Objective: To recover broad-neutralizing monoclonal antibodies (BnAbs) from avian influenza A (H5N1) virus infection cases and investigate their genetic and functional features. Methods: We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients. The genetic basis, biological functions, and epitopes of the obtained BnAbs were assessed and modeled. Results: Two BnAbs, 2-12D5, and 3-37G7.1, were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset. Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity (ADCC) activity. Albeit derived from distinct Ab lineages, , V 1-69-D2-15-J 4 (2-12D5) and V 1-2-D3-9-J 5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V 1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, respectively. Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus. The HA stem epitopes targeted by the BnAbs, and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.

BACKGROUND: Gestational diabetes mellitus (GDM) is usually diagnosed between 24th and 28th gestational week using the 75-g oral glucose tolerance test (OGTT). It is difficult to predict GDM before 24th gestational week because fast plasma glucose (FPG) decreases as the gestational age increases. It is controversial that if FPG ≥5.1 mmol/L before 24th gestational week should be intervened or not. The aim of this study was to evaluate the value of FPG to screen GDM before 24th gestational week in women with different pre-pregnancy body mass index (BMI). METHODS: This was a multi-region retrospective cohort study in China. Women who had a singleton live birth between June 20, 2013 and November 30, 2014, resided in Beijing, Guangzhou and Chengdu, and received prenatal care in 21 selected hospitals, were included in this study. Pre-pregnancy BMI, FPG before the 24th gestational week, and one-step GDM screening with 75 g-OGTT at the 24th to 28th gestational weeks were extracted from medical charts and analyzed. The pregnant women were classified into four groups based on pre-pregnancy BMI: Group A (underweight, BMI < 18.5 kg/m), Group B (normal, BMI 18.5-23.9 kg/m), Group C (overweight, BMI 24.0-27.9 kg/m) and Group D (obesity, BMI ≥28.0 kg/m). The trend of FPG before 24th week of gestation was described, and the sensitivity and specificity of using FPG before the 24th gestational week to diagnose GDM among different pre-pregnancy BMI groups were reported. Differences in the means between groups were evaluated using independent sample t-test and analysis of variance. Pearson Chi-square test was used for categorical variables. RESULTS: The prevalence of GDM was 20.0% (6806/34,087) in the study population. FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. FPG was higher in women with higher pre-pregnancy BMI. FPG before the 24th gestational week and pre-pregnancy BMI could be used to predict GDM. The incidence of GDM in women with FPG ≥5.10 mmol/L in the 19th to 24th gestational weeks and pre-pregnancy overweight or obesity was significantly higher than that in women with FPG ≥5.10 mmol/L and pre-pregnancy BMI <24.0 kg/m (78.5% [62/79] vs. 52.9% [64/121], χ = 13.425, P < 0.001). CONCLUSIONS FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. Pre-pregnancy overweight or obesity was associated with an increased FPG value before the 24th gestational week. FPG ≥5.10 mmol/L between 19 and 24 gestational weeks should be treated as GDM in women with pre-pregnancy overweight and obesity.
Adult ; Blood Glucose ; analysis ; Body Mass Index ; Diabetes, Gestational ; blood ; diagnosis ; epidemiology ; Fasting ; blood ; Female ; Gestational Age ; Glucose Tolerance Test ; Humans ; Incidence ; Pregnancy ; Prevalence ; ROC Curve ; Retrospective Studies

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) have been a challenging concern of health-care associated infections. The aim of the current study was to investigate the molecular epidemiology and clonal dissemination of CRAB isolates in a Chinese teaching hospital. METHODS: Non-duplicate clinical A. baumannii isolates were collected from inpatients, and we measured the minimal inhibitory concentrations to determine antimicrobial susceptibility. Polymerase chain reaction (PCR) and sequencing were performed to detect carbapenem-resistance genes and occurrence of transposons among CRAB isolates. Moreover, the genetic diversity among isolates and clonal dissemination were determined by repetitive element PCR-mediated DNA fingerprinting (rep-PCR) and multilocus sequence typing (MLST). RESULTS: A total of 67 CRAB isolates displayed resistance to most of the antibiotics tested in this study, except tigecycline. We detected blaOXA-23, blaOXA-51, blaOXA-58, and blaVIM genes in 94.0%, 100.0%, 1.5%, and 80.6% of the CRAB isolates, respectively. Nevertheless, 74.6% of the CRAB isolates co-harbored the blaOXA-23 and blaVIM. Only one type of transposons was detected: Tn2008 (79.1%, 53/67). Although 12 distinctive types (A-L) were determined (primarily A type) ST195 was the most prevalent sequence type (ST). ST368, ST210, ST90, ST829, and ST136 were also detected, and all belonged to clonal complex 208 (CC208) and global complex 2 (GC2). CONCLUSION The blaOXA-23 and blaVIM genes contributed to the resistance among CRAB isolates collected in our study. Notably, most of the CRAB strains co-harbored blaOXA-23 and blaVIM genes, as well as Tn2008, which could contribute to clonal dissemination. The prevalence of such organisms may underlie hospital acquired infections.

Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS) method was applied to analyze the prototypes and metabolites of the effective components of Polygonum orientale in SD rat serum and urine. The separation was performed on Agilent Eclipse Plus C_(18) column( 2. 1 mm×100 mm,1. 8 μm),with 0. 1% formic acid solution( A)-acetonitrile( B) as the mobile phase for gradient elution. Mass spectrometry data of biological samples were obtained under positive and negative electrospray ion mode. By comparing chromatogram differences between blank samples and drug treatment samples,prototype components and metabolites of the effective components of P. orientale extract were identified. The results showed that 12 metabolites were detected in serum and 26 metabolites in urine( including cross-components) of rats. The main metabolic pathways included hydrogenation,hydroxylation,glucuronidation,sulfation reaction,and methylation-glucuronidation,etc. The method established in this study was reliable and effective for studying the metabolic characteristics of the effective components of P. orientale in rats,and it can provide a reference for further studies on therapeutic material basis of this herb.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Flowers ; chemistry ; Phytochemicals ; blood ; urine ; Polygonum ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

The traditional Chinese medicine standard decoction is prepared on the basis of the theory of traditional Chinese medicine and clinical application. With reference to the modern extraction method,the single decoction of traditional Chinese medicine is prepared by the standardized process,and the establishment of its quality standards is conducive to standardizing clinical medication. This research is to set an evaluation standard for the quality of salt-processed Psoraleae Fructus standard decoction. Twelve batches of salt-processed Psoraleae Fructus standard decoctions were prepared. The contents of psoralen and isopsoralen were determined,the transfer and extract rates were calculated,and the pH value was measured; HPLC fingerprint method was established for analysis. The results of the 12 batches of samples revealed that the transfer rates of psoralen and isopsoralen were 17. 10%-26. 40%,14. 70%-22. 70%,respectively; the extract rate was between 14. 7%-27. 0%,and the pH value was between 5. 4-6. 9. Moreover,7 common chromatographic peaks were determined based on fingerprint by using similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine( 2012 A).The similarities of the 12 batches of samples were analyzed and compared,and the results showed that the similarities were all higher than0. 9. In this study,the preparation method for salt-processed Psoraleae Fructus decoction was standard,with high similarities in fingerprint. This study build a convenient and reliable method of comprehensive quality evaluation,with a high precision,stability and repeatability,which can provide a reference for the quality control of salt-processed Psoraleae Fructus dispensing granules.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; Fruit ; chemistry ; Medicine, Chinese Traditional ; Phytochemicals ; analysis ; Psoralea ; chemistry ; Quality Control

To determine the plasma protein binding rate of the nine compounds in Inula cappa extraction by the method of equilibrium dialysis. The proteins in plasma samples were precipitated by methanol, and the ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was developed for determination of the concentrations of the nine active compounds, namely chlorogenic acid, scopolin, neochlorogenic acid, cryptochlorogenic acid, 1,3-O-dicaffeoylquinic acid, galuteolin, 3,4-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, with the internal standard of puerarin. We found that all components have a good linearity(r≥0.999), and accuracy, precision, extraction recovery and stability conformed to the requirements of determination, without endogenous compounds disturbing within the range of optimum concentration. This suggested that the method was stable and reliable, and could be used for the determination of the plasma protein binding rates of the nine active compounds in rat and human plasma of I. cappa. The plasma protein binding rates of the nine active compounds in rat and human plasma respectively were(41.07±0.046)%-(94.95±0.008)%, and(37.66±0.043)%-(97.46±0.013)%. According to the results, there were differences in the plasma protein binding rates of the nine compounds in I. cappa extraction between rat and human.
Animals ; Blood Proteins ; metabolism ; Chromatography, High Pressure Liquid ; Humans ; Inula ; chemistry ; Phytochemicals ; metabolism ; Plant Extracts ; metabolism ; Protein Binding ; Rats ; Reproducibility of Results ; Tandem Mass Spectrometry

OBJECTIVE: To compare the sagittal morphological features of the spine and pelvis between L₅S₁ dysplastic spondylolisthesis and isthmus spondylolisthesis in adolescent. METHODS: Retrospective analysis of 24 cases of adolescent L₅S₁ spondylolisthesis with complete imaging data from May 2002 to December 2016. Those included 8 males and 16 females, aged from 10 to 18 years old with an average of (13.4±2.0) years. Among them, 9 cases were diagnosed as dysplastic spondylolisthesis (dysplasia group) and 15 cases isthmic spondylolisthesis (ischemic group). Radiographic parameters including slippage distance, slippage degree, slippage angle, sagittal vertical axis(SVA), thoracic kyphosis(TK), lumbar lordosis(LL), L₅ incidence(L₅I), pelvic incidence(PI), pelvic tilt(PT), sacral slope(SS), sagittal pelvic thickness(SPT), lumbosacral angle (LSA), sacral table angle (STA) were measured on the spinal lateral X-ray of the standing position. Independent-samples t-test was used in the comparison of each variable between two groups. <0.05 was considered statistically significant. RESULTS: There were no significant differences in slippage distance, slippage rate, slippage angle between two groups. In dysplasia group, SVA, L₅I, PT, SPT were (37.0±48.4) mm, (57.0±14.8)°, (42.3±15.4)°, (56.1±21.2) mm, respectively, and (-11.0±22.2) mm, (31.7±19.3) °, ( 15.5±10.2)°, (31.4±19.1) mm in ischemic group; and the differences between the two groups were significant(<0.05). In ischemic group, SS, LSA, STA were (44.1±12.6)°, (103.9±21.7)°, (92.7±9.9)°, respectively, and (25.9±20.2) °, (75.4±16.4) °, (75.4±9.7) ° in dysplasia group; and the differences between the two groups were significant(<0.05). There was no significant difference in TK, LL between two groups(>0.05). CONCLUSIONS Significant different from isthmic spondylolisthesis, adolescents with dysplastic spondylolisthesis present a different spino-pelvic sagittal alignment, characterized with trunk forward leaning and pelvic retroversion. In case of sagittal imbalance, early surgical intervention is required to restore a balanced spino-pelvic alignment.
Adolescent ; Child ; Female ; Humans ; Lumbar Vertebrae ; Male ; Pelvis ; Postural Balance ; Radiography ; Retrospective Studies ; Spine ; Spondylolisthesis ; surgery

Danggui Buxue Tang (DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague-Dawley(SD) rats were randomly divided into 3 groups including control (NC, Saline), the DBT (at a dose of 8.10 g), and blood deficiency(BD) (Cyclophosphamide (APH)-andCyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry (LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metaboliteswerescreened according to the multivariate statistical analysiscomparing the NC and BD groups, andthe hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, ChemMapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component-target protein interaction network and establish a component, protein and hub metabolite protein-protein interaction (PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-l-methionine, glycine, l-cysteine, arachidonic acid (AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signalling pathways. DBT can promote iron ion binding and haemopoiesis activities, restrain inflammation, production of reactive oxygen, block apoptosis, and contribute significantly to the DBT treat anaemia.
Anemia ; blood ; chemically induced ; drug therapy ; metabolism ; Animals ; Chromatography, Liquid ; Cyclophosphamide ; toxicity ; Disease Models, Animal ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Metabolic Networks and Pathways ; drug effects ; genetics ; Metabolome ; drug effects ; Metabolomics ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Tandem Mass Spectrometry

Four new corynanthe-type alkaloids, meloslines C-F (1-4), together with four known ones (5-8) were isolated from the roots of Alstonia scholaris. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation. Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.

OBJECTIVE: To study the clinical effect of white noise combined with glucose in reducing the procedural pain of retinopathy screening in preterm infants. METHODS: A total of 396 preterm infants with a gestational age of 28-34 weeks and a birth weight of ≤2 000 g were randomly divided into 4 groups according to the intervention method for reducing pain in retinopathy screening: control group with 100 infants (no white noise or glucose intervention), white noise group with 96 infants, glucose group with 98 infants and white noise + glucose group with 102 infants. The Premature Infant Pain Profile (PIPP) was used to determine pain score during retinopathy screening, and the four groups were compared in terms of PIPP score before and after retinopathy screening. RESULTS: There were no significant differences in PIPP score, heart rate and blood oxygen saturation between the four groups at 3 minutes before screening (P>0.05). At 1 and 5 minutes after screening, the white noise, glucose and white noise + glucose groups had significantly lower heart rate and PIPP score but significantly higher blood oxygen saturation than the control group (P<0.05).The white noise + glucose group had significantly lower heart rate and PIPP score but significantly higher blood oxygen saturation than the white noise and glucose groups (P<0.05). CONCLUSIONS White noise combined with glucose can reduce the procedural pain of retionopathy screening and keep vital signs stable in preterm infants.
Glucose ; Heart Rate ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Pain ; Pain Management