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Severe acute respiratory syndrome coronavirus 2 breakthrough infection in highly vaccinated populations raises study on the effectiveness for inactivated vaccine, including effectiveness of the vaccine dose, the continuance of effectiveness, the effectiveness against severe/critical coronavirus disease 2019 and against secondary attacks. A population of 10 870 close contacts were investigated in a Delta variant's epidemic. The effectiveness of vaccination was estimated in a test-negative case-control study. In addition, serum was used to detect neutralizing antibodies, to explore their correlation to effectiveness. The vaccine effectiveness (VE) values were estimated for populations aged 12 years or older. The overall adjusted VE was 56.2% and a two-dose vaccine was more effective than a one-dose vaccine (56.7% vs. 43.8%). In addition, the population that got the second dose vaccine within 2 months showed higher VE than the population vaccinated for longer than 2 months (61.5% vs. 52.3%). Among the population who vaccinated 2 doses or within 2 months, a higher level of neutralizing antibodies was observed. For infected cases, vaccinated populations showed lower rates of transmission (2.63% vs. 4.36%). Further, those vaccinated cases, who were not found causing transmission, had a higher level of antibodies. The study provided a full view of the effectiveness of inactivated vaccines in a real-world setting. The time-related VE against infection and lower transmission of breakthrough vaccinated cases were observed, which may indicate that a necessity of a booster vaccine to maintain the effectiveness and high level of neutralizing antibody.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Anticorpos Neutralizantes , COVID-19/prevenção & controle , Estudos de Casos e Controles , SARS-CoV-2 , Anticorpos AntiviraisRESUMO
BACKGROUND: Complex translocation of chromosomes often causes mental retardation, dysplasia, and a variety of abnormalities in patients, which can easily lead to sperm disorders in men, and carriers are often at high risk of adverse pregnancy. METHODS: The chromosome karyotypes of the patients were analyzed by collecting peripheral blood for lymphocyte culture, chromosome harvest, section and G-banding staining. RESULTS: The results of chromosome karyotype analysis in the patient were 46,XY, T (4; 11. 6; 8)(q33; p15; p12; Q22), the translocation occurred on chromosome 4, 11, 6 and 8, and the break points were q33, p15, p12 and q22, respectively. CONCLUSIONS: Translocation occurred in 4 chromosomes of the patient, which was a complex translocation and was rare in clinic. The meiosis of the germ cells can interfere with the normal pairing and distribution of chromosomes, resulting in a high probability of abnormal gamete formation. Therefore, patients are advised to avoid natural conception, or use other people's sperm to obtain normal offspring through artificial insemination, or adopt children to achieve a successful family combination.
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Infertilidade Masculina , Sêmen , Gravidez , Feminino , Criança , Humanos , Masculino , Translocação Genética , Cariotipagem , Cariótipo , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genéticaRESUMO
BACKGROUND: Chromosome is the carrier of genetic material. Chromosome aberrations will lead to the increase or loss of genetic material, which is an important factor for early miscarriages and birth defects of newborn. Prenatal diagnosis is one of the effective approaches to find fetus with early genetic abnormalities. METHODS: A retrospective analysis of chromosome karyotype abnormality studies of 45 pregnant women with indications of amniocentesis, referred to Affiliated Hospital of Putian University, Fujian Province, Putian, China in 2015 - 2019, was performed. Among those, 45 cases of amniotic fluid specimens were cultured. Furthermore, their parents' chromosome karyotypes in peripheral blood were examined. RESULTS: Among these 45 abnormal karyotypes, balanced translocation was seen in 19 cases, including 17 cases of the genetic parents and 2 newly developed. There were 2 cases of unbalanced translocation, all of which were inherited from the father. Aneuploidy was seen in 3 cases of abnormal autosome number and 1 case of number anomalies of gender chromosomes. Polymorphism (15 cases) were all inherited from the parents, most of which were inv(9) and inv(Y) polymorphism. CONCLUSIONS: The abnormal karyotype of amniotic fluid cells was found by amniocentesis. The parents should be called back for the karyotype examination of peripheral blood to determine the source of the abnormal karyotype, and provide guidance for clinical genetic consultation and intervention, which is of great practical significance to improve the birth rate and reduce birth defects.
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Líquido Amniótico , Transtornos Cromossômicos , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Feminino , Humanos , Cariótipo , Cariotipagem , Pais , Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND: Chromosomal diseases with chromosomal abnormalities are one of the most common genetic diseases in humans, including abnormal numbers and structural abnormalities. Patau syndrome (also known as trisomy 13), Edward syndrome (also called trisomy 18), and Down syndrome (also known as trisomy 21) are all clinically fatal diseases caused by abnormal numbers of autosomes. However, there is no reliable and effective cure for chromosomal diseases, mainly relying on fast and accurate prenatal diagnosis technology to reduce the rate of birth defects. METHODS: Fluorescent-labeled primers were designed and then used in fluorescence quantitative polymerase chain reaction (FQ-PCR) composite amplification, capillary electrophoresis typing, and gene fragment analysis technology to detect 64 amniotic fluid samples, which were indicated high risks of trisomy 18 and 21 by non-invasive prenatal diagnostic technology (NIPT). The results are compared with the results of karyotype analysis and chromo-some copy variations (CNVs). RESULTS: Sixty-four samples were determined by FQ-PCR technology with the help of short tandem repeat (STR) regarded as molecular marker (STR-FQ-PCR), the result showed 61 cases of chromosomal aneuploidy were positive, including 14 cases of Edward syndrome and 47 cases of Down syndrome. A total of 460 STR locus genotypes were detected, containing 84 STR locus genotypes of Edward syndrome and 376 STR locus genotypes of Down syndrome. Chromosome karyotype analysis showed that the detected samples were all chromosomal aneuploidy. Among them were 15 cases of trisomy 18, including 14 cases of homozygous type and 1 case of chimeric type, 49 cases of trisomy 21, consisting of 47 cases homozygous type and 2 cases chimeric type. Sixty-two cases of chromosomal aneuploidy were detected by CNVs with 14 cases of trisomy 18 and 48 cases of trisomy 21. CONCLUSIONS: The detectable rate of STR-FQ-PCR technology is 95.31% while the karyotype analysis is the highest with 100%. For non-chimera and non-structural abnormal samples, the coincidence rate of results between STR-FQ-PCR technology and karyotype analysis was 100%. All above manifested the application of multiple STR loci for rapid diagnosis of Down syndrome and Edward syndrome has high clinical value.
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Síndrome de Down , Aneuploidia , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Humanos , Repetições de Microssatélites , Reação em Cadeia da Polimerase , Gravidez , Trissomia , Síndrome da Trissomía do Cromossomo 18RESUMO
OBJECTIVE: The association between computed tomography (CT) and clinical severity of COVID-19 has been demonstrated. However, there are few studies on CT and laboratory indicators in patients in COVID-19. Our aim was to explore the correlation between chest CT images and laboratory indicators of patients with COVID-19 pneumonia. METHODS: This was a retrospective study of patients with COVID-19 diagnosed and treated at the Affiliated Hospital of Putian University from 24 January 2020 to 6 March 2020. The correlation test between first chest CT score and blood cell analysis, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), blood biochemistry and T lymphocyte subsets (T-Ls) was investigated. RESULTS: Among the 56 patients, there were 36 (64.3%) males and 20 (35.7%) females. The mean age of the patients was 46.54 ± 15.82 (range, 15-86) years. The CT score in the moderate group was higher than in the mild group (5.06 ± 0.77 vs 1.87 ± 0.88, P < .05), and higher in the severe group than in the moderate and mild groups (10.71 ± 4.21, P < .05). In addition, the ESR was significantly higher in the severe group than mild group (32.00 (26.04, 58.24) vs 11.00 (7.84, 24.70) mm/h, P < .05). The CD3, CD4, CD8 and CD4/CD8 cells were not different (all P > .05). The CT scores of all patients correlated positively with CRP, LDH and ESR (all P < .01). CONCLUSION: The chest CT characteristics of patients with COVID-19 correlated positively with CRP, ESR and LDH, which may use one of the indicators for the assessment of disease severity.
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COVID-19 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Laboratórios , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND Acute pancreatitis (AP) is a symptom of sudden pancreas inflammation, which causes patients severe suffering. In general, fibroblast growth factor (FGF) levels are increased and amylase and lipase activities are elevated during AP pathogenesis, but protein concentration are low. However, the mechanism through which FGF signaling regulates AP pathogenesis remains elusive. MATERIAL AND METHODS The concentrations of PGE2, TNF-alpha, sCRP, FGF1, and FGF2 in the serum samples of the AP group and healthy control group were detected by enzyme-linked immunosorbent assay. In addition, IkappaBalpha and p-IkappaBalpha levels were analyzed in the serum samples. Subsequently, the AP rat model was established, and FGF1, FGF2, anti-FGF1, and anti-FGF2 antibodies and Bay11-7082 were injected into AP rats. TNF-alpha, PAI-1 JNK, p-JNK, IkappaBalpha, and p-IkappaBalpha levels were also examined. RESULTS Results showed that levels of PGE2, TNF-alpha, sCRP, p-IkappaBalpha, FGF1, and FGF2, as well as amylase and lipase activity were increased in patients with AP compared with those in healthy people. In addition, protein concentrations were lower in patients with AP than in the healthy group. Activation of FGF signaling by injecting FGF1 or FGF2 also inhibited AP-induced inflammation response in the pancreas and increased amylase and lipase activities, as well as protein concentration. However, the injection of FGF1 and FGF2 antibodies accelerated AP-mediated inflammation responses in the serum. In addition, Bay11-7082 injection inhibited AP activation of inflammation response and amylase and lipase activities. Protein concentration were also increased in AP rats. CONCLUSIONS FGF signaling protects against AP-mediated damage by inhibition of AP-activating inflammatory responses.
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Fator 1 de Crescimento de Fibroblastos/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Inflamação/metabolismo , Pancreatite/patologia , Transdução de Sinais , Doença Aguda , Adulto , Amilases/metabolismo , Animais , Proteína C-Reativa/análise , Estudos de Casos e Controles , Dinoprostona/sangue , Feminino , Fator 1 de Crescimento de Fibroblastos/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Humanos , Inflamação/patologia , Lipase/metabolismo , Masculino , Pessoa de Meia-Idade , Inibidor de NF-kappaB alfa/sangue , Nitrilas/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonas/farmacologia , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Complex chromosome rearrangement (CCR) often results in patients with mental retardation, stunted growth, and multiple abnormalities. CCR carriers are at high risk of adverse pregnancy, and prenatal diagnosis should be made even in normal pregnancy. The incidence of spermatogenesis disorder is high in male CCR carriers, and the chromosome involved with CCR has an impact on the fertility of male carriers. METHODS: We report a case of complex chromosome translocation: 46, XY, t(4; 10; 13) (q31; q23; q12). The lymphocytes in peripheral blood were cultured to examine the patient's karyotype. RESULTS: The patient's karyotype was detected and identified as 46, XY, t(4;10;13) (4pterâ4q31::13q12â13qter; 10pterâ10q23::4q31â4qter; 13pterâ13q12::10q23â10qter). Complex chromosome translocations occurred on chromosomes 4, 10, and 13. When combined with normal gamete, one or two derived chromosomes may be obtained in the offspring, resulting in the increase or decrease of the translocation segments of a chromosome (part of trisomy or part of monomers), thus resulting in fetal abortion, stillbirth or deformed children, etc. Conclusions: Fertility and pregnancy outcome cannot be completely determined according to the complexity of karyotype. For patients with such chromosomal abnormalities, prenatal diagnosis should be strictly carried out to prevent the birth of children with chromosomal diseases if they want to have healthy children.
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Aborto Espontâneo/genética , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 4 , Transtorno 46,XY do Desenvolvimento Sexual/genética , Fertilidade/genética , Infertilidade Masculina/genética , Translocação Genética , Aborto Espontâneo/fisiopatologia , Adulto , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/fisiopatologia , Cariótipo , Masculino , Fenótipo , GravidezRESUMO
A digital detection strategy based on a portable personal glucometer (PGM) was developed for the simple, rapid, and sensitive detection of hepatitis C virus (HCV) RNA, involving the release of glucose-loaded nanoliposomes due to coupling-site-specific cleavage by the endonuclease BamHI. The glucose-loaded nanoliposomes were synthesized using a reversed-phase evaporation method and provided an amplified signal at the PGM in the presence of HCV RNA. Initially, a 21-mer oligonucleotide complementary to HCV RNA was covalently conjugated to a magnetic bead through the amino group at the 5' end of the oligonucleotide, and then bound to a glucose-loaded liposome by typical carbodiimide coupling at its 3' end. In the presence of the target HCV RNA, the target hybridized with the oligonucleotide to form double-stranded DNA. The symmetrical duplex sequence 5'-GGATCC-3' between guanines was then catalytically cleaved by BamHI, which detached the glucose-loaded liposome from the magnetic bead. Following magnetic separation of the bead, the detached glucose-loaded liposome was lysed using Triton X-100 to release the glucose molecules within it, which were then detected as an amplified signal at the digital PGM. Under optimal conditions, the PGM signal increased with increasing HCV RNA, and displayed a strongly linear dependence on the level of HCV RNA for concentrations ranging from 10 pM to 1.0 µM. The detection limit (LOD) of the system was 1.9 pM. Good reproducibility and favorable specificity were achieved in the analysis of the target HCV RNA. Human serum samples containing HCV RNA were analyzed using this strategy, and the developed sensing platform was observed to yield satisfactory results based on a comparison with the corresponding results from a Cobas® Amplicor HCV Test Analyzer. Graphical abstract A digital detection strategy utilizing a personal glucometer was developed for the detection of hepatitis C virus RNA. The strategy involved the use of the endonuclease BamHI along with a 21-mer oligonucleotide conjugated to both a magnetic bead and a glucose-loaded nanoliposome. Hybridization of the nucleotide with the target RNA triggered the coupling-site-specific cleavage of the duplex by BamHI, leading to the release of the glucose-loaded nanoliposome. Following separation of the magnetic bead, the free nanoliposome was dissolved, liberating the glucose molecules within it, which in turn were detected as an amplified signal by the glucometer.
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Técnicas Biossensoriais/métodos , Automonitorização da Glicemia/métodos , Desoxirribonuclease BamHI/química , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Ácidos Nucleicos Imobilizados/química , RNA Viral/análise , Sequência de Bases , DNA de Cadeia Simples/química , Glucose/análise , Hepatite C/sangue , Humanos , Limite de Detecção , Lipossomos/química , Hibridização de Ácido Nucleico/métodos , RNA Viral/sangue , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Sex reversal syndrome (SRS) is a human chromosomal abnormality disease with gender dysplasia, which is characterized by inconsistency between social sexuality and genetic sexuality. METHODS: We report a case of sex reversal syndrome with 46, XX. Chemiluminescence was used to detect serum sex hormones, including testosterone (T), luteinizing hormone (LH), and follicular stimulation (FSH), and 15 karyotype analysis. RESULTS: The levels of FSH and LH in serum were high, and the level of T in serum was low. The karyotype analysis showed that the nuclear type of the patient was 46, XX. The examination of the sex-determining region Y (SRY) gene showed positive results. CONCLUSIONS: The main principle of diagnosing the 46, XX male SRS is early determination of chromosome, gonad, and genitalia gender. When the prenatal ultrasound diagnosis of pregnant women is inconsistent with the results of cytogenetics, caution should be taken to avoid the birth of children with 46, XX male SRS.
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Transtornos Testiculares 46, XX do Desenvolvimento Sexual/genética , Genes sry/genética , Aberrações dos Cromossomos Sexuais , Transtornos Testiculares 46, XX do Desenvolvimento Sexual/sangue , Adulto , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Masculina/genética , Hormônio Luteinizante/sangue , Masculino , Testosterona/sangueRESUMO
Nitrogen-doped carbon quantum dots (N-CQDs) with citric acid and ethylenediamine as raw materials were synthesized by an efficient one-step strategy. The N-CQDs showed a special property that the fluorescence was quenched by Fe3+. The quenched fluorescence of N-CQDs could be recovered by glutathione (GSH). Therefore, a "signal-on" fluorescent sensor was developed to detect GSH. The fluorescent sensor could favorably avoid the interference of ascorbic acid, dopamine, glucose, oxidized glutathione, and other amino acids in the detecting process of GSH. The proposed sensor showed a great feature that GSH can be accurately detected in the range from 0.001 to 0.1 mol/L and can be applied to detect GSH in the human serum. Therefore, the proposed method has a promising application for monitoring the blood drug concentration of GSH in clinical studies.
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Carbono/química , Glutationa/sangue , Pontos Quânticos/química , Espectrometria de Fluorescência/métodos , Fluorescência , Glutationa/análise , Humanos , Limite de Detecção , Nitrogênio/química , ComprimidosRESUMO
Objectives: To comprehensively analyze the epidemiological features of human papillomavirus (HPV) and HPV-related cervical diseases in females aged 35-64 years. Methods: A total of 149,559 samples of exfoliated cervical cells screened for HPV and related cervical lesions from January 2018 to December 2023 were enrolled. The prevalence of 15 high-risk and 6 low-risk HPV genotypes were detected, and the cervical cytology were analyzed. The impact of single and multiple HPV infections was characterized, and the effect of age was studied. Results: The cervix cytology was normal in 86.60% of the females, while 7.13% of the females were diagnosed with cervix inflammation, 0.60% with ASC-US, 0.22% with ASC-H, 0.72% with LSIL, 0.49% with HSIL, 0.03% with ICC. The highest median age was observed in ASC-H group with 54 years old. Females with primary school education or lower have the highest positive rates. The overall HPV prevalence was 8.60%. The relatively prevalent HPV types were HPV52, 58, 16, 39, 51. HPV16, HPV18, HPV58, HPV33 and HPV52 were the top5 predominant types in ICC patients. 17.41% females suffered from multiple HPV infection with the most frequently co-infection subtypes being HPV52, HPV58 and HPV16. The prevalence of all HPV subtypes increased with age. Multiple HPV infections accounted for a larger proportion in those aged above 55 years. The peak HPV16 prevalence was observed in ICC group in cases aged 45-49 and 55-59. The peak HPV33 prevalence was observed in younger individuals aged 40-44 who developed ICC. Conclusion: More action should be taken against HPV33 infection.
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BACKGROUND: 2,5-dimethylcelecoxib (DMC), a derivative of celecoxib, is an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1). Our previous studies have demonstrated that DMC inhibits the expression of programmed death-ligand 1 on hepatocellular carcinoma (HCC) cells to prevent tumor progression. However, the effect and mechanism of DMC on HCC infiltrating immune cells remain unclear. METHODS: In this study, single-cell-based high-dimensional mass cytometry was performed on the tumor microenvironment of HCC mice treated with DMC, celecoxib and MK-886 (a known mPGES-1 inhibitor). Moreover, 16S ribosomal RNA sequencing was employed to analyze how DMC improved the tumor microenvironment of HCC by remodeling the gastrointestinal microflora. RESULTS: We found that (1) DMC significantly inhibited the growth of HCC and improved the prognosis of the mice, and this depended on the stronger antitumor activity of natural killer (NK) and T cells; (2) compared with celecoxib and MK-886, DMC significantly enhanced the cytotoxic and stem-like potential, and inhibited exhaustion of NK and T cells; (3) mechanistically, DMC inhibited the expression of programmed cell death protein-1 and upregulated interferon-γ expression of NK and T cells via the gastrointestinal microbiota (Bacteroides acidifaciens, Odoribacter laneus, and Odoribacter splanchnicus)-AMPK-mTOR axis. CONCLUSIONS: Our study uncovers the role of DMC in improving the tumor microenvironment of HCC, which not only enriches the relationship between the mPGES-1/prostaglandin E2 pathway and the antitumor function of NK and T cells, but also provide an important strategic reference for multitarget or combined immunotherapy of HCC.Cite Now.
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Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Exaustão das Células T , Proteínas Quinases Ativadas por AMP , Celecoxib/farmacologia , Celecoxib/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Dinoprostona , Microambiente TumoralRESUMO
BACKGROUND: Nucleic acid detection represents limitations due to its false-negative rate and technical complexity in the COVID-19 pandemic. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests are widely spread all over the world presently. However, there is no report on the effectiveness of anti-SARS-CoV-2 antibody testing methods in China. METHODS: We gathered 10776 serum samples from close contacts of the SARS-CoV-2 infections in Fujian of China and used 2 chemiluminescence immunoassays (Wantai Bio., Yahuilong Bio.) and 2 lateral flow immunoassays (Lizhu Bio. and Dongfang Bio.) to perform the anti-SARS-CoV-2 antibody tests in China. RESULTS: The 4 antibody tests have great diagnostic value for infected or uninfected, especially in the neutralizing antibodies tests, the AUC can reach 0.939 (Wantai Bio.) and 0.916 (Yahuilong Bio.). Furthermore, we used pseudoviruses and euvirus neutralization assay to validate the effectiveness of these antibody test, the results of pseudoviruses neutralization assay or euvirus neutralization assay shows a considerable correlation with the 4 antibody detection respectively, particularly in euvirus neutralization assay, neutralizing antibodies detected by Wantai Bio. or Yahuilong Bio., the correlation can get the level of 0.93 or 0.82. CONCLUSIONS: The findings of this study demonstrate that the detections of antibodies have profound value in the diagnosis of COVID-19.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Pandemias , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
Objective: To evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China. Methods: A total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis. Results: The Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10^9/L vs. 1.31 (0.94, 1.85)×10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28 (3.31, 8.13) vs. 9.10 (4.37, 15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13 (0.00, 0.09) vs. 0.12 (0.03, 0.41), p<0.05; 0.02 (0.00, 0.14) vs. 1.94 (0.54, 6.40), p<0.05; 5.46 (2.41, 9.26) vs. 73.63 (54.63, 86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13). Conclusion: Unvaccinated children may be an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2), which indicated an urgent need of vaccination for this particular population.
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COVID-19 , SARS-CoV-2 , Idoso , Vacinas contra COVID-19 , Criança , Humanos , Imunoglobulina M , SARS-CoV-2/genéticaRESUMO
Thyroid cancer (TC) is known with a high rate of persistence and recurrence. We aimed to develop a prognostic signature to monitor and assess the survival of TC patients. mRNA expression and methylation data were downloaded from the TCGA database. Then, R package methylmix was applied to construct a mixed model was used to identify methylation-driven genes (MDGs) according to the methylation levels. Furthermore, an MDGs based prognostic signature and predictive nomogram were constructed according to the analysis of univariate and multivariate Cox regression. Totally 62 methylation-driven genes that were mainly enriched in substrate-dependent cell migration, cellular response to mechanical stimulus, et al. were found in TC tissues. aldolase C (AldoC), C14orf62, dishevelled 1 (DVL1), and protein tyrosine phosphatase receptor type C (PTPRC) were identified to be significantly related to patients' survival, and may serve as independent prognostic biomarkers for TC. Additionally, the prognostic methylation signature and a novel prognostic, predictive nomogram was established based on the methylation level of 4 MDGs. In this study, we developed a 4-MDGs based prognostic model, which might be the potential predictors for the survival rate of TC patients, and this findings might provide a novel sight for accurate monitoring and prognosis assessment.
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Proteínas Desgrenhadas/genética , Frutose-Bifosfato Aldolase/genética , Antígenos Comuns de Leucócito/genética , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/genética , Algoritmos , Movimento Celular , Proliferação de Células , Metilação de DNA , Proteínas Desgrenhadas/metabolismo , Epigênese Genética , Frutose-Bifosfato Aldolase/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Antígenos Comuns de Leucócito/metabolismo , Prognóstico , RNA Longo não Codificante/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/fisiopatologiaRESUMO
PURPOSE: Acute kidney injury (AKI) is a devastating disorder associated with considerably high morbidity and mortality. Reports have shown that AST-120, an oral charcoal adsorbent, can reduce oxidative stress by lowering serum indoxyl sulfate levels. The effects of AST-120 and indoxyl sulfate on kidney injury and cardiac dysfunction were investigated in vivo and in vitro. PATIENTS AND METHODS: Patients were tracked for enrollment upon receiving a diagnosis of AKI. Plasma was collected to determine the renal and inflammatory parameters. Renal ischemia/reperfusion (I/R) induced AKI or sham operation was performed in C57BL/6J mice. Animals were divided into sham, AKI+vehicle, and AKI+AST-120 groups. Plasma and tissues were assembled after 48 h to assess apoptotic and inflammatory responses. We also conducted human umbilical vein endothelial cell (HUVECs) and HL-1 cardiomyocyte culture studies to determine the underlying mechanisms of indoxyl sulfate's effects. Echocardiography, histopathology, biochemical indexes, ELISA, terminal dUTP nick-end labeling (TUNEL) and Western blot analysis were performed. RESULTS: The cohort included 25 consecutive patients with AKI and 25 non-AKI. Plasma levels of creatinine, indoxyl sulfate, IL-1ß and ICAM-1 were significantly higher in patients with AKI than in non-AKI controls. Plasma levels of blood urea nitrogen, creatinine, indoxyl sulfate, IL-1ß and renal tubular injury were increased in mice after renal I/R and were decreased by AST-120 treatment. In addition, AST-120 therapy not only improved the parameters assessed by echocardiography but also substantially attenuated the elevation of plasma BNP. Oral administration of AST-120 significantly downregulated NF-κB/ICAM-1 expression and reduced cell apoptosis in both kidney and heart after renal I/R injury. CONCLUSION: Our investigations demonstrated that AST-120 administration improves cardiac dysfunction in AKI mice via the suppression of apoptosis and proinflammatory NF-κB/ICAM-1 signaling.
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It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.
Assuntos
Anticorpos Neutralizantes/genética , COVID-19/genética , Imunoglobulinas/genética , Adulto , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Sítios de Ligação/imunologia , COVID-19/imunologia , COVID-19/terapia , Epitopos/genética , Epitopos/imunologia , Feminino , Genes de Imunoglobulinas/genética , Variação Genética/genética , Humanos , Imunização Passiva/métodos , Imunoglobulinas/imunologia , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/metabolismo , Ligação Proteica/imunologia , Domínios Proteicos/genética , Receptores Virais/imunologia , Receptores Virais/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Soroterapia para COVID-19RESUMO
OBJECTIVE: To compare the trauma of 3 different surgical approaches and provide a reference for clinicians in choosing the operative procedure. PATIENTS AND METHODS: A total of 150 patients were divided into the total endoscopic thyroidectomy (TET), endoscopic-assisted thyroidectomy (EAT), and conventional open thyroidectomy (COT) groups, with 50 patients in each group. The peripheral blood C-reactive protein (CRP) levels at different postoperative time points, operative time, intraoperative blood loss, postoperative drainage volume, postoperative pain, degree of satisfaction with the incision appearance, postoperative extubation time, and swallowing discomfort 3 months after surgery were compared among the groups that received different surgical approaches. RESULTS: The operative time of TET was longer than that of COT and EAT. The intraoperative blood loss was significantly lower in the TET and EAT groups than in the COT group. The postoperative drainage volume was lowest after EAT and highest after TET. The extubation time was significantly shorter after EAT than after TET and COT. The 6-hour CRP level was significantly higher after TET than after EAT and COT, and the 24-hour CRP level was better in the EAT group than in the other 2 groups. The CRP levels at 72 hours postoperatively were lowest in the EAT group and highest in the TET group. Postoperative pain was significantly lower after EAT than after TET and COT. Cosmetic satisfaction was highest in the TET group and lowest in the COT group. Swallowing discomfort was lowest in the EAT group and highest in the TET group. There was a positive correlation between the drainage volume on the first postoperative day, the drainage tube removal time, dysphagia, and the CRP level in each period. There was a positive correlation between pain, cosmetic satisfaction and CRP in 2 of the time periods. CONCLUSIONS: All 3 types of thyroidectomy are safe and reliable in benign tumor resection. Therefore, in clinical practice, the age, sex, and cosmetic needs of the patients, and the oncological safety should all be considered to provide patients with the most appropriate recommendations. In view of oncological safety, TET should be carefully selected for malignant tumor resection.