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BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. METHODS: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5â×â1010, 1â×â1011, and 1·5â×â1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. FINDINGS: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. INTERPRETATION: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. FUNDING: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.
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Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Vacunas Virales/administración & dosificación , Adenoviridae , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Betacoronavirus , COVID-19 , Vacunas contra la COVID-19 , China , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunidad Celular , Inmunidad Humoral , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Linfocitos T/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/uso terapéutico , Vacunas Virales/efectos adversos , Vacunas Virales/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1â×â1011 viral particles per mL or 5â×â1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. FINDINGS: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1â×â1011 viral particles n=253; 5â×â1010 viral particles n=129) or placebo (n=126). In the 1â×â1011 and 5â×â1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1â×â1011 and 5â×â1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1â×â1011 and 5â×â1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1â×â1011 and 5â×â1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1â×â1011 viral particles dose group and one (1%) participant in the 5â×â1010 viral particles dose group. No serious adverse reactions were documented. INTERPRETATION: The Ad5-vectored COVID-19 vaccine at 5â×â1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. FUNDING: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
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Betacoronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Vacunas Virales/efectos adversos , Vacunas Virales/inmunología , Adenoviridae , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19 , Vacunas contra la COVID-19 , China , Infecciones por Coronavirus/inmunología , Método Doble Ciego , Femenino , Vectores Genéticos , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T/inmunología , Vacunas Virales/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Periprocedural myocardial infarction is a common complication following percutaneous coronary intervention. The present study was conducted with an aim to compare the safety and efficacy of loading doses of ticagrelor versus clopidogrel in preventing periprocedural myocardial infarction in Asian patients with acute coronary syndrome undergoing elective percutaneous coronary intervention. METHODS: A total of 114 patients with acute coronary syndrome undergoing elective percutaneous coronary intervention were assigned to clopidogrel group (n = 57, the loading and maintenance doses were 300 and 75 mg qd for clopidogrel, and 300 and 100 mg qd for aspirin), or ticagrelor group (n = 57, the loading and maintenance doses were 180 and 90 mg bid for ticagrelor, and 300 and 100 mg qd for aspirin). Cardiac biomarkers were measured before, 8 hours, and 24 hours after percutaneous coronary intervention. The percutaneous coronary intervention-related periprocedural myocardial infarction was defined according to the fourth universal definition of myocardial infarction (2018). RESULTS: The overall incidence of percutaneous coronary intervention-related periprocedural myocardial infarction was 21.1%. The ticagrelor group showed a significantly lower incidence of periprocedural myocardial infarction (12.3% vs 29.8%, p = 0.022) and numerically lower bleeding events (3.5% vs 8.8%, p = 0.242) as compared with clopidogrel group. No patient had major adverse cardiovascular events during the 1-month follow-up. The levels of high-sensitivity C-reactive protein did not differ significantly between the two groups (p > 0.05), indicating that the benefits of ticagrelor were not from its anti-inflammatory effects. Multivariable analysis showed that the use of ticagrelor (odds ratio: 0.50; 95% confidence interval: 0.29-0.87; p = 0.014) and number of stents (odds ratio: 2.75; 95% confidence interval: 1.25-6.06; p = 0.012) were independent predictors of periprocedural myocardial infarction. CONCLUSION: Pretreatment with a loading dose of ticagrelor seems to be superior in reducing the incidence of percutaneous coronary intervention-related periprocedural myocardial infarction in Asian patients with acute coronary syndrome as compared with clopidogrel.
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Síndrome Coronario Agudo , Clopidogrel/administración & dosificación , Infarto del Miocardio , Intervención Coronaria Percutánea , Ticagrelor/administración & dosificación , Síndrome Coronario Agudo/tratamiento farmacológico , Humanos , Infarto del Miocardio/etiología , Infarto del Miocardio/prevención & control , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Resultado del TratamientoRESUMEN
As an alternative to most of the reported nucleic acid amplification-based electrochemical DNA biosensors used for detection of trace levels of genomic DNA, we herein present a novel detection concept. The proposed system involves the conversion of two short double-stranded DNAs (dsDNAs), labeled with a thiol-tag or biotin-tag, into a single integrated dsDNA containing thiol and biotin at both terminals in the presence of target DNA through ligase chain reaction (LCR) and followed by the immobilization of these integrated dsDNAs on a bovine serum albumin (BSA)-modified gold electrode surface. Owing to rapid depletion of the two short dsDNAs via LCR, the integrated dsDNAs were generated in an exponential manner so that this sensoring approach offered a limit of detection of 25 yoctomoles (15 copies in 50 µL sample volumes), a high discrimination of single-base mismatch and a wide linear concentration range (across 6 orders of magnitude) for target DNA. Significantly, the proposed sensor, which has simplicity in operation and ease of miniaturization, detected the target of interest in total nucleic acid extracts derived from clinical serum samples with excellent results, thereby demonstrating its considerable diagnostic potential in fields ranging from virus detection to the diagnosis of genetic diseases.
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Técnicas Biosensibles/métodos , ADN/sangre , Genoma Humano , Animales , Bovinos , ADN/metabolismo , Técnicas Electroquímicas , Electrodos , Oro/química , Humanos , Técnicas de Amplificación de Ácido Nucleico , Polimorfismo de Nucleótido Simple , Albúmina Sérica Bovina/químicaRESUMEN
OBJECTIVE: To observe the effect of electric acupuncture (EA) on the Nogo receptors (NgR) protein expression in the cerebral cortex, the medulla oblongata, and the spinal cord of cerebral ischemia-reperfusion (I/R) stroke-prone renovascular hypertensive rats (RHRSP) with middle cerebral artery occlusion (MCAO) at different time points, and to investigate its possible mechanisms for remote-organ injury of acute cerebral infarction (ACI). METHODS: The RHRSP model was duplicated in male SPF grade SD rats. Then the MCAO model was prepared by a thread stringing method. Rats were divided into the hypertension group,the sham-operation group, the MCAO group, the EA group, and the sham-acupoint group by random number table method, 60 in each group. Rats in the MCAO group only received MCAO reperfusion treatment. Those in the sham-operation group only received surgical trauma. Baihui (DU20) and Dazhui (DU14) were needled in the EA group, once daily for a total of 28 days.The needles were acupunctured at the skin one cun distant from Baihui (DU20) and Dazhui (DU14) and then the same EA treatment was performed in the sham-acupoint group. At day 1, 7, 14, 28 after treatment, six rats were executed from each group, and their right cortex and medulla oblongata, and the left spinal cord were isolated. The infarct volume was detected by Nissl's staining method. The NgR expression was detect by Western blot. RESULTS: (1) In the cortex area: compared with the hypertension group,the NgR expression increased in the MCAO group at day 1,7,14,and 28 after MCAO (P < 0.05). Compared with the MCAO group, the NgR expression of the EA group and the sham-acupoint group were equivalent at 1 day af ter MCAO (P > 0.05). At day 7, 14,and 28 after MCAO, the NgR expression decreased in the EA group (P < 0.05), it was quite similar to that in the sham-acupoint group (P > 0.05). (2) In the medulla oblongata area: compared with the hypertension group, the NgR expression was equivalent in the sham-operation group. the MCAO group,the EA group, and the sham-acupoint group at 1 day after MCAO (P > 0.05). At day 7.14, and 28 after MCAO, the NgR expression increased in the MCAO group (P < 0.05). Compared with the MCAO group,the NgR expression decreased in the EA group at day 7, 14, and 28 after MCAO (P < 0.05), whereas it was similar in the sham-acupoint group (P > 0.05). (3) In the spinal cord area: compared with the hypertension group, the NgR expression was equivalent in the sham-operation group, the MCAO group,the EA group, and the sham-acupoint group at day 1 and 7 after MCAO (P > 0.05). At day 14 and 28 after MCAO, the NgR expression increased in the MCAO group (P < 0.05). Compared with the MCAO group, the NgR expression decreased in the EA group at day 14 and 28 after MCAO (P < 0.05), whereas it was equivalent in the sham-acupoint group (P > 0.05). CONCLUSIONS: Increased NgR expression in the cerebral cortex, the medulla oblongata, and the spinal cord of cerebral infarct rats was an important reason for involving remote-organ injury of ACI. The protective effect of EA on hypertensive I/R cerebral injury rats might be closely related to down-regulating central nervous system myelin growth inhibition mediated factors Nogo-A receptor NgR protein expression.
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Infarto Cerebral/metabolismo , Electroacupuntura , Hipertensión Renal/metabolismo , Proteínas de la Mielina/metabolismo , Receptores de Superficie Celular/metabolismo , Animales , Infarto Cerebral/terapia , Modelos Animales de Enfermedad , Proteínas Ligadas a GPI/metabolismo , Hipertensión Renal/terapia , Masculino , Bulbo Raquídeo/metabolismo , Receptor Nogo 1 , Ratas , Ratas Sprague-Dawley , Médula Espinal/metabolismoRESUMEN
Whether tumor deposits (TDs) should be classified as lymph node metastasis or distant metastasis remains controversial. To address this predicament, we conducted this study to identify the predictive value of TDs on the survival of patients diagnosed with stage III colon cancer (CC). 12,904 eligible patients diagnosed with stage III CC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The best cutoff point of TD quantity was determined based on the difference in survival. Cox proportional hazards model was employed to perform univariate and multivariate analyses. The Kaplan-Meier method and log-rank test were performed to calculate the differences between overall survival (OS). Our results showed that the number of TDs was a significant prognostic factor in patients with stage III CC (P < 0.0001). We added the number of TDs to the pN stage and devised a new pN stage, there were no significant differences in the survival of npN, except npN2a (P > 0.05). Upon re-staging to the same npN stage, the difference in survival between TDs+ and TDs- disappeared (P > 0.05). The median survival times for N2aTDs > 4 and N2bTDs > 4 were 33 and 37 months, respectively, which were significantly shorter than that of N2TDs- (65 months) and represented the worst survival rates among all groups. In conclusion, the number of TDs indicated a poor prognosis for patients with stage III CC. Incorporating TDs into the pN is feasible to predict prognosis.
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Background: People over 60 have been found to develop less protection after two doses of inactivated COVID-19 vaccines than younger people. Heterologous immunisation could potentially induce more robust immune responses compared to homologous immunisation. We aimed to assess the immunogenicity and safety of a heterologous immunisation with an adenovirus type 5-vectored vaccine (Ad5-nCOV, Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) previously. Methods: We did a randomised, observer-blinded, non-inferiority trial in healthy adults aged 60 years and older in Lianshui County (Jiangsu, China) between August 26, 2021 and May 15, 2022. 199 eligible participants who had received two doses of CoronaVac in the past 3-6 months were randomised (1:1) to receive a third dose of Convidecia (group A, n = 99) or CoronaVac (group B, n = 100), while 100 participants primed with one dose of CoronaVac in the past 1-2 months were randomised equally to receive a second dose of Convidecia (group C, n = 50) or CoronaVac (group D, n = 50). Participants and investigators were masked to the vaccine received. Primary outcomes were the geometric mean titers (GMTs) of neutralising antibodies against live SARS-CoV-2 virus 14 days after boosting and 28-day adverse reactions. This study was registered with ClinicalTrials.govNCT04952727. Findings: A heterologous third dose of Convidecia resulted in a 6.2-fold (GMTs: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralising antibodies against SARS-CoV-2 wild-type, delta (B.1.617.2) and omicron (BA.1.1) 14 days post boosting, respectively, compared with the homologous boost. The heterologous booster with Convidecia induced significantly higher neutralsing activities, with up to 91% inhibition in binding of Spike to ACE2 for BA.4 and BA.5 variants, compared with 35% inhibition induced by three doses of CoronaVac. For participants primed with one dose of CoronaVac, a heterologous dose of Convidecia induced higher neutralising antibodies against wild-type than two doses of CoronaVac (GMTs: 70.9 vs 9.3, p < 0.0001), but not for that against variants of concern (GMTs against delta: 5.0 vs 4.0, p = 0.4876; GMTs against omicron: 4.8 vs 3.7, p = 0.4707). Adverse reactions were reported by 8 (8.1%) participants in group A and 4 (4.0%) in group B (p ï¼ 0.05), and 8 (16.0%) in group C and 1 (2.0%) in group D (p = 0.031). Interpretation: In elderly individuals primed with two doses of CoronaVac, the heterologous immunisation with Convidecia induced strong antibodies against SARS-CoV-2 wildtype and variants of concern, which could be an alternative regimen for enhancing protection in this vulnerable population. Funding: National Natural Science Foundation of China, Jiangsu Provincial Key Research and Development Program, and Jiangsu Science Fund for Distinguished Young Scholars Program.
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The high geological background and the residual pollution of historical zinc smelting in the karst area of northwest Guizhou has led to serious soil heavy metal pollution. In order to understand the characteristics of soil heavy metal pollution in agricultural land, wasteland, and forestland, 126 surface and profile soil samples were collected from a typical zinc powder factory-polluted small watershed in Weining County, Northwest Guizhou Province. The concentrations and distribution characteristics of Cd, As, Pb, Cu, and Zn in soils were studied. The results showed that the average ω(Cd), ω(As), ω(Pb), ω(Cu), and ω(Zn) in the surface soil were 8.14, 45.07, 263.97, 41.36, and 716.98 mg·kg-1, respectively, which were 1.29-12.33 times higher than the background values. The content of heavy metals in soil of different land uses in descending order was agricultural land, wasteland, and forestland. From the perspective of spatial distribution, the soil with high heavy metal concentration was concentrated around the zinc smelting plant and slag, and the accumulation of heavy metals in soil was greatly affected by the pollution sources of mining activities but less affected by the land use mode. In soil profile, heavy metals in the surface layer were generally higher than those in bottom layers, showing a significant difference (P<0.05) in wasteland. Five heavy metals in 80-100 cm soil were higher than the background value, reflecting the existence of a high geological background value. Correlation analysis and principal component analysis showed that Pb, Zn, and As in the surface soil were mainly affected by human activities such as mining and transportation, whereas Cd and Cu were both affected by high geological background and human activities. The single ecological risk coefficient of Cd in soil was the highest, which reached very strong or very strong risk, whereas As, Zn, Cu, and Pb reached slight or medium risk. The comprehensive potential ecological risk index indicated strong ecological risk, which in agricultural land was higher than that in wasteland and forestland. In the karst high geological background area, the influence of lead and zinc smelting on the distribution and accumulation of heavy metals in soils was greater than that of land use; soil heavy metal pollution was serious, and ecological risk was high in this area. Therefore, strict control of heavy metal-contaminated soil should be strengthened.
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Metales Pesados , Contaminantes del Suelo , Cadmio/análisis , China , Monitoreo del Ambiente/métodos , Humanos , Plomo/análisis , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis , ZincRESUMEN
OBJECTIVE: To observe the clinical effect of acupotomy combined with warm needling on cervical spondylotic radiculopathy (CSR) of qi and blood stagnation syndrome. METHODS: A total of 90 CSR patients were randomly divided into an acupotomy group, a warm needling group and a combined treatment group, with 30 cases in each group. The patients in the acupotomy group were treated with acupotomy, once every 7 days, consecutively for 3 times. The patients in the warm needling group received warm needling, once daily, at the interval of 2 days after consecutive treatments for 5 days, 7 days as one session of treatment and 3 consecutive sessions were required. The patients in the combined treatment group were treated with acupotomy and warm needling, and the methods and the treatment session were same as the the previous two groups. Before and after the treatment, the pain rating index (PRI) of McGill pain questionnaire (MPQ) and the 20-point scale of CSR developed by Yasuhisa Tanaka (CSR20) were adopted in the assessment. The changes of clinical symptoms and functions of patients were observed and the clinical efficacy was assessed in each group. RESULTS: After the treatment, the PRI score was decreased (P<0.05) and the CSR20 score was increased (P<0.05) in the 3 treatment groups when compared with those before the treatment. After the treatment, compared with the acupotomy group and the warm needling group, the PRI score was decreased (P<0.05) and the CSR20 score was increased (P<0.05) in the combined treatment group. The total effective rate was 83.3% (25/30) in the acupotomy group, 76.7% (23/30) in the warm needling group and 93.3% (28/30) in the combined treatment group. The total effective rate in the combined treatment group was higher than those in the acupotomy group and the warm needling group (P<0.05). CONCLUSION: The combined treatment with acupotomy and warm needling may obviously improve the clinical symptoms and physical signs, e.g. pain and numbness in the patients with CSR of qi and blood stagnation syndrome. Its efficacy is remarkably higher than that of the simple application of acupotomy or warm needling.
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Terapia por Acupuntura , Radiculopatía , Espondilosis , Humanos , Radiculopatía/terapia , Qi , Espondilosis/terapia , Terapia por Acupuntura/métodos , Resultado del Tratamiento , Síndrome , DolorRESUMEN
BACKGROUND: The demonstration of batch-to-batch consistency is indispensable for quality control of vaccines. METHODS: We conducted a randomized, double-blind, parallel-controlled trial to evaluate the immunogenicity consistency of a single shot of Ad5-nCoV in healthy adults who had not previously received any COVID-19 vaccine. All eligible participants were randomly assigned equally to receive one of the three consecutive batches of Ad5-nCoV (5 × 1010 viral particles/vial, 0.5 mL). The primary endpoint was geometric mean titers (GMTs) of serum SARS-CoV-2 receptor-binding domain (RBD)-specific IgG on day 28 post-vaccination. RESULTS: One thousand fifty participants were enrolled, with 350 (33%) participants per group. On day 28 post-vaccination, GMTs in three groups were 78.3 binding antibody units (BAU)/mL (95% CI 70.3-87.3), 82.9 BAU/mL (73.9-92.9), and 78.8 BAU/mL (70.2-88.4), respectively. The two-sided 95% CIs for the GMT ratios between each pair of batches were all between 0.67 and 1.5. The highest incidence of solicited adverse reactions within 7 days post-vaccination was reported by batch 3 recipients (23.1% versus 15.1% in batch 1 recipients and 14.6% in bath 2 recipients; p = 0.0039). None of the serious adverse events were related to vaccination. CONCLUSIONS: Immunogenicity consistency between consecutive batches of Ad5-nCoV was well established in adults. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05313646).
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Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , COVID-19/prevención & control , Anticuerpos Antivirales , Método Doble Ciego , Inmunoglobulina G , Adenoviridae , Inmunogenicidad VacunalRESUMEN
The possible role of miR-194-5p in brain and neurodegenerative diseases has been reported, but its role in intracerebral hemorrhage (ICH) has not been studied. This study estimated the mechanism of miR-194-5p in ICH. ICH rat model was established by injecting collagenase type VII. miR-194-5p expression in brain tissue of ICH rats was overexpressed by injection of miR-194-5p agomir. Then neurological function score and brain water content were measured. The morphological changes of brain tissue and neuronal apoptosis were evaluated by histological staining. Levels of NLRP3 inflammasomes, IL-1ß and IL-18 were measured. The target relation between miR-194-5p and TRAF6 was verified and the binding of TRAF6 to NLRP3 was explored. miR-194-5p was decreased in ICH rats. After overexpression of miR-194-5p, the neuropathological injury in ICH rats was significantly reduced, and NLRP3-mediated inflammatory injury was inhibited. miR-194-5p targeted TRAF6. TRAF6 interacted with NLRP3 to promote the activation of NLRP3 inflammasomes. Overexpression of miR-194-5p reduced the interaction between TRAF6 and NLRP3, thereby alleviating the neuroinflammation. Collectively, overexpression of miR-194-5p reduced the TRAF6/NLRP3 interaction, thus inhibiting the activation of NLRP3 inflammasomes and reducing neuroinflammation during ICH. This study may shed new light on ICH treatment.
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Hemorragia Cerebral/metabolismo , Encefalitis/metabolismo , Inflamasomas/metabolismo , MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Regulación hacia Abajo , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The relationship between preoperative tibiofemoral position and failure of anterior cruciate ligament (ACL) reconstruction has been widely discussed. Most established methods for measuring tibiofemoral position on magnetic resonance imaging (MRI) mainly focus on anterior tibial subluxation (ATS), while a quantitative measuring method for rotational tibial subluxation (RTS) is still undetermined. Moreover, there are still controversies about the related factors for ATS. The aim of this study was to quantitatively describe preoperative ATS and RTS in ACL-injured and ACL-intact knees and identify the related factors for ATS and RTS based on MRI images. METHODS: Demographic data and preoperative MRIs of 104 ACL-injured patients were retrospectively analyzed. ACL-intact knees were 1:1 matched as control group. ATS was measured using longitudinal tibial axis, and RTS was determined by the difference between lateral and medial ATS. Related factors for ATS and RTS were examined. RESULTS: Increased lateral ATS (P < 0.0001), medial ATS (P < 0.0001) and RTS (P = 0.0479) were observed in ACL-injured knees compared with the control group. Increased posterior tibial slope (PTS), Beighton Score ≥ 4, presence of meniscal injury and long injury-to-MRI time were identified as being correlated with the increase of ATS. Factors for the increase of RTS were increased lateral PTS, Beighton score ≥ 4, presence of lateral meniscal injury, and left side. CONCLUSIONS: In ACL-injured knees, tibia not only subluxated anteriorly in both lateral and medial compartments, but also rotated internally. During preoperative planning, attentions should be paid to the factors that are correlated with altered tibiofemoral position.
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Lesiones del Ligamento Cruzado Anterior , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Humanos , Articulación de la Rodilla , Imagen por Resonancia Magnética , Estudios Retrospectivos , Tibia/diagnóstico por imagen , Tibia/cirugíaRESUMEN
COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.
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Vacunas contra la COVID-19 , COVID-19 , Inmunogenicidad Vacunal , SARS-CoV-2/inmunología , Adolescente , Adulto , COVID-19/sangre , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A 46-year-old Chinese woman presented with nausea, recurrent vomiting, and abdominal pain. Gastroduodenal endoscopic examination revealed an oval-shaped submucosal tumor at the prepyloric area on the posterior wall of the stomach. A degenerated gastrointestinal stromal tumor was suspected. Distal gastrectomy was performed and a histological diagnosis of heterotopic pancreas (HPs) was confirmed. The patient had an uneventful postoperative course and was discharged 7 d after operation. The patient remains healthy and symptom-free in the follow-up of 6 mo. This is a report of a case of gastric outlet obstruction resulting from pancreatic heterotopia in the gastric antrum in an adult woman.
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Coristoma/complicaciones , Coristoma/diagnóstico , Obstrucción de la Salida Gástrica/diagnóstico , Obstrucción de la Salida Gástrica/etiología , Páncreas , Coristoma/cirugía , Femenino , Obstrucción de la Salida Gástrica/cirugía , Humanos , Persona de Mediana Edad , Antro Pilórico/cirugíaRESUMEN
OBJECTIVE: To investigate genetic polymorphism of two X chromosome specific STR: DXS10011 and DXS8377 in male samples from Guangdong Han population. METHODS: The DNA samples were amplified by PCR and analyzed by polyacrylamide gel electrophoresis followed by silver staining. RESULTS: Among 113 samples, 20 alleles were found for DXS1011 and 12 alleles for DXS8377. Also, 72 DXS10011-DXS8377 haplotypes were shown. The most common haplotypes only occurred three times. When only female children were tested in motherless case, the exclusion probability of paternity was 0.9588 for DXS10011-DXS8377 haplotypes. Investigations in 83 family trios with female children and 29 pedigrees with two children suggested a co-dominant X-linked inheritance; mutations were not found. CONCLUSION: Our data indicate that DXS10011 and DXS8377 are highly informative X chromosome markers for complicated kinship analysis.
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Cromosomas Humanos X/genética , Haplotipos , Polimorfismo Genético , Secuencias Repetidas en Tándem , Alelos , Pueblo Asiatico/genética , China , ADN/sangre , ADN/genética , Electroforesis en Gel de Poliacrilamida , Ciencias Forenses , Frecuencia de los Genes , Ligamiento Genético , Humanos , Masculino , Paternidad , Reacción en Cadena de la PolimerasaRESUMEN
Vertically aligned SnO2 nanocones with different morphologies have been directly grown on fluorine-doped tin oxide (FTO) glass substrates in a large area by heating a mixture of stannous chloride dihydrate (SnCl2·2H2O) and anhydrous zinc chloride (ZnCl2) at 600 °C in air. Control over the SnO2 nanocone arrays with different morphologies is achieved by adjusting the heat treatment time. The SnO2 nanocones are single crystalline with the tetragonal structure. A single-layer SnO2 nanoparticle film is first formed via the vapor-solid (VS) process due to the decentralization function of ZnCl2 vapor, and the SnO2 nanoparticles served as seeds and grew into nanocone arrays via the VS process. The sharp-tipped nanostructure formation may originate from a concentration gradient of reactant in the growth process. The as-obtained whiskerlike nanocone arrays exhibit enhanced field emission properties in comparison with typical nanoconelike structure arrays and other SnO2 nanostructured materials reported previously, and the turn-on field and field-enhancement factor is 1.19 V/µm and 3110, respectively. The experimental result is consistent with the Utsumi's relative figure of merit for pillar-shaped emitters.
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ZnO nanorod arrays and nanodisk networks were grown directly on Si substrate by thermal evaporation of ZnCl(2) powder and a mixture of ZnCl(2) and InCl(3)·4H(2)O at 450 °C in air, respectively. The ZnO nanorods with the diameters of 0.64 to 0.91 µm and length of about 5.1 µm are single crystalline with the hexagonal structure and grow along the [001] direction. The nanodisk has perfect hexagonal shape, grow mainly along the [0110] directions, and are enclosed by ±(0001) top and bottom surfaces. ZnO nanoparticle films oriented in the [001] direction formed first served as seeds, and grow into nanorod arrays via the vapor-solid (VS) process. However, when InCl(3)·4H(2)O was introduced into the reaction system ZnO thick nanosheet films are first formed because of the local segregation of the doping element of indium. The ZnO thick nanosheet films served as seeds, and grow into nanodisk networks via the V-S process. Photoluminescence and field emission properties of the as-obtained ZnO nanorod arrays and hexagonal nanodisk networks have been studied. It was found that the hexagonal nanodisk networks exhibit strong blue-green emissions originated from defect states and enhanced field emission property.
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Unexpectedly high rates of venous thromboembolic events (VTE) induced by highly effective immune modulating drugs thalidomide and lenalidomide for treatment of multiple myeloma have focused attention on the incidence and underlying pathophysiology of VTE in patients with plasma cell dyscrasias, and on thromboprophylaxis approaches. While bleeding complications are relatively uncommon in the patients with lymphoproliferative disorders, acquired von Willebrand syndrome, typically occurring in the patients with monoclonal gammopathy of unknown significance, and acquired coagulopathies associated with primary amyloidosis can present with haemorrhagic complications and both are challenges to the management. This review highlights these important haemostasis-related complications of plasma cell dyscrasias and provides an overview of other uncommon bleeding and thrombotic events that can affect diagnosis and therapeutic management of clonal plasma cell disorders. Due to the infrequency of most these haemostasis complications, available information is typically based on retrospective cases or series analysis.