MicroRNA-7-5p Inhibits Migration,Invasion and Metastasis of Intrahepatic Cholangiocarcinoma by Inhibiting MyD88

Background and AimsIntrahepatic cholangiocarcinoma (ICC) is a malignant tumor derived from intrahepatic bile duct epithelial cells. Accumulating studies report that microRNAs are widely involved in tumor migration and metastasis by regulation of target genes. miR-7-5p has been confirmed to inhibit tumor metastasis and to be related to prognosis for several malignant tumors. Our study investigated the underlying functions of miR-7-5p in ICC.MethodsThe expression of miR-7-5p in ICC tissues but also in ICC cell lines was analyzed by real-time PCR. By analyzing the relationship between the clinicopathological parameters of 60 ICC patients and the expression level of miR-7-5p, the effect of miR-7-5p on the prognosis was clarified. After transfected with miR-7-5p mimics or miR-7-5p inhibitor, cell counting kit-8 assay was applied to evaluate the cells proliferation, flow cytometry was applied to analyze the cells apoptosis, wound healing assay and transwell chamber assay were applied to analyze the cell invasion and migration. A luciferase reporter assay was identified the relationship of miR-7-5p and myeloid differentiation factor 88 (MyD88). Western blotting was used to analyze the proteins expression. And immunochemistry was performed to determine the expression of MYD88 in ICC tissues.ResultsOur data showed the expression of miR-7-5p was down-regulated not only in ICC tissues but also in ICC cell lines compared with normal controls. Low expression of miR-7-5p was notably associated with poor prognosis in ICC patients. miR-7-5p negatively regulated cell proliferation, migration, invasion and apoptosis in ICC cells. We further verified that MyD88 was a novel target of miR-7-5p and was significantly overexpressed in ICC tissues. Overexpression of MyD88 counteracted the effects of miR-7-5p in ICC cells.ConclusionsThe present findings suggest that miR-7-5p plays a pivotal role in ICC invasion by regulating MyD88. Ampliative insight into the key factors of ICC invasion may result in the development of new treatment options for ICC.     

消化道肿瘤的"3P":预测、预防和个性化治疗

当今人类疾病的防治模式已发生了革命性的变化，国家中长期科学和技术发展规划纲要第8点人口与健康中发展思路的第2小点明确指出：疾病防治重心前移，坚持预防为主、促进健康和防治疾病结合：研究预防和早期诊断关键技术，显著提高重大疾病诊断和防治能力。因此，预测（prediction）、预防（prevention）和个性化治疗（personalized therapy）这“3P”成为医学研究领域的热门话题。据此，消化道肿瘤防治研究的重点也应转向以下几个方面：①预测：应用基因单核苷酸多态性（singlenucleotidepolymorphism，SNP）预测易感人群。     

Disseminated Carcinomatosis of Bone Marrow as the Initial Presentation of Intrahepatic Cholangiocarcinoma without Jaundice: An Autopsy Case Report

Disseminated carcinomatosis of the bone marrow (DCBM) is often accompanied by disseminated intravascular coagulation (DIC) and has a poor prognosis. DCBM develops most frequently in gastric cancer and is rarely associated with intrahepatic cholangiocarcinoma. A 41-year-old man was incidentally found to have DIC on his regular visit for ulcerative colitis and was diagnosed with DCBM with intrahepatic cholangiocarcinoma. He received intensive care, including chemotherapy, but died suddenly from hyperkalemia, possibly due to tumor lysis syndrome (TLS). The autopsy showed the periductal infiltrating type of intrahepatic cholangiocarcinoma and tumor necrosis, possibly due to chemotherapy, indicating the effectiveness of chemotherapy for DCBM with intrahepatic cholangiocarcinoma.     

丹参酮IIA通过调控自噬抑制乏氧诱导的肝内胆管细胞癌侵袭能力的研究

目的:探讨在乏氧状态下,丹参酮ⅡA对肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)自噬的调控,以及对侵袭能力的影响及其机制。方法:通过1%O_2培养建立肝内胆管细胞癌ICC-9810细胞乏氧状态,应用丹参酮ⅡA干预细胞后,通过划痕试验检测ICC-9810细胞迁移能力,趋化试验及侵袭试验检测细胞的趋化与侵袭能力;转染p GFP-LC3质粒后,应用荧光显微镜观察LC3融合蛋白及自噬小体在ICC-9810细胞中的表达情况,蛋白质印迹法检测ICC-9810细胞中的HIF-1α、自噬相关蛋白LC3Ⅱ/I和Beclin1表达差异。结果:在乏氧环境下,ICC-9810细胞运动能力增强(1.75±0.3)倍,趋化能力增加79.6%,侵袭力增强1.36倍,细胞自噬水平明显升高,丹参酮ⅡA干预后ICC-9810细胞自噬水平下调,HIF-1α、LC3Ⅱ/I和Beclin1蛋白表达水平分别降低3.9倍,2.4倍和1.1倍,侵袭能力下降4.7倍。结论:丹参酮ⅡA可以通过下调自噬,抑制肝内胆管癌细胞在乏氧条件下异常增高的侵袭力。     

Hepatocellular Carcinoma with Invasion of the Right Intrahepatic Bile Duct Observed by Peroral Cholangioscopy: a Case Report

A 48-year-old chronic alcoholic with previous hepatitis B virus infection presented with recurrent episodes of obstructive jaundice secondary to hepatocellular carcinoma. The obstructive nature of the jaundice was confirmed by the peroral cholangioscopic findings of a friable nodular mass partially obstructing the right hepatic duct, and by relief of obstructive signs and symptoms after endoscopic sphincterotomy freed the common bile duct of “dark greenish formed materials”.     

Clinical Significance of Abnormal Prothrombin (DCP) in Relation to Postoperative Survival and Prognosis in Patients with Hepatocellular Carcinoma

Objectives: In this study we correlate plasma des-y-carboxy prothrombin (DCP) levels with prognosis in patients with hepatocellular carcinoma (HCC) in combination with serum a-fetoprotein levels (AFP). Methods: Levels of DCP were measured in 165 patients with HCC by an enzyme immunoassay (EIA, E-1023) with an anti-DCP monoclonal antibody. Results: There was no correlation between the plasma DCP levels and the serum AFP levels. The positive rate obtained from the combination assay was 72.1%. The survival rates of the patients with elevated levels of both DCP and AFP were significantly lower than those of the groups with normal DCP and AFP levels ( P < 0.05). The disease-free survival rates of patients with elevated DCP and AFP levels were also significantly lower than those of patients with normal DCP and AFP levels ( P < 0.05). The recurrence rate within a postoperative period of 2 yr was higher in the patients with elevated DCP and AFP levels than in those with normal levels. Conclusions: The determination of plasma DCP levels combined with AFP levels appears to be useful for the diagnosis and prognosis of HCC, and is useful also in postoperative monitoring for recurrence.     

Prediction of Pulmonary Arterial Pressure Level after Repair of Congenital Cardiac Communications and Discharge from the Hospital: Role of Down Syndrome and Early Postoperative Hemodynamics

Background: Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications. Identifying patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up strategies. Methods: We analyzed a prospective cohort of 52 pediatric patients (age 3 to 35 months) looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery, defined as a systolic pressure greater than 30 mmHg by transthoracic echocardiography. This corresponds to a mean pulmonary arterial pressure of >20 mmHg. Clinical, echocardiographic and hemodynamic parameters were investigated. Perioperative hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling catheters. Early postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio (PAP/SAP) obtained per patient during the first 6 h of postoperative care. Results: Among the factors that were investigated as possible predictors, perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis (p < 0.030). Early postoperative PAP/SAP was correlated with PAP/SAP obtained in the operating room just after cardiopulmonary bypass (r = 0.70, p < 0.001), and it was higher in subjects with Down syndrome than in nonsyndromic individuals (p = 0.003). Early postoperative PAP/SAP was the only predictor selected using multivariate analysis. It was characterized as an independent predictor after adjustments for possible confounders. An early postoperative PAP/SAP of >0.35 was 76% sensitive and 74% specific at predicting a systolic pulmonary arterial pressure of >30 mmHg 6 months after surgery (hazard ratio with 95% CI 8.972 [2.428–33.158], p = 0.002). Conclusion: The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome, and it was characterized as an independent predictor of altered pulmonary arterial pressure after discharge from the hospital.     

Measuring Prognosis and Case Mix in Hospitalized Elders: The Importance of Functional Status

OBJECTIVE: Although physical function is believed to be an important predictor of outcomes in older people, it has seldom been used to adjust for prognosis or case mix in evaluating mortality rates or resource use. The goal of this study was to determine whether patients' activity of daily living (ADL) function on admission provided information useful in adjusting for prognosis and case mix after accounting for routine physiologic measures and comorbid diagnoses. SETTING: The general medical service of a teaching hospital. PARTICIPANTS: Medical inpatients (n = 823) over age 70 (mean age 80.7, 68% women). MEASUREMENTS: Independence in ADL function on admission was assessed by interviewing each patient's primary nurse. We determined the APACHE II Acute Physiology Score (APS) and the Charlson comorbidity score from chart review. Outcome measures were hospital and 1-year mortality, nursing home use in the 90 days following discharge, and cost of hospitalization. Patients were divided into four quartiles according to the number of ADLs in which they were dependent. MAIN RESULTS: ADL category stratified patients into groups that were at markedly different risks of mortality and higher resource use. For example, hospital mortality varied from 0.9% in patients dependent in no ADL on admission, to 17.4% in patients dependent in all ADLs. One-year mortality ranged from 17.5% to 54.9%, nursing home use from 3% to 33%, and hospital costs varied by 53%. In multivariate analyses controlling for APS, Charlson scores, and demographic characteristics, compared with patients dependent in no ADL, patients dependent in all ADLs were at greater risk of hospital mortality (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.1-58.8), 1-year mortality (OR 4.4; 2.7-7.4), and 90-day nursing home use (OR 14.9; 6.0-37.0). The DRG-adjusted hospital cost was 50% higher for patients dependent in all ADLs. ADL function also improved the discrimination of hospital and 1-year mortality models that considered APS, or Charlson scores, or both. CONCLUSIONS: ADL function contains important information about prognosis and case mix beyond that provided by routine physiologic data and comorbidities in hospitalized elders. Prognostic and case-mix adjustment methods may be improved if they include measures of function, as well as routine physiologic measures and comorbidity.     

Evolving Anatomic, Functional, and Molecular Imaging in the Early Detection and Prognosis of Hypertrophic Cardiomyopathy

Evolving imaging modalities in hypertrophic cardiomyopathy (HCM), such as tissue Doppler, speckle tracking, measures of myocardial blood flow, and cardiac magnetic resonance with gadolinium enhancement, have advanced our understanding of the pathogenesis of myocardial dysfunction in hypertrophic cardiomyopathy. These modalities have the potential to differentiate HCM from other causes of left ventricular hypertrophy when there is uncertainty about the diagnosis and to identify affected individuals in the pre-clinical phase of the disease process. Furthermore, preliminary data suggests that functional imaging techniques may add incremental value to conventional risk stratification tools to identify individuals at high risk for sudden death or progression to congestive heart failure.     

Racial,Ethnic, and Age Disparities in Incidence and Survival of Intrahepatic Cholangiocarcinoma in the United States; 1995-2014

Introduction. Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014).Materials and methods. We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality.Results. Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year all-cause mortality (HR = 1.11, 95%CI: 1.05-1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07-1.24). Survival rates were poor also for individuals age 45 years or older, men, Blacks, and American Indians/Alaska Natives.Conclusion. The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.     

Racial,Ethnic, and Age Disparities in Incidence and Survival of Intrahepatic Cholangiocarcinoma in the United States; 1995-2014

Introduction and aim. Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014).Material and methods. We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality.Results. Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year all-cause mortality (HR = 1.11, 95%CI: 1.05-1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07-1.24). Survival rates were poor also for individuals age 45 years or older, men, and Blacks and American Indians/Alaska Natives. Conclusion.ConclusionThe results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.     

The Association Between Body Mass Index and the Prognosis and Postoperative Complications of Hepatocellular Carcinoma: A Meta-Analysis

Previous studies have reported the association between excess body mass index (BMI) and increased risk of hepatocellular carcinoma (HCC). However, whether BMI is associated with the prognosis and postoperative complications of HCC is still not clear.We searched PubMed and Embase for relevant studies published until the date of August 30, 2014. Additional studies were manually identified by searching reference lists of retrieved articles. Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) for overall survival (OS), disease-free survival (DFS), and risk ratios (RRs) with 95% CIs for postoperative complications were calculated using random effects or fixed effects models according to heterogeneities between studies.A total of 14 studies were included in the present meta-analysis. The pooled results showed that excess BMI was not significantly associated with improved OS (HR = 0.94; 95% CI: 0.74–1.19, P = 0.588) or DFS (HR = 0.93; 95% CI: 0.79–1.10, P = 0.382). In addition, higher BMI was not associated with increased rate of a number of complications including ascites (RR = 1.25, 95% CI: 0.94–1.65, P = 0.119), bile leaks (RR = 1.22, 95% CI: 0.81–1.83, P = 0.345), and 30-day mortality (RR = 1.05, 95% CI: 0.57–1.96, P = 0.871). However, HCC patients with higher BMI had increased incidence of wound infections (RR = 2.17, 95% CI: 1.28–3.68, P = 0.004).BMI was not an independent prognostic factor for the evaluation of the prognosis in HCC patients, and it was not associated with postoperative complications except for wound infections that as significantly associated with higher BMI scores.