Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis.

Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma with T follicular helper phenotype (PTCL-TFH) are a group of complex clinicopathological entities that originate from T follicular helper cells and share a similar mutation profile. Their diagnosis is often a challenge, particularly at an early stage, because of a lack of specific histological and immunophenotypic features, paucity of neoplastic T cells and prominent polymorphous infiltrate. We investigated whether the lymphoma-associated RHOA Gly17Val (c.50G>T) mutation, occurring in 60% of cases, is present in the early "reactive" lesions, and whether mutation analysis could help to advance the early diagnosis of lymphoma. The RHOA mutation was detected by quantitative polymerase chain reaction with a locked nucleic acid probe specific to the mutation, and a further peptide nucleic acid clamp oligonucleotide to suppress the amplification of the wild-type allele. The quantitative polymerase chain reaction assay was highly sensitive and specific, detecting RHOA Gly17Val at an allele frequency of 0.03%, but not other changes in Gly17, nor in 61 controls. Among the 37 cases of AITL and PTCL-TFH investigated, RHOA Gly17Val was detected in 62.2% (23/37) of which 19 had multiple biopsies including preceding biopsies in ten and follow-up biopsies in 11 cases. RHOA Gly17Val was present in each of these preceding or follow-up biopsies including 18 specimens that showed no evidence of lymphoma by combined histological, immunophenotypic and clonality analyses. The mutation was seen in biopsies 0-26.5 months (mean 7.87 months) prior to the lymphoma diagnosis. Our results show that RHOA Gly17Val mutation analysis is valuable in the early detection of AITL and PTCL-TFH.

Angioimmunoblastic T-cell lymphoma contains multiple clonal T-cell populations derived from a common TET2 mutant progenitor cell.

Angioimmunoblastic T-cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting a role of antigenic drive in its development. Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (TET2, DNMT3A) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (RHOA, VAV1, PLCG1, CD28) critical for T-cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T-cell receptor ß (TRB) rearrangement in 119 AITL, 11 peripheral T-cell lymphomas with T follicular helper phenotype (PTCL-TFH), and 25 PTCL-NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent TET2, DNMT3A, and RHOA mutations in AITL (72%, 34%, 61%) and PTCL-TFH (73%, 36%, 45%) and showed multiple TET2 mutations (2 or 3) in 57% of the involved AITL and PTCL-TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2-4) in 18 cases (24%). In selected cases, we confirmed bi-clonal T-cell populations and further demonstrated that these independent T-cell populations harboured identical TET2 mutations by using BaseScope in situ hybridization, suggesting their derivation from a common TET2 mutant progenitor cell population. Furthermore, both T-cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL-TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common TET2 mutant haematopoietic progenitor pool in AITL and PTCL-TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

[Serotonergic neurons in the median raphe nucleus mediate anxiety- and depression-like behavior].

Serotonin (5-hydroxtryptamine, 5-HT), one of the central neurotransmitters, is the most important modulator for emotion regulation, sensory processing, cognitive control, etc. The serotonergic neurons are limited in amount and mainly distributed in the dorsal raphe nucleus (DR) and the median raphe nucleus (MR) in the midline of the brain stem. Previous studies mainly focused on the function of 5-HT neurons in the DR, but little is known about 5-HT neurons in MR. In the present study, with Pet1-Cre transgenic mice and DREADDs technology, we specifically activated or silenced 5-HT neurons in the MR, and aimed to explore their roles in anxiety- and depressive-like behaviors. The results showed that silencing 5-HT neurons in the MR decreased anxiety-like behaviors in the open field and elevated plus maze tasks. Inhibition of 5-HT neurons in the MR decreased depressive-like behaviors in the sucrose preference and forced swim test, while activation of 5-HT neurons in the MR enhanced depressive-like behaviors in the sucrose preference test. These results suggest that the 5-HT neurons in the MR play a key role in regulating anxiety- and depression-like behaviors.

[Photoluminescence of Silicon Nitride-Based ZnO Thin Film Developed with RF Magnetron Sputtering].

Owing to its merits of high corrosion resistance, high temperature stability as well as good mechanical strength etc., silicon nitride membrane (SiN) has been widely used as the experimental carrier of transmission electron microscope (TEM), scanning electron microscopy (SEM), atomic force microscope (AFM), X-ray photoelectron spectroscopy (XPS), energy dispersive X-Ray spectroscopy (EDX) and other characterization. In particular, SiN can be used as a low disturbing background for SEM observation. However, the poor luminescent property of SiN thin film has restricted its wide application in fluorescent devices. In order to enhance the fluorescence efficiency of silicon nitride membrane, a series of ZnO films were prepared on a SiNx film substrate with radio frequency magnetron sputtering (RF magnetron sputtering) technology during the experiment. Samples were then non-situ and in-situ annealed in nitrogen atmosphere, respectively. Then, atomic force microscope (AFM), scanning electron microscopy (SEM) and Raman spectroscopy (Raman) were applied to study the microstructure and photoluminescence (PL) properties of the prepared films. This paper also systemically studies the luminescence of the prepared thin films. The results show that, luminescent intensity increases after sputtering, while annealing further promoted the grain growth, a substantial increase in crystallization behavior and a decrease in grain boundary. The microstructure and luminescence properties of ZnO/SiN thin films prepared by RF magnetron sputtering were significantly influenced by annealing method. Compared with the SiNx film, near the band edge of the intrinsic emission intensity (about 380 nm) of untempered ZnO/SiNx films and N(2) atmosphere ex-situ annealed ZnO/SiNx films were increased by more than 7.7 times and 34.0 times. Compared with non-situ annealed films, in-situ annealed films contained more oxygen vacancy defects, thus showing a stronger visible light PL intensity. In-situ annealed films exhibited a higher photoluminescence capacity during the wavelength from 425 to 600 nm of visible light. These results can help to optimize the preparation parameters of silicon nitride based ZnO fluorescent films.

[Study on Photocatalytic Performance of LaPO4 Nanorods with Different Crystal Phases].

Rare earth phosphate has a wide application in optical materials, laser materials and many fields with great development prospects. In this paper, LaPO4 nanorods with different crystalline phases are prepared with hydrothermal method, its photocatalytic performance are discussed, as well as the structure and UV diffuse reflectance spectroscopy. The research indicates that the hydrothermal temperature plays a key role in the crystal phase, while it is hexagonal at 120 ℃, monoclinic at 180 ℃ and the mixed phase at 160 ℃. The UV absorption has no obvious change of each crystalline phase, and they all show nanorods. The photocatalytic activity of LaPO4 for the degradation of MB is studied; it is found that the monoclinic LaPO4 has the best photocatalytic activity. Furthermore, monoclinic LaPO4 could decrease the fluorescence quantum efficiency and increase the separation efficiency of electrons and holes, which improve the photocatalytic activity. Besides, the main active species are confirmed to be hydroxyl radicals with capture experiments during the photocatalytic process.

Giant conductivity enhancement of ferrite insulators induced by atomic hydrogen.

Hydrogen behavior in oxides has triggered much interest for its scientific and technological importance in a wide range of research fields from novel ion conductors to astrochemistry. Here, we report a giant conductivity enhancement in ZnFe2O4 ferrite insulators to the metallic state by over eleven orders of magnitude induced by electrochemically generated atomic hydrogen at room temperature. The conductivity and the amount of incorporated hydrogen increased in an exponential function with time. An activation energy for the atomic hydrogen chemisorption was measured to be 8.23 kJ mol(-1). Quantitative kinetics correlations among the adsorption of atomic hydrogen, hydrogen incorporation and conductivity enhancement are established, based on which hydrogen incorporation process is clarified herein. We demonstrate that the hydrogen incorporation in oxides can be adjusted by manipulating the kinetic factors. These findings have implications for research into hydrogen behavior in oxides in environments containing hydrogen atoms and offer possibilities for utilizing and controlling the modifications of oxide materials induced by atomic hydrogen.

[Superficial Esophageal Carcinoma and Esophageal Intraepithelial Neoplasia: a Pathological Study of 130 Cases].

OBJECTIVE: To identify the pathological features of superficial esophageal carcinoma and esophageal intraepithelial neoplasia resected through endoscopic submucosal dissection (ESD). METHODS: The clinical and pathologic profiles of 130 cases were reviewed, including gross type, histology type, infiltration depth, infiltrative growth pattern, presence of tumor budding, lymphatic and vascular invasion, and margin status. RESULTS: The patients had a median age of 62 years old. The predominant gross type was mixed type (78/130, 60.0%), followed by Type 0-II (49/130, 37.7%). The longest diameter of lesionshad a median of 13.8 mm. Morphologically, there were 3 cases (2.3%) of undetermined dysplasia, 25 cases (19.2%) of low grade intraepithelial neoplasia, 56 cases (43.1%) of high grade of intraepithelial neoplasia, and 46 cases (35.4%) of invasive carcinoma. No correlation was found between histological type and gross type. Intramucosal and submucosal invasive carcinoma accounted for 87.0% (40/46) and 13.0% (6/46) of the cases, respectively; sm1 and sm2 accounted for 4.3% (2/46) and 8.7% (4/46) of the cases, respectively. Infiltrative growth pattern was identified as infiltrative growth pattern (INF) a (23/46, 50.0%), INFbeta (17/46, 37.0%) and INFc (6/46, 13.0%). Tumor budding was found in 3 cases and lymphatic and vascular invasion was found in 2 cases. Margin was positive in 30 cases (23.1%). Invasive carcinomahad a higher margin positive rate (24/46, 52.1%) than low grade intraepithelial neoplasia (1/25, 4.0%) and high grade intraepithelial neoplasia (5/56, 89%) (P<0.001). No association between margin positivity and invasive pattern was found (P=0.208). Fifteen cases (11.5%) recurred, with invasive carcinoma being more likely to recur (17.4%, 8/46) than low grade intraepithelial neoplasia (8.0%, 2/25) and high grade intraepithelial neoplasia (8.9%, 5/56) (P<0.05). No association between margin positivity and recurrence rate was found (P= 0.590). CONCLUSION: The superficial esophageal carcinoma and esophageal intraepithelial neoplasia resected by ESD are predominantly mixed type under endoscope, with histological features of high grade intraepithelial neoplasia and invasive carcinoma. Invasive carcinomas are more likely to recur and present with a positive margin.

Immunohistochemical HER2 expression not associated with clinicopathological characteristics of stage I-III gastric cancer patients.

BACKGROUND/AIMS: The aim of this study was to investigate the association of human epidermal growth factor receptor 2 (HER2) expression with clinicopathological characteristics of resectable gastric cancer patients. METHODOLOGY: A total of 394 stage I-III surgical gastric cancer patients who were detected of immunohistochemical (IHC) HER2 expression postoperatively were included in this retrospective study. Association of IHC HER2 over-expression (3+) rate with clinicopathological characteristics was tested by univariate and multivariate analyses. RESULTS: IHC HER2 over-expression rate was 5.1% (95% CI 3.1%-7.7%). By univariate analyses, none of the clinicopathological characteristics was associated with the IHC HER2 over-expression compared to negative expression (0/1+) (p>0.05), with the exception of a higher rate (12.2%) of IHC HER2 (3+) in moderate differentiation subset (p=0.02). However, the multivariate analyses didn't selected any characteristic as an independent risk factor of IHC HER2 over-expression or the combination of IHC HER2 (2/3+). CONCLUSIONS: IHC HER2 over-expression rate is relatively low among stage I-III gastric cancer patients, and might be generally not associated with clinicopathological characteristics.

[Neurons in NAc core and BLA are activated during cocaine context-associated reward memory retrieval in mice].

The intense associative memories that develop between cocaine-paired contexts and rewarding stimuli make addiction hard to cure by contributing to cocaine seeking and relapse. So it's of great importance to examine the neurobiological basis of addiction memory. Cocaine conditioned place preference (CPP) used in this study is a form of Pavlovian conditioning which can establish associations between drug and contextual factors. c-Fos and Zif268 are commonly used immediate early gene (IEG) makers to identify neurons that are activated after a stimulus or behavioral conditioning. This study was designed to reveal neuronal c-Fos, Zif268 expression pattern in 10 brain regions following cocaine context-associated reward memory retrieval in mice, combining animal behavioral study and immunofluorescence method. C57BL/6 mice were randomly divided into 3 groups: Saline retrieval, Cocaine retrieval, and No retrieval of cocaine groups. Cocaine retrieval and No retrieval of cocaine underwent CPP training (one side paired with cocaine, and the other side with saline) except that No retrieval of cocaine group didn't undergo CPP test. Saline retrieval group received saline injections (i.p) on both sides. The results showed that: Neuronal c-Fos, Zif268 protein expression levels in nucleus accumbens (NAc) core both were elevated in Cocaine retrieval group compared with those in Saline retrieval (Control) group during cocaine context-associated reward memory retrieval. Zif268 protein expression level in basolateral amygdala (BLA) was also elevated in Cocaine retrieval group compared with that in control mice. Elevation was not seen in other regions such as hippocampus, prefrontal cortex (PFC). Thus, NAc core and BLA were activated during cocaine context-associated reward memory retrieval. The results suggest that neurons that are activated in NAc core and BLA are crucial basis of cocaine context-associated reward memory.

Clinicopathological features and long-term prognosis of purely cystic pancreatic neuroendocrine tumors: A single-center experience.

BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) are heterogenous neoplasms, of which the prognosis varies widely. Purely cystic pancreatic neuroendocrine tumors (C-pNETs) are a small subset of pNETs in which data are extremely rare. This study aimed to compare clinicopathological and long-term survival differences between C-pNETs and solid pNETs (S-pNETs). METHODS: A retrospective review of 242 patients with pNETs underwent resection in our institution from 2009 to 2019 was conducted. Demography characteristics, clinicopathological features and long-term outcomes of them were analyzed. RESULTS: Sixteen out of 242 patients (6.6%) were identified as C-pNETs. Compared with S-pNETs, C-pNETs were more frequently non-functional (75% vs 45%, P = 0.02), and the median tumor diameter of C-pNETs was smaller (36 mm vs. 47 mm, P = 0.001). And the accuracy of preoperative diagnosis of C-pNETs was significantly lower (31% vs 78%, P = 0.001). Of note, the majority of C-pNETs were well-differentiated with G1 (81% vs 35%, P = 0.001). And there were no G3 (0 vs 7%, P = 0.001) in C-pNETs. No T4 stage or R1/R2 surgical margin detected in C-pNETs. And only one C-pNETs (6%) had regional lymph node metastasis (N) or synchronous distant metastasis (M). Additionally, only one patient with C-pNETs (6%) suffered tumor recurrence, compared with 24 (13%) for S-pNETs. And survival analysis showed the patients with C-pNETs seemed to be with better disease-free survival (P = 0.26). CONCLUSION: C-pNETs are rare subtype with possibly less aggressive behavior comparing with their solid counterparts. Recurrence and tumor-related death still occurs in patients with resected C-pNETs, although they tend to be with more favorable prognosis.

Unusual 9,19 : 24,32-dicyclotetracyclic triterpenoids from Lygodium japonicum.

Lygodipenoids A (1) and B (2), two novel C33 tetracyclic triterpenoids with a new 9,19 : 24,32-dicyclopropane skeleton, were isolated from the whole grass of Lygodium japonicum. Their structures were elucidated by spectroscopic and chemical means. Compounds 1 and 2 were tested in transfected cultured human embryonic kidney 293 HEK293 cells for an agonist assay, and compound 1 was identified as a partial agonist for liver X receptor α.

[Clinical and pathological characteristics and surgical treatment of carotid body tumor with endocrine activity].

OBJECTIVE: To investigate the clinical and pathological characteristics and surgical treatment of carotid body tumor with endocrine activity (CBT). METHODS: Records of seven CBT patients with endocrine activity (Jan, 1991-Aug, 2011) who underwent surgical excision of tumor were retrospectively reviewed. The operations were performed with the careful peroperative preparation on the control of blood pressure, serum potassium and catecholamine. All the tumors were studied with the methods of HE staining, immunohistochemistry of chromogranin A (CgA) and S-100. RESULTS: All the operations were successfully accomplished and the patients recovered quickly. It was confirmed with pathological examination that all the tumors were CBT, coming from paraganglioma. Tumor cells and sertoli cells were found in HE staining, and all were positive of CgA and S-100. All patients were followed up for 12-60 months and no recurrence was found during the follow up. CONCLUSION: CBT with endocrine activity presents with identifiable clinical and pathological characteristics. The recommended treatment is surgical resection, careful perioperative preparation and care is important to avoid the severe complication due to the endocrine activity of tumor.

[Allele genotype analysis of Plasmodium vivax merozoite surface protein 1 (PvMSP-1) from Dangdong, Liaoning Province].

Nested PCR method was used to amplify the Plasmodium vivax merozoite surface protein 1 (PvMSP-1) gene fragment containing the ICB5 and ICB6 region from Plasmodium vivax in Liaoning Province. The PCR products were digested by Pvu II restriction endonuclease and the digested fragments were observed by 1.5% agarose gel electrophoresis, and all followed by sequencing analysis and comparison. In 11 field isolates of P. vivax, two kinds of DNA fragments with 470 and 400 bp were produced respectively. After PvuII digestion, two Sal-1 type fragments (120 and 350 bp) were obtained from 5 samples of 470 bp. Single band of 400 bp appeared in 1 samples as Belem type. Two bands of 120 and 280 bp appeared from another 1 sample as recombination type III, and other 4 bands with 120 and 240 bp as Korean isolate. The principal types of PvMSP-1 alleles exist in malaria endemic areas in Liaoning Province with no mixed infection of two different type alleles.

Development and Validation of a Novel Radiomics-Based Nomogram With Machine Learning to Preoperatively Predict Histologic Grade in Pancreatic Neuroendocrine Tumors.

Backgroud: Tumor grade is the determinant of the biological aggressiveness of pancreatic neuroendocrine tumors (PNETs) and the best current tool to help establish individualized therapeutic strategies. A noninvasive way to accurately predict the histology grade of PNETs preoperatively is urgently needed and extremely limited. Methods: The models training and the construction of the radiomic signature were carried out separately in three-phase (plain, arterial, and venous) CT. Mann-Whitney U test and least absolute shrinkage and selection operator (LASSO) were applied for feature preselection and radiomic signature construction. SVM-linear models were trained by incorporating the radiomic signature with clinical characteristics. An optimal model was then chosen to build a nomogram. Results: A total of 139 PNETs (including 83 in the training set and 56 in the independent validation set) were included in the present study. We build a model based on an eight-feature radiomic signature (group 1) to stratify PNET patients into grades 1 and 2/3 groups with an AUC of 0.911 (95% confidence intervals (CI), 0.908-0.914) and 0.837 (95% CI, 0.827-0.847) in the training and validation cohorts, respectively. The nomogram combining the radiomic signature of plain-phase CT with T stage and dilated main pancreatic duct (MPD)/bile duct (BD) (group 2) showed the best performance (training set: AUC = 0.919, 95% CI = 0.916-0.922; validation set: AUC = 0.875, 95% CI = 0.867-0.883). Conclusions: Our developed nomogram that integrates radiomic signature with clinical characteristics could be useful in predicting grades 1 and 2/3 PNETs preoperatively with powerful capability.

[Standard sample preparation method for quick determination of trace elements in plastic].

Reference sample was prepared by masterbatch method, containing heavy metals with known concentration of electronic information products (plastic), the repeatability and precision were determined, and reference sample preparation procedures were established. X-Ray fluorescence spectroscopy (XRF) analysis method was used to determine the repeatability and uncertainty in the analysis of the sample of heavy metals and bromine element. The working curve and the metrical methods for the reference sample were carried out. The results showed that the use of the method in the 200-2000 mg x kg(-1) concentration range for Hg, Pb, Cr and Br elements, and in the 20-200 mg x kg(-1) range for Cd elements, exhibited a very good linear relationship, and the repeatability of analysis methods for six times is good. In testing the circuit board ICB288G and ICB288 from the Mitsubishi Heavy Industry Company, results agreed with the recommended values.

HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China.

INTRODUCTION: In recent years, with the development of molecular epidemiology, molecular transmission networks based on evolutionary theory and sequence analysis have been widely used in research on human immunodeficiency virus (HIV)-1 transmission dynamics and precise intervention for high-risk populations. The HIV-1 molecular transmission network is a new method to study the population's access to the network, the characteristics of clustering, and the characteristics of interconnection in the network. Here, we analyzed the characteristics of the HIV-1 molecular transmission network of sexually transmitted people in Liaoning Province. METHODS: A study of HIV-infected persons who were sexually transmitted in Liaoning Province from 2003 to 2019. HIV-1 RNA was extracted, amplified and sequenced, and a phylogenetic tree was constructed to determine the subtype using the well matched pol gene region sequence. The gene distance between sequences was calculated, the threshold was determined, and the molecular transmission network was constructed. RESULTS: 109 samples of pol gene region were obtained. The main subtype of HIV-1 was CRF01_AE, followed by B, CRF07_BC, etc. 12.8% of them were resistant to HIV. At the threshold of 0.55 gene distance, 60.6% of them entered the HIV-1 molecular transmission network. Workers, sample source voluntary counseling and testing, other testing, subtype B and drug resistance are the factors influencing the access to HIV-1 molecular transmission network. The subtype of CRF01_AE formed 6 clusters in the molecular transmission network. In the network, the difference of connection degree between different subtypes was statistically significant. DISCUSSION: The three subtypes CRF01_AE, CRF07_BC and B that enter the molecular transmission network do not have interconnections, and they form clusters with each other. It shows that the risk of transmission among the three subtypes is less than the risk of transmission within each subtype. The factors affecting HIV-1 entry into the molecular transmission network were occupation, sample source, genotype and drug resistance. The L33F mutation at the HIV-1 resistance mutation site constitutes the interconnection in the largest transmission cluster in the network. The epidemiological characteristics of HIV-infected persons in each molecular transmission cluster show that 97% of the study subjects come from the same area and have a certain spatial aggregation. CONCLUSION: Constructing a molecular transmission network and conducting long-term monitoring, while taking targeted measures to block the spread of HIV can achieve precise prevention and control.

A comprehensive validation of the novel 8th edition of American Joint Committee on Cancer staging manual for the long-term survivals of patients with non-functional pancreatic neuroendocrine neoplasms.

Histologically, the World Health Organization has classified pancreatic neuroendocrine neoplasms (p-NENs) into well-differentiated pancreatic neuroendocrine tumors (G1/G2 p-NETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (G3 p-NECs) based on tumor mitotic counts and Ki-67 index. Recently, the 8th edition of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging manual has incorporated some major changes in 2017 that the TNM staging system for p-NENs should only be applied to well-differentiated G1/G2 p-NETs, while poorly-differentiated G3 p-NECs be classified according to the new system for pancreatic exocrine adenocarcinomas. However, this new manual for p-NENs has seldom been evaluated.Data of patients with both G1/G2 and G3 non-functional p-NENs (NF-p-NENs) from our institution was retrospectively collected and analyzed using 2 new AJCC 8th staging systems. We also made survival comparisons between the 8th and 7th edition system separately for different subgroups.For G1/G2 NF-p-NETs, there were 52 patients classified in AJCC 8th edition stage I, 40 in stage II, 41 in stage III and 19 in stage IV. As for G3 NF-p-NECs, 17, 19, 24, and 18 patients were respectively defined from AJCC 8th edition stage I to stage IV. In terms of the AJCC 7th staging system, the 230 patients with NF-p-NENs were totally distributed from stage I to stage IV (94, 63, 36, 37, respectively). For the survival analysis of both G1/G2 NF-p-NETs and G3 NF-p-NECs, the AJCC 7th edition system failed to discriminate the survival differences when compared stage III with stage II or stage IV (P > .05), while the 8th edition ones could perfectly allocate patients into 4 statistically different groups (P < .05). The HCIs of AJCC 8th stage for G1/G2 NF-p-NETs [HCI=0.658, 95% confidence interval (CI)=0.602-0.741] and stage for G3 NF-p-NECs (HCI=0.704, 95% CI=0.595-0.813) was both statistically larger than those of AJCC 7th stage for different grading NF-p-NENs [(HCI=0.578, 95% CI=0.557-0.649; P=.031), (HCI=0.546, 95% CI=0.531-0.636; P = .019); respectively], indicating a more accurate predictive ability for the survivals of NF-p-NENs.Our data suggested the 2 new AJCC 8th staging systems were superior to its 7th edition for patients with both G1/G2 NF-p-NETs and G3 NF-p-NECs.

Mediastinal myelolipoma/extramedullary hematopoiesis presenting as a mass: rare differential diagnosis among mediastinal tumors.

OBJECTIVES: Mediastinal myelolipoma/extramedullary hematopoiesis presenting as a mass is infrequent and can lead to misdiagnosis. Here we describe a large series aiming to illustrate the clinicopathologic features. METHODS: We retrospectively searched mediastinal tumors and myelolipoma diagnosed at the Department of Pathology, West China Hospital from 2010 to 2015 and collected 14 mediastinal myelolipoma/extramedullary hematopoiesis cases presenting as an encapsulated mass among 1324 mediastinal mass diseases and 252 myelolipomas. RESULTS: There were 8 females and 6 males aged from 35 to 67 years old, most of whom were diagnosed incidentally. Cross-sectional imaging revealed encapsulated masses located in the posterior mediastinum with fat and soft tissue density showing heterogeneous enhancement. Radiologic diagnosis was neurogenic tumor for most cases. All but one patient underwent surgery and postoperative pathologic findings showed fat and hematologic elements. Considering the accompanying hematologic disorders, 5 patients were diagnosed as extramedullary hematopoiesis and the remaining 9 as myelolipoma. The average hematopoietic tissue percentage in extramedullary hematopoiesis was 70%, significantly higher than it was in myelolipoma. Patients showed no sign of recurrence or metastasis apart from the patient with hepatocellular carcinoma. CONCLUSIONS: Mediastinal myelolipoma/extramedullary hematopoiesis is a rare entity of solid tumors in the posterior mediastinum, affecting patients from their third decades, with no sex predilection and lacking unique clinical symptoms, and may be misdiagnosed as a malignant tumor on cross-sectional imaging. The final diagnosis relies on pathologic findings, and the precise classification of myelolipoma or extramedullary hematopoiesis relies on percentage of hematopoietic tissue and accompanying clinical symptoms. Surgery is the recommended treatment.

Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites.

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL is unclear with few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis of ANKL is a frequent problem. Clinicopathologic characteristics of 35 retrospective cases of ANKL were investigated with the aim of improving diagnosis and to find the genetic/epigenetic aberrations associated with ANKL etiology. Because of the relatively low number of leukemic cells in the peripheral blood and bone marrow, diagnosis of ANKL can be missed; therefore, it is important to perform biopsy on solid tissues, if necessary. We describe the pathology of ANKL in the lymph nodes, bone marrow, spleen, liver, and skin, with focus on diagnosis and differentiated diagnosis. We observed young male predominance in our cohort, and the clinical course was more aggressive than reported previously. Low lactate dehydrogenase (<712 IU/L), chemotherapy or L-asparaginase administration were found to be associated with more favorable outcomes. SH2 domains of STAT5B and STAT3 also were screened for the presence of activating mutations. Moreover, CpG island methylation status of HACE1, a candidate tumor-suppressor gene, was determined in ANKL samples. We observed activating STAT5B mutations (1/5) and hypermethylation of HACE1 (3/4) in ANKL cases, suggesting that these aberrations may contribute to ANKL pathogenesis.

Suppressive effects of microRNA-16 on the proliferation, invasion and metastasis of hepatocellular carcinoma cells.

miR-16 is known to be abnormally expressed in hepatocellular carcinoma (HCC) cells, and the overexpression of miR-16 inhibits the proliferation, invasion and metastasis of various cancer cells. MicroRNAs (miRNAs or miRs) are closely related to the proliferation, invasion and metastasis of HCC. The present study aimed to explore the effects of miR-16 on the proliferation, invasion and metastasis of HCC cells, and to elucidate the mechanisms involved. A cell line with moderate levels of miR­16 expression was selected from the SMMC-7721, HepG2, SK-Hep-1 and Huh­7 HCC cells and validated by reverse transcription-PCR (RT-PCR). The effects of miR­16 on HCC cell viability were determined by MTT assay; cell migration and invasion were determined by Transwell cell invasion assay, and apoptosis was determined by flow cytometery (FCM). Western blot analysis was used to measure the expression levels of the apoptosis-related proteins, Bax, Bcl-2, matrix metalloproteinase (MMP)-2, MMP-9, as well as to examine epithelial-mesenchymal transition (EMT), and E-cadherin, vimentin, and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway-related protein expression. The mRNA expression levels of miR­16 were highest in the SMMC-7721 cells and lowest in the SK-Hep­1 and Huh­7 cells; moderate levels were observed in the HepG2 cells. The HepG2 cell line was selected as the cell line for use in the follow-up experiments, where we measured cell viability, and the expression of PI3k/Akt, Bax, Bcl-2, MMP-2 and MMP-9, and E-cadherin and vimentin. miR­16 overexpression significantly inhibited the proliferation, invasion and metastasis of the HepG2 cells, as shown by western blot analysis. This was achieved through the upregulation of Bax expression, the downregulation of Bcl-2 expression and the decrease in the expression of MMP-2 and MMP-9. In addition the expression of E-cadherin increased and vimentin expression decreased. miR­16 overexpression inhibited PI3K expression and Akt phosphorylation. The results of this study suggest that the overexpression of miR­16 inhibits the proliferation, invasion and metastasis of HepG2 HCC cells, and that these effects are associated with the PI3K/Akt signaling pathway.