Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors

BACKGROUND Patients with liver cancer complicated by portal hypertension present complex challenges in treatment.AIM To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition.METHODS Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group(n=50)and a control group(n=50)according to the treatment regimen.The research group received radiofrequency ablation(RFA)in combination with sorafenib,and the control group only received RFA.The short-term efficacy of both the research and control groups was observed.Liver function and portal hypertension were compared before and after treatment.Alpha-fetoprotein(AFP),glypican-3(GPC-3),and AFP-L3 levels were compared between the two groups prior to and after treatment.The occurrence of adverse reactions in both groups was observed.The 3-year survival rate was compared between the two groups.Basic data were compared between the survival and non-surviving groups.To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension,multivariate logistic regression analysis was employed.RESULTS When comparing the two groups,the research group's total effective rate(82.00%)was significantly greater than that of the control group(56.00%;P<0.05).Following treatment,alanine aminotransferase and aspartate aminotransferase levels increased,and portal vein pressure decreased in both groups.The degree of improvement for every index was substantially greater in the research group than in the control group(P<0.05).Following treatment,the AFP,GPC-3,and AFP-L3 levels in both groups decreased,with the research group having significantly lower levels than the control group(P<0.05).The incidence of diarrhea,rash,nausea and vomiting,and fatigue in the research group was significantly greater than that in the control group(P<0.05).The 1-,2-,and 3-year survival rates of the research group(94.00%,84.00%,and 72.00%,respectively)were significantly greater than those of the control group(80.00%,64.00%,and 40.00%,respectively;P<0.05).Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade,history of hepatitis,number of tumors,tumor size,use of sorafenib,stage of liver cancer,histological differentiation,history of splenectomy and other basic data(P<0.05).Logistic regression analysis demonstrated that high Child-Pugh grade,tumor size(6–10 cm),history of hepatitis,no use of sorafenib,liver cancer stage IIIC,and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension(P<0.05).CONCLUSION Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates.The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade,tumor size(6-10 cm),history of hepatitis,lack of sorafenib use,liver cancer at stage IIIC,and prior splenectomy.

不同临床分型胃神经内分泌肿瘤的临床病理特征及预后分析

背景近年来,胃神经内分泌肿瘤(neuroendocrine neoplasm,NEN)的发病率呈上升趋势.胃NEN具有明显的异质性,不同临床分型的胃NEN的临床病理特点及预后各不相同,结合国内外诊断标准,中国临床分型专家建议分4型.研究不同临床分型胃NEN的临床病理特点,对胃NEN患者的诊断和治疗具有重要意义.目的探讨不同临床分型胃NEN的临床病理特征,筛选转移危险因素,分析各型患者的预后.方法回顾性分析2011-2017年在郑州大学第一附属医院就诊的160例胃NEN患者的临床病理资料及随访资料,采用4型分类法将胃NEN分为4个基本类型,采用χ~2检验、t检验分析不同分型胃NEN的临床病理特征差异, Logistic回归分析转移危险因素, Kaplan-Meier法和Log-rank检验进行生存分析.结果全组160例胃NEN患者中,平均年龄为(58.3±10.8)岁,Ⅰ型41例(25.9%),Ⅱ型8例(5.1%),Ⅲ型25例(15.8%),Ⅳ型84例(53.2%),未明确分型者2例.Ⅰ、Ⅱ、Ⅲ、Ⅳ型肿瘤最大径中位数(下四分位数,上四分位数)分别为0.5 cm(0.3 cm, 0.7 cm)、1.5 cm(1.0 cm, 1.9 cm)、3.5 cm(2.0 cm, 4.8 cm)、5.0 cm(3.0 cm, 7.0 cm),四者比较差异有统计学意义(χ~2=64.532, P=0.000).150例报告转移情况的患者中,发生转移者83例,各型胃NEN患者中,有2例患者失访,156例患者获得随访,随访率98.7%,随访时间为1 mo-62 mo.截至随访结束,Ⅰ型患者总体生存率为97.6%(40/41),Ⅱ型患者总体生存率为85.7%(6/7),Ⅲ型患者总体生存率为64.0%(16/25),Ⅳ型患者总体生存率为55.4%(46/83).结论肿瘤最大径是转移的重要预测因素,不同分型胃NEN患者的预后不同,Ⅰ型和Ⅱ型预后较好,Ⅲ型和Ⅳ型预后较差,男性患者Ⅳ型多见.

Effect of NLRC5 on activation and reversion of hepatic stellate cells by regulating the nuclear factor-κB signaling pathway

BACKGROUND The formation of liver fibrosis is mainly caused by the activation of hepatic stellate cells(HSCs)and the imbalance of extracellular matrix(ECM)production and degradation.The treatment of liver fibrosis mainly includes removing the cause,inhibiting the activation of HSCs,and inhibiting inflammation.NOD-like receptor(NLR)family,caspase activation and recruitment domain(CARD)domain containing 5/NOD27/CLR16.1(NLRC5)is a highly conserved member of the NLR family and is involved in inflammation and immune responses by regulating various signaling pathways such as nuclear factor-κB(NF-κB)signaling.It has been found that NLRC5 plays an important role in liver fibrosis,but its specific effect and possible mechanism remain to be fully elucidated.AIM To investigate the role of NLRC5 in the activation and reversion of HSCs induced with transforming growth factor-β(TGF-β)and MDI,and to explore its relationship with liver fibrosis.METHODS A total of 24 male C57BL/6 mice were randomly divided into three groups,including normal,fibrosis,and recovery groups.Twenty-four hours after a liver fibrosis and spontaneous reversion model was established,the mice were sacrificed and pathological examination of liver tissue was performed to observe the degree of liver fibrosis in each group.LX-2 cells were cultured in vitro and treated with TGF-β1 and MDI.Real-time quantitative PCR(qPCR)and Western blot were used to analyze the expression levels of NLRC5,α-smooth muscle actin(α-SMA),and collagen type I alpha1(Col1a1)in each group.The activity of NF-κB in each group of cells transfected with NLRC5-siRNA was detected.RESULTS Compared with the normal mice,the expression level of NLRC5 increased significantly(P<0.01)in the fibrosis group,but decreased significantly in the recovery group(P<0.01).In in vitro experiments,the content of NLRC5 was enhanced after TGF-β1 stimulation and decreased to a lower level when treated with MDI(P<0.01).The expression ofα-SMA and Col1a1 proteins and mRNAs in TGF-β1-mediated cells was suppressed by transfection with NLRC5-siRNA(P<0.01).Western blot analysis showed that the expression of NF-κB p65 protein and phosphorylated IκBα(p-IκBα)was increased in the liver of mice in the fibrosis group but decreased in the recovery group(P<0.01),and the protein level of nuclear p65 and p-IκBαwas significantly increased after treatment with NLRC5-siRNA(P<0.01).CONCLUSION NLRC5 may play a key role in the development and reversal of hepatic fibrosis through the NF-κB signaling pathway,and it is expected to be one of the clinical therapeutic targets.

Long Noncoding RNA UCA1 Overexpression Is Associated with Poor Prognosis in Digestive System Malignancies: A Meta-analysis

Long noncoding RNA(IncRNA)urothelial carcinoma associated 1(UCA1)has been reported to be highly expressed in many kinds of cancers.This meta-analysis summarized its potential prognostic value in digestive system malignancies.A meta-analysis was performed through a comprehensive search in PubMed,EMBASE,the Cochrane Library,Web of Science and Chinese National Knowledge Infrastructure(CNKI)for suitable articles on the prognostic impact of UCA1 in digestive system malignancies from inception to June 27,2019.Pooled hazard ratios(HRs)with 95% confidence interval(95%CI)were calculated to summarize the effect.Sixteen studies were included in the study,with a total of 1504 patients.A significant association was observed between UCA1 abundance and poor overall survival(OS),and shorter disease-free survival(DFS)for patients with digestive system malignancies,with pooled HR of 2.07(95%CI:1.74-2.47),and of 2.50(95%CI:1.62-3.86).Subgroup analysis and sensitivity analysis suggested the reliability of our findings.It is suggested that UCA1 abundance may serve as a reliable predictive factor for poor prognosis in patients with digestive system malignancies.

Effects of refluxate pH values on duodenogastroesophageal reflux-induced esophageal adenocarcinoma

AIM： To determine the effects of duodenogastric juice pH on the development of esophageal adenocarcinoma （EAC）. METHODS： An animal model of duodenogastroesophageal reflux was established using Sprague-Dawley （SD） rats undergoing esophagoduodenostomy （ED）. The development of EAC was investigated in rats exposed to duodenogastric juice of different pH. The rats were di- vided into three groups： Iow-pH group （group A）, high- pH group （group B） and a sham-operated group as a control （group C） （n = 30 rats in each group）. The inci- dence of esophagitis, Barrett＇s esophagus （BE）, intestinal metaplasia with dysplasia and EAC was observed 40 wk after the treatment. RESULTS： The incidence rate of esophagitis, BE, intestinal metaplasia with dysplasia and EAC was higher in groups A and B compared with the control group after 40 wk （P 〈 0.01）, being 96% and 100% （P 〉 0.05）, 88% and 82.4% （P 〉 0.05）, 20% and 52.1% （P 〈 0.05）, and 8% and 39% （P 〈 0.05）, respectively. CONCLUSION： Non-acidic refluxate increases the occurrence of intestinal metaplasia with dysplasia and EAC while the Iow-pH gastric juice exerts a protective effect in the presence of duodenal juice. The non-acid reflux is particularly important in the progression from BE to cancer. Therefore, control of duodenal reflux may be an important prophylaxis for EAC.

Dhcr24 activates the PI3K/Akt/HKII pathway and protects against dilated cardiomyopathy in mice

Background: 24-dehydrocholesterol reductase(Dhcr24) catalyzes the last step of cholesterol biosynthesis, which is required for normal development and antiapoptotic activities of tissues. We found that Dhcr24 expression decreased in the cTnTR141 Wdilated cardiomyopathy(DCM) transgenic mice. Therefore, we tested whether rescued expression of Dhcr24 could prevent the development of DCM and its possible mechanism.Methods: Heart tissue specific transgenic overexpression mice of Dhcr24 was generated, then was crossed to c TnTR141 Wmouse to obtain the double transgenic mouse(DTG). The phenotypes were demonstrated by the survival, cardiac geometry and function analysis, as well as microstructural and ultrastructural observations based on echocardiography and histology examination. The pathway and apoptosis were analysed by western blotting and TUNEL assay in vivo and in vitro.Results: We find that Dhcr24 decreased in hearts tissues of cTnTR141 Wand LMNAE82 KDCM mice. The transgenic overexpression of Dhcr24 significantly improves DCM phenotypes in cTnTR141 Wmice, and activates PI3K/Akt/HKII pathway, followed by a reduction of the translocation of Bax and release of cytochrome c, caspase-9 and caspase-3 activation and myocyte apoptosis. Knockdown the expression of Dhcr24 reduces the activation of PI3K/Akt/HKII pathway and inhibition of the mitochondrial-dependent apoptosis. The anti-apoptotic effect of Dhcr24 could be completely removed by the inhibition of PI3K pathway and partly removed by the HKII inhibitor in H9c2 cell line.Conclusion: Compensatory expression of Dhcr24 protect against DCM through activated PI3K/Akt/HKII pathway and reduce Bax translocation. This is the first investigation for the molecular mechanism of Dhcr24 participate in development of DCM.

Rehmannia glutinosa exhibits anti-aging effect through maintaining the quiescence and decreasing the senescence of hematopoietic stem cells

Background: The time-related decline in regenerative capacity and organ homeostasis is a major feature of aging. Rehmannia glutinosa and Astragalus membranaceus have been used as traditional Chinese herbal medicines for enhanced immunity and prolonged life. However, the mechanism by which this herbal medicine slows aging is unknown. In this study, we investigated the mechanism of the herbal anti-aging effect.Methods: Mice were fed diets supplemented with R. glutinosa or A. membranaceus for 10 months; the control group was fed a standard diet. The phenotypes were evaluated using a grading score system and survival analysis. The percentages of the senescence phenotypes of hematopoietic stem cells(HSCs) were determined by fluorescence-activated cell sorting analysis. The function and the mechanism of HSCs were analyzed by clonogenic assay and the real-time polymerase chain reaction.Results: The anti-aging effect of R. glutinosa is due to the enhanced function of HSCs. Mice fed with R. glutinosa displayed characteristics of a slowed aging process,including decreased senescence and increased rate of survival. Flow cytometry analysis showed decreased numbers of Lin–Sca1^+c-kit–(LSK) cells, long-term HSCs(LT-HSCs) and short-term HSCs(ST-HSCs) in the R. glutinosa group. In vitro, clonogenic assays showed increased self-renewal ability of LT-HSCs from the R. glutinosa group as well as maintaining LSK quiescence through upregulated p18 expression. The R. glutinosa group also showed decreased reactive oxygen species levels and the percentage of β-gal^+ cells through downregulation of the cellular senescence-associated protein p53 and p16.Conclusion: Rehmannia glutinosa exerts anti-aging effects by maintaining the quiescence and decreasing the senescence of HSCs.

Exposure to gastric juice may not cause adenocarcinogenesis of the esophagus

AIM: To determine the effects of gastric juice on the development of esophageal adenocarcinoma (EAC). METHODS: A animal model of duodenogastroesophageal reflux was established in Sprague-Dawley rats undergoing esophagoduodenostomy. The development of EAC and forestomach adenocarcinoma was investigated 40 wk after the treatment. Intraluminal pH and bile of the forestomach were measured. RESULTS: There were no significant differences in pH (t=0.117, P=0.925) or bile (χ2=0.036, P=0.85) in the forestomach before and 40 wk after esophagoduodenostomy. There were also no significant differences between the model and controls during esophagoduodenostomy or 40 wk after esophagoduodenostomy. The incidence of intestinal metaplasia (88%) and intestinal metaplasia with dysplasia and adenocarcinoma (28%) in the esophagus in the model was higher than in the controls 40 wk after surgery (χ2=43.06, P < 0.001 and χ2=9.33, P=0.002, respectively) and in the forestomach in the model (χ2=32.05, P < 0.001 and χ2=8.14, P=0.004, respectively). The incidence rates of inflammation in the esophagus and forestomach were 100% and 96%, respectively (χ2=1.02, P=0.31) in the model, which was higher than in the esophageal control (6.8%) (χ2=42.70, P < 0.001). CONCLUSION: Gastric juice exposure may not cause intestinal metaplasia with dysplasia or adenocarcinoma of the forestomach and may not be related to EAC.

In vivo real-time imaging of gemcitabine-leaded growth inhibition in the orthotopic transplantation model of human pancreatic tumor

Human xenograft mouse models,which have been used in cancer research for over a century,provided significant advances for our understanding of this multifaceted family of diseases.Orthotopic transplantation tumor models are emerging as the preference for cancer research due to the increasing clinical relevance over subcutaneous mouse models.In this study,a stable luciferaseexpressed Capan-2 cell line was constructed and the expression of luciferase was tested.The results showed that the luminorescence intensity of Capan-2^(Luc) cells was associated with the number of cells and the minimal detectable cell population was 600 cells/well.We established an orthotopic transplantation model of pancreatic cancer using Capan-2^(Luc) cell line in athymic mice and investigated the inhibitory effects of gemcitabine(Gem)in vitro and in vivo.Optical imaging system was applied to evaluate the tumor growth of orthotopic transplantation model in vivo.The results suggested that the orthotopic transplantation model of pancreatic cancer was well established and the luminorescence intensity of Gem-treated group was markedly lower than that of control group with an inhibitory rate of 56.8%(P<0.001).Our orthotopic transplantation model of pancreatic cancer and real-time imaging observation method established in this study could be an ideal model and a useful tool for therapeutic approaches for pancreatic cancers.

Wild-type p53-induced Phosphatase I Deficiency Exacerbates Myocardial Infarction-induced Ischemic Injury

Background： Myocardial infarction （MI） is a major disease burden. Wild-type p53-induced phosphatase 1 （Wipl） has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wipl in cardiac adaptation to M I is unknown. We investigated the significance of Wipl in a mouse model of MI. Methods： The study began in June 2014 and was completed in July 2016. We compared Wipl-knockout （Wipl-KO） mice and wild-type （WT） mice to deternline changes in cardiac function and survival in response to MI. The heart weight/body weight （HW/BW） ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending （LAD） coronary artery under 1.5% isoflurane anesthesia. After M1, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin （H＆E） staining was used to determine the infarct size. Gene expression of interleukin-6 （IL-6）, turnor necrosis factor-α （TNF-α）, and interleukin-1β （IL-1β） was assessed by quantitative real-time polymerase chain reaction （qPCR）, and the levels of signal transducers and activators of transcription 3 （stat3） and phosphor-stat3 （p-stat3） were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired l-test, and one-way analysis of variance （ANOVA） were used for statistical analyses. Results： Wipl-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac fiinction before LAD ligation. Alter MI, Wipl-deficient mice exhibited increased mortality （57.14% vs. 29.17%; n = 24 [WT], n - 35 [WipI-KO], P 〈 0.05）, increased cardiac hypertrophy （HW/BW ratio： 7 days： 7.25±0.36 vs. 5.84 ± 0.18, n cross-sectional area： 7 days： 311.80 ± 8.29 vs. 268.90 ± 11.15, n P 〉 0.05）, and reduced cardiac function （ejection fraction： 7 days 10, p〈 0.01, and 4 weeks： 6.05± 0.17 vs. 5.87 ±0.24, n= 10, P〉0.05; P 〈 0.05, and 4 weeks： 308.80 ± 11.26 vs. 317.00 ±13.55, n = 6 29.37± 1.38 vs. 34.72 ± 1.81, P 〈 0.05, and 4 weeks： 19.06 ± 2.07 vs 26.37 ± 2.95, P〈 0.05; fractional shortening： 7 days： 13.72 ± 0.71 vs. 16.50 ± 0.94, P〈 0.05, and 4 weeks： 8.79 ±1.00 vs. 12.48 ±1.48, P 〈 0.05; n = l0 [WT], n = 15 [Wipl-KO]）. H＆E staining revealed a larger infarct size in Wipl-KO mice than in WT mice （34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P 〈 0.01 ）. The expression oflL-6 and p-stat3 was downregulated in Wipl-KO mice （IL-6：1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P 〈 0.01 ; and p-stat3/stat3：1.15 ±0.15 vs. 1.97 ± 0.23, n = 6, P 〈 0.05）. Conclusion： The results suggest that Wipl could protect the heart from MI-induced ischemic injury.