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Objective To establish a surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin, so as to provide insights into creation of a sensitive and highly efficient surveillance and early warning system for schistosomiasis. Methods National and international publications, documents, laws and regulations pertaining to schistosomiasis control were retrieved with keywords including schistosomiasis, surveillance, early warning and control interventions from 2008 to 2022, and a thematic panel discussion was held to preliminarily construct surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin. The index system was then comprehensively scored and screened using the Delphi method, and the weight of each index was determined using analytic hierarchy process and the modified proportional allocation method. In addition, the credibility of the Delphi method was evaluated using positive coefficient, authority coefficient, degree of concentration and degree of coordination of experts. Results Following two rounds of expert consultation, a surveillance and early warning index system for schistosomiasis transmission risk in endemic areas along the middle and lower reaches of the Yangtze River basin was preliminarily constructed, including 3 primary indicators, 9 secondary indicators and 41 tertiary indicators. The normalized weights of primary indicators epidemics, natural and social factors and comprehensive control were 0.639 8, 0.145 6 and 0.214 6, respectively, and among all secondary indicators, snail status (0.321 3) and schistosomiasis prevalence (0.318 5) had the highest combined weights, while social factors had the lowest combined weight (0.030 4). Of all tertiary indicators, human egg-positive rate (0.041 9), number of acute schistosomiasis cases (0.041 5), number of stool-positive bovine and sheep (0.041 1), and prevalence of Schistosoma japonicum in free-ranging livestock (0.041 1) had the highest combined weights. During two rounds of consultation, the positive coefficient of experts was both 100%, and the authority coefficient was both 0.9 and greater, while the coordination coefficients were 0.338 to 0.441 and 0.426 to 0.565 (χ2 = 22.875 to 216.524, both P values < 0.05). Conclusions The established surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin is of great scientific values and authority, which may provide insights into construction of the sensitive and highly efficient surveillance and early warning system for schistosomiasis in the context of low prevalence and low intensity of infection in China.
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Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control, light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.
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A new hydraulic oscillator was designed, which was able to adjust pressure fluctuations through two sets of dynamic and fixed valves. Hydraulic oscillators can meet the frequency and axial force requirements of drilling at lower drilling fluid flow than general hydraulic oscillators. Oscillator structure was described in detail and over-flow area between the two sets of dynamic and fixed valves was calculated. Based on drilling fluid flow difference, the influence of different fluid flows on oscillator pressure drops was analyzed, its influence law was determined by the finite element software Fluent, and its effect was verified by numerical simulations. The related research is of great significance in the selection of dynamic and fixed valves and provides the theoretical basis for the optimization of the structural parameters of double-valve hydraulic oscillators.
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Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. SARS-CoV-2 gains entry into host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. By screening a yeast surface-displayed library of synthetic nanobody sequences, we identified a panel of nanobodies that bind to multiple epitopes on Spike and block ACE2 interaction via two distinct mechanisms. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for SARS-CoV-2 Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains stability and function after aerosolization, lyophilization, and heat treatment. These properties may enable aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia, promising to yield a widely deployable, patient-friendly prophylactic and/or early infection therapeutic agent to stem the worst pandemic in a century.
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BackgroundCoronavirus disease 2019 (COVID-19) is an emerging infectious disease.It was first reported in Wuhan, China, and then broke out on a large scale around the world.This study aimed to assess the clinical significance of two different nutritional indices in 245 patients with COVID-19. MethodsIn this retrospective single-center study, we finally included 245 consecutive patients who confirmed COVID-19 in Wuhan University Zhongnan Hospital from January 1 to February 29. Cases were classified as either discharged or dead. Demographic, clinical and laboratory datas were registered, two different nutritional indices were calculated: (i)the Controlling nutritional status (CONUT) score; (ii) prognostic nutritional index (PNI). We used univariate and multivariate logistic regression analysis to explore the relationship between nutritional indices and hospital death. Results212 of them were discharged and 33 of them died. In-hospital mortality was signifcantly higher in the severe group of PNI than in the moderate and normal groups. It was also significantly worse in the severe-CONUT group than in the moderate-, mild-, and normal-CONUT groups. Multivariate logistic regression analysis showed the CONUT score (odds ratio3.371,95%CI (1.124-10.106), p = 0.030) and PNI(odds ratio 0.721,95% CI (0.581-0.896), P=0.003) were independent predictors of all-cause death at an early stage; Multivariate logistic regression analysis also showed that the severe group of PNI was the independent risk predictor of in-hospital death(odds ratio 24.225, 95% CI(2.147-273.327), p=0.010).The CONUT score cutoff value was 5.5 (56.00 and 80.81%; AUC 0.753; 95% CI (0.644-0.862); respectively). The PNI cutoff value was 40.58 (81.80 and 66.20%; AUC 0.778; 95% CI (0.686-0.809); respectively). We use PNI and the COUNT score to assess malnutrition, which can have a prognosis effect of COVID-19patients. ConclusionThe CONUT score and PNI could be a reliable prognostic marker of all-cause deathin patients with COVID-19.
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ObjectiveTo investigate the effect of direct-acting antiviral (DAA) on the recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after curative treatment. MethodsPubMed, Web of Science, Cochrane Library, CNKI, CBM, Wanfang Data, and VIP were searched for the clinical studies of DAA and the recurrence of HCV-related HCC published up to April 2020. Stata 14.0 software was used to perform the meta-analysis. The Cochran Q test was used to evaluate heterogeneity between studies; the fixed effects model was used for non-heterogeneous data, and the random effects model was used for heterogeneous data. The Egger regression method or the Begg rank correlation method was used to evaluate the presence or absence of publication bias. ResultsA total of 10 articles (11 studies) were included in our study, among which 8 articles (9 studies) compared the effect of DAA versus the absence of anti-HCV therapy on the recurrence of HCC after curative treatment. There were 991 patients in DAA group and 808 patients in untreated group. The results of the meta-analysis showed that DAA reduced the recurrence rate of HCC after curative treatment in patients with HCV infection (hazard ratio ［HR］=0.42, 95% confidence interval ［CI］: 0.28?0.36, P＜0.001). Three articles compared the effect of DAA versus interferon for the treatment of hepatitis C on the recurrence of HCC after curative treatment, with 267 patients in DAA group and 212 in interferon group, and the results of the meta-analysis showed that DAA and interferon had a similar effect on the recurrence rate of HCV-related HCC (HR=0.85, 95% CI: 0.64-1.15, P=0.298). ConclusionBoth interferon and DAA can significantly reduce the recurrence risk of HCV-related HCC after curative treatment, with no significant difference between them.
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Objective To analyze 10 WeChat official accounts of traditional Chinese medicine ( TCM) hospitals in Beijing and their data, to figure out the popular health topics well received by followers, for the purpose of disseminating health knowledge more precisely and efficiently in further work and public service. Methods Python and open API interface were used to scrawl the articles pushed by these accounts from July 1, 2018 to December 31, 2018, identifying topics of high Pviews and thumbs up as the text corpus of hot topics. Furthermore, working with text mining technology, the paper counted the term frequency(TF) and clustered the corpus to finally detect the most popular topics of health knowledge and needs of information by the public. Results Within the given period, the results showed that the top 5 key words with high TF in popular health science included: hypertension, cough, sleep, Gaofang( herbal paste) and pain. In the top 10 clustered hot topics, the followings received high level of public awareness and interpreted by more articles posted by the Wechat official accounts: kidney diseases, genital diseases(female/male) and seasonal affective disorder. Conclusions Methods used in the study can accurately round up popular TCM topics, practical needs of health knowledge of the people, and discover the disease diagnosis, treatment and health issues of the highest public concern, for guidance of the hospitals in their health education and popular science work using new media.
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Abnormal expression of miRNAs contributed to cancers through regulation of proliferation, apoptosis and drug resistance of cancer cells. The present study was designed to investigate the effect of miR-497 on renal cell carcinoma (RCC) and its possible mechanism. Forty paired clear cell RCC (ccRCC) tissues and adjacent normal kidney tissues were obtained from patients, who were not treated by chemotherapy or radiotherapy. RT-PCR was performed to detect expression of miR-497 in the ccRCC tissues. Effects of miR-497 on cell viability, apoptosis, migration and invasion were detected in ACHN cells. Western blotting (WB) was employed to detect the downstream targets of miR-497 We found that miR-497 in ccRCC tissues was decreased. We treated ACHN cells with miR-497 mimics and inhibitors in vitro and found that miR-497 inhibited viability, migration and invasion of ACHN cells. miR-497 promoted ACHN cells' apoptosis. VEGFR-2 was predicted as a possible target of miR-497 Luciferase reporter assay proved that miR-497 suppressed VEGFR-2 directly by binding to its 3'-UTR. Further studies showed that miR-497 influenced the MEK/ERK and p38 MAPK signalling pathways. Our findings demonstrated that miR-497 could suppress RCC by targeting VEGFR-2.
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Carcinoma de Células Renales/metabolismo , Genes Supresores de Tumor , Neoplasias Renales/metabolismo , MicroARNs/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Regiones no Traducidas 3'/genética , Análisis de Varianza , Apoptosis , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Recuento de Células , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Regulación hacia Abajo , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Sistema de Señalización de MAP Quinasas/genética , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Invasividad Neoplásica , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
In this paper, current status of doctor-nurse integration mode was reviewed, including the definition, history of development, way of working and main problems exist currently. We also analyzed the future trends of doctor-nurse integration mode by taking the latest research progress abroad into consideration. The future research should focus on developing indigenous scales to measure the behaviors and degree of cooperation in Chinese cultural background and medical environment. The role responsibilities need to be clarified, further more, a standardized and institutionalized organizational structure should be constructed on the basis of theories of modern hospital management.
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In this paper, current status of doctor-nurse integration mode was reviewed, including the definition, history of development, way of working and main problems exist currently. We also analyzed the future trends of doctor-nurse integration mode by taking the latest research progress abroad into consideration. The future research should focus on developing indigenous scales to measure the behaviors and degree of cooperation in Chinese cultural background and medical environment. The role responsibilities need to be clarified, further more, a standardized and institutionalized organizational structure should be constructed on the basis of theories of modern hospital management.
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After a description of the status quo of information literacy education in domestic colleges and universi-ties and the information literacy courses offered in University of Illinois according to The framework for information literacy in higher education, the information literacy courses offered in University of Illinois according to The frame‐work for information literacy in higher education were analyzed in aspects of their teaching target, teaching contents and teaching methods, with suggestions put forward for domestic information literacy education, including construc-tion of information literacy courses system and implementation of flexible teaching methods.
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Objective:To study the changes of cardiopulmonary function in patients with rheumatoid arthritis,and to analyze the correlation between the changes ofcardiopulmonary function with oxidative stress and the peripheral blood lymphocyte attenuation factor.Methods:130 cases of patients with rheumatoid arthritis were studied as case group, and 50 cases of healthy persons were studied as normal control group.Detected the heart function parameters of two groups,which contained EF%,SV%,FS%,E A,E/A;lung function parameters of FVC,FEV1,MVV,PEF;B and T lymphocyte attenuation factor expression and activation level.Peripheral Cytokine(IL-17 and TNF-α,IL-4,IL-35) and oxidative stress index (ROS,MDA,SOD,TAOC) were detected by enzyme linked immu-nosorbent assay.Results:The indexes of cardiac function in the case group were significantly lower than that in the control group.103 cases had abnormal cardiac function index in the case group,which accounted for 79.23% of the case group,while the E/A had the highest abnormal rate.The case group had thickening of LADd, increasing of peak A, decreasing of EF, E peak and E /A, than the normal control group,the differences were statistically significant (P<0.05).Compared with normal control group,pulmonary function parameters were significantly lower in case group.88 cases of case group had abnormal pulmonary function,accounting for 67.69% of the case group.Among them,the abnormal rate of PEF was the highest.Pulmonary function indexes of case group was significantly lower than that of the control group, the difference was statistically significant ( P<0.05 ).Correlation analysis showed that the correlation coefficient of cardiac function indexes EF with CD24+cells and CD19+CD24+cells were respectively -0.353 and -0.457,which had negative correlation,with ROS the correlation coefficient was 0.459,which had positive correlation.The correlation coefficient of the cardiac function indexes in FS with CD24+cells,and CD19+CD24+cells was -0.395 and -0.421,which had negative correlation; the correlation coefficient of peak A and CD19+cell was 0.423,which had positive correlation;the correlation coefficient of E/A and BTLA was 0.393,which had obvious positive correlation.SV and MDA,SOD were positively correlated.The parameters of lung function with hs-CRP and ESR had significantly negative correlation.The correlation coefficient of lung function parameters FVC with BTLA and CD19+CD24+were 0.513 and 0.596,which had a significant positive correlation,with the correlation coefficient and CD24+BTLA+, TNF-αwere -0.451 and-0.351,which had significantly negative correlation.The correlation coefficients of FEV1 with CD24+CD19+, TAOC and IL-4 were 0.535,0.466 and 0.519,which showed a positive correlation,with CD24+BTLA+,MDA were -0.461 and -0.358,which had significantly negative correlation.The correlation coefficient of PEF with SOD,TAOC,IL-4,IL-35 were 0.547,0.482, 0.643 and 0.452,which had significantly positive correlation,with MDA,ROS,IL-17 were -0.451,-0.423 and -0.417,which had a significant negative correlation ( P<0.05 ).Conclusion: RA imbalance of oxidative stress and cell immune disorders which runs through the whole process in the heart and lung injury.Therefore,in clinical treatment,treatment of joint symptoms in RA patients needs restore the body′s redox homeostasis,in order to increase the level of BTLA,activate B cell and,T cell,thereby inhibiting immune and inflammatory response,reducing the heart and lung function impairment.
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13 C isotopic abundance of intracellular free amino acid with a characteristic of fast- turnover can quickly reflect changes in intracellular metabolic state. But the concentration of intracellular free amino acid is low, the existed 13 C isotope detection method based on GC-MS can not satisfy the requirement with full scan mode. In this study, the selected ion monitoring method was used to detect accuracy higher likelihood of analysis of 13 C isotopic abundance of free intracellular amino acid. First, in the full scan mode we analyzed of the fracture law of different amino acids, found the feature corresponding to each amino acid fragments, and established 16 kinds of free intracellular amino acids characteristic fragment library. Then using this characteristic fragment library, only specific m/z signal was detected in sample analysis, which realized the selected ion monitoring and improved the quality of signal. The results of amino acid standards showed that the signal-to-noise ratio, measurement precision and accuracy were improved by 17, 2. 0 and 3. 8 times compared with the full scan mode. In the analysis of coenzyme Q10 producing strains of samples, this method was successfully used to detect isotopic abundance of 8 kinds of free intracellular amino acids. This method plays an important role in the detection of 13 C isotopic abundance of the intracellular free amino acid in cell metabolism research.
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In normal rat forebrain, the NR1/NR2A and NR1/NR2B dimmers are the main constitutional forms of NMDA receptors. The present study was carried out to determine the functional properties of the heteromeric NMDA receptor subunits and their inhibition by bis(7)-tacrine (B7T). Rat NR1, NR2A and NR2B cDNAs were transfected into human embryonic kidney 293 cells (HEK-293). The inhibition of NMDA-activated currents by B7T was detected in HEK-293 cell expressing NR1/NR2A or NR1/NR2B receptors by using whole-cell patch-clamp techniques. The results showed that in HEK-293 cells expressing NR1/NR2A receptor, 1 μmol/L B7T inhibited 30 μmol/L NMDA- and 1000 μmol/L NMDA-activated steady-state currents by 46% and 40%, respectively (P>0.05; n=5), suggesting that the inhibition of B7T on NR1/NR2A receptor doesn't depend on NMDA concentration, which is consistent with a non-competitive mechanism of inhibition. But for the NR1/NR2B receptor, 1 μmol/L B7T inhibited 30 μmol/L NMDA- and 1000 μmol/L NMDA-activated steady-state currents by 61% and 13%, respectively (P<0.05; n=6), showing that B7T appears to be competitive with NMDA. In addition, simultaneous application of 1 μmol/L B7T and 1000 μmol/L NMDA produced a moderate inhibition of peak NMDA-activated current, followed by a gradual decline of the current to a steady state. However, the gradual onset of inhibition produced by B7T applied simultaneously with NMDA was eliminated when B7T was given 5 s before NMDA. These results suggested that B7T inhibition of NMDA current mediated by NR1/NR2B receptor was slow onset, and it did not depend on the presence of the agonist. With holding potentials ranging from -50 to +50 mV, the B7T inhibition rate of NMDA currents didn't change significantly, and neither did the reversal potential. We are led to conclude that the NR1/NR2B recombinant receptor can serve as a very useful model for studying the molecular mechanism of NMDA receptor inhibition by B7T.
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Humanos , Línea Celular , Células HEK293 , N-Metilaspartato , Farmacología , Receptores de N-Metil-D-Aspartato , Genética , Tacrina , FarmacologíaRESUMEN
In normal rat forebrain, the NR1/NR2A and NR1/NR2B dimmers are the main constitutional forms of NMDA receptors. The present study was carried out to determine the functional properties of the heteromeric NMDA receptor subunits and their inhibition by bis(7)-tacrine (B7T). Rat NR1, NR2A and NR2B cDNAs were transfected into human embryonic kidney 293 cells (HEK-293). The inhibition of NMDA-activated currents by B7T was detected in HEK-293 cell expressing NR1/NR2A or NR1/NR2B receptors by using whole-cell patch-clamp techniques. The results showed that in HEK-293 cells expressing NR1/NR2A receptor, 1 μmol/L B7T inhibited 30 μmol/L NMDA- and 1000 μmol/L NMDA-activated steady-state currents by 46% and 40%, respectively (P>0.05; n=5), suggesting that the inhibition of B7T on NR1/NR2A receptor doesn't depend on NMDA concentration, which is consistent with a non-competitive mechanism of inhibition. But for the NR1/NR2B receptor, 1 μmol/L B7T inhibited 30 μmol/L NMDA- and 1000 μmol/L NMDA-activated steady-state currents by 61% and 13%, respectively (P<0.05; n=6), showing that B7T appears to be competitive with NMDA. In addition, simultaneous application of 1 μmol/L B7T and 1000 μmol/L NMDA produced a moderate inhibition of peak NMDA-activated current, followed by a gradual decline of the current to a steady state. However, the gradual onset of inhibition produced by B7T applied simultaneously with NMDA was eliminated when B7T was given 5 s before NMDA. These results suggested that B7T inhibition of NMDA current mediated by NR1/NR2B receptor was slow onset, and it did not depend on the presence of the agonist. With holding potentials ranging from -50 to +50 mV, the B7T inhibition rate of NMDA currents didn't change significantly, and neither did the reversal potential. We are led to conclude that the NR1/NR2B recombinant receptor can serve as a very useful model for studying the molecular mechanism of NMDA receptor inhibition by B7T.
