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1.
Article in Chinese | WPRIM | ID: wpr-934414

ABSTRACT

Objective:Exploring the " bottle neck" factors in the scientific research management of recipient hospitals, making good use of counterpart support resources to help identifying appropriate, tailored strategies of scientific research management that might improve the research capacity of recipient hospitals.Methods:Data were collected according to questionnaire survey and on-site interview, ABC classification method were used to perform statistical analysis, and " bottleneck" factors that constraint the scientific research work of the recipient hospital were summarized.Results:" Insufficient scientific research skills and lacking of talents" and " lacking of scientific research environment and recognition" are the two most prominent factors that negatively affect the scientific research capacity building of the recipient hospitals, followed closely by " the out-dated scientific research policies and lacking support from the hospital leadership" , insufficient of research platform or resources including research funding, as well as other factors. Based on such findings, this article took the First People's Hospital of Kashgar (Guangdong counterpart support) as an example, and tried to discuss some corresponding measures on how to make good use of counterpart support resources.Conclusions:The ABC classification method were used to identify the main " bottleneck" factors, and a series of effective measures that help to making good use of counterpart support resources were explored. As a result, the efficiency of the scientific research management of the recipient hospitals, which in terms of management methods, management concepts and management models, were improved.

2.
Journal of Biomedical Engineering ; (6): 1087-1096, 2021.
Article in Chinese | WPRIM | ID: wpr-921849

ABSTRACT

Fibrinogen (Fg) in human plasma plays an important role in hemostasis, vascular repair and tissue integrity. The surface chemistry of extracellular matrix or biological materials affects the orientation and distribution of Fg, and changes the exposure of integrin binding sites, thereby affecting its adhesion function to platelets. Here, the quantity, morphology and side chain exposure of Fg adsorbed on hydrophilic, hydrophobic and avidin surfaces were measured by atomic force microscopy (AFM) and flow cytometry (FCM), then the rolling behavior of platelets on Fg was observed through a parallel plate flow chamber system. Our results show that the hydrophobic surface leads to a large amount of cross-linking and aggregation of Fg, while the hydrophilic surface reduces the adsorption and accumulation of Fg while causing the exposure and spreading of the α chain on Fg and further mediating the adhesion of platelets. Fg immobilized by avidin / biotin on hydrophilic surface can maintain the monomer state, avoid over exposure and stretching of α chain, and bind to the platelets activated by the A1 domain of von Willebrand factor instead of inactivated platelets. This study would be helpful for improving the blood compatibility of implant biomaterials and reasonable experimental design of coagulation


Subject(s)
Adsorption , Blood Platelets , Fibrinogen , Humans , Platelet Adhesiveness , von Willebrand Factor
3.
Article in Chinese | WPRIM | ID: wpr-921828

ABSTRACT

Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither β2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.


Subject(s)
Cytoskeletal Proteins , Endothelial Cells , Extracellular Traps , Integrins , Intercellular Adhesion Molecule-1 , Lipopolysaccharides/pharmacology , Macrophages , Neutrophils
4.
Article in Chinese | WPRIM | ID: wpr-884511

ABSTRACT

Objective:Before the radiotherapy was performed, patients with pelvic tumors were analyzed for the consistency of bladder filling in the three steps of " Immobilization" , " CT Simulation" and " X-ray Simulation" .Methods:In 2014, 105 patients (68 cases of cervical cancer, 32 cases of rectal cancer, 3 cases of vaginal cancer and 2 cases of prostate cancer) with pelvic tumor radiotherapy were randomly assigned to monitor bladder urine volume to a target urine volume of 400 ml. First, patient were exhorted to empty the bladder, and the bladder volume meter BVI 9400 was used to measure the urine volume of the patient after emptying of the bladder. The patient immediately drank about 540 ml of water and suppressed urine, measurements were taken every 0.5 h. At the same time, when the patient complained of " urgency of urine" , bladder urine volume would be measured again and the time would also be recorded. Every other half an hour (emptying, 0.5 h after emptying, 1.0 h after emptying), when complaining of " urgency of urine" , when actually performing urine volume and time were described as: U 0 and t 0, U 0.5 and t 0.5, U 1.0 and t 1.0, U t and t, U T and T. Results:There was a statistically significant difference in gender and age, and women had stronger ability to urinate than men U 1.0( P=0.003), young people had stronger ability to urinate than middle-aged U 1.0( P=0.002). In the three-step comparison, there was no statistically difference between 1 hour after emptying urine volume U 1.0( P=0.177) and the actually performing urine volume U T ( P=0.052). And the final urine volume was concentrated at 298-526 ml. After the patient emptied the urine volume and complained of " urgency of urine" , the time slot was t=(75.2±49.9) min, with the urine volume of U t=(331.2±140.3) ml. And there was no statistically difference between U t and U T ( P=0.198) at X-ray Simulation. Conclusions:The patient emptied the bladder and immediately drank 540 ml of water. After 1 hour of suppressing urine, he complained of " urgency of urine" and achieved the target urine volume (400 ml). At this time, the bladder urine volume U 1.0 was consistency in the immobilization, CT Simulation, and X-ray Simulation.

5.
Article in Chinese | WPRIM | ID: wpr-912773

ABSTRACT

Primary hospitals are engaged in such responsibilities as diagnosis and treatment of endemic diseases and common illnesses of the locality, as well as relevant research work which bears more prominent importance than ever before. Given the importance of research, the hospitals are mostly plagued by such setbacks as obsolete research management concepts, poor experiences, poor perception of research, poor professional competency and lack of academic exchange among the medical workers. A primary hospital had set up a novel management mechanism, featuring " full-staff involvement, full-process supervision and full-dimensional guidance" , and " tight formal examination and tight content examination" . This mechanism has been in place since 2016 in research project management practice, achieving such progresses as significant rise in the number of research project applications, that of approved projects, and project implementation capabilities.Future improvements in this regard should be made in higher pertinence, optimized management flow and better research service system.

6.
Article in Chinese | WPRIM | ID: wpr-869919

ABSTRACT

Objective:To evaluate the role of heme oxygenase-1 (HO-1)-induced endogenous protection in lipopolysaccharide (LPS)-caused apoptosis in rat alveolar macrophages and the relationship with endoplasmic reticulum stress.Methods:Alveolar macrophages of rats were randomized into 4 groups ( n=32 each) using a random number table method: control group (group C), LPS group (group L), Con siRNA group and HO-1 siRNA group. Cells were cultured normally in group C, and 10 μg/ml LPS was added to the culture medium in the other three groups. Con siRNA and HO-1 siRNA transfection was performed at 48 h before adding LPS in Con siRNA and HO-1 siRNA groups. At 24 h of treatment with LPS, MTT method was used to measure the cell viability, flow cytometry was used to determine the cell apoptosis rate, and Western blot was used to detect the expression of glucose regulatory protein 78 (GRP78), phosphorylated kinase receptor-like endoplasmic reticulum kinase (p-PERK), CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylated type I endoplasmic reticulum transmembrane protein kinase (p-IRE-1), phosphorylated stress-activated protein kinase (p-JNK) and caspase-12. Results:Compared with group C, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1, GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in the other three groups ( P<0.05). Compared with group L, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1 was down-regulated, and the expression of GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in group HO-1 siRNA ( P<0.05), and no significant change was found in each parameter in group Con siRNA ( P>0.05). Compared with group Con siRNA, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1 was down-regulated, and the expression of GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in group HO-1 siRNA ( P<0.05). Conclusion:The mechanism of HO-1-induced endogenous protection is related to inhibiting endoplasmic reticulum stress and then reducing LPS-induced apoptosis in alveolar macrophages of rats.

7.
Chinese Journal of Urology ; (12): 434-438, 2020.
Article in Chinese | WPRIM | ID: wpr-869673

ABSTRACT

Objective:To evaluate the efficacy and safety of Tyrosine Kinase Inhibitors (TKIs) combined with stereotactic body radiation therapy(SBRT) in the treatment of renal cell carcinoma (RCC) patients with bone metastasis.Methods:The clinical data of 80 RCC patients with bone metastasis in Sun Yat-sen University Cancer Center from April 2010 to April 2020 were analyzed retrospectively. Among them, 64 patients were medium or high risk according to the International Metastatic Renal Cell Carcinoma Database Consortium(IMDC) score. Twenty-four patients received TKI therapy alone(Group A), and the other 56 cases received TKIs combined with SBRT to bone metastastic lesions (Group B).Results:The median follow-up period was 20.7 months (4.8-115.6 months), 70 patients received second or third-line targeted drug therapy, and 4 patients in group A and 15 patients in group B received TKI plus immunotherapy. Fifty-four patients had symptoms of bone pain before radiotherapy, 46 patients were satisfied with the analgesic effect after SBRT treatment. Twelve patients got complete response (CR) after bone lesions, and 32 patients achieved partial response (PR). Forty patients died of disease progression during follow-up. The median OS was: 20.7 months vs not reached(Group A vs. Group B), and the 2-y OS and 5-y OS were 50% vs. 62%, and 19% vs. 56%, respectively ( P=0.006). There were only 2 patients (3.6%) had grade 3 SBRT related adverse events. Conclusions:SBRT combined with TKIs improved the quality of life and prolonged the overall survival of RCC patients with bone metastasis.

8.
Journal of Medical Biomechanics ; (6): E331-E337, 2020.
Article in Chinese | WPRIM | ID: wpr-862389

ABSTRACT

Objective To investigate the mechanism of mechano-chemical coregulation in chemokine-induced calcium response of Jurkat T cells under fluid shear stress (FSS). Methods By using parallel-plate flow chamber combined with fluorescence microscope, the calcium response of Jurkat T cells on CXCL12 was observed to extract the corresponding characteristic parameters under static or flow state, with or without extracellular Ca2+, respectively. Results Immobilized CXCL12 could induce firm adhesion of the circulating Jurkat T cells, and the arrested cells increased with the increase of CXCL12 concentration. Force could trigger the calcium response of Jurkat T cells and sharply raised the activation ratio from 4% up to 75% when the FSS increased from 0 to 20 mPa. Under 20 mPa FSS, extracellular Ca2+ could stimulate quickly the calcium response by shortening the delay time (about 23 s), and enhance calcium intensity by prolonging the climbing time (about 7 s) and half time (about 20 s). Conclusions The cooperation between FSS and extracellular Ca2+ would accelerate and enhance CXCL12-mediated-calcium response of Jurkat T cells, which indicated a fast mechanosensitive pathway through ‘extracellular calcium influx-intracellular calcium store release’. The research results would contribute to understanding the process of T cells activation and providing the clue for relevant pathological and drug research.

9.
Journal of Medical Biomechanics ; (6): E195-E201, 2020.
Article in Chinese | WPRIM | ID: wpr-862312

ABSTRACT

Objective To investigate the interaction between von Willebrand factor (vWF) A1 and A3 domain, and type 2 M mutant W1745C-A3 effect on thermal stability and mechanical stability of A3/A1. Methods The crystal structures of A1 and A3 were downloaded from Protein Data Base (PDB). The wild-type (WT) A3/A1 structure was obtained by using SwarmDock Server, then W1745C-A3/A1 mutant was constructed by replacing the Trp1745 with Cys1745 in A3/A1. Through steered molecular dynamics simulation, formation and evolution of hydrogen bond and salt bridge between A1 and A3 interfaces were observed, and the differences in conformation, disrupted force and dissociation time between WT-A3/A1 and W1745C-A3/A1 were compared. Results There were 5 pairs of hydrogen bonds with survival rate > 0-2 and 1 pair of salt bridge with survival rate > 0-5 between A1 and A2. The W1745C-A3/A1 complex could withstand greater disrupted force and longer dissociation time compared with WT-A3/A1, by improving the stability of hydrogen bonds and increasing 1 pair of stable salt bridge. Conclusions The interaction between A1 and A3 would hinder the binding sites of A1 to GPIbα, and the W1745C-A3 mutation would further reduce the affinity of A1 to platelets. These results provide references for revealing the molecular mechanism of von Willebrand diseases in the clinic and developing the corresponding drugs targeted to hemostasis disorders.

10.
Chinese Journal of Endemiology ; (12): 416-419, 2020.
Article in Chinese | WPRIM | ID: wpr-866131

ABSTRACT

Objective:To analyze the dynamic characteristics of rodents population density distribution in plague foci of Yinchuan City, Ningxia, and to provide reference for early warning of the plague.Methods:The plague surveillance results and epidemic reports of Yinchuan City from 2015 to 2018 were collected retrospectively, and the data were obtained from the database of Yinchuan City Center for Disease Control and Prevention. Descriptive method was used to analyze the species, number, density, fleas, vector index, etiology and serology results of rodents in the plague foci.Results:From 2015 to 2018, 4 families, 8 genera, 13 species, and 8 843 rodents were captured in the plague foci of Yinchuan City, and Meriones unguiculatus (4 557 rodents) was the dominant species. The survey area of host animal density was 1 459 hm 2, 3 805 rodents were captured, and the average density was 2.61/hm 2, of which the Meriones unguiculatus density was 1.98/hm 2. A total of 41 488 traps of nocturnal rodents were investigated, and 2 660 rodents were captured, with an average capture rate of 6.41%. A total of 6 952 fleas were obtained, belonging to 4 families, 7 genera, and 8 species; Xenopsylla conformis conformis (4 597 fleas) and Nosopsyllus laeviceps kuzenkovi (1 761 fleas) were the dominant species. Among them, there were 2 286 flea-infected rodents, the body flea-infected rate was 25.85% (2 286/8 843), and the body flea-infected index was 0.76. A total of 220 gerbils nests were investigated, and the nest flea-infected rate was 34.55% (76/220), and the nest flea-infected index was 0.98. No plague bacterium was isolated by pathogen detection of rodents and fleas. The results of indirect hemagglutination test were all negative. Conclusion:The Meriones unguiculatus is the dominant species in the plague foci of Yinchuan City, the average density is still high, attention should be paid to the occurrence of plague outbreaks.

11.
Journal of Medical Biomechanics ; (6): E043-E048, 2020.
Article in Chinese | WPRIM | ID: wpr-804508

ABSTRACT

Objective To investigate the effects of fluid shear stress on rolling adhesion of neutrophils on immobilized platelets under flows. Methods Experiments were performed at the parallel plate flow chamber. Platelets were adhered to the functionalized flow chamber bottom which were coated with vWF-A1 first, and then washed with PBS under wall shear stress (WSS) of 1 Pa for different time (0 min, 2.5 min, 7.5 min). A high-speed camera was used to observe and record the rolling adhesion events of neutrophils on immobilized platelets under 50 mPa WSS, and the adhesion parameters such as the number of adhesion events, the tether lifetime of cells and rolling velocity. Results Neutrophils could specifically bind to the immobilized platelets on vWF-A1-coated bottom of the flow chamber. Mechanical stimulation on immobilized platelets had no effects on the tether lifetime of neutrophils on the platelets, but up-regulated the adhesive ratio of neutrophils on the platelets and slowed down the rolling of neutrophils on the platelets. Conclusions Mechanical stimulation on the immobilized platelets will significantly make the circulating neutrophils to be captured easily and promote the rolling adhesion of neutrophils on platelets.

12.
Article in Chinese | WPRIM | ID: wpr-745653

ABSTRACT

Objective To evaluate the effect of doxofylline on pulmonary inflammatory response induced by mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD).Methods Thirty adult male Sprague-Dawley rats,aged 8 weeks,weighing 200-250 g,were divided into 3 groups (n=10 each) using a random number table method:control group (C group),COPD group and doxofylline group (Dox group).Rats were fed in normoxia for 2 months,and normal saline 0.2 ml was injected into the trachea on 1st and 30th days in C group.Rats were exposed to cigarette smoke for 30 min every day,lasting for 2 months,and lipopolysaccharide 200 μg (0.2 ml) was injected into the trachea on 1st and 30th days in COPD and Dox groups.Two months later,rats in each group were anesthetized,tracheally intubated,and then mechanically ventilated.Doxofylline 50 mg/kg was intravenously injected immediately after intubation in Dox group,and the equal volume of normal saline was given instead in C and COPD groups.Pulmonary specimens were taken after 120 min of mechanical ventilation for examination of pathological changes and for determination of wet/dry weight ratio (W/D ratio) and tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) contents (by enzyme-linked immunosorbent assay).Results No significant pathological change of lung tissues was found in C group,and COPD pathological changes were observed in COPD and Dox groups.Compared with C group,the W/D ratio and TNF-α level were significantly increased,and the IL-10 level was decreased in COPD and Dox groups (P<0.05).Compared with COPD group,the W/D ratio and TNF-α level were significantly decreased,and the IL-10 level was increased in Dox group (P<0.05).Conclusion Doxofylline can reduce the pulmonary inflammatory response induced by mechanical ventilation in rats with COPD.

13.
Article in Chinese | WPRIM | ID: wpr-773315

ABSTRACT

Supported lipid bilayers (SLBs) have been widely used in biomedical and bioengineering research because its structure and function are similar to natural cell membrane. A fluorescence recovery after photobleaching (FRAP) technique was used to measure the lateral diffusion of the SLBs composed of 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1, 2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxyp-entyl) iminodiacetic acid)] (DGS-NTA) on the glass slide, and the effects of the DOPC-to-DGS-NTA ratio, small unilamellar vesicles (SUV) producing method, sizes of bleaching areas and concentrations of loading proteins on the SLBs fluidity and diffusion coefficient were studied systematically in this paper. The results demonstrated that: (1) SUV made by probe sonication exhibited more uniform and smaller size compared with that made by film extrusion, but the whole process of SLBs formation must not be exposed to air. (2) The fluorescence recovery rate and diffusion coefficient of the SLBs decreased with the increasing bleaching area size. With the mole ratio of DOPC to DGS-NTA decreasing from 98∶2 to 84∶16, the fluidity and fluorescence recovery degree decreased gradually, and the SLBs would lose its fluidity if the ratio reached to 82∶18. (3) The average fluorescence intensity of SLBs increased linearly with the loading protein concentration (10-40 nmol·L ), and the protein showed good mobility on the SLBs. The study would provide a good platform of bio-membrane for further research on interactions among cell membrane molecules and subsequent signals response.

14.
Journal of Medical Biomechanics ; (6): E083-E090, 2019.
Article in Chinese | WPRIM | ID: wpr-802509

ABSTRACT

Objective To investigate the shear rate and VWF-A1-mediated platelets calcium response. Methods Flou-4 AM was used as the fluorescent indicator of intracellular calcium, and the intracellular calcium concentrations of adherent platelets on VWF-A1 with different concentrations at different shear rates were detected by parallel plate flow chamber system combined with fluorescence microscope. The effect of shear stress and chemical signaling on intensity and speed of calcium response was also analyzed. Results VWF-A1 specifically mediated platelet adhesion and calcium response under flow. The shear rate and molecular concentrations had positive regulation of platelets activation ratio and negative regulation of delay time of calcium response. Compared with static conditions, the activation ratio was increased by 37 times at shear rate of 500 s-1. When the concentration of VWF-A1 was increased from 60 mg/L to 240 mg/L, the delay time of calcium response was shortened by 10 s. Conclusions The shear rate could modulate the calcium response of platelets in cooperation with VWF-A1. The result of this study will be helpful to deepen the understanding about the process of hemostatic reaction of platelet coagulation in bloodstream.

15.
Article in Chinese | WPRIM | ID: wpr-732887

ABSTRACT

Objective To investigate the impacts of garcinia acid on the proliferation and invasion abilities of human bladder cancer cell line(BIU-87), and to study the possible molecular mechanisms. Methods The BIU-87 cells were cultured in vitro, and then the cells were divided into control group, low-dose, middle-dose, and high-dose garcinia acid groups. The cells in the drug groups were treated with 20, 40, 80μmol/L of garcinia acid for 24, 48, and 72 h, and control group were incubated by normal medium. The inhibition of proliferation of BIU-87 cells was performed using CCK8 assay. The abilities of BIU-87 cell invasion were assessed using Transwell chambers, and the expression levels of vascular endothelial growth factor(VEGF) were analyzed using Western Blot technology.Results Compared with control group, the proliferation inhibitory rates of cells after treatment with low-, middle-, and high-dose garcinia acid for 24, 48, and 72 h were significantly decreased(P<0.05). Moreover, the proliferation inhibitory rates in different drug groups were greatly increased with the time extension. Compared with control group, the number of cells passing through the membrane(26 ± 4, 41 ± 4, 53 ± 5vs.119 ± 7) in low-, middle-, and high-dose garcinia acid group significantly decreased(P<0.05), the expression levels of VEGF (41.2 ± 6.2, 23.8 ± 5.2, 17.9 ± 4.7 vs. 14.8 ± 4.2) in low-, middle-, and high-dose garcinia acid group significantly decreased(P<0.05).Conclusions The Garcinia acid can inhibit the proliferation and invasion of BIU-87 cells via the down-regulation of VEGF expression.

16.
Article in Chinese | WPRIM | ID: wpr-806643

ABSTRACT

Objective@#Quadrivalent influenza vaccines contain two lineages of type B virus, this study aimed to assess whether the result of single radial immunodiffusion (SRID) are accurate. The cross-interference of two type B hemagglutinins remains unknown.@*Methods@#We detected the vaccine samples developed by Jiangsu GDK Biological Technology Co., ltd by SRID.@*Results@#There was no significant difference between the HA content of antigen reagent, bulk sample and mixed sample of two B bulk within 10 to 40 μg/ml (P>0.05). Then each hemagglutinin B was diluted respectively by other three HA, 30 μg/ml, the other hemagglutinin B or phosphate buffer solution were measured within 10-160 μg/ml. Within 10-40 μg/ml, the HA content was proportional to the diameters of immunodiffusion (R2=0.998), while within the higher content range, a ternary linear regression equation fitted best (R2=0.999).@*Conclusions@#No cross-interference between B/Brisbane and B/Phuket was found in SRID within both detection ranges.

17.
Article in Chinese | WPRIM | ID: wpr-806641

ABSTRACT

Objective@#To investigate the relationship between the mutations in precore/core (preC/C) region of hepatitis B virus (HBV) gene and the postoperative survival in patients with hepatocellular carcinoma.@*Methods@#A total of 81 cases in HBV associated hepatocellular carcinoma (HBV-HCC) patients with cancer tissue genomic DNA were extracted. The preC/C region of HBV was amplified and sequenced, and survival-associated HBV mutations were identified according to the NCBI database. The relationships between the mutations in the preC/C region and HCC survival was analyzed with the Kaplan-Meier method and the Cox proportional hazards model. Eleven mutational sites were identified as statistically significant independent predictors of HBV-HCC postoperative survival.@*Results@#The portal vein thrombosis, tumor TNM classification and size were identified as statistically significant independent predictors of survival in HBV-HCC patients. In the research, we found that seven mutational sites in preC/C region of HBV were associated with independent risk factors for postoperative survival in patients of HBV-HCC. The following five mutational sites were identified as statistically significant independent predictors of HBV-HCC survival: 1915, 2134, 2176, 2221, 2260. The mutational site of 1979 and 2245 were identified for the association with survival at a borderline significance level.@*Conclusions@#The portal vein thrombosis, tumor TNM classification, size and seven mutational sites in the PreC/C region were identified as independent predictors of postoperative survival in HCC patients.

18.
Article in Chinese | WPRIM | ID: wpr-806317

ABSTRACT

Objective@#To evaluate the immunogenicity of high-dose inactivated quadrivalent influenza serial vaccines (split virion) for elderly people.@*Methods@#Immunogenicity assays on mouse as research animal model with inactivated quadrivalent influenza serial vaccines (split virion) were carried out. Then rates of seroconversion and geometric mean hemagglutination inhibition titers (GMTs) at day 21 after the last vaccination among those who received high-dose (HD) A+ B influenza vaccine, were compared with those who received other vaccines by hemagglutination inhibition (HAI) test.@*Results@#The result of HAI test showed in HD serial vaccine groups, GMTs for all kinds of HA in the two HD serial vaccine groups were significantly different from that of the two SD serial vaccine groups, respectively (P<0.0001), but not the titers for A3 in one B dose first group. Further- more, GMTs for strain A in one B dose first groups were significantly higher than that of one B dose first groups in both HD and SD groups, and vice versa in the GMTs for strain B. The result of the assay of the impact of different immunization intervals of HD serial influenza vaccine on immunogenicity indicated that the immunity responses in 7 or 10 d groups were higher than that in 3 d group.@*Conclusions@#It is a new method to prevent the flu for elderly by HD A+ B serial influenza vaccine, whose HA dose per immunization was reduced into two injections, worked best when the immunization interval was 7-10 d. The protective immunity can be improved by selecting immune procedure of the serial vaccine according to the epidemic type surveillance of influenza virus A and B strains.

19.
Article in Chinese | WPRIM | ID: wpr-687602

ABSTRACT

The intracellular domain of clusters of differentiation 44 (CD44) binding to the FERM (protein 4.1-ezrin-radixin-moesin) domain of ERM (ezrin/radixin/moesin) proteins and furthermore triggering the recruitment of spleen tyrosine kinase (Syk) are very important in the process of tumor cell adhesion, migration and proliferation. At first, it was found that CD44/FERM structure was stable by observing CD44/FERM complex conformation and analyzing the interaction of interface residues both in static crystal structure and in equilibrium process. Meanwhile, unconventional immunoreceptor tyrosine-based activation motif (ITAM-like), and phosphorylation sites Y191 and Y205 were buried in FERM domain, which would hinder the phosphorylation of ERM proteins, the recruitment of Syk and subsequent signal transduction. Then, steered molecular dynamics simulation was applied to simulate the interaction between CD44 and FERM domain in the mechanical environment. The results showed that mechanical signal could induce the exposure of the ITAM-like motif and phosphorylation site Y205 by tracking and analyzing CD44/FERM complex conformational changes and the solvent-accessible surface area. This study revealed how the force regulates the activation of downstream signal through CD44 intracellular domain for the first time, and would be useful for further understanding the adhesion and migration pathway of cancer cells and the design of antitumor drugs.

20.
Journal of Medical Biomechanics ; (6): E248-E254, 2018.
Article in Chinese | WPRIM | ID: wpr-803796

ABSTRACT

Objective To investigate the effect of calcium on the stability of VWF-A2 domain. Methods The crystal structures of A2 (not containing calcium) and A2/Ca2+ (with calcium bound) were downloaded from protein data bank. For A2 domain, the conformational changes, unfolding pathway differences and the exposure degree variance of cleavage sites caused by calcium binding were observed and analyzed by steered Molecular Dynamics simulations under constant force. Results The unfolding pathway of A2 domain and exposure process of cleavage sites were force-dependent. Calcium binding did not affect the unfolding process of A2 in the early stage. As the conformational rearrangement of α3β4-loop reduced its localized dynamic properties, the movement among β1-β4-β5 strands was restrained, which suppressed its further unfolding to stay in the intermediate steady state and delayed the cleavage-site exposure. Conclusions Stretch force could induce β5 strand of A2 unfolding and the cleavage-site exposure, while calcium binding inhibited ADAMTS13 proteolysis efficiency through stabilizing A2 hydrophobic core and covering its cleavage sites. These results way help to understand how ADAMTS13 cleavages the VWF-A2 domain and regulates the hemostatic potential of VWF, and further provide useful guidance on the design of related anti-thrombus drugs.

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