Publications by authors named "Lian Ma"

151 Publications

Model-Informed Drug Development in Pediatric Dose Selection.

J Clin Pharmacol 2021 Jun;61 Suppl 1:S60-S69

Office of Clinical Pharmacology, Food and Drug Administration, Silver Spring, Maryland, USA.

Model-informed drug development (MIDD) has been a powerful and efficient tool applied widely in pediatric drug development due to its ability to integrate and leverage existing knowledge from different sources to narrow knowledge gaps. The dose selection is the most common MIDD application in regulatory submission related to pediatric drug development. This article aims to give an overview of the 3 broad categories of use of MIDD in pediatric dose selection: leveraging from adults to pediatric patients, leveraging from animals to pediatric patients, and integrating mechanism in infants and neonates. Population pharmacokinetic analyses with allometric scaling can reasonably predict the clearance in pediatric patients aged >5 years. A mechanistic-based approach, such as physiologically based pharmacokinetic accounting for ontogeny, or an allometric model with age-dependent exponent, can be applied to select the dose in pediatric patients aged ≤2 years. The exposure-response relationship from adults or from other drugs in the same class may be useful in aiding the pediatric dose selection and benefit-risk assessment. Increasing application and understanding of use of MIDD have contributed greatly to several policy developments in the pediatric field. With the increasing efforts of MIDD under the Prescription Drug User Fee Act VI, bigger impacts of MIDD approaches in pediatric dose selection can be expected. Due to the complexity of model-based analyses, early engagement between drug developers and regulatory agencies to discuss MIDD issues is highly encouraged, as it is expected to increase the efficiency and reduce the uncertainty.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcph.1848DOI Listing
June 2021

FDA Approval Summary: Selinexor for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Oncologist 2021 Jun 15. Epub 2021 Jun 15.

Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

In June 2020, the U.S. Food and Drug Administration granted accelerated approval to selinexor for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. Approval was based on SADAL, a multicenter trial of selinexor monotherapy in patients with DLBCL after two to five systemic regimens. Efficacy was based on independent review committee-assessed objective response rate (ORR) and duration of response using Lugano criteria. In 134 patients treated with the approved dosage (60 mg orally on days 1 and 3 of each week), the ORR was 29% (95% confidence interval, 22-38), with complete response in 13% and with 38% of responses lasting at least 6 months. Gastrointestinal toxicity developed in 80% of patients, hyponatremia in 61%, central neurological toxicity (such as dizziness and mental status changes) in 25%, and ocular toxicity in 18%. New or worsening grade 3 or 4 thrombocytopenia, lymphopenia, neutropenia, anemia, or hyponatremia developed in ≥15%. Adverse reactions led to selinexor dose interruption in 61% of patients, dose reduction in 49%, and permanent discontinuation in 17%, with thrombocytopenia being the leading cause of dose modifications. Postmarketing studies will evaluate reduced dosages of selinexor and further evaluate clinical benefit in patients with relapsed or refractory DLBCL. IMPLICATIONS FOR PRACTICE: Selinexor is a new potential option for adults with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, in the third-line setting or beyond. Toxicities are typically manageable but can be difficult to tolerate and necessitate close monitoring and supportive care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/onco.13859DOI Listing
June 2021

Three-dimensional MoS nanoflowers supported Prussian blue and Au nanoparticles: A peroxidase-mimicking catalyst for the colorimetric detection of hydrogen peroxide and glucose.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Oct 30;259:119886. Epub 2021 Apr 30.

Life and Health Research Institute, Tianjin Key Laboratory of Organic Solar Cells and photochemical Conversion, School of Chemistry & Chemical Engineering, Tianjin University of Technology, Tianjin 300384, PR China. Electronic address:

Well-dispersed Prussian blue (PB) and Au nanoparticles (Au NPs) loaded three dimensional MoS nanoflowers ([email protected] NFs) was synthesized by a simple and economical method. The structure, morphology and composition of the hybrid were characterized by XRD, SEM and EDS. Similar to the reported literature, MoS nanoflowers showed peroxidase-like activity in catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). This peroxidase-mimicking activity could be enhanced with the introduction of PB and Au NPs. Herein, [email protected] NFs could be used to establish a new platform for the determination of HO and glucose by the chromogenic reaction. Wide linear ranges with 0-15 μM and 0-120 μM for HO and glucose detection were finally obtained. The detection limits were as low as 0.25 μM and 3 μM (with signal to noise ratio of 3), respectively. The established platform was also used successfully for the determination of glucose in human serum and fruit juice samples with excellent sensitivity and stability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.saa.2021.119886DOI Listing
October 2021

Chimeric antigen receptor T cells targeting CD7 in a child with high-risk T-cell acute lymphoblastic leukemia.

Int Immunopharmacol 2021 Jul 6;96:107731. Epub 2021 May 6.

Department of Hematology and Oncology, Shenzhen Children's Hospital, No. 7019 Yitian Rd, Shenzhen, Guangdong, PR China. Electronic address:

Effective systemic treatments for relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) are limited. Recent clinical application of chimeric antigen receptor (CAR) immunotherapy has demonstrated successful control of B-cell malignancies by CAR-T cells; however, designing CARs for T-ALL remains a challenge. CD7 overexpression in T-cell malignancies may be an attractive target for immunotherapy in T-ALL. This study aimed to describe the safe and effective use of autologous CD7-CAR T cells (4SCAR7) for the treatment of T-ALL with induction failure in an 11-year-old patient. Based on The Chinese Children's Cancer Group-ALL (CCCG-ALL) study protocol, minimal residual disease (MRD) by flow cytometry (FC) analysis was detected on days 19 and 46 of remission induction. At the end of remission-induction chemotherapy, the patient achieved morphologic complete remission, though with MRD 16.13% and RT-PCR of KMT2A-MLLT1 fusion positive, which indicated induction failure. The cerebrospinal fluid (CSF) was negative for blasts at diagnosed. CAR-T therapy and allogeneic transplant were recommended as the next treatment options. CD3 lymphocytes were collected from the patient 18 days after the high-dose MTX chemotherapy through leukapheresis. The 4SCAR7 CD7-targeting CAR-T cells were generated thereafter. The patient received lymphodepleting chemotherapy prior to 4SCAR7 infusion. Oral administration of itraconazole and sulfamethoxazole was performed from day 0 after CAR-T cell infusion. The patient did not have hypotension, hypoxia, or serious biochemical change or abnormality, but had fever on day 9. Although grade 1 cytokine-release syndrome (CRS) was diagnosed, it was successfully treated with ibuprofen. Anti-CD7 CAR transgene copy numbers in peripheral blood were determined by qPCR, which showed effective expansion initially, then dropped quickly, and persisted at a low level. Although experienced cytopenia from days 14 to 21, the patient achieved remission on day 17. After complete remission, the patient received hematopoietic stem cell transplantation (HSCT) and has recovered well to thisdate. Overall, this report suggested that 4SCAR7 could be a safe and effective strategy for the treatment of pediatric patients with high-risk T-cell malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2021.107731DOI Listing
July 2021

Regulatory news: Dojolvi (triheptanoin) as a source of calories and fatty acids in long-chain fatty acid oxidation disorders: FDA approval summary.

J Inherit Metab Dis 2021 May 25;44(3):515-517. Epub 2021 Mar 25.

Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jimd.12377DOI Listing
May 2021

Circular RNA Involvement in the Protective Effect of Human Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Against Hypoxia/Reoxygenation Injury in Cardiac Cells.

Front Cardiovasc Med 2021 23;8:626878. Epub 2021 Feb 23.

Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.

Human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (HuMSC-EVs) can repair damaged tissues. The expression profile of circular RNAs (circRNAs) provides valuable insights into the regulation of the repair process and the exploration of the repair mechanism. AC16 cardiomyocytes were exposed to hypoxia/reoxygenation (H/R) injury and subsequently cultured with or without HuMSC-EVs (Group T and Group C, respectively). High-throughput RNA sequencing was implemented for the two groups. On the basis of the transcriptome data, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and network analyses were carried out to determine the differential gene expression profiles between the two groups. After screening the circRNA database, the results were proved by quantitative real-time polymerase chain reaction. The survival rate of cardiomyocytes exposed to H/R was increased by treatment with HuMSC-EVs. RNA-seq analysis showed that 66 circRNAs were differentially expressed in cardiomyocytes in the co-cultured group. The cellular responses to hypoxia and to decreased oxygen levels were at the top of the GO upregulated list for the two groups, while the vascular endothelial growth factor signaling pathway, long-term potentiation, and the glucagon signaling pathway were at the top of the KEGG pathway upregulated list for the two groups. In the same samples, the 10 most aberrantly upregulated circRNAs were chosen for further verification of their RNA sequences. Seven of the 10 most aberrant circRNAs were significantly upregulated in the co-cultured group and in the HuMSC-EVs. Our results revealed that upregulated circRNAs were abundant during the repair of damaged cardiomyocytes by HuMSC-EVs, which provides a new perspective for the repair of H/R by HuMSC-EVs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.626878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940380PMC
February 2021

Leukaemia Infection Diagnosis and Intestinal Flora Disorder.

Curr Mol Med 2021 Mar 2. Epub 2021 Mar 2.

Department of Hematology and Oncology, Shenzhen Children's Hospital of China Medical University, Shenzhen. China.

Leukaemia is the most common malignant tumor in childhood and can be cured by chemotherapy. Infection is an important cause of treatment-related death and treatment failure in childhood leukaemia. Recent studies have shown that the correlation between the occurrence of leukaemia infection and the intestinal flora has attracted more and more attention. Intestinal flora can affect the body's physiological defense and immune function. When intestinal microflora disorder occurs, metabolites/microorganisms related to intestinal flora alterations and even likely the associated morpho-functional alteration of the epithelial barrier may be promising diagnostic biomarkers for the early diagnosis of leukaemia infection. This review will focus on the interaction between leukaemia infection and intestinal flora, and the influence of intestinal flora in the occurrence and development of leukaemia infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1566524021666210302144720DOI Listing
March 2021

Effect of lead exposure from electronic waste on haemoglobin synthesis in children.

Int Arch Occup Environ Health 2021 Jul 20;94(5):911-918. Epub 2021 Jan 20.

Department of Hematology and Oncology, Shenzhen Children's Hospital of China Medical University, Shenzhen, 518038, China.

Background: Primitive electronic waste (e-waste) recycling is ongoing in Guiyu, so toxic heavy metals may continue to threaten the health of children in the area.

Objective: This study primarily aimed to evaluate the effect of e-waste exposure on haemoglobin (Hb) synthesis in preschool children.

Methods: Medical examinations were conducted with the permission of children's guardians and the approval of the Ethics Committee of the Medical College of Shantou University. This study recruited 224 children (aged 3-6 years, exposed group) who lived in Guiyu and 204 children (aged 3-6 years, control group) who lived in a town free of e-waste pollution. Blood levels of lead, Hb, ferritin, folate and vitamin B were tested in all children. Furthermore, all children were assessed for thalassemia, and their parents were asked to fill in questionnaires.

Results: There were no significant differences in the level of ferritin, folate, or vitamin B between the exposed and control groups (P > 0.05). No children were identified as having thalassemia in all study participants. Blood lead level (BLL) and the risk of children with BLL ≥ 10 µg/dL in the exposed group were significantly higher than those in the control group (all P < 0.01). Three subgroups of each group were created according to BLL (Group A: < 5.0 µg/dL; Group B: 5.0-9.9 µg/dL; Group C: ≥ 10.0 µg/dL). Hb level decreased with elevated BLL in the exposed group (P = 0.03), but not in the control group (P = 0.14). Hb levels in group B and group C were also significantly lower in the exposed group than in the control group (Group B: 122.6 ± 9.5 g/L versus 125.8 ± 8.2 g/L, P = 0.01; Group C: 120.3 ± 7.3 g/L versus 123.6 ± 8.3 g/L, P = 0.03). In addition, the prevalence of anaemia associated with BLLs above 10 µg/dL and between 5.0 and 9.9 µg/dL were both significantly higher in the exposed group than in the control group (4.0% vs. 0.5%, 5.4% vs. 1.5%, respectively, both P < 0.05).

Conclusion: Lead exposure more significantly inhibits Hb synthesis in children who live in e-waste dismantling areas than in those who live in non-e-waste dismantling areas. Other toxins released from e-waste may also contribute to the inhibition of Hb synthesis and may lead to anaemia in local children. Further investigations are needed to provide evidence for the development of relevant protective measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00420-020-01619-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238723PMC
July 2021

Halomonas humidisoli Sp. Nov., Isolated From Saline-Alkaline Soil.

Curr Microbiol 2021 Feb 2;78(2):803-809. Epub 2021 Jan 2.

Key Laboratory of Microbial Resources Collection and Preservation, Ministry of Agriculture and Rural Affair, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, 100081, People's Republic of China.

A Gram staining-negative, halophilic, aerobic, non-motile bacteria, designated strain WN018, were isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China (38°46'N, 117°13'E). Cells of strain WN018 were short rod-shaped, 0.3-0.4 µm wide and 0.5-1.9 µm long, and growth occurred optimally at 30-33 °C, pH 7.5-8.0, and in the presence of 4-8% (w/v) NaCl. Based on 16S rRNA gene sequence analysis, the isolates could be affiliated to the genus Halomonas, exhibiting highest sequence similarity of 97.50% to Halomonas venusta DSM 4743T. The DNA G+C content of the strain was 63.8%. The distinct phylogenetic position and phenotypic traits distinguished the novel isolate from its nearest neighbors. The major respiratory quinone of strain WN018 was Q-9 (91.0%) and Q-8 (9.0%), and the dominant fatty acids were C, C, C, C 3-OH. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), three phospholipids (PL), aminolipid (AL), and two unidentified lipids (L). The average nucleotide identity (ANI) based on whole-genome sequences of strain WN018 and Halomonas hydrothermalis DSM 15725 was 93.02%, and the dDDH value between these two strains was determined to be 49.7%. Therefore, we propose a novel species in the genus Halomonas to accommodate the novel isolate: Halomonas humidisoli sp. nov. (type strain WN018 = ACCC 19975 = KCTC 52854).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00284-020-02291-xDOI Listing
February 2021

[Research and development of new traditional Chinese medicine drugs for certain syndromes based on "theoretical innovation"].

Zhongguo Zhong Yao Za Zhi 2020 Oct;45(20):5048-5056

Dongzhimen Hospital, Beijing University of Chinese Medicine Beijing 100700, China.

Compound prescription of traditional Chinese medicine(TCM), the main form in prevention and treatment of diseases in TCM, has unique advantages in medical practice. New TCM drugs for certain syndromes serve as an important carrier of inheritance and innovation in TCM. The research and development of new TCM drugs for certain syndromes should be based on the theory of TCM, guided by clinical value, and based on the principle of quality, safety and effectiveness. Through the innovative understanding of disease development rules, clinicians carry out academic theory innovation to guide clinical practice, aiming to effectively promote academic innovation and the development of new TCM drugs for certain syndromes. In this paper, we expounded some understanding of the innovation system of TCM, and analyzed the research value of new TCM drugs for certain syndromes. Based on theoretical innovation, the overall research model was preliminarily put forward. Subsequently, a concrete discussion from three aspects, including pharmaco-logy and toxicology, pharmacy and clinic research, was made on the specific process and existing problems of new drug research and development of TCM. Our research group attempts to establish a new drug innovation ecosystem for TCM syndrome, with the purpose of providing reference for other researchers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20200229.501DOI Listing
October 2020

A review of the experience with pediatric written requests issued for oncology drug products.

Pediatr Blood Cancer 2021 02 27;68(2):e28828. Epub 2020 Nov 27.

Division of Biostatistics IX (DBIX), Office of Biostatistics (OB), Office of Translational Sciences (OTS), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Silver Spring, Maryland.

Background: Pediatric anticancer drug development has numerous challenges. The Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) were passed to address pediatric drug development deficiencies in general. Until recently, the requirements for pediatric evaluation of most oncology products developed for adult cancers have been waived. Because children typically do not have the same type of cancers, which occur commonly in adults, or the indication or drug had been granted an orphan designation, PREA therefore has had no impact. Pediatric studies for labeling updates are largely done through BPCA by a written request (WR) issued by the Food and Drug Administration (FDA). Because the cancers that occur in pediatric and adult populations do not share the same etiology or natural history, there are limited opportunities to extrapolate adult efficacy and safety to the pediatric population. The characteristics of individual pediatric studies included in WRs have varied greatly over time.

Procedure: In this study, we searched WRs that were issued by the FDA since 2001. We found 40 such requests issued for oncology drugs and biologics, which had been accepted by sponsors.

Results: Clinical trials included in 23 of the WRs have been concluded, 19 have resulted in exclusivity, and three drugs that were studied have been approved for use in pediatric populations. Herein, we present the spectrum of WRs from a regulatory, study design, dosing, formulation, analysis plan, evidentiary standard of efficacy, and safety perspective.

Conclusions: This provides information on requests issued in the past nearly 20 years and studies that are completed. As WRs have provided the only regulatory mechanism to assure pediatric cancer drug development, this can potentially provide insight on how pediatric cancer drug development may change in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28828DOI Listing
February 2021

Halovibrio salipaludis sp. nov., Isolated from Saline-Alkaline Soil.

Curr Microbiol 2021 Jan 21;78(1):429-434. Epub 2020 Nov 21.

Key Laboratory of Microbial Resources Collection and Preservation, Ministry of Agriculture and Rural Affair, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, 100081, People's Republic of China.

A Gram-staining-negative, halophilic, aerobic, oval-shaped or vibrio-shaped, motile by a polar flagellum strain, designated YL5-2, was isolated from natural saline-alkaline wetland soil of Binhai new district, Tianjin, China. Strain YL5-2 grew optimally at 35 °C, pH 7.5-8.0, and in the presence of 10-25% (w/v) NaCl on MA medium. Phylogenetic analyses based on 16S rRNA gene sequences showed that the isolate belonged to the genus Halovibrio and exhibited high sequence similarity of 97.7% to Halovibrio variabilis DSM 3050. The sole respiratory ubiquinone of strain YL5-2 is Q-9, and the dominant fatty acids were Cω9c, C, C cycloω8c, and Summed Feature 8. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC), and lipid (L). The DNA G+C content of the strain was 62.1 mol%. The average nucleotide identity (ANI) based on whole genome sequences of strain YL5-2 and Halovibrio variabilis DSM 3050 was 93.85%, and the dDDH value between these two strains was determined to be 52.0%. Phenotypic, chemotaxonomic, phylogenetic, and genomic analyses suggested that strain YL5-2 represent a novel species of the genus Halovibrio, for which the name Halovibrio salipaludis sp. nov. is proposed. The type strain is YL5-2 (=KCTC 52852=ACCC 19971).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00284-020-02282-yDOI Listing
January 2021

Maxillary Protraction Therapy in Class III Patients With and Without Cleft Lip and Palate: An Interim Report of a Prospective Comparative Study.

Cleft Palate Craniofac J 2021 04 28;58(4):429-437. Epub 2020 Sep 28.

Department of Orthodontics, 159460School and Hospital of Stomatology, Peking University, Beijing, China.

Objective: To investigate and compare the effects of maxillary protraction therapy on Class III patients with unilateral cleft lip and palate (UCLP) and Class III patients with noncleft.

Design: Prospective controlled clinical trial.

Patients: Twenty-six Class III patients with UCLP (mean age: 10.32 ± 1.29 years) and 26 Class III patients with noncleft (mean age: 9.82 ± 1.03 years) were included and treated with maxillary protraction therapy.

Interventions: Maxillary protraction therapy was performed with an intraoral Hyrax appliance and extraoral facemask. Cone beam computed tomography scans were taken before and after treatment. Pretreatment skeletal and dental characteristics and treatment changes were analyzed and compared.

Results: The average treatment duration was 18.44 ± 4.16 months in the UCLP group, which was substantially longer than the 12.46 ± 4.03-month average treatment duration in the noncleft group ( < .001). No significant difference was found in the maxillary changes (length, advancement of point A, and SNA angle) and improvement of intermaxillary relationship (ANB angle) between the 2 groups. The UCLP group had 1.40° more mandibular clockwise rotation ( = .034). Regarding dental changes, the UCLP group had more upper incisor proclination ( = .006) and less lower incisor retroclination ( = .023).

Conclusions: Approximately extended maxillary protraction therapy in patients with UCLP could be as effective as in patients with noncleft. Further study is required to follow patients until completion of growth to elucidate the long-term stability of the treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1055665620954058DOI Listing
April 2021

Intranasal administration of Cytoglobin modifies human umbilical cord‑derived mesenchymal stem cells and improves hypoxic‑ischemia brain damage in neonatal rats by modulating p38 MAPK signaling‑mediated apoptosis.

Mol Med Rep 2020 Oct 19;22(4):3493-3503. Epub 2020 Aug 19.

Department of Pediatrics, Shenzhen Children's Hospital, Shenzhen, Guangdong 518038, P.R. China.

Neonatal hypoxic‑ischemic brain damage (HIBD) is a common clinical syndrome in newborns. Hypothermia is the only approved therapy for the clinical treatment; however, the therapeutic window of hypothermia is confined to 6 h after birth and even then, >40% of the infants either die or survive with various impairments, including cerebral palsy, seizure disorder and intellectual disability following hypothermic treatment. The aim of the present study was to determine whether nasal transplantation of Cytoglobin (CYGB) genetically modified human umbilical cord‑derived mesenchymal stem cells (CYGB‑HuMSCs) exhibited protective effects in neonatal rats with HIBD compared with those treated without genetically modified CYGB. A total of 120 neonatal Sprague‑Dawley rats (postnatal day 7) were assigned to either a Sham, HIBD, HuMSCs or CYGB‑HuMSCs group (n = 30 rats/group). For HIBD modeling, rats underwent left carotid artery ligation and were exposed to 8% oxygen for 2.5 h. A total of 30 min after HI, HuMSCs (or CYGB‑HuMSCs) labeled with enhanced‑green fluorescent protein (eGFP) were intranasally administered. After modeling for 3, 14 and 29 days, five randomly selected rats were sacrificed in each group, and the expression levels of CYGB, ERK, JNK and p38 in brain tissues were determined. Nissl staining of the cortex and hippocampal Cornu Ammonis 1 area of rats in each group were compared after 3 days of modeling. TUNEL assay and immunofluorescence were performed 3 days after modeling. Long term memory in rats was assessed using a Morris‑water maze 29 days after modeling. The HIBD group demonstrated significant deficiencies compared with the Sham group based on Nissl staining, TUNEL assay and the Morris‑water maze test. HuMSC treated rats exhibited improvement on in all the tests, and CYGB‑HuMSCs treatment resulted in further improvements. PCR and western blotting results indicated that the CYGB mRNA and protein levels were increased from day 3 to day 29 after transplantation of CYGB‑HuMSCs. Furthermore, it was identified that CYGB‑HuMSC transplantation suppressed p38 signaling at all experimental time points. Immunofluorescence indicated the scattered presence of HuMSCs or CYGB‑HuMSCs in damaged brain tissue. No eGFP and glial fibrillary acidic protein or eGFP and neuron‑specific enolase double‑stained positive cells were found in the brain tissues. Therefore, CYGB‑HuMSCs may serve as a gene transporter, as well as exert a neuroprotective and antiapoptotic effect in HIBD, potentially via the p38 mitogen‑activated protein kinase signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2020.11436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453519PMC
October 2020

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells Protect Cardiac Cells Against Hypoxia/Reoxygenation Injury by Inhibiting Endoplasmic Reticulum Stress via Activation of the PI3K/Akt Pathway.

Cell Transplant 2020 Jan-Dec;29:963689720945677

Department of Pediatrics, 74599Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China.

Endoplasmic reticulum (ER) stress is implicated in the pathogenesis of many diseases, including myocardial ischemia/reperfusion injury. We hypothesized that human umbilical cord mesenchymal stromal cells derived extracellular vesicles (HuMSC-EVs) could protect cardiac cells against hyperactive ER stress induced by hypoxia/reoxygenation (H/R) injury. The H/R model was generated using the H9c2 cultured cardiac cell line. HuMSC-EVs were extracted using a commercially available exosome isolation reagent. Levels of apoptosis-related signaling molecules and the degree of ER stress were assessed by western blot. The role of the PI3K/Akt pathway was investigated using signaling inhibitors. Lactate dehydrogenase leakage and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) analysis were used for evaluating the therapeutic effects of HuMSC-EVs . The results showed that ER stress and the rate of apoptosis were increased in the context of H/R injury. Treatment with HuMSC-EVs inhibited ER stress and increased survival in H9c2 cells exposed to H/R. Mechanistically, the PI3K/Akt pathway was activated by treatment with HuMSC-EVs after H/R. Inhibition of the PI3K/Akt pathway by a specific inhibitor, LY294002, partially reduced the protective effect of HuMSC-EVs. Our findings suggest that HuMSC-EVs could alleviate ER stress-induced apoptosis during H/R via activation of the PI3K/Akt pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0963689720945677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563023PMC
July 2021

Giant sublingual hamartoma with medial cleft tongue: a case report and literature review.

J Int Med Res 2020 Aug;48(8):300060520942089

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.

Hamartomas commonly occur in respiratory and digestive organs, such as the lungs, pancreas, and liver; they rarely occur in the oral cavity, especially in the sublingual region. This report describes a 5-month-old boy who presented with a giant sublingual hamartoma and medial cleft tongue. He underwent corrective operations at 5 months, 11 months, and 31 months of age. Histopathological analysis revealed features suggestive of hamartoma. There have been no signs of recurrence. The boy exhibited normal speech development at 3 years of age; all other oral functions were unaffected at that time. This report includes a review of relevant literature. The findings in this report and previous literature suggest that a multidisciplinary approach, carefully planned staged surgery, and rehabilitation are needed to achieve favorable outcomes in patients with hamartoma in the oral cavity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300060520942089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450465PMC
August 2020

Divergent Roles of miR-3162-3p in Pulmonary Inflammation in Normal and Asthmatic Mice as well as Antagonism of miR-3162-3p in Asthma Treatment.

Int Arch Allergy Immunol 2020 1;181(8):594-605. Epub 2020 Jul 1.

Department of Hematology and Oncology, and Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen, China.

MicroRNA (miRNA) mimics or antagomirs hold great promise for asthma treatment compared with glucocorticoids as mainstay therapy for asthma. But the role of miRNA in regulating asthmatic inflammation is largely unclear. We previously reported that miR-3162-3p in the peripheral blood of children with asthma was obviously upregulated compared to that in healthy children. This study aimed to elucidate the role of miR-3162-3p in pulmonary inflammation in normal and asthmatic mice as well as preliminarily explore the potential of miR-3162-3p antagomir in asthma treatment. A noninvasive whole-body plethysmograph measured airway responsiveness. Both qRT-PCR and Western blot were used to detect the expression of miRNA, mRNA, or protein. Cells in bronchoalveolar lavage fluid were counted by platelet counting and Wright's staining. Inflammatory infiltration and mucus secretion were identified by hematoxylin and eosin and periodic acid-Schiff  staining, respectively. Cytokines in the lungs were detected by ELISA. The miR-3162-3p mimic intraperitoneally administered to normal mice decreased β-catenin levels in the lungs without obviously altering the lung histology and cytokine levels. Antagonizing miR-3162-3p in ovalbumin-induced asthmatic mice effectively alleviated the typical features of asthma, such as airway hyper-responsiveness, airway inflammation, and Th1/Th2 cytokine imbalance, and concomitantly rescued the total and active β-catenin expression. Collectively, we discovered divergent roles of miR-3162-3p in lung inflammation between normal and asthmatic mice. The anti-inflammatory effects of the miR-3162-3p antagomir were comparable to those of glucocorticoid treatment. Our study helped in understanding the contribution of miRNAs to the pathogenesis of asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000507250DOI Listing
January 2021

FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease.

Oncologist 2020 02 22;25(2):e328-e334. Epub 2019 Oct 22.

Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

On May 24, 2019, the Food and Drug Administration approved ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-271 (REACH-1; NCT02953678), an open-label, single-arm, multicenter trial that included 49 patients with grades 2-4 SR-aGVHD occurring after allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered at 5 mg twice daily, with dose increases to 10 mg twice daily permitted after 3 days in the absence of toxicity. The Day-28 overall response rate was 57.1% (95% confidence interval [CI]: 42.2-71.2). The median duration of response was 0.5 months (95% CI: 0.3-2.7), and the median time from Day-28 response to either death or need for new therapy for acute GVHD was 5.7 months (95% CI: 2.2 to not estimable). Common adverse reactions included anemia, thrombocytopenia, neutropenia, infections, edema, bleeding, and elevated transaminases. Ruxolitinib is the first drug approved for treatment of SR-aGVHD. IMPLICATIONS FOR PRACTICE: Ruxolitinib is the first Food and Drug Administration-approved treatment for steroid-refractory acute graft-versus-host disease in adult and pediatric patients 12 years and older. Its approval provides a treatment option for the 60% of those patients who do not respond to steroid therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011641PMC
February 2020

Antimicrobial Resistance and Resistance Determinant Insights into Multi-Drug Resistant Gram-Negative Bacteria Isolates from Paediatric Patients in China.

Infect Drug Resist 2019 22;12:3625-3634. Epub 2019 Nov 22.

Shenzhen Children's Hospital, Futian District, Shenzhen, Guangdong Province, People's Republic of China.

Introduction: The emergence of multi-drug-resistant Gram-negative bacteria (GNB) is a concern in China and globally. This study investigated antimicrobial resistance traits and resistance determinant detection in GNB isolates from paediatric patients in China.

Methods: In the present study, a total of 170 isolates of GNB including the most prevalent and were collected from Shenzhen Children's Hospital, China. ESBLs production was confirmed by using the combination disc diffusion method, and carbapenemase production was confirmed by using a carbapenem inactivation method followed by antimicrobial susceptibility. In addition, β-lactamase-encoding genes and co-existence of plasmid-borne colistin resistance gene were determined by PCR and sequencing.

Results: Overall, 170 etiological agents (GNB) were recovered from 158 paediatric patients. The most prevalent species was 40% (n=68), followed by 17.64% (n=30), and 14.11% (n=24). Of 170 GNB, 71.76% (n=122) were multi-drug-resistant, 12.35% (n=21) extreme-drug resistant, and 7.64% (n=13) single-drug-resistant, while 8.23% (n=14) were sensitive to all of the studied antibiotics. The prevalence of ESBLs and carbapenemase producers were 60% and 17%, respectively. was the most prevalent resistance gene (59.42%), followed by (41.17%), (34.270%), (34.11%), (18.82%) and (17.64%).

Conclusion: The present study provides insights into the linkage between the resistance patterns of GNB to commonly used antibiotics and their uses in China. The findings are useful for understanding the genetics of resistance traits and difficulty in tackling of GNB in paediatric patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IDR.S223736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878922PMC
November 2019

Mean Platelet Volume: A Novel Predictor for Bone Erosion in Gouty Arthritis?

Ann Clin Lab Sci 2019 Sep;49(5):661-665

Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong, China.

Objective: Gout is a type of inflammatory arthritis that can be complicated with bone erosion through several inflammatory factors. Mean platelet volume (MPV) is regarded as a marker in many inflammatory disorders, but despite this, the metric has not been used for gout.

Material And Methods: This study evaluates the relationship between MPV and bone erosion in patients with gout. In total, 299 patients were evaluated retrospectively, and 120 patients were ultimately included based on inclusion criteria.

Results: Both the duration of this disease and mean platelet volume were related to bone erosion in gout and may be regarded as independent predictors of bone erosion.

Conclusion: These results suggest that mean platelet volume can be a predictor of bone erosion in gout.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2019

Pax4 synergistically acts with Pdx1, Ngn3 and MafA to induce HuMSCs to differentiate into functional pancreatic β-cells.

Exp Ther Med 2019 Oct 5;18(4):2592-2598. Epub 2019 Aug 5.

Department of Pediatrics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.

It has been indicated that the combination of pancreatic and duodenal homeobox 1 (Pdx1), MAF bZIP transcription factor A (MafA) and neurogenin 3 (Ngn3) was able to reprogram various cell types towards pancreatic β-like cells (pβLCs). Paired box 4 (Pax4), a transcription factor, has a key role in regulating the maturation of pancreatic β-cells (pβCs). In the present study, it was investigated whether Pax4 is able to synergistically act with Pdx1, Ngn3 and MafA to induce human umbilical cord mesenchymal stem cells (HuMSCs) to differentiate into functional pβCs . HuMSCs were isolated, cultured and separately transfected with adenovirus (Ad) expressing enhanced green fluorescence protein, Pax4 (Ad-Pax4), Pdx1+MafA+Ngn3 (Ad-3F) or Ad-Pxa4 + Ad-3F. The expression of C-peptide, insulin and glucagon was detected by immunofluorescence. The transcription of a panel of genes was determined by reverse transcription-quantitative PCR, including glucagon (GCG), insulin (INS), NK6 homeobox 1 (NKX6-1), solute carrier family 2 member 2 (SLC2A2), glucokinase (GCK), proprotein convertase subtilisin/kexin type 1 (PCSK1), neuronal differentiation 1 (NEUROD1), ISL LIM homeobox 1 (ISL 1), Pax6 and PCSK type 2 (PCSK2). Insulin secretion stimulated by glucose was determined using ELISA. The results suggested that, compared with Ad-3F alone, cells co-transfected with Ad-Pax4 and Ad-3F expressed higher levels of INS and C-peptide, as well as genes expressed in pancreatic β precursor cells, and secreted more insulin in response to high glucose. Furthermore, the expression of GCG in cells transfected with Ad-3F was depressed by Ad-Pax4. The present study demonstrated that Pax4 was able to synergistically act with the transcription factors Pdx1, Ngn3 and MafA to convert HuMSCs to functional pβLCs. HuMSCs may be potential seed cells for generating functional pβLCs in the therapy of diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2019.7854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755441PMC
October 2019

Role of Model-Informed Drug Development in Pediatric Drug Development, Regulatory Evaluation, and Labeling.

J Clin Pharmacol 2019 09;59 Suppl 1:S104-S111

Food and Drug Administration, Silver Spring, MD, USA.

The unique challenges in pediatric drug development require efficient and innovative tools. Model-informed drug development (MIDD) offers many powerful tools that have been frequently applied in pediatric drug development. MIDD refers to the application of quantitative models to integrate and leverage existing knowledge to bridge knowledge gaps and facilitate development and decision-making processes. This article discusses the current practices and visions of applying MIDD in pediatric drug development, regulatory evaluation, and labeling, with detailed examples. The application of MIDD in pediatric drug development can be broadly classified into 3 categories: leveraging knowledge for bridging the gap, dose selection and optimization, and informing clinical trial design. In particular, MIDD can provide evidence for the assumption of exposure-response similarity in bridging existing knowledge from reference to target population, support the dose selection and optimization based on the "exposure-matching" principle in the pediatric population, and increase the efficiency and success rate of pediatric trials. In addition, the role of physiologically based pharmacokinetics in drug-drug interaction in children and adolescents and in utilizing ontogeny data to predict pharmacokinetics in neonates and infants has also been illustrated. Moving forward, MIDD should be incorporated into all pediatric drug development programs at every stage to inform clinical trial design and dose selection, with both its strengths and limitations clearly laid out. The accumulated experience and knowledge of MIDD has and will continue to drive regulatory policy development and refinement, which will ultimately improve the consistency and efficiency of pediatric drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcph.1478DOI Listing
September 2019

Double Tongue Flaps for Anterior Huge Palatal Fistula Closure.

Authors:
Xia Zhou Lian Ma

Plast Reconstr Surg Glob Open 2019 May 28;7(5):e2246. Epub 2019 May 28.

Cleft Lip and Palate Treatment Center, Oral and Maxillofacial Department, School of Stomatology, Peking University, Beijing, China.

Even though it is widely accepted that the tongue flap is effective and feasible for repair of huge palatal fistula, there still exist a few failed cases due to the severity or complicated situation. The aim of this paper is to report the validity and feasibility of using double tongue dorsal flaps to repair a huge anterior fistula. A 10-year-old boy diagnosed with Van de Woude syndrome with repaired bilateral cleft lip and palate presented with a huge anterior fistula divided by septum. A double tongue dorsal flap was designed to cover the fistula. The huge unusual anterior palatal fistula was repaired successfully by usage of double pedicle tongue flaps with a follow-up period of 1 month. The double tongue flap is an alternative choice to handle a large residual fistula in anterior part of palate which was divided into 2 fistulas by septum. This technique was indicated in the situation of large residual fistula in anterior part of palate which was divided into 2 fistulas by septum after bilateral cleft palate repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/GOX.0000000000002246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571300PMC
May 2019

Nicotine induces insulin resistance via downregulation of Nrf2 in cardiomyocyte.

Mol Cell Endocrinol 2019 09 14;495:110507. Epub 2019 Jul 14.

Department of Cardiovascular Medicine, Second Affiliated Hospital of Shantou University Medical College, No. 69, Dongxiabei Road, Shantou, Guangdong, China. Electronic address:

Clinical studies have demonstrated that cigarette smoking is strongly associated with insulin resistance and heart disease. Nicotine is considered the primary toxin constituent associated with smoking. However, the distinct molecular mechanism of nicotine-induced cardiac dysfunction remains unclear. Cardiomyocytes with nicotine-induced insulin resistance are characterized by decreased glucose uptake, as measured by 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG), a fluorescent derivative of glucose, and reactive oxygen species (ROS) generation. Immunoblotting was used to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), extracellular signal-related kinase (ERK) and phosphoinositide 3-kinase (PI3K, p85, Y607). We determined the impact of nicotine on insulin resistance and Nrf2, phospho-ERK and phospho-PI3K expression in the myocardial tissue of a mouse model. Nicotine increased ROS production and depressed insulin-induced glucose uptake in cardiomyocytes. Pretreatment with N-acetyl-L-cysteine (NAC), an antioxidant, reversed nicotine-inhibited glucose uptake induced by insulin. Nicotine exposure directly inhibited Nrf2 and increased ERK phosphorylation in cardiomyocytes, which were obstructed by NAC. Further exploration of signaling cascades revealed nicotine-induced ROS involved in inhibiting PI3K/Nrf2 and activating ERK in cardiomyocytes. Moreover, the mouse model treated with nicotine showed glucose intolerance and impaired insulin tolerance accompanied by inhibited PI3K/Nrf2 and increased ERK in myocardial tissues. Thus, nicotine induces insulin resistance via the downregulation of Nrf2 activity in cardiomyocytes, which is a potential mechanism of the pharmacological effects of nicotine. This study identified potential therapeutic targets against nicotine-related cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mce.2019.110507DOI Listing
September 2019

Phenotypic and genotypic characterization of multi-drug-resistant isolates harboring bla group extended-spectrum β-lactamases recovered from pediatric patients in Shenzhen, southern China.

Infect Drug Resist 2019 16;12:1325-1332. Epub 2019 May 16.

Department of Haematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong Province 518038, People's Republic of China.

The emergence and spread of extended-spectrum β-lactamases (ESBLs) particularly CTX-M producing multi-drug-resistant (MDR) () is one of the greatest challenges for community health globally. The study investigated the phenotypic and genotypic characteristics of ESBLs-producing recovered from pediatric patients from Shenzhen Children's Hospital, China. Present study, a total of 2,670 isolates of . were collected from Shenzhen Children's Hospital, China of which 950 were ESBLs producer. ESBLs production was confirmed by using the combination disc diffusion method, and antimicrobial susceptibility test was detected. In addition, β-lactamase-producing genes and co-existence of carbapenem/colistin resistance genes were determined by PCR assay and sequencing. The diversity and phylogenetic relationship were determined by multi-locus sequence typing method. Thirty-five percent (=950) prevalence of ESBLs-producing . we reported in Shenzhen, China of which 50 ESBLs producing were randomly selected for a further characterization. All 50 ESBLs- producing isolates revealed MDR phenotype and 100% were resistant to Ampicillin/sulbactam, Ampicillin, Cefazolin, and Ceftriaxone. All 50 ESBLs producers harbored at least one type of β-lactamase gene particular . The PCR and sequencing revealed the most common CTX-M subtype was (=18), followed by (=16), (=9), (=3), , and each (=1). Co-existence of with , , , and was detected in few isolates. Among identified sequence types, ST131 (12%) was more dominant in ESBLs-producing . Phylogenetic group A was the most prominent group among the ESBLs-producing based on multiplex PCR. Our study shows the prevalence of gene in ESBLs-producing in pediatric patients in Shenzhen, China. We highlight the importance to monitor the emergence and trends of ESBLs-producing isolates in a pediatric healthcare setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IDR.S199861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529603PMC
May 2019

Effects of N application on faba bean chocolate spot and canopy microclimate in wheat and faba bean intercropping system.

Ying Yong Sheng Tai Xue Bao 2019 Mar;30(3):951-960

College of Resources and Environment, Yunnan Agricultural University, Kunming 650201, China.

A field experiment was conducted to examine the effects of nitrogen application levels, i.e. N (0 kg·hm), N (45 kg·hm), N (90 kg·hm), N (135 kg·hm), on the severity of chocolate spot and canopy microclimate in wheat and faba bean intercropping system, and to explore the relationship of canopy microclimate change and severity of chocolate spot. The results showed that the disease index of chocolate spot increased by 27.2%-58.0% in the peak infection stage, and the area under disease progress curve (AUDPC) increased by 15.0%-101.8% for both monocropped and intercropped faba bean after nitrogen application. The peak value of disease index and AUDPC appeared at N (135 kg·hm) level. After nitrogen application, canopy temperature decreased by 0.2-1.1 ℃ and canopy light transmittance decreased by 1.7%-29.7%, but canopy relative humidity increased by 0.5%-28.7%. Compared with monocropped faba bean, wheat and faba bean intercropped significantly decreased the chocolate spot disease index by 36.3%-48.1% and AUDPC by 44.0%-53.6%. Canopy temperature and light transmittance of intercropped faba bean increased by 2.1%-8.7% and 12.0%-53.8%, respectively. The canopy relative humidity was decreased by 11.6%-31.6%. There were significantly negative correlation between canopy temperature and light transmittance with disease index of faba bean chocolate spot. The canopy humidity was positively correlated with disease index. Our findings showed that high nitrogen application deteriorated canopy microclimate of faba bean that led to occurrence and harm of chocolate spot, and that the improvement of canopy microclimate by intercropping would be helpful for controlling faba bean chocolate spot.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13287/j.1001-9332.201903.022DOI Listing
March 2019

PtNi bimetallic nanoparticles loaded MoS nanosheets: Preparation and electrochemical sensing application for the detection of dopamine and uric acid.

Anal Chim Acta 2019 May 21;1055:17-25. Epub 2018 Dec 21.

Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, School of Chemistry & Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, PR China. Electronic address:

Composite nanomaterials are particularly useful and offer many excellent opportunities for electrochemical sensing application. Depending on the high catalytic activity of bimetallic nanoparticles, the large specific surface area, abundant active edges and co-catalytic function of MoS nanosheets, we, for the first time, prepared a novel PtNi bimetallic nanoparticles loaded MoS nanosheets ([email protected]) hybrid material by a co-reduction method for the electrochemical sensing application. The nanocomposite is characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS), and then casted on a bare glassy carbon electrode (GCE) to fabricate an electrochemical sensor ([email protected]/GCE). The electrochemical investigation showed that the sensor performed good selectivity and wide linear ranges for the simultaneous detection of dopamine (0.5-150 μM) and uric acid (0.5-600 μM). And the detection limits were down to 0.1 μM (S/N = 3) for both analytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aca.2018.12.025DOI Listing
May 2019

Label-Free Aptamer-Based Biosensor for Specific Detection of Chloramphenicol Using AIE Probe and Graphene Oxide.

ACS Omega 2018 Oct 9;3(10):12886-12892. Epub 2018 Oct 9.

State Key Laboratory of Supramolecular Structure and Materials, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China.

A facile, sensitive, and label-free aptamer-based fluorescent biosensor (aptasensor) for chloramphenicol (CAP) detection was successfully developed based on an aggregation-induced emission (AIE) probe and graphene oxide (GO). In this aptasensor, the specific aptamer of CAP (C-Apt) is used as the recognition part, an AIE molecule, 9,10-distyrylanthracene (DSA) derivative with short alkyl chains (9,10-bis{4-[2-(,,-trimethylammonium)-ethoxy]styrene}anthracene dibromide, DSACN), as the fluorescent probe, and GO with a low oxidation degree as the fluorescent quencher. Initially, the AIE probe DSACN and C-Apt could be adsorbed on GO through π-stacking interactions, and the fluorescence of DSACN could be efficiently quenched due to the energy transfer between DSACN and GO. When CAP is added, C-Apt can preferentially bind with CAP and the newly formed complex (C-Apt-CAP) can be released from GO, resulting in the recovery of the fluorescence signal of DSACN. Thus, with the aid of GO, turn-on detection of CAP can be readily realized by monitoring the fluorescence signal of DSACN from "off" to "on". Under the optimized conditions, the aptasensor exhibits a high sensitivity toward CAP with a limit of detection of 1.26 pg/mL. Besides, we have successfully applied this aptasensor to the detection of CAP in spiked milk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.8b01812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217583PMC
October 2018

Comparison Study of Vocal Attack Time in Patients With Cleft Palate With and Without Glottal Stop in Mandarin.

J Voice 2019 Sep 23;33(5):803.e15-803.e21. Epub 2018 Aug 23.

Department of Chinese Language and Literature, Center for Chinese Linguistics, Peking University, Beijing, China. Electronic address:

Glottal stop (GS) is a typical compensatory articulation, which has a great impact on speech intelligibility in patients with cleft palate. It is usually detected by perceptual analysis. The aim of this study is to investigate the utility of vocal attack time (VAT) values in patients with cleft palate with and without GS, when unaspirated monosyllables are articulated in Mandarin, by using electroglottography. Unaspirated monosyllables /pa/ /pi/ /pu/ /ta/ /ti/ /tu/ /ka/ /ki/ /ku/ with tone one were analyzed. A total of 575 tokens were obtained from 42 patients with cleft palate, divided into a GS category (n = 312 tokens) and a nonglottal stop (NGS) category (n = 263 tokens), as assessed perceptually by three judges. Sound pressure and electroglottography recordings were also obtained from these tokens. The time lag of the cross-correlation function was used to gain VAT values. The results showed that the mean VAT values of tokens from the GS category (-0.25 ms) was significantly shorter than that of tokens in the NGS category (3.19 ms) (t = 7.326, P < 0.001). The results also showed that there was no significant difference in VAT values between the different combined monosyllables both in GS and in NGS group. The conclusion that can be drawn from this study is that the VAT value was sensitively decreased in cleft palate Mandarin speakers with GS comparing to those without GS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvoice.2018.04.020DOI Listing
September 2019
-->