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2.
Front Pharmacol ; 13: 864058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571140

RESUMO

Understanding metabolite profiles may aid in providing a reference for individualized treatment using PEG-rhGH. Therefore, this study aimed to evaluate the clinical efficacy of PEG-rhGH in treating GHD patients by using a metabolomic approach. Fifty-seven pediatric participants treated with PEG-rhGH were enrolled (28 GHD patients with high clinical efficacy and 29 GHD patients with lower clinical efficacy). Serum samples from all patients were first collected at baseline for biochemical detection; then metabolite levels were measured using gas chromatography time-of-flight mass spectrometry. The candidates included heptadecanoic acid, stearic acid, 2-hydroxybutyric acid, myristic acid, palmitoleic acid, D-galactose, dodecanoic acid, and oleic acid. The related metabolic pathways involved fatty acid metabolism and energy metabolism. This study suggested that growth gains of PEG-rhGH treatment might be differentiated by altered serum levels of fatty acid. Collectively, the metabolomic study provides unique insights into the use of PEG-rhGH as a therapeutic strategy for individualized treatment.

3.
Minerva Anestesiol ; 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35416464

RESUMO

BACKGROUND: Distinguishing light-echoed nerves from surrounding structures is challenging but may be important in nerve block administration. We evaluated the effect of patient characteristics on the echogenicity or visibility of the popliteal sciatic nerve (PSN). METHODS: This study included adult patients who presented to the operating room as volunteers. The primary outcome was the success rate of nerve identification by ultrasound using different PSN access paths. The secondary outcome included the PSN visibility score (VIS), scan time, and PSN depth. Logistic regression analysis was used to identify factors associated with the PSN identification success rate. The body mass index (BMI) proximal-based cut-off was used to compare the PSN identification success rate through different access paths. RESULTS: The PSN was successfully identified in 89.7% of the volunteers. The access paths (P < 0.01) and BMI (P = 0.01) were identified as independent predictors of successful PSN identification. A higher PSN identification success rate (P = 0.01), a higher VIS (P < 0.01), a more superficial PSN depth (P < 0.01), and a shorter scan time (P < 0.01) were observed in the above-knee lateral approach. Among volunteers with BMI ≥ 26.77 kg/m2, the PSN identification success rate through the above-knee lateral approach was significantly higher (P < 0.01), and PSN depth was shallower (P < 0.01) than through the medial approach. CONCLUSIONS: The ultrasound-guided above-knee lateral approach for PSN block improved the PSN identification success rate, ensured a more superficial nerve location, and provided a clearer image.

4.
Platelets ; : 1-8, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35343875

RESUMO

Protease-activated receptor 4 (PAR4) is a promising drug target to improve the efficacy/safety window of antiplatelet agents. The native peptide GYPGQV and the more potent peptide AYPGKF, are PAR4-specific activators. However, these PAR4 agonist peptides (APs) elicit an agonist response, for example, platelet aggregation, at concentrations of 50 to 1000 µM in platelet-function assays, thereby limiting their utility to monitor the pharmacodynamic effects of PAR4 antagonists over a wide concentration range. Improved pharmacodynamic assays are needed for clinical development of PAR4 antagonists. We attempted to identify potent PAR4 APs to aid development of robust assays for optimization of PAR4 antagonists. Using an AYPG-based biased phage display peptide library approach followed by chemical peptide optimization, A-Phe(4-F)-PGWLVKNG was identified. This peptide demonstrated an EC50 value of 3.4 µM in a platelet-aggregation assay, which is 16-fold more potent than AYPGKF. Using this new PAR4 AP, a platelet-rich plasma-aggregation assay using light-transmission aggregometry was developed and validated in a series of precision and reproducibility tests. PAR4 antagonist responses to PAR4 AP A-Phe(4-F)-PGWLVKNG (12.5 µM to 100 µM) were subsequently evaluated in this assay in vitro and ex vivo in a human study using BMS-986120, a PAR4 antagonist that entered clinical studies.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35351627

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increasing in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

6.
Ann Transl Med ; 10(2): 121, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35282114

RESUMO

Background: Nomograms are predictive tools widely used for estimating cancer prognosis. We aimed to develop/validate a nomogram to predict the postsurgical 5-year overall survival (OS) and disease-free survival (DFS) probability for patients with stages IB1, IB2, and IIA1 cervical cancer [2018 International Federation of Gynecology and Obstetrics (FIGO 2018)]. Methods: We retrospectively enrolled cervical cancer patients at 47 hospitals with stages IB1, IB2, and IIA1 disease from the Clinical Diagnosis and Treatment for Cervical Cancer in China database. All patients were assigned to either the development or validation cohort (75% of patients used for model construction and 25% used for validation). OS and DFS were defined as the clinical endpoints. Clinicopathological variables were analyzed based on the Cox proportional hazards regression model. A nomogram was established and validated internally (with bootstrapping) and externally, and its performance was assessed according to the concordance index (C-index), receiver-operating characteristic curve, and calibration plot. Results: In total, 4,065 patients were enrolled and assigned to the development cohort (n=3,074) or validation cohort (n=991). The OS nomogram was constructed based on age, FIGO stage, stromal invasion, and lymphovascular space invasion (LVSI). The DFS nomogram was constructed based on the FIGO stage, histological type, stromal invasion, and LVSI. Both nomograms showed greater discrimination than the FIGO 2018 staging system in the development cohort [OS nomogram vs. FIGO 2018: C-index =0.69 vs. 0.61, area under the curve (AUC): 69.8 vs. 60.3; DFS nomogram vs. FIGO 2018: C-index =0.64 vs. 0.57, AUC: 62.6 vs. 56.9], and the same results were observed the definition in the validation cohort. Calibration plots demonstrated good agreement between the predicted and actual probabilities of 5-year OS/DFS in the development and validation cohorts. We stratified the patients into 3 subgroups with differences in OS/DFS. Each risk subgroup presented a distinct prognosis. Conclusions: We successfully developed a robust and powerful model for predicting 5-year OS/DFS in stages IB1, IB2, and IIA1 cervical cancer (FIGO 2018) for the first time. Internal and external validation showed that the model had great prediction performance and was superior to the currently utilized FIGO staging system.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35172306

RESUMO

OBJECTIVES: The results of studies regarding the association between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) are controversial. DESIGN: This meta-analysis was conducted to evaluate the relationship between PCOS and GDM. METHODS: English language articles published before July 2021 were included by searching in databases: PubMed, EMBASE, Web of Science, Medline and Google Scholar. All these results were computed using STATA 12.0 software. The random-effects models were used to calculate summary odds ratio (OR) or relative risk (RR) and 95% confidence interval (CI) when the heterogeneity was high; Inversely, the fixed-effects models were used to calculate summary OR/RR and 95% CI when the heterogeneity was low. RESULTS: The present study showed that PCOS was significantly associated with an increased risk of GDM with a random effects model (OR/RR = 2.02, 95% CI 1.74 to 2.34, I2 = 79.5%, p < 0.0001). Subgroup analysis indicated an elevated risk of GDM in PCOS patients in both retrospective and prospective studies (retrospective studies: OR = 1.89, 95% CI 1.62 to 2.20; prospective studies: RR = 2.85, 95% CI 1.77 to 4.60). In addition, subgroup analysis indicated an elevated risk of GDM in PCOS patients in both Caucasian and Asian populations (Caucasian populations: OR/RR = 2.47, 95% CI 1.99 to 3.07; prospective studies: OR/RR = 1.58, 95% CI 1.23 to 2.02). CONCLUSION: Overall, findings of the meta-analysis showed that women with PCOS have an elevated risk of GDM compared to women without PCOS. LIMITATIONS: First, on account of sources of information, the role of several variables including BMI, the severity of GDM and serum lipid level in the association between PCOS and GDM can not be evaluated. Second, only studies published in English and Chinese were included, and the publish bias is impossible to avoid.

8.
Nat Chem Biol ; 17(12): 1281-1288, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34764473

RESUMO

Most lectins bind carbohydrate ligands with relatively low affinity, making the identification of optimal ligands challenging. Here we introduce a point accumulation in nanoscale topography (PAINT) super-resolution microscopy method to capture weak glycan-lectin interactions at the single-molecule level in living cells (Glyco-PAINT). Glyco-PAINT exploits weak and reversible sugar binding to directly achieve single-molecule detection and quantification in cells and is used to establish the relative kon and koff rates of a synthesized library of carbohydrate-based probes, as well as the diffusion coefficient of the receptor-sugar complex. Uptake of ligands correlates with their binding affinity and residence time to establish structure-function relations for various synthetic glycans. We reveal how sugar multivalency and presentation geometry can be optimized for binding and internalization. Overall, Glyco-PAINT represents a powerful approach to study weak glycan-lectin interactions on the surface of living cells, one that can be potentially extended to a variety of lectin-sugar interactions.


Assuntos
Lectinas/química , Polissacarídeos/química , Imagem Individual de Molécula/métodos , Bibliotecas de Moléculas Pequenas/química , Animais , Células CHO , Membrana Celular , Permeabilidade da Membrana Celular , Cricetulus , Cinética , Ligantes , Análise Multivariada , Ligação Proteica , Relação Estrutura-Atividade
9.
Pestic Biochem Physiol ; 179: 104970, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802520

RESUMO

The widespread use of herbicides has raised considerable concern with regard to their harmful consequences on plant growth, crop yield and the soil ecological environment. It has been well documented that colonization of rhizobacteria in the plant root system has a positive effect on activation of plant defenses to protect the plant from damage. Using the platform of high-throughput analysis with tandem mass spectrometry and Illumina sequencing, we identified the specific activated rhizobacteria, the key growth stimulating substances and the metabolic pathways involved in seedling stage tolerance to mefenacet stress in rice. The relative abundance of beneficial rhizospheremicrobes such as Acidobacteria and Firmicutes increased with mefenacet treatment, indicating that the rhizosphere recruited some beneficial microbes to resist mefenacet stress. Mefenacet treatment induced alterations in several interlinked metabolic pathways, many of which were related to activation of defense response signaling, especially the indole-3-pyruvate pathway. Indole-3-acetaldehyde and indole-3-ethanol from this pathway may act as flexible storage pools for indole-3-acetic acid (IAA). Our findings also suggest that a significant increase of IAA produced by the enrichment of beneficial rhizospheremicrobes, for example genus Bacillus, alleviated the dwarfing phenomenon observed in hydroponic medium following mefenacet exposure, which may be a key signaling molecule primarily for phytostimulation and phytotolerance in microbe-plant interactions.


Assuntos
Oryza , Rizosfera , Acetanilidas , Benzotiazóis , Raízes de Plantas , Microbiologia do Solo
10.
BMC Cancer ; 21(1): 1091, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627169

RESUMO

BACKGROUND: Current opinions on whether surgical patients with cervical cancer should undergo para-aortic lymphadenectomy at the same time are inconsistent. The present study examined differences in survival outcomes with or without para-aortic lymphadenectomy in surgical patients with stage IB1-IIA2 cervical cancer. METHODS: We retrospectively compared the survival outcomes of 8802 stage IB1-IIA2 cervical cancer patients (FIGO 2009) who underwent abdominal radical hysterectomy + pelvic lymphadenectomy (n = 8445) or abdominal radical hysterectomy + pelvic lymphadenectomy + para-aortic lymphadenectomy (n = 357) from 37 hospitals in mainland China. RESULTS: Among the 8802 patients with stage IB1-IIA2 cervical cancer, 1618 (18.38%) patients had postoperative pelvic lymph node metastases, and 37 (10.36%) patients had para-aortic lymph node metastasis. When pelvic lymph nodes had metastases, the para-aortic lymph node simultaneous metastasis rate was 30.00% (36/120). The risk of isolated para-aortic lymph node metastasis was 0.42% (1/237). There were no significant differences in the survival outcomes between the para-aortic lymph node unresected and resected groups. No differences in the survival outcomes were found before or after matching between the two groups regardless of pelvic lymph node negativity/positivity. CONCLUSION: Para-aortic lymphadenectomy did not improve 5-year survival outcomes in surgical patients with stage IB1-IIA2 cervical cancer. Therefore, when pelvic lymph node metastasis is negative, the risk of isolated para-aortic lymph node metastasis is very low, and para-aortic lymphadenectomy is not recommended. When pelvic lymph node metastasis is positive, para-aortic lymphadenectomy should be carefully selected because of the high risk of this procedure.


Assuntos
Excisão de Linfonodo/mortalidade , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/cirurgia , Estudos de Casos e Controles , China , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Histerectomia/mortalidade , Histerectomia/estatística & dados numéricos , Excisão de Linfonodo/estatística & dados numéricos , Metástase Linfática , Pessoa de Meia-Idade , Pelve , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias do Colo do Útero/patologia
11.
Eur J Anaesthesiol ; 38(11): 1180-1186, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34617919

RESUMO

BACKGROUND: Nasotracheal intubation is usually required in patients undergoing oromaxillofacial, otolaryngological or plastic surgery to prevent the airway encroaching into the operating field. Epistaxis is the most common complication, but which nostril is associated with a lower incidence and severity of epistaxis is still unclear. OBJECTIVE: When both nostrils are patent, to determine the preferred nostril for nasotracheal intubation under general anaesthesia. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). The primary outcome was the incidence of epistaxis and the secondary outcomes included the incidence of severe epistaxis, the time required to pass the tube through the nasal passage and total intubation time. DATA SOURCES: PubMed, Embase and the Cochrane Register of Controlled Trials were searched from database inception to 1 March 2020. ELIGIBILITY CRITERIA: The only studies included were RCTs comparing epistaxis related to nasotracheal intubation via right or left nostril, in adult surgery patients undergoing general anaesthesia. RESULTS: Ten RCTs with 1658 patients were included. Compared with the left nostril, intubation via the right nostril was associated with a significantly lower incidence of epistaxis: risk ratio (RR) and 95% confidence intervals (CI) were 0.78 (0.62 to 0.99), P = 0.04: a lower incidence of severe epistaxis (five studies, n=923), RR 0.40 (0.22 to 0.75), P = 0.004: and a shorter intubation time (three studies, n=345), mean difference -7.28 (-14.40 to -0.16) seconds, P = 0.05. In two studies (n=310), no significant difference between the right and left nostril was observed in the time to pass the tube through the nasal passages, mean difference -0.59 (-1.95 to 0.77) s, P = 0.40. CONCLUSION: On the basis of the current available evidence, when both nostrils are patent, the right nostril is more appropriate for nasotracheal intubation, with a lower incidence and severity of epistaxis and faster intubation time. TRIAL REGISTRATION: The study protocol has been registered in PROSPERO (CRD42020169949).


Assuntos
Epistaxe , Intubação Intratraqueal , Adulto , Anestesia Geral , Epistaxe/diagnóstico , Epistaxe/epidemiologia , Epistaxe/prevenção & controle , Humanos , Intubação Intratraqueal/efeitos adversos , Cavidade Nasal , Razão de Chances
12.
Mitochondrial DNA B Resour ; 6(10): 3028-3030, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568572

RESUMO

Chrysosplenium nudicaule Bunge, Tibetan name 'Yajima,' growing in the highlands of China is a perennial herb belonging to the genus Chrysosplenium Saxifragaceae. As a traditional Chinese medicine, it has been used to treat digestive diseases for hundreds of years. The complete chloroplast genome of Chrysosplenium nudicaule is 152,775 bp in length and comprises two inverted repeats (IR, 25,962 bp), a large single-copy region (LSC, 83,533 bp), and a small single-copy region (SSC, 17,318 bp). It harbors 112 genes, including 78 protein-coding genes, four ribosomal RNA genes, and 30 transfer RNA genes. In addition, the rpl32 gene was deleted. The GC content of the whole chloroplast genome is 37.54%. This chloroplast genome resource will be useful for study on the evolution and genetic diversity of C. nudicaule in the future.

13.
Clin Transl Med ; 11(9): e538, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34586744

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment-naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC-related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top-ranked prognostic proteins X-prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well-known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi-omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.


Assuntos
Biologia Computacional/métodos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteoma/genética , Transcriptoma/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/terapia , Perfilação da Expressão Gênica , Humanos , Proteômica
14.
Thromb Haemost ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34555861

RESUMO

The objective of this study was to assess the relationship between factor XI (FXI) deficiency and the risks of bleeding and cardiovascular (CV) events. We conducted a retrospective cohort study using data from Maccabi Healthcare Services (MHS). We identified adults with FXI deficiency (severe: <15%, partial: 15 to <50%, any deficiency: <50%) that had been tested for FXI between 2007 and 2018 and matched to patients from the general MHS population. We estimated 10-year risks of outcomes using the Kaplan-Meier approach. Using Cox proportional hazards regression, we compared outcomes among patients with versus without FXI deficiency. Less than 10% of patients tested for FXI activity had activity levels <50% (mean age: 39 years; 72.2% females). Compared with the general population, patients with any FXI deficiency were at higher risk of severe bleeding (adjusted hazard ratio [aHR]: 2.56, 95% confidence interval [CI]: 1.13-5.81; 10-year risk: 1.90%, 95% CI: 0.50-3.20% vs. 0.90%, 95% CI: 0.50-1.30%) and clinically relevant nonsevere bleeding (CRNSB) (aHR: 1.45, 95% CI: 1.08-1.97; 10-year risk: 11.60%, 95% CI: 8.30-14.80% vs. 9.20%, 95% CI: 8.00-10.40%). Severe FXI deficiency was associated with a greater risk of CRNSB. While few CV events (N = 2) and venous thromboembolisms (VTE) (N = 1) were observed in the FXI overall deficient group, there was a nonsignificant negative association between any FXI deficiency and CV events (aHR: 0.55; 95% CI: 0.13-2.36) and VTEs (aHR: 0.45; 95% CI: 0.06-3.47). Overall FXI deficiency was associated with an increased risk of severe bleeding and CRNSB. Further research is warranted to explore the lower risk of CV and VTE among patients with FXI deficiency compared with the general population.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 889-895, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34535202

RESUMO

OBJECTIVES: To investigate the incidence of maternal group B Streptococcus (GBS) colonization and neonatal early-onset GBS disease (GBS-EOD), and to study the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. METHODS: A total of 16 384 pregnant women and 16 634 neonates delivered by them were enrolled prospectively who had medical records in Xiamen Maternal and Child Care Hospital, Beijing Obstetrics and Gynecology Hospital of Capital Medical University, and Zhangzhou Zhengxing Hospital from May 1, 2019 to April 30, 2020. Unified GBS screening time, culture method, and indication for intrapartum antibiotic prophylaxis (IAP) were adopted in the three hospitals. The incidence rates of maternal GBS colonization and neonatal GBS-EOD were investigated. A multivariate logistic regression analysis was used to identify the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. RESULTS: In these three hospitals, the positive rate of GBS culture among the pregnant women in late pregnancy was 11.29% (1 850/16 384), and the incidence rate of neonatal GBS-EOD was 0.96‰ (16/16 634). The admission rate of live infants born to the GBS-positive pregnant women was higher than that of those born to the GBS-negative ones (P<0.05). The live infants born to the GBS-positive pregnant women had a higher incidence rate of GBS-EOD than those born to the GBS-negative ones [6.38‰ (12/1 881) vs 0.27‰ (4/14 725), P<0.05]. The multivariate logistic regression analysis showed that placental swabs positive for GBS and positive GBS in neonatal gastric juice at birth were independent predictive factors for the development of GBS-EOD (P<0.05), while adequate IAP was a protective factor (P<0.05) in the offspring of pregnant women with GBS colonization. CONCLUSIONS: GBS colonization of pregnant women in late pregnancy has adverse effects on their offspring. It is important to determine prenatal GBS colonization status of pregnant women and administer with adequate IAP based on the indications of IAP to reduce the incidence of neonatal GBS-EOD. Citation.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Antibioticoprofilaxia , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Placenta , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Prospectivos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae
16.
Int J Infect Dis ; 111: 347-353, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34454120

RESUMO

AIMS: To explore the contagiousness and new SARS-CoV-2 mutations in pediatric COVID-19. METHODS: This cohort study enrolled all pediatric patients admitted to 8 hospitals in Zhejiang Province of China between 21 January and 29 February 2020, their family members and close-contact classmates. Epidemiological, demographic, clinical and laboratory data were collected. Bioinformatics was used to analyze the features of SARS-CoV-2. Individuals were divided into 3 groups by the first-generation case: Groups 1 (unclear), 2 (adult), and 3 (child). The secondary attack rate (SAR) and R0 were compared among the groups. RESULTS: The infection rate among 211 individuals was 64% (135/211). The SAR in Groups 2 and 3 was 71% (73/103) and 3% (1/30), respectively; the median R0 in Groups 2 and 3 was 2 (range: 1-8) and 0 (range: 0-1), respectively. Compared with adult cases, the SAR and R0 of pediatric cases were significantly lower (p<0.05). We obtained SARS-CoV-2 sequences from the same infant's throat and fecal samples at a two-month interval and found that the new spike protein A958D mutation detected in the stool improved thermostability theoretically. CONCLUSIONS: Children have lower ability to spread SARS-CoV-2. The new A958D mutation is a potential reason for its long residence in the intestine.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Adulto , COVID-19/virologia , Criança , China/epidemiologia , Estudos de Coortes , Humanos , Incidência , Lactente , Mutação , SARS-CoV-2/genética
17.
J Vasc Access ; : 11297298211038452, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387514

RESUMO

BACKGROUND: Ultrasound-guided axillary vein (AxV) cannulation has been described as an effective alternative to internal jugular vein cannulation in adult cardiac surgical patients. However, the learning curve for this technique has not yet been addressed. This study aimed to determine the number of cases required to achieve proficiency in performing AxV cannulation among novice anesthesiologists. METHODS: This prospective study included the first 60 patients who underwent ultrasound-guided AxV cannulation performed by a single third-year resident who was trained in adult cardiac anesthesia. This study investigated the number of cases required to gain technical proficiency by applying cumulative sum analysis on the learning curve (LC-CUSUM) of ultrasound-guided AxV cannulation. RESULTS: Based on the assessment of the CUSUM plots, a descending inflection point for decreasing the overall procedural time for AxV cannulation was observed after patient 29. Regarding the procedural outcomes, comparing the early-experience group with the late-experience group (29 vs 31 cases), the former group had longer operating time (1526 s vs 1120 s, p < 0.001) and identification time (110 s vs 92 s, p < 0.001) and lower first-attempt success rate (8, 27.6% vs 30, 96.8%, p < 0.001) than the latter group. CONCLUSIONS: CUSUM demonstrated that at least 29 successful cases are required to achieve an expertized manipulation in ultrasound-guided AxV cannulation for inexperienced novices. The learning curve for ultrasound-guided AxV cannulation was observed in 29 cases. After adequate training, the overall procedural time and the first-attempt success rate, and puncture-related complications for AxV cannulation improved with increased experience.

18.
Nat Commun ; 12(1): 4586, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321486

RESUMO

Heterogeneous immunoassays such as ELISA have become indispensable in modern bioanalysis, yet translation into point-of-care assays is hindered by their dependence on external calibration and multiple washing and incubation steps. Here, we introduce RAPPID (Ratiometric Plug-and-Play Immunodiagnostics), a mix-and-measure homogeneous immunoassay platform that combines highly specific antibody-based detection with a ratiometric bioluminescent readout. The concept entails analyte-induced complementation of split NanoLuc luciferase fragments, photoconjugated to an antibody sandwich pair via protein G adapters. Introduction of a calibrator luciferase provides a robust ratiometric signal that allows direct in-sample calibration and quantitative measurements in complex media such as blood plasma. We developed RAPPID sensors that allow low-picomolar detection of several protein biomarkers, anti-drug antibodies, therapeutic antibodies, and both SARS-CoV-2 spike protein and anti-SARS-CoV-2 antibodies. With its easy-to-implement standardized workflow, RAPPID provides an attractive, fast, and low-cost alternative to traditional immunoassays, in an academic setting, in clinical laboratories, and for point-of-care applications.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Imunoensaio/normas , Medições Luminescentes/normas , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/sangue , COVID-19/imunologia , COVID-19/virologia , Teste Sorológico para COVID-19/instrumentação , Calibragem , Proteínas de Ligação ao GTP/química , Genes Reporter , Humanos , Imunoconjugados/química , Limite de Detecção , Luciferases/genética , Luciferases/metabolismo , Testes Imediatos , SARS-CoV-2/genética
19.
Front Pharmacol ; 12: 686992, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149430

RESUMO

Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP), and pancreatic stellate cells (PSCs) are considered to be the key cells. Puerarin is the most important flavonoid active component in Chinese herb Radix Puerariae, and it exhibited anti-fibrotic effect in various fibrous diseases recently. However, the impact and molecular mechanism of puerarin on CP and pancreatic fibrosis remain unknown. This study systematically investigated the effect of puerarin on CP and pancreatic fibrosis in vivo and in vitro. H&E staining, Sirius Red staining, qRT-PCR and Western blotting analysis of fibrosis and inflammation related genes of pancreatic tissues showed that puerarin notably ameliorated pancreatic atrophy, inflammation and fibrosis in a model of caerulein-induced murine CP. Western blotting analysis of pancreatic tissues showed the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2 and p38 MAPK) significantly increased after modeling of cerulein, while puerarin could inhibit their phosphorylation levels to a certain extent. We found that puerarin exerted a marked inhibition on the proliferation, migration and activation of PSCs, determined by CCK-8 assay, transwell migration assay, scratch wound-healing assay and expression levels of α-SMA, Fibronectin, Col1α1 and GFAP. Western blotting result demonstrated that puerarin markedly inhibited the phosphorylation of MAPK family proteins (JNK1/2, ERK1/2 and p38 MAPK) of PSCs in a dose-dependent manner whether or not stimulated by platelet-activating factor. In conclusion, the present study showed that puerarin could be a potential therapeutic candidate in the treatment of CP, and the MAPK pathway might be its important target.

20.
J Clin Endocrinol Metab ; 106(11): e4520-e4530, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34160619

RESUMO

CONTEXT: Although gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP), it is invasive, expensive, and time-consuming, requiring multiple blood samples to measure gonadotropin levels. OBJECTIVE: We evaluated whether urinary hormones could be potential biomarkers for prepuberty or postpuberty, aiming to simplify the current diagnosis and prognosis procedure. METHODS: We performed a cross-sectional study of a total of 355 girls with CPP in National Clinical Research Center for Child Health in China, including 258 girls with positive and 97 girls with negative results from GnRHST. Twenty patients received GnRH analogue (GnRHa) treatment and completed a 6-month follow up. We measured luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, prolactin, progesterone, testosterone, and human chorionic gonadotropin in the first morning voided urine samples. RESULTS: Their urinary LH levels and the ratios of LH to FSH increased significantly with the advancement in Tanner stages. uLH levels were positively associated with basal and peak LH levels in the serum after GnRH stimulation. A cutoff value of 1.74 IU/L for uLH reached a sensitivity of 69.4% and a specificity of 75.3% in predicting a positive GnRHST result. For the combined threshold (uLH ≥ 1.74 + uLH-to-uFSH ratio > 0.4), the specificity reached 86.6%. After 3 months of GnRHa therapy, the uLH and uFSH levels decreased accordingly. CONCLUSION: uLH could be a reliable biomarker for initial CPP diagnosis and screening; uLH could also be an effective marker for evaluating the efficacy of clinical treatment.


Assuntos
Hormônios Esteroides Gonadais/urina , Gonadotropinas/urina , Puberdade Precoce/urina , Biomarcadores/urina , Criança , Pré-Escolar , China , Estudos Transversais , Estradiol/urina , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/urina , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Leuprolida/uso terapêutico , Hormônio Luteinizante/sangue , Hormônio Luteinizante/urina , Puberdade , Puberdade Precoce/tratamento farmacológico , Curva ROC , Pamoato de Triptorrelina/uso terapêutico
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