ABSTRACT
The incidence of intrahepatic cholangiocarcinoma has been increasing worldwide in recent years. Hepatectomy is the first choice for surgical treatment of intrahepatic cholangiocarcinoma. However, due to high tumor invasion, early lymph node metastasis and other factors, only less than 30% of cases are resectable, and the overall prognosis of patients is very poor. Theoretically, liver transplantation can not only remove the tumor, but also replace the damaged liver. Therefore, many scholars have proposed liver transplantation for the treatment of intrahepatic cholangiocarcinoma in order to obtain better results. Intrahepatic cholangiocarcinoma was once listed as a contraindication of liver transplantation due to limited cases, tumor recurrence, and shortage of donors. However, with the optimization of recipient screening criteria and the development of neoadjuvant therapy, part of patients can also benefit from it, making liver transplantation a potential therapeutic strategy. Based on the literature review and the author′s experience, this article introduced the current situation of surgical treatment of intrahepatic cholangiocarcinoma, the comparison between hepatectomy and liver transplantation, the latest progress of liver transplantation treatment and the future challenges and solutions.
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With the increasing number of patients waiting for liver transplantation worldwide, the development of living donor liver transplantation can not only alleviate the shortage of donor liver, but also expand the donor pool. Compared with classical liver transplantation, living donor liver transplantation is more complex and delicate in surgical operation, with many problems to be further discussed and solved. The authors retrospectively analyze relevant research results, combined with clinical practice, investigate the selection and evaluation of donor, selection of donor liver, surgical innovation and treatment of hepatocellular carcinoma in living donor liver transplan-tation, in order to provide helps for alleviating the shortage of donor liver and improving the prognosis of recipients.
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The purpose of this study was to investigate how Zuogui pills from the Kidney-tonifying and Nourishing Yin formula, in combination with the gonadotrophin-releasing hormone antagonist cetrorelix, affected the ovarian local oxidative stress response in decreasing ovarian reserve (DOR) mice. All animal experiments were carried out in accordance with the guidelines and standards established by Jinan University's Experimental Animal Management Committee. Cyclophosphamide (CTX)-treated DOR mice were given Zuogui pills, cetrorelix, or a combination of the two drugs intragastrically. After treatment, there were changes in the estrous cycle, serum sex hormone levels, oxidative stress-related indexes, growth biochemical factor levels, and SIRT1/P53/P21 expression. In comparison to the model group, the Zuogui pills and the cetrorelix+Zuogui pills group had significantly prolonged estrous periods and shortened interestrous periods, and the cetrorelix+Zuogui pills group had a significantly shortened cycle length. Follicle-stimulating hormone (FSH) decreased and estradiol (E2) increased in all treatment groups compared to the model group, oxidative stress indexes nitric oxide synthase (NOS), nitric oxide (NO), and reactive oxygen species (ROS) decreased, growth biochemical factors brain derived neurotrophic factor (BDNF) and growth differentiation factor 9 (GDF-9) concentrations increased significantly, and leukemia inhibitory factor (LIF) showed no significant change. SIRT1/P53/P21 immunohistochemical results revealed that, when compared to the model group, the expression of SIRT1 increased while the expression of P53 and P21 proteins decreased in all treatment groups, with the cetrorelix+Zuogui pills group having the largest decrease, with significant differences in all indicators. We conclude that cetrorelix combined with Zuogui pills for kidney nourishing and Yin recipe improved the oxidative stress response in the follicle by regulating the SIRT1/P53/P21 pathway, reducing peroxide product production, protecting ovarian function, and regulating ovarian hormone secretion, and its efficacy is superior to that of cetrorelix or Zuogui pills alone.
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Three sesquiterpenoids were isolated and purified from the 95% ethanol extract of Atractylodis Macrocephalae Rhizoma by column chromatography on silica gel, Sephadex LH-20, ODS, and high-performance liquid chromatography(HPLC). Their chemical structures were identified on the basis of spectroscopic analysis and physiochemical properties as(7Z)-8β,13-diacetoxy-eudesma-4(15),7(11)-diene(1), 7-oxo-7,8-secoeudesma-4(15),11-dien-8-oic acid(2), and guai-10(14)-en-11-ol(3). Compounds 1 and 2 are new compounds and compound 3 was obtained from Compositae family for the first time. Compounds 1, 2, and 3 showed weak inhibitory activities against sterol regulatory element-binding proteins(SREBPs).
Subject(s)
Atractylodes/chemistry , Drugs, Chinese Herbal/chemistry , Rhizome/chemistry , Sesquiterpenes, Eudesmane/pharmacology , Sterol Regulatory Element Binding Proteins/antagonists & inhibitorsABSTRACT
@#【Objective】To measure the orbital fat fraction（FF）of Graves ophthalmopathy（GO）patients and normal individuals with MR Water- fat separation（Dixon） technology ，and to explore the value of orbit MR quantitative fat analysis in diagnosis and treatment for GO patients.【Methods】Forty GO patients and 20 normal individuals who underwent orbital MR imaging were analyzed prospectively from February 2017 to February 2019 in the First Affiliated Hospital of Sun Yat- sen University. All participants received bilateral orbital MR examination with oblique coronary FSE T2- weighted imaging combined with two-point Dixon technique，and then the signal intensity values of ipsilateral extraocular muscles and lacrimal glands on water and fat phase images were measured to calculate FF. The differences of mean FF between the two groups were evaluated，and the correlation between FF of GO and TRAb，CAS score，and the course of GO were conducted by Spearman rank correlation analysis. 【Results】 The median FF of extraocular muscles in GO patients was higher than that of normal individuals，and the result showed a statistically significant difference（P < 0.05）， while the FF of lacrimal glands in the two groups showed no statistical difference. The FF of extraocular muscles in the GO group were correlated with TRAb，CAS score and the course of GO（P < 0.05），especially the course was more correlative.【Conclusions】The fat content of extraocular muscles in GO patients were higher than that of normal individuals ，and there was a positive correlation in the fat content among TRAb，CAS score and the course of GO，suggesting that MR fat quantitative analysis may provide a new reference indexes for the evaluation of clinical staging ，curative effect assessment in GO patients.
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Because of a limited capacity of information processing in the brain, the efficient processing of visual information requires selecting only a very small fraction of visual inputs at any given moment in time. Attention is the main mechanism that controls this selection process, namely selective attention. Selective attention is the mechanism by which the subset of incoming information is preferentially processed from the complex external environment. Research on selective attention has two key issues. One is what targets (inputs) are selected by attention. There are three different types of selective attention according to its selected target: space-based, feature-based, and object-based attention. Another issue is how selective attention is generated. There are two different types of selective attention according to its generating source: top-down and bottom-up attention. In this review, these two issues are introduced to systematically discuss the neural mechanism of visual selective attention.
Subject(s)
Humans , Attention , Brain , Physiology , Cognition , Visual PerceptionABSTRACT
PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p 0 copy/mL, GTVtotal 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Subject(s)
Humans , Biomarkers , Cohort Studies , DNA , Herpesvirus 4, Human , Lymph Nodes , Nasopharynx , Plasma , Prognosis , Radiotherapy , Tumor BurdenABSTRACT
Objective To investigate the clinical value of liver transplantation for intrahepatic cholangiocarcinoma (ICC).Methods A retrospective analysis was performed on 68 patients with ICC who underwent hepatic resection or liver transplantation between January 2007 and September 2013.In the surgical treatment of ICC,overall survival and prognostic risk factors were analyzed to determine the clinical value of liver transplantation for ICC compared with hepatic resection.Results Of the patients with ICC,55 underwent hepatic resection and 13 were given liver transplantation.The 1 and 3-year survival rate was significantly higher in the liver transplantation group than in the hepatic resection group (76.9％ versus 52.7％,and 61.5％ versus 27.3％,P＜0.05).In addition,liver transplantation resulted in higher tumor recurrence-free survival rate than hepatic resection (69.2％ versus 41.8％,and 61.5％ versus 20.0％,P＜0.05).The multivariate analysis showed that tumor size larger than 5 cm was an independent risk factor and HBV infection was an independent protective factor of ICC.Conclusion The prognosis of patients who underwent liver transplantation was better than hepatic resection,suggesting that liver transplantation is perhaps a prior treatment in strictly selected and unresectable patients with ICC.
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Cholangiocarcinoma (CCA) is a malignant neoplasm derived from cholangiocytes. The incidence of CCA is only lower than that of hepatocellular carcinoma and ranked the second in liver malignant cancers. The prognosis of CCA patients is poor and most patients will die within a few months after diagnosis. CCA is related to various risk factors, including primary sclerosing cholangitis, cirrhosis, certain chemical agents and liver fluke. Establishment of proper animal models of CCA can not only be helpful for understanding the mechanisms of incidence and development, but also lay a solid foundation for developing novel treatment strategies. Common animal models of CCA include carcinogen-induced models, implantation models, operation models, and genetically engineered models.
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Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.