ABSTRACT
Iron is essential to organisms, the liver plays a vital role in its storage. Under pathological conditions, iron uptake by the intestine or hepatocytes increases, allowing excess iron to accumulate in liver cells. When the expression of hepcidin is abnormal, iron homeostasis in humans cannot be regulated, and resulting in iron overload. Hepcidin also regulates the release of iron from siderophores, thereby regulating the concentration of iron in plasma. Important factors related to hepcidin and systemic iron homeostasis include plasma iron concentration, body iron storage, infection, inflammation, and erythropoietin. This review summarizes the mechanism and regulation of iron overload caused by hepcidin, as well as related liver diseases caused by iron overload and treatment.
Subject(s)
Digestive System Diseases , Iron Overload , Liver Diseases , Humans , Hepcidins , Iron/metabolism , Liver/pathology , Liver Diseases/metabolismABSTRACT
Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.
Subject(s)
Anesthetics, Local , Hepatectomy , Anesthetics, Local/therapeutic use , Double-Blind Method , Hepatectomy/adverse effects , Humans , Morphine/therapeutic use , Pain Measurement , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Ultrasonography, InterventionalABSTRACT
OBJECTIVE: Shortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo. DESIGN: 3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production. RESULTS: 3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah-/-Rag2-/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice. CONCLUSIONS: Our results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.
Subject(s)
Bioprinting/methods , Liver Failure/surgery , Liver Transplantation/methods , Liver/cytology , Liver/metabolism , Printing, Three-Dimensional , Animals , Cell Differentiation , Cell Proliferation , Cell Survival , Disease Models, Animal , Graft Survival , Liver Function Tests , Mice , Survival RateABSTRACT
Hepatic reactive lymphoid hyperplasia (RLH) is a rare benign tumor of the liver that exhibits similar imaging characteristics to those of other hepatic malignant tumors; therefore, it requires novel biomarkers to be differentiated from the other tumors. A 69-year-old female was found to have a mass in the liver and was admitted to Peking Union Medical College Hospital for further evaluation. Most laboratory tests, including liver function tests, tumor biomarkers, and autoimmune markers were within normal range, except for positive antinuclear antibody and anti-smooth muscle antibody (SMA) tests. Diagnostic imaging, including ultrasonography, computerized tomography and magnetic resonance imaging displayed a small hepatic mass suggestive of hepatocellular carcinoma (HCC). Partial hepatectomy was performed, and histological diagnosis suggested RLH. Postoperative treatments included anti-infection, nutritional enhancement and liver protection. The suspicion of autoimmune hepatitis could not be confirmed. No recurrence or autoimmune disease was observed over 6-month follow-up. Positive anti-nuclear antibody (ANA) and anti-SMA may be potential biomarkers for hepatic RLH.
ABSTRACT
AIM: To investigate the prognostic role of fibrinogen-to-albumin ratio (FAR) on patients with gallbladder cancer (GBC) in this study. METHODS: One hundred and fifty-four GBC patients were retrospectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve (ROC curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses. RESULTS: ROC curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age (P = 0.045), jaundice (P < 0.001), differentiation (P = 0.002), resection margin status (P < 0.001), T stage (P < 0.001), TNM stage (P < 0.001), and CA199 (P < 0.001) as well as albumin levels (P < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio (HR): 2.343, 95% confidence interval (CI): 1.532-3.581, P < 0.001], TNM stage (P = 0.035), albumin level (HR = 0.595, 95%CI: 0.385-0.921, P = 0.020) and FAR (HR: 2.813, 95%CI: 1.765-4.484, P < 0.001) were independent prognostic factors in GBC patients. CONCLUSION: An elevated preoperative FAR was significantly correlated with unfavorable overall survival in GBC patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with GBC. The preoperative FAR could be used to predict the prognosis of GBC patients, which was easily accessible, cost-effective and noninvasive.
Subject(s)
Biomarkers, Tumor/blood , Fibrinogen/analysis , Gallbladder Neoplasms/blood , Serum Albumin/analysis , Adult , Aged , Aged, 80 and over , Cholecystectomy , Feasibility Studies , Female , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/surgery , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Preoperative Period , Prognosis , ROC Curve , Retrospective Studies , Risk FactorsABSTRACT
AIM: To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width (RDW) in esophageal cancer (EC). METHODS: We searched the PubMed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible: (1) Studies including EC patients who underwent radical esophagectomy; (2) studies including patients with localized disease without distant metastasis; (3) studies including patients without preoperative neoadjuvant therapy; (4) studies including patients without previous antiinï¬ammatory therapies and with available preoperative laboratory outcomes; (5) studies reporting association between the preoperative RDW and overall survival (OS)/disease-free survival (DFS)/cancer-specific survival (CSS); and (6) studies published in English. RESULTS: A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 0.97-1.57, P = 0.000] or DFS (HR = 1.42, 95%CI: 0.96-1.88, P = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13% (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000), when the patient number ≤ 400 (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) and when the study type was retrospective (HR = 1.42, 95%CI : 1.16-1.69, P = 0.000). CONCLUSION: Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value.
Subject(s)
Adenocarcinoma/blood , Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Erythrocyte Indices , Esophageal Neoplasms/blood , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Disease-Free Survival , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma , Esophagectomy , Esophagus/pathology , Esophagus/surgery , Humans , Neoadjuvant Therapy/methods , Prognosis , Proportional Hazards Models , Survival RateABSTRACT
BACKGROUND: Thermally significant blood flows into locally cooled diseased tissues and warm them during cryosurgery so that the iceball is often hard to cover the whole diseased volume. This paper is aimed at investigating the effects of large arterial bifurcation on the temperature distribution during cryosurgery through simulation method. METHODS: A parametric geometry model is introduced to construct a close-to-real arterial bifurcation. The three-dimensional transient conjugate heat transfer between bifurcated artery and solid tissues with phase change during cryosurgery is performed by finite volume method. RESULTS: The discussion was then made on the effects of the relative position between cryoprobe and artery bifurcation, the inlet velocity of root artery and the layout of multiple cryoprobes on the temperature distribution and iceball evolution. The results show that the thermal interaction between blood flow and iceball growth near bifurcation is considerable complex. The thermal effects of bifurcation could modulate the iceball morphology, severely weaken its freezing volume and prevent the blood vessel from being frozen. CONCLUSION: The present work is expected to be valuable in optimizing cryosurgery scheme of the situation that the bifurcated artery is embedded into the disease tissue.
Subject(s)
Arteries/anatomy & histology , Computer Simulation , Cryosurgery , Temperature , Arteries/physiology , Hemodynamics , Ice , Models, BiologicalABSTRACT
Circular RNAs (circRNAs) are pervasively expressed circles of noncoding RNAs. Even though many circRNAs have been reported in humans, their expression patterns and functions remain poorly understood. In this study, we employed a pipeline named RAISE to detect circRNAs in RNAseq data. RAISE can fully characterize circRNA structure and abundance. We evaluated inter-individual variations in circRNA expression in humans by applying this pipeline to numerous nonpoly(A)-selected RNAseq data. We identified 59,128 circRNA candidates in 61 human liver samples, with almost no overlap in the circRNA of the recruited samples. Approximately 89% of the circRNAs were detected in one or two samples. In comparison, 10% of the linear mRNAs and noncoding RNAs were detected in each sample. We estimated the variation in other tissues, especially the circRNA high-abundance tissues, in advance. Only 0.5% of the 50,631 brain circRNA candidates were shared among the 30 recruited brain samples, which is similar to the proportion in liver. Moreover, we found inter- and intra-individual diversity in circRNAs expression in the granulocyte RNAseq data from seven individuals sampled 3 times at one-month intervals. Our findings suggest that careful consideration of inter-individual diversity is required when extensively identifying human circRNAs or proposing their use as potential biomarkers and therapeutic targets in disease.
Subject(s)
RNA/biosynthesis , Animals , Brain/metabolism , Brain/physiology , Brain Chemistry , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Gene Expression Profiling/methods , Granulocytes/chemistry , Granulocytes/physiology , Humans , Individuality , Liver/chemistry , Liver/metabolism , Liver/physiology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Mice , RNA/analysis , RNA/genetics , RNA, Circular , RNA, Long Noncoding/analysis , RNA, Long Noncoding/biosynthesis , RNA, Long Noncoding/genetics , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Sequence Analysis, RNA , TranscriptomeABSTRACT
Knowledge of the collagen structure of an Achilles tendon is critical to comprehend the physiology, biomechanics, homeostasis and remodelling of the tissue. Despite intensive studies, there are still uncertainties regarding the microstructure. The majority of studies have examined the longitudinally arranged collagen fibrils as they are primarily attributed to the principal tensile strength of the tendon. Few studies have considered the structural integrity of the entire three-dimensional (3D) collagen meshwork, and how the longitudinal collagen fibrils are integrated as a strong unit in a 3D domain to provide the tendons with the essential tensile properties. Using second harmonic generation imaging, a 3D imaging technique was developed and used to study the 3D collagen matrix in the midportion of Achilles tendons without tissue labelling and dehydration. Therefore, the 3D collagen structure is presented in a condition closely representative of the in vivo status. Atomic force microscopy studies have confirmed that second harmonic generation reveals the internal collagen matrix of tendons in 3D at a fibril level. Achilles tendons primarily contain longitudinal collagen fibrils that braid spatially into a dense rope-like collagen meshwork and are encapsulated or wound tightly by the oblique collagen fibrils emanating from the epitenon region. The arrangement of the collagen fibrils provides the longitudinal fibrils with essential structural integrity and endows the tendon with the unique mechanical function for withstanding tensile stresses. A novel 3D microscopic method has been developed to examine the 3D collagen microstructure of tendons without tissue dehydrating and labelling. The study also provides new knowledge about the collagen microstructure in an Achilles tendon, which enables understanding of the function of the tissue. The knowledge may be important for applying surgical and tissue engineering techniques to tendon reconstruction.
Subject(s)
Achilles Tendon/ultrastructure , Collagen/ultrastructure , Imaging, Three-Dimensional/methods , Second Harmonic Generation Microscopy/methods , Animals , Microscopy, Atomic Force , RabbitsABSTRACT
Gallbladder cancer (GBC), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. The late diagnosis and abysmal prognosis present challenges to treatment. The overall 5-year survival rate for metastatic GBC patients is extremely low. BRCA1 and BRCA2 are the breast cancer susceptibility genes and their mutation carriers are at a high risk for cancer development, both in men and women. Olaparib, an oral poly ADP-ribose polymerase inhibitor, has been approved by the Food and Drug Administration and the European Commission for the treatment of ovarian cancer with any BRCA1/2 mutations. The first case of a BRCA1-mutated GBC patient who responded to olaparib treatment is reported here.
Subject(s)
Antineoplastic Agents/therapeutic use , Gallbladder Neoplasms/drug therapy , Genes, BRCA1 , Liver Neoplasms/drug therapy , Phthalazines/therapeutic use , Piperazines/therapeutic use , Aged , Gallbladder Neoplasms/diagnostic imaging , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/pathology , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Male , Mutation , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Combined hepatocellular cholangiocarcinoma (CHC) accounts for 0.4%-14.2% of primary liver cancer cases and possesses pathological features of both hepatocellular carcinoma and cholangiocarcinoma. Since this disease was first described and classified in 1949, the classification of CHC has continuously evolved. The latest definition and classification of CHC by the World Health Organization is based on the speculation that CHC arises from hepatic progenitor cells. However, there is no evidence demonstrating the common origin of different components of CHC. Furthermore, the definition of CHC subtypes is still ambiguous and the identification of CHC subtype when a single tumor contains many components has remained unresolved. In addition, there is no summary on the newly recognized histopathology features or the contribution of CHC components to prognosis and outcome of this disease. Here we provide a review of the current literature to address these questions.