Dose-response relationship between risk factors and incidence of COVID-19 in 325 hospitalized patients: A multicenter retrospective cohort study.

BACKGROUND: The epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients have been widely reported, but the assessment of dose-response relationships and risk factors for mortality and severe cases and clinical outcomes remain unclear. AIM: To determine the dose-response relationship between risk factors and incidence of COVID-19. METHODS: In this retrospective, multicenter cohort study, we included patients with confirmed COVID-19 infection who had been discharged or had died by February 6, 2020. We used multivariable logistic regression and Cox proportional hazard models to determine the dose-response relationship between risk factors and incidence of COVID-19. RESULTS: It clarified that increasing risk of in-hospital death were associated with older age (HR: 1.04, 95%CI: 1.01-1.09), higher lactate dehydrogenase [HR: 1.04, 95% confidence interval (CI): 1.01-1.10], C-reactive protein (HR: 1.10, 95%CI: 1.01-1.23), and procalcitonin (natural log-transformed HR: 1.88, 95%CI: 1.22-2.88), and D-dimer greater than 1 µg/mL at admission (natural log transformed HR: 1.63, 95%CI: 1.03-2.58) by multivariable regression. D-dimer and procalcitonin were logarithmically correlated with COVID-19 mortality risk, while there was a linear dose-response correlation between age, lactate dehydrogenase, D-dimer and procalcitonin, independent of established risk factors. CONCLUSION: Higher lactate dehydrogenase, D-dimer, and procalcitonin levels were independently associated with a dose-response increased risk of COVID-19 mortality.

Microvascular invasion and positive HB e antigen are associated with poorer survival after hepatectomy of early hepatocellular carcinoma: A retrospective cohort study.

BACKGROUND: We aimed to identify the independent predictive factors of microvascular invasion (MVI) for curative resection of HCC and to investigate the impacts of MVI and HBeAg on long-term recurrence and survival after resection. METHODS: The clinicopathological parameters of 237 patients with HCC with MVI who underwent hepatic resection from April 2005 to November 2010 were investigated. Clinical features and factors associated with the clinical outcomes of 386 patients with HCC without MVI were used for comparison. RESULTS: Multivariate stepwise logistic regression analysis revealed that alpha-fetoprotein level>100µg/L, positive HBeAg, and tumour size were independent prognostic factors in patients with HCC with MVI. The overall survival (OS) of patients in the HCC with MVI group was significantly poorer compared with the HCC without MVI group (P<0.001). However, patients with HCC without MVI group exhibited a significantly better recurrence-free survival rate (RFS) (P<0.001). While the HCC with positive HBeAg group exhibited significantly lower OS compared with the HCC with negative HBeAg group (P=0.007). CONCLUSIONS: AFP level>100µg/L, positive HBeAg, and tumour size>2cm are independent indicators of poorer prognosis for HCC with MVI. The present study confirmed that microvascular invasion itself had a negative impact on patient survival; moreover, HBeAg was an independent risk factor influencing OS, while not RFS of patients with HCC underwent hepatectomy. It is important to predict the presence of MVI before hepatic resection to determine treatment strategies.

Exosomal miR-9-3p suppresses HBGF-5 expression and is a functional biomarker in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. Exosomes are secreted membrane vesicles that play important roles in various diseases by transporting proteins and RNAs, including microRNAs, between cells. However, the function of exosomal miRNA in HCC has not been fully investigated. METHODS: Exosomes were obtained from the sera by ultracentrifugation and were processed for transmission electron microscopy (TEM). Real time PCR were revealed changes of miRNA between patients and normal donors. Predicted targets of miRNA were described by bioinformatics analysis, luciferase reporter assay was used to confirmed whether miR-9-3p regulates target expression. And then miRNA were over-expressed in HCC cell line to study its function, western blotting were used to test expression of miRNA targets, Cell viability and proliferation were analyzed after over-expressed miR-9-3p using MTT and BrdU assay. RESULTS: Serum exosomes from patients with HCC contained significantly lower levels of the miR-9-3p than did serum exosomes from normal donors, suggesting a potential role for this microRNA in HCC. Bioinformatics analysis identified fibroblast growth factor 5 (HBGF-5), which plays an important role in cell proliferation, as a potential miR-9-3p target mRNA. Luciferase reporter assay confirming that miR-9-3p can directly regulate HBGF-5 expression. Consistent with this finding, overexpression of miR-9-3p in three HCC cell lines significantly downregulated HBGF-5 expression at both the mRNA and protein levels. Finally, overexpression of miR-9-3p reduced HCC cell viability and proliferation, and additionally reduced ERK1/2 expression, suggesting a potential mechanism by which miR-9-3p acts. CONCLUSIONS: These results provide new insight into the functions of miR-9-3p and HBGF-5 in HCC and identify miR-9-3p as a potential therapeutic target for HCC.

MeCP2 level is associated with hepatocellular carcinoma development in chronic hepatitis B patients under antiviral therapy.

AIM: Hepatocellular carcinoma (HCC) is a common and aggressive malignant tumor with especially high prevalence in Asia. This present study aimed to investigate the association of MeCP2 with HCC development in patients with undetectable HBV DNA by antiviral therapy. METHODS: We retrospectively reviewed the 258 patients that were recruited into the present study. The control patients were matched with the HCC patients by age, gender, hepatitis e antigen (HBeAg) status, and duration of NA therapy in a 1:1:1 ratio. Area under ROC curve (AUC) was also used to compare diagnostic significance of MeCP2 using the Hanley and McNeil method. RESULTS: For the entire cohort of 258 patients, MeCP2 was overexpressed in HCC tissues, which was significantly higher than that in cirrhosis and non-cirrhosis tissues (P<0.001). MeCP2 significantly increased in HCC cell lines compared with the control group of THLE-2 including SMMC-7721 (P<0.001), Huh-7 (P<0.001), and Hep3B (P<0.001). Overexpression of MeCP2 was closely related to liver cirrhosis (P=0.001) and TNM stage (P=0.017). The AUROC for the entire cohort, cirrhotic patients and non-cirrhotic patients, was 0.741 (95% CI: 0.629-0.804), 0.682 (95% CI: 0.526-0.782), and 0.776 (95% CI: 0.646-0.903), respectively. The predictive accuracies of MeCP2 in different groups of patients were further compared. For the whole cohort, this test had a high specificity in identifying patients without HCC development (85%). Among patients without cirrhosis, this test had a high sensitivity in identifying patients with future HCC development (83%). CONCLUSIONS: We found that MeCP2 was expressed significantly higher in HCC tissues compared with cirrhosis and non-cirrhosis tissues. MeCP2 could be a novel risk marker to predict HCC development in CHB patients with profound viral suppression under NA therapy. MeCP2 measurement may serve as a useful strategy for risk stratification in terms of follow up interval and HCC surveillance.

Overexpression of long non-coding RNAs DUXAP9 and DUXAP10 is associated with prognosis in patients with hepatocellular carcinoma after hepatectomy.

AIM: Hepatocellular carcinoma (HCC) is a common and aggressive malignant tumor with an especially high prevalence in Asian populations. This study aimed to identify differentially expressed lncRNAs using expression microarray and to explore the association between differential expression of lncRNAs and prognosis of HCC. METHODS: We retrospectively reviewed 63 patients with primary HCC that underwent a curative liver resection at the Department of General Surgery, Jingmen First People's Hospital. The expression level of lncRNAs DUXAP9 and DUXAP10 were detected by real-time PCR. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: By microarray profiling of lncRNAs, 256 were found to be differentially expressed, including 162 upregulated and 94 downregulated (P<0.05, fold change >2). Two candidate lncRNAs were determined as targets in this study, including DUXAP9 (upregulated by 6.35 fold) and DUXAP10 (upregulated by 4.53 fold). DUXAP9 and DUXAP10 were downregulated in the normal liver cell lines Chang liver, HL7702, THLE-2, THLE-3, FL62891, and AML12, which were significantly lower than HCC cell lines SMMC-7721, Hep3B, HuH7, MHCC-97H, HCC-LM, and SK-Hep-1 (P<0.05). Overexpression of lncRNAs DUXAP9 and DUXAP10 were associated with decreasing OS rates, respectively (P=0.0263 and P=0.0285). Meanwhile, Overexpression of DUXAP9 and DUXAP10 was associated with decreasing PFS rates, respectively (P=0.0174 and P=0.0041). After adjusting for competing risk factors, we identified microvascular invasion (P=0.014), tumor size (P=0.026), and lncRNAs DUXAP9 (P=0.001) and DUXAP10 (P=0.036) expression levels as independent prognostic factors associated with prognosis of patients with HCC. CONCLUSIONS: We found that lncRNAs DUXAP9 and DUXAP10 are expressed significantly higher in HCC tissues compared with non-tumorous tissues. Overexpression of DUXAP9 and DUXAP10 were independent risk factors associated with prognosis of patients with HCC.

Partial hepatectomy for spontaneous tumor rupture in patients with hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: The impact of ruptured hepatocellular carcinoma (HCC) on a patients outcome after hepatic resection remains insufficient. We aimed to identify the independent predictive factors of spontaneous tumor rupture (STR) for curative resection of HCC and to investigate the impact of STR of HCC on long-term survival after resection. PATIENTS AND METHODS: The clinicopathological parameters of 106 patients with ruptured HCC and 201 patients with non-ruptured HCC who underwent hepatic resection from 2007 to 2011 were investigated. Clinical features and factors associated with the clinical outcomes were compared between both groups. RESULTS: Of 774 HCC patients who underwent surgical resection, 106 (13.7%) had tumor rupture. Multivariate stepwise logistic regression analysis revealed hypertension, liver cirrhosis, total bilirubin (TB), tumor size and ascites to be independent prognostic factors for patients with ruptured HCC. The overall survival (OS) of patients in the ruptured HCC group was significantly poorer compared with those in the non-ruptured HCC group. The 1-, 3- and 5-year OS rates were 77.7%, 56.9% and 41.6%, respectively, in the non-ruptured HCC group and 37.7%, 19.7%, 14.%, respectively, in the ruptured HCC group (P<0.001). Similar OS rates were found in patients with non-ruptured and ruptured HCC; patients in the non-ruptured HCC group had a significantly better recurrence-free survival (RFS) rate compared with those in the ruptured group (P=0.016). CONCLUSION: The presence of hypertension, liver cirrhosis, higher TB levels, tumor size >5 cm and ascites are the independent indicators of poorer prognosis for patients undergoing hepatic resection after ruptured HCC. The present study confirmed that tumor rupture itself had a negative impact on patient survival, but hepatic resection, when technically feasible, is safe and appropriate in selected patients and can result in OS and RFS rates comparable to that of patients with non-ruptured HCC.

Hepatogenic differentiation from human adipose-derived stem cells and application for mouse acute liver injury.

Adipose-derived stem cells (ADSCs) derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm, and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, human ADSCs were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD71, CD73, CD90, CD105, CD166, CYP3A4, and ALB were detected by immunofluorescence assays. Human ADSCs were cultured in a specific hepatogenesis differentiation medium containing HGF, bFGF, nicotinamide, ITS, and oncostatin M for hepatogenic differentiation. The hepatocyte markers were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Hepatocytes derived from ADSCs or ADSCs were transplanted into the mice of liver injury for observation cells colonization and therapy in liver tissue. The result demonstrated that human ADSCs were positive for the CD13, CD71, CD73, CD90, CD105, and CD166 but negative for hepatocyte markers, ALB and CYP3A4. After hepatogenic differentiation, the hepatocytes were positive for liver special markers, gene expression level showed a time-lapse increase with induction time. Human ADSCs or ADSCs-derived hepatocyte injected into the vein could improve liver function repair and functionally rescue the CCl4-treated mice with liver injury, but the ADSCs transplantation was better than ADSCs-derived hepatocyte transplantation. In conclusion, our research shows that a population of hepatocyte can be specifically generated from human ADSCs and that cells may allow for participation in tissue-repair.

[Scale-dependency of spatial variability of surface soil moisture under different land use types in Heihe Oasis, China].

To study the surface soil moisture spatial variability and its scale effect is of significance to understand the real variability of soil moisture and to objectively provide a reference for constructing a logical sampling scheme. By using "re-sampling" method, this paper studied the scale-dependency of the spatial variability of soil surface moisture in the woodland and farmland in the oasis ecological system in the middle reaches of Heihe River. The results showed that the variation degree of the surface soil moisture in the test woodland and farmland increased with increasing soil moisture content, and the coefficient of variation (CV) became closer to the true value when the sampling scale increased. Under both dry and moist conditions, and when the sampling amplitude increased within a definite range, the CV, Moran's I index, nugget, and sill of soil moisture in the woodland and farmland as well as the variation range in the woodland all increased, while the variation range in the farmland under arid condition did not show a stable regular pattern. When the sampling density increased within a definite range, the nugget and variation range increased, but the CV, Moran's I index, and sill showed less change.