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Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by the foamy CD68+CD1a- histiocytes infiltrating multiple organs and tissues. ECD might be asymptomatic or present with variable manifestations. The diagnosis of ECD requires characteristic radiological findings and pathological features. Herein, we described a 52-year-old female patient who was admitted to our hospital for recurrent pericardial effusion for two months. She has a medical history of papillary thyroid carcinoma (PTC) and underwent a total thyroidectomy two years before admission. The radiological findings suggested a potential diagnosis of ECD. Cytological analysis of the effusion cytology specimen revealed CD68+CD1a - histiocytes, confirming the ECD diagnosis. The BRAF V600E mutation was identified in the histiocytes, prompting the administration of vemurafenib, a BRAF inhibitor. After two months of standard-dose vemurafenib treatment, the disease was well controlled with pericardial effusion regression., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type has a favorable outcome with radiation therapy alone, and the addition of chemotherapy shows no survival benefit. Nonetheless, a proportion of patients will relapse or progress, with a dismal outcome, highlighting the need for a novel therapeutic strategy. Promising preliminary findings indicate the efficacy of PD-1/PD-L1 inhibitors in extranodal natural killer/T-cell lymphoma, nasal type, with good toxicity profiles. Here we describe the design of a phase II study (CLCG-NKT-2101), which is evaluating the safety and efficacy of adding anti-PD-1 antibody to the current radiation therapy regimen in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type patients. Tislelizumab will be added in an inductive and concurrent way to radiation therapy. The primary end point will be the complete response rate after induction immunotherapy. Clinical trial registration: ClinicalTrials.gov (NCT05149170).

Background: Epigenetic alteration plays an essential role in the occurrence and development of extranodal natural killer/T cell lymphoma (ENKTL). Histone methyltransferase (HMT) KMT2D is an epigenetic regulator that plays different roles in different tumors, but its role and mechanism in ENKTL are still unclear., Methods: We performed immunohistochemical staining of 112 ENKTL formalin-fixed paraffin-embedded (FFPE) samples. Then, we constructed KMT2D knockdown cell lines and conducted research on cell biological behavior. Finally, to further investigate KMT2D-mediated downstream genes, ChIP-seq and ChIP -qPCR was performed., Results: The low expression of KMT2D was related to a decreased abundance in histone H3 lysine 4 mono- and trimethylation (H3K4me1/3). In KMT2D knockdown YT and NK-YS cells, cell proliferation was faster (P < 0.05), apoptosis was decreased (P < 0.05), the abundance of S phase cells was increased (P < 0.05), and the level of H3K4me1 was decreased. Notably, ChIP-seq revealed two crucial genes and pathways downregulated by KMT2D., Conclusions: KMT2D is a tumor suppressor gene that mediates H3K4me1 and influences ENKTL proliferation and apoptosis by regulating the cell cycle. Moreover, in ENKTL, serum- and glucocorticoid-inducible kinase-1 (SGK1) and suppressor of cytokine signaling-1 (SOCS1) are downstream genes of KMT2D., (© 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.)

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT., (© 2023 UICC.)

Extranodal natural killer/T-cell lymphoma (ENKTL) with hepatosplenic involvement is rare, accounting for approximately 0.2% of ENKTL cases. The clinicopathologic features of ENKTL with hepatosplenic involvement are still poorly understood. Seven cases of ENKTL with hepatosplenic involvement were investigated retrospectively by clinical features, pathology, immunophenotype, genotype, Epstein-Barr virus (EBV) status, and survival analysis. The median age was 36 years; three patients (3/7) had a history of primary nasal ENKTL. Six cases (6/7) presented liver or spleen structures that were replaced by neoplasms, and the neoplastic cells displayed diffuse infiltration; one case (1/7) displayed neoplastic cells scattered in hepatic sinuses and portal areas. The cellular morphology and immunohistochemical features were similar to those of ENKTL involving other sites. Follow-up data were available in five of the seven patients. All five patients received first-line chemotherapy based on L-asparaginase. Three patients died, and two were still alive by the last follow-up. The median overall survival (OS) was 21 months. ENKTL with hepatosplenic involvement is rare, regardless of whether it is initial or secondary. There are two histopathologic patterns of ENKTL with hepatosplenic involvement, and L-asparaginase-based chemotherapy combined with AHSCT might yield good efficacy. Morphological features of ENKTL in the spleen and liver A The architecture of the spleen was affected, and dense infiltration of the neoplastic cells was observed in the left part; B Focal infiltration of the neoplastic cells was located in the red pulp; C Dense infiltration of the neoplastic cells in the liver, accompanied by fatty change of hepatocytes and congestion; D More neoplastic cells accumulated in sinusoidal region., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Limited research exists on factors influencing the place of death (POD) or hospital deaths among lymphoma patients in China, despite the country's significant burden of lymphoid neoplasms. This study aimed to describe the distribution of POD among lymphoma patients and identify the factors associated with hospital lymphoma deaths to provide evidence for developing targeted healthcare policies. Data in this study were obtained from the National Mortality Surveillance System (NMSS). The distribution of POD among individuals who died from lymphoma was analyzed, and factors influencing the choice of dying in the hospital were examined. Chi-square test was employed to analyze the differences in characteristic distributions. Multilevel logistic regression analysis was identify the relationship between hospital deaths due to lymphoma and individual factors, as well as socioeconomic contextual variables. During 2013-2021, there were 66772 lymphoma deaths reported by the NMSS, including 44327 patients (66.39%) who died at home and 21211 (31.77%) died in the hospital. Female patients, those had a higher level of educational attainment, retired individuals, those died of non-Hodgkin lymphoma, residents of urban areas, patients between the ages of 0 and 14, and unmarried individuals had a higher probability of dying in hospitals. Improving health care providers' understanding of palliative care for cancer patients and prioritizing accessible services are essential to enhance the quality of end-of-life care. These approaches ensure the equitable allocation of healthcare resources and provide diverse options for minorities with specific preferences regarding end-of-life care., Competing Interests: None., (AJCR Copyright © 2023.)

Background: The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI-ENKTL)., Methods: The clinical data of GI-ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively., Results: A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty-nine patients received chemotherapy, of whom 15 patients received asparaginase-based (ASP-based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP-based regimens, and 50.0% and 25.0% for those treated with non-ASP-based regimens, respectively. The median follow-up was 12.9 months and the 1-year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP-based regimens resulted in a superior 1-year progression-free survival rate compared to non-ASP-based regimens (100.0% vs. 36.0%, p = .07). However, ASP-based regimens did not improve survival in patients at an advanced stage., Conclusion: GI-ENKTL still has a poor prognosis, even in the era of modern asparaginase-based treatment strategies., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Anaplastic lymphoma kinase (ALK)-positive histiocytosis, a novel rare histiocytic proliferation, was first described in 2008; it occurs in early infancy with liver and hematopoietic involvement. The spectrum was subsequently broadened to include localized diseases in older children and young adults. However, its full clinicopathological features and molecular lineage have not been fully elucidated., Results: Here, we report four cases of multisystem ALK-positive histiocytosis without hematopoietic involvement. Clinically, three patients were adults aged between 32 and 51 years. Two patients', whose main manifestations were intracranial mass and numerous micronodules in the thoracoabdominal cavity organs and skin papules respectively, had a partial response to ALK inhibitors after surgery. One patient presented with mediastinal neoplasm without surgical treatment, and progressive disease occurred after two years of ALK inhibitor therapy. The fourth patient was a 17-month-old male with a large intracranial mass and presented with a poor response to ALK inhibitor and chemoradiotherapy; he died eight months after surgery. Pathologically, the histiocytes were large, with abundant eosinophilic cytoplasm, and mixed with variable numbers of foamy cells and Touton giant cells. Interstitial fibrosis was also observed. Histiocytes were positive for macrophage markers (CD68 and CD163) and ALK. KIF5B-ALK fusions were detected in two cases, EML4-ALK in one, and both DCTN1-ALK and VRK2-ALK fusions were detected in one case., Conclusions: We observed that ALK inhibitors present robust and durable responses in adult patients but a poor response in young children with central nervous system involvement. There is no consensus on the optimal treatment regimen and long-term prognosis requires further observation. Moreover, every unusual histiocytic proliferative lesion, especially unresectable and multisystem involvement, should be routinely tested for ALK immunohistochemical staining to identify this rare disease., (© 2023. The Author(s).)

P53 prognostic cut-off values differ between studies of mantle cell lymphoma (MCL), and its immunohistochemistry (IHC) interpretation is still based on semiquantitative estimation, which might be inaccurate. This study aimed to investigate the optimal cut-off value for p53 in predicting prognosis of patients with MCL and the possible use of computer image analysis to identify the positive rate of p53. We calculated p53 positive rate using QuPath software and compared it with the data obtained by manual counting and semiquantitative estimation. Survival curves were generated by using the Youden index and the Kaplan-Meier method. The chi-squared (χ2) test was used to compare MIPI, Ann Arbor stage, and cell morphology with p53. Spearman rank correlation test and Bland-Altman analysis were used to compare manual counting, computer image analysis and semiquantitative estimation, as well as the consistency between different observers. The optimal cut-off value of p53 for predicting prognosis was 20% in MCL patients. Patients with p53 ≥ 20% had a significantly worse overall survival (OS) than those with p53 < 20% (P < 0.0001). MCL patients with MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant cell morphology had more p53 ≥ 20%. There was a strong correlation between computer image analysis and manual counting of p53 from the same areas in MCL tissues (Spearman's rho = 0.966, P < 0.0001). The results of computer analysis are completely consistent between observers, and computer image analysis of Ki-67 can predict the prognosis of MCL patients. MCL patients with p53 ≥ 20% had a shorter OS and a tendency for MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant. Computer image analysis could determine the actual positive rate of p53 and Ki-67 and is a more attractive alternative than semiquantitative estimation in MCL., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We herein present an overview of the upcoming 5 th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4 th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5 th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms., (© 2022. The Author(s).)

Background and Aims: The clinical outcome of relapsed and refractory (RR) extranodal natural killer/T-cell lymphoma (ENKTL) is poor. It is necessary to identify RR patients in ENKTL and find novel therapeutic targets to improve the prognosis of patients with RR ENKTL., Methods: A total of 189 ENKTL patients with effective clinical characteristics were enrolled. Paraffin specimens were collected for PD-L1 expression identification. Kaplan-Meier curve analysis was performed for survival analysis. Whole exome sequencing (WES) was performed for identifying the mutational characterization of RR and effective treatment (ET) patients., Results: Univariate and multivariate Cox proportional hazards regression analysis showed that negative PD-L1 expression (HR = 1.132, 95% CI = 0.739-1.734, P = 0.036) was an independent predictor of poor prognosis in patients with ENKTL. The overall survival (OS) of PD-L1 positive patients was significantly higher than that of PD-L1 negative patients ( P = 0.009). Then, we added PD-L1 expression as a risk factor to the model of Prognostic Index of Natural Killer Lymphoma (PINK), and named as PINK+PD-L1. The PINK+PD-L1 model can significantly distinguish RR patients, ET patients, and the whole cohort. Moreover, our data showed that PD-L1 expression was lower than 25% in most RR patients, suggesting that RR subtypes may be associated with low expression of PD-L1 ( P = 0.019). According to the whole exome sequencing (WES), we found that the mutation frequencies of JAK-STAT ( P = 0.001), PI3K-AKT ( P = 0.02) and NF-kappa B ( P < 0.001) pathways in RR patients were significantly higher than those in ET patients., Conclusion: Patients tend to show RR when PD-L1 expression is lower than 25%. The model of PINK+PD-L1 can stratify the risk of different groups and predict OS in ENKTL patients. The mutational profile of ENKTL patients with RR is different from that of patients with ET., Competing Interests: Author XS, JW, and YL were employed by OrigiMed Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Zhang, Shi, Liu, Wang, Zhang and Liu.)

Anopheles anthropophagus (Xu and Feng 1975) is the major vector of malaria in Eastern and Southern China. The species An. anthropophagus is considered a synonym of An. lesteri (Baisas & Hu, 1936), although they differ in several key biological characteristics. Here, we report the complete mitochondrial genome of An. anthropophagus for the first time. The mitogenome of An. anthropophagus is a typical circular, double-stranded molecule with a total length of 15,413 base pairs, and contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and an AT-rich control region. A phylogenetic analysis of the complete mitogenomes of 16 species of Anopheles (Culicidae) revealed that An. anthropophagus is closely related to An. sinensis (Wiedemann 1828), in the family Culicidae. The An. anthropophagus mitogenome provides new data for further taxonomic and phylogenetic studies of the genus Anopheles ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

A new fluorescence probe method for the detection of Hg(II) in serum was established, which has the detection limit of 3.57 nM and quantification limit of 5 nM, based on the electrostatic induced agglomeration quenching and complexation between Hg(II) and silicon-nitrogen-doped carbon nanodots (Si/N-CDs). Furthermore, the fluorescence probe also showed the satisfactory results in the determination of Hg(II) in human serum. Subsequently, take advantage of the uric acid (UA) to recover the fluorescence of the Si/N-CDs-Hg(II) complex probe, another enzyme-free ways to determine UA was developed. The complex probe can selectively detect the UA content in the 0.5-30 μM range, and its detection limit can reach 0.14 μM, which has successfully detected the UA in total serum, and the results were no significant difference comparing with the controls., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Herein, cobalt and nitrogen co-doped carbon dots (Co-N-CDs) were fabricated via a one-pot hydrothermal approach. The obtained Co-N-CDs displayed peroxidase-like activity and fluorescence properties. It could catalyze the oxidization of guaiacol (GA) in the presence of hydrogen peroxide (H 2 O 2 ), and thus, resulted in color change, accompanied by a new absorption peak in 470 nm. Owing to the inner filter effect, the oxidized product of GA (known as 2-PQ) largely absorbed the Co-N-CD fluorescence which was excited at 380 nm. Such changes in absorbance and fluorescence intensity were H 2 O 2 concentration-dependent. Specifically, H 2 O 2 could be generated by glucose oxidase to catalyze the oxidation of glucose, and thus, a colorimetric and fluorimetric sensor for glucose was established with high selectivity and excellent sensitivity. After the optimization of experimental conditions, this colorimetric sensor has a good linear range from 2 to 100 μM for glucose and the detection limit was 1.16 μM. Besides, the linear relationship between the fluorescence quenching value (ΔF) and the glucose concentration (0.4-40 μM) was obtained with a detection limit of 0.18 μM. Meanwhile, the proposed sensor has also been successfully applied for glucose detection in human serum samples, and the results were consistent with those of the standard method.

Purpose: To assess the performance of the Antibody Prevalence in Chinese Patients with Epilepsy and Encephalopathy (APE 2 -CHN) and Response to Immunotherapy in Chinese Patients with Epilepsy and Encephalopathy (RITE 2 -CHN) scores in Chinese patients with epilepsy of unknown etiology., Methods: We conducted a retrospective study of selected patients from Xiangya Hospital, Central South University (01/01/2017-02/28/2019) whose serum and/or cerebrospinal fluid (CSF) samples were examined for autoimmune encephalitis antibodies. Of these, patients with diagnostic code of seizure or epilepsy were selected in our study. An APE 2 -CHN score was assigned to each patient and a RITE 2 -CHN score was calculated for each patient who received immunotherapy. Receiver-operating characteristic (ROC) curve was used to assess each score., Results: 191 patients were enrolled in our study. 36 were identified with specific etiologies. The remaining 155 patients had unknown etiology. Central nervous system-specific antibodies were detected in 76 (49.0 %) patients, after excluding patients with only anti-thyroid peroxidase or glutamic acid decarboxylase antibodies. N-methyl-d-aspartate receptor (NMDAR) antibody (48.7 %, 37/76) was the most common subtype of our sample, followed by γ-aminobutyric acid type B receptor (GABAR) (14.5 %, 11/76). Clinical features including new-onset epilepsy, neuropsychiatric changes, speech disorder, movement disorder and inflammatory CSF profile correlated with positive antibody results. The sensitivity and specificity of APE 2 -CHN ≥ 5 in predicting the presence of neural-specific autoantibodies in our study were 85.5 % and 58.9 % respectively. In the subset of patients who received immunotherapy (n = 112), sensitivity and specificity of a RITE 2 -CHN ≥ 8 in predicting favorable seizure outcome were 98.6 % and 63.2 % respectively. The area under the curve (AUC) of RITE 2 -CHN was greater than that of RITE 2 (Z = 3.196, p < 0.05) while there was no significant difference in AUC between APE 2 and APE 2 -CHN (Z = 1.058, p = 0.290)., Conclusion: The APE 2 -CHN and RITE 2 -CHN scores may be useful screening tools in predicting positive antibody findings and prognosis of suspected autoimmune seizures or associated epilepsy in the Chinese population., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Inter- and intratumoral heterogeneity is a hallmark of glioblastoma (GBM) that facilitates recurrence, treatment resistance, and worse prognosis. O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic marker for Temozolomide (TMZ) resistance in GBM patients. YKL-40 is a molecular marker for the mesenchymal subtype of GBMs and is responsible for TMZ resistance. However, underlying mechanisms by which MGMT epigenetics impacts patient outcomes and the function of YKL-40 are not fully determined. Herein, we performed in vitro and in vivo experiments, six human IDH1/2 wild-type glioblastoma stem-like cells (GSCs) were established and studied to further determine a potential interaction of YKL-40 and MGMT promoter methylation. We demonstrated that YKL-40 functioned differently in human IDH1/2 wild-type GSCs. In MGMT promoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, in MGMT promoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason that YKL-40 played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function of MGMT promoter methylation status and involves the RAS-MEK-ERK pathway. YKL-40 mediated TMZ sensitivity by activating DNA damage responses (DDRs) in MGMT-m GSCs, and it mediated resistance to TMZ by inhibiting DDRs in MGMT-um GSCs. Our report demonstrated that MGMT promoter methylation status might influence a gene's function in human cancer. Moreover, our data also highlight the point that gene function should be investigated not only according to the molecular tumor classification, but also the epigenetic signature.

BACKGROUND Parasitic helminths in the esophagus are rare. Here, we report a case of esophageal scab mimicking a parasite. CASE REPORT A 65-year-old man was admitted to our hospital because after choking on food. Gastroscopy showed 2 foreign bodies adherent to the esophagus wall 28 and 34 cm from the incisor, which appeared to be a fluke. Two fluke-like foreign bodies (1.5 and 1.8 cm in length) were removed from the esophageal ulcer with forceps. After fixation with alcohol, the suspected fluke-like foreign bodies were noted to be brown and woody. Under a light microscope, the structure of the foreign body was not apparent, and no typical flatworm tegument structure was demonstrated on pathologic sections, but it had a blood clot-like structure. Administration of albendazole did not expel any helminths. A stool examination showed no eggs of the putative flukes. The genomic DNA of the suspected flukes was extracted and a 700 bp fragment was amplified by universal barcoding primers. The sequencing showed that the homology with human cytochrome c oxidase subunit I gene was 98.8%. CONCLUSIONS The scab formed by the esophageal ulcer was identified based on clinical manifestations, anti-helminth and stool examinations, parasite morphology, and molecular biology. Our experience with this case suggests that the universal barcoding technique can be used for identification of foreign bodies suspected to be parasites.

Background: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL-N) is an aggressive lymphoma typically diagnosed by examining small biopsy specimens. Flow cytometry is very valuable for the diagnosis and classification of several kinds of hematolymphoid neoplasms but has not been widely used for diagnosing ENKTL-N., Methods: We systematically investigated the flow cytometry characteristics of 26 solid tissue biopsy specimens of ENKTL-N at initial diagnosis and compared the results with those from reactive NK-cells in the nasal/nasopharyngeal region and peripheral blood., Results: Our study revealed seven flow cytometry (FCM)-based characteristics for distinguishing between the neoplastic cells and reactive NK-cells, including (1) the proportion of NK-cells among total lymphocytes >10%; (2) forward scatter >10 5 ; (3) mean fluorescence intensity of CD56 > 5,000; (4) aberrant antigen expression or loss; (5) skewed killer cell immunoglobulin-like receptor repertoire; (6) homogenously positive for CD38; and (7) positive for CD30 or CD336. FCM-based immunophenotyping is a potentially feasible and convenient approach for discriminating cellular lineages, evaluating the activation status of NK-cells, and selecting potential therapy targets of ENKTL-N., Conclusions: Flow cytometry is very valuable for facilitating routine diagnosis, confirming clonality, predicting the cellular lineage, and guiding individual treatment for ENKTL-N. © 2019 International Clinical Cytometry Society., (© 2019 International Clinical Cytometry Society.)

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL-N) initially presented in larynx is a rare condition without distinctive clinicopathologic features, with a challenging pathologic diagnosis. This study aimed to evaluate the clinicopathologic features and diagnosis of laryngeal ENKTL-N and spread awareness regarding ENKTL-N. A series of 31 cases of laryngeal ENKTL in one Chinese institution over a 9-year interval was retrospectively analyzed. Median age was 50 years (range, 13 to 77 y) with a male/female ratio of 5.2:1 (26/5). All patients initially presented with hoarseness and/or laryngalgia, and 10 patients (32.3%) experienced B symptoms. The supraglottic region was the most common site of occurrence (58.1%), the glottic area being the rarest site (6.5%). The mucosal squamous epithelium was detected in 26 specimens and pseudoepitheliomatous hyperplasia was observed in 8 cases (8/26, 30.8%). "Keratin-pearls" and a "pseudoinvasive" pattern were observed in 2 cases. Follow-up data were available for 26 patients (83.9%), the median survival duration was 9 months, and the overall survival rate at 5 years was 29.6%. Univariate analysis revealed that patients experiencing B symptoms (P=0.019) and age above 60 years had a significantly low survival (P=0.049) and that combined radiotherapy and chemotherapy prolongs overall survival (P<0.001). Laryngeal ENKTL-N is a rare entity with high aggressiveness and a poor prognosis. Multiple biopsies are usually required owing to secondary infection and massive necrosis. Laryngeal EKTL-N may mimic inflammatory lesions or well-differentiated squamous cell carcinoma. Therefore, clinical vigilance is essential to prevent misdiagnosis or a delayed diagnosis.

Background: The value of prophylactic antiviral therapy in patients with past hepatitis B virus (HBV) infection (HBV surface antigen-negative/anti-HBV core antibody-positive/HBV DNA negative) is still controversial., Patients and Methods: This study compared the safety, efficacy, and cost-effectiveness of prophylactic entecavir (ETV) with regular monitoring alone in lymphoma patients with past HBV infection. Patients were randomly assigned to chemotherapy alone (control) or prophylactic ETV before chemotherapy and at least 6 months after completion of chemotherapy. All patients underwent close virologic and biochemical surveillance. The primary end points were the incidence rates of HBV reactivation (appearance of HBV DNA) and HBV reactivation-related hepatitis (defined as a greater than 3-fold increase in serum alanine aminotransferase levels exceeding 100 IU/L)., Results: A total of 190 patients were included, 141 (74.2%) of whom were positive for anti-HBV surface antibody (HBs). The incidence rates of HBV reactivation and HBV reactivation-related hepatitis were 0 (0/95) and 0 (0/95) in the prophylactic ETV group, respectively, and 3.2% (3/95) and 1.1% (1/95) in the control group, respectively (P = .246 and 1.000, respectively). One patient experienced HBV reactivation-related hepatitis, resulting in premature termination of chemotherapy. All 3 patients with HBV reactivation recovered after therapeutic ETV treatment. No HBV-related deaths were observed during the follow-up period. The cost in the prophylactic ETV group was higher than that in the control group ($125 per month)., Conclusion: Prophylactic antiviral therapy is not a cost-effective strategy for the management of lymphoma patients with past HBV infection, especially those positive for anti-HBs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Limited studies are available on the molecular pathogenesis of Epstein-Barr virus (EBV)-associated T or natural killer (NK) cell lymphoproliferative disorders (EBV+T/NK-LPD). In this retrospective study, we aim to elucidate the mutation profile of EBV+T/NK-LPD using capture-based targeted sequencing with a panel consisting of 64 lymphoma-related genes to identify driver genes associated with the development of EBV+T/NK-LPD. Targeted sequencing of 169 EBV+T/NK-LPD cases was performed using a panel of 64 lymphoma-related genes. Of the 169 EBV+T/NK-LPD cases, 123 had extra-nodal NK/T-cell lymphoma (ENKTL), 12 had aggressive NK-cell leukemia (ANKL) and 34 had EBV+ T-cell lymphoma of childhood (EBV+TL). The mutation profile revealed that all three subtypes of EBV+T/NK-LPDs had high mutation rates in STAT3, KMT2D, DDX3X, NOTCH1 and TET2 . Target sequencing revealed that ENKTL, ANKL and EBV+TL were molecularly distinct, the mutation in nasal-ENKTL and extra-nasal-ENKTL are also different. Survival analysis revealed that ENKTL patients with gene mutations or loss of protein expression in either KMT2D or TET2 were significantly correlated with shorter overall survival. And although the EBV+TL and ANKL groups were too small to confirm survival disadvantage, the adverse prognosis trends of KMT2D or TET2 were showed in these two groups. We conclude that EBV+T/NK lymphoproliferative disorders have very distinct molecular profiles. Our findings also suggest the likely involvement of KMT2D and TET2 in the development of ENKTL, and possibly EBV+T/NK-LPDs in general.

Background: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein-Barr virus (EBV)-associated lymphoma that mainly affects children., Objectives: To examine the similarities and differences in the clinical pathological features, EBV infection status, and gene rearrangements in adults and children patients with HVLPD., Methods: We compared the clinical manifestations, histopathology, immunophenotypical features, EBV infection status, and T-cell receptor gene rearrangements in the adult and children HVLPD groups., Results: Clinical manifestations differed between children and adults groups. The children were characterized by blisters and severe facial swelling, whereas the adults were characterized by mild facial swelling and papules. Mosquito bite was significantly related to morbidity in the children group. Histologically, the number of mast cells in the adult group was greater than in the children group (P < 0.05). There were no significant differences in EBV infection status or TCR-γ gene rearrangements between 2 groups., Conclusions: There were differences in clinical pathology and prognosis between the 2 groups. A higher mast cell count and T-cell phenotype might be associated with a poor prognosis.

Background: Paddy soil dissolved organic matter (DOM) represents a major hotspot for soil biogeochemistry, yet we know little about its chemodiversity let alone the microbial community that shapes it. Here, we leveraged ultrahigh-resolution mass spectrometry, amplicon, and metagenomic sequencing to characterize the molecular distribution of DOM and the taxonomic and functional microbial diversity in paddy soils across China. We hypothesized that variances in microbial community significantly associate with changes in soil DOM molecular composition., Results: We report that both microbial and DOM profiles revealed geographic patterns that were associated with variation in mean monthly precipitation, mean annual temperature, and pH. DOM molecular diversity was significantly correlated with microbial taxonomic diversity. An increase in DOM molecules categorized as peptides, carbohydrates, and unsaturated aliphatics, and a decrease in those belonging to polyphenolics and polycyclic aromatics, significantly correlated with proportional changes in some of the microbial taxa, such as Syntrophobacterales, Thermoleophilia, Geobacter, Spirochaeta, Gaiella, and Defluviicoccus. DOM composition was also associated with the relative abundances of the microbial metabolic pathways, such as anaerobic carbon fixation, glycolysis, lignolysis, fermentation, and methanogenesis., Conclusions: Our study demonstrates the continental-scale distribution of DOM is significantly correlated with the taxonomic profile and metabolic potential of the rice paddy microbiome. Abiotic factors that have a distinct effect on community structure can also influence the chemodiversity of DOM and vice versa. Deciphering these associations and the underlying mechanisms can precipitate understanding of the complex ecology of paddy soils, as well as help assess the effects of human activities on biogeochemistry and greenhouse gas emissions in paddy soils.

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., Competing Interests: None., (IJCEP Copyright © 2018.)

Interstitial pneumonia (IP) is a lethal complication in lymphoma patients undergoing chemotherapy. A total of 2212 consecutive patients diagnosed with lymphoma between 2009 and 2014 were enrolled in the present study. IP was defined as diffuse pulmonary interstitial infiltrate found on computed tomography scans. IP was observed in 106 patients. Of these, 23 patients were excluded from the study. Finally, 83 patients with IP were included in this study. The incidence of IP was 3.9% (7/287) in Hodgkin lymphoma and 2.4% (76/1925) in non-Hodgkin lymphoma (P = 0.210). The median number of chemotherapy cycles before IP was 3. The median time from the cessation of chemotherapy to IP was 17 days. Eighty-two (98.8%) patients recovered after the treatment with glucocorticoids. Sixty-six (79.5%) patients had a delay in chemotherapy, and 14 (16.9%) patients had premature termination of chemotherapy. Sixty-nine patients were re-treated with chemotherapy after remission from IP, of which 22 (31.9%) experienced IP recurrence. The incidence of IP recurrence was significantly higher in patients re-treated with a similar regimen than in those re-treated with an alternative regimen (65.4 vs. 11.6%, P < 0.001). In a multivariate Cox regression analysis, B symptoms and a history of drug allergies were identified as risk factors for IP. In conclusion, IP is a life-threatening complication in lymphoma patients. Glucocorticoid therapy with continuous monitoring of chest radiographic changes may be a favourable strategy for treating IP. However, IP may recur, especially in patients re-treated with a similar chemotherapy regimen.

Objective: To investigate the changes in the expression of EphA5 and its ligand ephrinA5 in the hippocampus of rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy (TLE)., Methods: A total of 240 Sprague-Dawley rats were randomly divided into control group and TLE group, with 120 rats in each group. A rat model of lithium-pilocarpine TLE was established, and then the rats were divided into subgroups at 12 and 24 hours and 7, 15, 30, and 60 days after epilepsy was induced. In-situ hybridization was used to measure the mRNA expression of ephrinA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; immunohistochemistry was used to measure the protein expression of EphA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; Neo-Timm silver staining was used to observe mossy fiber sprouting in the CA3 region of the hippocampus in 2 rats., Results: In-situ hybridization showed mRNA expression of ephrinA5 in the CA3 region of the hippocampus, but this was not found in the dentate gyrus. Compared with the control group at the same time point, the TLE group had a significant reduction in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced (P<0.05); at 30 and 60 days after epilepsy was induced, the TLE group had a gradual increase in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus, and there was no significant difference between the TLE and control groups (P>0.05). Immunohistochemistry showed that EphA5 protein was expressed in the CA3 region and the dentate gyrus of the hippocampus and had a similar trend of change as ephrinA5 mRNA. Neo-Timm silver staining showed that the TLE group developed marked mossy fiber sprouting in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced., Conclusions: Downregulation of ephrinA5 and EphA5 in the CA3 region of the hippocampus may participate in the mechanism of mossy fiber sprouting and is closely associated with the development and progression of epilepsy.

Somatic mutation in the epidermal growth factor receptor (EGFR) predict clinical response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) and is a promising target for personalised medicine. EGFR mutations have prognostic value. Initially patients respond well to tyrosine kinase inhibitors but finally they would develop resistance and about 50% of this resistance can be attributed to the emergence of EGFR resistant mutation, T790M. This necessitates the need for genetic testing for clinical management of patients. Molecular testing has become the standard of care in patients with NSCLCs based on the recommendations of standard guidelines. Though there are several platforms for EGFR mutation detection, highly sensitive platforms for clinical applicability as companion diagnostics for ctDNA based testing are emerging. Due to the dynamic changes in the T790M mutation during tyrosine kinase inhibitor (TKI) treatment, real-time monitoring of these genetic alterations is mandate for planning treatment strategies. With the advent of third generation TKIs that potentially target T790M, improvement in clinical outcome is documented in patients with NSCLCs. Managing these outcomes with appropriate companion diagnostics using ctDNA in early detection of these genetic alterations will improve patient care., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Nasal-type, extranodal NK/T cell lymphoma (ENKTCL) is a special type of lymphomas with geographic and racial specificity. Up to now, the standard first-line treatment is still not unified. In our previous report, the "sandwich" protocol produced good results. Continuing to use the "sandwich" mode, a new chemotherapy composed of L-asparaginase, cisplatin, etoposide and dexamethasone (LVDP) plus concurrent chemoradiotherapy (CCRT) was conducted in more patients with newly diagnosed, I/II stage ENKTCL. The results showed that 66 patients were enrolled. Overall response rate was 86.4% including 83.3% complete response and 3.0% partial remission. With the median follow-up of 23.5 months, 3-year overall survival and 3-year progression-free survival were 70.1% and 67.4%, respectively. The survival rate in stage II and extra-cavity stage I was significantly less than that in limited stage I (p < 0.05). Therefore, we thought that the "sandwich" mode was worthy of being generalized and LVDP combined with CCRT was an effective protocol for I/II stage ENKTCL. But this regimen was not suitable for all stage I/II patients and warrants larger sample and layering investigation. This study was a registered clinical trial with number ChiCTR-TNC-12002353.

Background: It is a great challenge for pathologists to initially diagnose metastatic malignant mesothelioma (MM) by the lymph node biopsy without any history of primary MM. Because the onset of MM is hidden and the metastatic MM in lymph node is relatively uncommon. Besides, morphologic and immuohistochemistry features of MM are similar to other tumors., Methods: In order to improve the initial diagnostic accuracy of metastatic MM from LN biopsy and to reduce or avoid the possibility of missed diagnosis or misdiagnosis, we had collected the clinical and pathological data of the metastatic MM cases in our department, and summarized the characteristics of morphological, immunohistochemical and fluorescence in situ hybridization (FISH) results., Results: Seven patients (4 males and 3 females) with 21-73 year-old had been included in our study. Six cases showed serous cavity effusion, serosal thickening and systemic multiple lymph node enlargement. The "moderate, nice" tumor cells were arranged in variable patterns. Mitosis was hardly to be found and necrosis was absent. Four immunohistochemical staining panels and FISH detection had been used for diagnosis and differential diagnosis of MM. All cases expressed broad-spectrum epithelial markers and at least 2 mesothelial-cell-origin markers. None were positive for specific-tissue-origin markers, and all cases were diagnosed of malignancy according to immunohistochemical markers and detection of pl6 gene deletion., Conclusion: It is necessary for us to keep our awareness of metastatic MM in lymph node. Correct diagnosis of MM metastasis by lymph node biopsy were based on detailed understanding of the clinical manifestation and the image data, careful observation of morphologic characteristics, and properly using immunohistochemical markers or FISH detection if necessary for diagnosis and differential diagnosis., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objectives: To discover the incidence and characteristics of EGFR mutations in non-small cell lung cancer (NSCLC) in a single, large cohort as a part of routine diagnostic investigations., Methods: We reviewed EGFR mutations investigated by Amplification Refractory Mutation System (ARMS) PCR (covering 29 known mutations) using DNA samples from FFPE tissue or cell clot specimens in a total of 3894 cases of NSCLC analysed between 2012-2014., Results: EGFR mutations are preferentially associated with adenocarcinomaand adenosquamous histology, particularly those well to moderately differentiated, and were significantly more common in female than male patients irrespective of histological subtypes. Exon 19 deletion (45.7%) and exon 21 L858R (45.6%) accounted for the vast majority of the EGFR mutations detected, with the remaining mutations being infrequent (<2%). Compound mutations were seen in 51 (3%) of the mutant cases, the combination of these compound mutations could be classified into three subgroups according to the potential impact of individual mutations on EGFR TKI therapy. Accordingly, 7 cases had both sensitive mutations, 4 cases harboured one sensitive and one less responsive /uncertain mutation, 19 cases contained one sensitive and one resistant change, and a further 21 cases had two less responsive /uncertain mutations., Conclusion: Our data represents the largest EGFR mutation survey based on routine clinical diagnostic laboratory data from a single institution, it confirms the incidence and characteristics of EGFR mutations in NSCLC seen in Asian patients, and also unravels the combinatorial nature of rare compound EGFR mutations.

Level of adenosine, an endogenous astrocyte-based neuromodulator, is primarily regulated by adenosine P1 receptors. This study assessed expression of adenosine P1 receptors, ADORA1 (adenosine A1 receptor) and ADORA2A (adenosine A2a receptor) and their association with glioma development and epilepsy in glioma patients. Expression of ADORA1/ADORA2A was assessed immunohistochemically in 65 surgically removed glioma tissue and 21 peri-tumor tissues and 8 cases of normal brain tissues obtained from hematoma patients with cerebral trauma. Immunofluorescence, Western blot, and qRT-PCR were also used to verify immunohistochemical data. Adenosine P1 receptor ADORA1 and ADORA2A proteins were localized in the cell membrane and cytoplasm and ADORA1/ADORA2A immunoreactivity was significantly stronger in glioma and peri-tumor tissues that contained infiltrating tumor cells than in normal brain tissues (p < 0.05). The World Health Organization (WHO) grade III gliomas expressed even higher level of ADORA1 and ADORA2A. Western blot and qRT-PCR confirmed immunohistochemical data. Moreover, higher levels of ADORA1 and ADORA2A expression occurred in high-grade gliomas, in which incidence of epilepsy were lower (p < 0.05). In contrast, a lower level of ADORA1/ADORA2A expression was found in peri-tumor tissues with tumor cell presence from patients with epilepsy compared to patients without epilepsy (p < 0.05). The data from the current study indicates that dysregulation in ADORA1/ADORA2A expression was associated with glioma development, whereas low level of ADORA1/ADORA2A expression could increase susceptibility of tumor-associated epilepsy.

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.

The exact incidence and severity of hepatitis B virus (HBV) reactivation after the withdrawal of prophylactic antiviral therapy (delayed HBV reactivation) is unknown. We retrospectively analyzed 107 newly diagnosed diffuse large B cell lymphoma patients with HBV infection who received chemotherapy. The median time from the cessation of antitumor therapy to the withdrawal of prophylactic antiviral therapy was 6.1 months. The incidence of delayed HBV reactivation was 21.7% in HBsAg-positive group and 0 in HBsAg-negative/anti-HBc-positive group (P < 0.001). No HBV-related fulminant hepatitis or hepatitis-related death occurred. The multivariate analysis showed that female gender and lengthy cycles of chemotherapy (>8 cycles) were independent risk factors of HBV reactivation in HBsAg-positive patients. In conclusion, prophylactic antiviral therapy could be withdrawn 6 months after the cessation of chemotherapy in HBsAg-negative/anti-HBc-positive patients. However, a longer course of prophylactic antiviral drug administration may be an optimal option to prevent delayed HBV reactivation for HBsAg-positive patients.

The "sandwich" protocol, was first proposed by us and comprised of l-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy, results in 2-year overall survival and progression-free survival rates that surpass traditional therapies for patients with newly diagnosed, stage IE-IIE, nasal type, extranodal natural killer/T-cell lymphoma. The results had been published by cancer. These patients were followed up over a median period of 67 months, for which updates and the results of prognostic factors analyses are presented. The 5-year overall survival and progress-free survival rates were both 64%. The highest rates of death occurred during the first 6 months, and between the second and third year after enrollment. The initial therapeutic response (odds ratio = 5.83; P = 0.001) and B symptoms (odds ratio = 6.13; P = 0.043) were significant prognostic factors for overall survival. However, the international prognostic index was not significant for progress-free survival and overall survival. There were no severe long-term side effects. These results indicate that the "sandwich" protocol may benefit the long-term survival of patients with newly diagnosed stage IE-IIE, nasal type, extranodal natural killer/T-cell lymphoma. However, additional studies with larger samples are required to confirm these results. This study is registered at www.Chictr.org (ChicTR-TNC-09000394)., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: To investigate the prevalence of nosocomial infections, the distribution of nosocomial infection sites, the use of antibiotic and the situation of detected nosocomial infection pathogens in the Inner Mongolia Autonomous Region of China from 2012 to 2014, to grasp the current conditions of regional nosocomial infections in timely, for the development of infection prevention and control measures to provide a basis for effective hospital., Methods: A survey of the prevalence of nosocomial infections was conducted in target hospitals using the combination of a bedside survey and medical record review., Results: In total, 101,907 inpatients were surveyed from 2012 to 2014. There were 1,997 cases of nosocomial infections, accounting for an average prevalence of 1.96%. The infection site was mainly the lower respiratory tract. Higher prevalence of nosocomial infections occurred in the comprehensive intensive care unit (ICU), Neurosurgery Department, and Hematology Department. The average rate of antibiotic use was 33.72%, and the average submission rate for bacterial cultures for patients who received therapeutic treatment with antibiotics was 28.26%. The most common pathogens associated with nosocomial infections were Gram-negative (G(-)) bacteria, and frequently detected bacterial pathogens included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus., Conclusions: The survey of the prevalence of nosocomial infections helped to identify problems in the control process of nosocomial infections and to develop targeted measures for the prevention and control of these infections accordingly.

Objective: To investigate the expression and clinical significance of ubiquitin-specific protease 9X (USP9X) protein in non-small cell lung cancer (NSCLC)., Methods: USP9X proteins were detected in 71 cases of NSCLC and 20 cases of benign pulmonary tissues by immunohistochemical staining. The correlation between USP9X expression and 51 NSCLC clinicopathological parameters as well as survival rates were indicated., Results: Higher rate [69. 0% (49/71)] of the expression of USP9X was observed in NSCLC samples, compared with 20. 0% (4/20) in benign pulmonary tissues (P<0. 001). Furthermore, the expression of USP9X proteins was positively associated with both histological types and lymph node metastasis (P<0. 05). The survival analysis showed that the survival rate was lower in patients with positive expressions of USP9X than in patients with negative expressions (P< 0. 05). USP9X expression, together with histological types and TNM stage was an independent predictor for overall survival in the multivariate Cox regression model (P < 0. 05)., Conclusion: Up-regulation of USP9X plays an important role in the invasion and progression of NSCLC and could be considered as a prognostic predictor for NSCLC.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive disease characterized by frequent deletions on 6q, and constitutive activation of signal transducer and activator of transcription 3 (STAT3). Phosphorylation at Tyr705 activates STAT3, inducing dimerization, nuclear translocation, and DNA binding. In this study, we investigated whether receptor-type tyrosine-protein phosphatase κ (PTPRK), the only protein tyrosine phosphatase at 6q that contains a STAT3-specifying motif, negatively regulates STAT3 activation in NKTCL. PTPRK was highly expressed in normal NK cells but was underexpressed in 4 of 5 (80%) NKTCL cell lines and 15 of 27 (55.6%) primary tumors. Significantly, PTPRK protein expression was inversely correlated with nuclear phospho-STAT3(Tyr705) expression in NKTCL cell lines (P = .025) and tumors (P = .040). PTPRK restoration decreased nuclear phospho-STAT3(Tyr705) levels, whereas knockdown of PTPRK increased such levels in NKTCL cells. Phosphatase substrate-trapping mutant assays demonstrated the binding of PTPRK to STAT3, and phosphatase assays showed that PTPRK directly dephosphorylated phospho-STAT3(Tyr705). Restoration of PTPRK inhibited tumor cell growth and reduced the migration and invasion ability of NKTCL cells. Monoallelic deletion and promoter hypermethylation caused underexpression of PTPRK messenger RNA in NKTCL, and methylation of the PTPRK promoter significantly correlated with inferior overall survival (P = .049) in NKTCL patients treated with the steroid-dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide regimen. Altogether, our findings show that PTPRK underexpression leads to STAT3 activation and contributes to NKTCL pathogenesis., (© 2015 by The American Society of Hematology.)

Wnt/β-catenin and Hedgehog/Gli signalings play key roles in multiple biogenesis such as embryonic development and tissue homeostasis. Dysregulations of these 2 pathways are frequently found in most cancers, particularly in colon cancer. Their crosstalk has been increasingly appreciated as an important mechanism in regulating colon cancer progression. Our studies into the link between Wnt/β-catenin and Hedgehog/Gli signalings in colon cancer revealed several possible crosstalk points and suggested potential therapeutic strategies for colon cancer.

To analyze the differentiation characteristics of extranodal natural killer/T-cell lymphoma, nasal type, one nude mouse model, cell lines SNK6 and SNT8, and 16 fresh human samples were analyzed by flow cytometry immunophenotyping and immunohistochemistry staining; and 115 archived cases were used for phenotypic detection and prognostic analysis. We found that CD25 was expressed by most tumor cells in all samples, and CD56(+)CD25(+) cells were the predominant population in the mouse model, the 2 cell lines, and 10 of the 16 fresh tumor samples; in the other 6 fresh tumor samples, the predominant cell population was of the CD16(+)CD25(+) phenotype, and only a minor population showed the CD56(+)CD25(+) phenotype. The phenotype detected by immunohistochemistry staining generally was consistent with the phenotype found by flow cytometry immunophenotyping. According to the expression of CD56 and CD16, 115 cases could be classified into 3 phenotypic subtypes: CD56(-)CD16(-), CD56(+)CD16(-), and CD56(dim/-)CD16(+). Patients with tumors of the CD56(dim/-)CD16(+) phenotype had a poorer prognosis than patients with tumors of the other phenotypes. Differentiation of extranodal natural killer/T-cell lymphoma, nasal type apparently resembles the normal natural killer cell developmental pattern, and these tumors can be classified into 3 phenotypic subtypes of different aggressiveness. Expression of CD56(dim/-)CD16(+) implies a poorer prognosis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Burkitt lymphoma (BL) is a highly aggressive subtype of non-Hodgkin lymphomas (NHL). Lymphoma related granulomatous reaction rarely occurs in sporadic BL. Herein, we describe the first case of HIV related Burkitt lymphoma with florid granulomatous reaction. A 41-year-old HIV-positive Chinese male presented lymphadenopathy in the right cervical region for 3 months. The enlarged lymph node biopsies revealed the presence of prominent granulomas of varying size with Langhans giant cells, leading to the misdiagnosis of tuberculous lymphadenitis in other hospital. Subsequently, the case was sent to us for consultation. The morphology, immunophenotype, special staining, interphase FISH analysis and blood tests confirmed a diagnosis of HIV related Burkitt lymphoma with granulomatous reaction. Without radiotherapy and chemotherapy, the patient was alive and well with no evidence of lymphoma during the observation period of 24 months. The case suggested that lymphoma with florid granulomatous reaction can easily be misdiagnosed as benign lesions since the large number of epithelioid granulomas could obscure the primary lesion. Moreover, the granulomatous reaction may be an indicator for favorable prognosis in HIV related Burkitt lymphoma.

A ultraperformance liquid chromatography (UPLC)-photodiode array (PDA) detection method was established for the simultaneous determination of seven constituents in Fructus aurantii-Magnolia bark decoction: naringin, hesperidin, neohesperidin, narirutin, meranzin hydrate, honokiol and magnolol. These were separated in <17 min using a C18 column with gradient elution using (a) acetonitrile, (b) water and (c) acetic acid at a flow rate of 0.3 mL/min, and with a PDA detector. All calibration curves showed good linear regression (r(2) > 0.9992) within the test ranges. The method was validated for specificity, accuracy, precision and limits of detection. The proposed method was found to be suitable for the quality assessment of the formula., (© The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To investigate the clinicopathologic features, immunophenotype, and the prognosis related factors of Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) in west-southern China., Methods: There were 42 cases of EBV+ DLBCL in a total 586 DLBCL, the clinical and pathologic profiles of these patients were evaluated. Immunohistochemical study and in situ hybridization (ISH) of EBER1/2 were performed on formalin fixed tissues by tissue chips. The prognosis related factors were analyzed., Results: The median age of these 42 EBV+ DLBCL patients was 62.5 years. The male-to-female ratio was 2.23 : 1. The site of occurrence included lymph node (69.05%) and spleen, stomach, tonsil, nasal cavity and nasopharynx. The mostly common initial clinical presentations were non-specific symptoms, such as lymphadenopathy, splenomegaly, hepatomegaly, fever, and fatigue. Morphologically, the majority (90.48%, 38/42) were pleomorphic subtypes and only 4 cases (9.52%) were simplex subtypes. Immunophenotype showed non-GCB type of DLBCL was predominance (83.33%, 35/42) by Hans classification. The expression of CD30, CD5, BCL-2, P53 and NF-kappaB/ P65 were 52.38% (22/42), 54.76% (23/42), 54.76% (23/42), 87.5% (35/40) and 0% (0/40) respectively. Follow-up data was available in 23 (54.76%) patients, 14 (60.87%) patients died of the tumor. 5-years overall survival was 16.5%. The median survival time was 40 months. The expression of BCL-2, increased LDH level and starry-sky morphologic character were associated with a poor prognosis., Conclusion: EBV positive DLBCL is not uncommon. Most lesions locate in lymph nodes. Pleomorphic histologic subtype is predominant. The tumor has worse prognosis with increased LDH level, starry-sky morphologic character and BCL-2 expression.

Objective: To describe the clinical characteristics, overall survival as well as to evaluate the prognostic factors in Chinese diffuse large B cell lymphoma (DLBCL) patients., Methods: DLBCL patients who were initially diagnosed and treated in Peking University Cancer Hospital from January 1995 to December 2008 were identified and analyzed,retrospectively.The 5-year OS rates were estimated with Kaplan-Meier. Log-rank test was used to compare the survival curves of the different groups. The multivariate analysis of prognostic factors was conducted with Cox regression model, which included all statistically significant prognostic factors in the univariate analyses., Results: A total of 525 DLBCL patients were included in this retrospective analysis, of whom, 294 were male and 231 female (male:female=1.27:1). The median age at the initial diagnosis was 55 (range 16-90) years, and 37.0% (n=194) were 60 years and above. Regarding the clinical staging at the initial diagnosis, 54 patients (10.3%) were diagnosed as Stage I of the disease, 152 (28.9%) as Stage II, 117 (22.3%) as Stage III and 202 (38.5%) as Stage IV. The "B symptoms" and increased serum LDH were presented in 206 (39.2%) and 192 (36.6%) patients, respectively. A total of 197 (37.5%) patients were treated with rituximab (R). The survival follow-up continued till 31 January 2014 with a median follow-up time of 77.5 (range: 0-205) months. A total of 267 patients (50.9%) died during the follow-up period. The medial overall survival (OS) time was 84 months, and 5-year OS rate was 52.3%. There were six statistically significant prognostic factors that were identified in both univariate and multivariate analyses: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. The relative risk (RR) of these prognostic factors in the multivariate analyses were: age > 60 years / ≤ 60 years=1.380 (95%CI 1.078-1.765), male / female=1.315 (95%CI 1.025-1.687), stage III/stage I=3.034 (95%CI 1.667-5.522), stage IV/I=3.748(95%CI 2.102-6.681), with B symptoms/without B symptoms=1.278(95%CI 0.999-1.636), serum LDH increased/LDH not increased=1.351(95%CI 1.057-1.726), without R treatment / with R treatment=1.543 (95%CI 1.182-2.015).Compared with the IPI, age >50 years/ ≤ 50 years was a statistically significant factor in both univariate and multivariate analyses RR=1.478 (95%CI 1.148-1.902), P=0.002., Conclusion: Six factors were related to DLBCL survival: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. Compared with the IPI, several specific factors may predict a poor prognosis in Chinese DLBCL patients: male, age>50 years and the presence of "B symptoms". But this result is not conclusive until these factors are further tested.