Objective To investigate the value of the liver imaging reporting and data system v2018(LI-RADS v2018)and other imaging features in predicting preoperative risk and postoperative prognosis of isolated macrotrabecular-massive hepatocellular carcinoma(MTM-HCC).Methods Patients with isolated hepatocellular carcinoma(HCC)confirmed by pathology after preoperative MRI examination were selected,and all patients were randomly assigned to a training group(n=146)and a validation group(n=62)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression and multivariate logistic regression were used to screen independent prognostic factors of MTM-HCC and construct a nomogram.Patients were stratified into high-risk and low-risk subgroups based on the nomogram scores.Kaplan-Meier survival curves and Log-rank tests were used to compare the recurrence-free survival(RFS)among different subgroups of patients.Results Multivariate logistic regression analysis revealed that intratumoral vessels[odds ratio(OR)=3.480,95％confidence interval(CI)1.110-10.912,P=0.032],arterial phase hypovascular component ≥20％(OR=4.615,95％CI 1.728-12.321,P=0.002),and corona enhancement(OR=4.814,95％CI 1.816-12.766,P=0.002)were independent predictors of MTM-HCC.The nomogram constructed based on these indicators demonstrated area under the curve(AUC)of the receiver operating characteristic(ROC)curve was 0.834 and 0.764 for predicting MTM-HCC in the training and validation groups,respectively.The RFS predicted by the nomogram was significantly different between the high-risk and low-risk subgroups and both the pathologically confirmed MTM-HCC positive and negative groups(P＜0.05).Conclusion Intratumoral vessels,arterial phase hypovascular component ≥20％,and corona enhancement are independent predictors of MTM-HCC.The constructed nomogram based on these predictors demonstrates good diagnostic efficacy for MTM-HCC and has significant prognostic value for patients'RFS.

Objective:To analyze the hepatobiliary phase (HBP) image manifestation classification and pathological features of nodules in nodules accompanied by hepatocellular carcinoma (NIN-HCC).Methods:Twenty-five cases cases (27 lesions) with cirrhosis who were confirmed as NIN-HCC by surgical pathology and underwent gadoxetate disodium-enhanced MRI examination before surgery at Nantong Third Hospital affiliated with Nantong University from July 2015 to November 2022 were retrospectively enrolled. The size, signal intensity, enhancement pattern, and pathological features of internal and external nodules were analyzed in NIN-HCC. The lesions score were recorded according to the 2018 version of the Liver Imaging Reporting and Data Systems (LI-RADS) classification criteria. NIN-HCCs were grouped and typed according to the different HBP signal intensities of the inner and outer nodules. The independent-samples t-test, Mann-Whitney U test or Fisher's exact probability method were used to compare the differences in imaging features and LI-RADS scores between the groups. The Spearman correlation coefficient was used to evaluate the correlation between the pathological differentiation degree of internal and external nodules and the HBP signal intensity. The Kaplan-Meier curve was used to analyze recurrence-free survival (RFS) following NIN-HCC surgery. Results:The internal nodules of the 27 NIN-HCCs showed altered hypervascularity with a maximum diameter of (13.2±5.5) mm during the arterial phase. 51.9% (14/27) and 48.1% (13/27) showed "fast in and fast out" and fast in and slow out"enhancement patterns. The external nodules showed altered hypovascularity with a maximum diameter of (25.7±7.3) mm, and 13 (48.1%) of them were accompanied to manifest during the arterial phase. NIN-HCC was divided into two groups according to the signal intensity of HBP of the outer nodules with the background liver parenchyma signal intensity as a reference: the hyposignal group ( n=17, 63.0%) and the isosignal group ( n=10, 37.0%). The hyposignal group and the isosignal group were divided into A~C type and D~F type, a total of six types, according to the hypo, iso, and hyper signals of the inner nodules and the signal intensity of the outer nodules as a reference. Within the hyposignal group, 7.4% (2/27) of the inner nodules showed hyposignal (type A), 37.0% (10/27) showed isosignal (type B), and 18.5% (5/27) showed hypersignal (type C). Within the isosignal group, 29.6% (8/27) of the inner nodules showed hyposignal (type D), 7.4% (2/27) showed isosignal (type E), and there was no hypersignal (type F). 40.7% (11/27) of the lesions were LR-4 in LI-RADS score, and 59.3% (16/27) were LR-5. There was no statistically significant difference ( P>0.05) in the maximum diameter, enhancement pattern, and LI-RADS score of internal and external nodules between the hypo and iso signal group. Histologically, NIN-HCC showed fine trabecular/pseudoglandular duct type without microvascular invasion, among which the inner nodules were mainly moderately differentiated HCC, and the outer nodules were mainly well-differentiated HCC. The degree of differentiation between the inner and outer nodules and the HBP signal intensity had no statistically significant difference ( r=0.290, P=0.143; r=0.079, P=0.697). The median RFS follow-up time after NIN-HCC radical resection was 31.7 months, and the cumulative RFS rates at 1, 3, and 5 years were 96.0%, 76.0%, and 64.0%, respectively. Conclusions:NIN-HCC can serve as a morphological marker for early-stage diagnosis of multi-step cancer evolution in HCC, with certain imaging and pathological features. HBP imaging classification is helpful to enhance the diagnostic recognition of this disease.

Objective To observe the value of the scoring model of MRI features for predicting proliferative hepatocellular carcinoma(HCC).Methods Data of 241 patients with pathologically confirmed HCC,including 90 cases of proliferative HCC and 151 cases of non-proliferative HCC were analyzed retrospectively.Univariate and multivariate logistic regression were used to compare the clinical and MRI findings evaluated according to liver imaging reporting and data system version 2018 between groups.The independent predictive factors of proliferative HCC were screened,and scores were assigned according to the weight,then a scoring model was constructed.Receiver operating characteristic(ROC)curve was drawn,and the area under the curves(AUC)were calculated to assess the predictive efficacy of this model.The patients were divided into high and low proliferation risk subgroups based on the optimal score thresholds.The recurrence free survival(RFS)rates and early RFS rates were compared between groups and subgroups.Results MRI showed tumor corona enhancement,arterial phase annular hyper-enhancement,intratumoral vessels,much focus parenchymal low enhancement and irregular tumor margins were all independent predictive factors for proliferative HCC(OR=3.287,2.362,4.542,2.997,2.379,all P＜0.05),which were then were scored with 7,5,9,7 and 5,respectively,with a total score of 0-33.AUC of the obtained scoring model for predicting proliferative HCC was 0.818.Taken 9 points as the optimal score thresholds,97 cases were assigned into high proliferation subgroup and 144 into low proliferation risk subgroups).Significant differences of RFS rates and early RFS rates were found between groups and subgroups(all P＜0.05).Conclusion MRI features scoring model could effectively predict proliferative HCC.

Purpose To investigate the pathological characteristics of hepatocellular carcinoma(HCC)with irregular rim-like arterial phase enhancement(IRE)using gadoxetic acid-enhanced,and its early recurrence prognostic significance after surgery.Materials and Methods This retrospective study included 131 patients with surgically confirmed HCCs who underwent gadoxetic acid-enhanced MRI from February 2015 to September 2021 in the Third People's Hospital of Nantong.According to the enhancement pattern of gadoxetic acid-enhanced MRI in arterial phase,HCC were divided into IRE-HCC and non-IRE-HCC.Clinical,pathological and imaging characteristics were compared between IRE-HCC and non-IRE-HCC.Logistic regression analyses were performed to identify clinical,pathological and imaging features associated with IRE-HCC.Early recurrence(within 2 years)was evaluated by using Kaplan-Meier analysis.Cox regression analysis was performed to determine independent predictors of early recurrence.Results Cytokeratin 19(CK19)(OR=9.027,95%CI 2.533-32.170,P=0.001),microvascular invasion(OR=3.606,95%CI 1.024-12.701,P=0.046)and diffusion weighted imaging target signs(OR=10.370,95%CI 3.046-35.303,P=0.000)were independent predictors for IRE-HCC.The 2-year cumulative recurrence-free survival rate postoperative of IRE-HCC was 24.1%,which was significantly shorter than that of non-IRE-HCC(55.9%,χ2=19.971,P=0.000).Microvascular invasion(HR=2.206,95%CI 1.152-4.226,P=0.017)and IRE(HR=2.454,95%CI 1.408-4.275,P=0.002)were independent predictors of early postoperative recurrence of HCC.Conclusion IRE-HCC are associated with CK19,microvascular invasion and diffusion weighted imaging target signs,and have a high recurrence rate and poor prognosis in the early postoperative period.

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective:To investigate the effect of ultrasound-guided midline catheter placement on the incidence of catheter-related bloodstream infection (CRBSI) in severe emergency patients.Methods:Five hundred and twenty-nine patients were chosen as the research objects from March 2018 to December 2019 at Emergency Intensive Care Unit, which was divided into the experimental group ( n=278) and the control group ( n=251). In the experimental group, ultrasound-guided midline catheter was used as central venous catheter (CVC) removal method of sequential, and in the control group, peripheral venous indwelling needle was used as sequential method after removal of CVC. CVC, midline catheter and the indwelling time of indwelling needle were counted. The utilization rate of CVC was compared between the two groups. Kaplan-Meier survival curve was plotted to describe the CVC indwelling time of the two groups and log-rank test was performed. Cox regression analysis was performed to analyze the influencing factors of CVC indwelling time and compare the incidence of CRBSI and other catheter-related complications. Results:The CVC indwelling time of the experimental group was significantly shorter than that of the control group (8 d vs. 13 d, P=0.000). The CVC utilization rate of the experimental group was significantly lower than that of the control group (49.83% vs. 80.45%, P=0.000). Multivariate Cox regression analysis showed that difficult intravenous access, length of ICU stay, the site of catheter placement, and midline catheter implantation without ultrasound-guidance were independent risk factors for prolonged CVC indwelling time ( P=0.000). The CRBSI rate of the experimental group was significantly lower than that of the control group (0.571‰ vs. 3.802‰, P=0.038). There was no significant difference in the incidence of other catheter-related complications between the two groups ( P=0.403). Conclusions:Ultrasound-guided midline catheter implantation can shorten the indwelling time of CVC, reduce the utilization rate of CVC, and reduce the incidence of CRBSI, which is worthy of clinical promotion.

Objective:To investigate the clinical characteristics and prognosis in adult acute myeloid leukemia (AML) patients with FLT3-ITD and CEBPA double-mutated (CEBPAdm) co-mutation.Methods:Clinical data and prognostic factors were retrospectively analyzed in adult AML patients with FLT3-ITD and CEBPAdm co-mutation at The First Affiliated Hospital of Zhengzhou University from January 2016 to September 2018.Results:Among 599 non-acute promyelocytic leukemia (APL) patients, 268 received gene mutation detection, who were divided into 4 groups including 19 FLT3-ITD positive (FLT3-ITD +) and CEBPAdm positive (CEBPAdm +) cases (group A) , 84 FLT3-ITD + and CEBPAdm - cases (group B) , 95 FLT3-ITD - and CEBPAdm + cases (group C) , 70 double negative mutation cases (group D) . Gender, platelet count, FAB classification, induction treatment regimen and fusion gene mutation were comparable among four groups ( P>0.05) , while age onset, peripheral white blood cell (WBC) count, hemoglobin, percentage of blasts in peripheral blood, percentage of blasts in bone marrow, complete remission rate (CR 1 rate) after the first induction chemotherapy, the relapse rate, the median progression-free survival (PFS) time, and median overall survival (OS) time were significantly different between groups ( P<0.05) . When compared in pairs, gender, age onset, hemoglobin, platelet count, FAB classification in group A were not statistically different compared to group B, C and D ( P>0.05) , while patients in group A had higher WBC count, blasts in peripheral blood, minimal residual disease (MRD) in bone marrow. The CR 1 rates of group A, B, C, and D were 50.0%、32.4%、59.8%、39.0% respectively ( P=0.003) , and the relapse rates were 55.6%, 50.0%, 21.1%, 40.0% ( P<0.001) . As to survival, the median OS in each group was 6.25, 3.0, 15.5, 10.5 months respectively ( P<0.001) , and the median PFS was 5.0, 4.0, 10.0, 6.7 months ( P=0.032) . Conclusion:Adult AML patients with FLT3-ITD and CEBPAdm co-mutation have a higher leukemia load and low CR 1 rate, which translates into poor prognosis with high relapse rate and short survival time.

Objective To investigate the effectiveness of T1 mapping on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA-enhanced) MRI for the assessment of liver function.Methods One hundred and twenty six patients with clinically suspected focal liver lesions and chronic viral hepatitis B underwent MRI were prospectively enrolled.Patients were divided into four subgroups as follows: chronic viral hepatitis B (n=22), liver cirrhosis with Child-Pugh A (n=52), Child-Pugh B(n=41),Child-Pugh C(n=11).Twenty three healthy volunteers with normal liver function were enrolled as control group.Non-enhanced and Gd-EOB-DTPA enhanced MRI of liver were performed in all subjects.Look-Locker sequences with exactly the same scan parameters and geometry position(the level of porta hepatis) were performed pre and post-contrast separately at 5, 10, 15 and 20 minutes after Gd-EOB-DTPA administration.T1 relaxation times and reduction rates of T1 relaxation times[ΔT1(%)]of the liver parenchyma were measured and calculated.One-way ANOVA was used to compare T1 relaxation times and ΔT1(%) for control group, chronic viral hepatitis B group, liver cirrhosis with Child-Pugh A group, Child-Pugh B group,and Child-Pugh C group.ROC curve analysis was performed to compare the diagnostic performance of T1 relaxation times and ΔT1(%) values in discriminating control group + chronic viral hepatitis B group + liver cirrhosis with Child-Pugh A group from Child-Pugh B + C group. Results T1 relaxation times and ΔT1(%)showed significant difference(P<0.05)among control group and different liver function groups. T1 relaxation times and ΔT1(%) of both liver cirrhosis with Child-Pugh B group and Child-Pugh C group were significantly different(P<0.05)in comparison with those of control group,chronic viral hepatitis B group and liver cirrhosis with Child-Pugh A group at all time points.T1 relaxation times of the control group,chronic viral hepatitis B group,liver cirrhosis with Child-Pugh A group and Child-Pugh B group reduced with the scanning time increase,ΔT1(%)raised with the scanning time increase.T1 relaxation times progressively increased from control group to Child-Pugh C group at every time point.ΔT1(%)showed a constant decrease from control group to Child-Pugh C group at all time points.The areas under ROC curve of T1 relaxation time pre and post-contrast at 5,10,15 and 20 minutes for assessment of liver function were 0.817,0.952,0.950,0.946,and 0.949 respectively.The areas under ROC curve of ΔT1(%)post-contrast at 5, 10, 15 and 20 minutes for evaluation of liver function were 0.873, 0.876, 0.885, and 0.898, respectively. Conclusion Gd-EOB-DTPA-enhanced T1 mapping MRI is useful for the evaluation of liver function, and helpful for distinguishing patients with moderate and severe liver damage from normal and mild liver damage.

Objective: To identify the expression pattern of TIM-3 in natural killer/T-cell lymphoma (NK/TCL) cell lines, and to investigate the effect and mechanism of its ligand galectin-9 (GAL-9) inducing apoptosis of NK/TCL cell lines. Methods: Expression of TIM-3 in NK cell of peripheral blood from healthy donors and NK/TCL cell lines (SNK-1、SNK-6、SNT-8) was detected by Western blotting. After being treated with rhGAL-9 at various concentrations for 24h, the cell proliferation ability was analyzed with CCK-8 assay. Apoptosis ratio of the cells was determined by flow cytometry. Expressions of caspase-3, PARP and their cleavages were detected by Western blotting; moreover, phosphorylation levels of proteins in MAPK signaling pathway were also detected by Western blotting. Results: The expression of TIM-3 in SNK-1, SNK-6 and SNT-8 cell lines was significantly higher than that of NK cells from healthy donors (P<0.05). CCK-8 result showed that rhGAL-9 obviously inhibited the proliferation of NK/TCL cell lines in a concentration dependent manner. Flow cytometry showed that rhGAL-9 induced the apoptosis of NK/TCLcells; and Western blotting proved that the expression of cleaved caspase-3, cleaved-PARP, and p-JNK in MAPK signaling pathway were significantly elevated. Conclusion: TIM-3 was over-expressed in NK/TCL cell lines, and its ligand galectin-9 induced cell apoptosis probably through the activation of JNK kinase pathways.

Objective To investigate the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI in assessing liver reserve function in patients with normal liver function and abnormal liver function.Methods Totally 99 hepatitis B cirrhosis patients with abnormal liver function were classified into the following three groups,i.e.Child-Pugh A group (n=48),Child Pugh B group (n=40),Child Pugh C group (n=11),while 21 patients without chronic liver disease were taken as normal liver function group.All patients underwent Gd-EOB-DTPA enhanced MRI.At 3 min,10 min and 20 min after intravenous administration of Gd-EOB-DTPA,the relative enhancement (RE) of whole liver and liver segments (S1-S8) was calculated,and the differences of liver RE were compared among different liver function groups and liver segments.Results At 3 min,10 min and 20 min after intravenous administration of Gd EOB-DTPA,the differences of whole liver RE and segmental liver RE among the Child Pugh A group,Child-Pugh B group,Child Pugh C group and normal liver function group were statistically different (all P＜0.05).At 3 min,10 min and 20 min after injection,RE of normal liver function group and Child Pugh A group was significantly different among different liver segments (S1-S8).At 10 min and 20 min after injection,RE of Child-Pugh B group was significantly different among different liver segments,while at 20 min after injection,RE of Child-Pugh C group was significantly different among different liver segments.Conclusion Gd-EOB-DTPA enhanced MRI can accurately assess whole liver and segmental liver function.