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@#Abstract: Objective In order to explore the application prospects of the phenyl pyrazole insecticide fipronil for mosquito control and identify potential target genes involved in the resistance of Aedes aegypti to fipronil, and lay the foundation for an in-depth study of the resistance mechanism of Aedes aegypti to fipronil. Methods Using Aedes aegypti sensitive strains as experimental materials, Aedes aegypti larvae were treated with fipronil, and the differences in gene expression of Aedes aegypti larvae before and after drug administration were compared at the transcriptome level using transcriptome sequencing combined with bioinformatics analysis, and the differential genes were analyzed. Results A total of 757 differentially expressed genes were identified between the fipronil-treated group and control group, including 217 and 540 up- and down-regulated genes, respectively. Among these, the expression of glutamate-gated chloride channel (GluCls) genes varied significantly before and after treatment. Gene ontology analysis revealed that differentially expressed genes were enriched in catalytic activity, binding, metabolic processes, and membrane-related functions, while KEGG pathway analysis indicated enrichment in biosynthesis, metabolism, and life regulation processes, while the glutathione metabolic pathway was enriched in 15 differentially expressed genes. Conclusions The transcriptome results revealed that GST gene expression was significantly upregulated in fipronil-treated Aedes aegypti larvae, indicating that GST gene is involved in the development of fipronil resistance in Aedes aegypti larvae. In addition, GluCls gene expression was also significantly different before and after treatment, suggesting that GluCls migh be a potential target receptor for fipronil resistance in Aedes aegypti. As GluCls is an ideal target receptor found only in invertebrates, this discovery provides a reference and basis for further exploration of the toxicological mechanism of fipronil on Aedes aegypti.
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This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.
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Humains , Tumeurs de l'estomac/métabolisme , Médecine traditionnelle chinoise , Simulation de docking moléculaire , Pronostic , Biologie informatiqueRésumé
Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.
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Mâle , Humains , Femelle , Marqueurs biologiques tumoraux/analyse , Tumeurs gastro-intestinales/anatomopathologie , Protéines S100/analyse , MélanomeRésumé
Objective:To analyze the activation characteristics of trapezius muscle in normal people, and explore whether different interventions could restore the activation pattern of people with abnormal trapezius muscles to normal during subsequent exercises. Methods:From September to October, 2017, 20 persons with normal shoulder joints (control group) and 20 persons with mild discomfort in shoulder joints (observation group) participated in the study. All of them were treated randomly with four steps, including no intervention, static traction of upper trapezius muscle (UT), isometric contraction of lower trapezius muscle (LT) and combined intervention. Then, they were asked to complete three actions, including straight arm side lifting, sitting in rowing and flying birds. Myoelectric signal was recorded before and after test. Results:Compared with the control group, the UT activation degree increased (P < 0.05), and the activation time shortened (P < 0.05); the activation degrees of middle trapezius muscle (MT) and LT decreased (P < 0.05), and the activation time delayed (P < 0.05); the ratios of UT/LT and UT/MT increased (P < 0.05) in the observation group with no intervention. After static traction of UT, isometric contraction of LT, and both interventions, the MVE%, activation time and the ratios of activation varied in different muscles under different actions in both groups (P < 0.05). Conclusion:In different actions, the activation degree and activation time of three trapezius muscles are different. Static traction of UT and isometric contraction of LT before exercise could improve the activation pattern of trapezius muscles of people with shoulder joint discomfort during exercise, which is conducive to the normal function of the shoulder joint.
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BACKGROUND: Proximal femoral anti-rotation intramedullary nail for treating intertrochanteric fracture is widely used in clinical practice, but there are still some cases of failure of internal fixation after operation, and osteoporosis of proximal femur is considered as an important reason. Singh index is an important index to evaluate the severity of osteoporosis in the proximal femur. Based on the Singh index, it is of great significance to explore the effect of different degrees of osteoporosis on the treatment of intertrochanteric fracture with anti-rotation intramedullary nail in the proximal femur, so as to reduce the failure rate of internal fixation and increase the success rate of operation. OBJECTIVE: To explore the effect of different osteoporosis on the treatment of intertrochanteric fracture with proximal femoral anti-rotation intramedullary nail, so as to provide new ideas and experimental basis for clinical treatment of intertrochanteric fracture. METHODS: CT data of one patient with intertrochanteric fracture of the left femur were imported into Mimics 19.0 and Geomagic studio 2017 software to extract and optimize the three-dimensional model of the right femur. SolidWorks 2017 software was used to draw the internal fixation model and assemble it with the femur model according to the standard operation technology, and import it into HyperMesh 14.0 software in STEP format to cut the bone according to AO-2.1 type of intertrochanteric fracture. Trabecular bone based on Singh index 1-6 was established to obtain six models of A-F. Material property parameters, boundary conditions and applied loads were set. Finally, the data were stored as K files and imported into LS-DYNA software for solution. RESULTS AND CONCLUSION: (1) When the femoral head was stressed, the spiral blade in the bone block of the femoral head and neck of Singh 6-Singh 1 was cut, the common bone trabecula disappeared, the stress bone trabecula wrapped with the spiral blade did not disappear, but loaded with certain stress, so that the spiral blade still had a large contact area and holding force, maintained the reduction of the fracture, and reduced the varus and rotation of the bone block of the femoral head and neck. (2) From Singh 6-Singh 1, with the disappearance of stress bone trabecula, the more serious osteoporosis is, the more likely failure will be in the treatment of intertrochanteric fracture with proximal femoral anti-rotation intramedullary nail. (3) The spongy bone trabeculae, especially the stress bone trabeculae, play an important role in maintaining the elastic stability of the proximal femur by resisting and buffering the bending strain.
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BACKGROUND@#Hypothermia is associated with many adverse clinical outcomes in pediatric patients, and thus, it is important to find an effective and safe method for preventing peri-operative hypothermia and its associated adverse outcomes in pediatric patients. This study aimed to investigate the effect of forced-air warming blankets with different temperatures on changes in the transforming growth factor-β (TGF-β), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 levels in children undergoing surgical treatment for developmental displacement of the hip (DDH).@*METHODS@#The study included 123 children undergoing surgery for DDH under general anesthesia. The patients were randomly assigned to three groups, using a random number table: the 32, 38, and 43°C groups according to the temperature setting of the forced-air warming blankets. For each patient, body temperature was recorded immediately after anesthesia induction and intubation (T0), at initial incision (T1), at 1 h after incision (T2), at 2 h after incision (T3), at the end of surgery (T4), immediately upon return to the ward after surgery (T5), and then at 12 h (T6), 24 h (T7), 36 h (T8), and 48 h (T9) after the surgery. The serum levels of TGF-β, TNF-α, IL-1β, and IL-10 were measured at T0 and T4 for all groups.@*RESULTS@#The number of patients with fever in the 38°C group was significantly less than those in the 32 and 43°C groups (χ = 6.630, P = 0.036). At T0, the body temperatures in the 38 and 43°C groups were significantly higher than that in the 32°C group (F = 17.992, P < 0.001). At T2, the body temperature was significantly higher in the 43°C group than those in the 32 and 38°C groups (F = 12.776, P < 0.001). Moreover, at T4, the serum levels of TGF-β (F = 3286.548, P < 0.001) and IL-10 (F = 4628.983, P < 0.001) were significantly increased in the 38°C group, and the serum levels of TNF-α (F = 911.415, P < 0.001) and IL-1β (F = 322.191, P < 0.001) were significantly decreased in the 38°C group, compared with the levels in the 32 and 43°C groups.@*CONCLUSION@#Force-air warming blankets set at 38°C maintained stable body temperature with less adverse outcome and effectively inhibited the inflammatory response in pediatric patients undergoing surgery for DDH.@*CLINICAL TRIAL REGISTRATION@#ChiCTR1800014820; http://www.chictr.org.cn/showproj.aspx?proj=25240.
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The present study was performed to establish the UPLC fingerprints of Bolbostemmatis Rhizoma and determine the contents of three saponins by quantitative analysis of multi-components by single marker(QAMS), and provide basis for quality evaluation of Bolbostemmatis Rhizoma. The analysis was carried out on an analytical column of Waters Cortecs T3(2.1 mm×100 mm,1.6 μm)with gradient elution by acetonitrile-0.1% phosphoric acid solution, at a flow rate of 0.3 mL·min~(-1). The detection wavelength was 203 nm, the column temperature was 30 ℃ and the injection volume was 1 μL. The UPLC fingerprints of Bolbostemmatis Rhizoma were established and evaluated by similarity calculation, cluster analysis and principal component analysis. The relative calibration factors of toberoside B and toberoside C were determined with toberoside A as internal reference. The content was calculated by relative calibration factors to develop a method of QAMS. Comparing the results of QAMS with those of ESM, the accuracy and feasibility of one-eva-luation and multi-evaluation can be determined. RESULTS:: showed that the fingerprints of 19 batches of Bolbostemmatis Rhizoma have four common peaks with similarities ranging from 0.754 to 1.000. Cluster analysis and principal component analysis classified 19 batches of Bolbostemmatis Rhizoma into three categories, which was consistent with the similarity evaluation results. The relative deviation between the content of tubeicosides B and C in 19 batches of Bolbostemmatis Rhizoma determined by QAMS and ESM is less than 5.0%, indicating that there was no significant difference between the two methods. Therefore, the UPLC fingerprints combined with QAMS and similarity evaluation can be effectively used to evaluate the quality of Bolbostemmatis Rhizoma.
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Chromatographie en phase liquide à haute performance , Médicaments issus de plantes chinoises , Analyse en composantes principales , Contrôle de qualité , RhizomeRésumé
INTRODUCTION@#In this study, we described paediatric sports injuries seen in the paediatric emergency department of a large, tertiary paediatric hospital in Singapore and evaluated risk factors for severe sports injuries.@*METHODS@#This is a retrospective review of a paediatric trauma surveillance registry from February 2012 to October 2017, including patient demographics, type of sports, circumstances, type of injuries, and clinical management in the hospital. Patients 5 to 17 years old with a sports-related injury were included. We performed logistic regression to identify predictors of severe sports injuries (defined by Injury Severity Score of ≥9), injuries requiring hospitalisation, trauma team activation, resuscitation, or those that resulted in death.@*RESULTS@#Among 10,951 patients analysed, the most common injuries sustained were fractures (4,819, 44.0%), sprains and contusions (3,334, 30.4%). For patients with severe injuries, the median length of hospital stay was 2 days (IQR 1-3 days), and time away from sports was 162 days (IQR 104-182 days). Predictors for severe injuries include transportation by emergency medical service (aOR 6.346, 95% CI 5.147-7.823), involvement in rugby (aOR 2.067, 95% CI 1.446-2.957), neurological injuries (aOR 4.585, 95% CI 2.393-4.365), dislocations (aOR 2.779, 95% CI 1.744-4.427), fractures (aOR 1.438, 95% CI 1.039-1.990), injuries to the head and neck (aOR 2.274, 95% CI 1.184-4.365), and injuries to the abdomen and pelvis (aOR 5.273, 95% CI 3.225-8.623).@*CONCLUSION@#Predictors for severe sports injuries identified may aid in risk stratification and resource allocation.
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Objective To understand infection status of human immunodeficiency virus (HIV) and analyze the influencing factors among men who have sex with men (MSM) in Guangzhou. Methods Men who have sex with men (MSM) were recruited from 2014 to 2017. Face-to-face questionnaire survey was conducted to collect information of characterisitc and behaviors. Blood samples were used to detect HIV antibodie. Data were analyzed using SPSS 19.0. Results Among 2 419 MSM, 200(8.27%) participants were confirmed positive for HIV. Multivariate Logistic regression analysis showed that with Guangzhou and monthly economic income >0.5 million as reference, non-Guangzhou (OR=1.712, 95% CI: 1.176-2.492,P=0.005) and monthly economic income ≤0.5 million (OR=1.998, 95% CI: 1.409-2.833,P<0.001) were associated with HIV infection among MSM. Diagnosed syphilis (OR=2.461, 95% CI: 1.375-4.405,P=0.002) , undetected syphilis (OR=2.333, 95% CI: 1.635-3.331,P<0.001), anal sex role passive (OR=2.015, 95% CI: 1.244-3.267,P=0.004), both active and passive (OR=2.115, 95% CI: 1.374-3.251,P=0.001), non-using condoms every time during anal sex (OR=1.955, 95% CI: 1.374-2.781,P<0.001), non-fixed anal sex objects (OR=2.150, 95% CI: 1.463-3.160,P<0.001) were major risk factors for HIV infection among MSM. Conclusions The prevalance of HIV infection and high-risk sexual behavior were high among MSM in Guangzhou. It is urgent to expand the scope of HIV testing and advocate safe sexual behaviors among MSM.
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Positron emission tomography (PET) is a powerful non-invasive molecular imaging technique for the early detection, characterization, and "real-time" monitoring of disease, and for investigating the efficacy of drugs (Phelps, 2000; Ametamey et al., 2008). The development of molecular probes bearing short-lived positron-emitting radionuclides, such as 18F (half-life 110 min) or 11C (half-life 20 min), is crucial for PET imaging to collect in vivo metabolic information in a time-efficient manner (Deng et al., 2019). In this regard, one of the main challenges is rapid synthesis of radiolabeled probes by introducing the radionuclides into pharmaceuticals as soon as possible before injection for a PET scan. Although many potential PET probes have been discovered, only a handful can satisfy the demand for a highly efficient synthesis procedure that achieves radiolabeling and delivery for imaging within 1-2 radioisotope half-lives. Only a few probes, such as 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) and [18F]fluorodopa, are routinely produced on a commercial scale for daily clinical diagnosis (Grayson et al., 2018; Carollo et al., 2019).
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Laboratoires sur puces , Tomographie par émission de positons/méthodes , Radio-isotopes/composition chimique , Radiopharmaceutiques/synthèse chimique , Extraction en phase solideRésumé
Treatment of large bone defects caused by trauma, osteomyelitis, and tumors has been a major challenge in clinical. In the past, there have been many ways to repair and reconstruct the large bone defects. However, there is a long period of treatment, high technical requirement and complications such as ununion. After Masquelet reported the induced membrane technology in 2000, the technique was widely used in treatment of trauma, osteomyelitis, and large bone defects caused by tumors. It has been obtained good results. It has the advantages of short course, high healing rate, easy operation and easy to master. The induced membrane has unique structural characteristics and biological characteristics. There are many kinds of osteogenic factors that are included in the membrane, such as vascular endothelial growth factor, and morphogenetic protein-2, transforming growth factor-β1, etc. These osteogenic factors contribute to accelerate bone healing. With the development of induced membrane technology. The technology of Reamer Irrigator Aspirator technology, engineering tissue technology and internal fixation is used in clinic.It can provide bone source, promote bone defect reconstruction, improve long-term limb function and reduce complications.This paper retrospectively summarizes the experimental research and clinical progress of Masquelet technique in the treatment of large bone defects.
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Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy of uncertain etiology. The aim of our study was to identify changes in C-telopeptide of type II collagen (CTX-II), pyridinoline (PYD), and deoxypyridinoline (DPD) among KBD patients. 54 KBD patients and 78 healthy controls were included this study. Urinary samples were collected and measured by ELISA. The median quantities of PYD, CTX-II, and DPD of KBD patients were 1107.73 ng/μmol.cre, 695.11 ng/μmol.cre, and 1342.34 pml/μmol.cre, while the median quantities of healthy controls were 805.59 ng/μmol.cre, 546.47 ng/μmol.cre, and 718.15 pml/μmol.cre, respectively. The differences between KBD patients and healthy controls were statistically significant (Z = 4.405, 3.653, and 3.724; P < 0.001). The higher levels of PYD, CTX-II, and DPD detected in KBD patients indicate that they could be used as biomarkers of KBD.
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Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Acides aminés , Urine , Marqueurs biologiques , Urine , Chine , Collagène de type II , Urine , Maladie de Kashin-Beck , Diagnostic , Urine , Fragments peptidiques , UrineRésumé
Brucellosis is one of the most widespread zoonotic diseases, with the most frequent complication being osteoarticular changes. The aim of this study was to assess the changes of C-terminal telopeptide of type II collagen (CTX-II) in patients infected with brucellosis. A total of 84 brucellosis patients and 43 volunteers were selected and divided into brucellosis vs. control groups. Serum samples were subjected to serological tests for brucellosis, and CTX-II levels in all samples were measured simultaneously with ELISA. The results showed that serum CTX-II levels in human brucellosis were higher than those of healthy controls, without a statistically significant difference, but serum CTX-II levels in male patients were significantly higher than those of female patients (P<0.05). This finding could indicate the biological changes in the cartilage and bone in human brucellosis.
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Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Brucellose , Sang , Épidémiologie , Chine , Épidémiologie , Collagène de type II , Sang , Génétique , Régulation de l'expression des gènes , Allergie et immunologie , Fragments peptidiques , Sang , Génétique , Facteurs sexuelsRésumé
We here systematically summarize our practice and its effectiveness in the creation and development of the discipline proteomics in Academy of Military Medical Sciences,and the establishment of a system for identifying and training talented researchers in proteomics.The methods we used to train the researchers and to develop a vigorous team are discussed.These practices contributed much to the development of proteomics in China.
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<p><b>OBJECTIVE</b>To explore the factors influencing failure of an immunization to interrupt perinatal (mother-to-child) transmission of hepatitis B virus (HBV).</p><p><b>METHODS</b>Between June 2006 and March 2010, a total of 1355 pregnant women testing positive for the hepatitis B surface antigen (HBsAg), at gestational weeks 20 to 42, and without use of antiviral or immunomodulatory drugs during the pregnancy were prospectively recruited to the study. The mothers were given a choice of receiving hepatitis B immunoglobulin (HBIG; three 200 IU intramuscular injections give at four-week intervals starting from gestation week 28) or not. All neonates (1360, including five sets of twins) received hepatitis B vaccine (10 mug) plus HBIG (200 IU) combined immunization within 24 h of birth, as early as possible. Peripheral venous blood samples were collected from the neonates within 24 h of birth and at 7 and 12 months of age for detection of HBV markers, including hepatitis B e antigen (HBeAg) and HBV DNA. The infants were classified according to HBV perinatal transmission status (infection group and non-infection group) and various factors (maternal-related: age, gravidity, parity; pregnancy/birth-related: threatened premature labor, complications; neonate-related: sex, birth weight, apgar score) were compared between the two groups by using non-conditional logistic regression analysis to determine their potential influence on failure of immunization to inhibit transmission.</p><p><b>RESULTS</b>After 12 months of follow-up, 1.54% (21/1360) of the neonates had presented with HBV infection. Analysis of the HBV-infected neonates revealed differences in infection rates between neonates born to mothers with HBIG injection (2.22% vs. without HBIG injection: 1.11%, P less than 0.05) and caesarean section (1.35% vs. vaginal delivery: 1.73%) but neither reached statistical significance (P less than 0.05); only the practice of breastfeeding showed a significant difference for infection rate, with neonates fed artificial formula having higher infection rate (3.13%) than the breastfed neonates (0.27%, P less than 0.05). The neonate HBV infection rate was also significantly higher for neonates born to HBeAg-positive mothers (4.44% vs. HBeAg-negative mothers: 0%, P less than 0.05) and HBV DNA-positive mothers (3.13% vs. HBV DNA-negative mothers: 0%, P less than 0.05). When the mothers were stratified by serum level of HBV DNA, there was a significant difference in HBV-infected neonates born to mothers with more than or equal to 1*10(7) IU/ml(6.01% vs. 10(3)-10(6) IU/ml: 0.56% and less than 1*10(3) IU/ml: 0%, both P less than 0.05). Logistic regression analysis indicated that the independent risk factors for HBV perinatal transmission despite immunization were maternal serum HBeAg-positive status (relative risk (RR)=31.74, 95% confidence interval (CI): 3.88-259.38) and maternal HBV DNA of ≥ 10⁷ copies/mL (RR=22.58, 95% CI: 4.75-107.40).</p><p><b>CONCLUSION</b>Failure of vaccine plus HBIG to interrupt mother-to-child transmission of HBV is influenced by maternal serum HBeAg-positive status and maternal HBV DNA of ≥10⁷ copies/mL.</p>
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Adulte , Femelle , Humains , Nouveau-né , Grossesse , ADN viral , Sang , Hépatite B , Virologie , Antigènes de surface du virus de l'hépatite B , Sang , Vaccins anti-hépatite B , Utilisations thérapeutiques , Virus de l'hépatite B , Immunoglobulines , Utilisations thérapeutiques , Transmission verticale de maladie infectieuse , Complications infectieuses de la grossesse , Virologie , Deuxième trimestre de grossesse , Troisième trimestre de grossesse , Études prospectives , Facteurs de risque , Charge viraleRésumé
<p><b>BACKGROUND</b>The 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are attractive candidates for screening for risk of neural tube defects (NTDs). The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China.</p><p><b>METHODS</b>Fifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses.</p><p><b>RESULTS</b>There was a significant difference for MTHFR genotype distribution for one site (C677T) between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group (55.9% vs. 35.3%, P < 0.05). A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype.</p><p><b>CONCLUSION</b>Genetic interaction between MTHFR and MS genes raises the probability of neural tube defects.</p>
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Femelle , Humains , 5-Methyltetrahydrofolate-homocysteine s-methyltransferase , Génétique , Chine , Fréquence d'allèle , Génétique , Prédisposition génétique à une maladie , Génétique , Génotype , Methylenetetrahydrofolate reductase (NADPH2) , Génétique , Anomalies du tube neural , Épidémiologie , Génétique , Polymorphisme génétique , GénétiqueRésumé
The purpose of this study is to find out anti-HIV-1 reverse transcriptase (RT)/protease (PR) activity and inhibition of virus replication in cell cultures of novel coumarin analogs and determine their structure-activity relationship. Coumarin derivatives have been demonstrated to inhibit the activity of HIV-1 RT/PR in cell free system. It also shows inhibition effects to HIV-1 replication in cell culture. Based on the Chinese traditional pharmacological characteristics and protein three dimension computer aided design, analogs of tetracyclic dipyranocoumarin were synthesized from natural leading compounds. We studied the relationship of antiviral effects and chemical structures via HIV-1 PR/RT enzyme models and cell culture model system. Seven compounds were designed and tested. Several compounds showed anti-HIV-1 activity in varying degrees, especially V0201 showed much higher anti-HIV-1 activity with 3.56 and 0.78 micromol x L(-1) of IC50 against HIV-1 PR/RT and 0.036 micromol x L(-1) against HIV-1 replication in PBMC cultures. V0201 with a novel structure may be a new leading compound. These new compounds are valuable for development of new anti-HIV drugs in the future.
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Humains , Agents antiVIH , Chimie , Pharmacologie , Cellules cultivées , Protéine de capside p24 du VIH , Métabolisme , Protéase du VIH , Métabolisme , Transcriptase inverse du VIH , Métabolisme , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Physiologie , Concentration inhibitrice 50 , Agranulocytes , Biologie cellulaire , Métabolisme , Virologie , Pyranocoumarines , Chimie , Pharmacologie , Inhibiteurs de la transcriptase inverse , Chimie , Pharmacologie , Relation structure-activité , Réplication viraleRésumé
In order to find antiviral compounds with novel structures, geldanamycin and lamivudine with different antiviral mechanisms were conjunctively synthesized to acquire a new compound TC-GM, and the antiviral activity of TC-GM was measured. The antiviral activity against HIV-1 was examined by p24 antigen ELISA kit. The activity against HBV was examined by dotblot. The activity against HSV and CoxB virus was examined by CPE. TC-GM exhibited broad-spectrum antiviral activities similarly like geldanamycin. TC-GM inhibited the replication of different viruses, including HIV-1, HBV, HSV 1 and 2, CoxB6. TC-GM showed more potent inhibitory activity against HIV-1 and HBV than other detected virus.
Sujets)
Animaux , Humains , Agents antiVIH , Chimie , Pharmacologie , Antiviraux , Chimie , Pharmacologie , Benzoquinones , Chimie , Pharmacologie , Lignée cellulaire tumorale , Chlorocebus aethiops , Entérovirus humain B , Physiologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Physiologie , Cellules HepG2 , Virus de l'hépatite B , Physiologie , Herpèsvirus humain de type 1 , Physiologie , Herpèsvirus humain de type 2 , Physiologie , Lactames macrocycliques , Chimie , Pharmacologie , Lamivudine , Chimie , Pharmacologie , Cellules rénales canines Madin-Darby , Leucémie-lymphome lymphoblastique à précurseurs B et T , Anatomopathologie , Virologie , Cellules Vero , Réplication viraleRésumé
Objective An analysis was conducted to investigate the iodine nutrition level of children aged 8 - 10 in low-coverage area of iodized salt of Yushu Qinghai province for providing a scientific basis for the development of effective preventive measures. Methods Yushu, Chengduo, Nangqian and Zaduo counties with higher non-iodized salt coverage rate in Yushu Qinghai province were chosen as survey counties in 2009. Three townships were selected in each county, and 2 primary schools were selected in each township and 40 urine samples of children aged 8-10 were collected randomly in each primary school. The content of urinary iodine was analyzed by As-Ce catalytic spectrophotometery. Results Median urinary iodine of children aged 8 - 10 in Nangqian and Zaduo was < 100 μg/L. The percentage of median urinary iodine < 50 μg/L in Yushu was over 20%. Median urinary iodine of children aged 10 in Zaduo was 81.5 μg/L, the percentage of median urinary iodine < 50 μg/L of children aged 9 and 10 was over 20%. The percentage of median urinary iodine < 50 μg/L in children aged 9 and 10 of Yushu was over 20%. Median urinary iodine of girls in Zaduo was 87.1 μg/L, the percentage of median urinary iodine < 50 μg/L of boys in Zaduo was over 20%. The percentage of median urinary iodine < 50 μg/L of girls in Yushu was over 20%. Conclusions The iodine nutrition level of children aged 8 - 10 in Nangqian, Zaduo and Yushu counties were very low due to the impact of non-iodized salt. We propose salt market in the region to strengthen management and improve the coverage and consumption rates of iodized salt to improve the level of iodine nutrition for effective prevention of iodine deficiency disorders.
Résumé
Cycloheximide (CHX) inhibits protein synthesis in most eukaryotic cells and it is a well-known tool commonly used in biochemical research. In this paper, the antiviral spectrum of CHX against several DNA and RNA viruses have been evaluated. CHX showed strong inhibitory activities against several RNA viruses such as HIV-1, influenza viruses, coxsackie B virus, enterovirus (EV71) and several DNA viruses such as HSV and HCMV. Especially the strong inhibitory activities of CHX against coxsackie B virus and enterovirus caught our attention, since effective drugs available in clinic are limited. The SAR of CHX derivatives also has been discussed in the paper. The hydroxyl group at C-2' and carbonyl group at C-2" of CHX are essential for its antiviral activity. And modification to these groups results its derivatives' antiviral activities reduced or lost.