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As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.
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Objective:To investigate whether hepatitis B virus X protein (HBx) mediates the podocyte injury through reactive oxygen species (ROS) /nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway.Methods:HBx-overexpressing lentivirus was transfected into renal podocytes of mouse to mimic the pathogenesis of hepatitis B virus-associated glomerulonephritis. Podocytes were divided into the following five groups: blank control group (no special treatment), negative control group (transfected with control lentivirus), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+NLRP3 siRNA group (transfected with HBx overexpression lentivirus and NLRP3 siRNA), and HBx overexpression+ROS inhibitor group (transfected with HBx overexpression lentivirus and adding ROS inhibitor). The morphological changes of podocytes were observed with electron microscope. The generation of ROS was detected by dichlorodihydrofluorescein diacetate assay (DCFH-DA). Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to detect caspase-1 activity, and the levels of lactate dehydrogenase, interleukin (IL)-1β and IL-18. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression levels of mRNA and protein of pyroptosis-related protein, such as NLRP3, apoptosis-associated speck-like protein containing card (ASC), caspase-1, IL-1β and IL-18. TUNEL staining and flow cytometer were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression levels of desmin and nephrin.Results:After successful infection of podocytes with HBx-overexpressing lentivirus, pyroptosis-related morphological changes in the cells were observed under electron microscope. The level of ROS in the HBx overexpression group was significantly higher compared to the negative control group ( P<0.05). Hoechst 33342 staining revealed condensed nuclei in the HBx overexpression group. TUNEL staining and flow cytometer demonstrated that podocytes underwent increased pyroptosis in the HBx overexpression group. The mRNA and protein expression levels of pyroptosis-related proteins such as NLRP3, ASC, caspase-1, IL-1β and IL-18 were up-regulated upon HBx overexpression (all P<0.05). Caspase-1 enzyme activity, lactate dehydrogenase and desmin expression levels were enhanced after HBx overexpression (all P<0.05). However, NLRP3 knockdown or addition of ROS inhibitors attenuated the pyroptosis and increased expression levels of pyroptosis-related proteins caused by HBx overexpression (all P<0.05). Conclusion:ROS/NLRP3 pathway plays an important role in HBx-induced podocyte pyroptosis.
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Objective To investigate the pathology, epidemiology of severe pneumonia in Xicheng District of Beijing. Methods From 2014 to 2020, in 3 sentinel hospitals, collected and detected the respiratory tract specimens of the severe pneumonia patients. Multiple pathogens including Stenotrophomonas maltophilia, Streptococcus pyogenes, Staphylococcus aureus, Klebsiella Pneumoniae, Haemophilus influenzae, Legionella pneumophila, Mycobacterium tuberculosis, Acinetobacter baumannii, Moraxella catarrhalis, Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Pneumocystis,Parainfluenza virus, Bocavirus, Rhinovirus, Coronavirus, Influenza, Human metapneumovirus, Adenovirus, Respiratory syncytial virus, Enterovirus, Mycoplasma pneumoniae, Chlamydia pneumoniae were detected with PT-PCR. Analyze epidemic characteristics of the cases. Results Of the 1 247 respiratory samples cultured during the period from 2014 to 2020, 560(44.91%) are positive. The positive rates of virus(29.91%) is higher than Bacteria(20.21%). The top five pathogens were Acinetobacter baumannii(9.22%), Pseudomonas aeruginosa(8.26%), Stenotrophomonas maltophilia(7.78%), Klebsiella Pneumoniae（6.74%） and Parainfluenza virus（6.58%）. Conclusion There was a variety of pathogen in the severe pneumonia patients. Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Klebsiella Pneumoniae and Parainfluenza virus were the main pathogens of respiratory infections in Xicheng district of Beijing. It is necessary to strengthen the surveillance of the disease.
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Objective To determine the effect of trunk motion control on knee biomechanics during single-leg landing. Methods Twenty male healthy basketball players were recruited. The kinematics, kinetics parameters and surface electromyogram (EMG) of knee joints under trunk motion control during single-leg landing were studied by using Vicon motion Analysis system, Kistler force platform and Noraxon surface EMG system. Results Compared with natural landing, there were significant differences in flexion angle at initial contact moment, peak flexion angle and peak flexion moment during deeply inspiratory landing and landing with a stick, and a significantly larger flexion angle at initial contact moment, a larger peak flexion angle and smaller peak flexion moment were also found. Compared with natural landing, there was no statistical difference in peak valgus angle and peak valgus moment, as well as EMG activity of hamstrings, quadriceps muscles of the knee during deeply inspiratory landing and landing with a stick. Conclusions Deeply inspiratory landing or landing with a stick reduce the risk of anterior cruciate ligament (ACL) injury, and the results provide the theoretical basis for prevention of ACL injuries in basketball players during landing.
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Epstein-Barr virus (EBV) is a common viral pathogen in children.EBV infection can cause childhood tumors,immune-related diseases and respiratory-related diseases.The proportion of EBV infection in Chinese children is high and the age of primary infection is early.Its pathogenesis is closely related to B lymphocytes,natural killer cells and gene defects.Clinical EBV infection is not only associated with childhood tumors and immune-related diseases,but also causes respiratory-related diseases that deserve more attention.
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Objective@#To understand the situation of inoculation and influencing factors of children in the Xicheng District of Beijing after the enterovirus 71（EV71）vaccine was marketed .@*Methods@#A questionnaire survey was conducted among the parents of children aged 6 to 35 months in the vaccination clinics in Xicheng District from May to September 2017. Demographic characteristics,awareness of hand-foot-mouth disease and EV71 vaccine,the access to these knowledge,acceptance of the vaccine price and advice on the management were collected. The influencing factors for EV71 vaccination were analyzed by multivariate logistic regression .@*Results@# There were 1 850 out of 1 885 parents investigated,with the effective rate of 98.14%. The EV71 vaccination rate of children aged 6 to 35 months was 27.03%. The awareness rate of hand-foot-mouth disease and EV71 vaccine in parents was 55.95%. The results of logistic regression analysis showed that the parents with the annual household income of 50 000 yuan and above （OR50 000 yuan- =2.665,95%CI：1.535-4.628;OR100 000 yuan-=4.732,95%CI：2.830-7.914;OR200 000 yuan-=3.576,95%CI：2.084-6.135）,with acceptance of 100 yuan and above in the price of the vaccine （OR100 yuan-= 9.487,95%CI：6.873-13.096;OR200 yuan-=5.940,95%CI：3.465-10.183;OR300-500 yuan-=2.415,95%CI：1.183-4.933）,with more than two sources of the information for EV71 vaccine （OR=3.062,95%CI：2.306-4.065）,without the care about the management of the EV71 vaccine（OR=1.650,95%CI：1.156-2.356）were more likely to have their children vaccinated;while the parents who lived in bungalows and cabinets （OR=0.589,95%CI：0.386-0.899）,who were medical staff（OR=0.240,95%CI：0.118-0.487）,who were not residents of Beijing（OR=0.587,95%CI：0.399-0.863）,who had more than one children （OR=0.338,95%CI：0.236-0.483） were less likely to have their children vaccinated .@*Conclusion@#The parents of children aged below three years in Xicheng District of Beijing should improve their awareness of hand-foot-mouth disease and EV71 vaccine. The vaccination rate of EV71 were mainly related to the registration,occupation,number of children, household income,the access to the information about vaccine,acceptance of the vaccine price and advice on the management in parents.
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Epstein-Barr virus (EBV) is a common viral pathogen in children.EBV infection can cause childhood tumors, immune-related diseases and respiratory-related diseases.The proportion of EBV infection in Chinese children is high and the age of primary infection is early.Its pathogenesis is closely related to B lymphocytes, natural killer cells and gene defects.Clinical EBV infection is not only associated with childhood tumors and immune-related diseases, but also causes respiratory-related diseases that deserve more attention.
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Objective To investigate the clinical applications of the chain locking-type tension bands. Methods89 cases with patellar bone fractures,27 olecranal fractures patients,18 patients with fractures of surgical neck of humerus,16 patients with dislocation of the acromioclavicular joints and 12 patients with clavicular lateral fractures were treated with chain locking-type tension bands. ResultsTheResultsshowed that all patients wound were postoperative first intention.The healing time of the fractures were 6 ～ 18 months(average 10 months).The Kirschner's pins lapping,steel wire breaks and tension bands out of control were not found. ConclusionCompared with the traditional tension bands,the chain locking-type tension bands had stronger stability,stress distribution more even and less complications.