ABSTRACT
Conjunctivitis is an inflammatory disease of the conjunctival tissue caused by a variety of causes; despite the conjunctiva being directly exposed to the external atmospheric environment, the important role of air pollution is not fully evaluated, especially in areas with poor air quality undergoing rapid economic and industrial development. Information on 59,731 outpatient conjunctivitis visits from 1 January 2013 to 31 December 2020 was obtained from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China), and data on six air pollutants including particulate matter with a median aerometric diameter of less than 10 and 2.5 mm (PM10 and PM2.5, respectively), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) from eleven standard urban background fixed air quality monitors were also recorded. A time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) were used to fit the effect of exposure to air pollutants on the risk of conjunctivitis outpatient visits. Further subgroup analyses were conducted for gender, age, and season, as well as the type of conjunctivitis. Single and multi-pollutant models showed that exposure to PM2.5, PM10, NO2, CO, and O3 was associated with increased risk of outpatient conjunctivitis visits on the lag 0 day and various other lag days. Variations in the effect estimates on direction and magnitude were found in different subgroup analyses. We conducted the first time-series analysis with the longest duration as well as the largest sample size in Northwest China, which provides evidence that outpatient conjunctivitis visits is significantly associated with air pollution in Urumqi, China. Meanwhile, our results demonstrate the effectiveness of SO2 reduction in reducing the risk of outpatient conjunctivitis visits in the Urumqi region and reaffirm the need to implement special air pollution control measures.
Subject(s)
Air Pollutants , Air Pollution , Conjunctivitis , Humans , Outpatients , Nitrogen Dioxide/analysis , Air Pollution/analysis , Air Pollutants/analysis , Particulate Matter/analysis , China/epidemiology , Conjunctivitis/chemically inducedABSTRACT
This study investigates the influence expression of the MYCN oncogene has on the DNA damage response, replication fork progression and sensitivity to PARP inhibition in neuroblastoma. In a panel of neuroblastoma cell lines, MYCN amplification or MYCN expression resulted in increased cell death in response to a range of PARP inhibitors (niraparib, veliparib, talazoparib and olaparib) compared to the response seen in non-expressing/amplified cells. MYCN expression slowed replication fork speed and increased replication fork stalling, an effect that was amplified by PARP inhibition or PARP1 depletion. Increased DNA damage seen was specifically induced in S-phase cells. Importantly, PARP inhibition caused a significant increase in the survival of mice bearing MYCN expressing tumours in a transgenic murine model of MYCN expressing neuroblastoma. Olaparib also sensitized MYCN expressing cells to camptothecin- and temozolomide-induced cell death to a greater degree than non-expressing cells. In summary, MYCN expression leads to increased replication stress in neuroblastoma cells. This effect is exaggerated by inhibition of PARP, resulting in S-phase specific DNA damage and ultimately increased tumour cell death. PARP inhibition alone or in combination with classical chemotherapeutics is therefore a potential therapeutic strategy for neuroblastoma and may be more effective in MYCN expressing tumours.
ABSTRACT
The purpose of this study was to establish and validate an animal brain ischemia model in the recovery and sequela stages. A middle cerebral artery occlusion/reperfusion (MCAO/R) model in male Sprague-Dawley rats was chosen. By changing the rat's weight (260-330 g), the thread bolt type (2636/2838/3040/3043) and the brain infarct time (2-3 h), a higher Longa's score, a larger infarct volume and a greater model success ratio were screened using the Longa's score and TTC staining. The optimum model condition (300 g, 3040 thread bolt, 3 h brain infarct time) was acquired and used in a 1-90 day observation period after reperfusion via assessment of sensorimotor functions and infarct volume. At these conditions, the bilateral asymmetry test had a significant difference from 1 to 90 days, and the grid-walking test had a significant difference from 1 to 60 days; both differences could be a suitable sensorimotor functional test. Thus, the most appropriate condition of a novel rat model in the recovery and sequela stages of brain ischemia was found: 300 g rats that underwent MCAO with a 3040 thread bolt for a 3 h brain infarct and then reperfused. The appropriate sensorimotor functional tests were a bilateral asymmetry test and a grid-walking test.
Subject(s)
Brain Ischemia/physiopathology , Disease Models, Animal , Stroke Rehabilitation , Stroke/pathology , Animals , Brain/physiopathology , Brain Ischemia/rehabilitation , Infarction, Middle Cerebral Artery/pathology , Male , Rats , Rats, Sprague-Dawley , Reperfusion , Reperfusion InjuryABSTRACT
OBJECTIVE: To establish a novel method to isolate endothelial progenitor cellsï¼EPCï¼ from cryopreserved umbilical cord blood (cryoUCB), to investigate the biological characteristics of EPC and to improve the rate of EPC obtained from cryoUCB. METHODS: Twelve cryoUCB samples during 2000 to 2001 years were collected from allogeneic cord blood bank, cryoUCB was thawed rapidly in a water bath at 37 â, total nucleated cells (TNCs) were washed by phosphate-buffered saline (PBS). TNCs were seeded onto fibronectin-coated dishes to isolate EPC. Flow cytometry and immunofluorescence were used to identify EPC. The function of EPC was identified in vitro, such as the incorporation of Dil-Ac-LDL and FITC-UEA-I, the formation of capillary-like structure in matrigel, and the release of VEGF by ELISA. RESULTS: One to five cluster of cobble stone-like cells appeared at 2-3 weeks after seeding. Flow cytometric analysis showed that positive rates of CD31, CD34, CD144, and VEGFR (CD309) wereï¼92.91±5.20ï¼%, ï¼30.0±23.27ï¼%, ï¼88.55±3.83ï¼% and ï¼67.21±12.12ï¼% in passage 1 to passage 3 of EPC. EPC could uptake Dil-Ac-LDL and FITC-UEA-I, form capillary-like network on Matriget and release VEGF. CONCLUSION: EPC had been successfully isolated from cryopreserved umbilical cord blood by this method with high stability and reproducibility. EPC can be obtained in 85% frozen umbilical cord blood. This method may lay a foundation to supply abundant EPC for clinical application.
Subject(s)
Endothelial Progenitor Cells , Fetal Blood , Cell Differentiation , Cells, Cultured , Reproducibility of Results , Stem CellsABSTRACT
OBJECTIVE@#To establish a novel method to isolate endothelial progenitor cells(EPC) from cryopreserved umbilical cord blood (cryoUCB), to investigate the biological characteristics of EPC and to improve the rate of EPC obtained from cryoUCB.@*METHODS@#Twelve cryoUCB samples during 2000 to 2001 years were collected from allogeneic cord blood bank, cryoUCB was thawed rapidly in a water bath at 37 ℃, total nucleated cells (TNCs) were washed by phosphate-buffered saline (PBS). TNCs were seeded onto fibronectin-coated dishes to isolate EPC. Flow cytometry and immunofluorescence were used to identify EPC. The function of EPC was identified in vitro, such as the incorporation of Dil-Ac-LDL and FITC-UEA-I, the formation of capillary-like structure in matrigel, and the release of VEGF by ELISA.@*RESULTS@#One to five cluster of cobble stone-like cells appeared at 2-3 weeks after seeding. Flow cytometric analysis showed that positive rates of CD31, CD34, CD144, and VEGFR (CD309) were(92.91±5.20)%, (30.0±23.27)%, (88.55±3.83)% and (67.21±12.12)% in passage 1 to passage 3 of EPC. EPC could uptake Dil-Ac-LDL and FITC-UEA-I, form capillary-like network on Matriget and release VEGF.@*CONCLUSION@#EPC had been successfully isolated from cryopreserved umbilical cord blood by this method with high stability and reproducibility. EPC can be obtained in 85% frozen umbilical cord blood. This method may lay a foundation to supply abundant EPC for clinical application.
Subject(s)
Cell Differentiation , Cells, Cultured , Endothelial Progenitor Cells , Fetal Blood , Reproducibility of Results , Stem CellsABSTRACT
OBJECTIVE: To investigate the effects of Ningmitai Capsules (NMT) combined with doxycycline hydrochloride (DH) on chronic prostatitis induced by Ureaplasma urealyticum (Uu). METHODS: This randomized controlled trial included 240 male patients with Uuîpositive chronic prostatitis, treated orally with NMT at 4 capsules tid (n= 35), DH at 100 mg bid (n = 78), and NMT+DH at the corresponding doses (n = 127), respectively, all for 2 successive weeks. At 1 week after drug withdrawl, we conducted routine urine analysis, EPS examination, and drug sensitivity test of the cultured Uu. RESULTS: The positiveîtoînegative rate of Uu was significantly higher in the NMT+DH group than in the NMT and DH groups (89.0% ï¼»113/127ï¼½ vs 54.3% ï¼»19/35ï¼½ and 71.8% ï¼»56/78ï¼½, P< 0.05), so were the cure rate (25.2% vs 20.0% and 20.5%, P< 0.05) and total effectiveness rate (89.0% vs 54.3% and 71.8%, P< 0.05). CONCLUSIONS: The combination of Ningmitai Capsules and doxycycline hydrochloride is more effective than either Ningmitai Capsules or doxycycline hydrochloride used alone in the treatment of Uuîpositive chronic prostatitis.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Doxycycline/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Prostatitis/drug therapy , Ureaplasma Infections/drug therapy , Ureaplasma urealyticum , Capsules , Chemotherapy, Adjuvant , Chronic Disease , Humans , Male , Prostatitis/microbiology , Ureaplasma Infections/microbiologyABSTRACT
Objective To develop a teaching and examination system based on Delphi for the obstetric nurse. Methods The teaching materials were collected for the obstetric nurse, the teaching and examination mode was analyzed, and Delphi was used for programming and MySQL database was applied to teaching and examination data. Results The system had easy operation, high stability and rapid response to the database, and could meet the requirements for the teaching and examination of the trainee nurse. Conclusion The system realizes informatization and high expansibility of obstetric teaching and examination, and thus is worthy promoting practically.
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Objective To design an Android-based hand-hold intelligent terminal to meet the requirements for the portability of hyperbaric oxygen therapy information management system. Methods MT6582 processor was used as the primary control unit, which integrated the modules for display, communication, input and output. RAD Studio XE7 was applied to program development, and the main interface had the functions of charging and appointment. Results The hand-hold intelligent terminal gained advantages in stable connection with the server and rapid response, and enhanced the efficiency of hyperbaric oxygen therapy information management system greatly. Conclusion The terminal increases the portability of hyperbaric oxygen therapy information management system, and thus is worthy promoting practically.
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Objective To design a self-service terminal for hyperbaric oxygen therapy in order to improve the orderliness and efficiency of hyperbaric oxygen therapy.Methods The hardware included mainframe and cabinet,and the software used human-computer interface.Network database was connected with ADO technology,and Delphi 7.0,Pascal compiling code were applied to code compilation.Results The self-service terminal involved the patient into the information chain of hyperbaric oxygen therapy to enhance the working efficiency and therapy orderliness.Conclusion The terminal behaves well in hardware,software,network database and human-computer interaction,and thus is worthy promoting to medium and large hyperbaric oxygen chambers.
ABSTRACT
Objective To design and develop an information management system based on network database for hyperbaric oxygen therapy to solve the problems in repeated operation,excessive data,copying and etc.Methods Network database was used to establish the information storage unit,design software and hardware architecture as well as develop information treatment units for medical terminal,self service,hand-hold intelligent terminal,appointment App program and etc.Results The system realized rapid printing and recognition of patient information,quick response of server,high accuracy of charging module,and high efficiency of self service terminal and appointment registration.Conchusion The system optimizes hyperbaric oxygen therapy flow,enhances working efficiency of medical staffs and gains high patient satisfaction,and thus is worthy promoting clinically.
ABSTRACT
Objective To design a self-service terminal for hyperbaric oxygen therapy in order to improve the orderliness and efficiency of hyperbaric oxygen therapy.Methods The hardware included mainframe and cabinet,and the software used human-computer interface.Network database was connected with ADO technology,and Delphi 7.0,Pascal compiling code were applied to code compilation.Results The self-service terminal involved the patient into the information chain of hyperbaric oxygen therapy to enhance the working efficiency and therapy orderliness.Conclusion The terminal behaves well in hardware,software,network database and human-computer interaction,and thus is worthy promoting to medium and large hyperbaric oxygen chambers.
ABSTRACT
Objective To design and develop an information management system based on network database for hyperbaric oxygen therapy to solve the problems in repeated operation,excessive data,copying and etc.Methods Network database was used to establish the information storage unit,design software and hardware architecture as well as develop information treatment units for medical terminal,self service,hand-hold intelligent terminal,appointment App program and etc.Results The system realized rapid printing and recognition of patient information,quick response of server,high accuracy of charging module,and high efficiency of self service terminal and appointment registration.Conchusion The system optimizes hyperbaric oxygen therapy flow,enhances working efficiency of medical staffs and gains high patient satisfaction,and thus is worthy promoting clinically.
ABSTRACT
Adverse experiences early in life hamper the development and maturation of the hippocampus, but how early-life stress perturbs the developmental trajectory of the hippocampus across various life stages and the underlying molecular mechanisms remain to be investigated. In this study, we stressed male mice from postnatal day 2 (P2) to P9, and examined the potential role of CRHR1 in postnatal stress-induced structural remodeling of hippocampal CA3 pyramidal neurons directly after stress (P9), in mid-adolescence (P35) and in adulthood (P90). We found that early-life stress exposure significantly reduced apical dendritic arborization and spine density in CA3 neurons on P9 and P90. Moreover, postnatally stressed neurons underwent increased pruning of spines, especially thin spines, between P35 and P90. These stress-induced immediate and long-term structural abnormalities could be abolished by daily systemic administration of the CRHR1 antagonist antalarmin (20 µg/g of body weight) during stress exposure. However, such treatment strategy failed to attenuate the deleterious stress effects in mid-adolescence on P35. We then extended antalarmin treatment until the end of the second postnatal week, and found that prolonged blockade of CRHR1 could prevent the mid-term impact of early postnatal stress on structural remodeling of CA3 neurons. Our study characterized the influences of early-life stress on the developmental trajectory of hippocampal pyramidal neurons, and highlighted the critical role of CRHR1 in modulating these negative outcomes evoked by early-life stress.
Subject(s)
CA3 Region, Hippocampal/growth & development , Pyramidal Cells/physiology , Receptors, Corticotropin-Releasing Hormone/physiology , Stress, Psychological/physiopathology , Animals , CA3 Region, Hippocampal/pathology , Dendritic Spines/pathology , Female , Male , Mice , Mice, Inbred C57BL , Pyramidal Cells/pathology , Pyrimidines/administration & dosage , Pyrroles/administration & dosage , Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors , Stress, Psychological/pathologyABSTRACT
Magnetic skyrmions are topologically protected nanoscale objects, which are promising building blocks for novel magnetic and spintronic devices. Here, we investigate the dynamics of a skyrmion driven by a spin wave in a magnetic nanowire. It is found that (i) the skyrmion is first accelerated and then decelerated exponentially; (ii) it can turn L-corners with both right and left turns; and (iii) it always turns left (right) when the skyrmion number is positive (negative) in the T- and Y-junctions. Our results will be the basis of skyrmionic devices driven by a spin wave.
ABSTRACT
OBJECTIVE: This study was to expand the cytotoxic T lymphocytes (CTL) through inducing the differentiation of umbilical blood monomuclear cells (UBMNC) by using various combination of cytokines, and to investigate the functions of expanded CTL. METHODS: The MNC were isolated by ficoll density gradient centrifugation. Then, the PHA-P, IFN-γ combined with IL-2, IL-15 and other cytokines were used for induction and expansion of the cord blood-derived CTL. The biological function of CTL was examined by phenotype analysis, cytotoxic tests and real-time fluorescence quantitative PCR. RESULTS: After expansion for 15 days, the cell number increased by 1522% ± 137%. The content of CD3(-)CD8(-) cells in uncultured cord blood MNC was 95%, and the CD3(+)CD8(+) CTL cells reached 82.77% in cultured cord blood MNC after expansion for 15 days. The expanded CTL cell showed the cytotoxic activity against K562 and HeLa cell line. The killing rate of MNC was 61.88 ± 1.08%. After expansion, the killing rate could reach to 90% with the average value of 90.33 ± 2.02%. The expanded CTL cells highly expressed some key cytokines, such as granzyme A, granzyme B, GM-CSF, granulysin, IFN-γ, TGF-ß, TNF-α and perforin. Compared with the control group, the expression of IFN-γ and TGF-ß significantly increased (P < 0.05), and the other factors dramatically increased (P < 0.01). CONCLUSION: The cord blood-derived CTL can be expanded by different combinations of cytokines. These protocols may provide alternative choices for CTL cell expansion in tumor adoptive immunotherapy.
Subject(s)
Fetal Blood , T-Lymphocytes, Cytotoxic , Cytokines , Granulocyte-Macrophage Colony-Stimulating Factor , Granzymes , Histocompatibility Antigens Class I , Histocompatibility Antigens Class II , Humans , Immunotherapy, Adoptive , Perforin , PhytohemagglutininsABSTRACT
During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 µg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities.
Subject(s)
Prefrontal Cortex/abnormalities , Prefrontal Cortex/growth & development , Receptors, Corticotropin-Releasing Hormone/metabolism , Stress, Psychological/pathology , Stress, Psychological/physiopathology , Animals , Animals, Newborn , Anxiety Disorders/pathology , Anxiety Disorders/physiopathology , Anxiety Disorders/prevention & control , Cognition Disorders/pathology , Cognition Disorders/physiopathology , Cognition Disorders/prevention & control , Dendritic Spines/drug effects , Dendritic Spines/pathology , Dendritic Spines/physiology , Disease Models, Animal , Female , Hormone Antagonists/pharmacology , Male , Mice, Inbred C57BL , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiopathology , Pyramidal Cells/drug effects , Pyramidal Cells/pathology , Pyramidal Cells/physiology , Pyrimidines/pharmacology , Pyrroles/pharmacology , Random Allocation , Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors , Stress, Psychological/drug therapyABSTRACT
<p><b>OBJECTIVE</b>This study was to expand the cytotoxic T lymphocytes (CTL) through inducing the differentiation of umbilical blood monomuclear cells (UBMNC) by using various combination of cytokines, and to investigate the functions of expanded CTL.</p><p><b>METHODS</b>The MNC were isolated by ficoll density gradient centrifugation. Then, the PHA-P, IFN-γ combined with IL-2, IL-15 and other cytokines were used for induction and expansion of the cord blood-derived CTL. The biological function of CTL was examined by phenotype analysis, cytotoxic tests and real-time fluorescence quantitative PCR.</p><p><b>RESULTS</b>After expansion for 15 days, the cell number increased by 1522% ± 137%. The content of CD3(-)CD8(-) cells in uncultured cord blood MNC was 95%, and the CD3(+)CD8(+) CTL cells reached 82.77% in cultured cord blood MNC after expansion for 15 days. The expanded CTL cell showed the cytotoxic activity against K562 and HeLa cell line. The killing rate of MNC was 61.88 ± 1.08%. After expansion, the killing rate could reach to 90% with the average value of 90.33 ± 2.02%. The expanded CTL cells highly expressed some key cytokines, such as granzyme A, granzyme B, GM-CSF, granulysin, IFN-γ, TGF-β, TNF-α and perforin. Compared with the control group, the expression of IFN-γ and TGF-β significantly increased (P < 0.05), and the other factors dramatically increased (P < 0.01).</p><p><b>CONCLUSION</b>The cord blood-derived CTL can be expanded by different combinations of cytokines. These protocols may provide alternative choices for CTL cell expansion in tumor adoptive immunotherapy.</p>
Subject(s)
Humans , Cytokines , Fetal Blood , Granulocyte-Macrophage Colony-Stimulating Factor , Granzymes , Histocompatibility Antigens Class I , Histocompatibility Antigens Class II , Immunotherapy, Adoptive , Perforin , Phytohemagglutinins , T-Lymphocytes, CytotoxicABSTRACT
This study was objective to explore the effect of IFN-γ on immunosuppressive capability of mesenchymal stem cells (MSC) derived from umbilical cord. The immunomodulating capability of MSC was changed by stimulating cell surface receptors like Toll-like receptors (TLR). The inhibition of T-lymphocyte proliferation by MSC was tested via cell co-cultures. Further RT-PCR and ELISA were performed to examine the expression changes in gene and protein level. The results showed that the IFN-γ could promote the immunosuppressive effect of umbilical cord derived MSC. IFN-γ-stimulated MSC could suppress the proliferation of T cells more effectively. IFN-γ stimulation up-regulated the expression of immunosuppressive genes like IDO1, COX2, HLA-G, and soluble suppressive proteins such as HLA-G, KYN, IL10, PGE2 of MSC. And the immuno suppression capability of IFN-γ-stimulated MSC was 2-7 folds higher than control in MSC and lymphocyte co-culture tests. It is concluded that IFN-γ can effectively enhance the immunosuppressive capability of MSC.
Subject(s)
Interferon-gamma/pharmacology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/immunology , Cells, Cultured , Humans , Immunosuppression Therapy , Mesenchymal Stem Cells/cytology , Umbilical Cord/cytologyABSTRACT
Combined methods of first-principles calculations and Landau-Lifshitz-Gilbert (LLG) macrospin simulations are performed to investigate the coherent magnetization switching in the MgO/FePt/Pt(001)-based magnetic tunnel junctions triggered by short pulses of electric field through the control of magnetic anisotropy energy (MAE) electrically. First-principles calculations indicate that the MAE of MgO/FePt/Pt(001) film varies linearly with the change of the electric field, whereas the LLG simulations show that the change in MAE by electric field pulses could induce the in-plane magnetization reversal of the free layer by tuning the pulse parameters. We find that there exist a critical pulse width τmin to switch the in-plane magnetization, and this τmin deceases with the increasing pulse amplitude E0. Besides, the magnetization orientation cannot be switched when the pulse width exceeds a critical value τmax, and τmax increases asymptotically with E0. In addition, there exist some irregular switching areas at short pulse width due to the high precessional frequency under small initial angle. Finally, a successive magnetization switching can be achieved by a series of electric field pulses.