Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of cancers worldwide,ranking fifth among men and seventh among women,resulting in more than 7 million deaths annually.With the development of medical tech-nology,the 5-year survival rate of HCC patients can be increased to 70%.How-ever,HCC patients are often at increased risk of cardiovascular disease(CVD)death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients.Moreover,CVD and cancer have become major disease burdens worldwide.Thus,further research is needed to lessen the risk of CVD death in HCC patient survivors.METHODS This study was conducted on the basis of the Surveillance,Epidemiology,and End Results database and included HCC patients with a diagnosis period from 2010 to 2015.The independent risk factors were identified using the Fine-Gray model.A nomograph was constructed to predict the CVM in HCC patients.The nomograph performance was measured using Harrell’s concordance index(C-index),calibration curve,receiver operating characteristic(ROC)curve,and area under the ROC curve(AUC)value.Moreover,the net benefit was estimated via decision curve analysis(DCA).RESULTS The study included 21545 HCC patients,of whom 619 died of CVD.Age(<60)[1.981(1.573-2.496),P<0.001],marital status(married)[unmarried:1.370(1.076-1.745),P=0.011],alpha fetoprotein(normal)[0.778(0.640-0.946),P=0.012],tumor size(≤2 cm)[(2,5]cm:1.420(1.060-1.903),P=0.019;>5 cm:2.090(1.543-2.830),P<0.001],surgery(no)[0.376(0.297-0.476),P<0.001],and chemotherapy(none/unknown)[0.578(0.472-0.709),P<0.001]were independent risk factors for CVD death in HCC patients.The discrimination and calibration of the nomograph were better.The C-index values for the training and validation sets were 0.736 and 0.665,respectively.The AUC values of the ROC curves at 2,4,and 6 years were 0.702,0.725,0.740 in the training set and 0.697,0.710,0.744 in the validation set,respectively.The calibration curves showed that the predicted probab-ilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities.DCA demonstrated that the prediction model has a high net benefit.CONCLUSION Risk factors for CVD death in HCC patients were investigated for the first time.The nomograph served as an important reference tool for relevant clinical management decisions.

Intratumoural microorganism can affect the progression of hepatocellular carcinoma

BACKGROUND Several recent studies have confirmed that intratumoural microorganisms can affect the occurrence and development of hepatocellular carcinoma(HCC);however,their role in tumor progression remains unclear.Hence,there is a need for further research on the role of intratumoural microorganisms in HCC.AIM To investigate the changes in intratumoural microorganisms in HCC and the effect of Propionibacterium on HCC progression.METHODS HCC and normal liver tissue specimens were subjected to fluorescence in situ hybridization(FISH).After performing 16S rRNA sequencing on HCC and peritumoral tissues to analyze the differences between the two groups.Propionibacterium was cocultured with HCC cells in vitro.Changes in cell proliferation and migration capacity were evaluated.The expression of NF-κB pathway related proteins in tumor cells was compared.The orthotopic liver implantation model and the subcutaneous xenograft model were constructed.liver tissues and subcutaneous tumors were collected 2 weeks later.RESULTS FISH demonstrated the presence of microorganisms in HCC and normal liver tissues.16S rRNA sequencing revealed an abundance of Lysobacter,Lachnospiraceae,Pseudomonas,and Lactobacillus in HCC tissues.The distribution and abundance of Propionibacterium showed differences between HCC and peritumoral tissues(P<0.05).In vitro studies demonstrated that Propionibacterium and its metabolite propionic acid(PA)inhibited the proliferation and migration of HCC cells(P<0.05).The expression of the proteins in NF-κB signaling pathway also decreased in HCC cells(P<0.05).CONCLUSION Microorganisms in HCC and normal liver tissues displayed significant disparities.The PA-producing bacterium Propionibacterium in HCC exerts an effect on the NF-κB pathway,thereby affecting the biological behavior of HCC.

he Spectrum of Biopsy-Proven Glomerular Disease in China： A Systematic Review

Background： Chronic kidney disease has become a leading public health concern in China, as it is associated with increased morbidity, mortality, and costs. However, the overall situation regarding common glomerular diseases in China remains unclear. Hence, the aim of this study was to assess the national profile of the common types ofglomerulonephritis in China. Methods： We searched Medline, Embase, Cochrane Library, CNKI, SinoMed, VIP, and Wanfang databases for English and Chinese language articles from inception to September 2017. We also collected potentially relevant studies and reviews using a manual search. The fbllowing words in combinations are as keywords： ＂renal biopsy＂, ＂kidney pathological diagnosis＂, and ＂spectrum of pathological types＂. Results： We identified 23 studies involving 176,355 patients from 15 provinces/cities in China. The detection rates of primary glomerulonephritis （PGN） and secondary glomerulonephritis （SGN） were 0.740 and 0.221, respectively. Over the past 30 years, the top five types of PGN were immunoglobulin A nephropathy （IgAN; 24.3%）, mesangial proliferative glomerulonephritis （MsPGN; 10.5%）, membranous nephropathy （MN; 12.6%）, minimal change disease （MCD; 9.8%）, and tbcal segmental glomerulosclerosis （FSGS; 4.6%）, and the top four types of SGN were lupus nephritis （LN; 8.6%）, Henoch-Sch6nlein purpura glomerulonephritis （4.1%）, hepatitis B virus-associated glomerulonephritis （HBV-GN; 2.6%）, and diabetic nephropathy （DN; 1.6%）. The proportion of MN, MCD, HBV-GN, and DN tended to increase, while those of IgAN, MsPGN, FSGS, and LN tended to drop. Conclusions： Although the incidence of SGN is increasing gradually, PGN is still the leading lbrm of kidney disease in patients undergoing renal biopsies in China. IgAN and LN are the most common types of PGN and SGN, respectively. Differences between regions are related to various factors such as nationality, environment, and diet. Furthermore, unified standards and norms for evahlating renal biopsies are urgently needed.

Salvianolic acid B decreases interleukin-1b-induced colitis recurrence in mice

Background:Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease(IBD).Increasing evidences has proved that tight junction(TJ)barrier dysfunction is one of the pathological mechanisms of IBD.The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence.Methods:Eighty C57BL/6 mice were randomly divided into four groups including normal group,colitis group,sulfasalazine(SASP)treated group,and traditional Chinese drug salvianolic acid B(Sal B)treated group.Colitis was established in mice by free drinking water containing dextran sulfate sodium,after treatments by SASP and Sal B,recombinant human interleukin-1b(IL-1b)was injected intraperitoneally to induce colitis recurrence.Results:Compared with sham control,cell apoptosis in colitis group was increased from 100.85±3.46%to 162.89±11.45%(P=0.0038),and TJ dysfunction marker myosin light chain kinase(MLCK)was also significantly increased from 99.70±9.29%to 296.23±30.78%(P=0.0025).The increased cell apoptosis was reversed by both SASP(125.99±8.45%vs.162.89±11.45%,P=0.0059)and Sal B(104.27±6.09%vs.162.89±11.45%,P=0.0044).High MLCK expression in colitis group was reversed by Sal B(182.44±89.42%vs.296.23±30.78%,P=0.0028)but not influenced by SASP(285.23±41.04%vs.296.23±30.78%,P>0.05).The recurrence rate induced by recombinant human IL-1b in Sal B-treated group was significantly lower than that in SASP-treated group.Conclusions:These results suggested a link between intestinal mucosal barrier dysfunction,especially TJ barrier dysfunction,and colitis recurrence.The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence.This study might provide potential treatment strategies for IBD recurrence.