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The Khanka Massif forms the easternmost part of the Central Asian Orogenic Belt (CAOB) and represents an ideal location for examination of the timing and processes involved in the transition from the Palaeo-Asian to Palaeo-Pacific Ocean tectonic systems. However, it is obstructed because the late Palaeozoic tectonic attributes of the eastern margin of this massif remain unclear. In this paper, we provide zircon U-Pb ages and Hf isotopic, as well as the whole-rock Sr-Nd-Pb-Hf isotopic data for Permian granitic and volcanic rocks within the eastern margin of the Khanka Massif, with the aim of exploring the petrogenesis and their geodynamics significance. These data suggest that the Permian magmatism within the eastern margin of the Khanka Massif, composed of monzogranites and rhyolites, can be split into two stages; i.e. middle (ca. 264 to ca. 263 Ma) and late (ca. 252 Ma) Permian. The highly fractionated middle Permian monzogranites are formed in an N-S extensional setting and represent the magmatic response to the amalgamation of the Khanka and Jiamusi massifs. Middle-late Permian rhyolites with decoupled Nd-Hf isotopic compositions were derived from partial melting of metasedimentary crustal rocks. Their moderate-high zircon saturation temperatures (796–817°C) are thought to represent the involvement of ridge subduction of the Palaeo-Asian Ocean beneath the western margin of the Khanka Massif. Our findings further reinforce the existence of the ridge subduction of the Palaeo-Asian Ocean at the western margin of Khanka Massif in the Permian, while excluding the possibility of Permian Palaeo-Pacific oceanic plate subduction occurred beneath the eastern margin of the Khanka Massif in the Permian. [ABSTRACT FROM AUTHOR]

When the Paleo‐Asian Ocean closed and the Paleo‐Pacific subduction started in NE China remains controversial. To constrain these key issues, we carried out zircon U‐Pb‐Hf isotopic and whole‐rock geochemical studies of Early Mesozoic igneous rocks in central southern Jilin Province, NE China. Early Mesozoic igneous rocks in region were formed at three stages: the middle Triassic (246 Ma), the late Triassic (219–220 Ma), and the early Jurassic (172–194 Ma). Middle Triassic trachyandesites in southern Jilin Province were solely generated through partial melting of ancient lower crust of the North China Craton (NCC), implying ongoing southward subduction of Paleo‐Asian Ocean Plate beneath the NCC at this time. Late Triassic trachyandesites in southern Jilin Province were derived from the magma mixing/mingling of the NCC lithospheric mantle and juvenile eastern Central Asian Orogenic Belt crustal sources. Late Triassic hornblende gabbros in central Jilin Province were derived from depleted lithospheric mantle previously metasomatized by subduction‐related fluids. Coeval adakitic granodiorites were likely produced through the partial melting of thickened juvenile lower crust. Spatially, these rocks occurred on both sides of the Solonker‐Xra‐Moron‐Changchun Suture Zone and record N–S directed extension accompanied by the final closure of the Paleo‐Asian Ocean. Early Jurassic andesites were produced through mixing/mingling between partial melts derived from eastern Central Asian Orogenic Belt lithospheric mantle and ancient NCC crust. In contrast, Early Jurassic felsic rocks, including A‐type granites, were derived from the partial melting of Neoproterozoic accreted lower crust, jointly implying an extensional setting as the result of the initial subduction from Paleo‐Pacific Plate at this time. Key Points: Three magmatism stages are recognized in central southern Jilin Province, NE ChinaMiddle–Late Triassic rocks record the subduction and termination of Paleo‐Asian Ocean tectonic regimeEarly Jurassic rocks record the onset of the Paleo‐Pacific tectonic regime [ABSTRACT FROM AUTHOR]

Haemophagocytic lymphohistiocytosis (HLH) is a rare and severe clinical syndrome that can be classified as either primary or secondary. Secondary HLH can be triggered by a variety of diseases. Pregnancy-related HLH has already been observed clinically. However, most of these cases occur during pregnancy. Considering that the periods before and after delivery have different clinical features, we presented the first case series of HLH that presented during the postpartum stage of pregnancy. From these cases, we concluded that postpartum HLH is a common form of pregnancy-related HLH. Patients with postpartum HLH may suffer more complicated pathogenesis. Cytopenia was not as common as in other types of HLH, but liver dysfunction was present in almost all cases. The standard therapy of HLH-94/04 was very effective, and the outcomes of postpartum HLH were better. [ABSTRACT FROM AUTHOR]

A layer of Mesoproterozoic tsunami deposits from the North China Craton was recently discovered and investigated in the Xingcheng area, Liaoning Province, China. They occur at the bottom of the Dahongyu Formation of the Changcheng Group (1.8-1.6 Ga). The tsunami deposits are identified based on the analysis of the sedimentary facies. They are markedly different from the normal deposits of shore-shallow sea siliciclastics, and are characterized by rip-up clasts, poorly sorted gravels, fining-upward sequences, redeposited underlying materials, complex sources of underlying strata and erosional bases at the bottom of beds. They are compelling features of tsunamiites when they occur together. During the Mesoproterozoic, the Xingcheng area was in an active tectonic belt, the Yanshan Taphrogenic Trough. The origin of the tsunami was probably triggered by the earthquake, which resulted from the the activities of the Luanxian-Jianchang Fault in early Mesoproterozoic times. The deposition of tsunamiites occurred in a coastal environment and involved several stages, from the origin, propagation, inundation, and deposition to the backwash flow. The geodynamic backgrounds of the tsunami event in the North China Craton are consistent with the breakup event of the Columbia supercontinent in the Mesoproterozoic. Some events, such as tsunamis and volcanism, are all controlled by extensional rift systems and should be recognized as effects of the breakup of the Columbia supercontinent in the North China Craton. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the changes in function of CD8 + T cell subsets, and explore its significance in pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH)., Methods: Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8 + T cell, as well as the secretion levels of interferon γ (IFN-γ) and expression of ΔCD107a after the stimulation; the numbers of effector-memory CD8 + T cells, regulatory T cells and double negative T cells were also detected., Results: The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8 + T cells of sHLH patients were 40.73±22.64, 15.97±14.45 and 0.73 (0-37.41), respectively, which were significantly higher than those of the control group (P<0.001). In contrast, the expression of ΔCD107a (4.49±2.71 vs 6.07±2.14, P=0.035) and secretion level of IFN-γ (37.30±24.46 vs 55.17±22.23, P=0.034) were significantly lower. The number of effector-memory CD8 + T cells in sHLH patients was also lower as compared with that in control group (14.35±10.37 vs 22.92±11.12, P=0.016). But there was no significant difference in the number of regulatory T cell and double negative T cell. In addition, the expressions of PD-1, TIM3 and LAG-3 in active stage of sHLH were 38.09±21.87, 14.35±13.70 and 0.82 (0-13.22), respectively, which were significant higher than those in remission stage [24.27±17.23 (P=0.03), 8.64±5.60 (P=0.014) and 0.13 (0-3.69)]., Conclusion: The exhausted CD8 + T lymphocytes may play a critical role in the development of sHLH.

Objective: To establish a secondary hemophagocytic lymphohistiocytosis(HLH) mouse model, and to investigate the effect of ruxolitinib on the disease manifestation of model mice., Methods: Wild type C57BL/6 mice were randomly divided into 4 groups: two groups of mice were intraperitoneally injected with CpG oligodeoxynucleotide 1826 (CpG-ODN1826) every other day to induce HLH, and other two groups were control groups. One group of the CpG-ODN1826 groups and one of the control groups were given ruxolitinib, and other two groups were given the same amount of PBS. Blood samples, serum ferritin and hepatic/spleen weights of experimental mice were detected and serum cytokine levels were measured by ELISA., Results: Compared with the control groups, the levels of white blood cells, hemoglobin and platelets in the CpG-ODN1826 groups were significantly lower (P＜0.05); and liver/body weight, spleen/body weight, serum ferritin, sCD25, IL-10, IL-1β, IFN-Ƴ, IL-12p70, GM-CSF, TNF-α and IL-18 levels significantly increased (P＜0.05). There was no significant difference in the levels of IL-2, IL-4, IL-5, IL-6, IL-22, IL-13, IL-27 and IL-23 between the two groups (P＞0.05). The spleen in CpG group had disordered internal structure, expanding red pulp and hyperplastic nucleated cells. The liver had severe perivascular inflammations. The spleen/weight of the ruxolitinib-treated mice in the CpG-ODN1826 group was significantly smaller than that of the unapplied ruxolitinib (P＜0.05)., Conclusion: The CpG-ODN1826 can induce secondary HLH symptoms in wild type C57BL/6 mice. Ruxolitinib can alleviate the symptoms of splenomegaly in HLH model mice.

Objective: To detect the erythrocyte life by breath carbon monoxide assay and to analyze the effect of erythrocyte life on the anemia in patients with hemophagocytic syndrome., Methods: The breath carbon monoxide test and erythrocyte life assay were performed for 20 cases of hemophagocytic syndrome, at the same time the detection of 20 healthy persons was used as control. The difference of anemia-related indexes was compared between hemophagocytic syndrome patients and healthy persons., Results: The average erythrocyte life of patients with hemophagocytic syndrome was 45.3 days, which was 65% shorter than that of healthy persons. Hemoglobin levels positively correlated with erythrocyte life, while sCD25, breath carbon monoxide concentration and hemophagocytosis negatively correlated with erythrocyte life. Bilirubin level and reticulocyte count showed no correlation with erythrocyte life. Serum level of IL-1β, IL-2, sCD25, IL-6, IL-10, IL-17A, GM-CSF, TNF-α and IFN-γ in patients with newly diagnosed hemophagocytic syndrome were significantly higher than those of healthy persons (P＜0.05)., Conclusion: Breath carbon monoxide assay is a rapid and efficient method to assess erythrocyte life. Increased erythrocyte destruction may be an important pathogenic factor for anemia in hemophagocytic syndrome.

Objective: To investigate the clinical characteristics, therapeutic outcomes and prognostic factors of primary central nervous system lymphoma (PCNSL)., Methods: Clinical records of 31 cases of PCNSL were collected, the clinical charactenstics were analyzed retrospectively. Survival curves were estimated using Kaplan-Meier survival methodology and statistical significance of continuous variables was assessed via the Cox proportional hazard model., Results: The median age was 52 years, with a ratio of male to female 1:1. Headache/dizzy/limb numbness were the most common presentation and the lesions of PCNSL were primarily located at the frontal, parietal, temporal lobes and corpus callosum. All the cases were pathologically diffuse large B cell lymphoma (DLBCL), 6 cases were the type of germinal center (GC) and 25 cases of non-GC type, after craniotomy operation and biopsy. Among 31 cases, 17 patients accepted the combined treatment, 3 patients underwent simple chemotherapy, 8 patients received simple radiotherapy, the other patients accepted support therapy. The median follow-up for surviving patients was 24 months. The 1-, 3-, and 5-year survival rates were 80.6%, 55.1%, and 36.4%, respectively. The median overall survival time in the combined treatment group was significantly longer than that in simply radiotherapy. There was no significant difference in OS between the groups with and without rituximab. ECOG PS≥2 and elevated serum LDH predicted inferior survival., Conclusion: The clinical manifectation of PCNSL is various and complicated, and for the time being there is no optimal treatment scheme. The overall survival time of the combined treatment is longer than that in simply radiotherapy. ECOG PS≥2 and elevated serum LDH often are poor prognostic factors.

Langerhans cell tumor is a kind of tumor that originates from Langerhans cells (LC) and maintain their specific phenotype profile and ultrastructural features. Based on cell morphology, immunohistochemical and ultrastructural characteristics, Langerhans cell tumor has two main subcategories: Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS). LCH is a benign clonal proliferative disease of the LC, whereas LCS is an extremely rare neoplastic proliferation of Langerhans cells with overtly malignant cytologic features and spreads aggressively, which is considered to be a high level malignant type of LCH. Both LCH and LCS can involved various tissues and organs and have complex and diverse clinical manifestation, which cause different severity. The diagnosis depends on histopathological morphology and immunohistochemistry; the electron microscopy was used to assists diagnosis when necessary. The treatment includes surgery, chemotherapy, radiotherapy, immunotherapy and hematopoietic stem cell transplantation, etc, but lack of generally accepted optimal treatment options currently, individualized treatment is needed. The prognosis of LCH is primarily related to the number of damaged organ, while LCS has a poor overall prognosis as its invasion and rapid progress. This article reviews the pathogenesis, clinical manifestations, diagnosis, treatment and prognosis of both LCH and LCS.

Objective: To introduce the clinical manifestations and laboratory tests of adult onset of primary hemophagocytic syndrome (HPS), and to investigate the essentials of diagnosis and the genotype characteristics in adult onset patient., Methods: The definite diagnosis of HPS was made according to HLH-2004. Exons of PRF1, STX11, UNC13D, SH2D1A and RAB27A genes coding region were amplified using polymerase chain reaction., Results: A 48-year-old man was admitted to our hospital because of recurrent fever, pancytopenia and lymph node enlargement. His laboratory test revealed bone marrow hemophagocytosis, elevated ferritin level (2000 µg/L), reduced level of NK cell activity (20.13%) and elevated soluble CD25 level (12277 U/ml). Based on the HLH-2004 diagnostic criteria, the patient was diagnosed as HPS. The patient had viral infection, and no other primary disease was identified that would cause HPS. The patient responded poorly to anti-viral therapy. DNA sequencing was used to confirm that perforin gene mutations might be one of the causes of the patient suffered from primary HPS., Conclusions: Although primary HPS usually affects infants and young children, it also occurred in teens and adults. It is essential to perform genetic screenings to patient whose illnesses recur with unknown causes. In addition, detection of molecular genetic alterations can be used to distinguish primary HPS from acquired HPS.

In order to explore the serum levels and clinical significance of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in patients with hemophagocytic syndrome (HPS). The clinical data of HPS patients in Capital Medical University Beijing Friendship Hospital from October 2008 to October 2010 were collected. The serum concentration of TNF-α and IFN-γ in HPS patients and 20 healthy controls was measured with enzyme-linked immunosorbent assay (ELISA). The correlations between the levels of TNF-α and primary disease were analyzed, the levels of hemoglobin, ferritin, triglyceride, NK cell activity and sCD25 were detected on the same day, the correlations between the concentrations of TNF-α and IFN-γ and these laboratory indicators were analyzed. The results indicated that the serum levels of TNF-α and IFN-γ in 30 cases of HPS was higher than that in control group (p < 0.05, p < 0.01); the difference of TNF-α concentration was statistically significant in rheumatism-related and tumor-related HPS groups(p = 0.04), the level of TNF-α in HPS patients showed negative correlation with hemoglobin. It is concluded that the high levels of TNF-α and IFN-γ in HPS patients may play certain roles in the pathogenesis and progress of HPS. These data indicated that the high level of TNF-α may be the main factor for anemia in patients with HPS.

The aim of study was to establish an accurate and stable technique for the detection of NK cell activity in the diagnosis of hemophagocytic lymphohistiocytosis (HLH). 21 suspected acquired HLH patients and 20 healthy subjects as controls were enrolled in the study, and the suspected HLH patients were divided into confirmedly diagnosed group and excluded group according to HLH-2004 diagnostic criteria. The plasmid pEGFP-N1 was transfected into K562 cells. After scanned with G4l8 and monoclone, the EGFP-K562 cell line stably expressing enhanced green fluorescent protein was obtained. PBMNC and EGFP-K562 were mixed at the effector to target ratio of 10:1. After incubation for of 2 hours, propidium iodine (PI) was added to stain dead cells, and then cytotoxic activity was analyzed by using flow cytometry. Meanwhile, the cytotoxic activity of NK cells in peripheral blood on K562 cells was detected by LDH release assay, and was compared with results detected by flow cytometry. The results showed that a K562 cell line stably expressing EGFP was constructed and were used to measure NK cytotoxicity against the target cells by flow cytometry without pre-staining or pre-labeling target cells. There was significant difference in killing rate of NK cells between the diagnostic group and the control group. This new technique correlated strongly with the results by LDH release assay. In conclusion, this study provides a novel, simple, rapid, repeatable and reproducible method to measure NK activity by flow cytometry using EGFP-K562 without pre-staining or pre-labeling target cells. It may be widely used in the diagnosis of hemophagocytic lymphohistiocytosis.

Objective: To explore early diagnosis of hemophagocytic syndrome (HPS) and effective treatment., Methods: A multicenter retrospective study was carried out to analyze the causes, clinical features, laboratory findings, treatment and clinical outcomes of 72 patients with HPS., Results: Among the 72 patients, EBV infection and T lymphoma were the most common initiating diseases. The most common clinical features were persistent fever (100%) and splenomegaly (83.3%). The diagnostic sensitivity was persistent fever (100%), peripheral cytopenia in two or more lineages (97.2%), high concentration of serum soluble CD25 (93.1%) and low NK cell activity (94.4%). The median percentage of serum glycosylated ferritin was significantly lower in patients in HPS group \[(17.4 +/- 16.0)%\] than in control group \[(53.6 +/- 13.3)%\] (P < 0.01). And the median level of serum TNF-alpha was significantly higher in patients group \[(143.2 +/- 64.8) microg/L\] than in controls \[(66.9 +/- 19.4) microg/L\] (P < 0.01). Hepatic dysfunction was seen in most patients (83.6%) mainly manifested as elevated liver enzymes and hypoalbuminemia. The 15-week total survival rate was 46.8% in 47 treated patients, and was 63% in 27 treated with fludarabine in combination with high dose methylprednisolone. The platelet count and fibrinogen level were significantly lower in death group than in survival group., Conclusions: The diagnostic sensitivities of presistent fever, peripheral cytopenia in two or more lineages, high concentration of serum soluble CD25 and low NK cell activity are relatively high and lacking hemophagocytosis does not exclude the diagnosis. Low percentage of glycosylated ferritin and high concentration of TNF-alpha would be helpful to the diagnosis. High dose methylprednisolone combined with fludarabine is an effective therapy. Platelet count and fibrinogen level are poor prognostic factors for HPS.

Objective: To explore the significance of NK cell activity, interleukin-2 receptors (sCD(25)) and glycosylated ferritin in the early diagnostic of acquired hemophagocytic lymphohistiocytosis (HLH)., Methods: 57 patients suspected of HLH from June 2005 to May 2008 and 25 healthy subjects were enrolled in the study. The patients suspected of HLH were divided into three groups i.e. (1) a group with diagnosis confirmed at first visit; (2) a group with diagnosis confirmed at subsequent visit and (3) a group with diagnosis unconfirmed according to HLH-2004 diagnostic criteria. Healthy subjects were enrolled as control. NK cell activity was determined with a released LDH assay. The percentage of glycosylated ferritin was determined with phytohemagglutinin adsorption assay. sCD(25) was examined with ELISA double antibody sandwich assay. We compared the coincidence of each diagnostic index before and after diagnosis., Results: The median percentage of NK cell activity was significantly lower in the first group (18.3 +/- 5.6)% and the second (16.7 +/- 6.7)% than that in the third group (33.4 +/- 6.8)% or in the controls (36.6 +/- 5.0)%. The median percentage of glycosylated ferritin was also significantly lower in the first group (15.4 +/- 2.0)% and the second group (16.9 +/- 3.4)% than that in the third group (40.4 +/- 3.0)% or in the controls (45.2 +/- 2.2)%. Meanwhile, the median level of sCD(25) was significantly higher in the first group (12 916 +/- 4328) ng/L and the second group (12 117 +/- 5465) ng/L than that in the third group (4728 +/- 1482) ng/L or in the controls (3841 +/- 993) ng/L. Furthermore, NK cell activity, sCD(25) and glycosylated ferritin were abnormal in all the patients in the early stage of HLH., Conclusion: NK cell activity, sCD(25) and glycosylated ferritin may be helpful markers for the early diagnosis of HLH.

This study was aimed to explore the level of glycosylated ferritin in the patients with secondary hemophagocytic lymphohistiocytosis (HLH) and its diagnostic significance. 29 suspected HLH patients from October 2007 to October 2008 were enrolled in the study, and 25 healthy subjects were selected as control. The 29 suspected HLH patients were divided into confirmed group (22 out of 29) and unconfirmed group (7 out of 29) according to HLH-2004 diagnostic criteria. The percentage of glycosylated ferritin in peripheral blood was determined by phytohemagglutinin adsorption assay. The results showed that the median level of total serum ferritin in patients of confirmed group (2897.6+/-1837.2 microg/L) was significantly higher than that in patients of unconfirmed group (653.1+/-249.1 microg/L) (p<0.01), and was also higher than that in controls (414.6+/-212.6 microg/L) (p<0.01). The median percentage of glycosylated ferritin in patients of confirmed group was significantly lower (17.0+/-4.2%) than that in patients of unconfirmed group (40.7+/-4.5%) (p<0.01) and was lower than that in controls (53.6+/-13.3%) (p<0.01). The sensitivity (86.4% vs 77.3%) and specificity (71.4% vs 42.9%) of glycosylated ferritin for the diagnosis of HLH were higher than that of total serum ferritin. In conclusions, glycosylated ferritin may be a helpful marker for the diagnosis of HLH.