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To investigate the expression of programmed death receptor-1 (PD-1) and inducible costimulator (ICOS) on the surface of CD8A total of 28 ITP patients treated in Tianjin Medical University General Hospital from September to December 2020 were selected, including 13 patients with newly diagnosed ITP, 15 patients with chronic ITP, and 22 healthy volunteers were recruited as control group. Flow cytometry was used to detect the expression levels of PD-1 and ICOS, and evaluate their correlation with clinical indicators.The percentage of CD8In ITP patients, the unbalanced expression of PD-1 and ICOS may interfere with the immune homeostasis of the body, which can be used as a therapeutic target for ITP patients.PD-1、ICOS在ITP患者中的表达及意义.检测原发免疫性血小板减少症（ITP）患者外周血CD8选取2020年9月至12月于天津医科大学总医院血液科就诊的ITP患者28例，包括 13例新诊断患者，15例慢性患者，同时选取健康志愿者22名作为对照组。采用流式细胞术检测外周血CD8慢性组ITP患者CD8在ITP患者中，PD-1和ICOS的不平衡表达可能干扰机体的免疫稳态，可以作为ITP患者的治疗靶标。.

Autoimmune diseases are primary immune diseases in which autoreactive antibodies or sensitized lymphocytes destroy and damage tissue and cellular components, resulting in tissue damage and organ dysfunction. Helper T cells may be involved in the pathogenesis of autoimmune diseases under certain conditions. This review summarizes recent research on the role of helper T cells in autoimmune diseases from two aspects, helper T cell-mediated production of autoantibodies by B cells and helper T cell-induced activation of abnormal lymphocytes, and provides ideas for the treatment of autoimmune diseases. The abnormal expression of helper T cells promotes the differentiation of B cells that produce autoantibodies, which leads to the development of different diseases. Among them, abnormal expression of Th2 cells and T follicular helper cells is more likely to cause antibody-mediated autoimmune diseases. In addition, abnormal activation of helper T cells also mediates autoimmune diseases through the production of abnormal cytokines and chemokines. Helper T cells play an essential role in the pathogenesis of autoimmune diseases, and a full understanding of their role in autoimmune diseases is helpful for providing ideas for the treatment of autoimmune diseases.

To investigate the inhibitory effect of ascorbic acid single or combination of decitabine on tumor cells of myelodysplastic syndrome (MDS) and explore its related mechanism.The human MDS cell lines SKM-1 and MUTZ-1 were treated with different concentrations of ascorbic acid, and the cell proliferation activity was detected by the CCK-8 assay. The reactive oxygen species (ROS) level, labile iron pool (LIP), cell cycle, and apoptosis of SKM-1 and MUTZ-1 cells were detected by flow cytometry. The control group, ascorbic acid monotherapy group, decitabine monotherapy group, and combination group of ascorbic acid and decitabine were set up, the cell proliferation activity and apoptosis were detected in each group.High-dose ascorbic acid could reduce the cell proliferation activity of SKM-1 (R=0.886, p=0.000) and MUTZ-1 (R=0.880, p=0.000). With the increase of ascorbic acid concentration, the ROS level in SKM-1 and MUTZ-1 cells increased (r=0.816, r=0.942), the proportion of cells stagnation in GHigh-dose ascorbic acid shows a cytotoxic effect on MDS tumor cells, inhibiting cell proliferation and increasing apoptosis. Ascorbic acid combined decitabine have a synergistic effect of anti-MDS tumor cells.抗坏血酸对骨髓增生异常综合征细胞的抑制作用及相关机制.观察抗坏血酸单药或与地西他滨联合用药对抑制骨髓增生异常综合征（MDS）肿瘤细胞的抑制作用，并探讨其相关机制。.用不同浓度抗坏血酸干预人MDS细胞系SKM-1和MUTZ-1，CCK-8法检测细胞增殖活性，流式细胞术检测细胞内活性氧和不稳定铁池水平、细胞周期及凋亡程度。分别设立对照组、抗坏血酸组、地西他滨单药组及二者联合用药组，检测细胞增殖活性和凋亡程度。.高剂量抗坏血酸可降低SKM-1和MUTZ-1细胞的增殖活力，且这种抑制增殖作用呈剂量依赖性（复相关系数R=0.886，p=0.000和复相关系数R=0.880，p=0.000）；随着抗坏血酸浓度升高，SKM-1和MUTZ-1细胞内活性氧水平增高（r=0.816，r=0.942），停滞在G高剂量抗坏血酸对MDS肿瘤细胞存在细胞毒作用，抑制细胞增殖并增加其凋亡；抗坏血酸与地西他滨有协同抗MDS肿瘤细胞的作用。.

Congenital pure red cell aplasia, also known as Diamond-Blackfan anemia (DBA), is a hereditary disease characterized by pure red cell aplasia and congenital malformation. Its main clinical features are anemia, dysplasia, and tumor susceptibility. Ribosomal protein (RP) gene mutation is the main pathogenesis of DBA. The most common type of gene mutation is RPS19 gene mutation. Heterozygous mutations in as many as 19 RP genes and other non-RP genes mutations have been identified in DBA. This review summarized briedfly the latest research advances in the pathogenesis of DBA.先天性纯红细胞再生障碍性贫血发病机制的研究进展.先天性纯红细胞再生障碍又名Diamond-Blackfan贫血（DBA），是以单纯红系再生障碍和先天性畸形为特征的遗传性疾病，以贫血、身体发育异常和肿瘤易感性为主要临床特征。核糖体蛋白质（RP）基因突变是DBA的主要发病机制，最常见的基因突变类型为RPS19基因突变，目前已在DBA患者中发现了19个RP基因的杂合突变及其他非RP基因的突变。本文对基因突变引起DBA的最新研究进展进行综述。.

Aim Splicing factor proline and glutamine rich (SFPQ) is an RNA-DNA binding protein that is dysregulated in Alzheimer's disease and frontotemporal dementia. Dysregulation of SFPQ, specifically increased intron retention and nuclear depletion, has been linked to several genetic subtypes of amyotrophic lateral sclerosis (ALS), suggesting that SFPQ pathology may be a common feature of this heterogeneous disease. Our study aimed to investigate this hypothesis by providing the first comprehensive assessment of SFPQ pathology in large ALS case-control cohorts. Methods We examined SFPQ at the RNA, protein and DNA levels. SFPQ RNA expression and intron retention were examined using RNA-sequencing and quantitative PCR. SFPQ protein expression was assessed by immunoblotting and immunofluorescent staining. At the DNA level, SFPQ was examined for genetic variation novel to ALS patients. Results At the RNA level, retention of SFPQ intron nine was significantly increased in ALS patients' motor cortex. In addition, SFPQ RNA expression was significantly reduced in the central nervous system, but not blood, of patients. At the protein level, neither nuclear depletion nor reduced expression of SFPQ was found to be a consistent feature of spinal motor neurons. However, SFPQ-positive ubiquitinated protein aggregates were observed in patients' spinal motor neurons. At the DNA level, our genetic screen identified two novel and two rare SFPQ sequence variants not previously reported in the literature. Conclusions Our findings confirm dysregulation of SFPQ as a pathological feature of the central nervous system of ALS patients and indicate that investigation of the functional consequences of this pathology will provide insight into ALS biology.

To investigate the expression of IL-9 and IL-6 in patients with BCR-ABL- bone marrow proli- ferative tumor (MPN), and to explore its role in the occurrence and development of MPN.A total of 71 newly diagnosis MPN patients treated in Tianjin Medical University General Hospital from 2018 to 2019 were selected, including 32 patients with polycythemia vera (PV) and 22 patients with primary thrombocytosis (ET), and 17 patients with primary myelofibrosis (PMF). Then 58 patients who retestine after treatment were selected as therapy group，and 20 healthy volunteers were recruited as control group. ELISA was used to detect the expression level of IL-6 and IL-9 in bone marrow supernatant, and the relative expression level of IL-6 and IL-9 mRNA in BMMNC was detected by real-time PCR. The proportion of Th9 cells in peripheral blood were detected by flow cytometry (FCM). The expression level of IL-6 mRNA and IL-9 mRNA of BMMNC and clinical indicators were analyzed, and the correlation between JAK2 gene mutation load and IL-9 level was further analyzed.The level of IL-6 in bone marrow supernatant and the expression of IL-6 mRNA in BMMNC were higher in the newly diagnosed group as compared with those in the treated group and the control group (P0.001). The expression level of IL-9 in bone marrow supernatant and the expression of IL-9 mRNA in BMMNC were lower in the newly diagnosed group as compared with those in the treated group and the control group (P0.05). The proportion of Th9 cells in peripheral blood was lower in the newly diagnosed group as compared with that in the treated group and the control group (P0.001). The level of IL-6 in bone marrow supernatant and the expression of IL-6 mRNA in BMMNC in JAK2The increased expression of IL-6 in MPN and hyperfunction may promote the progression of BCR-ABL- MPN disease. The expression of IL-9 in MPN decreases, and it negatively correlates with the mutation load of JAK2 gene, which may be related with the decrease of tumor environmental antitumor immune effect.IL-9和IL-6在BCR-ABL- MPN患者中的表达及其意义.检测BCR-ABL- 骨髓增殖性肿瘤（MPN）患者的IL-9和IL-6的表达，探讨其在MPN疾病中的意义.选取2018年至2019年间于天津医科大学总医院血液科就诊的MPN初治患者71例（初诊组），包括32例真性红细胞增多症（PV），22例原发性血小板增多症（ET）和17例原发性骨髓纤维化（PMF），治疗后复查患者58例作为治疗组，同时选取健康志愿者20名作为对照组。采用ELISA法检测骨髓上清液中IL-6和IL-9的水平，采用RT-PCR技术检测骨髓单个核细胞IL-6和IL-9 mRNA相对表达水平，应用流式细胞术(FCM)检测外周血Th9细胞的比例，将骨髓单个核细胞IL-6 mRNA和IL-9 mRNA表达水平与临床指标进行相关性分析，并进一步追踪分析JAK2基因突变负荷与IL-9水平之间的关系.初诊组骨髓上清液中IL-6水平及骨髓单个核细胞中IL-6 mRNA表达水平均高于治疗组和对照组（P0.001），初诊组骨髓上清液中IL-9水平及骨髓单个核细胞中IL-9 mRNA表达水平均低于治疗组和对照组（P0.05）；初诊组外周血Th9细胞比例低于治疗组和对照组（P0.001）；JAK2IL-6在MPN中表达水平增加，功能亢进，可能促进BCR-ABL- MPN疾病进展；IL-9在MPN中表达水平减低，且与JAK2基因突变负荷呈负相关关系，这可能与肿瘤微环境抗肿瘤免疫作用减低有关.

Summary Background Intravenous arsenic trioxide plus all-trans retinoic acid (ATRA) without chemotherapy is the standard of care for non-high-risk acute promyelocytic leukaemia (white blood cell count ≤10 × 10 9 per L), resulting in cure in more than 95% of cases. However, a pilot study of treatment with oral arsenic realgar-Indigo naturalis formula (RIF) plus ATRA without chemotherapy, which has a more convenient route of administration than the standard intravenous regimen, showed high efficacy. In this study, we compare an oral RIF plus ATRA treatment regimen with the standard intravenous arsenic trioxide plus ATRA treatment regimen in patients with non-high-risk acute promyelocytic leukaemia. Methods We did a multicentre, non-inferiority, open-label, randomised, controlled phase 3 trial at 14 centres in China. Patients aged 18–70 years with newly diagnosed (within 7 days) non-high-risk acute promyelocytic leukaemia, and a WHO performance status of 2 or less were eligible. Patients were randomly assigned (2:1) to receive treatment with RIF-ATRA or arsenic trioxide-ATRA as the induction and consolidation therapy. Randomisation was done centrally with permuted blocks and stratification according to trial centre and was implemented through an interactive web response system. RIF (60 mg/kg bodyweight daily in an oral divided dose) or arsenic trioxide (0·15 mg/kg daily in an intravenous dose) and ATRA (25 mg/m 2 daily in an oral divided dose) were used until complete remission was achieved. The home-based consolidation therapy was RIF (60 mg/kg daily in an oral divided dose) or intravenous arsenic trioxide (0·15 mg/kg daily in an intravenous dose) in a 4-week on 4-week off regimen for four cycles and ATRA (25 mg/m 2 daily in an oral divided dose) in a 2-week on 2-week off regimen for seven cycles. Patients and treating physicians were not masked to treatment allocation. The primary outcome was event-free survival at 2 years. A non-inferiority margin of −10% was used to assess non-inferiority. Primary analyses were done in a modified intention-to-treat population of all patients who received at least one dose of their assigned treatment and the per-protocol population. This study was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-13004054), and the trial is complete. Findings Between Feb 13, 2014, and Aug 31, 2015, 109 patients were enrolled and assigned to RIF-ATRA (n=72) or arsenic trioxide-ATRA (n=37). Three patients in the RIF-ATRA and one in the arsenic trioxide-ATRA did not receive their assigned treatment. After a median follow-up of 32 months (IQR 27–36), 67 (97%) of 69 patients in the RIF-ATRA group and 34 (94%) of 36 in the arsenic trioxide-ATRA group had achieved 2-year event-free survival in the modified intention-to-treat population. The percentage difference in event-free survival was 2·7% (95% CI, −5·8 to 11·1). The lower limit of the 95% CI for the difference in event-free survival was greater than the −10% non-inferiority margin, confirming non-inferiority (p=0·0017). Non-inferiority was also confirmed in the per-protocol population. During induction therapy, grade 3–4 hepatic toxic effects (ie, increased liver aspartate aminotransferase or alanine transaminase concentrations) were reported in six (9%) of 69 patients in the RIF-ATRA group versus five (14%) of 36 patients in the arsenic trioxide-ATRA group; grade 3–4 infection was reported in 15 (23%) of 64 versus 15 (42%) of 36 patients. Two patients in the arsenic trioxide-ATRA group died during induction therapy (one from haemorrhage and one from thrombocytopenia). Interpretation Oral RIF plus ATRA is not inferior to intravenous arsenic trioxide plus ATRA for the treatment of patients with non-high-risk acute promyelocytic leukaemia. This study suggests that a completely oral, chemotherapy-free model might be an alternative to the standard intravenous treatment for patients with non-high-risk acute promyelocytic leukaemia. Funding Foundation for innovative research group of the National Natural Science Foundation of China, the Beijing Municipal Science and Technology Commission, the National Key R&D Program of China, and the National Natural Science Foundation of China.

This study aimed to investigate the role of miR‐138 in human coronary artery endothelial cell (HCAEC) injury and inflammatory response and the involvement of the PI3K/Akt/eNOS signalling pathway. Oxidized low‐density lipoprotein (OX‐LDL)‐induced HCAEC injury models were established and assigned to blank, miR‐138 mimic, miR‐138 inhibitor, LY294002 (an inhibitor of the PI3K/Akt/eNOS pathway), miR‐138 inhibitor + LY294002 and negative control (NC) groups. qRT‐PCR and Western blotting were performed to detect the miR‐138, PI3K, Akt and eNOS levels and the protein expressions of PI3K, Akt, eNOS, p‐Akt, p‐eNOS, Bcl‐2, Bax and caspase‐3. ELISAs were employed to measure the expressions of TNF‐α, IL‐4, IL‐6, IL‐8, IL‐10 and nitric oxide (NO) and the activities of lactate dehydrogenase (LDH) and eNOS. MTT and flow cytometry were performed to assess the proliferation and apoptosis of HCAECs. Compared to the blank group, PI3K, Akt and eNOS were down‐regulated in the miR‐138 mimic and LY294002 groups but were up‐regulated in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups showed decreased concentrations of TNF‐α, IL‐6, IL‐8 and NO and reduced activities of LDH and eNOS, while opposite trends were observed in the miR‐138 inhibitor group. The concentrations of IL‐4 and IL‐10 increased in the miR‐138 mimic and LY294002 groups but decreased in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups had significantly decreased cell proliferation and increased cell apoptosis compared to the blank group. These findings indicate that up‐regulation of miR‐138 alleviates HCAEC injury and inflammatory response by inhibiting the PI3K/Akt/eNOS signalling pathway.

To investigate the phenotype and molecular mechanism of DCA on MDS cell model, and to study the response of chemotherapeutic medicines to MDS cells through multiple dimensions, such as cell proliferation, invasion, migration and apoptosis, thus revealing the molecular mechanism of DCA treatment of MDS and its relationship with SHP-1 gene methylation.MTT assay was used to determine the survival rate of MDS cells after treated by different concentrations of DCA. The effect of DCA on the invasion and migration of MDS cells was detected by Transwell assay method. Apoplexin V-FITCPI was used to detect apoptosis, the MDS treatment on the mechanism of DCA was investigated by Western blot and Real-time PCR experiment.According to the experiment, it was found that tumor proliferation could be inhibited when MDS skm-1 cells was treated by DCA, and the absorbance was lower and the inhibitory effect was more obvious in the 2.0, 5.0 μmol/L DCA group than in the 0.5 μmol/L DCA group and the negative control group. Compared with the control group, the number of MDS skm-1 cells crossing through the transwell upper chamber was significantly decreased after DCA application. After treated with 0.5, 2.0 and 5.0 μmol/L DCA, the apoptosis rate of MDS cells was 4.54%, 9.31% and 16.58% respectively, while the apoptosis rate of the control group was 3.20%, which shows the apoptosis rate increased significantly with the concentration of DCA. After treatment of MDS cell lines with different concentration of DCA, the methylation status of SHP-1 gene was decreased with the increase of drug concentration, the expression of SHP-1 was increased, the expression of STAT3 was decreased and the level of phosphorylation was decreased.By analyzing the phenotypic response of DCA treatment on MDS cells, it was found that interfere with MDS can be performed by inhibiting proliferation, metastasis, and inducing apoptosis in a dose-dependent way. It revealed that the molecular mechanism by DCA treatment can improve the methylation of SHP-1 gene and inhibit the expression of p-STAT3.地西他滨抑制SHP-1基因甲基化对MDS细胞株Skm-1增殖及凋亡影响.探讨DCA作用于MDS细胞模型后的表型及分子机制，通过细胞增殖、侵袭迁移及细胞凋亡等多重维度研究化疗药物作用于MDS细胞后的反应，揭示DCA治疗MDS的分子机理及其与SHP-1基因甲基化的关系.采用MTT法测定不同浓度DCA处理后的MDS细胞存活率，采用Transwell实验检测DCA对MDS细胞侵袭和迁移能力的影响，应用AnnexinV-FITC/PI法检测细胞凋亡情况，Western blot免疫蛋白印迹和real time PCR实验研究DCA治疗MDS的作用机制.实验发现，DCA作用于MDS skm-1细胞能抑制肿瘤增殖，且2.0及5.0 μmol/L DCA组相对0.5 μmol/L DCA组与阴性对照组相比吸光度降低、抑制效应更加明显。与对照组比较，应用DCA后MDS skm-1细胞穿过Transwell上室底膜的数量显著下降。在0.5、2.0及5.0 μmol/L DCA处理后，MDS细胞凋亡率依次为4.54%、9.31%及16.58%，对照组细胞凋亡率为3.20%。这表明，细胞凋亡率随DCA浓度显著增加。在经不同浓度DCA处理的MDS细胞系中，SHP-1基因甲基化状态随着药物浓度升高而减弱，SHP-1表达量升高，STAT3表达量减少，而STAT3磷酸化水平则受到明显抑制.通过对DCA作用于MDS细胞后的表型反应分析，发现其主要通过抑制增殖和转移并诱导凋亡来干预MDS，并具有药物剂量依赖性，这揭示了DCA治疗能够改善SHP-1基因的甲基化进而抑制p-STAT3表达的分子机制.

To evaluate the use of dual-energy CT imaging of the lung perfused blood volume (PBV) for the detection of pulmonary fat embolism (PFE). Dual-energy CT was performed in 24 rabbits before and 1 hour, 1 day, 4 days and 7 days after artificial induction of PFE via the right ear vein. CT pulmonary angiography (CTPA) and lung PBV images were evaluated by two radiologists, who recorded the presence, number, and location of PFE on a per-lobe basis. Sensitivity, specificity, and accuracy of CTPA and lung PBV for detecting PFE were calculated using histopathological evaluation as the reference standard. A total of 144 lung lobes in 24 rabbits were evaluated and 70 fat emboli were detected on histopathological analysis. The overall sensitivity, specificity and accuracy were 25.4 %, 98.6 %, and 62.5 % for CTPA, and 82.6 %, 76.0 %, and 79.2 % for lung PBV. Higher sensitivity (p

Summary Aims We evaluate safety and efficacy of autologous bone marrow-derived mesenchymal stem cells (MSCs) as a potential treatment for neuromyelitis optica spectrum disorder (NMOSD). Methods Fifteen patients with NMOSD were recruited. All patients received a single intravenous infusion of 1.0 × 108 autologous MSC within 3–4 generations derived from bone marrow. The primary endpoints of the study were efficacy as reflected by reduction in annualized relapse rates (ARRs) and inflammatory lesions observed by MRI. Results At 12 months after MSC infusion, the mean ARR was reduced (1.1 vs. 0.3, P = 0.002), and the T2 or gadolinium-enhancing T1 lesions decreased in the optic nerve and spinal cord. Disability in these patients was reduced (EDSS, 4.3 vs. 4.9, P = 0.021; visual acuity, 0.4 vs. 0.5, P = 0.007). The patients had an increase in retinal nerve fiber layer thickness, optic nerve diameters and upper cervical cord area. We did not identify any serious MSC-related adverse events. At 24 months of MSC infusion, of 15 patients, 13 patients (87%) remained relapse-free, the mean ARR decreased to 0.1; the disability of 6 patients (40%) was improved, and the mean EDSS decreased to 4.0. Conclusions This pilot trial demonstrates that MSC infusion is safe, reduces the relapse frequency, and mitigates neurological disability with neural structures in the optic nerve and spinal cord recover in patients with NMOSD. The beneficial effect of MSC infusion on NMOSD was maintained, at least to some degree, throughout a 2-year observational period.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of upper and lower motor neurons. ALS exhibits high phenotypic variability including age and site of onset, and disease duration. To uncover epigenetic and transcriptomic factors that may modify an ALS phenotype, we used a cohort of Australian monozygotic twins (n = 3 pairs) and triplets (n = 1 set) that are discordant for ALS and represent sporadic ALS and the two most common types of familial ALS, linked to C9orf72 and SOD1. Illumina Infinium HumanMethylation450K BeadChip, EpiTYPER and RNA-Seq analyses in these ALS-discordant twins/triplets and control twins (n = 2 pairs), implicated genes with consistent longitudinal differential DNA methylation and/or gene expression. Two identified genes, RAD9B and C8orf46, showed significant differential methylation in an extended cohort of >1000 ALS cases and controls. Combined longitudinal methylation-transcription analysis within a single twin set implicated CCNF, DPP6, RAMP3, and CCS, which have been previously associated with ALS. Longitudinal transcriptome data showed an 8-fold enrichment of immune function genes and under-representation of transcription and protein modification genes in ALS. Examination of these changes in a large Australian sporadic ALS cohort suggest a broader role in ALS. Furthermore, we observe that increased methylation age is a signature of ALS in older patients.

To investigate the infection status of intestinal nematodes and their risk factors in rural residents of Jiangxia District, Wuhan City, so as to provide the reference for the establishment of targeted prevention and control measures.According to the requirements of cross-sectional study of the national human key parasitic diseases, the residents in Shanpo Sub-district, Jiangxia District were randomly selected as the objects for the investigation of the infection status ofTotally 236 residents received the stool tests, and only the hookworm eggs were found, with an infection rate of 7.63% (18 cases). The survey of intestinal parasitic infection status and their risk factors in 600 residents found 397 cases of suspected roundworm infection, 355 cases of suspected hookworm larvae dermatitis, 295 cases of suspected hookworm infection, and 145 cases of suspected whipworm infection, respectively. The Logistic regression analysis found that the risk factors of suspected roundworm infection included not always washing hands after toilet, using manure and fertilizer, and not often wearing shoes when doing farm work; the protective factors included knowing how roundworm infection was gained, and not using fresh dung for fertilization. The risk factors of suspected hookworm infection included using well water and pond water as the source of drinking water, eating food off the ground, using manure and fertilizers, and not washing when there was only one cutting board, and its protective factors included using tap water and well water as drinking water source, knowing how the roundworm infection was gained, and sometimes or not suing fresh feces for fertilization. The risk factors for suspected whipworm infection included eating food off the ground.The intestinal parasite prevalence in the residents of the Shanpo Sub-district, Jiangxia District in Wuhan City is relatively high, and some risk factors associated with their infection indeed exist. Therefore, the regional government and health department should strengthen the health education to improve the residents' knowledge about parasitic diseases and selfprotection awareness. At the same time, the residents should take physical examination regularly and take necessary deworming treatment to effectively control the prevalence and spread of intestinal parasitic diseases.[

Rationale: Most patients with hepatocellular carcinoma (HCC) have lost the chance of radical treatment at the time of their visit, and the prognosis of metastatic HCC is even worse. Sorafenib is currently regarded as a first-line systemic therapy in patients with advanced and metastatic HCC. Apatinib is a new inhibitor of vascular endothelial growth factor receptor 2 tyrosine kinase, which has been reported to be effective in some solid tumors. We herein report a case of apatinib in the treatment of the patient with metastatic HCC who was resistant to sorafenib. Patient concerns: A 41-year-old Chinese man with a history of chronic hepatitis B had undergone an emergency partial hepatectomy for tumor ruptured. Despite the treatment with transcatheter arterial chemoembolization and sorafenib, the progression of tumor failed to control. Diagnoses: Although the patient had been treated with sorafenib (400 mg, twice daily) for 10 months, computed tomography documented radiological progression. Interventions: Due to disease progression, failure of sorafenib and positive expression of vascular endothelial growth factor (VEGF), the drug regimen was changed to apatinib 250 mg once daily. Due to some degree of resistance, the dose was increased up to 425 mg once daily. Outcomes: The patient had a disease-free progression of 7 months at 250 mg apatinib. The dosage was adjusted to 425 mg due to drug resistance and the side effects were tolerable. The patient has survived a total of 19 months under apatinib. Lessons: Apatinib may be a substitute for the HCC patients with sorafenib resistance in the future, especially for those with high expression of VEGF.

To analyze the number of myeloid-derived suppressor cells(MDSC) and the level of prostaglandin E2(PGE2) in the bone marrow of adult ITP patients, and to explore their possible mechanisms involved in the pathogenesis of this disease.Twenty-five patients of newly diagnosed ITP, 25 patients of complete remission group and 15 patients of control group were selected. The number of MDSC in the bone marrow between 3 groups was detect by flow cytometry (FCM). The serum level of prostaglandin E2 (PGE2) in 3 groups was determined by enzyme linked immunosorbent assay (ELISA). The relative expression of IFN-γ mRNA in bone marrow mononuclear cells was measured by real time fluorescence quantitative polymerase chain reaction (RT-qPCR) in each groups.The number of MDSC in the complete remission group was significantly higher than that in the control group (P0.05); the number of MDSC in the newly diagnosed group was higher than that in the control group; the number of MDSC in the complete remission group was higher than that in the newly diagnosed group. The serum level of PGE2 in bone marrow of ITP patients in the newly diagnosed group was higher than that of the control group（P0.05）. The serum level of PGE2 in the bone marrow of ITP patients of the complete remission group was higher than that of the control group (P0.05）. The level of PGE2 in bone marrow serum of ITP patients of the newly diagnosed group was lower than that in the complete remission group(P0.05）. The relative expression level of IFN-gamma in bone marrow mononuclear cells of the ITP patients in newly diagnosed group was higher than that in the control group and the complete remission group（P0.001）. The relative quantification (RQ) of IFN-γ in bone marrow mononuclear cells was 2.60 between the newly diagnosed group and the complete remission group.When adult ITP disease is remitted, the number of MDSC rises and correlates with the therapeutic response and PGE2 level in the bone marrow.

Background The management of invasive fungal infection (IFI) is challenging in immunocompromised patients who do not fully satisfy the EORTC/MSG diagnostic criteria of proven or probable IFI. Our study assessed caspofungin efficacy in 582 Chinese patients with hematological malignancies exhibiting unclassified signs or symptoms of IFI. Material/Methods This retrospective study included caspofungin treatment outcomes of an unclassified group A (n=401) of patients without microbiological or biomarker results and group B (n=181) patients with positive microbiological or biomarker results. Factors that correlated with clinical outcomes were determined using univariate and multivariate analyses. Results Cough (41.8%), expectoration (29.6%), and chest tightness (14.6%) were the most common clinical features, and changes in CT images (88.1%) were more frequently detected than in X-ray images (19.6%) in all patients. Favorable response rates for caspofungin as first-line treatment were 58.2% for group A and 56.3% for group B. Eastern Cooperative Oncology Group (ECOG) score, cardiovascular disease, hemoptysis, and absolute neutrophil count (ANC) 1000/mm3 were significantly associated with favorable (complete or partial resolution) outcome. Conclusions Caspofungin was effective for treating unclassified IFIs of immunocompromised patients. Cardiovascular disease, ECOG score, cough, and/or hemoptysis, as well as ANC count, represent a potential index for estimating response of unclassified IFI patients to caspofungin treatments.

Background Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterised by the degeneration of motor neurons, which are responsible for voluntary movement. There remains limited understanding of disease aetiology, with median survival of ALS of three years and no effective treatment. Identifying genes that contribute to ALS susceptibility is an important step towards understanding aetiology. The vast majority of published human genetic studies, including for ALS, have used samples of European ancestry. The importance of trans-ethnic studies in human genetic studies is widely recognised, yet a dearth of studies of non-European ancestries remains. Here, we report analyses of novel whole-exome sequencing (WES) data from Chinese ALS and control individuals. Methods WES data were generated for 610 ALS cases and 460 controls drawn from Chinese populations. We assessed evidence for an excess of rare damaging mutations at the gene level and the gene set level, considering only singleton variants filtered to have allele frequency less than 5 × 10–5 in reference databases. To meta-analyse our results with a published study of European ancestry, we used a Cochran–Mantel–Haenszel test to compare gene-level variant counts in cases vs controls. Results No gene passed the genome-wide significance threshold with ALS in Chinese samples alone. Combining rare variant counts in Chinese with those from the largest WES study of European ancestry resulted in three genes surpassing genome-wide significance: TBK1 (p = 8.3 × 10–12), SOD1 (p = 8.9 × 10–9) and NEK1 (p = 1.1 × 10–9). In the Chinese data alone, SOD1 and NEK1 were nominally significantly associated with ALS (p = 0.04 and p = 7 × 10–3, respectively) and the case/control frequencies of rare coding variants in these genes were similar in Chinese and Europeans (SOD1: 1.5%/0.2% vs 0.9%/0.1%, NEK1 1.8%/0.4% vs 1.9%/0.8%). This was also true for TBK1 (1.2%/0.2% vs 1.4%/0.4%), but the association with ALS in Chinese was not significant (p = 0.14). Conclusions While SOD1 is already recognised as an ALS-associated gene in Chinese, we provide novel evidence for association of NEK1 with ALS in Chinese, reporting variants in these genes not previously found in Europeans. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0487-0) contains supplementary material, which is available to authorized users.

JAK2, MPL and CALR gene mutations play an important role in the onset of myeloproliferative disease(MPD). The latest researches show that the difference of ATP binding ability between the wild type JAK2 protein and mutated JAK2 protein can help us understand the pathogenesis of the MPD further, and the clinical manifestation is related to the mutation burden of the JAK2. In some ET and PMF patients, research find the expression of MPL mutation, which can affects the progress of the disease by collaborating with the JAK2 mutation. CALR mutation is a gene related with the MPD that has been found recently. The pathogenesis of the CALR is similar to that of the JAK2, while there are some features in clinical manifestation comparing with the other mutations.

To analyze the subtype and functional biomarker expression changes of natural kill cells(NK) in peripheral blood of patients with myelodysplastic syndrome(MDS) and normal people, so as to evaluate the relationships between these changes and hematopoietic functions and to explore the role of NK cells in the pathogenesis of MDS.The quantity of NK cells and the expression of biomarkers(NKp30,NKp46,NKG2A) on NK cells were detected by flow cytometry in 35 MDS patients from 2015 to 2016 in our hospital and 34 normal controls. The correlation between these changes and hematopoietic functions, including the percentages of neutrophil(ANC), hemoglobin in peripheral blood and the hematopoietic function in bone marrow(CD34The percentage and quantity of NK cells and CD56The decrease of NK number and function may cause the immune surveillance and lead to disease progression.

To evaluate the efficacy and safety of high-dose intravenous mecobalamin (HDIME) for the treatment of bortezomib-induced peripheral neuropathy(BIPN) in the patients with multiple myeloma (MM).A total of 65 newly diagonsed patients with multiple myeloma receiving bortezomib in Tianjin Medical University General Hospital were enrolled in this single-centre randomized clinical trial from July 2012 to May 2016. Out of 65 patients 38 in control group received bortezomib-based chemotherapy and 27 patients in HDIME group received the additional high-dose intravenous mecobalamin.The incidence of BIPN in HDIME group was lower than that in control group(29.63% vs 55.26%, χHDIME has a good efficacy for the prophylaxis BIPN and and without serious side effects.

To explore the single nucleotide polymorphism(SNP) of mitochondrial DNA (mtDNA) D-LOOP region in peripheral blood lymphocytes of immuno-related pancytopenia (IRP) patients and its correlation with immune parameters.The D-LOOP region in mitochondrial DNA of lymphocytes in peripheral blood mononuclear cells from 43 patients with untreated IRP was detected by polymerase chain reaction(PCR). The PCR products were sequenced by the pros and cons direct sequencing methods. The sequencing results were compared with the revised Cambridge reference sequence (rCRS) and the Polymorphic Sites of Human Mitochondrial Genome Database.Among total of 110 variant positions of D-LOOP region in 43 patients, 62 was SNP sites and 48 was mutation sites, of which 14 were the new mutation sites not yet registered in the database, 516 base variations were observed at 110 positions, the most common variations were base substitutions, among them T/C and A/G was 184/410 and 113/410 respectively. In the 110 variant positions, the high frequency variation sites were 73 and 263 for 43/43,311 for 32/43,310 and 16 224 for 27/43,16 519 for 25/43, 489 and 16 362 for 24/43. By the analysis of mitochondrial DNA D-LOOP polymorphism and related clinical immunology indicators of the patient's lymphocytes, it was found that D-loop in adult patients (age≥ 18 years old) significantly correlated with CD15 IgM, GLYCoAThe high frequency of polymorphism exists in mitochondrial DNA D-loop region of lymphocytes in IRPA patients, and was significantly correlates with the autoantibodies in bone marrow mononuclear cells in adult patients, which may be associated with the IRP occurrence.

Objective: To determine the effect of a lower dose of rituximab in depleting B lymphocytes, maintaining low B-cell counts, and relapse in patients with neuromyelitis optica (NMO) and NMO spectrum disorders. Methods: We treated 5 Chinese patients with deteriorating NMO and NMO spectrum disorders with a 100-mg IV infusion of rituximab once a week for 3 consecutive weeks, followed by additional infusion of the same dosage depending on circulating B-cell repopulation. Results: This reduced dosage of rituximab was sufficient to deplete B cells and maintain low B-cell counts. None of the treated patients experienced relapse, and all patients exhibited stabilized or improved neurologic function during the 1-year follow-up period. MRI revealed the absence of new lesions, no enhancement in spinal cord and brain, a significant shrinkage of spinal cord segments, and a reduction/disappearance of previous brain lesions. Conclusion: A lower dosage of rituximab may be sufficient in depleting B cells, maintaining low B-cell counts, and preventing disease progression in Chinese patients with NMO.

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10−8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10−3). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS., Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Nutrient sulfate has numerous roles in mammalian physiology and is essential for healthy fetal growth and development. The fetus has limited capacity to generate sulfate and relies on sulfate supplied from the maternal circulation via placental sulfate transporters. The placenta also has a high sulfate requirement for numerous molecular and cellular functions, including sulfate conjugation (sulfonation) to estrogen and thyroid hormone which leads to their inactivation. Accordingly, the ratio of sulfonated (inactive) to unconjugated (active) hormones modulates endocrine function in fetal, placental and maternal tissues. During pregnancy, there is a marked increase in the expression of genes involved in transport and generation of sulfate in the mouse placenta, in line with increasing fetal and placental demands for sulfate. The maternal circulation also provides a vital reservoir of sulfate for the placenta and fetus, with maternal circulating sulfate levels increasing by 2-fold from mid-gestation. However, despite evidence from animal studies showing the requirement of maternal sulfate supply for placental and fetal physiology, there are no routine clinical measurements of sulfate or consideration of dietary sulfate intake in pregnant women. This is also relevant to certain xenobiotics or pharmacological drugs which when taken by the mother use significant quantities of circulating sulfate for detoxification and clearance, and thereby have the potential to decrease sulfonation capacity in the placenta and fetus. This article will review the physiological adaptations of the placenta for maintaining sulfate homeostasis in the fetus and placenta, with a focus on pathophysiological outcomes in animal models of disturbed sulfate homeostasis.

To investigate the expression pattern of HOXA9 in myelodysplastic syndrome (MDS) patients and its relation with clinical characteristics and treatment response.The mRNA and protein expression levels of HOXA9 in bone marrow cells from 33 cases of MDS, 12 cases of AML, 20 cases of ITP and 18 normal controls were detected by real-time guautitative PCR(RT-PCR) and flow cytometry, respectively.The percentage of HOXA9(+)/CD34(+) and HOXA9(+)/CD34(+)CD38(-) in MDS patients were significantly higher than that in control group (P0.05), and the mRNA and protein expression of HOXA9 in MDS patients had a similar trend. The percentages of HOXA9(+)/CD34(+) and HOXA9(+)/CD34(+)CD38(-) before decitabine treatment were (50.64±27.59)% and (55.67±28.57)% respectively, which were both higher than those in control group (P0.05). After decitabine treatment, expression of HOXA9 significantly decreased (P0.05).HOXA9 is overexpressed in MDS patients and associated with several clinical characteristics. The detection of HOXA9 expression may have guide roles for diagnosis and treatment of MDS patients.

To explore the effect of costimulatory signaling molecules (CD80, CD86) expression on the quantity and function of B lymphocytes in peripheral blood (PB) of the patients with immune thrombocytopenia (ITP).A total of 55 ITP patients (30 cases were newly diagnosed and 25 cases were in remission), 25 healthy volunteers as controls were enrolled in this study. The levels of CD19(+)CD5(+), CD19(+)CD80(+), CD19(+)CD86(+), CD41a(+)IgG, CD41a(+)IgM and IgG, IgM in CD19(+)B cells were measured by flow cytometry (FCM). The correlation of CD19(+)B cells with clinical parameters of ITP patients was analyzed.The level of B1 (CD19(+)CD5(+)) of newly diagnosed ITP patients was significantly higher than that of remitted ITP patients and controls (P0.05). The level of CD19(+)CD80(+) of newly diagnosed ITP patients was significantly higher than that of remitted ITP patients and controls (P0.05). And the expression of IgG and IgM in CD19(+)B cells of newly diagnosed ITP patients was significantly higher than that of remitted ITP patients and controls (P0.05). The levels of IgG and IgM in remitted ITP patients after treatment were significantly lower than that before treatment (P0.05). The level differences of IgG and IgM before and after treatment in refractory ITP patients were not statistically significant (P0.05). The expression of CD19(+)CD80(+) in newly diagnosed ITP patients positively correlated with the level of Th1 and Th1/Th2 (r=0.502, r=0.471, P0.05). The expression of CD19(+)CD80(+) of newly diagnosed ITP patients positively correlated with the level of IgG and IgM in CD19(+)B cells (r=0.552, r=0.467, P0.05), and negatively correlated with PB platelet count (r= -0.424, P0.05). The levels of IgG and IgM in CD19(+)B cells of newly diagnosed ITP patients negati- vely correlated with PB platelet count (r=-0.658, r=-0.526, P0.05).The enhacement of costimulatory signaling pathway of CD19(+)B cells in ITP patients results in the abnormal activation of B lymphocytes, thereby mediates the dysfunction of immune system and involves in the pathogenesis of ITP.

MicroRNAs (miRNAs) are known to regulate the expression of genes that are important for brain development and function, but the roles of other classes of small non-coding RNAs (sncRNAs) are less well understood. Additionally, although miRNA expression studies have been conducted in post-mortem brain samples from schizophrenia (SCZ) patients, other classes of sncRNAs are yet to be investigated in SCZ. We profiled the expression of miRNAs, piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and small nuclear RNAs (snRNAs) in SCZ by applying small RNA sequencing (RNA-Seq) to sncRNA isolated from post-mortem anterior cingulate cortex (ACC) of SCZ-affected individuals (n=22) and matched controls (n=22). We identified about one-third of annotated miRNAs, one-quarter of snoRNAs and a small proportion of piRNAs and snRNAs. No sncRNAs were significantly differentially expressed between SCZ and controls, but there was evidence for an interaction between disease status and sex on the expression level of a number of miRNAs and snoRNAs. Many of these transcripts exhibited differential expression between male and female cases, and/or between female cases and controls, suggesting sex based dysregulation in ACC of SCZ. These findings require replication in an independent sample, but our study provides further insights into the potential involvement of sncRNAs in brain function and SCZ.

Myelodysplastic syndromes (MDS) are a group of bone marrow failure diseases. The bone marrow microenvironment consists of bone marrow stromal cells (BMSC), growth factors and cytokines. The BMSC supporting haemopoiesis include mesenchymal stem cells (MSC), osteoblasts, endothelial cells and macrophages, but the adipocytes play a role in the suppression of hematopoiesis. Recently more and more researches indicate that the abnormality of bone marrow microenvironment involves in the pathogenesis and progression of MDS. In this review the abnormality of MDS bone marrow microenvironment is summarized briefly.

We have developed a simple, colorimetric iron telluride (FeTe) nanorods (NRs) based system for the detection of mercury, mainly based on the cation exchange reaction between FeTe NRs and Hg(2+). FeTe NRs (length, 105 ± 21 nm) react with Hg(2+) to form HgTe NRs (length, 112 ± 26 nm) and consequently release Fe(2+) ions that catalyzes the oxidation between a peroxidase substrate 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) and H(2)O(2). The concentration of Fe(2+) and thereby Hg(2+) can be determined by measuring the absorbance of the ABTS oxidized product at 418 nm. This approach allows the detection of Hg(2+), with a limit of detection of 1.31 nM at a signal-to-noise ratio 3 and a linear range 5-100 nM (R(2)=0.99). The low-cost, simple, sensitive, and reproducible assay has been validated for the detection of Hg(2+) in a blood sample (SRM 955c), with the result being in good agreement with that provided by National Institute of Standards and Technology.

We prepared four differently shaped Te nanomaterials (NMs) as antibacterial reagents against Escherichia coli. By controlling the concentrations of hydrazine (N(2)H(4)) as reducing agent, NaCl, and temperature, we prepared Te nanowires, nanopencils, nanorices, and nanocubes. These four Te NMs resulted in a live/dead ratio of E. coli cells of less than 0.1, which is smaller than that of Ag nanoparticles. The order of antibacterial activity against E. coli is nanocubes ≈ nanorices > nanopencils ≈ nanowires. This is in good agreement with the concentration order of tellurite (TeO(3)(2-)) ions released from Te NMs in E. coli cells, revealing that TeO(3)(2-) ions account for the antibacterial activity of the four Te NMs. We found that spherical Te nanoparticles (32 nm in diameter) with TeO(3)(2-) ions were formed in the E. coli cells. Compared to Ag nanoparticles that are commonly used as antibacterial reagents, Te NMs have higher antibacterial activity and lower toxicity. Thus, Te NMs hold great practical potential as a new and efficient antibacterial agent.

Cube-DB is a database of pre-evaluated results for detection of functional divergence in human/vertebrate protein families. The analysis is organized around the nomenclature associated with the human proteins, but based on all currently available vertebrate genomes. Using full genomes enables us, through a mutual-best-hit strategy, to construct comparable taxonomical samples for all paralogues under consideration. Functional specialization is scored on the residue level according to two models of behavior after divergence: heterotachy and homotachy. In the first case, the positions on the protein sequence are scored highly if they are conserved in the reference group of orthologs, and overlap poorly with the residue type choice in the paralogs groups (such positions will also be termed functional determinants). The second model additionally requires conservation within each group of paralogs (functional discriminants). The scoring functions are phylogeny independent, but sensitive to the residue type similarity. The results are presented as a table of per-residue scores, and mapped onto related structure (when available) via browser-embedded visualization tool. They can also be downloaded as a spreadsheet table, and sessions for two additional molecular visualization tools. The database interface is available at http://epsf.bmad.bii.a-star.edu.sg/cube/db/html/home.html. Published version

Myelodysplastic Syndrome (MDS) is a group of clonal disorders of hematopoietic stem cells characterized by peripheral cytopenia, ineffective hematopoiesis, morphologically apparent multilineage dysplasia, and enhanced risk of evolution towards acute myeloid leukemia (AML). Most of the research findings have verified the abnormal proliferation and differentiation of hematopoietic cells in MDS. The defects of cellular and molecular factors such as transcription factors (GATA-1~GATA-3, FOG1, Pu.1), growth factors (Epo, G-CSF, GM-CSF) and anti-apoptosis genes ultimately affect the cell cycle regulation and mismatch repair of DNA, changes of hematopoietic microenvironment and immune response. These defects result in ineffective hematopoiesis and dysplasia.

CD22 is a type I transmembrane protein expressed on most mature B lymphocyte, and plays a significant role in signal transduction pathways. CD22 acts as a co-receptor of the B-cell receptor (BCR) that inhibits the BCR signaling by antigen-receptor interaction. The phosphorylation of CD22 can be triggered by cross-linking of CD22 with the BCR through antigen, then predominantly triggers the dephosphorylation and inactivation of downstream proteins and inhibit the BCR signaling. Autoimmune disease could be caused by the abnormal expression or dysfunction of CD22 which interrupts BCR signaling and then influences the quantity and function of B cells. The further study of the function and regulation of CD22 would help us understanding the pathogenesis of autoimmune disease and setting theoretical basis for its targeting treatment. In this article, the structure and expression of CD22, the ligands of CD22, the regulation of BCR and transmenbrane signaling, the effect of CD22 on B cells, and CD22 and autoimmune diseases were reviewed.

CD4+ CD25+ regulatory T cells (Treg) play a fundamental role in the establishment and maintenance of immune tolerance. In a some of experimental models, it was found that Tregs can quench autoimmune diseases, maintain allogeneic transplants, and prevent allergic diseases. A major obstacle to their clinical application is related to their definitive phenotype and very limited number of these cells in peripheral circulation, no more than 5%-10% of total CD4+ T cells. Recent progress of technologies for Treg sorting with multicolor flow cytometry and immuno-absorbing columns has overcome these obstacles, and opened the doors to the clinical application of Treg. This review highlight the characteristics of Treg, describe the current information of cell sorting and ex vivo expansion techniques, and outline the adoptive transfer experiments and clinical trials of immunotherapy that have been developed in recent years. It is foreseeable that Treg adoptive transfusion will be a promising immunosuppressive therapy.

IgG is the main immunoglobulin, brings the immunolgic effects in body. The human IgG can be divided into four kinds; IgG1, IgG2, IgG3, IgG4, respectively. The structures of IgG1, IgG2, IgG3, IgG4 are different, therefore, their functions are also different. The defects, increase or imbalance of the IgG subtypes in autoimmune diseases, infectious diseases, cancer and other diseases are indicators of the immune response. IgG1, IgG2, IgG3 and IgG4 also play a different important roles in the disease progress. The analysis of IgG subtypes is beneficial to study the etiology, pathogenesis and prognosis of above menthioned deseases. This review briefly summarizes the characteristics of IgG subtypes in thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, hemophilia, lymphoma and leukemia.

HOX gene encodes a group of homeodomain transcription factors which are highly conserved. The caudal-type homeobox (CDX) , ten-eleven translocation (TET) genes and polycomb group (PcG) , trithorax group (TrxG) proteins act as upstream regulators of HOX genes that manipulate the targeted gene expression through genetic and epigenetic mechanisms. The abnormal expression of HOX genes and their fusions contribute to myelodysplastic syndromes (MDS) pathogenesis. Aberrant DNA methylation and NUP98-HOX translocation serve as molecular mediators of dysfunction in MDS which can be used for the evaluation of biology and therapy. This article provides an overview of recent advances of studies on HOX gene and its abnormal molecular mechanisms, as well as potential correlation with MDS.

Databases and computational tools are increasingly important in the study of allergies, particularly in the assessment of allergenicity and allergic cross-reactivity. ALLERDB database contains sequences of allergens and information on reported cross-reactivity between allergens. It focuses on analysis of allergenicity and allergic cross-reactivity of clinically relevant protein allergens. The official IUIS allergen data were extracted from the IUIS Allergen Nomenclature Sub-Committee website, and their sequence information from the public databases, and reference publications. The analysis tools assist allergen data analysis and retrieval, and include keyword searching, BLAST, prediction of allergenicity, modification of BLAST that displays cross-reactive allergens, and graphics representation of cross-reactivity data. ALLERDB is new brand of allergen databases with a rich set of tools for sequence comparison, pattern identification, and visualization of results. It is accessible at http://research.i2r.a-star.edu.sg/Templar/DB/Allergen.

Transforming growth factor beta receptor 2 (TGFBR2) plays a central role in normal heart development, and we investigated whether TGFBR2 polymorphism confers the risk of congenital ventricular septal defect (CVSD). The case–control study included 115 CVSD children and 188 healthy children in a Chinese population. TGFBR2 rs6785358 polymorphism was genotyped with polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Enzyme-linked immunoassay (ELISA) was used to detect serum TGFBR2 levels. The genotype and allele frequency of TGFBR2 rs6785358 were significantly higher in the CVSD group than in the controls (all P

Th17 cells are a newly discovered subsets of T cells. It can specifically secrete IL-17. The RORγt and STAT3 are specific transcription factors of Th17 cells. In recent researches, it has been found that Th17 cells and their proportion increased in a variety of autoimmune diseases. This article briefly reviews Th17 cells and its relationship with the occurrence and severity of several immune-related blood diseases, including aplastic anemia, autoimmune hemolytic anemia, immune thrombo-cytopenia and immune-related pancytopenia.

In an attempt to establish the advantages of fluorescence in situ hybridization (FISH) studies over conventional cytogenetic (CC) analysis, a total of 2302 de novo MDS patients from 31 Chinese institutions were prospectively selected in the present study for both CC and standardized FISH analysis for +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities. CC analysis was successful in 94.0% of the patients; of these patients, 35.9% of the cases were abnormal. FISH analysis was successful in all 2302 patients and detected at least one type of common cytogenetic abnormality in 42.7% of the cases. The incidences of +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities by FISH were 4.1% to 8.7% higher than those by CC. FISH identified abnormalities in 23.6% of the patients exhibiting normal CC results and revealed that 20.7% of the patients with adequate normal metaphases (≥20) had abnormal clones. FISH identified cytogenetic abnormalities in 50.4% of the patients with failed CC analysis. In summary, our multicenter studies emphasised and confirmed the importance of applying standardized FISH testing based on an appropriate panel of probes to detect common cytogenetic abnormalities in Chinese de novo MDS patients, particularly those with normal or failed CC results.

This study was purposed to investigate the role of regulatory T cells (Treg) in the immune unbalance for patients with acquired severe aplastic anemia (SAA). The flow cytometry was used to detect the quantity of CD4(+) CD25(+) CD127(dim) Tregs, T cell subset (CD4(+)/CD8(+) ratio), dendritic cell(DC) subset(mDC/pDC ratio) in 44 SAA patients(25 untreated patients and 19 recovery patients) and 23 normal controls. The correlation between Tregs and T cell subset, DC subset and hemogram were analyzed. The results showed that the percentage of CD4(+) CD25(+) CD127(dim) Tregs in peripheral blood lymphocyte(PBL) of untreated patients was (0.83 ± 0.44) %, which was obviously lower than that in recovery patients (2.91 ± 1.24)% and normal controls (2.18 ± 0.55)% (P0.05), but the difference was not statistically significant between latter two groups. The ratio of CD4(+)/CD8(+) was (0.5 ± 0.3) in untreated patients, which was obviously lower than that in recovery patients (1.2 ± 0.4) and normal controls (1.11 ± 0.24) (P0.05). The ratio of mDC/pDC was (3.08 ± 0.72) in untreated patients, which was significantly higher than that in recovery patients(1.61 ± 0.49) and normal controls (1.39 ± 0.36) (P0.05). The percentage of CD4(+) CD25(+)CD127(dim) Tregs in PBL positively correlated with CD4(+)/CD8(+) ratio (r = 0.695, P0.01), and that negatively correlated with mDC/pDC ratio (r = -0.796, P0.01). There were significant positive correlations between CD4(+)CD25(+)CD127(dim) Tregs/PBL and WBC, Ret% (r = 0.761, 0.749 respectively, P0.01). It is concluded that the decrease of CD4(+)CD25(+)CD127(dim) Tregs quantity in SAA may be one of mechanisms underlying bone marrow failure resulting from the deterioration of immune tolerance and hyperfunction of T-cells.

This study was purposed to detect the quantity and function of bone marrow (BM) T follicular helper (Tfh) cells of patients with immune thrombocytopenia, and to explore the role of Tfh cells in the pathogenesis of ITP. Twenty-one newly diagnosed ITP patients, twenty ITP patients in recovery stage and eighteen normal controls were enrolled in this study. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21 in BM were detected by flow cytometry (FCM), and the mRNA expression of BCL-6 in BMMNC was determined by semi-quantitive RT-PCR. Correlation of Tfh cell level with the disease severity of ITP patients was analysed. The results showed that the ratio of CD4(+)CXCR5(+)/CD4(+) cells in newly diagnosed ITP patients [(5.532 ± 2.599)%] was significantly higher than that in ITP patients with recovery stage [(4.064 ± 2.026)%] and controls [(4.048 ± 1.413)%] (P0.05). The ratio of CD4(+)CXCR5(+)ICOS(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(14.586 ± 8.561)%] was higher than that in recovery stage ITP patients [(12.884 ± 10.161)%] and controls [(7.487 ± 5.176)%]. The differences be-tween newly diagnosed ITP patients and controls were statistically significant (P0.05). The ratio of CD4(+)CXCR5(+) CD40L(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(15.309 ± 10.756)%] and in ITP patients with recovery stage [(18.242 ± 12.243)%] were significantly higher than that in controls [(8.618 ± 5.719) %] (P0.05). The ratio of intracytoplasm CD4(+) CXCR5(+) IL-21(+)/CD4(+)CXCR5(+) cells in newly diagnosed ITP patients [(58.560 ± 26.285)%] and in ITP patients with recovery stage [(57.035 ± 30.936)%] were significantly higher than that in controls [(36.289 ± 24.868)%] (P0.05). The relative expression levels of BCL-6 mRNA in BMMNC of three groups were (1.407 ± 0.264), (1.149 ± 0.217) and (0.846 ± 0.157), respectively. The differences between 3 groups were significant(P0.05). It is concluded that the quantity and function of Tfh cells in ITP patients increase, which may play an important role in the pathogenesis of ITP.

Recent advances in next-generation sequencing technology allow high-throughput cDNA sequencing (RNA-Seq) to be widely applied in transcriptomic studies, in particular for detecting differentially expressed genes between groups. Many software packages have been developed for the identification of differentially expressed genes (DEGs) between treatment groups based on RNA-Seq data. However, there is a lack of consensus on how to approach an optimal study design and choice of suitable software for the analysis. In this comparative study we evaluate the performance of three of the most frequently used software tools: Cufflinks-Cuffdiff2, DESeq and edgeR. A number of important parameters of RNA-Seq technology were taken into consideration, including the number of replicates, sequencing depth, and balanced vs. unbalanced sequencing depth within and between groups. We benchmarked results relative to sets of DEGs identified through either quantitative RT-PCR or microarray. We observed that edgeR performs slightly better than DESeq and Cuffdiff2 in terms of the ability to uncover true positives. Overall, DESeq or taking the intersection of DEGs from two or more tools is recommended if the number of false positives is a major concern in the study. In other circumstances, edgeR is slightly preferable for differential expression analysis at the expense of potentially introducing more false positives.

Relapse of immune-related pancytopenia (IRP) has often occurred and is very difficult to cure; the pathogenesis of relapsed IRP was unclear. The aim of this work is to investigate whether memory B lymphocytes (Bm) in bone marrow were involved in pathogenesis of relapsed IRP.Seventy-nine patients with IRP (26 untreated, 32 relapsed, and 21 remittent after relapsed) were assessed, the category and the titer of autoantibodies on bone marrow mononuclear cell (BMMNC-Ab), Bm (CD19+CD27+) cells, and activated Bm (CD19+CD27+HLA-DR+) cells in bone marrow were detected by fluorescence-activated cell sorting (FACS).The percentages of Bm cells (CD19+CD27+/CD19+) and activated Bm cells (CD19+CD27+HLA-DR+/ CD19+CD27+) were 34.73 +/- 11.93% and 69.46 +/- 25.22%, respectively, which were significantly higher than those of untreated IRP (4.73 +/- 0.85%, 12.47 +/- 8.29%) and remittent after relapsed IRP (1.32 +/- 3.52%, 4.35 +/- 6.61%) correspondingly (p0.05). The majority of BMMNC-Ab in relapsed patients were IgG (75%), and the positive rates and the titers of IgG autoantibody of relapsed IRP were significantly more elevated than those of untreated IRP (p0.05). The positive rate of IgM autoantibody in patients with untreated IRP was 69.23%, and the titer was 28.38 +/- 28.00%, but no significant differences were found in the positive rate and titers of IgM between untreated IRP and relapsed IRP (p0.05).In patients with relapsed IRP, Bm cells in bone marrow were increased and hyperactive. The predominant autoantibody was IgG. These findings suggest that autoreactive Bm cells may be involved in the pathogenesis of relapsed IRP.

This study was aimed to investigate the expression of microRNA-21 and its correlation with PTEN in diffuse large B cell lymphoma (DLBCL) paraffin-embedded tissues, and evaluate its potential relevance with clinical characteristics. The expression levels of miR-21 in 26 primary DLBCL and 10 normal lymph node tissue specimens were examined by real-time polymerase chain reaction. The expression of PTEN was detected by immunohistochemical staining. The results indicated that the expression of miR-21 was significantly higher in tumor tissues [6.586(1.10,38.22)] than that in normal tissues [0.791 (0.35,2.87)] (P0.05). Among 26 patients with DLBCL the expression of PTEN protein was positive in 6 patients (23%), and was negative in 20 patients (77%). In patients with DLBCL, the expression level of miR-21 was negatively correlated with the level of PTEN protein. The high expression of miR-21 was positively correlated with the level of serum LDH. The expression level of miR-21 in patients with Ann Arbor III-IV stage was obviously higher than that of patients with Ann Arbor I-II stage, but did not correlate with the subtype of patients in clinic (P0.05). It is concluded that the expression of miR-21 is high in DLBCL and its overexpression may be related with poor prognosis of DLCBL. These findings suggest that PTEN is possibly one of the targets of miR-21 in DLBCL.

BACKGROUND A case with 17-year detailed illness history including evolution of polycythemia vera (PV) to myelofibrosis (MF) and then biphenotype acute leukemia (BAL) was reported. Ten years of PV followed by seven years of MF and then BAL, the patient experienced a classical "complete course" of myeloproliferative neoplasm (MPN). High WBC counts as well as low Hb and platelet counts in MF phase, long disease course, older than 50 years age, and positive JAK2 were her high risk factors of transformation from MPN to leukemia. Pancytopenia in her secondary MF phase responded well to the therapy of corticosteroids, which indicated that the immune mechanism was involved in the pathogenesis of MF. Progression of PV to MF and then BAL might be related to discontinuation of interferon-alpha because of poor tolerance.

Leukocyte interleukin-3 receptor α (CD123) is regarded as a marker of leukemia stem cells. We previously found that CD123 was also highly expressed on CD34(+)CD38(-) cells in myelodysplastic syndrome (MDS) patients, but it is unclear whether the level and the characteristics of CD34(+)CD38(-)CD123(+) cells in MDS are similar to those in acute myeloid leukemia (AML). Based on previous research by our team, we further enlarged the specimens and found that the mean proportion and the mean MFI of CD34(+)CD38(-)CD123(+) cells in low-grade MDS were lower than that in AML, and those in high-grade MDS were similar to those in AML. CD34(+)CD38(-)CD123(+) cells expressed lower granulocyte stimulating factor receptor, CD11b, and apoptosis molecule (Annexin V), meanwhile, these cells showed upregulation of transcription factors (GATA-1, GATA-2) and transferrin receptor (CD71) in MDS and AML. Furthermore, an increase in CD34(+)CD38(-)CD123(+) cells was closely related to the number of cytopenias involving hematopoietic lineages, anemia, blast count in bone marrow smear, fluorescence in situ hybridization analysis and WHO prognostic scoring system score. Thus, increases in CD34(+)CD38(-)CD123(+) cells may reflect malignant clonal cells with aberrant differentiation, overproliferation, and decreased apoptosis in MDS, which were similar to AML. CD123 may thus be a promising indicator for identifying malignant clonal cells in MDS and a candidate for targeted therapy.