Melatonin-Mediated Inhibitory Effect on Hyperimmune Status of Acquired Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients.@*METHODS@#The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro.@*RESULTS@#The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4+ and CD8+ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4+ and CD8+ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01).@*CONCLUSION@#The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.

MiR-335-5p-Mediated Dysfunction of T Lymphocytes in Patients with Acquired Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of miR-335-5p/ADCY3 interaction on the lymphocyte function in the patients with aplastic anemia (AA).@*METHODS@#Blood samples were collected from 22 healthy volunteers (HC) and 50 AA patients including 38 severe AA (SAA) and 12 non-severe AA (NSAA). Peripheral blood mononuclear cells (PBMNC) were isolated. The expression of miR-335-5p and ADCY3 mRNA was detected by using RT-PCR. Negative control miR-335-5p (NC group) and miR-335-5p mimic (mimic group) were transfected to AA-PBMNC by using RNAimax reagent, respectively. The proliferative ability, activation and cytokines of CD4 T and CD8 T cells were measured by flow cytometry. Dual-luciferase reporter assay was used to verify the targeted relationship between miR-335-5p and target gene.@*RESULTS@#The expression of miR-335-5p was significantly downregulated in SAA-PBMNC and NSAA-PBMNC compared with HC-PBMNC (0.08±0.01 vs 0.74±0.10, P＜0.01; 0.17±0.02 vs 0.74±0.10, P＜0.01). Meanwhile, the expression of miR-335-5p in SAA-PBMNC was very statistically significantly lower than that in NSAA-PBMNC (P＜0.01). Compared with NC group, upregulation of miR-335-5p in vitro could significantly inhibited the proliferation of CD4 T and CD8 T cells in AA-PBMNC (P＜0.05 and P＜0.05, respectively). And, upregulating miR-335-5p in AA-PBMNC could significantly inhibited the activation of CD4 and CD8 T cells (P＜0.01 and P＜0.01, respectively). The ratio of CD4TNFα T, CD8IFNγ+T and CD8TNFα T cell by up-regulating the expression of miR-335-5p from AA-PBMNC in vitro was also significantly lower (P＜0.01, P＜0.05 and P＜0.05, respectively). In addition, the expression of ADCY3 was higher in AA-PBMNC than that in HC-PBMNC (1.70±0.15 vs 0.76±0.12, P＜0.01). Furthermore, by means of dual-luciferase reporter assay, the luciferase activity of ADCY3'UTR wildtype could be inhibited by miR-335-5p.@*CONCLUSIONS@#The expression of miR-335-5p was significantly downregulated in AA, and that correlates with disease severity. Up-regulating miR-335-5p can correct the hyperimmune status in AA patients by targeting ADCY3. These changes may relates with the strengthen of inhibition for targeted gene ADCY3.

CT-guided minimally-invasive penile fracture repair

ABSTRACT We present the case of a 28 year old patient with an incomplete tear of the tunica albuginea occurred after having sexual intercourse in the female superior position. The diagnostic assessment was performed first clinically, then with CT, owing to its high resolution, allowed to exactly detect the tear location leading to precise preoperative planning. After adequate diagnosis through imaging and proper planning, the patient was performed a selective minimally invasive surgical approach to repair the lesion. The patient had good erection with no angular deformity or plaque formation after a 3-month follow-up.

Clonal evolution and clinical significance of trisomy 8 in acquired bone marrow failure / 中华血液学杂志

Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r(s)=0.109, P=0.125; r(s)=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions: AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn't significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.

Clinical features and laboratory data analysis of decreased glycosylated hemoglobin related to hemolytic disease / 中华血液学杂志

Objective: To compare the effects of different hemolytic diseases on the level of glycosylated hemoglobin (HbA(1c)) to further explore the relationship between HbA(1c) and laboratory indexes to disclose implications of HbA(1c) in hemolytic diseases. Methods: The distribution of 192 decreased HbA(1c) cases in 4 categories of hemolytic diseases was analyzed. Laboratory indexes related to hemolysis were tested and analyzed in each kind of disease, and relationship between laboratory indexes and HbA(1)c was statistically explored. Results: Diagnoses of decreased HbA(1c) cases mainly included erythrocyte membranopathies (88 cases), immunohemolytic anemia (72 cases), hemoglobinopathy (4 cases) and erythrocyte enzymopathy (5 cases). The distribution of HbA(2) and normal HbF subjects in immunohemolytic anemia and hemoglobinopathy was significantly different from those of HbA(2) and / or abnormal HbF subjects (41.7% vs 22.0%, χ(2)=5.574, P=0.018; 0.7% vs 7.3%, P=0.031). Compared with non-hemolytic disease patients, those who suffered from 4 categories of hemolytic diseases showed lower HbA(1c) level and higher reticulocyte percentage (Ret), indirect bilirubin (IBIL) and free hemoglobin (F-Hb). Different levels of Ret, reticulocyte hemoglobin content (Ret-He), mean corpuscular volume (MCV), IBIL and F-Hb among the 4 kinds of diseases were observed, but the causes of the differences were not the same. HbA(1c) was negatively correlated with other laboratory indexes in erythrocyte membranopathies and immunohemolytic anemia. Conclusions: Hemolytic disease resulted in false lower HbA(1c), but impact of difference on HbA1c between different diseases was not significant. HbA(1c) was closely connected to laboratory indexes related to hemolysis, which might have potential implications for hemolytic diseases such as erythrocyte membranopathies and immunohemolytic anemia.

Outcomes of splenectomy in relapsed/refractory autoimmune hemolytic anemia / 中华血液学杂志

Objective: To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA). Methods: Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up. Results: Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years. Conclusion: The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.

Tetracycline-resistant Neisseria gonorrhoeae strains isolated in a GradeⅢhospital in eastern China:molecular characteristics and genetic diversity / 中华微生物学和免疫学杂志

Objective To analyze the genotypes of Neisseria gonorrhoeae ( N. gonorrhoeae) epi-demic strains in Wenzhou, eastern China, and to study the mechanism of tetracycline resistance in these strains. Methods A total of 77 N. gonorrhoeae strains were isolated from patients with gonorrhea. Antimi-crobial susceptibility of these strains to penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone and azithromycin was analyzed using E-test. PCR and DNA sequencing were used to detect the genes associ-ated with tetracycline resistance, such as Tet-M, mtrR promoter region and mtrR coding region. N. gonor-rhoeae multi-antigen sequence typing ( NG-MAST) and multilocus sequence typing ( MLST) were used to determine the molecular characteristics of all clinical isolates and tetracycline-resistant isolates, respectively. Results Among the 77 N. gonorrhoeae isolates, 74 (96. 10％), 27 (35. 06％) ,70 (90. 91％) and 15 (19. 48％) were resistant to penicillin, tetracycline, ciprofloxacin and azithromycin, respectively. All tested isolates were susceptible to spectinomycin and ceftriaxone. Nineteen isolates were resistant to tetracycline and all of them carried Tet-M gene. Among them, 17 had one deletion mutation of base A in mtrR promoter region and three had G45D mutation in mtrR coding region. NG-MAST classified the 19 tetracycline-resistant isolates into 11 different sequence types (ST). ST14781, ST1766 and ST1866 each accounted for 15. 79％(three strains). Two ST (10. 52％, 2/19) found in the present study had not been reported previously in the NG-MAST database. MLST showed the 19 tetracycline-resistant isolates belonged to 12 different STs, in which ST10899 accounted for 26. 32％ (five strains) and ST1600 accounted for 15. 79％ (three strains). Conclusions Mutations in mtrR promoter region and carrying Tet-M gene were associated with tetracycline resistance in N. gonorrhoeae. Clinical strains isolated in Wenzhou showed considerable molecular diversity. Measures should be implemented to monitor the spread of NG-MAST ST1766 and MLST ST1600 N. gonor-rhoeae clones with high resistance to tetracycline in Wenzhou.

Host modulation therapy in periodontitis / 口腔疾病防治

@#Host modulation therapy (HMT), as a treatment concept for periodontitis, aims to modulate the host immune responses during the pathogenesis of periodontitis. Various drugs have been evaluated as HMT, including subdose doxycycline (SDD), nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, and cytokine receptors, to modify or modulate inflammatory mediators and associated signaling pathways in the immune-inflammatory response, as well as connective tissue breakdown and bone resorption. SDD, a member of the tetracycline drug family, has been reported to improve periodontal treatment outcomes by inhibiting periodontal breakdown through inhibiting MMPs. NSAIDs may suppress periodontal inflammation by reducing cyclooxygenase-2(COX-2) activity. Combined application of SSD and NSAIDs may achieve a better clinical outcome. Recent studies of HMT treatment have focused on the prevention of excessive inflammation by regulating mediators using endogenous lipid mediators. Local administration of bisphosphonates and histone deacetylase inhibitors can inhibit osteoclast activity and regulate bone tissue remodeling. Currently, SSD is approved by the FDA for periodontal treatment. Other drugs, such as COX-2 selective inhibitor, nonsteroidal anti-inflammatory drugs, bisphosphonates, triclosan and iNOS inhibitors, have good application prospects in the prevention and treatment of periodontal disease, and the mechanism and side effects of these drugs remain to be further investigated.

Comparison of hemolytic characteristics among paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia and hereditary spherocytosis / 中华血液学杂志

Objective: To determine the valuable hemolytic characteristics in differential diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA) and hereditary spherocytosis (HS). Method: The clinical and hemolytic characteristics of 108 PNH patients, 127 AIHA patients and 172 HS patients diagnosed from January 1998 to April 2017 were compared. Results: ①Reticulocyte percentage (Ret%) of PNH patients [6.70% (0.14%-22.82%)] was significantly lower than that of AIHA [14.00%(0.10%-55.95%), P<0.001] and HS patients [11.83%(0.60%-57.39%), P<0.001]. The Ret% in PNH patients were significantly lower than those in AIHA and HS patients at the same levels of anemia, except for in mild anemia between PNH and AIHA patients. However, when comparing the Ret% between AIHA and HS patients, there was significant difference only in mild anemia [7.63%(1.87%-29.20%)% vs 11.20%(3.31%-22.44%), z=-2.165, P=0.030]. ②The level of TBIL in HS patients was significantly higher than that in AIHA and PNH patients [79.3 (11.2-244.0) μmol/L vs 57.6 (7.6-265.0) μmol/L, z=5.469, P<0.001; 79.3(11.2-244.0) μmol/L vs 26.2(4.6-217.7) μmol/L, z=-2.165, P<0.001], and the proportion of HS patients with TBIL more than 4 times the upper limit of normal (ULN) (64.1%) was significantly higher than that of AIHA (37.7%, χ(2)=19.896, P<0.001) and PNH patients (4.6%, P<0.001). ③The LDH level of PNH patients was significantly higher than that of AIHA and HS [1 500 (216-5 144) U/L vs 487 (29-3 516) U/L, z=-9.556, P<0.001; 1 500 (216-5 144) U/L vs 252 (132-663) U/L, z=-11.518, P<0.001], and the proportion of PNH patients with LDH more than 1 000 U/L (79.1%) was significantly higher than that of AIHA patients (13.0%, χ(2)=93.748, P<0.001) and HS patients (0, P<0.001). ④Splenomegaly occurred in 43.5% of PNH patients, including 16.0% with severe splenomegaly. In contrast, the occurrence of splenomegaly was 98.6% in AIHA patients and 100.0% in HS patients (P<0.001), and 63.0% of AIHA patients (P<0.001) and 90.4% of HS patients (P<0.001) were with severe splenomegaly. ⑤The prevalence of cholelithiasis in HS patients was up to 43.1%, significantly higher than that in AIHA patients (10.5%, P<0.001) and PNH patients (2.9%, P<0.001). Conclusion: The comprehensive assessment of the five hemolytic characteristics is simplified, practical and efficient, with great clinical significance, providing specific indicators for differential diagnosis and efficient approach for making further work-up.

Effect of CD106 Mesenchymal Stem Cell on Bone Marrow Vascular Failure in Patients with Aplastic Anemia / 中国医学科学院学报

Objective To investigate the vascularization ability of mesenchymal stem cells(MSCs)and explore its influencing factors in aplastic anemia(AA) patients. Methods MSCs were isolated from the bone marrow of AA patients(AA MSCs) and normal controls(N MSCs) were cultured and then evaluated by flow cytometry and immunofluorescene staining technique.The expression level of vascular cell adhesion molecule-1(CD106) was detected by gene sequencing,and the content and fluorescene intensity of CD106MSCs was determined by fluorescence-activated cell sorting.The content of CD105CD106MSCs in fresh AA bone marrow was measured,followed by the determination of the capability of endothelial differentiation from AA MSCs and N MSCs with immunofluorescene analysis;finally,the capability of CD31cell differentiation from CD106-blocking N MSCs and its tubular structures formation in matrigel were tested.Results The expression of CD106 in AA patients was defective(decreased by 12.13 times when compared with N MSCs) and the concentration and fluorescene degree of CD106MSCs was also decreased in AA patients [(28.03±17.71)% vs.(59.61±12.26)%,P=0.000].The content of CD105CD106MSCs decreased significantly in the fresh bone marrow [(0.33±0.10)% vs.(2.98±0.46)%,P=0.0005].Besides, the capability of CD31cell differentiation from AA MSCs was significantly delayed [(13.67±1.50)% vs.(43.24±0.96)%,P=0.0004].Also,the capability of CD31cell differentiation and tubular structures formation of CD106-blocking N MSCs was also obviously decreased [(26.00±2.65)% vs.(91.78±2.44)%,P=0.000;(13.81±1.98)mm vs.(68.12±6.78)mm,P=0.0015].Conclusion The deficient or decreased expression of CD106MSCs accelerate the bone marrow vascularization failure in AA patients.

Clinical Features and Laboratory Data Analysis of Glucose-6- Phosphate Dehydrogenase Deficiency / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore clinical features and laboratory data of glucose-6-phosphate dehydrogenase（G6PD）deficiency and to investigate the relationship between them.</p><p><b>METHODS</b>Clinical data of 43 patients with G6PD deficiency was analyzed, the statistical method was applied to investigate the relationship between clinical features and laboratory data.</p><p><b>RESULTS</b>Among 43 patients，neonatal jaundice occurred as the first symptom in 10 cases，while acute hemolytic anemia occurred as the first symptom in 23 cases. The major clinical symptoms of G6PD deficiency included icteric skin and/or sclera，dark urine，fever，gastrointestinal symptoms，fatigue and lethargy. Symptoms of 26 patients were caused by obvious inducement，including fava beans（61.5%），infection（34.6%）and miocardial infarction（3.8%）. All of 43 patients showed decreased G6PD activity，while the level of their indirect serum bilirubin（IBIL）was positively correlated with reticulocyte percentage（Ret%，r=0.5881，P=0.013） and mean corpuscular volume（MCV，r=0.6854，P=0.0024）. Patients with neonatal jaundice as the first symptom，showed higher level of Ret%（P<0.01）and MCV（P<0.001）and low RBC count（P<0.01）and low Hb level（P<0.01）. as compard with patients with acute hemolytic anemia as first symptome.</p><p><b>CONCLUSION</b>Neonatal jaundice and acute hemolytic anemia are common clinical features of G6PD deficiency. Laboratory results of IBIL，Ret% and MCV have auxiliary value to evaluate the severity of hemolysis induced by G6PD deficiency. Patients with neonatal jaundice as their first symptom show more severe hemolysis than those only suffered from acute hemolytic anemia.</p>

Differential Expression Profiles of MicroRNAs between de novo and Complete Response Severe Aplastic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect the expression of miRNA in de novo and complete response SAA patients and predict the targets of the miRNAs.</p><p><b>METHODS</b>The expression profiles of miRNA from bone marrow mononuclear cells of the SAA patients with de novo and CR were detected by miRNA microarray.</p><p><b>RESULTS</b>Totally 35 up-regulated and 37 down-regulated miRNA were identified in CR SAA patients in comparison with de novo SAA patients. Furthermore, by predicting the targets of the differentlly expressed miRNA, it was found that some targets associated with T cell receptor signaling pathway and cell adhesion molecules.</p><p><b>CONCLUSION</b>Some miRNA may be involved in the pathogenesis of SAA.</p>

Clinical Characteristics and Gene Mutations of Gilbert Syndrome Complicated with Myeloproliferative Neoplasm / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and gene mutations of patients with Gilbert syndrome complicated with myeloproliferative neoplasms (MPN).</p><p><b>METHODS</b>Peripheral blood samples from 1 patient with Gilbert syndrome complicated with MPN and his son were collected to analyse all exon mutations of UGT1A1 gene.</p><p><b>RESULTS</b>The patient with leukocytosis, thrombocythemia, mild anemia and positive JAK2/V617F mutation was initially diagnosed as MPN. The hyperbilirubinemia suggested concurrent disease. Further gene evaluation disclosed a insertion mutation in the (TA)TAA box, and a missense mutation(G→A) at 211 bp of exon 1, corresponding to the deficiency in the bilirubin-conjugating enzyme uridine-diphosphoglucuronosyl transferase1A1 (UGT1A1). His son only carried some polymorphism mutation without manifestation of this disease.</p><p><b>CONCLUSION</b>It is a first report case of MPN complicated with Gilbert syndrome that can highlight the differential diagnosis for hyperbilirubinemia.</p>

Investigation of low vision in patients with diabetes mellitus and related risk factors in Tangshan / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the current status of diabetic patients with low vision in Tangshan,and to explore the risk factors of low vision.METHODS:A sampling survey was conducted to select 2000 diabetic residents in Tangshan area from January to December 2016 to examine the incidence of diabetic low vision in Tangshan area.The diabetic patients with low vision included in the observation group,another 2 times the number of cases of diabetes with normal vision were selected as control group.Logistic regression was used to analyze the related history data of two groups of patients were investigated,to analyze the risk factors to low vision.RESULTS:Of the 2000 diabetic patients involved in visual acuity examination,there were 189 patients (275 eyes) with poor vision,the incidence rate was 6.90％.Among them,102 patients (102 eyes) with monocular vision deficit (2.55％),binocular vision was poor in 87 cases (174 eyes,4.35％).Logistic multivariate regression analysis showed that the age,course of disease and retinopathy of diabetes were the major risk factors of low vision in diabetic patients.CONCLUSION:The incidence of low vision in diabetic patients in Tangshan area is low.The age,course of disease and retinopathy of diabetes are the main causes of low vision.Therefore,strengthening the retinopathy visual examination,early prevention and treatment,in elderly patients,and patients with long course of disease,can reduce the occurrence and development of low vision in patients with diabetes mellitus.

Long-term Follow-up of Patients with Hepatitis-Associated Aplastic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristic, therapeutic efficacy and prognosis of patients with hepatitis-associated aplasitc anemia (HAAA).</p><p><b>METHODS</b>the clinical data and labrotatory examination results of 30 cases of HAAA were analyzed retrospectively, the 6-month response ratio and overall survival (OS) were assessed.</p><p><b>RESULTS</b>HAAA most commonly occured in males, with the occurence rate of males and females was 4:1, the median onset age was 16 (4-43) years old, HAAA oriented focus on sever aplastic anemia (SAA)(4 cases,13%) and very sever aplastic anemia (VSAA)(22 cases,73%). Aplastic anemia (AA) could be seen on occurence of hepatitis (accompanied aplastic anemia) (7 cases,23%), or after the onset of hepatits (delayed aplastic anemia) (23 cases,77%), but more often occured in the latter. Statistical analysis showed that when compared with the patients of delayed aplastic anemia, patients accompanied aplastic anemia possesses lower levels of glutamic-pyruvic transaminase(ALT), aspertate aminotransferase (AST) and total bilirubin (TBIL)(P=0.042,0.012,0.001), and possessed a more obvious lymphoid cell disorder when AA occured, with more lower peripheral blood CD19B cells proportion (P=0.046) and more obvious imbalance of CD4/CD8ratio, but the difference was no statistical significant (P=0538). Factors affecting the 6-month respose were the severity of AA (P=0.044), the peak level of bilirubin of hepatitis (P=0.006) and the propotion of mature monocyte in bone marrow (P=0.034). The long-term follow-up showed that the 2-year OS of HAAA was 64.3±9.2%, the 6-month curative efficacy significantly affect the prognosis (P<0.001).</p><p><b>CONCLUSION</b>HAAA more often occur in young male, HAAA is mainly SAA and VSAA and mostly non-A-C hepatitis associated aplastic anemia, patients usually have a high incidence of early infection. Patients acompanied with aplastic anemia possess more obvious immunological derangement; the treatment efficacy for HAAA is poor, patients who haven't obtained 6-month response indicate a sinister prognosis, allogeneic hematopoietic stem cell transplantion is a better choice for these patients.</p>

Association of ADAMTS-1 gene polymorphisms with ischemic stroke caused by large artery atherosclerosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of a disintegrin and metallo-proteinase with thrombospondin type 1 motifs (ADAMTS-1) gene polymorphism and ischemic stroke caused by large artery atherosclerosis (LAA).</p><p><b>METHODS</b>In total 767 patients and 506 controls were recruited. Single nucleotide polymorphisms (SNPs) rs416905 (T/C) and rs402007 (G/C) of the ADAMTS-1 gene were genotyped by polymerase chain reaction and DNA sequencing.</p><p><b>RESULTS</b>Frequencies of the rs402007 GC+CC genotype and the C allele were significantly different between the two groups (68.84% vs. 60.67%, χ2=9.012, P=0.003, OR=1.432; 45.24% vs. 38.54%, χ2=11.208, P=0.001, OR=1.318). Binary logistic regression has confirmed that the above difference was significant (P=0.001, OR=1.521, 95%CI: 1.183-1.955). The frequencies of TC+CC and GC+CC genotypes were similar between the two groups, and so was it with the C allele. The two SNPs had been in complete linkage disequilibrium (D'=1.0, r2=1.0).</p><p><b>CONCLUSION</b>The rs416905 and rs402007 polymorphisms of the ADAMTS-1 gene may be associated with ischemic stroke caused by LAA. The C allele of the rs402007 locus may be a susceptibility factor for this subtype of stroke.</p>

Clinical Analysis of 70 Adult Patients with Paroxysmal Nocturnal Hemoglobinuria / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics of Chinese patients with paroxysmal nocturnal hemoglobinuria (PNH).</p><p><b>METHODS</b>The clinical data of 70 adult PNH cases in our hospital from January 2000 to December 2009 were analyzed retrospectively, and the clinical manifestation, laboratory examination, treatment, complications and prognostic factors influencing survival rate were assessed.</p><p><b>RESULTS</b>The nosopoietic median age of 70 cases(41 male cases and 29 female cases) was 37 (18-73) years old. The clinical manifestation included fatigue (87.1%), hemogolobinuria (44.3%), infection (22.9%), bleeding (37.1%), and abdominal pain (2.9%). FHb (free hemoglobin) in 56 patients (80%) was <50 mg/L. Hp (haptoglobin) in 54 patients (77.1%) was <0.5 g/L, and LDH in 49 patients (70.0%) was <220 U/L. The overall 10 year-survival rate after diagnosis was 72.2% estimated by Kaplan-Meier. The complications in this study were as follow: recurrent abdominal pain crisis (2.9%), infections (30.0%), thrombotic events (8.6%), evolution to MDS/AML (5.7%), calculus (11.4%) and death (17.1%). Both univariate and multivariate analyses identified risk factors affecting survival, including development of thrombotic events, progression to myelodysplastic syndrome or acute myelogenous leukemia (MDS/AML) and recurrent infections.</p><p><b>CONCLUSION</b>This larger number of cases for the first time allowed us to carry out a detailed analysis of prognostic factors for this rare disease. Evaluation of PNH prognostic factors may provide a basis to assess the current and future therapies of this disease.</p>

Association of MMP-14 gene polymorphism with cerebral infarction - a case-control study / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between cerebral infarction (CI) and single nucleotide polymorphism (SNP) in the exon of membrane-type 1 matrix metalloproteinase (MMP-14) gene in Chinese Han population.</p><p><b>METHODS</b>Five hundred seventy four patients with CI and 463 healthy individuals were recruited. Serum MMP-14 level was measured with enzyme-linked immunosorbent assay (ELISA). rs1042704 and rs2236307 polymorphisms of the MMP-14 gene were genotyped with a TaqMan assay. Multivariate logistic regression was carried out to analyze the risk factors of CI.</p><p><b>RESULTS</b>A significant lower risk of CI was found in individuals with MMP-14 rs2236307 TC and CC genotypes (vs. TT genotype: P<0.05). The frequencies of MMP-14 rs2236307 C allele were significantly different between the CI group (37.46%) and the control group (43.95%) (P=0.003). Serum level of MMP-14 was higher in the CI group (P=0.003) and was also higher in the group with MMP-14 rs2236307 TT genotype compared with those with CT and CC genotypes (P=0.000; P=0.009). Logistic regression analysis indicated that the MMP-14 rs2236307 CT+CC genotypes was a protective factor, and that history of hypertension, smoking status, triglycerides, diastolic blood pressure and systolic blood pressure were the independent risk factors of CI (AOR:2.027, 1.302, 1.296, 1.434, 2.087; P<0.05).</p><p><b>CONCLUSION</b>The rs2236307 polymorphism of MMP-14 gene is associated with CI, for which the C allele maybe a protective factor. No association of MMP-14 gene rs1042704 polymorphism with CI has been found.</p>

Association between -1296T/C and -915A/G polymorphisms of matrix metalloproteinase inhibitor-3 gene and atherosclerotic cerebral infarction in an ethnic Han Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between -1296T/C and -915A/G polymorphisms in the promoter region of matrix metalloproteinase inhibitor-3 gene (TIMP-3) and atherosclerotic cerebral infarction in an ethnic Han Chinese population.</p><p><b>METHODS</b>Peripheral blood samples were collected from 485 patients with atherosclerotic cerebral infarction and 525 healthy controls. Serum levels of TIMP-3 were measured with an enzyme-linked immunosorbent assay (ELISA). The polymorphisms of the TIMP-3 gene were analyzed with DNA sequencing.</p><p><b>RESULTS</b>There were significant differences in genotype and allele frequencies in -1296T/C and -915A/G between the patients and healthy controls (chi-square: 5.227 and 5.869; P: 0.022 and 0.015, respectively). Besides, there was a strong linkage disequilibrium between -1296T/C and -915A/G (D'=1.0, r(2)=0.991). The serum levels of TIMP-3 in patients were significantly higher than the control group [(248.90 ± 97.10) pg/mL vs. (200.17 ± 79.70) pg/mL, t=2.098, P=0.039].</p><p><b>CONCLUSION</b>The -1296T/C and -915A/G polymorphisms of the TIMP-3 gene are associated with increased risk for atherosclerotic cerebral infarction in ethnic Han Chinese and may be used as molecular markers for the disease. There is also strong linkage disequilibrium between the two loci.</p>

Study on abnormal iron metabolism and iron overload in patients with aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the abnormalities of iron metabolism, the prevalence and risk factors of iron overload and clinical characteristics of patients with aplastic anemia (AA).</p><p><b>METHODS</b>A cross-sectional study was conducted on 520 newly diagnosed AA patients.</p><p><b>RESULTS</b>Iron overload was observed in 66(13%) of 520 AA patients,in which a higher prevalence of iron overload was seen not only in patients with infections(19/86, 22%)than those without infections (47/434, 11%, P<0.01), but also in patients with hepatitis associated AA(HAAA) (6/22, 19%) than the idiopathic cases (60/488, 12%, P>0.05). Excluded the patients with infections and/or HAAA, 43 of 405(11%)cases had iron overload, including 14 of 248(6%) cases without history of blood transfusion and 29 of 157 patients (18%, P<0.01) with transfusion. In univariate analysis, higher levels of serum ferritin (SF), serum iron (SI) and transferrin saturation (TS) were mainly observed in adult male patients with severe AA (SAA) and significantly upward with increasing blood transfusion (P<0.01). No differences of soluble transferrin receptor (sTfR) were observed between adults and children, males and females, hepatitis and idiopathic AA. However, patients with infections had significantly lower level of sTfR (0.50 mg/L) than cases without infections (0.79 mg/L, P<0.01). The level of sTfR in SAA patients (0.70 mg/L) was only half of that in non-SAA (NSAA) (1.36 mg/L, P<0.01). Patients with increasing blood transfusion had significantly downward levels of sTfR (P<0.01). In multivariate analysis, more than 8 U blood transfusion (OR=10.52, P<0.01), adults (OR=3.48, P<0.01), males (OR=3.32, P<0.01) and infections (OR=2.09, P<0.01) were independent risk factors.</p><p><b>CONCLUSION</b>AA patients had higher iron burden and were high-risk populations occurring iron overload. The iron overload occurred in 18% of patients with blood transfusion and in 6% of patients without transfusion.</p>