RESUMO
The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case-control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18-59 years who consisted of SARS-CoV-2 test-positive cases (n = 74) and test-negative controls (n = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6-89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40-59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%.
Assuntos
Vacinas contra COVID-19/normas , COVID-19/prevenção & controle , SARS-CoV-2/genética , Adolescente , Adulto , Distribuição por Idade , COVID-19/classificação , Vacinas contra COVID-19/administração & dosagem , Estudos de Casos e Controles , China , Surtos de Doenças , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/normas , Adulto JovemRESUMO
BACKGROUND: Osteoarthritis is caused by cartilage dysplasia and has fetal origin. Prenatal dexamethasone exposure (PDE) induced chondrodysplasia in fetal rats by inhibiting transforming growth factor ß (TGFß) signaling. This study aimed to determine the effect of dexamethasone on fetal cartilage development and illustrate the underlying molecular mechanism. METHODS: Dexamethasone (0.2 mg/kg.d) was injected subcutaneously every morning in pregnant rats from gestational day (GD) 9 to GD21. Harvested fetal femurs and tibias at GD21 for immunofluorescence and gene expression analysis. Fetal chondrocytes were treated with dexamethasone (100, 250 and 500 nM), endoplasmic reticulum stress (ERS) inhibitor, and ryanodine receptor 1 (RYR1) antagonist for subsequent analyses. RESULTS: In vivo, prenatal dexamethasone exposure (PDE) decreased the total length of the fetal cartilage, the proportion of the proliferation area and the cell density and matrix content in fetal articular cartilage. Moreover, PDE increased RYR1 expression and intracellular calcium levels and elevated the expression of ERS-related genes, while downregulated the TGFß signaling pathway and extracellular matrix (ECM) synthesis in fetal chondrocytes. In vitro, we verified dexamethasone significantly decreased ECM synthesis through activating RYR 1 mediated-ERS. CONCLUSIONS: PDE inhibited TGFß signaling pathway and matrix synthesis through RYR1 / intracellular calcium mediated ERS, which ultimately led to fetal dysplasia. This study confirmed the molecular mechanism of ERS involved in the developmental toxicity of dexamethasone and suggested that RYR1 may be an early intervention target for fetal-derived adult osteoarthritis.
Assuntos
Dexametasona/efeitos adversos , Feto/metabolismo , Feto/patologia , Osteocondrodisplasias/induzido quimicamente , Osteocondrodisplasias/embriologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Animais , Cálcio/metabolismo , Cartilagem Articular/embriologia , Cartilagem Articular/patologia , Cartilagem Articular/ultraestrutura , Condrócitos/metabolismo , Condrócitos/patologia , Estresse do Retículo Endoplasmático , Matriz Extracelular/metabolismo , Feminino , Masculino , Osteocondrodisplasias/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos Wistar , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Acute respiratory infections (ARIs) remain a significant public threat with high morbidity and mortality worldwide; viruses are significant pathogens that cause ARIs. This study was conducted to better understand the epidemiological characteristics of respiratory viruses circulating in southern China. METHODS: We collected 22,680 respiratory samples from ARI patients in 18 hospitals in southern China during 2009-2018; seven common respiratory viruses including Flu, RSV, PIV, hMPV, ADV, HCoV, and HBoV were screened using in-house real-time PCR. RESULTS: Of all samples, 9760 ARI cases (9760/22680, 43.03%) tested positive for the seven common respiratory viruses. The most detected virus was Flu (14.15%), followed by RSV (10.33%) and PIV (5.43%); Flu-A, PIV3, and HCoV-OC43 were the predominant subtypes. Although most of the viruses were detected in male inpatients, Flu was more likely detected in female outpatients. Flu infection was more likely to cause URTI (upper respiratory tract infection), whereas RSV infection was more likely to cause pneumonia and bronchitis. The prevalence of Flu was particularly high in 2009. The epidemic level was found notably high in 2014-2018 for RSV, in 2016-2018 for PIV, in the summer of 2018 for ADV, in the summer of 2016 and winter of 2018 for HCoV, and in the summer of 2011 and autumn of 2018 for HBoV. The co-detection rate of the seven viruses was 4.70%; RSV, PIV, and Flu were the most commonly co-detected viruses. CONCLUSIONS: This work demonstrates the epidemiological characteristics of seven common respiratory viruses in ARI patients in southern China.
Assuntos
Infecções Respiratórias/virologia , Vírus/isolamento & purificação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , Feminino , Hospitais/estatística & dados numéricos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Prevalência , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Estações do Ano , Vírus/classificação , Vírus/genética , Adulto JovemRESUMO
Autophagy has been reported to play protective and pathogenetic roles in cerebral ischemia/reperfusion (I/R)-induced neuronal injury. Our previous studies have shown that TP53-induced glycolysis and apoptosis regulator (TIGAR) ameliorates I/R-induced brain injury and reduces anti-cancer drug-induced autophagy activation. However, if TIGAR plays a regulatory role on autophagy in cerebral I/R injury is still unclear. The purpose of the present study is to investigate the role of TIGAR on I/R-induced autophagy activation and ischemic neuronal injury in vivo and in vitro stroke models using TIGAR-transgenic (tg-TIGAR) mice and TIGAR-knockout (ko-TIGAR) mice. The present study confirmed that autophagy was activated after I/R. Overexpression of TIGAR in tg-TIGAR mice significantly reduced I/R-induced autophagy activation and alleviated brain damage, while knockout of TIGAR in ko-TIGAR mice enhanced I/R-induced autophagy activation and exacerbated brain injury in vivo and in vitro. The different activity of autophagy in tg-TIGAR and ko-TIGAR primary neurons after OGD/R were largely reversed by knockdown or re-expression of TIGAR in these neurons. The autophagy inhibitor 3-methyladenine (3-MA) partly prevented exacerbation of brain damage induced by ko-TIGAR, whereas the autophagy inducer rapamycin partially abolished the neuroprotective effect of tg-TIGAR. Knockout of TIGAR reduced the levels of phosphorylated mTOR and S6KP70, which were blocked by 3-MA and NADPH after I/R and OGD/R in vivo and in vitro, respectively. Overexpression of TIGAR increased the levels of phosphorylated mTOR and S6KP70 under OGD/R condition, this enhancement effect was suppressed by rapamycin. In conclusion, our current data suggest that TIGAR protected against neuronal injury partly through inhibiting autophagy by regulating the mTOR-S6KP70 signaling pathway.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Isquemia Encefálica/metabolismo , Encéfalo/patologia , Neurônios/fisiologia , Monoéster Fosfórico Hidrolases/metabolismo , Traumatismo por Reperfusão/metabolismo , Adenina/análogos & derivados , Adenina/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Autofagia , Células Cultivadas , Artérias Cerebrais/cirurgia , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Fármacos Neuroprotetores , Monoéster Fosfórico Hidrolases/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Rabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients. METHODS: The most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures. RESULTS: The results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990-1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins. CONCLUSION: While the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation.
Assuntos
Vacina Antirrábica/uso terapêutico , Raiva/epidemiologia , Raiva/prevenção & controle , Animais , Mordeduras e Picadas/virologia , China/epidemiologia , Países em Desenvolvimento , Humanos , Incidência , Avaliação de Resultados em Cuidados de Saúde , Vigilância da População , Raiva/terapiaRESUMO
The technique of stent-assisted coil embolization has been widely used in the clinic, while its efficacy and safety have yet to be evaluated. This study investigates the values of computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) in evaluating the Enterprise stent-assisted coil embolization in the treatment of intracranial wide-necked aneurysm.A total of 578 intracranial wide-necked aneurysm patients confirmed by MRAâ+âCTAâ+âDSA examinations were included and treated with Enterprise stent-assisted coil embolization in this study. All patients were assigned into complete embolization (CE) group and incomplete embolization (IE) group according to the results of postoperative MRAâ+âCTAâ+âDSA examinations and Raymond grades. Hunt-Hess grades, incidence of complication and Glasgow Outcome Scale (GOS) grades of patients were investigated to assess the therapeutic effect of Enterprise stent-assisted coil embolization in intracranial wide-necked treatment. Multivariate logistic regression analysis was performed to assess risk factors for the therapeutic effect of Enterprise stent-assisted coil embolization in intracranial wide-necked aneurysm.CTA images offered a better and clearer view than MRA and DSA images in both the CE and IE groups. Both the sensitivity and specificity of CTA were apparently higher than those of MRA. Patients in the CE group enjoyed a higher good GOS rate but a lower incidence of complication than those in the IE group. In Enterprise stent-assisted coil embolization treatment, the Hunt-Hess grade, hypertension, and size of artery aneurysm were independent factors affecting the therapeutic effect of Enterprise stent-assisted coil embolization in intracranial wide-necked aneurysm.Compared with MRA, CTA shows a higher value in evaluating the therapeutic effect of Enterprise stent-assisted coil embolization for the treatment of intracranial wide-necked aneurysm, and can thus serve as an important means of predicting the therapeutic effect of endovascular intervention in treating patients with intracranial wide-necked aneurysm.
Assuntos
Prótese Vascular/normas , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Stents/normas , Adulto , Angiografia Digital/métodos , Angiografia por Tomografia Computadorizada/métodos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/classificação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Escala de Resultado de Glasgow , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Desenho de Prótese , Fatores de Risco , Resultado do TratamentoRESUMO
The inflammatory response of glial cells contributes to neuronal damage or repair after brain ischemia/reperfusion insult. We previously demonstrated a protective role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in ischemic neuronal injury through increasing the flow of pentose phosphate pathway (PPP). The present study investigated the possible role of TIGAR in ischemia/reperfusion-induced inflammatory response of astrocytes. Male ICR mice were subjected to middle cerebral artery occlusion for 2â¯h followed by 24â¯h reperfusion and cultured primary astrocytes were subjected to oxygen glucose deprivation for 9â¯h followed by 24â¯h reoxygenation (OGD/R). Adenoviral vectors were used to alter the levels of TIGAR protein in brain and in culture primary astrocytes. We showed that during the OGD/R insult the protein levels of TIGAR were rapidly increased in astrocytes. Overexpression of TIGAR mediated increased the viability, levels of NADPH and rGSH, and reduced intracellular reactive oxygen species (ROS) in cultured primary astrocytes. Overexpression of TIGAR not only significantly reduced infarct volume after stroke insult but also markedly reduced long-term mortality and improved recovery of neurological functions. Overexpression of TIGAR tempered OGD/R- or ischemia/reperfusion-induced the upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenases COX2 and the release of pro-inflammatory cytokines interleukin 1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α), while TIGAR knockdown produced opposite effects on these parameters. Moreover, Overexpression of TIGAR suppressed OGD/R-induced degradation of IκBα and NF-κB nuclear translocation in cultured primary astrocytes. The present study elucidates a novel mechanism by which TIGAR protects neurons against ischemia/reperfusion injury.
Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , Inflamação/metabolismo , Neuroproteção/fisiologia , Proteínas/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Proteínas Reguladoras de Apoptose , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Glucose/deficiência , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Inflamação/tratamento farmacológico , Masculino , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Neuroproteção/efeitos dos fármacos , Via de Pentose Fosfato/fisiologia , Monoéster Fosfórico Hidrolases , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologiaRESUMO
Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010-2015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those <3 years old) and old people (>50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013-2014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013-2014 in Guanzhou, south China.
Assuntos
Coronavirus/isolamento & purificação , Filogenia , Infecções Respiratórias/epidemiologia , China/epidemiologia , Coronavirus/classificação , Coronavirus/patogenicidade , HumanosRESUMO
BACKGROUND: The rapid transmission and high mortality rate made severe acute respiratory syndrome (SARS) a global threat for which no efficacious therapy is available now. Without sufficient knowledge about the SARS coronavirus (SARS-CoV), it is impossible to define the candidate for the anti-SARS targets. The putative non-structural protein 2 (nsp2) (3CL(pro), following the nomenclature by Gao et al, also known as nsp5 in Snidjer et al) of SARS-CoV plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development, so we carried on this study to have an insight into putative polymerase nsp2 of SARS-CoV Guangdong (GD) strain. METHODS: The SARS-CoV strain was isolated from a SARS patient in Guangdong, China, and cultured in Vero E6 cells. The nsp2 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into eukaryotic expression vector pCI-neo (pCI-neo/nsp2). Then the recombinant eukaryotic expression vector pCI-neo/nsp2 was transfected into COS-7 cells using lipofectin reagent to express the nsp2 protein. The expressive protein of SARS-CoV nsp2 was analyzed by 7% sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The nucleotide sequence and protein sequence of GD nsp2 were compared with that of other SARS-CoV strains by nucleotide-nucleotide basic local alignment search tool (BLASTN) and protein-protein basic local alignment search tool (BLASTP) to investigate its variance trend during the transmission. The secondary structure of GD strain and that of other strains were predicted by Garnier-Osguthorpe-Robson (GOR) Secondary Structure Prediction. Three-dimensional-PSSM Protein Fold Recognition (Threading) Server was employed to construct the three-dimensional model of the nsp2 protein. RESULTS: The putative polymerase nsp2 gene of GD strain was amplified by RT-PCR. The eukaryotic expression vector (pCI-neo/nsp2) was constructed and expressed the protein in COS-7 cells successfully. The result of sequencing and sequence comparison with other SARS-CoV strains showed that nsp2 gene was relatively conservative during the transmission and total five base sites mutated in about 100 strains investigated, three of which in the early and middle phases caused synonymous mutation, and another two base sites variation in the late phase resulted in the amino acid substitutions and secondary structure changes. The three-dimensional structure of the nsp2 protein was successfully constructed. CONCLUSIONS: The results suggest that polymerase nsp2 is relatively stable during the phase of epidemic. The amino acid and secondary structure change may be important for viral infection. The fact that majority of single nucleotide variations (SNVs) are predicted to cause synonymous, as well as the result of low mutation rate of nsp2 gene in the epidemic variations, indicates that the nsp2 is conservative and could be a target for anti-SARS drugs. The three-dimensional structure result indicates that the nsp2 protein of GD strain is high homologous with 3CL(pro) of SARS-CoV urbani strain, 3CL(pro) of transmissible gastroenteritis virus and 3CL(pro) of human coronavirus 229E strain, which further suggests that nsp2 protein of GD strain possesses the activity of 3CL(pro).
Assuntos
Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Animais , Células COS , Cisteína Endopeptidases/biossíntese , Variação Genética , Humanos , Modelos Moleculares , Proteínas Recombinantes/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/química , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Difração de Raios XRESUMO
BACKGROUND: Rabies is very common in People's Republic of China. Henan province, in the central portion of China, is one of the most densely populated provinces in the entire country. With the new rabies epidemic trend noted in northern and western China, it is necessary to investigate the characteristics of human rabies in this area and control the disease. METHODS: We chose patients in hospital isolation in 18 municipalities in Henan province as the investigation subjects. Data were collected through systematic reporting from these hospitals, whereas a questionnaire was applied to the relatives of patients. RESULTS: A total of 1022 rabies cases were reported. The incidence of human rabies in Henan has increased rapidly since 2005, having peaked in 2007, and maintained a high level in the remaining years. The cases were found mainly in rural areas in the south and east of the province. Rabies was often noted in summer and with the highest number in August. Most cases were noted in males and often in farmers. The patients aged between 40 and 60 years accounted for 36.8 % of all the cases. The wound treatment rate (12.2 %) and vaccination rate (2.6 %) of rabies cases after exposure were relatively low, while the rabies immunoglobulin utilization rate was only 2.8 %. CONCLUSIONS: Rabies epidemic cases at the county level overall were increasing in Henan province during the period of 2005-2013; the epidemic has spread quickly. The data in this study imply that the disease could be better managed by more integrated surveillance across human health and veterinary sectors, improved education and better government policies.
RESUMO
OBJECTIVES: To evaluate the performance of clustering methods used in the prognostic assessment of categorical clinical data for hepatocellular carcinoma (HCC) patients in China, and establish a predictable prognostic nomogram for clinical decisions. MATERIALS AND METHODS: A total of 332 newly diagnosed HCC patients treated with hepatic resection during 2006-2009 were enrolled. Patients were regularly followed up at outpatient clinics. Clustering methods including the Average linkage, k-modes, fuzzy k-modes, PAM, CLARA, protocluster, and ROCK were compared by Monte Carlo simulation, and the optimal method was applied to investigate the clustering pattern of the indices including platelet count, platelet/lymphocyte ratio (PLR) and serum aspartate aminotransferase activity/platelet count ratio index (APRI). Then the clustering variable, age group, tumor size, number of tumor and vascular invasion were studied in a multivariable Cox regression model. A prognostic nomogram was constructed for clinical decisions. RESULTS: The ROCK was best in both the overlapping and non-overlapping cases performed to assess the prognostic value of platelet-based indices. Patients with categorical platelet-based indices significantly split across two clusters, and those with high values, had a high risk of HCC recurrence (hazard ratio [HR] 1.42, 95% CI 1.09-1.86; p<0.01). Tumor size, number of tumor and blood vessel invasion were also associated with high risk of HCC recurrence (all p<0.01). The nomogram well predicted HCC patient survival at 3 and 5 years. CONCLUSIONS: A cluster of platelet-based indices combined with other clinical covariates could be used for prognosis evaluation in HCC.
Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Método de Monte Carlo , Aspartato Aminotransferases/sangue , Plaquetas , Carcinoma Hepatocelular/cirurgia , China , Análise por Conglomerados , Humanos , Neoplasias Hepáticas/cirurgia , Contagem de Linfócitos , Recidiva Local de Neoplasia/mortalidade , Nomogramas , Contagem de Plaquetas , PrognósticoAssuntos
Síndrome Respiratória Aguda Grave/etiologia , Enzima de Conversão de Angiotensina 2 , Moléculas de Adesão Celular/fisiologia , Quimiocinas/fisiologia , Citocinas/fisiologia , Predisposição Genética para Doença , Humanos , Lectinas Tipo C/fisiologia , Peptidil Dipeptidase A/fisiologia , Receptores de Superfície Celular/fisiologia , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/imunologiaRESUMO
To describe the recombination features of human enterovirus 71 strain Guangzhou09 isolated in Guangzhou in 2009, the complete nucleotide sequences of Guangzhou09 were analyzed by various of bioinformatics software. Phylogenetic analysis based on P1, P2 and P3 regions indicated that recombination occurred between EV71 and CVA4. Phylogenetic, similarity plot and bootscan analysis further revealed the recombination between EV71 genotype C strain Shanghai-FJ713317 and CVA4 strain HQ728260 at region 2B was close to the nucleotide position 4 027. This represents the first evidence for intertypic recombination between EV71 subtype C4 and CVA4 in Guangzhou.
Assuntos
Enterovirus Humano A/genética , Enterovirus Humano A/isolamento & purificação , Doença de Mão, Pé e Boca/virologia , Recombinação Genética , Sequência de Bases , China/epidemiologia , Enterovirus Humano A/química , Enterovirus Humano A/classificação , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Dados de Sequência Molecular , Filogenia , Homologia de Sequência do Ácido Nucleico , Proteínas Virais/química , Proteínas Virais/genéticaAssuntos
Síndrome Respiratória Aguda Grave/diagnóstico , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/isolamento & purificação , Adulto , Anticorpos Antivirais/sangue , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/virologia , Fatores de TempoRESUMO
To compare and analyze the variation of PB1-F2 genes of Influenza A Viruses from Guangzhou during 2009 to 2011 with the Influenza A Viruses from all over the world, to lay the foundation of functional research and interaction mechanism of the PB1-F2 protein. 17 Novel H1N1 influenza viruses and 1 seasonal H1N1 influenza virus have been isolated from human in Guangzhou during 2009 to 2011 that were cloned into pMD 18-T Vector for sequencing. Then, 68 PB1-F2 genes of IAVs from human around the world were downloaded from GenBank database and analyzed using molecular biological software. The phylogenetic tree result shows that the PB1-F2 genes of IAV from the world separated into two main groups. There is high homology of PB1-F2 genes of one Seasonal H1N1 virus and Novel H1N1 viruses which were isolated in Guangzhou compared with the global Novel H1N1 viruses. And all of them got the 11 amino acids truncated protein by mutation included one seasonal H1N1 strain isolated by our laboratory. There is no variation of PB1-F2 genes of Novel H1N1 virus in Guangzhou compared with the worldwide strains. However, one seasonal H1N1 virus which isolated by our laboratory shows analogous truncated mutation of PB1-F2 of Novel H1N1 virus, it reveals that the PB1-F2 gene might has done the early reassortment between the Novel H1N1 virus and seasonal H1N1 virus.
Assuntos
Evolução Molecular , Variação Genética , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Proteínas Virais/genética , Sequência de Aminoácidos , China , Clonagem Molecular , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Dados de Sequência Molecular , Mutação , Filogenia , Proteínas Virais/químicaRESUMO
PSM-E is a newly discovered alternatively spliced variant of prostate-specific membrane antigen (PSMA). In the current study, its role on the proliferation, invasiveness and migration in prostate cancer cell lines was analyzed. PSM-E and PSMA (as a comparison) eukaryotic expression vectors pcDNA3.0/PSM-E and pcDNA3.0/PSMA were constructed, validated by RT-PCR and Western blotting, and PSMA/PSM-E overexpression PC-3 cell models were built. Gene interference was used to block PSMA and the expression of its splice variants in LNCap cells. Three shRNA fragments were synthesized against PSMA, cloned into the vector pSilencer 2.1-U6-neo, their interference effect was evaluated by RT-PCR and Western blotting, and pSilencer 2.1-U6-neoshRNA3 (named pshRNA3) was chosen in further analyses. Growth curves were drawn to observe the proliferation change, which showed that PSM-E had the potential to suppress proliferation (P<0.05), but no significant change was observed in PSMA/PC-3 cells and in PSMA/PSM-E interfering LNCap cells (P>0.05). Cross-river test showed that the migration speeds of PSM-E/PC-3 and PSMA/PC-3 were both significantly slower than the vector negative control, and faster in p-shRNA3 interfering LNCap cells compared with its vector negative control (P<0.05), and no significant difference existed between PSM-E/PC-3 and PSMA/PC-3 (P>0.05). Transwell assay showed that the invasive cells of both PSMA/PC-3 and PSM-E/PC-3 were fewer compared to the vector negative control (P<0.05), and the invasive suppression effect of PSM-E was weaker than PSMA (P<0.05), and accordingly, invasiveness of interfering LNCaP cells was enhanced compared with the vector negative control (P<0.05). These results showed that PSM-E could suppress proliferation, migration and invasiveness of prostate cancer cells. Its suppression effect on cell proliferation is stronger compared to PSMA and the suppression effect on invasiveness is weaker than that of PSMA.
Assuntos
Antígenos de Superfície/genética , Movimento Celular , Proliferação de Células , Glutamato Carboxipeptidase II/genética , Neoplasias da Próstata/patologia , Antígenos de Superfície/metabolismo , Linhagem Celular Tumoral , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Invasividade Neoplásica , Neoplasias da Próstata/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMO
Human bocavirus (HBoV) is a novel parvovirus associated with respiratory tract diseases and gastrointestinal illness in adult and pediatric patients throughout the world. To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. Specimens were screened for HBoV by real-time PCR and other 6 common respiratory viruses by RT-PCR or PCR. HBoV was detected in 58 (1.68%) out of 3460 samples, mostly from pediatric patients (52/58) and inpatient children (47/58). Six adult patients were detected as HBoV positive and 5 were emergency cases. Of these HBoV positive cases, 19 (32.76%) had co-pathogens including influenza virus (n = 5), RSV (n = 5), parainfluenza (n = 4), adenovirus (n = 1), coronavirus (n = 7). The complete genome sequences of 2 HBoVs strains (Genbank no. JN794565 and JN794566) were analyzed. Phylogenetic analysis showed that the 2 HBoV strains were HBoV1, and were most genetically close to ST2 (GenBank accession number DQ0000496). Recombination analysis confirmed that HBoV strain GZ9081 was an intra-genotype recombinant strain among HBoV1 variants.
Assuntos
Bocavirus Humano/genética , Bocavirus Humano/metabolismo , Infecções Respiratórias/virologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Primers do DNA/genética , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Filogenia , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Análise de Sequência de DNA/métodos , Análise de Sequência de RNA/métodosAssuntos
Virus da Influenza A Subtipo H5N1/genética , Humanos , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/patogenicidade , Vacinas contra Influenza/imunologia , Influenza Humana/tratamento farmacológico , Influenza Humana/prevenção & controle , Influenza Humana/transmissão , VacinaçãoAssuntos
Síndrome Respiratória Aguda Grave/prevenção & controle , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Vacinas Virais/imunologia , Humanos , Glicoproteínas de Membrana/imunologia , Glicoproteína da Espícula de Coronavírus , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/imunologia , Proteínas do Envelope Viral/imunologia , Vírion/imunologiaRESUMO
Background Rabies is very common in Peoples Republic of China. Henan province, in the central portion of China, is one of the most densely populated provinces in the entire country. With the new rabies epidemic trend noted in northern and western China, it is necessary to investigate the characteristics of human rabies in this area and control the disease.Methods We chose patients in hospital isolation in 18 municipalities in Henan province as the investigation subjects. Data were collected through systematic reporting from these hospitals, whereas a questionnaire was applied to the relatives of patients.Results A total of 1022 rabies cases were reported. The incidence of human rabies in Henan has increased rapidly since 2005, having peaked in 2007, and maintained a high level in the remaining years. The cases were found mainly in rural areas in the south and east of the province. Rabies was often noted in summer and with the highest number in August. Most cases were noted in males and often in farmers. The patients aged between 40 and 60 years accounted for 36.8 % of all the cases. The wound treatment rate (12.2 %) and vaccination rate (2.6 %) of rabies cases after exposure were relatively low, while the rabies immunoglobulin utilization rate was only 2.8 %.Conclusions Rabies epidemic cases at the county level overall were increasing in Henan province during the period of 20052013; the epidemic has spread quickly. The data in this study imply that the disease could be better managed by more integrated surveillance across human health and veterinary sectors, improved education and better government policies.