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Three pathogenic human coronaviruses have emerged within the last 20 years, with SARS-CoV-2 causing a global pandemic. Although therapeutic antibodies targeting the SARS-CoV-2 spike currently focus on the poorly conserved receptor-binding domain, targeting essential neutralizing epitopes on the more conserved S2 domain may provide broader protection. We report an antibody binding an epitope conserved in the pre-fusion core of MERS-CoV, SARS-CoV and SARS-CoV-2 spike S2 domains. Antibody 3A3 binds a conformational epitope with ~2.5 nM affinity and neutralizes spike from SARS-CoV, SARS-CoV-2 and variants of concern in in vitro pseudovirus assays. Hydrogen-deuterium exchange mass spectrometry identified residues 980-1006 in the flexible hinge region at the S2 apex as the 3A3 epitope, suggesting 3A3 prevents the S2 conformational rearrangements required for conversion to the spike post-fusion state and virus-host cell fusion. This work defines a conserved vulnerable site on the SARS-CoV-2 S2 domain and guides the design of pan-protective spike immunogens.
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Objective To establish a standardized and feasible family health assessment index system based on the family practice system in Shanghai urban communities.Methods On the basis of literature review and special topic discussion, a preliminary index system framework was developed and an expert consultation questionnaire was compiled.Twenty one experts of general practice, medical specialties, health administration and public health management were invited and two rounds of improved Delphi expert consultation were conducted.The results of statistical analysis were summarized and the evaluation index system was established.Results The evaluation index system included 5 first-level indicators, 17 second-level indicators and 63 third-level indicators.The weight coefficients of first-level indicators in basic information, family structure, family function, family resources and health status of the family members were 0.199 6, 0.197 5, 0.201 7, 0.185 0, 0.216 2, respectively.In the two rounds of consultation, the positive coefficient of experts was both 100%, the degree of expert authority was 0.867 and 0.880, and the coordination coefficient was 0.294 and 0.415, respectively (P<0.05).The operational coordination coefficients were 0.320 and 0.402 (P<0.05), respectively.Conclusion The family health assessment index system constructed by the Delphi expert consultation method can provide reference for family doctors to carry out family health assessment in urban communities.
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number of goblet cells, mucus secretion and mucin MUC5AC content in lung tissues. Results S100A9 in BALF of group B was (11.89±0.77) ng/mL, S100A9 integrated optical density (IOD) value in airway epithelial cells was 13.96±1.62, PAS stain area /epithelial cell area was (12.53±1.21)%, relative value of MUC5AC / NADPH was 173.91±4.29, all of the above were higher than those of group A [(6.19±0.61) ng/mL, 4.97±0.30, (1.94±0.18)%, 1];S100A9 levels, IOD of S100A9 in airway epithelial cells, PAS stain area / epithelial cell area (%), relative value of MUC5AC / NADPH in group C [(10.69±0.79) ng / ml, 11.80±0.72, (10.61±0.61)%, 94.65±1.59], group D[(9.49±0.99) ng/mL, 10.39±0.59, (8.63±0.62)%, 82.08±1.12], group E [(7.54± 0.42) ng/mL, 5.63±0.84, (4.59±0.87)%, 26.30±1.94] were lower than group B, which showed a dose-dependent reduction and the difference was statistically significant (P<0.05 or P<0.01). Conclusion DB downregulates the expression level of Ca2+-binding protein S100A9 and the mucus secretion amount of the airway goblet cells in rats.
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Objective To evaluate the effect of denatonium benzoaten on α-smooth muscle actin (α-SMA),subepithelial collagen and airway inflammation in asthmu mice.Methods Forty-five BALB/c mice were divided into 3 groups,normal control group (A group),asthma model group (B group),asthma model+ denatonium benzoaten group(C group);α-SMA detected by using immunohistochemistry,lung sections were stained with Masson to detect subepithelial collagen,HE stain method was used to observe the airway inflammation the images were analyzed with semi-quantitative computer.Results The deposition of α-SMA、subepithelial collagen and inflammation degree in C group was significantly reduced compared with B group,the difference were statistically significant(P＜0.05).Conclusion Denatonium benzoaten can improve airway remodeling in asthmatic mice.
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OBJECTIVE: A possible relationship between fibrosis along the route of cerebrospinal fluid (CSF) flow and the subsequent development of hydrocephalus has been indicated in previous studies. These changes in the fibrosis index may reflect the severity of hydrocephalus and could potentially become a diagnostic tool. The object of this study was to analyze the levels of procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), hyaluronic acid (HA), and laminin (LN) in the CSF of patients with post-traumatic hydrocephalus and determine the significance of their presence. SUBJECTS AND METHODS: Forty-four patients were included in the study: 24 patients with shunt-dependent post-traumatic hydrocephalus (group A - hydrocephalus group); ten brain trauma patients without any sign of hydrocephalus (group B - trauma group); ten patients without brain trauma and hydrocephalus (group C - normal control group). CSF levels of PICP, PIIINP, HA, LN and transforming growth factor-ß1(TGF-ß1) were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: Levels of PICP, PIIINP, HA, and LN in the group of hydrocephalus patients were significantly higher than those in the post-trauma patients without hydrocephalus (p < 0.05) and normal control patients (p < 0.05). Moreover, the increased levels of PICP, PIIINP, HA, and LN were positively correlated with the level of TGF-ß1 (p < 0.05). CONCLUSION: We demonstrated an increase of fibrosis factors including PICP, PIIINP, HA, and LN, that was positively correlated with TGF-ß1 levels. This indicates an important role for the process of fibrosis in the development of post-traumatic chronic hydrocephalus and shows the potential utility of PICP, PIIINP, HA, and LN as a diagnostic index in shunt-dependent post-traumatic chronic hydrocephalus.
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AIM:To compare the biological characteristics , surface markers and multi-differentiation potential of the mesenchymal stem cells (MSCs) derived from the umbilical cord and bone marrow in the green fluorescent protein (GFP) transgenic mice.METHODS:Umbilical cord MSCs (UCMSCs) were isolated by collagen type II enzymatic diges-tion and bone marrow MSCs ( BMSCs) were isolated by density gradient centrifugation .The growth of the 2 types of MSCs was observed under inverted microscope .The cell proliferation was detected by determining the growth curve and MTT as-say.The Trypan blue method was performed to analyze the cell viability rate .The cell cycle and cell surface markers were measured by flow cytometry .The differentiation potentials of the 2 types of MSCs were tested by the differentiation kits to-ward adipocytes and osteoblasts .RESULTS:The UCMSCs attached to the culture surface 1 d after the isolation , and the cells showed spiral shape with notable growth and proliferation after 2 d of culture.After 3 d, the cell arrived sub-confluent and was ready for passage .BMSCs still showed circular shape and started to attach to the surface 4 d after culture .They formed the small colony shape only after 5 d with obvious proliferative potential .The cells became confluent 7 d after the culture.The original generation of cultivating UCMSCs growth curve was shown typically an “S” shape.But the BMSCs growth was slower than the UCMSCs .The cell proliferation was obvious for UC-MSCs in 3~5 d.BMSCs proliferated signif-icantly only after 7 d.The viability rate arrived more than 96%for both types of MSCs .The cell cycle of both MSCs did not show significant difference (G0/G1 phases were above 85%, P>0.05).Both MSCs positively expressed CD44, CD90 and CD105 (60.7%±2.3%) but the expression of CD45, CD19, CD14 and CD79 was negative (less than 25.6%±4.8%, P>0.05).More than 90%of the MSCs from the umbilical cord and bone marrow differentiated towards the adipocytes and osteoblasts without significant difference (P<0.05).CONCLUSION:UCMSCs have stronger ability of proliferation and multi-directional differentiation potentials .UCMSCs in GFP transgenic mice as a high-quality tracer can serve for tracking the stem cells in vivo.
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Objective To investigate the incidence, main relative risk factors and preventive therapeutic strategies of hypertension. Methods Investigating the incidence, main relative risk factors and complications of hypertension at 520 inhabitants over 35 years with the way of Questionnaire survey at the Zhao incidence of hypertension complicated with coronary heart disease, analysis shows that smoking, drinking, high-fat diet, high-salt diet, no exercise and family history were main risk factors of hypertension. Conclusion The morbidity of hypertension in this community were higher, the main risk factors were smoking, drinking, high-fat diet, high-salt diet, no exercise and family history. Carry out regular health education in accordance with the main relative risk factors, establishing and improving personal health file, fulfil hierarchical management system gradually, promote a reasonable diet and raise the awareness of self-care had important effect in reducing the morbidity and improving the life quality in patients with hypertension. Meanwhile, it's a long-term and arduous task for Community Doctor.
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OBJECTIVE: To establish a quantitative preliminary evaluation of introduced drugs. METHODS: A quantitative form was designed for new drugs’ preliminary evaluation, which included many factors, such as qualification of pharmaceutical factory or company, category of drugs in medical insurance, the result of the biding drugs, comparison with other drugs of the same category, PK and PD data,special use and clinical demand. Each factor was given a definite score .If the total scores of a given drug amounted to the expected figure, this drug could pass the preliminary evaluation and enter the next step, and if not, the drug may be eliminated. RESULTS&CONCLUSION: The purpose of evaluating the new drugs scientifically and objectively can be basically achieved through quantitative method, which can lessen the blindness in introduction of new drugs.
