An electrochemical aptasensor for Pb2+ was constructed based on the layer-by-layer assembly of graphene (GR) and anthraquinone -2-sulfonic acid sodium salt (AQMS) on the surface of Pb2+ aptamer. The mercapto-modified Pb2+ aptamer was first anchored on a gold electrode. Then the highly conductive material of GR was adsorbed on apt through the unique π-π stacking interaction, which was further used for the assembly and signal amplification of the electroactive AQMS. Upon interaction with Pb2+ ions, the apt on the aptasensor undergone conformational switch from a single-stranded form to the G-quadruplex structure, causing the GR assembled with AQMS releasing from the electrode surface into solution. As a result, the electrochemical signal of AQMS on the aptasensor was substantially reduced. Base on this concept, a useful platform for detection of Pb2+ ions was constructed. Under the optimal experimental conditions, the attenuation of peak currents (△Ipa ) showed linear relationship with the logarithm of Pb2+ concentrations (lgCPb2+) over the range from 5. 0×10-10 to 5. 0×10-8 mol/ L. The detection limit was estimated to be 6. 0×10-11 mol/ L.

Objective To investigate the association between single nucleotide polymorphisms (SNPs) of ATP-binding cassette B1 (ABCB1),ATP-binding cassette C2 (ABCC2) and solute carrier organic anion transporter 1B1 (SLCO1 B1) genes with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL).Methods This study was designed as a casecontrol.From September of 2005 to December of 2011,the blood samples were randomly collected from 142ALL patients from Nanjing Children's Hospital,Enzyme-multiplied immunoassay technique (EMIT) was used to measure the plasma concentration of MTX,Seven SNPs in ABCB1 (rs1045642,rs2032582,rs1128503),ABCC2 (rs717620,rs2273697) and SLCO1 B1 (rs4149081,rs11045879) genes were detected by polymerase chain reaction-ligase detection reaction (PCR-LDR).Results A significantly increased risk of MTX-induced toxicity was observed in patients with MTX elimination delay (OR ＝ 2.828,95％ CI:1.217-6.571,P ＜ 0.05).Two SNPs in SLCO1B1,rs4149081 and rs11045879 were linkage disequilibrium (LD) with each other (R2 =0.979,P ＜ 0.05).Multivariate analysis revealed that individuals with SLCO1B1 rs4149081 AA genotype or SLCO1B1 rs11045879 CC genotype showed increased incidence of MTX elimination delay (OR =4.41,95％ CI:1.537-12.654,P =0.042),and the two genotypes were also associated with significantly increased risk of MTX-induced toxicity (OR =4.118,95％ CI:1.135-14.944,P =0.022).No association of MTX elimination delay or MTX-induced toxicity with the other SNPs analyzed was found.Conclusions SLCO1B1 rs4149081 AA or SLCO1B1 rs11045879 CC genotypes might be a risk factor for the susceptibility to MTX-induced toxicity in children with ALL.

An auxiliary training system was explored for the development of creativity of long-termsystem medical undergraduates through scientific researches in spare time.In practice,professionals from research groups of different disciplines were recruited for developing wide-scope theoretical and technical bases of the undergraduates through training among these research groups followed by focused researches on topics of the running projects of these professionals.The undergraduates were engaged in a serial of research activities,including the discovery of problems for reasoning out scientific research projects,the writing of their project proposals,the summary of their data and the writing of reports,to develop their creativity and their qualification for scientific researches.

Osteonecrosis is the most common disorder in femoral head and scaphoid. However, avascular necrosis (AVN) in metacarpal head is a rare disease. In the present study, a 14-year-old male patient complained of right-hand pain with a limited range of motion for one month. Physical examination showed that the active flexion was 70° and the extension was limited to 30° of the metacarpophalangeal (MCP) joints. The grip strength decreased to 60% of the contralateral hand. X-rays demonstrated flattening and sclerotic changes in the long finger and ring finger of metacarpal head. CT scanning indicated cystic, osteochondral defects and sclerotic changes in metacarpal head. Imaging examination further confirmed the diagnosis of AVN in the long metacarpal finger and ring finger. After conservative treatments including splint immobilization, non-steroidal anti-inflammatory drugs (NSAIDs) and physiotherapy, the local pain symptoms of the MCP joint gradually disappeared. The range of motion of MCP joint returned to normal with the grip strength score as 105% of the contralateral hand. MRI confirmed excellent remodeling and regeneration in the metacarpal head at two years later. The clinical characteristics, diagnosis and treatments of AVN of metacarpal head were reviewed. Although radiograph examination is commonly used, early-stage osteonecrosis of the metacarpal head should be confirmed by MRI. Given the rarity of this disorder, there is no consensus on the treatments. Metacarpal necrosis is the more common disorder in adolescent patients with a history of trauma. Considering the potential of bone remodeling, juveniles with metacarpal head necrosis could recover by conservative treatments.

AIM:To investigate the influence of continuous subculturing of human umbilical cord mesenchymal stem cells (hUC-MSCs) on the mRNA expression of all 23 family members of NOD-like receptors (NLRs), and to search for the way of improving the subculture quality of hUC-MSCs and increasing the quantity and safety in the experimental and clinical application .METHODS:Neonatal umbilical cord was collected to isolate and purify the hUC-MSCs with the colla-genase II digestion and adherence screening methods .These cells were continuously subcultured .The hUC-MSCs at pas-sage 3 and passage 28 were identified by flow cytometry and induced differentiation .The mRNA expression of NLRs in the passage 3 and passage 28 hUC-MSCs was detected by RT-qPCR.RESULTS: The cell phenotypes of both passage 3 and passage 28 hUC-MSCs were CD29 +/CD44 +/CD105 +/CD31 -/CD34 -/CD40 -/CD45 -/CD106 -/HLA-DR-, and both of the cells were induced into osteoblasts and adipocytes , which were conformed to the criteria of International Society for Cellular Therapy to define MSCs .All the NLR family members were expressed in passage 3 hUC-MSCs.NOD1, NLRC4, NLRC5, NLRP1, NLRP3, NLRP10, NAIP, NLRX1 and APAF1 at mRNA levels were highly expressed , and the rest were lowly expressed.When hUC-MSCs were subcultured to passage 28, NLRP10 mRNA was increased, NLRC5 mRNA and NLRX1 mRNA were hardly changed , and all of the rest members were decreased .The difference of NLRP1 mRNA expres-sion between passage 3 and passage 28 hUC-MSCs was observed with statistical significance (P<0.05).CONCLU-SION:The effects of subculturing on the expression of NLR family in hUC-MSCs are pleiotropic .It requires further investi-gation to confirm whether these effects are related to the proliferation , differentiation and immunomodulation of MSCs .

Objective To investigate the influences of the functional polymorphisms of cytochrome P450 isozymes 2A6 (CYP2A6),2B6 (CYP2B6),2C9 (CYP2C9),and 2C19 (CYP2C19) on plasma concentration of sodium valproate.Methods A total of 131 Chinese children with epilepsy receiving sodium valproate after a period of more than 5 half-time were recruited.The genotypes of CYP2A6 were detected by multiplex polymerase chain reaction (PCR),and the genotypes of CYP2B6,CYP2C9,and CYP2C19 were detected by PCR-ligase detection reaction.Enzyme-multiplied immunoassay technique was used to measure the plasma concentration of sodium valproate.The association between the polymorphisms and the plasma concentration of sodium valproate were analyzed by one-way ANOVA or Student' s t-test.Results Patients were divided into 4 groups according to the genotyping results of CYP2C9 and CYP2C19 (G1:extensive metabolizers in both CYP2C9 and CYP2C19; G2:CYP2C19 intermediate metabolizers; G3:CYP2C19 poor metabolizers; G4:CYP2C9 poor metabolizers),the mean normalized steady-state sodium valproate concentrations were significantly higher in G3 (3.70 ± 0.95) and G4 (4.35 ± 1.48) patients when compared to those in G 1 (2.57 ± 1.30,t =3.056,4.490,both P ＜ 0.01) and G2 (2.76 ± 1.19,t =2.827,4.462,both P ＜ 0.01) patients.The daily doses (mg/d) of sodium valproate received by G3 (19.46 ± 5.20) and G4 (19.30 ±7.67) patients were significantly lower than that of G1 patients(24.10 ±6.97,t =2.359,2.297,both P ＜ 0.05).There were no differences in daily doses or normalized steady-state concentrations of sodium valproate among the CYP2A6* 4 or CYP2B6* 6 genotypic groups.Conclusions The CYP2C9 and CYP2C19 polymorphisms have dramatic effects on the plasma concentration of sodium valproate.The daily doses of sodium valproate in G3 and G4 patients should be lower than usual.

AIM:Toinvestigatetheeffectofnicotinicacidamide(NAA)ontheinfusiondamageofhuman umbilical cord mesenchymal stem cells ( hUC-MSCs) under the condition of instant blood-mediated inflammatory reaction ( IBMIR) .METHODS:Normal peripheral blood without anticoagulant at volume of 2.7 mL was mixed with 0.3 mL phys-iological saline (as blank group), CFSE labeled hUC-MSCs (1 ×106 cells in 0.3 mL as MSC group) and CFSE labeled hUC-MSCs (1 ×106 cells in 0.3 mL) preprocessed with NAA at concentration of 10 mmol/L for 24 h ( as MSC+NAA group) , respectively.The mixture was immediately injected into the improved Chandler Loop model, placed in 37℃water bath, and then started the peristaltic pump at the speed of 20 mL/min for 1 h.The number of CFSE labeled hUC-MSCs, platelets, white blood cells were counted and the concentration of complement C3a was measured before and after cycling, respectively.RESULTS: After 1 h circulation, the platelet dissipation rate were ( 29.96 ±10.88 )% in blank group, (77.76 ±19.29)% in MSC group all and (50.13 ±18.10)% in MSC +NAA group; and the leukocyte counts were (37.82 ±13.81)%in blank group, (64.57 ±17.08)% in MSC group and (41.52 ±17.26)% in MSC+NAA group. Compared with blank group, the differences of the dissipation rates in MSC group and MSC+NAA group all had statistical significance.The hUC-MSCs relative survival rate in MSC+NAA group was higher than that in MSC group.C3a concentra-tions in blank group, MSC group and MSC+NAA group were (206.27 ±58.10), (230.47 ±39.61) and (208.37 ± 40.66) μg/L, respectively.CONCLUSION:Co-circulating the mixture of hUC-MSCs with normal peripheral blood with-out anticoagulant in the improved Chandler Loop for 1 h depletes a large number of hUC-MSCs and blood components, and increases C3a, suggesting that this model can induce IBMIR.NAA has a protective effect on the hUC-MSCs in the infusion damage by inhibiting IBMIR, reducing the wastage of the blood components and enhancing the survival rate of the hUC-MSCs.

AIM:To explore the effect of HbA1c level in the patients with type 2 diabetes mellitus (T2DM) on the rheological properties of erythrocytes and the structure of hemoglobin (Hb).METHODS:The patients with T2DM were classified into 3 groups:the patients with good glycaemic control (group A, HbA1c<7.0%), the patients with poor glycaemic control (group B, 7.0%≤HbA1c<9.0%) and the patients with persistent hyperglycemia (group C, HbA1c≥9.0%) .The rheological properties of a single living erythrocyte were analyzed by the techniques of static imaging and anal -ysis.Ultraviolet-visible spectroscopy was used to study the structure of Hb .RESULTS: Compared with group H , the roundness effect factor (REF) of erythrocytes, which was positively related with HbA1c level, was significantly increased in groups A, B and C (P<0.05).The contact area of erythrocytes in group B and all the morphological parameters of erythrocytes in group C were significantly higher than those in group H ( P <0.05 ) .There were significant differences among groups A , B and C in deformation capacity and elastic parameters of the cell membrane ( P<0.05 ) , but with no difference in the long axis and short axis between group A and group B .Compared with group H , no obvious change in the spectral pattern and spectrum peak of Hb in groups A , B and C was observed.However, the absorbance of Hb, which showed a trend of gradual decline with the increase in HbA 1c level, in group B and group C was significantly decreased as compared with group H (P<0.01), and the Hb absorbance in group C were also lower than that in group A (P<0.05). CONCLUSION:With the increase in HbA1c level, the morphology along with the deformation function of erythrocytes in T2DM changes and declines gradually , and the structure of Hb may also change .

Autophagy is a dynamic process that allows recycling of long-lived proteins and damaged organelles into biosynthetic materials for maintaining the normal cellular homeostasis. Recently, accumulating evidence has indicated that autophagy played important roles in the pathogenesis of neuronal diseases. In this article, the research progress of autophagy in the pathogenesis and regulation mechanism of common nervous system diseases were reviewed to deepen the understanding of autophagy, and arouse researchers' attention on dynamic regulation of autophagy and alleviating autophagic flow injury.

Objective:To assess the clinical effects of closed reduction and intramedullary fixation with antegrade Kirschner wire plus rod rotation technique in the treatment of the fifth metacarpal neck fracture.Methods:In this retrospective study, 26 patients with the fifth metacarpal neck fracture were treated by closed reduction and intramedullary fixation with antegrade Kirschner wire plus rod rotation technique at Department of Orthopaedics, Central Hospital of Karamay from August 2015 to October 2017. They were 23 males and 3 females, aged from 12 to 53 years with an average age of 25.2 years. In the intramedullary nailing, a Kirschner wire pre-bent by 10° to 15° was inserted from the base of the fifth metacarpal into the medullary canal before closed reduction. After satisfactory reduction was achieved, the Kirschner wire was inserted across the fracture site into the metacarpal head for further reduction and fixation using rod rotation technique. After operation, a plaster was applied to protect the fixation for 2 weeks. Functional exercise was started after removal of the plaster. The Kirschner wire was not removed under local anaesthesia at the outpatient department until about 10 to 16 weeks postoperation when X-ray showed fracture healing. Records of their operation time, head/shaft angle of the fifth affected metacarpal, active range of motion of the metacarpophalangeal joints and Total Active Movement (TAM) of hand function at the last follow-up were collected.Results:Their operation time averaged 21 minutes (from 12 to 35 minutes). Anatomical reduction was achieved in 23 cases but not in 3 ones whose metacarpal head/shaft angle and alignment were obviously improved. Follow-ups for 6 to 29 months (average, 15.8 months) showed all the patients obtained solid fracture healing with no infection or delayed fracture healing. The head/shaft angle was improved significantly from preoperative 61.2°±11.2° to postoperative 14.7°±3.5° ( P<0.05) which was not significantly different from that of the healthy side (14.6°±1.7°)( P>0.05). The active range of motion of the metacarpophalangeal joint was 89.3°±4.2° after fixation removal, not significantly different from that of the healthy side (90.7°±1.5°) ( P>0.05). According to TAM scores at the last follow-up, 22 cases were rated as excellent, 3 as good and one as fair. Conclusion:In the treatment of the fifth metacarpal neck fracture, closed reduction and intramedullary fixation with antegrade Kirschner wire plus rod rotation technique is effective, because it is simple and limitedly invasive, and leads to limited complications, low costs and secondary reduction.