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Jiangchuanmycin (1), a new indole containing pyrrolizidine, and six known peptides (2-7) were obtained from the fermentation broth of a Streptomyces isolate collected from a sediment sample of Xingyun Lake, Jiangchuan, China. Their structures were elucidated on the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, ECD, and X-ray crystallographic data. Jiangchuanmycin (1) presented weak inhibitory effects on cell lines of H1299, MHCC97H, HCT116 with the IC50 values of 97.6â µM, 98.6â µM and 40.6â µM, respectively.
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Antineoplásicos , Streptomyces , Streptomyces/química , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Espectroscopía de Resonancia MagnéticaRESUMEN
Sonic hedgehog (SHH) signaling pathway and glioma-associated oncogene homolog 1 (GLI1) play important roles in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). GS homeobox 2 (GSX2, formerly GSH2) is a downstream target of SHH signaling, but its role in pancreatic cancer remains unclear. This study evaluates the role of GSH2 in the development and drug resistance of pancreatic cancer. Both cell culture and xenograft mouse model were used. Immunohistochemistry, Western blotting and quantitative RT-PCR were used to examine the expression of GSH2 and other related molecules. CCK8 assay was used to test the cell proliferation, and flow cytometry used to examine cell apoptosis upon gemcitabine treatment. It was found that GSH2 is overexpressed in human pancreatic cancer tissues and cells. The expression of SHH and GLI1 was reversely correlated with GSH2 in pancreatic cancer cells. SHH and GLI1 have protein-protein interactions with GSH2. GSH2 silencing in pancreatic cancer cells inhibited cell proliferation, migration and invasion, increased cell apoptosis and sensitized pancreatic cancer cells to gemcitabine treatment. Furthermore, in vivo study demonstrated that silencing GSH2 increased the efficacy of gemcitabine-based treatment. Our results indicate that GSH2 is overexpressed in pancreatic cancer. GSH2 silencing in pancreatic cancer alleviates gemcitabine resistance by activating SHH/GLI1 pathway. Thus, targeting GSH2 in PDAC could be a novel cancer therapeutic strategy.
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Carcinoma Ductal Pancreático , Proteínas de Homeodominio , Neoplasias Pancreáticas , Animales , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Línea Celular Tumoral , Proliferación Celular , Desoxicitidina/análogos & derivados , Silenciador del Gen , Genes Homeobox , Proteínas Hedgehog/genética , Proteínas de Homeodominio/genética , Humanos , Ratones , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Transducción de Señal , Proteína con Dedos de Zinc GLI1/genética , Gemcitabina , Neoplasias PancreáticasRESUMEN
BACKGROUND: Perinatal complications are common burdens for neonates born from mother with pPROM. Physicians and parents sometimes need to make critical decisions about neonatal care with short- and long-term implications on infant's health and families and it is important to predict severe neonatal outcomes with high accuracy. METHODS: The study was based on our prospective study on 1001 preterm infants born from mother with pPROM from August 1, 2017, to March 31, 2018 in three hospitals in China. Multivariable logistic regression analysis was applied to build a predicting model incorporating obstetric and neonatal characteristics available within the first day of NICU admission. We used enhanced bootstrap resampling for internal validation. RESULTS: One thousand one-hundred pregnancies with PROM at preterm with a single fetus were included in our study. SNO was diagnosed in 180 (17.98%) neonates. On multivariate analysis of the primary cohort, independent factors for SNO were respiratory support on the first day,, surfactant on day 1, and birth weight, which were selected into the nomogram. The model displayed good discrimination with a C-index of 0.838 (95%CI, 0.802-0.874) and good calibration performance. High C-index value of 0.835 could still be reached in the internal validation and the calibration curve showed good agreement. Decision curve analysis showed if the threshold is > 15%, using our model would achieve higher net benefit than model with birthweight as the only one predictor. CONCLUSION: Variables available on the first day in NICU including respiratory support on the first day, the use of surfactant on the first day and birthweight could be used to predict the risk of SNO in infants born from mother with pPROM with good discrimination and calibration performance.
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Recien Nacido Prematuro , Madres , Peso al Nacer , Femenino , Rotura Prematura de Membranas Fetales , Humanos , Lactante , Recién Nacido , Embarazo , Estudios Prospectivos , TensoactivosRESUMEN
Glutathione-S-transferases (GSTs) not only show cytoprotective role and their involvement in the development of anticancer drug resistance, but also transmit signals that control cell proliferation and apoptosis. However, the role of GST isoforms in chemotherapy resistance remains elusive in pancreatic cancer. Here, we demonstrated that gemcitabine treatment increased the GSTM2 expression in pancreatic cancer cell lines. Knockdown of GSTM2 by siRNA elevated apoptosis and decreased viability of pancreatic cancer cells treated with gemcitabine. Moreover, in vivo experiments further showed that shRNA induced GSTM2 downregulation enhanced drug sensitivity of gemcitabine in orthotopic pancreatic tumor mice. We also found that GSTM2 levels were lower in tumor tissues than in non-tumor tissues and higher GSTM2 expression was significantly associated with longer overall survival. In conclusion, our findings indicate that GSTM2 expression is essential for the survival of pancreatic cancer cells undergoing gemcitabine treatment and leads to chemo resistance. Downregulation of GSTM2 in pancreatic cancer may benefit gemcitabine treatment. GSTM2 expression in patients also shows significant correlation with overall survival. Thus, our study suggests that GSTM2 is a potential target for chemotherapy optimization and prognostic biomarker of pancreatic cancer.
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Desoxicitidina/análogos & derivados , Regulación hacia Abajo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glutatión Transferasa/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Antineoplásicos/farmacología , Biomarcadores de Tumor , Desoxicitidina/farmacología , Resistencia a Antineoplásicos/genética , Marcadores Genéticos , Glutatión Transferasa/genética , Humanos , Interferencia de ARN , GemcitabinaRESUMEN
In this study, human enterovirus C117 (EV-C117) was detected in a 3-month-old boy diagnosed with pneumonia in China. A phylogenetic analysis showed that this strain was genetically closer to the Lithuanian strain than to the USA strain.
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Enterovirus Humano C/genética , Infecciones por Enterovirus/diagnóstico , Genoma Viral/genética , Neumonía Viral/virología , Secuencia de Bases , China , Enterovirus Humano C/clasificación , Enterovirus Humano C/aislamiento & purificación , Infecciones por Enterovirus/virología , Humanos , Lactante , Masculino , Filogenia , Neumonía Viral/diagnóstico , ARN Viral/genética , Análisis de Secuencia de ARNRESUMEN
We demonstrate maintenance and transmission of severe fever with thrombocytopenia syndrome virus by Haemaphysalis longicornis ticks in the larva, nymph, and adult stages with dissemination in salivary gland, midgut, and ovarian tissues. The H. longicornis tick is a competent vector to transmit this virus in both transovarial and transstadial modes.
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Vectores Arácnidos/virología , Infecciones por Bunyaviridae/transmisión , Infecciones por Bunyaviridae/virología , Ixodidae/virología , Phlebovirus/aislamiento & purificación , Animales , Femenino , Larva/virología , Masculino , Ninfa/virologíaRESUMEN
AIM: To assess the immunogenicity of Peginterferon alpha-2 b(Pegberon) and its effect on the efficacy and safety in phase III clinical trial, by comparing it with the control drug Pegasys. METHODS: 770 patients were recruited in total. 509 were treated with Pegberon plus ribavirin and 261 were treated with Pegasys plus ribavirin. After treatment of 12 and 24 weeks, plasma samples were collected from individual patients for detecting the anti-therapeutic antibodies (ATA) and hepatitis C RNA(HCV RNA), to evaluate the production of antibodies and their adverse effect on the efficacy and safety of the treatments. With data obtained from the treatments with Pegberon or Pegasys, gross comparison analysis was performed. RESULTS: The incidence of treatment-induced neutralizing antibodies (NAb) of Pegberon group (0.7%, 3/454) was significantly lower than Pegasys group (5.0%,12/238)(p < .001). Among all patients, the rates of sustained virological response 24 (SVR24) were significantly different between baseline ATA positive (60.7%,34/56) and baseline ATA negative patients (76.2%,544/714)(p = .010), between baseline NAb positive (36.0%,9/25) and baseline NAb negative patients (76.4%,569/745)(p < .001) and between induced ATA positive (72.7%,40/55) and sustained ATA negative patients(84.0%,492/586)(p = .034). The incidence of potential immunogenicity-related adverse reactions (AR) showed no significant difference between Pegberon (55.6%,283/509) and Pegasys groups (53.6%,140/261)(p = .605) and the profiles of these AR were also similar between the two groups. CONCLUSION: The incidence of treatment-induced Nab in Pegasys group was significantly higher than the Pegberon group. Baseline ATA, induced ATA and baseline NAb all affected the efficacy. The profiles of potential immunogenicity-related AR were similar between two drug groups, indicating the immunogenicity had no significant adverse effect on safety.
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Anticuerpos Neutralizantes , Hepatitis C/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Femenino , Hepatitis C/sangre , Hepatitis C/inmunología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interferón-alfa/antagonistas & inhibidores , Masculino , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Ribavirina/administración & dosificación , Ribavirina/efectos adversosRESUMEN
Myxovirus resistance A (MxA) is an antiviral protein induced by type I interferons α and ß (IFN-α and IFN-ß) that can inhibit virus replication. We examined whether the MxA polymorphisms were related to the risk and severity of enterovirus 71 (EV71) infection in Chinese populations. The MxA C-123A and G-88T polymorphisms were genotyped in two independent case-control populations in China by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). MxA messenger RNA was quantified by real-time quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 45 healthy children and 19 patients with EV71 infection. Significantly decreased susceptibility to EV71 infection was observed for the -123A allele and -88T allele carriers, with ORs (95% CIs) estimated as 0.56 (0.39-0.81) and 0.64 (0.47-0.88), respectively, in the northern population. This association was confirmed in the southern population, with ORs (95% CIs) estimated as 0.58 (0.38-0.89) and 0.67(0.47-0.95), respectively. The A- 123T- 88 haplotype was also significantly associated with lower risk of EV71 infection in both the northern (OR = 0.62; 95% CI = 0.44-0.85) and the southern population (OR = 0.63; 95% CI = 0.43-0.92). Furthermore, we observed higher MxA messenger RNA levels in IFNß1a-stimulated PBMCs from the -123A or -88T allele carriers compared with that from nocarriers. Our findings suggest that polymorphisms in the MxA promoter may play a role in mediating the susceptibility to EV71 infection in Chinese population.
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Enterovirus Humano A/fisiología , Infecciones por Enterovirus/genética , Proteínas de Resistencia a Mixovirus/genética , Polimorfismo Genético/genética , Preescolar , China/epidemiología , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/virología , Heces/virología , Femenino , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Lactante , Masculino , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Vigilancia de Guardia , Análisis de Secuencia de ADN , Índice de Severidad de la EnfermedadRESUMEN
As widely acknowledged, wastewater treatment plants (WWTPs) stand as significant contributors to the presence of microplastics in surface water. Nonetheless, there exists a notable research gap regarding the extent of potential pollution resulting from the concurrent and uninterrupted discharges originating from multiple WWTPs into small-scale receiving water bodies. This study endeavors to address this knowledge deficit by conducting a thorough investigation into the prevalence of microplastics in surface water. The research encompasses seven distinct locations within the Changzhou section of the Beijing-Hangzhou Grand Canal and the effluent of three WWTPs situated along the tributary. The results indicate differences in the distribution of microplastics in surface waters of mainstream and tributaries. While the microplastic abundance and composition showed little variation along the main stream, the tributaries displayed an overall increasing trend in microplastic abundance from upstream to downstream. Notably, the major contributors to this increase were fragments, fiber particles, and microplastics with particle sizes ranging from 100 to 300 µm. Considering that the primary distinction between the tributaries and the mainstream is the presence of the three WWTPs along the tributaries, the study conducted a correlation analysis between river surface water and effluents from these plants. The results indicated a stronger correlation between the tributaries and the effluents, suggesting that WWTPs are one of the primary factors contributing to the elevated levels of microplastics in the tributaries. Finally, a comparative analysis of microplastic abundance in the Beijing-Hangzhou Grand Canal's Changzhou section and other regions was conducted. The findings revealed that the microplastic pollution level in the Beijing-Hangzhou Grand Canal's Changzhou section is higher than that in most other rivers. Therefore, the issue of microplastic pollution in the Beijing-Hangzhou Grand Canal's Changzhou section warrants our attention, particularly with regard to the effectiveness of microplastic removal by the WWTPs along its course.
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BACKGROUND: The standardised management of neonatal critical care centres can help improve health outcomes of vulnerable newborns. Guidance is required to update evidence related to construction and management of neonatal critical care centres in China. OBJECTIVE: To establish expert consensus on the essential capability lists for neonatal critical care at three levels in China. DESIGN AND SETTING: According to China's administrative divisions, the Chinese guidelines stratifies neonatal critical care into three levels: county level (basic and special care), city level (intensive care) and province level (comprehensive care including neonatal surgery and more subspecialty interventions). A modified Delphi study was conducted. A group of 20 neonatologists from the Chinese Association of Neonatologists rated the importance of capability items on a 5-point Likert scale. RESULTS: At county level, the list consisted of 29 items related to basic and special care, and 3 items were unanimously rated very important by all experts: neonatal resuscitation, endotracheal intubation and continuous positive airway pressure ≥72 hours. At city level, group consensus defined 38 items as essential. Besides the essential items of county level, more items for intensive care were included in city level. At province level, 64 items reached consensus, including neonatal surgery and more advanced subspecialty interventions. The Kendall's W values showed good agreement among experts in both rounds, and an increase from round 1 to round 2. CONCLUSIONS: We developed the capability lists for neonatal critical care at three levels in China. Neonatal resuscitation should be provided by all levels. Interventions for preterm newborns are stratified according to gestational age and birth weight. Congenital abnormalities requiring surgical services need to be managed in high-level centres.
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Cuidados Críticos , Resucitación , Humanos , Recién Nacido , Técnica Delphi , Intubación Intratraqueal , ChinaRESUMEN
BACKGROUND: The wide distribution and high case-fatality ratio of severe fever with thrombocytopenia syndrome (SFTS) have made it a significant public health problem. This study was designed to identify the predictors of fatal outcomes and to evaluate the effectiveness of antiviral therapy in treating SFTS virus (SFTSV)-infected patients. METHODS: A cross-sectional study was performed in a general hospital located in Xinyang city, whereas the largest number of patients with SFTS in China were treated during 2011-2012. The primary outcome for the treatment effect analysis was death. Other outcomes included sequential platelet levels and viral loads observed throughout the hospitalization and the interval between the initiation of ribavirin therapy and the return of the platelet count to a normal level. RESULTS: A total of 311 SFTSV-infected patients were included in the study. The most frequent clinical presentations were fever, weakness, myalgia, and gastrointestinal symptoms. Each patient had thrombocytopenia, leukopenia, or both. The case-fatality ratio (CFR) was 17.4% (95% confidence interval [CI], 13.1%-21.6%). Older age (odds ratio [OR], 1.061; 95% CI, 1.023-1.099; P = .001), decreased level of consciousness (OR, 5.397; 95% CI, 2.660-10.948; P < .001), and elevated levels of lactate dehydrogenase (>1200 U/L; OR, 2.620; 95% CI, 1.073-6.399; P = .035) and creatine kinase (>800 U/L; OR, 2.328; 95% CI, 1.129-4.800; P = .022) were significantly associated with fatal outcome. The CFRs were similar between patients who received ribavirin and those who did not. Ribavirin treatment showed no significant effect on either platelet counts or viral loads during hospitalization of patients with fatal or nonfatal cases. CONCLUSIONS: These findings can improve knowledge about the characteristics of patients with fatal outcomes and the use of antiviral drug for SFTS.
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Antivirales/uso terapéutico , Fiebre por Flebótomos/tratamiento farmacológico , Fiebre por Flebótomos/mortalidad , Phlebovirus/aislamiento & purificación , Ribavirina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mortalidad , Fiebre por Flebótomos/patología , Fiebre por Flebótomos/virología , ARN Viral/genética , Análisis de Secuencia de ADN , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
Birnaviruses, including the genus Entomobirnavirus, are socio-economically important viruses. Currently, only Drosophila X virus has been formally assigned to the genus Entomobirnavirus, but two more viruses were recently isolated, Espirito Santo virus (ESV) and Culex Y virus. The host mosquito has been reported to carry many viruses, but seldom entomobirnaviruses. To discover potential pathogens in mosquitoes, we exploited small-RNAs high-throughput sequencing of three mosquito species caught in South China. A virus that genetically likes entomobirnavirus, Mosquito X virus (MXV), was identified from Anopheles sinensis and was 97% identical to ESV, which co-infects with Dengue virus (DENV). However, the absence of DENV in the A. sinensis suggested the independence of MXV infection from dengue co-infection. Our discovery complements prior research on entomobirnaviruses and proved that MXV may be widespread in mosquitoes on different continents. This work also highlights the applying of high-throughput sequencing of small RNAs to survey viruses carried by insect vectors.
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Anopheles/virología , Culex/virología , Virus del Dengue/aislamiento & purificación , Entomobirnavirus/aislamiento & purificación , Secuencia de Aminoácidos , Animales , China , Regulación Viral de la Expresión Génica , Genoma Viral , Datos de Secuencia Molecular , Filogenia , ARN Viral/genética , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
This retrospective study was conducted in a neonatal intensive care unit in Beijing. Patients whose blood culture yielded Candida utilis during hospitalisation from January 2009 to December 2017 were enrolled. Thirteen preterm infants of median gestational age 29.85 weeks were included. Laboratory tests on the day of onset showed thrombocytopaenia in 11 patients, granulocytopaenia in eight and elevated C-reactive protein in seven. No fungal endophthalmitis, renal infection, carditis or involvement of other end organs was observed in any of the cases. All 13 patients were cured after fluconazole therapy.
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Candida , Candidemia , Lactante , Humanos , Recién Nacido , Recien Nacido Prematuro , Estudios Retrospectivos , Antifúngicos/uso terapéutico , Candidemia/diagnóstico , Candidemia/tratamiento farmacológico , Candidemia/microbiologíaRESUMEN
The transition of households towards cleaner energy is crucial for achieving sustainable development goals. However, the impacts and associated mechanisms of early-life experiences on household energy transition have not been considered. Based on data from the 2015 Chinese General Social Survey, this study aimed to investigate whether people experiencing China's Great Famine (1959-1961) in their early life promoted household energy transition in adulthood. The varying severity of the Great Famine in different provinces was characterised as a quasi-natural experiment and was used to perform difference-in-differences (DID) estimation analysis for birth cohorts. The results showed that the transitions from firewood, agricultural waste, and animal waste to liquefied petroleum gas and electricity were significant in households with the Great Famine experiences. Specifically, the long-term energy transition effect of the famine was exhibited mostly in those who experienced the famine during childhood (4-11 years old) and adolescence (12-17 years old). Besides, early-life famine experiences led to poor physical health, and more modern forms of energy, such as electricity, were consumed to avoid further deteriorating health. Early-life famine experience also brought psychological trauma to people at that time, which led them to increase Internet use to gain emotional support, and the increased Internet use provided better access to information about the energy transition. Moreover, the household energy transition influenced by early-life famine experience occurred more in female-headed, rural, more educated, and low-income households. Our results illustrated the role of early-life famine experience in household energy transition and provided new insights into developing effective energy policies.
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BACKGROUND: Neutrophil extracellular traps (NETs) is the key means for neutrophils to resist bacterial invasion. Sepsis is a systemic inflammatory response syndrome caused by infection. METHODS: In our study, qRT-PCR was used to detect the gene expression in neutrophils, Western blot was used to detect the protein expression in mouse tissues and neutrophils, flow cytometry was used to detect the purity of neutrophils in the whole blood and immunofluorescence was used to detect the NETs formation. RESULTS: In this study, we analyzed the NETs formation in the blood of patients with sepsis. The results showed that a large number of NETs appeared. And the expression of GPR109A in neutrophils of patients with sepsis was significantly up regulated. Then we collected neutrophils from WT mice and GPR109A-/- mice and found that GPR109A knockout could significantly inhibit the early NETs formation of neutrophils. The results also showed that knockout of GPR109A or inhibition of the NETs formation could increase the inflammatory response of liver, spleen, lung and kidney in mice, thus affecting the disease process of sepsis. Then we observed the death of mice in 16 days. The results showed that inhibiting the NETs formation could significantly affect the early mortality of mice, while knocking out GPR109A could directly affect the mortality of the whole period. CONCLUSIONS: This study confirmed the regulatory effect of GPR109A on early NETs formation for the first time, and provided a new target for the treatment of sepsis.
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BACKGROUND: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac). METHODS: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. FINDINGS: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001). INTERPRETATION: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents. FUNDING: National Key R&D Program of China.
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COVID-19 , Adulto , Humanos , Niño , Adolescente , SARS-CoV-2 , Vacunas de Productos Inactivados , Anticuerpos NeutralizantesRESUMEN
Ulcerative colitis (UC), one of the foremost common forms of inflammatory bowel disease, poses a serious threat to human health. Currently, safe and effective treatments are not available. This study investigated the protective effect of ginkgolide C (GC), a terpene lactone extracted from Ginkgo biloba leaves, on UC and its underlying mechanism. The results showed that GC remarkably mitigated the severity of DSS-induced colitis in mice, as demonstrated by decreased body weight loss, reduced disease activity index, mitigated tissue damage, and increased colon length. Furthermore, GC inhibited DSS-induced hyperactivation of inflammation-related signaling pathways (NF-κB and MAPK) to reduce the production of inflammatory mediators, thereby mitigating the inflammatory response in mice. GC administration also restored gut barrier function by elevating the number of goblet cells and boosting the levels of tight junction-related proteins (claudin-3, occludin, and ZO-1). In addition, GC rebalanced the intestinal flora of DSS-treated mice by increasing the diversity of the flora, elevating the abundance of beneficial bacteria, such as Lactobacillus and Allobaculum, and decreasing the abundance of harmful bacteria, such as Bacteroides, Oscillospira, Ruminococcus, and Turicibacter. Taken together, these results suggest that GC administration effectively alleviates DSS-induced colitis by inhibiting the inflammatory response, maintaining mucosal barrier integrity, and regulating intestinal flora. This study may provide a scientific basis for the rational use of GC in preventing colitis and other related diseases.
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Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Ratones , Humanos , Animales , Sulfato de Dextran/metabolismo , Modelos Animales de Enfermedad , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Lactonas/metabolismo , Colitis Ulcerosa/metabolismo , Colon/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas de Uniones Estrechas/genética , Proteínas de Uniones Estrechas/metabolismo , Ratones Endogámicos C57BLRESUMEN
To find the risk of time thresholds of PROM for infectious diseases of term neonates. A multi-center prospective cohort study including pregnancies with PROM at term with a single fetus were conducted. Time thresholds of the duration from PROM to delivery were examined in 2-h increments to assess the rates of infectious neonatal diseases. 7019 pregnancies were included in the study. Neonatal pneumonia and sepsis were most frequent infectious diseases in neonates born from mother with PROM at term. Rates of early-onset pneumonia varied significantly when comparing length of time of PROM greater than 16 h vs. less than 16 h (for EOP in 3 days of life, adjusted OR 1.864, 95% CI 1.159 ~ 2.997, p = 0.010; for EOP in 7 days of life, adjusted OR 1.704, 95% CI 1.104 ~ 2.628, p = 0.016). Neonates born from mother of whom the length of time from PROM to delivery ≥ 16 h were at a higher risk of acquiring EOP.
Asunto(s)
Enfermedades Transmisibles , Rotura Prematura de Membranas Fetales , Enfermedades del Recién Nacido , Enfermedades Transmisibles/epidemiología , Femenino , Humanos , Recién Nacido , Medición de Resultados Informados por el Paciente , Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: Drug-eluting beads transarterial chemoem-bolization (DEB-TACE) has the advantages of slow and steady release, high local concentration, and low incidence of adverse drug reactions compared to the traditional TACE. DEB-TACE combined with sequentially ultrasound-guided radiofrequency ablation (RFA) therapy has strong anti-cancer effects and little side effects, but there are fewer related long-term studies until now. AIM: To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma (HCC). METHODS: Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited. Forty patients with untreated HCC were included in Group A, and 36 patients with recurrent HCC were included in Group B. In addition, 40 patients with untreated HCC who were treated with hepatectomy were included in Group C. The serological examination, preoperative magnetic resonance imaging examination, and post-treatment computed tomography enhanced examination were performed for all patients. The efficacy was graded as complete remission (CR), partial remission (PR), stable disease and progressive disease at the 3rd, 6th, and 9th. All patients were followed up for 3 years and their overall survival (OS), disease-free survival (DFS) were assessed. RESULTS: The efficacy of Group A and Group C was similar (P > 0.05), but the alanine aminotransferase, aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C (all P < 0.05). The proportions of CR (32.5%), PR (37.5%) were slightly higher than Group A (CR: 27.5%, PR: 35%), but the difference was not statistically significant (χ 2 = 0.701, P = 0.873). No operational-related deaths occurred in Group A and Group C. The OS (97.5%, 84.7%, and 66.1%) and the DFS (75.0%, 51.7%, and 35.4%) of Group A at the 1st, 2nd, and 3rd year after treatment were similar with those of Group C (OS: 90.0%, 79.7%, and 63.8%; DFS: 80.0%, 59.7%, and 48.6%; P > 0.05). The OS rates in Group A and Group B (90%, 82.3%, and 66.4%) were similar (P > 0.05). The DFS rates in Group B (50%, 31.6%, and 17.2%) were lower than that of Group A (P = 0.013). CONCLUSION: The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy. Patients with recurrent HCC could get a longer survival time through the combined treatment.
RESUMEN
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family, causing SFTS with high mortality rate. Haemaphysalis longicornis ticks has been demonstrated as a competent vector of SFTSV by experimental transmission study and field study. However, there has been query whether other tick species that infest human beings in the SFTS endemic regions are capable of transmitting the pathogen. Here by performing experimental transmission study, we compared the capable of transmitting SFTSV among Ixodes sinensis, Ixodes persulcatus and Dermacentor silvarum ticks. The transovarial transmission was seen in the I. sinensis ticks with a rate of 40%, but neither in I. persulcatus nor in D. silvarum ticks. I. sinensis ticks also have the ability to transmit SFTSV horizontally to uninfected mice at 7 days after feeding, but not for I. persalcatus or D. silvarum ticks. In the transstadial transmission of I. persulcatus and D. silvarum ticks, I. persulcatus ticks were tested negative from larvae to adults. But the D. silvarum ticks were tested positive from larvae to nymphs, with the positive rate of 100% (10/10) for engorged larval ticks and 81.25% (13/16) for molted nymphs. However, the mice bitten by SFTSV-infected D. silvarum nymphs were negative for SFTSV detection. Therefore, there is not enough evidence to prove the transstadial transmission of SFTSV in I. persalcatus and D. silvarum ticks.