Hybrid Membrane-Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease.

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD.

Alzheimer's disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling.

Amyloid-ß, tau pathology, and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease (AD). However, these proteins represent only a fraction of the complex biological processes underlying AD, and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers. More AD-specific early diagnostic and disease staging biomarkers are needed. In this study, we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid (CSF) and serum samples in a discovery cohort comprising 98 participants. Candidate biomarkers were validated by parallel reaction monitoring-based targeted proteomic assays in an independent multicenter cohort comprising 288 participants. We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort, identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers, respectively. In the validation cohort, 58 and 21 CSF proteins, as well as 12 and 18 serum proteins, were verified as early diagnostic and staging biomarkers, respectively. Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment (MCI) due to AD from normal cognition with areas under the curve of 0.984 and 0.881, respectively. The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases. Moreover, we identified 21 CSF and 18 serum stage-associated proteins reflecting AD stages. Our findings provide a foundation for developing blood-based tests for AD screening and staging in clinical practice.

Nuclear DJ-1 Regulates DNA Damage Repair via the Regulation of PARP1 Activity.

DNA damage and defective DNA repair are extensively linked to neurodegeneration in Parkinson's disease (PD), but the underlying molecular mechanisms remain poorly understood. Here, we determined that the PD-associated protein DJ-1 plays an essential role in modulating DNA double-strand break (DSB) repair. Specifically, DJ-1 is a DNA damage response (DDR) protein that can be recruited to DNA damage sites, where it promotes DSB repair through both homologous recombination and nonhomologous end joining. Mechanistically, DJ-1 interacts directly with PARP1, a nuclear enzyme essential for genomic stability, and stimulates its enzymatic activity during DNA repair. Importantly, cells from PD patients with the DJ-1 mutation also have defective PARP1 activity and impaired repair of DSBs. In summary, our findings uncover a novel function of nuclear DJ-1 in DNA repair and genome stability maintenance, and suggest that defective DNA repair may contribute to the pathogenesis of PD linked to DJ-1 mutations.

Identification and functional characterization of novel variants of MAPT and GRN in Chinese patients with frontotemporal dementia.

Frontotemporal dementia (FTD) is the second most common cause of dementia after Alzheimer's disease, characterized by distinct changes in behavior, personality, and language. Our study performed whole exome sequencing and repeat-primed PCR analysis in 29 unrelated FTD patients. Consequently, 2 known pathogenic variants (MAPT: p.P301L; TBK1: p.I450Kfs), and 4 novel variants (MAPT: p.R406Q, p.D430H, p.A330D; GRN: c.350-2A>G) were identified. The functional analysis results showed that phosphorylated tau levels were higher in cells expressing p.R406Q and p.D430H tau than those expressing wild-type tau, especially at the Thr205, Thr231, and Ser396 phosphorylation epitopes. Besides, the p.R406Q and p.D430H variants of MAPT impaired the ability of tau to bind to the microtubules and increased tau self-aggregation. Furthermore, we found that the c.350-2A>G variant caused exon 5 skipping. Our results showed that p.R406Q, p.D430H, and c.350-2A>G variants were classified as pathogenic. Finally, we summarized the clinical characterization of patients carrying pathogenic variants of MAPT in the East Asia populations. Our results broaden the genetic spectrum of FTD with MAPT and GRN variants.

Discerning the Role of Blood Brain Barrier Dysfunction in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of neurodegenerative disease. The predominant characteristics of AD are the accumulation of amyloid-ß (Aß) and hyperphosphorylated tau in the brain. Blood brain barrier (BBB) dysfunction as one of the causative factors of cognitive impairment is increasingly recognized in the last decades. However, the role of BBB dysfunction in AD pathogenesis is still not fully understood. It remains elusive whether BBB dysfunction is a consequence or causative fact of Aß pathology, tau pathology, neuroinflammation, or other conditions. In this review, we summarized the major findings of BBB dysfunction in AD and the reciprocal relationships between BBB dysfunction, Aß pathology, tau pathology, and neuroinflammation. In addition, the implications of BBB dysfunction in AD for delivering therapeutic drugs were presented. Finally, we discussed how to better determine the underlying mechanisms between BBB dysfunction and AD, as well as how to explore new therapies for BBB regulation to treat AD in the future.

Microglial Activation, Tau Pathology, and Neurodegeneration Biomarkers Predict Longitudinal Cognitive Decline in Alzheimer's Disease Continuum.

Purpose: Biomarkers used for predicting longitudinal cognitive change in Alzheimer's disease (AD) continuum are still elusive. Tau pathology, neuroinflammation, and neurodegeneration are the leading candidate predictors. We aimed to determine these three aspects of biomarkers in cerebrospinal fluid (CSF) and plasma to predict longitudinal cognition status using Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Patients and Methods: A total of 430 subjects including, 96 cognitive normal (CN) with amyloid ß (Aß)-negative, 54 CN with Aß-positive, 195 mild cognitive impairment (MCI) with Aß-positive, and 85 AD with amyloid-positive (Aß-positive are identified by CSF Aß42/Aß40 < 0.138). Aß burden was evaluated by CSF and plasma Aß42/Aß40 ratio; tau pathology was evaluated by CSF and plasma phosphorylated-tau (p-tau181); microglial activation was measured by CSF soluble TREM2 (sTREM2) and progranulin (PGRN); neurodegeneration was measured by CSF and plasma t-tau and structural magnetic resonance imaging (MRI); cognition was examined annually over the subsequent 8 years using the Alzheimer's Disease Assessment Scale Cognition 13-item scale (ADAS13) and Mini-Mental State Exam (MMSE). Linear mixed-effects models (LME) were applied to assess the correlation between biomarkers and longitudinal cognition decline, as well as their effect size on the prediction of longitudinal cognitive decline. Results: Baseline CSF Aß42/Aß40 ratio was decreased in MCI and AD compared to CN, while CSF p-tau181 and t-tau increased. Baseline CSF sTREM2 and PGRN did not show any differences in MCI and AD compared to CN. Baseline brain volumes (including the hippocampal, entorhinal, middle temporal lobe, and whole-brain) decreased in MCI and AD groups. For the longitudinal study, there were significant interaction effects of CSF p-tau181 × time, plasma p-tau181 × time, CSF sTREM2 × time, and brain volumes × time, indicating CSF, and plasma p-tau181, CSF sTREM2, and brain volumes could predict longitudinal cognition deterioration rate. CSF sTREM2, CSF, and plasma p-tau181 had similar medium prediction effects, while brain volumes showed stronger effects in predicting cognition decline. Conclusion: Our study reported that baseline CSF sTREM2, CSF, and plasma p-tau181, as well as structural MRI, could predict longitudinal cognitive decline in subjects with positive AD pathology. Plasma p-tau181 can be used as a relatively noninvasive reliable biomarker for AD longitudinal cognition decline prediction.

A study on UHPLC-MS/MS analyses of DNA and RNA oxidative damage metabolites in patients with cervical carcinoma: 8-oxoG in urine as a potential biomarker of cervical carcinoma.

Objective: The purpose of this study was to compare the levels of 8-oxoG and 8-oxodG in urine of patients with cervical carcinoma and healthy women to evaluate their influences on cervical carcinoma. Methods: In this study, urine samples were collected from 70 patients with cervical carcinoma, 24 patients with one-year follow-up, and 100 healthy women. The contents of 8-oxodG and 8-oxoG in urine were assayed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Results: The levels of 8-oxoG and 8-oxodG were higher in patients with cervical carcinoma (P < 0.000), while AUC of 8-oxoG and 8-oxodG was higher than 0.7. Specifically, the high-risk HPV (HR-HPV) positive group had higher 8-oxoG levels (P < 0.000), but there was no difference in 8-oxodG levels. Yet, 8-oxoG level was associated with lymphatic metastasis, lymph-vascular space infiltration (LVSI) and stromal infiltration, while 8-oxodG level was affected by the differentiation degree and stromal infiltration. According to statistics, the distinct cut-off index of lymphatic metastasis was 7.282 nmol/mmol creatinine. After operation, the concentrations of 8-oxoG and 8-oxodG dropped significantly (8-oxoG P < 0.000, 8-oxodG P = 0.004). Except for chemotherapy group, the urinary 8-oxoG dose of all treatment groups and 8-oxodG dose of chemo-radiotherapy group declined obviously. Conclusions: 8-oxoG may be a potential biomarker for cervical carcinoma.

Early-Onset Parkinson's Disease and Brain Iron Accumulation Caused by a Novel Homozygous DJ-1 Mutation.

DJ-1 mutations are rare causes of autosomal recessive early-onset Parkinson's disease (AR-EOPD) and relatively rarely reported in the Chinese population. Here, we used the whole-exome sequencing and Sanger sequencing to investigate DJ-1 mutations in the Chinese population and confirmed the pathogenicity of the mutation using primary fibroblasts established from skin biopsies. We identified a novel homozygous mutation (c.390delA, p.D131Tfs*3) in DJ-1 in a consanguineous Chinese family. The proband in this family had parkinsonism at the age of 22. His brain MRI indicated brain iron accumulation in the basal ganglia and cerebellum. The novel mutation caused DJ-1 protein deficiency, led to mitochondrial dysfunction, inhibited cell proliferation, and anti-oxidant defense.

[The Effects of Decitabine Combined with All-Trans Retinoic Acid on the Number of Immune Cells in Myeloid Neoplasms].

OBJECTIVE: To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients. METHODS: Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared. RESULTS: There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P>0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P<0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P<0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P<0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P<0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P>0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P>0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P<0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group. CONCLUSION: The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.

Alzheimer's disease susceptibility locus in CD2AP is associated with increased cerebrospinal fluid tau levels in mild cognitive impairment.

INTRODUCTION: Rs9296559 within CD2-associated protein (CD2AP) has been identified as a susceptibility locus for Alzheimer's disease (AD). Recent studies indicated that CD2AP functioned as a regulator of endocytic trafficking to modulate the ß-amyloid (Aß) generation in neurons. Moreover, knockdown of cindr, the Drosophila ortholog of CD2AP, enhanced tau-induced neurodegeneration, implying CD2AP also participated in tau pathology. However, the role of rs9296559 in regulating Aß and tau metabolism in AD was still unclear. METHODS: Here, the associations of rs9296559 with CSF Aß1-42, p-tau, and t-tau were performed using a linear regression model in a total of 543 cognitive normal (CN), mild cognitive impairment (MCI), and AD subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI) cohort. The results were replicated in an independent cohort consisting of 198 Chinese subjects recruited from our hospital. RESULTS: In the ADNI cohort, CC + TC genotypes significantly increased CSF t-tau and p-tau levels in MCI patients but did not alter CSF tau levels in AD. This association was also observed in the replication cohort. Moreover, there was no association between rs9296559 and CSF Aß1-42 level at different disease statuses in the two cohorts. CONCLUSION: Our findings showed that rs9296559 was associated with higher CSF t-tau and p-tau levels in MCI, supporting that CD2AP modified AD risk by altering tau-related neurodegeneration in the early stage of the AD continuum. To the best of our knowledge, this is the first study to evaluate the association between CD2AP genotypes and AD CSF biomarkers.

Loss of Growth Differentiation Factor 11 Shortens Telomere Length by Downregulating Telomerase Activity.

Maintenance of telomere length is essential to delay replicative cellular senescence. It is controversial on whether growth differentiation factor 11 (GDF11) can reverse cellular senescence, and this work aims to establish the causality between GDF11 and the telomere maintenance unequivocally. Using CRISPR/Cas9 technique and a long-term in vitro culture model of cellular senescence, we show here that in vitro genetic deletion of GDF11 causes shortening of telomere length, downregulation of telomeric reverse transcriptase (TERT) and telomeric RNA component (TERC), the key enzyme and the RNA component for extension of the telomere, and reduction of telomerase activity. In contrast, both recombinant and overexpressed GDF11 restore the transcription of TERT in GDF11KO cells to the wild-type level. Furthermore, loss of GDF11-induced telomere shortening is likely caused by enhancing the nuclear entry of SMAD2 which inhibits the transcription of TERT and TERC. Our results provide the first proof-of-cause-and-effect evidence that endogenous GDF11 plays a causal role for proliferative cells to maintain telomere length, paving the way for potential rejuvenation of the proliferative cells, tissues, and organs.

Optimal Combinations of AT(N) Biomarkers to Determine Longitudinal Cognition in the Alzheimer's Disease.

Background: National Institute on Aging-Alzheimer's Association (NIA-AA) proposed the AT(N) system based on ß-amyloid deposition, pathologic tau, and neurodegeneration, which considered the definition of Alzheimer's disease (AD) as a biological construct. However, the associations between different AT(N) combinations and cognitive progression have been poorly explored systematically. The aim of this study is to compare different AT(N) combinations using recognized biomarkers within the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Methods: A total of 341 participants were classified into cognitively unimpaired (CU; n = 200) and cognitively impaired (CI; n = 141) groups according to the clinical manifestations and neuropsychological tests. Cerebrospinal fluid (CSF) Aß42 and amyloid-PET ([18F]flutemetamol) were used as biomarkers for A; CSF phosphorylated tau (p-tau) and tau-PET ([18F]flortaucipir) were used as biomarkers for T; CSF total tau (t-tau), hippocampal volume, temporal cortical thickness, [18F]fluorodeoxyglucose (FDG) PET, and plasma neurofilament light (NfL) were used as biomarkers for (N). Binary biomarkers were obtained from the Youden index and publicly available cutoffs. Prevalence of AT(N) categories was compared between different biomarkers within the group using related independent sample non-parametric test. The relationship between AT(N) combinations and 12-year longitudinal cognition was assessed using linear mixed-effects modeling. Results: Among the CU participants, A-T-(N)- was most common. More T+ were detected using p-tau than tau PET (p < 0.05), and more (N)+ were observed using fluid biomarkers (p < 0.001). A+T+(N)+ was more common in the CI group. Tau PET combined with cortical thickness best predicted cognitive changes in the CI group and MRI predicted changes in the CU group. Conclusions: These findings suggest that optimal AT(N) combinations to determine longitudinal cognition differ by cognitive status. Different biomarkers within a specific component for defining AT(N) cannot be used identically. Furthermore, different strategies for discontinuous biomarkers will be an important area for future studies.

The role of P2X7R in neuroinflammation and implications in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia and is set to rise in prevalence as the global trends in population aging. The extracellular deposition of amyloid protein (Aß) and the intracellular formation of neurofibrillary tangles in the brain have been recognized as the two core pathologies of AD. Over the past decades, the presence of neuroinflammation in the brain has been documented as the third core pathology of AD. In recent years, emerging evidence demonstrated that the purinergic receptor P2X7 (P2X7R) serves a critical role in microglia responses and neuroinflammation. Besides, targeting P2X7R by genetic or pharmacological strategies attenuates the symptoms and pathological changes of AD models, and P2X7R has been recognized as a promising therapeutic target for AD. In this review, we summarized the recent evidence concerning the roles of P2X7R in neuroinflammation and implications in AD pathogenesis.

Genome sequencing and functional annotation of Bacillus sp. strain BS-Z15 isolated from cotton rhizosphere soil having antagonistic activity against Verticillium dahliae.

In the present study, antagonistic activity of bacterial strain BS-Z15, was evaluated against Verticillium dahlia. The fermented broth of BS-Z15 inhibited the growth of Verticillium dahliae. The genome of strain BS-Z15 had a total size of 4,068,702 base pairs and contained 4318 genes, of which 4196 are coding sequences and 122 are non-coding RNA. Among these genes, nine genomic islands, 86 tRNAs, 13 sRNAs, and one prophage was determined. With the help of annotation databases, most unigene functions were identified. At the same time, genomic comparison between BS-Z15 and 12 Bacillus members showed that the genes of BS-Z15 were closely related to the Bacillus group, and were conserved between the two groups, including most of the genes associated with fungal antagonism. BS-Z15 contains genes involved in a variety of antagonistic mechanisms, including genes encoding or synthesizing mycosubtilin, chitinases (but not CHIA and CHIB), glycoside hydrolases, iron nutrients, and antibiosis. However, it only contained the complete mycosubtilin- and bacilibactin-related operators in the reported main antifungal gene cluster of B. subtilis. Mycosubtilin and bacilibactin may be the main active antifungal substance. Besides, some genes could encode products related to biofilm production, which may be related to the colonization ability of the strain in plant rhizospheres. The complete genome of B. subtilis BS-Z15 provided new insights into the potential metabolites it produces related to its biocontrol activity.

Genetic Analysis of Chinese Patients with Early-Onset Dementia Using Next-Generation Sequencing.

OBJECTIVE: Early-onset dementia (EOD) is a relatively uncommon form of dementia that afflicts people before age 65. Only a few studies analyzing the genetics of EOD have been performed in the Chinese Han population. Diagnosing EOD remains a challenge due to the diverse genetic and clinical heterogeneity of these diseases. The aim of this study was to investigate the genetic spectrum and clinical features of Chinese patients with EOD. MATERIALS AND METHODS: A total of 49 EOD patients were recruited. Targeted next-generation (NGS) analyses were performed to screen for all of the known genes associated with dementia. Possible pathogenic variants were confirmed by performing Sanger sequencing. The genetic spectrum and clinical features of the EOD patients were analyzed. RESULTS: Seven previously reported pathogenic variants (p.I213T and p.W165C in PSEN1; p.D678N in APP; c.1349_1352del in TBK1; p.P301L and p.R406W in MAPT; p.R110C in NOTCH3) and two novel variants of uncertain significance (p.P436L in PSEN2; c.239-11G>A in TARDBP) were identified. CONCLUSION: Our study demonstrated the genetic spectrum and clinical features of EOD patients, and it reveals that genetic testing of known causal genes in EOD patients can help to make a precise diagnosis.

Effect of Momordica charantia protein on proliferation, apoptosis and the AKT signal transduction pathway in the human endometrial carcinoma Ishikawa H cell line in vitro.

Endometrial carcinoma (EC) is one of the most common female malignancies, and there is an urgent requirement to explore new therapeutic strategies. In the present study, Ishikawa H cells were treated with Momordica charantia protein (MCP30). The cell morphology, growth inhibition rate, cell cycle distribution, and expression of phosphate and tensin homolog, P-AKT and AKT were measured. DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate/propidium iodide double staining assay were used to analyze cell apoptosis. MCP30 decreased the viability of Ishikawa H cells in a dose- and time-dependent manner. The early apoptotic rates of Ishikawa H cells treated with MCP30 at 666.67 pM reached to 16.07±0.15%, following 72 h of treatment. DNA ladder was observed in cells treated with 333.33 and 666.67 pM MCP30 following 72 h of treatment. MCP30 blocks Ishikawa H cells from progressing between the S-phase and the G2/M-phase in a time- and concentration-dependent manner. Western blotting revealed that MCP30 treatment decreased the levels of P-AKT in a dose-dependent manner. It was revealed that MCP30 decreases cell proliferation, and induces apoptosis and S-phase cell cycle arrest through the AKT signaling pathway in Ishikawa H cells.

Nomogram Predicting Overall Survival in Operable Cervical Cancer Patients.

OBJECTIVE: Nomograms are widely used as predictive tools to predict oncological outcomes intuitively and precisely. The aim of our study was to develop a nomogram for predicting overall survival (OS) of patients with early stage cervical cancer. METHODS: In this retrospective study, the clinical, pathological, and hematological data and prognosis of 795 cervical cancer patients were investigated. We identified and incorporated independent significant prognostic factors for OS to develop a nomogram. The predictive accuracy and discriminative ability were measured by concordance index. RESULTS: By univariable analysis and subsequent multivariable analysis, we identified body mass index, albumin, platelet, leukocyte, tumor differentiation, and the status of the pelvic lymph node (PLN) (all P < 0.05) as independent prognostic factors. The concordance index of the nomogram integrating these 6 variables was 0.74. The calibration curves for probability of 3- and 5-year OS also demonstrated ideal agreement between nomogram prediction and actual observation. CONCLUSIONS: We developed a novel nomogram that can provide prediction of OS for patients with early stage cervical cancer individually. Furthermore, studies are required to validate whether it can be applied to other cohorts.

[Serum levels of tumor necrosis factor α and interferon γ in patients with hemophagocytic syndrome and its clinical significance].

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.

[Expression of serum sHLA-G in patients with hemophagocytic syndrome and its clinical significance].

In order to investigate the expression of serum sHLA-G in hemophagocytic syndrome (HPS) patients and to evaluate its clinical significance, the clinical data of HPS patients in Capital Medical University Beijing Friendship Hospital during the period from September 2008 to July 2010 were collected. They were divided into infection-associated HPS, tumor-associated HPS and rheumatological disease-associated HPS according to cause of diseases. The serum concentration of sHLA-G in HPS patients and 25 healthy controls was measured by enzyme-linked immunosorbent assay (ELISA), the correlations between sHLA-G level and laboratory indicators were analyzed. The results showed that the level of serum sHLA-G in HPS patients was significantly higher than that in healthy controls (p = 0.003), but the difference was not statistically significant between HPS groups of different causes (p = 0.233). The positive correlation of sHLA-G level in HPS patients with platelet count was found, but there was no positive correlation of their sHLA-G levels with WBC, Hb, Plt, ALT, AST, LDH, Alb, TBil, DBil, IBil, Cr, BUN, TG, fibrinogen and ferritin levels detected on same day. It is concluded that the the increase of serum sHLA-G levels in HPS patients may be caused by different factors such as infection, tumor, T cell activation and over-stimulation of several cytokines. sHLA-G can inhibit NK cell activity, resulting in formation of abnormal immune storm, and may be play a role in the pathogenesis of HPS.