Characterization of an imported HIV-1 A1/A7/G recombinant in China.

BACKGROUND: International migration has accelerated the HIV-1 spread across national borders, gradually reducing the restrictions on the geographical distribution of HIV-1 subtypes. Subtypes A and G are globally recognized as the third and sixth most dominant HIV-1 genotypes, mainly prevalent in Africa, but rarely detected in China. Here we reported an imported HIV-1 recombinant which was composed of sub-subtypes A1 and A7 of subtype A and subtype G genes in a Chinese female. This virus was the first HIV-1 recombinant including A7 genes reported in the world. CASE PRESENTATION: The near full-length genome (NFLG) was obtained from the plasma sample of the female in an HIV-1 molecular epidemiological survey with 853 participants in China. Phylogenetic analyses showed that this NFLG sequence contains three A7 segments, four G segments and one A1 segment with seven breakpoints, and all these segments were closely related to HIV-1 references circulating in Africa. The evidence from epidemiological investigation indicated that this female participant had a more-than-two-years heterosexual contact history with a fixed partner from Nigeria, a country in west Africa, which further supported the results of phylogenetic analyses. By the Bayesian phylogenetic analyses, the times of most recent common ancestors (tMRCA) of the partial pol gene (nt2308-3284, A7 region) and full-length vpr-vpu plus partial env gene (nt5534-6858, G region) were estimated around 1989 and 1984, respectively. CONCLUSIONS: In this study, by using the NFLG sequencing, we identified an imported HIV-1 A1/A7/G recombinant which was estimated to originate around 1980s in Africa and introduced into China with international migration. This study highlighted the complexity of the global HIV-1 epidemic, the necessity of using genome sequences to determine HIV-1 genotypes and the importance of real-time monitoring of HIV-1 infection among international migrants and travelers.

Switchable Synthesis of Spirodihydroindolizines and Indolizines from Aurones and Pyridin-2-yl Active Methylene Compounds.

A novel and flexible domino reaction of aurones with pyridin-2-yl active methylene compounds promoted by I2/BF3 has been developed to afford spirodihydroindolizines and indolizines in a controllable manner. When the reaction was performed in 1,2-dichloroethane at 80 °C, a variety of spirodihydroindolizines were obtained, whereas it almost exclusively provided a series of indolizines when the reaction was performed in a mixed solvent of 1,2-dichloroethane and N,N-dimethylformamide at a relatively higher temperature of 100 °C. Being metal-free, excellent product selectivity, high atom economy, good functional group tolerance, and feasibility for large-scale synthesis are the salient features of the developed methodology.

Aerobic CuBr2-Catalyzed Oxidative Coupling Reaction of Amidines with Exocyclic α,ß-Unsaturated Cycloketones for the Synthesis of Spiroimidazolines.

A CuBr2-catalyzed cascade reaction of amidines with exocyclic α,ß-unsaturated cycloketones was developed, affording a large variety of spiroimidazolines in moderate to excellent yields. The reaction process involved the Michael addition and copper(II)-catalyzed aerobic oxidative coupling, in which O2 from air acted as the oxidant and H2O was the sole byproduct.

Identification of a novel HIV-1 second-generation circulating recombinant form (CRF136_0107) among MSM in China.

OBJECTIVE: To investigate the molecular epidemiology of HIV-1 in Heilongjiang, China, and try to spot signs of new circulating recombinant form (CRF) in this region. DESIGN: A molecular epidemiological study was conducted in Heilongjiang, China during 2011-2020. METHODS: Plasma samples were collected from three HIV-1-positive patients (two MSM and one man lacking risk factor information). The near full-length genome sequences (NFLGs) of a novel CRF were then obtained and subjected to phylogenetic analysis using Mega 7.0.26. Recombination analysis was performed by the jumping profile Hidden Markov Model (jpHMM). Finally, the origin time of this novel CRF was inferred using the Bayesian phylogenetic analysis in Beast v1.10.4. RESULTS: The three NFLGs formed a distinct monophyletic cluster in the neighbor-joining (NJ) tree. Recombination analysis revealed that the recombinant genome was composed of five segments derived from CRF01_AE, subtypes B, and C, but further confirmed to be a second-generation recombinant form of CRF01_AE/CRF07_BC by a comparison of genome maps and subregion phylogenetic analysis and, therefore, designated as CRF136_0107. With Bayesian phylogenetic analysis, CRF136_0107 was estimated to originate around 2010-2011. CONCLUSION: A novel HIV-1 CRF01_AE/CRF07_BC second-generation CRF called CRF136_0107 was identified among MSM in Heilongjiang, a northeast province of China.

Young MSM changed temporal HIV-1 epidemic pattern in Heilongjiang Province, China.

Background: Human immunodeficiency virus type 1 (HIV-1) epidemic in China is featured by geographical diversity of epidemic patterns. Understanding the characteristics of regional HIV-1 epidemic allows carrying out targeted prevention and controlling measures. This seven-year cross-sectional study was conducted in Heilongjiang, one province of Northeast China, where newly diagnosed infection is fast increasing yearly, but temporal HIV-1 epidemic trend is largely unknown. Methods: Information of 1,006 newly diagnosed HIV-1-infected participants were collected before antiretroviral therapy during 2010-2016 in Heilongjiang province. HIV-1 genotype was identified based on the viral gag and env gene sequences. Recent infection was determined by Limiting-Antigen Avidity assays. Comparison analyses on the median ages, CD4 counts, proportions of stratified age groups and CD4 count groups, and rates of recent HIV-1 infection among different population and sampling times were performed to understand temporal HIV-1 epidemic features. Results: Homosexual contact among men who have sex with men (MSM) was the main transmission route and CRF01_AE was the most dominant HIV-1 genotype. During 2010-2016, the HIV-1 epidemic showed three new changes: the median age continued to decline, the cases with a CD4 count more than 500 cells/µl (CD4hi cases) disproportionally expanded, and the recent HIV-1 infection rate steadily increased. MSM cases determined the temporal trend of HIV-1 epidemic here. Increase of young MSM cases (aged <30 years) made the main contribution to the younger age trend of MSM cases. These young MSM exhibited a higher median CD4 count, a higher proportion of CD4hi cases, and a higher rate of recent HIV-1 infection than cases aged 30 years and more. MSM infected by CRF01_AE virus mostly affected HIV-1 epidemic patterns among MSM population. Conclusion: Young MSM have become a new hotspot and vulnerable group for HIV-1 transmission in Heilongjiang Province, Northeast China. The rapid increase in the number of young MSM cases, mainly those with CRF01_AE infection, changed temporal HIV-1 epidemic pattern here. Measures for prevention and control of HIV-1 infection among this population are urgently needed in the future.

Iron chelators reverse organ damage in type 4B hereditary hemochromatosis: Case reports.

RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin. PATIENT CONCERNS: Here we report 2 elderly Chinese Han men, who were brothers, presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia as well as high transferrin saturation. DIAGNOSIS: Subsequent genetic analyses identified a heterozygous mutation (p. Cys326Tyr) in the SLC40A1 gene in both patients. INTERVENTIONS: We treated the patient with iron chelator and followed up for 3 years. OUTCOMES: Iron chelator helped to reduce the serum ferritin and improve the condition of target organs, including skin, pancreas, liver as well as pituitary. LESSONS: Type 4B HH is rare but usually tends to cause multiple organ dysfunction and even death. For those patients who have difficulty tolerating phlebotomy, iron chelator might be a good alternative.

Assessment of Serum Tumor Markers for Predicting Ocular Metastasis in Lung Adenocarcinoma: A Retrospective Study.

The purpose of this study was to detect clinical variations between lung adenocarcinoma patients with and without ocular metastasis (OM) to identify risk factors for OM and assess the diagnostic values. We included 1153 patients with lung adenocarcinoma in this study. Independent t-tests and chi-square tests were used to compare patients' clinical characteristics. Statistically significant parameters were analyzed by binary logistic regression to detect risk factors of OM. The results showed that the OM group had increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21-1), carbohydrate antigen- (CA-) 125, CA-153, and total prostate-specific antigen (TPSA) compared with the NOM group. CYFRA21-1 is the most useful biomarker for detecting OM in this population.

Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance.

Cetuximab and panitumumab, as the highly effective antibodies targeting epidermal growth factor receptor (EGFR), have clinical activity in the patients with metastatic colorectal cancer (mCRC). These agents have good curative efficacy, but drug resistance also exists at the same time. The effects of KRAS, NRAS, and BRAF mutations and HER2 amplification on the treatment of refractory mCRC have been elucidated and the corresponding countermeasures have been put forward. However, the changes in EGFR and its ligands, the mutations or amplifications of PIK3CA, PTEN, TP53, MET, HER3, IRS2, FGFR1, and MAP2K1, the overexpression of insulin growth factor-1, the low expression of Bcl-2-interacting mediator of cell death, mismatch repair-deficient, and epigenetic instability may also lead to drug resistance in mCRC. Although the emergence of drug resistance has genetic or epigenetic heterogeneity, most of these molecular changes relating to it are focused on the key signaling pathways, such as the RAS/RAF/mitogen-activated protein kinase or phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway. Accordingly, numerous efforts to target these signaling pathways and develop the novel therapeutic regimens have been carried out. Herein, we have reviewed the underlying mechanisms of the resistance to anti-EGFR therapy and the possible implications in clinical practice.

Altered white matter integrity in patients with monocular blindness: A diffusion tensor imaging and tract-based spatial statistics study.

BACKGROUND: Visual deprivation can lead to abnormal and plastic changes in the brain's visual system and other systems. Although the secondary changes of gray matter in patients have been well studied, the study of white matter is rare. In fact, subtle changes in white matter may be revealed by diffusion tensor imaging, and tract-based spatial statistics can be used to analyze DTI image data. PURPOSE: In the present study, diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) were used to investigate abnormal structural changes in the white matter (WM) of patients with monocular blindness (MB). METHODS: We recruited 16 healthy controls (HC) (fourteen males and two females) and 16 patients (fifteen males and one female) with right-eye blindness (without differences in left-eye vision). All patients were of similar age. Data acquisition was performed using magnetic resonance imaging (MRI) and DTI. Voxel-based whole brain comparisons of fractional anisotropy (FA) and radial diffusivity (RD) of WM fibers in patients and HC were performed using the TBSS method. The mean FA and RD values for altered brain regions in MB patients were analyzed via the receiver operating characteristic (ROC) curve. Correlation analysis was performed to investigate the relationships between the average FA (RD) value of the whole brain and anxiety score, depression score, and visual function questionnaire score in MB patients. RESULTS: In MB patients, the mean FA of the whole brain was decreased versus HC. Moreover, the FA values of the corpus callosum, the corona radiata, the posterior thalamic radiation, and the right retrolenticular part of internal capsule were significantly decreased. In addition, the average RD value of the whole brain in MB patients was higher than that observed in HC. The mean FA and RD values of brain regions were analyzed using the ROC curve, and the results showed that the area under the ROC curve was more accurate. Furthermore, the average FA and RD values of the whole brain were significantly correlated with anxiety score, depression score, and visual function-related quality of life score. CONCLUSION: DTI and TBSS may be useful in examining abnormal spontaneous alterations in the WM of MB patients. The observed changes in FA and RD values may imply the larvaceous neurological mechanism involved in MB.

Central network changes in patients with advanced monocular blindness: A voxel-based morphometric study.

OBJECTIVE: To study the changes in gray matter volume (GMV) in patients with advanced monocular blindness (MB) using voxel-based morphometry (VBM). METHODS: Thirty-one patients with advanced MB (25 males and six females) and 31 normal controls (25 males and six females) were enrolled. The t test was applied to determine the differences in GMV, white matter volume (WMV), and volume of cerebrospinal fluid in different regions of the brain. The local characteristics of spontaneous concentrations of brain tissue were evaluated by the VBM method. The effects of blindness duration on differences in the GMV were evaluated by correlation and regression analyses. RESULTS: Compared with the control group, the GMV was decreased in the upper right margin, bilateral insular cortex, right cingulate gyrus, left occipital gyrus, and right suboccipital lobe, and negatively correlated with blindness duration in the upper right posterior margin, bilateral insular cortex, and right cingulate cortex. CONCLUSIONS: We found that patients with MB showed abnormal WMV and GMV, as evidenced by local changes in the brain. In addition, reduced GMV in specific parts of the brain was associated with the duration of blindness, which may indicate neuropathological mechanisms of visual loss in patients with MB.

Apolipoprotein A1 and B as risk factors for development of intraocular metastasis in patients with breast cancer.

Objective: Breast cancer is the most common primary lesion resulting in intraocular metastasis (IOM). In this study, we investigated the differences between breast cancer patients with and without IOM, and clarified the risk factors for IOM in patients with breast cancer. Methods: A total of 2,381 patients with breast cancer were included in this study from January 2005 to December 2017. The chi-square test and Student's t-test were applied to evaluate differences between the IOM and non-IOM (NIOM) groups. Risk factors were calculated using binary logistic regression analysis. Receiver operating curve (ROC) analysis was used to assess the diagnostic value of IOM in patients with breast cancer. Results: The IOM incidence in patients with breast cancer was 1.35%. No significant differences were detected in age, gender, menopausal status, or histopathology between the IOM and NIOM groups. The IOM group had more axillary lymph node metastases, lower ApoA1 and higher ApoB, compared with the NIOM group. Binary logistic regression indicated that ApoA1 and ApoB were risk factors for IOM in breast cancer patients (P-values<0.001 and P-values=0.005, respectively). ROC curve analysis revealed area under the curve values for ApoA1 and ApoB of 0.871 and 0.633, using cutoff values of 1.165 and 0.835 g/L, respectively. The sensitivity and specificity values for ApoA1 were 0.813 and 0.849, respectively, while those for ApoB were 0.813 and 0.481. Conclusion: Our data indicate that ApoA1 and ApoB are risk factors for IOM in patients with breast cancer and that ApoA1 is more reliable than ApoB at distinguishing IOM from NIOM in patients with breast cancer.

Altered brain activity in patients with strabismus and amblyopia detected by analysis of regional homogeneity: A resting­state functional magnetic resonance imaging study.

Previous studies have demonstrated that strabismus or amblyopia can result in marked brain function and anatomical alterations. However, differences in spontaneous brain activity in strabismus and amblyopia (SA) patients as compared with control individuals remain unclear. The present study aimed to analyze the potential brain activity changes in SA patients and their association with behavioral performance. In total, 16 patients with SA (10 women and 6 men) and 16 healthy controls (HCs; 6 men and 10 women) with matched age and sex were recruited. All subjects were examined with resting­state functional magnetic resonance imaging (rs­fMRI), and changes in the spontaneous brain activity of SA patients were evaluated by the regional homogeneity (ReHo) method. The diagnostic ability of the ReHo method was assessed using receiver operating characteristic (ROC) curve analysis. In addition, the association between the mean ReHo value in different brain regions and the behavioral performance was explored by correlation analysis. It was observed that the ReHo value was significantly increased in SA patients compared with HCs in the following brain regions: left lingual gyrus, right middle occipital gyrus/precuneus, bilateral anterior cingulate, left middle occipital gyrus and bilateral precentral gyrus. By contrast, the ReHo value of the left inferior frontal gyrus was significantly lower than that in HCs. ROC curve analysis indicated that the ReHo method has certain credibility for the diagnosis of SA patients. In addition, no similar changes were detected in other brain regions. These results revealed abnormal spontaneous brain activity in certain parts of the brain in adult patients with SA, which suggests the involvement of the neuropathological or compensatory mechanism in these patients, and may be beneficial for clinical treatment.

Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.

OBJECTIVE: The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China. DESIGN: Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE. Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses. METHODS: The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06. Coreceptor usage was predicted by Geno2Pheno algorithm. Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software. The properties of amino acid sequences were analyzed by the online ProtParam tool. RESULTS: CRF01_AE become the main HIV-1 genotype since 2010. Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/µl. Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses. CONCLUSION: CRF01_AE has dominated HIV-1 genotype in Northeast China. Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.

Gray Matter Volume Changes in Patients With Acute Eye Pain: A Voxel-Based Morphometry Study.

PURPOSE: The present study was attempted to compare the differences in gray matter volume (GMV) between the acute eye pain (EP) patients and the healthy controls (HCs) using voxel-based morphometry (VBM), and to explore the relationship with clinical features and behavioral performance. METHODS: A total of 24 patients (17 males, 7 females) with acute EP and 24 (17 males, 7 females) age-, sex-, and education-matched HCs were recruited from the Ophthalmology Department of the First Affiliated Hospital of Nanchang University. Functional magnetic resonance imaging (fMRI) scans were conducted in all subjects. We analyzed the original three-dimensional (3D) T1 brain images by VBM and compared the GMV values with the HCs. The acute EP patients can be distinguished from the HCs by receiver operating characteristic (ROC) curve. RESULTS: Compared with HCs, the acute EP patients had significantly lower GMV values in the brain regions of the left cerebellum posterior lobe, the left limbic lobe, the right insula, the left insula, the left thalamus, the left caudate, and the right cuneus. In addition, the WMV values of the whole brain in acute EP patients decreased slightly. CONCLUSIONS: These results demonstrated that the acute EP patients showed an abnormal reduction in GMV in some brain regions, which might provide valuable information for further exploration of underlying neural mechanisms. These abnormal brain regions may reflect the functional disorders of acute EP patients in somatosensory, motor, cognitive functions, and so on. TRANSLATIONAL RELEVANCE: The VBM study provides a diagnostic method for identifying the cause of acute EP, additionally, a novel direction was presented for further exploration of underlying neural mechanisms of acute EP.

Measuring abnormal intrinsic brain activities in patients with retinal detachment using amplitude of low-frequency fluctuation: a resting-state fMRI study.

OBJECTIVE: The targets of this study were to access the alternations of spontaneous brain activity in RD patients by amplitude of low-frequency fluctuation (ALFF) method and to explore their relationships with clinical behavioral performance. METHODS: A total of 20 patients with RD (6 males and 14 females), and 20 healthy controls (HCs) (6 males and 14 females) were recruited, and were matched in sex and age. All participants finished the functional magnetic resonance imaging (fMRI) scanning. We applied the ALFF method to detect the spontaneous brain activity. Receiver operating characteristic (ROC) curve was applied to distinguish RD Patients from HCs. RESULTS: RD patients showed decreased ALFF values in the right occipital lobe and right medial frontal gyrus and increased ALFF values in the right frontal superior orbital and left inferior temporal gyrus when compared with HCs. In RD patients, we did not find any relationship between the mean ALFF values and the clinical behavioral performances. CONCLUSION: The RD patients exhibited abnormal spontaneous brain activity in vision and vision related brain regions, which might explore potential pathological mechanism of acute vision loss in RD patients.

Lymphadenitis associated with cat-scratch disease simulating a neoplasm: Imaging findings with histopathological associations.

The lymphadenitis associated with cat-scratch disease (CSD) is often confused with neoplasms by a number of radiologists and clinicians, and consequently, unnecessary invasive procedures or surgeries are performed. In the present study, the contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) findings of 10 patients (6 men and 4 women) with clinically and pathologically confirmed lymphadenitis associated with CSD were retrospectively analyzed (CT in 3 patients, MRI in 6 patients, and CT and MRI in 1 patient) at The Second Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China) between January 2007 and November 2014. As a result, 17 enlarged lymph nodes were identified in 10 cases. The 5 nodes identified by CT scan exhibited relatively inhomogeneous isodensity to muscle, with patchy low density in the center. All 14 nodes identified by MRI scan exhibited homogeneous or heterogeneous isointensity to muscle or slightly increased intensity compared with that of muscle on T1-weighted images (T1WI), and homogeneous or heterogeneous hyperintensity on fat-suppressed T2WI. Following enhancement, all 17 enlarged lymph nodes associated with CSD demonstrated the following 3 different enhancement patterns: Moderate homogeneous enhancement (n=8), which was associated with histologically identified early disease stage; marked heterogeneous enhancement with no enhancement of the necrotic areas (n=4), and heterogeneous enhancement with progressively 'spoke-wheel-like' (defined as radiating enhancement from the center) enhancement of the patchy low-density area (n=1), which was associated with histologically identified intermediate disease stage; and astral low-density/hypointensity with marked enhancement (n=2) or a 'rose flower' sign (n=2), which was associated with histologically identified late disease stage. We hypothesized that the CT and MRI results of lymphadenitis in CSD may be associated with the pathological features. It may be suggested that the diagnosis of CSD may be formed when considering the characteristic CT and MRI features of astral low-density/hypointensity with marked enhancement or a 'rose flower' sign (defined as marginal petaloid enhancement) in the late disease stage, or the MRI results of homogeneous, moderate enhancement in the early disease stage, or the CT/MRI data of heterogeneous enhancement with non-enhancing area in the center in the intermediate disease stage, in solitary or multiple enlarged lymph nodes associated with general subcutaneous edema in the vicinity of the nodes on CT/MRI and with a history of cat exposure.

Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of ovarian cancer by down-regulating MMP2 and MMP9.

Ovarian cancer is the third most common cancer in the female reproductive organs and epithelial ovarian cancer has the highest lethality of all gynecological cancers. Pomegranate fruit juice (PFJ) has been shown to inhibit the growth of several types of cancer other than ovarian cancer. In this study, we exposed the ovarian cancer cell line A2780 to PFJ and two of its components (ellagic acid and luteolin). MTT and wound healing assays demonstrated that all three treatments suppressed the proliferation and migration of the ovarian cancer cells. In addition, western blotting and ELISA assays showed that the expression levels of MMP2 and MMP9 gradually decreased after treatment with increasing concentrations of ellagic acid and luteolin. To confirm our findings in the in vitro experiments, we used another ovarian cancer cell line, ES-2, in nude mice experiments. All three treatments inhibited tumor growth without obvious side-effects. Furthermore, compared with the control group, the expression levels of MMP2 and MMP9 were depressed. Ellagic acid induced a greater effect than luteolin, suggesting that ellagic acid might be a promising candidate for further preclinical testing for treatment of human ovarian cancer.

Contrast-enhanced multiple-phase imaging features of intrahepatic mass-forming cholangiocarcinoma and hepatocellular carcinoma with cirrhosis: A comparative study.

The intrahepatic mass-forming cholangiocarcinoma (IMCC) is frequently misdiagnosed as hepatocellular carcinoma (HCC) in patients with cirrhosis, by numerous radiologists and clinical doctors, which results in the incorrect therapeutic treatment. A retrospective case-control study was conducted, and the contrast-enhanced multiple-phase (CEMP) computed tomography (CT) and magnetic resonance imaging (MRI) findings of 22 pathologically confirmed IMCC patients and 22 HCC controls with underlying liver cirrhosis were analyzed at the present hospital, from January 2010 to December 2015. In addition, serum tests were conducted and clinical symptoms of patients evaluated. A statistical analysis revealed that the enhancement pattern, signal on MRI delayed phase (P<0.001), maximum diameter, capsule retraction, portal vein invasion, bile duct dilation and abdominal lymphadenectasis characteristics were different between IMCC and HCC patients with cirrhosis. On CEMP CT and MRI analysis, the most frequently occurring enhancement patterns of IMCC were progressive patterns (P=0.001 or P<0.001). Conversely, the most frequently occurring enhancement patterns present in HCC were the washout patterns (P<0.001). Therefore, the diagnosis of IMCC in cirrhotic patients should be verified with CEMP CT and MRI analysis for the future, to determine presence or absence of progressive and/or peripheral rim-like enhancement, a hyperintensive delayed phase with capsule retraction, portal vein invasion, bile duct dilation, abdominal lymphadenectasis and increased levels of CA199.

Enterolactone has stronger effects than enterodiol on ovarian cancer.

BACKGROUND: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. METHODS: We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. RESULTS: The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. CONCLUSION: END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.