CD147 Sparks Atherosclerosis by Driving M1 Phenotype and Impairing Efferocytosis.

BACKGROUND: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance. METHODS AND RESULTS: We generated mice with a myeloid-specific knockout of CD147 and mice with restricted CD147 overexpression, both in an apoE-deficient (ApoE-/-) background. Here, the myeloid-specific deletion of CD147 ameliorated atherosclerosis and inflammation. Consistent with our in vivo data, macrophages isolated from myeloid-specific CD147 knockout mice exhibited a phenotype shift from proinflammatory to anti-inflammatory macrophage polarization in response to lipopolysaccharide/IFN (interferon)-γ. These macrophages demonstrated a weakened proinflammatory macrophage phenotype, characterized by reduced production of NO and reactive nitrogen species derived from iNOS (inducible NO synthase). Mechanistically, the TRAF6 (tumor necrosis factor receptor-associated factor 6)-IKK (inhibitor of κB kinase)-IRF5 (IFN regulatory factor 5) signaling pathway was essential for the effect of CD147 on proinflammatory responses. Consistent with the reduced size of the necrotic core, myeloid-specific CD147 deficiency diminished the susceptibility of iNOS-mediated late apoptosis, accompanied by enhanced efferocytotic capacity mediated by increased secretion of GAS6 (growth arrest-specific 6) in proinflammatory macrophages. These findings were consistent in a mouse model with myeloid-restricted overexpression of CD147. Furthermore, we developed a new atherosclerosis model in ApoE-/- mice with humanized CD147 transgenic expression and demonstrated that the administration of an anti-human CD147 antibody effectively suppressed atherosclerosis by targeting inflammation and efferocytosis. CONCLUSIONS: Myeloid CD147 plays a crucial role in the growth of plaques by promoting inflammation in a TRAF6-IKK-IRF5-dependent manner and inhibiting efferocytosis by suppressing GAS6 during proinflammatory conditions. Consequently, the use of anti-human CD147 antibodies presents a complementary therapeutic approach to the existing lipid-lowering strategies for treating atherosclerotic diseases.

Three Inorganic-Organic Hybrid Gallo-/Alumino-Borates with Porous-Layered Structures Containing [MB4O10(OH)] (M = Al/Ga) Cluster Units.

Three inorganic-organic hybrid gallo-/alumino-borates [Ga2B7O14(OH)]·H2dah (1, dah = 1,6-diaminohexane), K2[Ga2B7O14(OH)(en)0.5] (2, en = ethylenediamine), and K2[Al2B7O14(OH)(en)0.5]·H2O (3) were synthesized under solvothermal conditions. Compound 1 features a 3D porous-layered structure built by the alternation of [GaB4O10(OH)]6-, [B3O6]3- clusters and GaO4 tetrahedra, in which the novel [GaB4O10(OH)]6- cluster is first observed. Compounds 2 and 3 are isostructural and made by [MB4O10(OH)]6-, [B3O6(en)0.5]3- clusters and MO4 tetrahedra (M = Ga/Al); their 3D porous layers are similar to those of 1 and further bridged by en linkers through the rare B-N-C covalent bonds, resulting in the 3D inorganic-organic hybrid framework. This is the first main-group metal borate with organic molecules participating in the oxoboron frameworks through B-N bonds. Optical diffuse-reflectance spectra reveal that 1, 2, and 3 are potential wide-band-gap semiconductors.

Using Bioinformatics Approach to Explore the Pharmacological Mechanisms of Multiple Ingredients in Shuang-Huang-Lian.

Due to the proved clinical efficacy, Shuang-Huang-Lian (SHL) has developed a variety of dosage forms. However, the in-depth research on targets and pharmacological mechanisms of SHL preparations was scarce. In the presented study, the bioinformatics approaches were adopted to integrate relevant data and biological information. As a result, a PPI network was built and the common topological parameters were characterized. The results suggested that the PPI network of SHL exhibited a scale-free property and modular architecture. The drug target network of SHL was structured with 21 functional modules. According to certain modules and pharmacological effects distribution, an antitumor effect and potential drug targets were predicted. A biological network which contained 26 subnetworks was constructed to elucidate the antipneumonia mechanism of SHL. We also extracted the subnetwork to explicitly display the pathway where one effective component acts on the pneumonia related targets. In conclusions, a bioinformatics approach was established for exploring the drug targets, pharmacological activity distribution, effective components of SHL, and its mechanism of antipneumonia. Above all, we identified the effective components and disclosed the mechanism of SHL from the view of system.

A hydrogel-based ratiometric fluorescent sensor relying on rhodamine B labelled AIE-featured hyperbranched poly(amido amine) for heparin detection.

The fluorescent flexible sensor for point-of-care quantification of clinical anticoagulant drug, Heparin (Hep), is still an urgent need of breakthrough. In this research, a hyperbranched poly(amido amine) (HPA) was decorated with tetraphenylethene (TPE) and Rhodamine B (RhB), constructing a ratiometric fluorescent sensor (TR-HPA) for Hep. When the sensor was exposed to Hep, the TPE units within the probe skeleton would aggregate, resulting in an increasing fluorescent emission at 483 nm. The 580 nm of fluorescence came from RhB enhance, simultaneously, due to the fluorescence resonance energy transfer. As a result, there are two good linear correlation between the fluorescence emission ratio (E483/E580) of TR-HPA and the Hep concentration over a range of 0-1.0 µM, with a low limit of detection of 3.0 nM. Furthermore, we incorporate the TR-HPA probe into a polyvinyl alcohol (PVA) hydrogel matrix to create a flexible fluorescent sensing system platform, denoted as TR-HPA/PVA. This approach offers a straightforward visual detection method by causing a fluorescence color change from pink to blue when trace amounts of Hep are present. The hydrogel-based fluorescent sensor streamlines the detection procedures for Hep in biomedical applications. It shows great potential in rapid and point-of-care human blood clotting condition monitoring, making it suitable for next-generation wearable medical devices.

CD147-specific chimeric antigen receptor T cells effectively inhibit T cell acute lymphoblastic leukemia.

T cell acute lymphoblastic leukemia (T-ALL) is invasive and heterogeneous, and existing therapies are sometimes unsuccessful. Chimeric antigen receptor (CAR) T cell therapy is a breakthrough tumor treatment method, particularly for B cell acute lymphoblastic leukemia. We found that CD147 was highly expressed in tumor T cells of T-ALL patients and T cell lymphoma. Therefore, CD147-CAR T cells that contain a humanized single-chain variable fragment targeting human CD147 and a second-generation CAR frame were constructed for treating T-ALL. CD147-CAR T cells were able to maintain a healthy proliferation rate, preserving a subset of CD62L+/CCR7+ memory T cells. CD147-CAR T cells showed a potent anti-tumor activity against human T-ALL cell line and T-ALL blasts, releasing high level of cytokines in the process. However, CD147-CAR T cells exhibited potential safety toward human normal cells and CD147-deficent cells. NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt mice were used to establish a T-ALL xenograft model and CD147-CAR T cells conferred robust protection against T-ALL progression and significantly improved survival in mice. Overall, we found that CD147 is a potential antigen target of CAR T cell therapy for T-ALL.

Endothelial genetic deletion of CD147 induces changes in the dual function of the blood-brain barrier and is implicated in Alzheimer's disease.

AIMS: The blood-brain barrier (BBB) is a specialized and indispensable structure in brain blood vessels that is damaged during Alzheimer's disease (AD). CD147 is expressed on the BBB and deeply engaged in the AD pathological process. In this study, we aimed to provide a better understanding of the roles of CD147 in BBB function in health and neurodegenerative disease. METHODS AND RESULTS: We measured CD147 expression in mouse brains and demonstrated that CD147 is exclusively expressed in brain endothelial cells (BECs), and its expression decreases with age. After constructing endothelial-specific CD147 knockout mice, we performed RNA-sequencing on BECs isolated from mice of different ages as well as a range of database analyses. We found that endothelial CD147 is essential for the dual functions of the BBB, including barrier maintenance and transporter regulation. This study also shows that CD147 plays a pivotal role in neurodegenerative diseases, particularly in AD. CONCLUSIONS: Our findings suggested that targeting CD147 in BECs may represent a novel therapeutic strategy, which promoted the design of future experimental investigations and the mechanistic understanding of neurodegenerative diseases.

Emergency craniotomy in patient with intracranial metastatic choriocarcinoma: a case report.

Choriocarcinoma is a highly malignant gynaecological tumour. This disease becomes life-threatening once brain haemorrhage or brain herniation occurs. Timely and accurate brain surgery can gain treatment time for patients that have a large number of cerebral haemorrhages and/or brain herniation. This current report describes a case of choriocarcinoma secondary to a hydatidiform mole in a 55-year-old woman that presented with neurological symptoms. Following admission to hospital, computed tomography examination found that lung and brain metastases were accompanied by cerebral haemorrhage. Cerebral hernia occurred during induction chemotherapy treatment and emergency surgery was performed. The patient recovered after individual chemotherapy and rehabilitation treatment. Patients with a very high risk of choriocarcinoma with brain metastasis should be referred to a comprehensive medical centre. Necessary surgical treatment and individualized chemotherapy can reduce the mortality of patients with choriocarcinoma brain metastasis.

Two novel 3D borates: porous-layer and layer-pillar frameworks.

Two new borates, NaK1.5[B{B5O9(OH)}{B5O8(OH)2}1/2] (1) and Na3.5[Al{B3O6(OH)}{B5O10}1/2{BO(OH)}] (2), have been made by a solvothermal method. Structure 1 is made of two types of oxoboron clusters ([B5O9(OH)]4- and [B5O8(OH)2]3-) and BO4 tetrahedra to form a 3D porous layer, in which the [B5O9(OH)]4- clusters are bridged by BO4 groups to produce a 2D B-O layer with 11-membered ring (MR) windows, while the [B5O8(OH)2]3- clusters as 2-connected pillars join the adjacent B-O layers to make a 3-D porous layer. Structure 2 is built from two types of oxoboron clusters ([B3O6(OH)]4- and [B5O12]9-), AlO4 units and BO2(OH) triangles to produce 3D pillar-layered aluminoborate (ABO), in which the [B5O12]9- clusters are linked together to form a 2-D B-O layer; the [B3O6(OH)]4- clusters and AlO4 groups join each other to form 1D tubular ABO; and the BO2(OH) triangles act as linkers to connect the adjacent B-O layer and the ABO tubes, resulting in 3D pillar-layered ABO. Interestingly, the ABO tubes decorated with the BO2(OH) triangles act as pillars to make a 3D layer-pillared structure. UV-vis diffuse spectra indicate that both have cut-off edges below 190 nm, and the calculated band gaps are 5.75 and 5.78 eV, respectively.

Blockade of Macrophage CD147 Protects Against Foam Cell Formation in Atherosclerosis.

The persistence of macrophage-derived foam cells in the artery wall fuels atherosclerosis development. However, the mechanism of foam cell formation regulation remains elusive. We are committed to determining the role that CD147 might play in macrophage foam cell formation during atherosclerosis. In this study, we found that CD147 expression was primarily increased in mouse and human atherosclerotic lesions that were rich in macrophages and could be upregulated by ox-LDL. High-throughput compound screening indicated that ox-LDL-induced CD147 upregulation in macrophages was achieved through PI3K/Akt/mTOR signaling. Genetic deletion of macrophage CD147 protected against foam cell formation by impeding cholesterol uptake, probably through the scavenger receptor CD36. The opposite effect was observed in primary macrophages isolated from macrophage-specific CD147-overexpressing mice. Moreover, bioinformatics results indicated that CD147 suppression might exert an atheroprotective effect via various processes, such as cholesterol biosynthetic and metabolic processes, LDL and plasma lipoprotein clearance, and decreased platelet aggregation and collagen degradation. Our findings identify CD147 as a potential target for prevention and treatment of atherosclerosis in the future.

Inductively Coupled Plasma Mass Spectrometry as a Reference Method to Evaluate Serum Calcium Measurement Bias and the Commutability of Processed Materials during Routine Measurements.

BACKGROUND: Measuring total serum calcium is important for the diagnosis of diseases. Currently, results from commercial kits for calcium measurement are variable. Generally, the performance of serum calcium measurements is monitored by external quality assessment (EQA) or proficiency testing schemes. However, the commutability of the EQA samples and calibrators is often unknown, which limits the effectiveness of EQA schemes. The aim of this study was to evaluate the bias of serum calcium measurements and the commutability of processed materials. METHODS: Inductively coupled plasma mass spectrometry was applied as a comparative method, and 14 routine methods were chosen as test methods. Forty-eight serum samples from individual patients and 25 processed materials were quantified. A scatter plot was generated from patient samples, and 95% prediction intervals were calculated to evaluate the commutability of the processed materials and measurement bias at three concentration levels was used to determine the accuracy of routine assays. RESULTS: All assays showed high precision (total coefficient of variation [CV] <2.26%) and correlation coefficients (r > 0.99). For all assays, the mean bias for the 48 patient samples ranged from -0.13 mmol/L to 0.00 mmol/L (-5.61-0.01%), and the ranges for the three concentrations were -0.10-0.04 mmol/L (-5.71-2.35%), -0.14--0.01 mmol/L (-5.80--0.30%), and -0.19-0.04 mmol/L (-6.24-1.22%). The EQA samples, calibrators, and animal sera exhibited matrix effects in some assays; human serum pools were commutable in all assays; certificate reference materials were commutable in most assays, and only GBW09152 exhibited a matrix effect in one assay; and aqueous reference materials exhibited matrix effects in most assays. CONCLUSIONS: Biases for most assays were within the acceptable range, although the accuracy of some assays needs improvement. Human serum pools prepared from patient samples were commutable, and the other tested materials exhibited a matrix effect.

Investigation and Analysis of Hemoglobin A1c Measurement Systems' Performance for 135 Laboratories in China.

BACKGROUND: Hemoglobin A1c (HbA1c) measurement is of great value for the diagnosis and monitoring of diabetes. Many manufacturers have developed various experiments to determine the HbA1c concentration. However, the longitudinal use of these tests requires strict quality management. This study aimed to analyze the quality of HbA1c measurement systems in China using six sigma techniques to help improve their performances. METHODS: A total of 135 laboratories were involved in this investigation in 2015. Bias values and coefficients of variation were collected from an HbA1c trueness verification external quality assessment program and an internal quality control program organized by the National Center of Clinical Laboratories in China. The sigma (σ) values and the quality goal index (QGI) were used to evaluate the performances of different groups, which were divided according to principles and instruments. RESULTS: The majority of participants (88, 65.2%) were scored as "improvement needed (σ < 3)", suggesting that the laboratories needed to improve their measurement performance. Only 8.2% (11/135) of the laboratories were scored as "world class (σ ≥ 6)". Among all the 88 laboratories whose σ values were below 3, 52 (59.1%) and 23 (26.1%) laboratories needed to improve measurement precision (QGI <8.0) and trueness (QGI >1.2), respectively; the remaining laboratories (13, 14.8%) needed to improve both measurement precision and trueness. In addition, 16.1% (5/31) and 15.0% (3/20) of the laboratories in "TOSOH" and "ARKRAY" groups, respectively, were scored as "world class", whereas none of the laboratories in "BIO-RAD" group were scored as "world class". CONCLUSIONS: This study indicated that, although participating laboratories were laboratories with better performance in China, the performances were still unsatisfactory. Actions should be taken to improve HbA1c measurement performance before we can include HbA1c assays in diabetes diagnosis in China.

SAGE reveals expression of Wnt signalling pathway members during mouse prostate development.

To identify genes and pathways not previously implicated in the mesenchymal-epithelial (M/E) interactions that are critical for normal mouse prostate development, we constructed six serial analysis of gene expression (SAGE) libraries. Bioinformatic analyses revealed expression of various members of numerous signalling pathways and the differential expression of several members of the wingless-related MMTV integration site (Wnt) signalling pathway. This pathway has not been previously implicated in prostate development thus expression of selected Wnt pathway members in the developing prostate was confirmed by RT-qPCR. Of particular interest, an antagonist of the Wnt pathway, secreted frizzled related protein 2 (Sfrp2), was highly expressed in the early prostate libraries and down regulated at later developmental stages. The expression levels of four Wnt ligands reported to interact with Sfrp2 were, therefore, examined by RT-qPCR. We found that only Wnt4 transcripts were detectable in the developing prostate. Expression of Sfrp2 was validated using RT-qPCR and localization of Sfrp2 transcripts and protein was carried out using in situ hybridization and immunofluorescence, respectively. These studies provide the first evidence that Wnt pathway members are expressed in the developing prostate. Functional analyses are now required to establish the biological significance of this observation.

[Identification of coupling relationship between urbanization and ecological environment in Jilin from entropy change perspective].

By using the entropy change equation of the second law of thermodynamics, entropy method and PSE model, this article made an analysis on coupling relationship between urbanization and ecological environment in Jilin Province from 2001 to 2011. In the study period, the urbanization development had been out of normal evolution track: The economic urbanization and space urbanization dominated the whole urbanization process, while population urbanization was neglected too seriously, with an apparent characteristic of extensive and inefficient input of resources (especially land resource). According to the levels of ecological environment on the basis of PSE model, not only the pressure index, sensitivity index and the elasticity index, but also the comprehensive index showed considerable growth with obvious stage characteristics: ascending-descending-ascending. The total entropy values of the urbanization were less than zero during the time, which meant an unstable rising curve. While the total trophy values of the ecological environment varied below and above zero, and 2003, 2006, 2010 and 2011 were the "turning points", reflecting the instability of the ecological environment. The coupling total entropy values between urbanization and ecological environment had the same characteristics with the ecological environment: the same "turning points" and shape of the curve, in which, the "turning points" corresponded to the type of antagonistic evolution pattern, while the rest of years responded to the type of coordination evolution pattern.

[Effects of different iron oxides on methane emission in paddy soil as related to drying/wetting cycles].

This study investigated the effects of iron oxides with different crystallinities, ferrihydrite (SF) and hematite (SH), on the methane emission in paddy soil of South China under different water conditions, alternative drying/wetting cycles (DW) and continuous flooding (CF). The rates of methane emission, methane production potential and concentrations of Fe(II) and Fe(III) were determined. Results showed that compared with CF, the average methane emission rate was greatly inhibited by DW over 61%, and the addition of iron oxides reduced methane emission rates by 53%. Under the circumstance of DW and iron oxides addition, the combined inhibition effect on the average methane emission (65%-94%) and methane production potential (57%-93%) was significantly higher than the single effect caused by DW or iron oxides. Interestingly, DW coupling poorly crystalline ferrihydrite (SF-DW, 94%) posed a more significantly inhibitory effect on the methane emission than coupling crystalline hematite (SH-DW, 65%). Statistical analysis showed that there was a significantly negative correlation between the Fe(III) concentrations and the methane emission rates (R2 = -0.98, P < 0.01). Experimental results showed that DW facilitated the cyclic regeneration of Fe(III), and the Fe(III)/Fe(II) cycle in poorly crystalline ferrihydrite was more susceptible to DW than hematite. This study suggested that alternative drying/wetting cycles can remarkably enhance the inhibitory effect of iron oxides on methane emission from paddy soil, and the coupled suppression effect of DW and poorly crystalline ferrihydrite is more obvious than the coupled effect of DW and crystalline hematite.

[Clinical features and survival analysis in primary myelodysplastic syndromes patients with immunological abnormalities].

OBJECTIVE: To analyze the clinical features and survival time in primary myelodysplastic syndromes (MDS) patients accompanied with immunological abnormalities. METHODS: The clinical information, laboratory findings and survival time in 194 untreated primary MDS patients with complete immunological laboratory tests or a past history of autoimmune disease were analyzed retrospectively. RESULTS: There were 37/194 cases (19.07%) with autoimmune abnormalities, including 16/194 (8.25%) with autoimmune disease and 21/194 asymptomatic cases (10.82%) with serologic immunological abnormalities only. There was significant differences in the distribution of age < 60 years old, female, CD4(+)T-cell/CD8(+)T-cell ration < 1 and trisomy 8 (P < 0.05) between the cases with autoimmune disease and without autoimmune abnormalities. The former had a higher 2-year OS, but there was no significance (P = 0.065). There was no significant differences in the distribution of age, MDS-subtype, IPSS risk groups, haemoglobin, absolute neutrophil count, platelets count, the severity of anemia and neutropenia, high level of serologic TNF, chromosomal abnormalities, cytogenetic risk groups and bone marrow cellularity (P > 0.05). CONCLUSION: MDS patients with autoimmune disease are mainly female and younger than 60 years old, with high proportion of trisomy 8 and better prognosis.

[A preliminary study of prognostic value of thrombocytopenia in patients with primary myelodysplastic syndromes].

OBJECTIVE: To investigate the prognostic value of thrombocytopenia in patients with primary myelodysplastic syndromes (MDS). METHODS: Four hundred and nineteen primary MDS patients were retrospectively analyzed. Kaplan-Meier method, Log-rank test and COX regression model were used to evaluate factors that influence the prognosis. RESULTS: Two hundred and fifty-six cases (61.1%) had thrombocytopenia (PLT < 100×10(9)/L), one hundred and three cases (24.6%) had severe thrombocytopenia (PLT < 30×10(9)/L). Overall survival (OS) tended to shorten along with the decreasing of platelet count. Univariate analysis indicated that PL < 30×10(9)/L, MCV ≤ 95 fl, LDH ≥ 300 U/L, lymphocyte-like micromegakaryocyte, nucleated RBC PAS positive, IPSS cytogenetic intermediate- and poor-risk were all related with poor prognosis. Moreover, the prognosis of patients with RCMD, RAEB-Ior RAEB-IIwas poorer than that of the other subgroups. Among these parameters, PLT < 30×10(9)/L, MCV ≤ 95 fl, IPSS cytogenetic intermediate- and poor-risk group and RCMD, RAEB-I and RAEB-II had independent prognostic significance in multivariate analysis. Modified WPSS prognostic model was proposed by adopting PLT, MCV, chromosomal karyotype and WHO classification. The OS of patients with low risk, intermediate-1 risk, intermediate-2 risk and high risk were 59, 28, 14 and 4 months, respectively, and there was a statistically significant difference between the groups (P < 0.05). CONCLUSION: Severe thrombocytopenia indicated unfavorable prognosis, in combination with MCV, chromosomal karyotype and WHO classification, a modified WPSS prognostic model was proposed and worked well for prognostic indication in patients with MDS.

[Analysis of in vitro characteristics of colony-forming cells in myelodysplastic syndrome and comparison with that in non-severe aplastic anemia].

OBJECTIVE: To investigate in vitro characteristics of colony-forming cells (CFC) in patients with myelodysplastic syndrome (MDS) and to compare that in patients with non-severe aplastic anemia (NSAA). METHODS: Data of in vitro CFC and correlation with other related laboratory tests in 155 newly diagnosed MDS patients were analyzed retrospectively, and to compare with data of in vitro CFC in 122 newly diagnosed NSAA patients. RESULTS: Median number of burst-forming units-erythroid (BFU-E) was 9 (0 - 157)/10(5) bone marrow mononuclear cells (BMMNC), colony forming unit-erythroid (CFU-E) 30 (0 - 425)/10(5)BMMNC and colony forming unit-granulocytes/macrophages (CFU-GM) 14 (0 - 125)/10(5)BMMNC in patients with MDS, being significantly lower than those in healthy control; number of BFU-E and/or CFU-E was lower than the lower limit of normal control in 66 cases (42.6%), CFU-GM lower in 3 cases (1.9%) and BFU-E and/or CFU-E with CFU-GM lower in 70 cases (45.2%). Cluster/CFU-GM ratio was significantly lower in low blast group (MDS < 5% blast in bone marrow smear) than that in high blast group (MDS ≥ 5% blast) (0.65 vs 1.0, P = 0.049). In all MDS patients, cluster had positive correlation with each type of CFC (r = 0.415, 0.338, 0.642 for BFU-E, CFU-E, CFU-GM, respectively, P = 0.000), but had negative correlation with neutrophil alkaline phosphatase (N-ALP) positive rate and scores (r(rate) = -0.315, P = 0.001 and r(scores) = -0.257, P = 0.006). The median number of each type of CFC was significantly higher in MDS group than that in NSAA group (BFU-E 9 vs 5/10(5)BMMNC, P = 0.017; CFU-E 30 vs 19.5/10(5)BMMNC, P = 0.023; CFU-GM 14 vs 10/10(5)BMMNC, P = 0.003, respectively). Positive correlation between BFU-E and CFU-E were revealed in both MDS and NSAA group (r(MDS) = 0.712, P = 0.000 and r(NSAA) = 0.757, P = 0.000), with a lower correlation coefficient in MDS (P < 0.05). CONCLUSIONS: Early onset MDS present markedly decreased hematopoietic progenitor cells (HPC), and particularly in erythroid progenitors extensively and severely. The number of BFU-E, CFU-E and CFU-GM can reflect HPC number in vivo but not stand for normal hematopoietic clones, the number of clusters represent pathologic HPC clones but not exactly leukemic blasts.

[Study on prognostic significances of different cytogenetic risk categories in patients with primary myelodysplastic syndromes].

OBJECTIVE: To analyze significances of different cytogenetic categories for prognostic stratification in patients with primary myelodysplastic syndromes (MDS). METHODS: Chromosomal abnormalities of 532 primary MDS patients were categorized according to cytogenetic categories of International Prognostic Scoring System (IPSS), Revised IPSS (IPSS-R), and German-Austrian (G-A). Prognostic impacts of different cytogenetic categories and frequent isolated anomalies were investigated. RESULTS: Of 532 patients, 346(65%) patients had clonal cytogenetic abnormalities, including 200(38%) patients had 1 abnormality, 61(11%) patients had 2 abnormalities, and 85(16%) patients had complex abnormalities. Trisomy 8 was the most frequent karyotype abnormality, occurring in 31% of the patients with clonal cytogenetic abnormalities, other frequent anomalies were -7/del(7q)(13%), del(20q)(12%), del(5q)(9%), -18(5%), -21(5%), i(17q)(5%), -Y(4%), -17(4%), +21(4%), -13/del(13q)(4%), and -22(4%). The proportion of poor karyotypes of IPSS was higher in RAEBI and RAEBII among the World Health Organization classifications than in subgroups with less than 5% blasts. The follow-up data were available for 310 patients with a median follow-up duration of 14.5 months. Median survival was 59 months for patients with normal karyotypes and 26 months for those with abnormal karyotypes. According to IPSS cytogenetic categories, the median survivals of good-risk subgroup, intermediate-risk subgroup and poor-risk subgroup were 59, 43 and 12 months, respectively (P < 0.01). For IPSS-R cytogenetic groups, the median survivals of good-risk subgroup, intermediate-risk(int-risk) subgroup, poor-risk and very poor-risk subgroup were 59, 36, 15, and 10 months, respectively (P < 0.01). According to G-A classification, the median survivals of good-risk subgroup, int-1-risk subgroup, int-2-risk subgroup and poor-risk subgroup were 59, 44, 15, and 11 months, respectively (P < 0.01). In frequent isolated karyotypic abnormalities, +8 had a median survival of 44 months, i(17q) had a median survival of 12 months, and -7/del(7q) had a median survival of 14 months. CONCLUSION: In comparison with IPSS and G-A categories, IPSS-R cytogenetic categories are more sophisticated, and can stratify prognosis effectively, but prognostic significances of some karyotypes in IPSS-R still need to be confirmed.