF-β1 was measured by enzyme-linked immunosorbent assay.Liver biopsies were stained with hematoxylin-eosin to determine the pathological stage.Results were evaluated using KrustalWallis test followed by Mann-Whitney U tests for comparisons of Th17 population between patients with early and late PBC,patients with chronic hepatitis B (CHB) and health controls (HCs).ANOVA followed by LSD t-tests were used for comparing IL-17 mRNA,TGF-β1 mRNA and TGF-β1 serum concentration between groups.The correlations between Mayo risk score and peripheral Th17 of PBC patients,Mayo risk score and serum concentration of TGF-β1 was analyzed by Pearson correlation analysis separately.Results The peripheral Th17 population increased in patients with early PBC (1.03±0.33)％,compared to those with late PBC [(0.48± 0.13％,U=14.0,P＜0.01],CHB [(0.56±0.35)％,U=104.5,P＜0.01],and HCs [(0.36±0.17)％,U=8.0,P＜0.01],while TGF-β1 changed in the opposite direction.Serum concentration of TGF-β1 elevated in late PBC (43.0± 18.7) ng/ml compared with early PBC (29.5±12.2) ng/ml,t=2.85,P=0.006.Conclusion The opposite changes of Th17 population and TGF-β1 level in early and late PBC indicated their different roles in different stages.Th17 may contribute to the autoimmune response in early PBC,participate in the occurrence of autoimmune inflammation,while TGF-β1 to fibrogenesis in late stage.In addition,the possible regulation mechanisms of differentiation of Th17 by TGF-β1 cannot be ignored.

Telomere and telomerase in chronic liver disease and hepatocarcinoma.

The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a genetic predisposition may contribute to the development of cirrhosis and HCC. Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years. In addition to the results from epidemiological studies, polymorphisms studies and data on twins, the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed. Here we review the literature on telomerase mutations, telomere shortening and liver disease including hepatocellular carcinoma.

Experience of surgical treatment for autoimmune hepatitis complicated with cirrhosis and hyper-splenism / 临床外科杂志

Objective To investigate the effect of splenectomy on autoimmune hepatitis complicated with cirrhosis and hypersplenism.Methods Nine cases of autoimmune hepatitis complicated withcirrhosis and hypersplenism were treated with splenectomy and periesophagogastric devascularization.Results All patients recovered well.Their liver functions recovered to the preoperative level within twoweeks after operation.No significant differences were found between preoperative and postoperative levelsof transaminase and bilirubin(P >0.05).The count of leukocyte and platelet rose to the normal level andthere were significant differences between the preoperative and postoperative levels(P <0.05).Patients'symptoms of hypersplenism were corrected and their coagulation function improved significantly (P <0.05).Conclusion In patients with autoimmune hepatitis complicated with cirrhosis and hypersplenism,splenectomy with periesophagogastric devascularization is an effective procedure for improving hypersplenism,enhancing blood coagulation,and reducing bleeding.

Effect of American cockroach extract on NF-κB andα-SMA expression in CCl4 caused liver fibrosisrat model / 重庆医学

Objective To investigate the effect of American cockroach extract on the expression of NF-κB andα-SMA in experi-mental liver fibrosis tissue,and to observe its antifibrotic efficacy.Methods The rat model of hepatic fibrosis was duplicated by car-bon tetrachloride and simultaneously given with American cockoach extract 0.5 g/kg by lavage.The level of serum alanine amin-otransferase enzyme (ALT),aspartate aminotransferase (AST)and albumin (Alb)were determined.The expression levels of NF-κB and a-SMA in liver tissue were determined by the immunohistochemical method and the liver histological changes were observed by light microscopy for conducting the grading of inflammatory activity and the fibrosis classification.Results American cockroach extract could reduce serum ALT,AST and liver tissue NF-κB andα-SMA levels.The serum Alb level had significant difference a-mong the APA group,Pseudo-ginseng Danshen group and the model group.The degeneration and necrosis of liver cells and the fi-brosis degree after medication were significantly reduced.Conclusion The American cockroach extract has certain anti-fibrosis effect,its mechanism may be related with the inhibition of expression of NF-κB andα-SMA.

Impacto del consumo nocivo de alcohol en accidentes y enfermedades crónicas en México / Impact of harmful consumption of alcohol in accident-related mortality and chronic diseasses in Mexico

Objetivo. Analizar el consumo de alcohol, su relación con accidentes de tránsito y su impacto en enfermedades crónicas. Material y métodos. Usando encuestas nacionales de salud, registros de colisiones, lesionados y muertes, así como encuestas económicas, se estimaron indicadores de prevalencia, mortalidad y consumo. Resultados. Entre 2000 y 2012, la prevalencia de consumo de alcohol en adolescentes se mantuvo estable con un incremento importante en adultos. La tasa de colisiones de tránsito con presencia de alcohol fue de 0.36 y 0.58 en adolescentes y adultos, respectivamente. De la población con lesiones de tránsito, 8.4% estaba bajo efectos del alcohol al momento de lesionarse. La mortalidad por dos enfermedades atribuibles al alcohol se ha mantenido en alrededor de 18 000 fallecimientos anuales. Conclusiones. El abuso en el consumo alcohol implica graves daños a la salud. El incremento de impuestos al alcohol, junto con otras medidas, reduciría el consumo nocivo y la mortalidad asociada.

Objective. To analyze alcohol consumption, and its impact on road traffic-related mortality and chronic diseases. Materials and methods. Through the analysis of national health surveys, registry of traffic collisions, mortality records and economic surveys, we estimated prevalence, mortality and consumption indicators. Results. Between 2000 and 2012, alcohol consumption in adolescents remained stable, with a significant increase among adults. Traffic collision rates related with alcohol were 0.36 and 0.58 among adolescents and adults, respectively; 8.4% of the population who suffered traffic injuries was under alcohol effects when the accident occurred. The trend in mortality from two alcohol-attributable diseases has been constant, with an average of 18 000 deaths per year. Conclusion. Alcohol abuse causes serious health damages. Tax raises to alcohol, along with other policies, could reduce harmful alcohol consumption and its associated mortality.

The effect of the balance between cytokines in the serum of hepatic fibrosis rats on the expression of β-catenin in their livers / 中华传染病杂志

Objective To investigate the effect of the balance between helper T lymphocyte (Th) 1 cytokines and Th2 cytokines in the serum of hepatic fibrosis rats induced by CCl4 on the expression of β-catenin in their livers. Methods Seventy-five rats were divided into control group,treatment group and model group. Hepatic fibrosis models were built by subcutaneous injection of CCl4in male Wistar rats, then rats in treatment group were treated with pentoxifylline(PTX) by intragastric administration. The model rats without PTX treatment served as treatment control. The serum levels of Th1 cytokines(interferon-γ, IFN-γ; tumor necrosis factor-α, TNF-α), Th2 cytokines (interleukin-4,IL-4;interleukin-6,IL-6) and type Ⅳ collagen were measured by enzyme-linked immunosorbent assay (ELISA). The expression and distribution of β-catenin in liver tissue and the percentage of area of type Ⅳ collagen accounted in the liver were analyzed by immunohistochemical analyses. The changes in serum cytokines were depicted by using One-way ANOVA, and the correlation between β-catenin expression and cytokines levels or hepatic fibrosis development was elucidated by Bivariate.Results The serum levels of Th2 cytokines in model group were significantly higher than those in treatment group, and even higher than those in control group (F=71. 260,91. 732, all P＜0.05).However, the levels of Th1 cytokines in model group were significantly lower than in treatment group while even lower than those in control group(F= 50. 420,10. 625, all P＜0.05). Serum cytokines came out to be Th2 polarized. Meanwhile, the percentage of type Ⅳ collagen area accounted in the liver,which was corresponding to the degree of liver fibrosis, was lower in the treatment group than the model group and even lower in control group (F=3 000,both P<0.05). β-catenin expression in the liver of model group was stronger than that in the treatment group, and even stronger than that in normal group (F=92. 030, both P＜0. 05). According to β-catenin immunohistochemical analyses based on patho-photos, livers from the model group showed dark color in both cell cytoplasm and nucleus, while the liver from the treatment group only showed weak color in cytoplasm and no straining color in nucleus and the liver from normal group showed colors neither in cytoplasm nor in the nucleus.The expression of β-eatenin had a positive correlation with either the level of Th2 cytokines in serum of rats (r=0. 560,P＜0.01) or the percentage of area of type Ⅳ collagen accounted in the liver of rats (r=0. 757, P＜0. 01). Conclusions Th2 polarization in serum cytokines can aggravate the development of liver fibrosis by inducing the expression of β-catenin, which in the livers of rats is a reflection of the degree of the liver fibrosis.

Evaluation of Clinical Effect of Serum FT_3,FT_4 in Patients With Liver Cirrhosis / 中国医师杂志

Objective To study the relationship between changes of contents of serum free-triiodothyronine(FT 3),Free-thyroxine(FT 4) and liver cirrhosis,and analyse it's clinical significanec.Methods The concentration of serum FT 3 and FT 4 were determined by radioimmunoassay in 69 patients with liver cirrhosis,compared with liver function classification(Child-Pugh).Results Contents of serum FT 3,FT 4 in cirrhosis patients were markedly lower than that of controls(P