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Objective:To explore the paths and goals of organized construction for scientific research platforms in large-scale hospitals under the background of organized scientific research in China.Methods:By reviewing the relevant literature, and analyzing the construction of existing international and domestic research platforms for organized scientific research, this article elaborated on the importance and necessity of building a research platform for clinical hospitals under the background of organized scientific research and made suggestions for the platform construction.Results:Organized scientific research requires the organized construction of scientific research platforms. The construction of organized scientific research platforms should always focus on the major national needs, serve major scientific plans, carry out organized talent training, and internal efficient and orderly organization and operation, under the principle of interdisciplinary and multi-level collaborative innovation and development.Conclusions:In response to the strategic needs of national science and technology in the 14-Five Year Plan, the hospital scientific research platforms should be upgraded, integrated, expanded, and improved in an organized way, to form a multi-disciplinary and cross-dimensional platform structure to ensure the smooth development of organized scientific research.
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Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used in treating COVID-19 patients recently. However, both drugs have some contradictions and rare but severe side effects, such as hypoglycemia, retina and cardiac toxicity. To further uncover the toxicity profile of CQ and HCQ in different tissues, we evaluated the cytotoxicity of them in 8 cell lines, and further adopted the physiologically-based pharmacokinetic models (PBPK) to predict the tissue risk respectively. Retina, myocardium, lung, liver, kidney, vascular endothelium and intestinal epithelium originated cells were included in the toxicity evaluation of CQ and HCQ respectively. The proliferation pattern was monitored in 0-72 hours by IncuCyte S3, which could perform long-term continuous image and video of cells upon CQ or HCQ treatment. CC50 and the ratio of tissue trough concentrations to CC50 (RTTCC) were brought into predicted toxicity profiles. The CC50 at 24 h, 48 h, 72 h of CQ and HCQ decreased in the time-dependent manner, which indicates the accumulative cytotoxic effect. HCQ was found to be less toxic in 7 cell types except cardiomyocytes H9C2 cells (CC50-48 h=29.55 M; CC50-72 h=15.26 M). In addition, RTTCC is significant higher in CQ treatment group compared to HCQ group, which indicates that relative safety of HCQ. Both CQ and HCQ have certain cytotoxicity in time dependent manner which indicates the necessity of short period administration clinically. HCQ has the less impact in 7 cell lines proliferation and less toxicity compared to CQ in heart, liver, kidney and lung.
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Background To study the pathogenesis and management of diabetic retinopathy (DR) has an important clinical significance.With the development of biomedical photonics in recent years,photobiomodulation therapy has been paid more and more attention.However,the sudy on biological regulation of light to DR is rarely reported.Objective This study was to explore the photobiomodulating effects on the apoptosis of retinal neuronal cells induced by high glucose environment and tried to offer a basis for the management of DR.Methods The retinal neurons were isolated from Wistar rats using immunomagnetic beads and primarily cultured in Neurobasal,and the cells were identified by Nissl staining.The cells were divided into normal control group,high-glucose group and high-glucose+LED group.The glucose at the concentration of 25 mmol/L was added into medium for 48 hours in the high-glucose group,and the cells induced by high-glucose were irradiated in incubator by LED for consecutive 300 seconds per time in a 12-hour interval with the wavelength of 620 nm,maximal power of 1 W,central light radiation exposure of 6.67 mW/cm2 and spot diameter of 2.0 cm.The apoptosis rate of the cells was assayed by flow cytometry;the intracellular Ca2+ content was determined by laser scanning confocal microscope;the relative expression level of phosphorylated serine-threonine kinase (p-AKT) protein in the cells was detected by Western blot.Results The cells grew well 2-3 days after cultured with the polygon and oval shape,and nucleolus were visible.More neuronal processes were obtained in 5-7 days after culture.Nissl staining showed the blue violet color in cytoplasma of neurons.The proportion of neurons and glial cells was 91%.The apoptosis rates of the cells were (7.634±3.176)%,(33.642 ±9.315)% and (23.914±6.375)% in the normal control group,high-glucose group and high-glucose+LED group,respectively,and the apoptosis rates of high-glucose group and high-glucose + LED group were significantly higher than that in the normal control group,while the apoptosis rate in the high-glucose+LED group was lower than that in the high-glucose group (all at P<0.01).The fluorescence of Ca2+ in the cytoplasma was strong in the highglucose group and weak in the normal control group.The fluorescence pixel values in the high-glucose group and highglucose+LED group were significantly higher than that in the normal control group,and that in the high-glucose+LED group was reduced in comparison with high-glucose group (all at P<0.05).The expressing band of p-AKT protein was strong in the normal control group and weak in the high-glucose group.The relative expressing levels were 10.34± 3.18,2.16±0.46 and 7.15 ±1.72 in the normal control group,high-glucose group and high-glucose+LED group,and relative expression level of high-glucose+LED group was significatly lower than that in the high-glucose group (P< 0.05).Conclusions High-glucose environment inhibits PI3K/AKT pathway and calcium homeostasis of retinal neurons,which results in cell apoptosis.Low intensity of LED light irradiation activates the anti-apoptotic PI3K/AKT pathway and therefore reduces apoptosis induced by high glucose.
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Objective To evaluate the effect of external application therapy combined with chiropractic therapy on the pediatric asthma.Methods A total of 55 patients were randomly assigned into the treatment group (28 patients) and the control group (27 patients), The treatment group was treated with external application therapy combined with chiropractic therapyin the the hottest and coldest weather of each year; while the control group was only treated with chiropractic therapy. Both groups were treated for 3 years. After the treatment, the total effective rate, the clinical control rate, and the frequency of asthma attacks were detected.Results The total effective rate was 92.9% (26/28) and the clinical control rate was 64.3% (18/28) in observation group, which were better than those of 70.4% (19/27) and 22.2% (6/27) in the control group (χ2=4.073,P=0.044, andχ2=8.823,P=0.003). After 3 years’ treatment, the asthma grading distributionin the treatment group was significantly different from the control group (χ2=10.776,P=0.005). The frequency of asthma attacks in the treatment group after the first year treatment (4.5 ± 0.5 timesvs. 5.0 ± 0.5 times,t=3.708,P<0.01) was significantly lower than that in the control group; so did the second years after treatment (3.0 ± 0.5 timesvs.4.3 ± 0.5 times,t=9.728,P<0.01), and the third years (1.5 ± 0.5 times vs. 3.0 ± 0.5 times,t=11.225,P<0.01).ConclusionsThe external application therapy combined with chiropractic therapy could prevent asthma in children patients.
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OBJECTIVE:To explore the potential correlation between clinical efficacy of pemetrexed in the treatment of ad-vanced breast cancer and TS mRNA expression. METHODS:Patients with advanced breast cancer were recruited in our study. Three cycles of pemetrexed was given to these patients,TS mRNA expression of their tumor tissues were detected. The relationship of ther-apeutic efficacies of different chemotherapy with TS mRNA expression were observed and compared during the study period. RE-SULTS:58 patients received pemetrexed chemotherapy and therapeutic efficacies of them were evaluated. One patient (1.7%) had complete response,19 patients(32.8%)had partial response,31 patients(53.4%)had stable response and 7 patients(12.1%)has progressive disease. Objective response rate was 34.5%,and disease control rate was 87.9%. TS mRNA expression level of 55 pa-tients with completed TS mRNA expression analysis varied from 0.04 to 5.11,with a median of 0.62. Mann-Whitney rank test showed that,responders had lower TS mRNA expression than nonsponders at all visits,there was statistical significance (P<0.05). Chi-square test showed that patients with low expression level of baseline(before chemotherapy)TS mRNA had significantly higher objective response rate(63.3%)than those with high expression(36.7%),there was statistical significance(P<0.05). CON-CLUSIONS:TS mRNA expression level is related to therapeutic efficacy of pemetrexed,which may be useful for predicting thera-peutic efficacy of pemetrexed therapy in patients with advanced breast cancer.
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Background The measurement of retinal nerve fiber layer (RNFL) by Cirrus optical coherence tomography (OCT) has been applied widely in ophthalmology.However,previous assessment of RNFL is based on spatial measurement,while the evaluation based on optical characteristics of OCT can offset the shortcomings of spatial measurement in some eye diseases.Objective This study was to analyze the optical characters of RNFL measured by OCT and its correlation with age in healthy Chinese individuals.Methods Four hundred and six normal healthy subjects were collected in Shanghai Shibei Hospital from June 2011 to June 2012,with the age of 40-83 years old.Macular RNFL was unilateral imaged using a Cirrus OCT device with 5 line raster macular scan mode under the approval of Ethic Committee of Shanghai Shibei Hospital and informed consent of subjects.A customized software was used to measure RNFL optical characters,including absorbance (A value) and attenuate coefficient.The difference of the measured parameters in different genders was compared.The correlations between RNFL optical characters and age were analyzed by linear regression analysis.Results The data of 353 eyes were included in the final outcomes.The RNFL thickness,A value and attenuate coefficient were (35.1 ±4.4) μm,121.6 ±5.3 and 2.06 ±0.25,respectively.RNFL thickness and A value showed significantly negative correlations with age (r=-0.487,-0.571,both at P<0.01) with the regression equation Y=-0.17 X+45.23 and Y=-0.24 X+ 135.82,while a positive correlation was found between the attenuate coefficient and age (r=0.368,P<0.01) with the regression equation Y=0.01 X+1.63.RNFL thickness and A value showed weaker positive correlations with OCT signal intensity (rs =0.128,P =0.016;rs =0.284,P<0.01),but no remarked correlation was seen between the attenuate coefficient and OCT signal intensity (rs =-0.053,P=0.319).Conclusions Age of subjects affects the parameters of OCT optical characteristics in normal populaition.Age-related RNFL change in optical characters of OCT should be considered before concluding optical parameters.
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Objective To investigate the clinical efficacy of integrated Chinese and western medicine for the treatment of anovulatory dysfunctional uterine bleeding. Methods A total of 108 anovulatory dysfunctional uterine bleeding patients were evenly randomized into treatment group and control group. Both groups were given basic conventional treatment, estrogen-progestogen sequential therapy for 3 menstrual cycles for dysfunctional uterine bleeding patients at puberty and child-bearing period, and Marvelon for patients at menopause transition period after excluding uterine tumor by diagnostic curettage. Additionally, the treatment group was given Chinese herbal decoction of Radix Rehmanniae Preparata, Semen Cuscutae, Fructus Corni, Placenta Hominis, Herba Ecliptae, Fructus Schisandrae Chinensis, Rhizoma Alismatis, raw Rhizoma Dioscoreae, Rhizoma Atractylodis Macrocephalae, Rhizoma Cyperi, Radix Codonopsis, Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Alba, Pericarpium Citri Reticulatae, and charred Herba Schizonepetae. Therapeutic effect, bleeding-arresting time, and recurrence rate during 3-month follow-up were observed in the two groups. Results ( 1) The treatment group had a total effective rate of 100.0%, higher than 94.4%in the control group, the difference being significant (P<0.05). (2) Bleeding-arresting time was (45.50 ± 13.0) hours in the treatment group and was (58.0 ± 15.0) hours in the control group, and the difference was statistically significant (P<0.05). (3) During the 3-month follow-up, the treatment group had the recurrence rate of 16.7% ( 9 cases) , lower than 29.6% ( 16 cases) in the control group, and the difference was statistically significant ( P<0.05). Conclusion Integrated Chinese and western medicine has certain effect for the treatment of anovulatory dysfunctional uterine bleeding, showing good prospects for extensive application in gynecological clinic.
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Objective To investigate whether 5, 7-dihydrox-8-nitrochrysin (NOC) induces apoptosis in U937 monocytic leukae-mia cells is involved in the regulation of the activity of PKD 2.Methods U937 cell line cells were cultured in vitro .Apoptosis rate was analyzed by flow cytometry (FCM) using propidium iodide (PI) staining.DNA ladder bands were observed by DNA agarose gel electro-phoresis.The phosphorylated protein expression of PKD 2 was analyzed using Western blot .Results NOC (2.5, 5.0, and 10.0μmol/L) increased apoptosis rate in U937 cells in a concentration-dependent manner ( P <0.05).After treatment with NOC (5.0 and 10.0μmol/L) for 24 h, U937 cells presented typical DNA ladder bands .At the same time, not only did NOC effectively down-regulate the ex-pression of PDK2 phosphorylated protein , but also increased apoptosis rate in U 937 cells in the presence of G?6976, a specific inhibitor of PKD2.Conclusions The effect that NOC induces apoptosis in U 937 cells is related to the inhibition of the activity of PKD 2.
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<p><b>OBJECTIVE</b>To investigate the therapeutic effect of mustard seed on allergic contact dermatitis (ACD) in mice and explore the mechanism.</p><p><b>METHODS</b>Eighteen BALB/c mice were randomly divided into normal control group, model group and mustard seed group. The mice in the normal control group and model group were fed with normal chow, and those in mustard seed group were given 5% mustard seed mixed in the chow. Three weeks later, ACD was induced on the ear using 2, 4-dinitrofluorobenzene. After 24 h, the swelling of the ear was examined, and the rats were sacrificed to collect the ear tissue ears and blood for histopathological and immunohistochemical examinations, RT-PCR and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>In mice with ACD, feeding with mustard seeds significantly lessened the ear swelling, improved the tissue histopathology, lowered the number of infiltrating Langerhans cells, and reduced the expressions of IL-1β, TNF-α and IL-6 mRNA in the ear, but did not cause significant changes in serum levels of IL-4, IFN-γ and IL-17.</p><p><b>CONCLUSION</b>Mustard seed inhibits ACD in mice possibly by suppressing the expressions of IL-1β, TNF-α and IL-6 mRNA and inhibiting Langerhans cell migration in the epidermis.</p>
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Animales , Femenino , Ratones , Dermatitis Alérgica por Contacto , Quimioterapia , Metabolismo , Dinitrofluorobenceno , Interleucina-1beta , Metabolismo , Interleucina-6 , Metabolismo , Ratones Endogámicos BALB C , Planta de la Mostaza , Semillas , Factor de Necrosis Tumoral alfa , MetabolismoRESUMEN
Objective:To clone the mice interleukin-23(mIL-23) and express it in Pichia efficiently.Methods:Two subunits of IL-23 were amplified by PCR from pcDNA3/mIL-23,and ligated together with adaptor by over-PCR.The IL-23 cDNA confirmed by sequencing was inserted into expressing vector pPICZαA and expressed in Pichia X-33 strain.IL-23 protein expression was induced by methanol and ammonia.The recombinant IL-23 was identified by immunoblot and its biological activity was analyzed.Results:DNA sequencing confirmed that cloned cDNA was identical to the published sequence of mIL-23.The recombinant plasmid pPICZαA/mIL-23 was electroprated into X-33.An expected 72 kD protein of mIL-23 was founded both in the induced pellets and supermatants by SDS-PAGE and coomassie blue staining.The 72 kD protein could be recognized in Western blot.While we could detect bands at 72 kD in cell pellets induced more than 24 h by Western blot.Detected by Western blot using anti-His antibody,we could see positive band at 72 kD from supernatants induced 24 and 36 h.While we could detect band at 72 kD in cell pellets induced between 24 h and 96 h.Meanwhile,we could see obviously proliferation of mice peripheral blood mononuclear cells(PBMC) treated with the induced pellets and supermanants.Conclusion:We have successfully expressed mIL-23 protein in Pichia and the expressed product has its bioactivity in promoting the proliferation on PBMC.
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Objective To investigate the cellular and humoral immune responses and protective effect induced by co-immunization with two multi-epitope combinant antigens. Methods Mice were co-im-munized with the muhi-epitope HCV-T and HCV-E1 antigens three times. Sera antibodies IgG, IgG1 and IgG2a were tested by ELISA. Spleens from BALB/c mice immunized were removed 10 days after the last im-munization. CTL activity was assessed using LDH cytotoxicity assay kit. IFN-γ- and IL-4-secreting cells were quantified using ELISPOT kit. Two weeks after the final immunization, the mice were challenged sub-cutaneously(s, c. ) at the back with 106 SP2/0-NS3 cells, and protective effect was observed. For therapy, 106 SP2/0-NS3 cells were implanted into the back of BALB/c mice. Seven days later, mice were immuniza-tion three times. Therapy effect was observed. Results Co-immunization with HCV-T and HCV-E1 induced high tiers of HCV-El-specific IgG, IgG1 and IgG2a antibodies, and high level of CTL activity. Synergistic effect in frequencies of both specific IFN-γ-secreting cells and IL-4-secreting cells was observed in mice co-immunized. Prophylactic as well as therapeutic administration of mT + mE1 in mice led to protecting mice against SP2/0-NS3 cells. These results suggested that mT + mE1 was potential as a prophylactic as well as therapeutic HCV vaccine. Conclusion Co-immunization with HCV-T + HCV-EI induced protective humor-al and cellular immune response. HCV-T + HCV-E1 was potential as a recombinant HCV vaccine.