Four crystalline forms of clopidogrel bisulfate were characterized by analytical techniques. Aiming to research the absorption characteristics of clopidogrel bisulfate polymorphs after taken orally by rat, and to estimate the influence of crystal form to pharmacodynamic action, four crystalline forms of clopidogrel bisulfate were administered intragastrically to rats, and high performance liquid chromatography (HPLC) was used to measure the contents of clopidogrel bisulfate and its metabolite in rat plasma. The metabolite of clopidogrel bisulfate was detected in rat plasma. There were significant deviations among four crystalline forms in the areas under curve of the metabolite of clopidogrel bisulfate. We concluded that the different crystal forms of clopidogrel bisulfate showed different pharmacokinetic characteristics, which might affect pharmacodynamic action.

Objective To observe the characteristics of folate binding proteins (FBP) in myelodysplastic syndromes (MDS) and leukemia and to study the clinical significance of reduced folate carrier (RFC) present in MDS and its relationship with multidrug resistance (MDR).Methods The features of FBP on bone marrow cells were analyzed using radiolabeled 3 H-folic acid (3 H-FA) binding membrane proteins and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). In the same time, P-glucoprotein and mRNA of MDR gene were detected using immunocytochemistry and reverse transcription ploymerase chain reaction (RT-PCR) respectively in patients with MDS and leukemia.Results Two kinds of FBP, folate receptor (FR) and reduced folate carrier (RFC), were found on the leukemic cells. The same results were presented on mononuclear cells of bone marrow in 5 out of 14 MDS patients, and MDR positive was seen in 4 patiens of them. In normal control and other 9 cases of MDS FRs were only found on the mononuclear cells of bone marrow.Conclusion Reduced folate carrier, which is present in the leukemic cell, is a product of neoplastic cell. It might reveal preleukmic state and have the same significance with MDR that RFC is found in MDS patients.

Aiming at the application of big data of biobank , this paper briefly analyzed the ethical and legal is-sues.Combined with the potential legal attribute of biobank namely creditor ' s right, virtual property right , and new intellectual property right , this paper also detailed the legal basis of biobank .Regarding the disputes existing in the big data ' s ownership of biobank and non -establishment of the sharing system of big data , this paper mean-while put forward some planning assumptions and suggestions .Firstly, the boundary between privacy protection and the development of big data should be determined .Secondly , the legal attribute and ownership of the big data of biobank should be confirmed .Finally, it should establish a sharing system of biobank when strengthen the protec-tion of intellectual property right .

Objective: To investigate the impact of bladder filling status on the movement of uterine and on the volume of organs at risk(OAR), so as to provide theoretical basis for individualized internal target volume (ITV) and planning target volume (PTV). Methods: Simulation CT images for a total of 27 patients with locally advanced cervical cancer were acquired with empty bladder, 1.0 h after bladder filling, 1.5 h after bladder filling, respectively. The volumes of uterine corpus, cervix, OARs, CTV and PTV 1.0 h after bladder filling were delineated. The impact of bladder filling status on the displacements of cervix and corpus, volumetric changes of rectum, small intestine, and the volumes of small intestine, bladder and rectum within PTV were analyzed. The correlation between bladder filling status and uterine displacement and volume of OAR was also investigated, as well as the volume of cervix and corpus in the PTV with empty bladder and 1.5 h after bladder filling. Results: Bladder filling status is different for individual cases. The maximum movement range of cervix and uterine body with bladder filling state was 0-3.04 cm and 0-4.31 cm respectively. The anterior displacements of corpus (F=7.818, P<0.05), the volumetric changes of blander, as well the volume of bladder and small intestine in the PTV (F=46.197, 44.609, 29.546, P<0.05) were significantly different between different bladder filling status. The bladder filling status was correlated with the displacements of the anterior of corpus, volumetric changes of small intestine, and the volumes of bladder and small intestine within the PTV (r=-0.232, -0.298, 0.915, -0.336, P<0.05). The volumes of cervix and corpus out of the PTV were significantly different between the empty bladder and 1.5 h after bladder filling (t=-1.326, -1.559, P<0.05). Conclusions Bladder filling status was different for individual patients. The displacements of the anterior of the corpus were significantly affected by the bladder filling status. Increasing the anterior margin of PTV was recommended. The consistency of bladder filling status was critical for the precise cervical cancer IMRT.

The tumors of central nervous system refer to a group of benign and malignant diseases originating from tissues or structures within the central nervous system. Common tumors of central nervous system are sporadic, but a few have familial onset. Compared with sporadic brain tumors, the clinical symptoms, diagnostic ideas and follow-up review plans of familial brain tumors are more complicated. The multidisciplinary diagnosis and treatment (MDT) mode usually refers to a treatment mode in which a case involving multiple organs and systems is discussed, and the best treatment plan is formulated for the patient based on the comprehensive opinions of various disciplines. Because familial brain tumors often involve multiple organs, multiple disciplines and multiple systems, and their low incidence leads to less clinical experience for neurosurgeons, the MDT model is more conducive to efficient diagnosis, treatment and management of familial brain tumors. This review elaborates on the neurosurgeon-led MDT model, and introduces the latest research on the epidemiology, genetic characteristics, clinical manifestations, diagnostic ideas and multidisciplinary management of familial brain tumors.

Objective Compared with chest CT,endoscopic ultrasonography (EUS) can more accurately determine the upper and lower margins of esophageal cancer,and marking the upper and lower margins of the esophageal cancer with titanium clip contributes to the delineation of target area of esophageal cancer during radiotherapy.To compare the effects of esophageal X-ray,chest computed tomography (CT)scan and EUS-assisted placement of marker clip in the determination of the length of gross target volume (GTV),aiming to provide reference for the determination of GTV during esophageal cancer radiotherapy.Methods Thirty patients who were initially diagnosed with thoracic esophageal cancer by histological and cytological examinations and scheduled to receive radiotherapy were recruited in this investigation.All patients received esophageal X-ray,CT scan,and EUS-assisted placement of marker clip.The length of GTV was quantitatively measured and statistically compared among three different methods.Results The length of GTV was (6.1 ± 1.4) cm,(6.8± 1.9) cm and (6.3± 1.9) cm determined by esophageal X-ray,CT scan and EUS-assisted placement of marker clip,respectively.Compared with CT scan,the length of GTV determined by EUS-assisted placement of marker clip did not significantly differ (P=0.11).The length of GTV determined by esophageal X-ray was significantly shorter than that by CT scan (P =0.03).Among all patients,the length of GTV determined by EUS-assisted placement of marker clip was longer compared with that by chest CT scan in 22.2％ of patients.The length of GTV determined by EUS-assisted placement of marker clip was the same as that by chest CT scan in 11.1％ of patients.The length of GTV determined by EUS-assisted placement of marker clip was shorter compared with that by chest CT scan in 66.7％ of patients.Conclusions EUS-assisted placement of marker clip differs from esophageal X-ray and CT scan in determining the length of GTV,which acts as one of the effective methods in the determination of the length of GTV during esophageal cancer radiotherapy.

Objective:To observe the effect of ubiquilin 2 gene (UBQLN2) on the radiosensitivity of human esophageal squamous cell carcinoma cells (ESCC) of EC109 and KYSE30, and explore underlying molecular mechanism.Methods:siRNA and lentivirus transfection techniques were used to establish UBQLN2-knockdown and UBQLN2-overexpression cell lines. The cells were irradiated with a dose of 4 Gy X-rays. UPLC-Q-TOF-MS technique was used for metabolite difference analysis and KEGG pathway analysis. The results of metabonomics analyses were verified by qRT-PCR assay. The influence of UBQLN2 level on the radiosensitivity of ESCC was confirmed by CCK-8 cell proliferation assay and clone formation assay and further verified by treating the cells with metabolic enzyme inhibitors and exogenous metabolites.Results:Compared with irradiation alone, down-regulating UBQLN2 in EC109 and KYSE30 cell lines reduced the cell survival by 32.29% and 16.42% ( t=5.35, 4.88, P<0.05), and reduced the clone formation rate by 11.07% and 7.47% after 4 Gy irradiation, respectively ( t=4.18, 5.09, P<0.05). On the contrary, up-regulating UBQLN2 in EC109 and KYSE30 cell lines increased the survival rate by 14.07% and 10.64% ( t=5.88, 4.21, P<0.05), and increased the clone formation rate by 6.53% and 7.87% after 4 Gy irradiation, respectively ( t=8.60, 8.26, P<0.05). Metabonomics study showed that the purine metabolic pathway was significantly enriched after down-regulating UBQLN2 in EC109 cell. The qRT-PCR experiment showed a positive correlation between the expression level of UBQLN2 and the mRNA level of five purine metabolism enzymes. The viability of irradiated UBQLN2-overexpression cells decreased by 18.28% and 25.58%, respectively ( t=7.76, 10.95, P<0.05), and the clone formation rate decreased by 9.33% and 9.93%, respectively ( t=5.97, 8.02, P<0.05) after adding mycophenolic acid(MPA). However, the survival rate of cells increased by by 8.28% and 10.74% ( t=2.83, 6.20, P<0.05), and the clone formation rate increased by 7.33% and 5.80%, respectively ( t=7.16, 5.49, P<0.05), when exogenous supplementation of nucleotides (ATP + GTP) were added. Conclusion:The expression level of UBQLN2 was negatively related to the radiosensitivity of ESCC by up-regulating purine metabolism.

Objective To investigate the effect of decitabine (DAC) on human acute myeloid leukemia (AML) cell line HL-60 and the regulating of natural killer (NK) cell activating receptor (NKG2D) ligands(NKG2DL), and to detect the molecular mechanism of JAK-STAT3-SOCS signaling pathway. Methods The effect of DAC on the proliferation of HL-60 was detected by using CCK-8 assay. The cell apoptosis was analyzed by using Annexin-V/PI double standard method. The expressions of receptor NKG2DL including MICA/B and ULBPs in HL-60 cells were detected by using flow cytometry (FCM). The killing activity of NK cells was analyzed by using carboxy fluorescein diacetate succinimidyl ester (CFSE). The expressions of JAK/STAT3 signaling pathway or molecules including STAT3, its upstream kinases JAK1, JAK2 and the negative regulator of STAT3,SOCS-1,SOCS-3 were examined by Western blot.Methylation level of the SOCS-1,SOCS-3 gene after the treatment of DAC was analyzed by using methylation-sensitive high resolution melting(MS-HRM). Results There was an obvious inhibitory effect of DAC on HL-60 cells. The cell viability of HL-60 treated with 0.2, 0.5, and 1.0 μmol/L DAC for 48 h was decreased by (25±11) %, (39±8) % and (50±7)%(P<0.01)respectively compared with those cells without DAC treatment.The incidence of apoptosis was (24.77±7.50) %, (27.10±4.48) % and (30.53±3.93) % after DAC treatment for 48h respectively, which were higher than that of untreated cells[(3.11±0.50)%](P<0.01).DAC induced a significant up-regulation of MICA/B, ULBP-1, ULBP-3 in HL-60 cells, and enhanced the sensitivity of HL-60 cells to NK cytotoxicity. Western blot results showed that a down-regulating expression of STAT3 and JAK1, JAK2 protein was detected, in addition to the phosphor-STAT3 and phosphor-JAKs in HL-60 cells after DAC treatment, but the expressions of SOCS-1 and SOCS-3 protein were increased. HRM results showed that DAC could inhibit the methylation of SOCS-3 gene. Conclusion DAC can inhibit the proliferation of HL-60 cells, upregulate the expression of NKG2DL and enhance the cytotoxicity of NK targeted to HL-60 cells, which might be related to the activity regulation of intracellular JAK-STAT3-SOCS signaling pathway.

Innate immunity is the first line of the host cell defensing against viral infection,in which the pattern recognition re-ceptors(PRRs)such as Toll-like receptors(TLRs)and retinoic acid induces gene Ⅰ-like receptors(RLRs)play an important role.After virus infection,mitochondrial antiviral signaling protein(MAVS)in PRRs-mediated signaling pathway,which are of the com-mon linker molecule for downstream signal transmission,can receive signals transmitted by upstream TLR and RIG-Ⅰ,activate down-stream NF-κB and IRF3/7 signaling pathways leading to the activation of interferon(IFN)expression.Therefore MAVS acts as a bridge in the innate immune signaling pathway.More and more studies have shown that viruses have evolved a series of mechanism to escape the innate immune response over the long course of their evolution,and evaded the host's antiviral immune response by interfer-ing with multiple sites in the MAVS-mediated signaling pathway so as to complete its own replication and proliferation.In this paper,the role of MAVS in IFN-Ⅰ pathway and its latest research progress in the mechanism of anti-DNA viruses and anti-RNA viruses reac-tion are reviewed,providing theoretical basis for further studying the detailed mechanism of anti-virus of MAVS.

Objective To explore the patterns of functional gait asymmetry during the support phase and the differentiation of bilateral foot functions,to gain insights into the human movement compensa-tion mechanisms and stability control characteristics,so as to provide theoretical references for the pre-vention and rehabilitation treatment of unilateral foot and ankle injuries.Methods Twelve young females with normal feet were recruited,and the time percentage of each phase of the support period,the change of longitudinal arch angle,the vertical ground reaction force and the center of plantar pressure trajectory of the dominant and non-dominant feet were collected by using a three-dimensional motion capture and a high-frequency plantar pressure testing system when the subjects walked at the optimum speed with the incremental loading of weights[0%body weight(BW),10%BW and 20%BW].The ef-fects of laterality(dominant foot,non-dominant foot)and load(0%BW,10%BW,20%BW)on arch changes and gait parameters,and the interactions between them,were analyzed using a two-way re-peated-measures ANOVA.Results The factors of laterality and load interacted significantly on arch changes,but not on gait parameters.(2)Compared with 0%BW,the time percentage of the buffering phase of the nondominant feet with the load of 20%BW increased(P<0.05),while that of the domi-nant ones decreased(P<0.05),with an increase in the buffering load of both feet with the load of 20%BW(P<0.05)and the buffering force excursion of both feet with the load of 10%BW(P<0.05).More-over,changes in longitudinal arch angle increased(P<0.05)with the load of 10%and 20%BW,the pedal extension load rate increased(P<0.05)with the above BW load in the non-dominant feet,and the horizontal slope of pedal extension decreased(P<0.05)with 20%BW load in the dominant feet.Compared with 10%BW,when the feed was loaded 20%BW,the time percentage in the buffering phase and the buffering force offset of the dominant feet decreased(P<0.05),while the buffering load of both feet increased(P<0.05).(3)Compared with the non-dominant feet,for the dominant feet,the buffering load rate at the load of 10%and 20%BW and changes in the longitudinal arch angle at the load of 20%BW decreased(P<0.05),while the horizontal slope of the pedal extension without load in-creased(P<0.05).Conclusion Walking with load induces function differentiation in bilateral feet.The dominant foot has more efficient horizontal extension without load and better buffering function in the vertical direction with loads,while the non-dominant feet perform a more adequate weight-bearing and extension function vertically with larger load.It is suggested that unilateral injury feet should not be given too much load,and it is inappropriate to select a single foot to represent and evaluate the func-tion and injury risk of the double feet in loaded walking.