Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective: To evaluate the non-carcinogenic health risk of heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) in residential indoor dust for young children around an e-waste dismantling area in South China. Methods: A village around an e-waste dismantling area in South China was selected as a research site in October 2016. Convenience sampling method was used to select 36 houses in the village and 36 dust samples were collected by vacuum cleaner. The concentrations of heavy metals (Cd, Cr, Cu, Mn, Pb and Zn) in each sample were determined and expressed by the average value. Non-carcinogenic health risk assessment was conducted using the US Environmental Protection Agency (EPA) Health Risk Assessment (HRA) model, the American Toxicology and Disease Registry (ATSDR) Target-organ Toxicity Dose (TTD) approach and the ATSDR Binary Weight-of-Evidence (BINWOE) model. Results: The mean ± SD of concentrations of As, Cd, Cr, Cu, Mn, Pb and Zn were (48.90±33.91), (5.95±3.89), (173.57±580.37), (412.71±1 190.00), (612.82±540.70), (297.41±293.22) and (1 052.81±1 156.48) mg/kg, respectively. The HI value of TTD (2.670) and BINWOE (2.933) were higher than the safety threshold of EPA recommended non-carcinogenic health risk. The HI value of TTD and BINWOE were 1.93 and 2.12 times higher than the HI value of HRA (1.386). Conclusion There was non-carcinogenic health risk of heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) via residential indoor dust around the e-waste dismantling area for local children.

Objective To investigate human pulpal response to mineral trioxide aggregate (MTA) and calcium hydroxide (CH) as pulp capping agents. Methods This study was conducted on 90 intact first and second premolars of human maxillary and mandibular teeth of 30 volunteers. The patients were randomly assigned into three groups with 10 in each group. Under local anesthesia, the teeth were exposed and capped either with MTA, or CH. After 30, 60, and 90 days, 10 teeth of each group were extracted and prepared for histologic ob-servation. The data were analyzed with Wilcoxon rank sum test and paired t-tests (α = 0.05). Results MTA had a higher success rate and resulted in less pulpal inflammatory response and more predictable hard dentin bridge formation than CH (P < 0.05). Conclusion MTA appears to be a suitable replacement for CH in direct pulp capping.

Objective To compare the fracture resistances of teeth restored with 3 different posts-core and failure modes. Methods 54lower premolarsendodontically treated teeth were selected for thisstudy and divided into three groups randomly (without ferrule, 1 mm ferrule and 2 mm ferrule). Each group was then divided into 3 sub-groups (6 teeth in each group) and restored with cast post-core, glass fiberpost-core, andceramic post-core respectively. After thermocycling specimens , the fracture resistance was measured using a cyclic fatigue testing machine. Data were analyzed with 2-way ANOVA (α = 0.05). Results Fiber post-core group exhibited significantly higher resistance to fracture compared with groups of cast post-core and ceramic post-core (P<0.05). Preparing dentin ferrules increased significantly fatigue resistance (P < 0.05). Conclusions Glassfiber posts were able to preserve and reinforce the remaining tooth structures. Dentin ferrule preparation is necessary to enhancefractureresistance.

Objective To evaluate a rapid biochip system for the determination of muhidrugresistant tuberculosis (MDR-TB) in Mycobacterium tuberculosis isolates. MethodsA total of 1 186 clinical strains, including 800 rifampin (RFP) resistant isolates, 797 isoniozid (INH)resistant isolates, 791 MDR-TB and 380 susceptible strains, were selected from Beijing Chest Hospital, Shanghai Pulmonary Hospital and Guangzhou Chest Hospital respectively using stratified sampling method. Biochips were used to detect loci of rpoB 511 (T→C), 513 (A→C, C→A), 516 (G→T, A→T, A→G) , 526 (C→T, C→G, A→T, A→G), 531 (C→T, C→G), 533 (T→C), katG 315 ( G→C, G→A) and inhA -15 (C→T). Absolute concentration drug susceptibility test of RFP and INH were performed to serve as the gold standard to calculate susceptibility, specificity and overall concordance of biochip test. All polymerase chain reaction (PCR) products were sequenced to confirm the mutations. ResultsThe concordances between the biochip system and absolute concentration drug susceptibility test were 93.7％ ( 1 108/1 183 ) for RFP, 83. 8％(994/1 186) for INH and 82.4％ (975/1 183) for MDR-TB. Compared with absolute concentration drug susceptibility test, the biochip method displayed a sensitivity of 92. 0％ (733/797) and 77. 4％ (617/797)and a specificity of 97. 2％ (375/386) and 96. 9％ (377/389) for RIF and INH, respectively. For MDR-TB, the biochip system reached a sensitivity of 74. 6％ ( 588/788 ) and a specificity of 98.0％ ( 387/395 ).Among rpoB mutants, mutations were mostly detected at codon 531[64. 5％ (480/744)]. In stains with mutations in katG or inhA, 77.4％ ( 487/629 ) had mutation at codon 315 ( TCG ) of katG only. The sequencing results had a high concordance with that of the biochip method. There were slight differences in 5 strains, among which one strain was detected by biochip as katG 315(G→C) mutant, but was identified by sequencing as wild type, and mutation types other than those detected by the biochip were confirmed in the other 4 strains by sequencing. Conclusion This biochip system is adapted for extensive application in clinical diagnosis, as it allows fast and reliable detection of resistance to isoniazid and rifampin in tuberculosis clinical isolates.

Objective To investigate the expressions of interferon γ(IFNγ), interferon inducible protein-10(IP-10). chemokine receptor CXCR3 and their significance in infection-associated hemophagocytic syndrome(IAHPS). Methods Forty-three patients with IAHPS, 35 infection patients without HPS and 25 healthy controls were included in the study. The serum IFNγ and IP-10 levels were measured by enzyme linked immunosorbent assay(ELISA). The expression of CXCR3 on cell surface of CD_4~+ and CD_8~+ T cells in peripheral blood was determined by flow cytometry. SPSS 13.0 was used for data processing, and independent-sample t test was performed to compare the differences among the groups. Results The serum IFNγ and IP-10 levels in patients with IAHPS were( 608±135) pmol/L and(939±141) pmol/L respectively, which were significantly higher than those in without HPS group[(154±45) pmol/L and (385±119) pmol/L, t=4.97 and 4.02, P<0.05] and healthy controls[(56±18) pmol/L and (248±98) pmol/L, t=5.27 and 4.77, P<0.05]. The expressions of CXCR3 on CD_4~+ and CD_8~+ T cells in IAHPS group were (35±11)% and (23±8)% respectively, which were significantly higher than those in without HPS group[(24±7)% and (16±7)%, t=3.12 and 3.62, P<0.05] and healthy controls[(20±6)% and (12±5)%, t=4.46 and 4.93, P<0.05]. Conclusion The expressions of IFNγ, IP-10 and CXCR3 are increased significantly in patients with IAHPS, which may be related to the disease pathogenesis.

Objective To investigate the clinical application of VCS parameters of leukocyte in the detection of blood bacterial infection, Methods The subjects consisted of 120 patients with blood bacterial infection,69 non-infectious fever patients and 67 health controls.The VCS parameters of neutrophil and lymphocyte were examined with Coulter LH 750 hematology analyzer.The parameters examined including mean channel of neutrophil volume(MNV),neutrophil volume distribution width (NDW) ,mean channel of neutrophil conductivity (MNC),mean channel of neutrophil scatter (MNS),mean channel of lymphocyte volme(MLV),lymphocyte volume distfibufion width (LDW),mean channel of lymphocyte conductivity (MLC) and mean channel of lymphocyte scatter (MLS).Additionally,120 blood bacterial infection patients were grouped according to WBC count(WBC≤10×109/L group and WBC＞10×109/L group),neutrophii rate(≥85%group and＜85%group)and bacterial stain(Gram positive bacteria group and Gram negative bacteria group).VCS parameters among these groups were compared.Results The results of blood infection group were as follows:MNV 156±15,NDW 23.31±3.72,MNS 137±7,MLV 87±12,LDW 17.50±3.38.MLC 110±5 and MLS 69±12.The results of non-infectious fever group were as follows:MNV 151±8,NDW 21.33 ±2.62,MNS 132±10,MLV 91±4.LDW 15.78±1.96.MLC 117±4 and MLS 62±6.The results of control group were as follows:MNV145 ±5.NDW 18.43±0.93.MNS 143 ±4,MLV 84±2,LDW 13.30±0.76.MLC 108±1 and MLS 62±2.There were significant diffierences among these three groups (F value were 19.295,26.272,32.767,6.226,31.016,23.739 and 12.662 respectively,P＜0.05 or P＜0.01).In the infection group.the MNV and NDW were 152 ±16 and 22.19±3.45 respectively for WBC≤10×109/L group.159±12 and 25.29±3.43 respectively for WBC＞10×109/L group.They were both significantly different compared with control group (F valRe were 21.575 and 40.856 respectively,P＜0.01).Also in the infection group.the MNV and NDW were 159±12 and 24.88 ±3.74 respectively for neutrophil rate≥85%group.151±16 and 21.68±2.29 respectively for neutrophil rate＜85%group.They were both significantly different compared with control group(F value were 23.76 and 43.22 respectively,P＜0.01).The MNV and NDW were 157±15 and 24.25±3.39 respectively in those cases with gram-negative bacteremia,153±14 and 21.51±3.78 respectively in those cases with gram-positive bacteremia.They were both signifieanfly difierent compared with control group (F value were 18.74 and 37.47 respectively,P＜0.01).With a cut-off value of 20.50 for the NDW,a sensitivity of 76.7%and specificity of 98.3% were achieyed in diagnosing blood hacterial infection.Conclusion The VCS parameters can reflect the morphologic change of leukocyte in blood bacterial infection.Additionally.the NDW can detect blood bacterial infection more sensitively and specifically.

Objective Analyze the historical data of critical values lists,providing scientific evidence for continuous improvement of critical value systems.Methods Screen out critical value lists data of 2006 from laboratory information system,after pretreatment and transformation of data,calculate the percentage of critical value,and its daily distribution,weekly distribution and department distribution, evaluate the range and turnaround time for critical value.Results The rate of critical value was 1.67%.It was mainly concentrated from 8 to 13 O'clock.Monday and Thursday have more critical value than other days.From the perspective of department,the majority critical value was from hematology department and transplantation department.After the evaluation of distribution diagram of critical value range,the lower critical value limit of blood potassium was adjusted from 3.0 mmol/L to 2.8 mmol/L,the blood platelet and leukocyte counts for parlents with hematology disease were a(Ijusted from 20×109/L,1.5×109/L to 10×1O9/L,1.0×109/L respectively.The laboratory turnaround time for 76.2% critical value was less than 1 hour.Conclusion Review and analyze critical value lists data regularly can improve the work efficiency and quality for the laboratory and clinic department and better meet patients' safety needs.

Objective To evaluate the clinical application of HLA-peptides tetramer staining flow cytometry for determining HBV specific CD8+ cells.Methods HBV specific CD8+ cells in whole blood samples of chronic hepatitis B patients were stained with tetramer complex of HLA-A2 and HBV core 18-27 peptide and counted by flow cytometry. Results The medians of percentages of HBV specific CD8+ cells of total CD8+ cells were 0.20%(0.02%～2.04%) in 11 acute hepatitis B patients and 0.05%(