Publications by authors named "Guanghua Liu"

72 Publications

Age-specific risk factors of severe pneumonia among pediatric patients hospitalized with community-acquired pneumonia.

Ital J Pediatr 2021 Apr 23;47(1):100. Epub 2021 Apr 23.

Department of Pediatrics, Fujian Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China.

Background: Risk factors that predispose the development of severe community-acquired pneumonia (CAP) among pediatric CAP patients of different age ranges are yet to be identified.

Methods: We retrospectively analyzed pediatric in-patients (< 6 years old) diagnosed with CAP in our hospital. We subdivided patients into four age groups (< 6 months, 6 months-1 year, 1-2 years, and 2-6 years). Their medical records, including demographic information, clinical features, laboratory findings, and chest radiographic reports, were reviewed and collected for further analysis. Univariate logistic regression analysis and stepwise regression analysis were applied to identify risk factors associated with severe CAP and ICU admission for overall patients and age-stratified subgroups.

Results: A total of 20,174 cases were initially included. Among them, 3309 (16.40%) cases were identified as severe CAP, and 2824 (14.00%) cases required ICU admission. Potential risk factors for severe CAP and ICU admission identified by univariate analysis included younger age, rural residency, premature birth, low birth weight (LBW), formula feeding, congenital heart disease (CHD), history of pneumonia or neonatal jaundice, patients with other health issues, certain symptoms (manifesting wheezing, dyspnea, cyanosis, but have no cough or fever), abnormal laboratory findings (abnormal levels of white blood cells, albumin, and C-reactive protein and RSV infection), and chest X-ray (odds ratio [OR] > 1 for all). CHD, low albumin, proteinuria, abnormal chest x-ray were independent risks factors across different age groups, whereas birth or feeding history, history of pneumonia, cyanosis or dyspnea on admission, and RSV infection were independent risk factors for only younger kids (< 1 year), and wheezing was an independent risk factor only for older children (2-5 years old).

Conclusions: Risk factors predicting disease severity among children hospitalized with CAP vary with age. Risk factor stratification of pediatric CAP based on age-specific risk factors can better guide clinical practice.

Trial Registration: This study has been registered in China, with the registration number being ChiCTR2000033019 .
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http://dx.doi.org/10.1186/s13052-021-01042-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062938PMC
April 2021

Gene diagnosis and pedigree analysis of two Han ethnicity families with propionic acidemia in Fujian.

Medicine (Baltimore) 2021 Mar;100(10):e24161

Neonatal Screening Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou.

Abstract: Propionic acidemia is associated with pathogenic variants in PCCA or PCCB gene. We investigated the potential pathogenic variants in PCCA or PCCB genes in Fujian Han population.Two probands and their families of Han ethnicity containing two generations were subject to newborn screening using tandem mass spectrometry, followed by diagnosis using urine gas chromatography mass spectrometry. Sanger sequencing was used to identify potential mutations in PCCA and PCCB genes.Compound heterozygous variants were identified in PCCB gene in two siblings of the first family, the youngest girl showed a novel missense variant c.1381G>C (p.Ala461Pro) in exon 13 and a heterozygous missense variant c.1301C>T (p.Ala434Val) in exon 13, which were inherited respectively from their parents. The oldest boy is a carrier with a novel missense variant c.1381G>C (p.Ala461Pro) in exon 13 which were inherited from his father. In the second family, c.1535G>A homozygous mutations were identified in the baby girl, which were inherited respectively from their parents. In silico analysis, several different types of bioinformatic software were utilized, which predicted that the novel variant c.1381G>C in PCCB gene was damaged. According to ACMG principle, the missense variant c.1381G>C (p.Ala461Pro) in exon 13 was a Variant of Undetermined Significance (VUS).One novel missense variant and two missense variants in PCCB gene were identified in the study. The novel variant of PCCB gene identified VUS was identified for the first time in the Chinese population, which enriched the mutational spectrum of PCCB gene.
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http://dx.doi.org/10.1097/MD.0000000000024161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969319PMC
March 2021

Retroperitoneoscopic partial nephrectomy using a 980/1470-nm dual-diode laser for small exophytic renal tumors.

Lasers Med Sci 2021 Mar 13. Epub 2021 Mar 13.

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Laser-supported laparoscopic partial nephrectomy is a promising new technique, but remains under experiment. We presented our single institutional experience of laparoscopic partial nephrectomy using the 980/1470-nm dual-diode laser system to investigate its feasibility, and oncological and functional outcomes. The study retrospectively evaluated 25 patients with small exophytic renal tumors, who underwent laparoscopic partial nephrectomy using a 980/1470-nm dual-diode laser. The demographics, surgical data, complications, pathological variables, oncological, and functional outcomes were reviewed. The changes in hemoglobin and estimated glomerular filtration rate (eGFR) before and after surgery were statistically analyzed. The investigators operated on a total of 25 patients. The off-clamping technique was performed for 23 cases, while the other two cases required renal artery clamping due to unsatisfactory hemostasis. The tumor diameter was 24.6± 6.2 mm, and the mean operative time was 104.4± 23.4 min. The median estimated intraoperative blood loss (EBL) was 100 ml (range 50-600 ml). No major complications (Clavien-Dindo >II) occurred perioperatively. The mean change in hemoglobin before and after the operation was 9 g/l, with a P value of <0.001. The mean decrease in eGFR from before the surgery to the 6-month follow-up was 1.4 ml/min, with a P value of 0.463. The postoperative histopathology evaluation did not demonstrate a positive surgical margin. No recurrence or metastasis was found during the follow-up (mean 24 months). Laparoscopic partial nephrectomy using a 980/1470 nm dual-diode laser appears to be a feasible and oncological satisfactory technique for the treatment of small renal mass (SRM), with the advantages of reducing warm ischemia time.
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http://dx.doi.org/10.1007/s10103-021-03284-3DOI Listing
March 2021

Knowledge Graphs of Kawasaki Disease.

Health Inf Sci Syst 2021 Dec 27;9(1):11. Epub 2021 Feb 27.

Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Kawasaki Disease is a vasculitis syndrome that is extremely harmful to children. Kawasaki Disease can cause severe symptoms of ischemic heart disease or develop into ischemic heart disease, leading to death in children. Researchers and clinicians need to analyze various knowledge and data resources to explore aspects of Kawasaki Disease. Knowledge Graphs have become an important AI approach to integrating various types of complex knowledge and data resources. In this paper, we present an approach for the construction of Knowledge Graphs of Kawasaki Disease. It integrates a wide range of knowledge resources related to Kawasaki Disease, including clinical guidelines, clinical trials, drug knowledge bases, medical literature, and others. It provides a basic integration foundation of knowledge and data concerning Kawasaki Disease for clinical study. In this paper, we will show that this disease-specific Knowledge Graphs are useful for exploring various aspects of Kawasaki Disease.
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http://dx.doi.org/10.1007/s13755-020-00130-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910781PMC
December 2021

Gene spectrum and clinical traits of 10 patients with primary carnitine deficiency.

Mol Genet Genomic Med 2021 02 9;9(2):e1583. Epub 2021 Feb 9.

Neonatal Screening Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Background: Rare studies focused on the tandem mass spectrometry (MS/MS) findings for the primary carnitine deficiency (PCD) in the neonates in China mainland. In this study, we aim to analyze the gene mutation spectrum of PCD in Fujian Province in China mainland.

Methods: Primary carnitine deficiency (PCD) samples used in this study were selected from 95,453 cases underwent neonatal screening between May 2015 and February 2020. SLC22A5 gene sequencing was performed on the neonates and their parents with C0 level of less than 8.8 μmol/L.

Results: Ten patients (male: 7; female: 3) were finally included in this study. Among these patients, nine were neonates, and one was maternal decline of C0 of less than 8.8 μmol/L. The maternal case showed two types of mutations of SLC22A5 including c.760C>T(p.R254*) and c.1400C>G(p.S467C). The other nine neonates showed compound mutations involving nine types in 18 sites, among which two mutations [i.e., c.37G>T(p.E13*) and c.694A>G(p.T232A)] were novel that had never been reported before. Bioinformatic analysis indicated that c.37G>T(p.E13*) was a pathogenic mutation, while the c.694A>G (p.T232A) was considered to be likely pathogenic.

Conclusion: MS/MS screening on PCD contributed to the early diagnosis and screening. In addition, SLC22A5 gene mutation analysis contributed to the PCD screening.
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http://dx.doi.org/10.1002/mgg3.1583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077093PMC
February 2021

A Risk Score Model Based on Nine Differentially Methylated mRNAs for Predicting Prognosis of Patients with Clear Cell Renal Cell Carcinoma.

Dis Markers 2021 14;2021:8863799. Epub 2021 Jan 14.

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Hutong, Dongcheng District, Beijing 100730, China.

Purpose: DNA methylation alterations play important roles in initiation and progression of clear cell renal cell carcinoma (ccRCC). In this study, we attempted to identify differentially methylated mRNA signatures with prognostic value for ccRCC.

Methods: The mRNA methylation and expression profiling data of 306 ccRCC tumors were downloaded from The Cancer Genome Atlas (TCGA) to screen differentially methylated lncRNAs and mRNAs (DMLs and DMMs) between bad and good prognosis patients. Uni- and multivariable Cox regression analyses and LASSO Cox-PH regression analysis were used to select prognostic lncRNAs and mRNAs. Corresponding risk scores were calculated and compared for predictive performance in the training set using Kaplan-Meier OS and ROC curve analyses. The optimal risk score was then identified and validated in the validation set. Function enrichment analysis was conducted.

Results: This study screened 461 DMMs and 63 DMLs between good prognosis and bad prognosis patients, and furthermore, nine mRNAs and six lncRNAs were identified as potential prognostic molecules. Compared to nine-mRNA status risk score model, six-lncRNA methylation risk score model, and six-lncRNA status risk score model, the nine-mRNA methylation risk score model showed superiority for prognosis stratification of ccRCC patients in the training set. The prognostic ability of the nine-mRNA methylation risk score model was validated in the validation set. The nine prognostic mRNAs were functionally associated with neuroactive ligand receptor interaction and inflammation-related pathways.

Conclusion: The nine-mRNA methylation signature (DMRTA2, DRGX, FAM167A, FGGY, FOXI2, KRTAP2-1, TCTEX1D1, TTBK1, and UBE2QL1) may be a useful prognostic biomarker and tool for ccRCC patients. The present results would be helpful to elucidate the possible pathogenesis of ccRCC.
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http://dx.doi.org/10.1155/2021/8863799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822694PMC
January 2021

Risk factors associated with wheezing in severe pediatric community-acquired pneumonia: a retrospective study.

Minerva Pediatr 2021 Jan 13. Epub 2021 Jan 13.

Department of Pediatrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China -

Background: Wheezing is a common clinical manifestation in children with pneumonia. However, the risk factors associated with the development of wheezing pneumonia and its clinical features are not fully characterized, especially in children with severe pneumonia.

Methods: We retrospectively recruited 1434 pediatric patients diagnosed with severe pneumonia between April 2012 and September 2019 in Fujian Maternity and Child Health Hospital. The medical records regarding demographic information, clinical manifestations, radiographic/laboratory findings, and complications were collected. Based on the presence or absence of wheezing symptoms and signs, subjects were divided into wheezing cohort (n=684) and non-wheezing cohort (n=750), and their clinical data were compared. Multivariate cox regression analysis was performed to identify independent risk factors of wheezing.

Results: Demographic features including gender, weigh, onset season, birth weight, full-term birth or not, history of pneumonia were significantly associated with the occurrence of wheezing in severe CAP (P<0.05). Specifically, male gender, onset seasons in autumn/winter, and absence of a history of pneumonia were identified as independent risk factors of wheezing in multivariate analysis (P<0.05). As for clinical features, wheezing cohort differed from the non-wheezing one in terms of clinical manifestation (higher incidence of cough and breathless, but lower incidence of fever), laboratory finding (higher levels of red blood cells, hemoglobin, and albumin and lower levels of total or indirect bilirubin and creatine), pathogen detection (higher incidence of respiratory syncytial viral infection), and clinical complications (lesser risk of sepsis and hydrothorax) (P<0.05).

Conclusions: Severe CAP with wheezing is a special clinical entity of severe pneumonia in children, which has specific risk factors and differ from non-wheezing pneumonia in terms of clinical features and etiologic pathogens.
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http://dx.doi.org/10.23736/S0026-4946.20.06065-XDOI Listing
January 2021

Production of lentiviral vectors in suspension cells using low proportion of supercoiled circular plasmid DNA.

Cytotechnology 2020 Oct 29. Epub 2020 Oct 29.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.

The supercoiled circular (SC) topology form of plasmid DNA has been regarded to be advantageous over open circular or linearized analogue in transfection and expression efficiency, and therefore are largely demanded in the biopharmaceutical manufacturing. However, production of high-purity SC plasmid DNA would result in high manufacturing cost. The effect of SC proportion in plasmid DNA on the quality of packaged lentiviral vectors has never been reported. In this study, we established an efficient system for production of high-titer lentiviral vectors using suspension HEK293SF cells in serum-free media, and the lentiviral titer was not associated with the proportion of SC plasmid DNA. Plasmids DNA with different proportion of SC, open-circular, and linearized forms were prepared using the thermal denaturation method, and were transfected to adherent HEK293T or suspension HEK293SF cells for packaging of lentiviral vectors. The titer of lentiviral vectors from HEK293T cells, but not from HEK293SF cells, was significantly impaired when the proportion of SC plasmid DNA decreased from 60-80% to 30-40%. Further decrease of SC plasmid proportion to 3% led to a dramatic reduction of lentiviral titer no matter the packaging cell line was. However, lentiviral vectors from HEK293SF cells still showed a high titer even when the proportion of SC plasmid DNA was 3%. This study demonstrated that extremely high proportion of SC plasmid DNA was not required for packaging of high-titer lentiviral vector in HEK293SF cells, at least under our manufacturing process.
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http://dx.doi.org/10.1007/s10616-020-00433-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695760PMC
October 2020

Phase-Selective Epitaxial Growth of Heterophase Nanostructures on Unconventional 2H-Pd Nanoparticles.

J Am Chem Soc 2020 11 21;142(44):18971-18980. Epub 2020 Oct 21.

Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.

Heterostructured, including heterophase, noble-metal nanomaterials have attracted much interest due to their promising applications in diverse fields. However, great challenges still remain in the rational synthesis of well-defined noble-metal heterophase nanostructures. Herein, we report the preparation of Pd nanoparticles with an unconventional hexagonal close-packed (2H type) phase, referred to as 2H-Pd nanoparticles, via a controlled phase transformation of amorphous Pd nanoparticles. Impressively, by using the 2H-Pd nanoparticles as seeds, Au nanomaterials with different crystal phases epitaxially grow on the specific exposed facets of the 2H-Pd, i.e., face-centered cubic () Au (-Au) on the (002) facets of 2H-Pd while 2H-Au on the other exposed facets, to achieve well-defined -2H- heterophase [email protected] core-shell nanorods. Moreover, through such unique facet-directed crystal-phase-selective epitaxial growth, a series of unconventional -2H- heterophase core-shell nanostructures, including [email protected], [email protected], [email protected], and [email protected], have also been prepared. Impressively, the -2H- heterophase [email protected] nanorods show excellent performance toward the electrochemical carbon dioxide reduction reaction (CORR) for production of carbon monoxide with Faradaic efficiencies of over 90% in an exceptionally wide applied potential window from -0.9 to -0.4 V (versus the reversible hydrogen electrode), which is among the best reported CORR catalysts in H-type electrochemical cells.
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http://dx.doi.org/10.1021/jacs.0c09461DOI Listing
November 2020

Novel compound variants of the gene cause cobblestone lissencephaly-like syndrome: A case report.

Exp Ther Med 2020 Nov 16;20(5):97. Epub 2020 Sep 16.

Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China.

Biallelic variants in the transmembrane O-mannosyltransferase targeting cadherins 3 () gene have been reported to cause two distinct types of neuron migration defect diseases, known as cobblestone lissencephaly (COB) and periventricular nodular heterotopia (PVNH), combined with intellectual disability and nocturnal seizures. The aim of the current study was to identify the genetic cause of a 22-month-old Chinese boy who presented with white matter plaques, a small frontal lobe, myelin dysplasia, microcephaly, psychomotor delay, language development delay, truncal hypotonia, intractable epilepsy, infantile spasm and bilateral single transverse palmar creases. Whole-exome sequencing revealed novel heterozygous variant compounds in the gene (c.1123G>A, p.Glu375Lys and c.1126_1129del, p.Arg376Tyrfs*13). Most of the clinical features of the patient are consistent with COB. However, the deformities in the brain (white matter plaques, small frontal lobe and myelin dysplasia) in the patient were more severe compared with those generally exhibited by PVNH, but less severe compared with those presented by COB. Moreover, the patient exhibited bilateral single transverse palmar creases, which, to the best of our knowledge, have not been described previously in patients with a variation. In summary, the current study reported a pediatric Chinese patient with COB-like syndrome caused by gene variations. The present results indicated that variation in the gene can lead to highly variable clinical phenotypes.
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http://dx.doi.org/10.3892/etm.2020.9226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507045PMC
November 2020

[Clinical and genetic analysis of two patients with congenital neutropenia caused by ELANE gene mutation].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Oct;37(10):1097-1101

Department of Pediatrics, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China.

Objective: To explore the clinical characteristics of congenital neutropenia caused by ELANE gene mutations.

Methods: Clinical manifestations, absolute blood neutrophil count, high-throughput exome sequencing for mutation screening, suspected locus Sanger sequencing verification, processes of diagnosis and treatment of two patients with congenital neutropenia caused by ELANE gene mutation were retrospectively analyzed.

Results: High-throughput sequencing has found that proband 1 has carried a heterozygous c.170C>T (p.Ala57Val) missense mutation in exon 2 of the ELANE gene, which was known to be pathological, and a heterozygous c.251T>G (p.Leu84Arg) mutation in exon 3 of proband 2, which was unreported previously. Sanger sequencing confirmed that neither mutation was inherited from their parents.

Conclusion: ELANE mutation is an important cause for congenital neutropenia. Detection of new pathogenic variants has enriched the mutation spectrum of the ELANE gene.
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http://dx.doi.org/10.3760/cma.j.cn511374-20190922-00487DOI Listing
October 2020

The prevalence of mental distress and association with social changes among postgraduate students in China: a cross-temporal meta-analysis.

Public Health 2020 Sep 24;186:178-184. Epub 2020 Aug 24.

Evidence-Based Social Sciences Research Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China; Evidence-Based Medicine Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China. Electronic address:

Objective: This study aims to estimate the mental distress prevalence of Chinese postgraduate students and the association with the social changes based on the data between 2000 and 2019.

Study Design: This is a cross-temporal meta-analysis study.

Methods: The literature was retrieved with both English and Chinese electronic databases, including articles published from 2002 to 2019. Statistical analyses were performed with R 3.6.1 and SPSS 22.

Results: Eighty-nine primary studies with 99 reports were included in our meta-analysis, totaling 54,722 Chinese postgraduate students. The result showed that: (a) the prevalence of mental distress was 28% (95% confidence interval [CI]: 25%-31%), and the prevalence of moderately positive symptoms was 9% (95% CI: 7%-11%); (b) the prevalence of positive symptoms was negatively correlated with the years of data collection and the prevalence of mental distress decreased by at least 16% from 2000 to 2019; and (c) social changes, particularly the policies of mental health and the educational environment had a significant contribution to these changes.

Conclusions: More than a quarter of postgraduate students have mental illness in China, whereas the prevalence of their mental distress has been decreasing. Social changes are shown to play an important role in contributing to this change.
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http://dx.doi.org/10.1016/j.puhe.2020.06.014DOI Listing
September 2020

A machine learning approach to predict intravenous immunoglobulin resistance in Kawasaki disease patients: A study based on a Southeast China population.

PLoS One 2020 27;15(8):e0237321. Epub 2020 Aug 27.

StarCore Co. Ltd., Fuzhou, Fujian, China.

Kawasaki disease is the leading cause of pediatric acquired heart disease. Coronary artery abnormalities are the main complication of Kawasaki disease. Kawasaki disease patients with intravenous immunoglobulin resistance are at a greater risk of developing coronary artery abnormalities. Several scoring models have been established to predict resistance to intravenous immunoglobulin, but clinicians usually do not apply those models in patients because of their poor performance. To find a better model, we retrospectively collected data including 753 observations and 82 variables. A total of 644 observations were included in the analysis, and 124 of the patients observed were intravenous immunoglobulin resistant (19.25%). We considered 7 different linear and nonlinear machine learning algorithms, including logistic regression (L1 and L1 regularized), decision tree, random forest, AdaBoost, gradient boosting machine (GBM), and lightGBM, to predict the class of intravenous immunoglobulin resistance (binary classification). Data from patients who were discharged before Sep 2018 were included in the training set (n = 497), while all the data collected after 9/1/2018 were included in the test set (n = 147). We used the area under the ROC curve, accuracy, sensitivity, and specificity to evaluate the performances of each model. The gradient GBM had the best performance (area under the ROC curve 0.7423, accuracy 0.8844, sensitivity 0.3043, specificity 0.9919). Additionally, the feature importance was evaluated with SHapley Additive exPlanation (SHAP) values, and the clinical utility was assessed with decision curve analysis. We also compared our model with the Kobayashi score, Egami score, Formosa score and Kawamura score. Our machine learning model outperformed all of the aforementioned four scoring models. Our study demonstrates a novel and robust machine learning method to predict intravenous immunoglobulin resistance in Kawasaki disease patients. We believe this approach could be implemented in an electronic health record system as a form of clinical decision support in the near future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237321PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451628PMC
October 2020

Type 2 diabetes mellitus worsens the prognosis of intermediate-stage hepatocellular carcinoma after transarterial chemoembolization.

Diabetes Res Clin Pract 2020 Nov 19;169:108375. Epub 2020 Aug 19.

Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:

Aims: The aim of this study was to investigate the impact of type 2 diabetes mellitus (T2DM) on the prognosis of hepatocellular carcinoma (HCC) patients following transarterial chemoembolization (TACE).

Methods: Time to progression (TTP) and cancer-specific mortality (CSM) in competing risk model were compared in patients with (n = 289) or without (n = 763) T2DM. Propensity score matching (PSM) was used to reduce bias between the two groups. Multivariate competing risk regression was used to evaluate independent risk factors for TTP and CSM.

Results: The T2DM group showed significantly worse 5-year TTP and CSM rates than the non-T2DM group both in the whole cohort (n = 1052) and the PSM cohort (n = 514) (81.3% vs. 70.9%, P < 0.001, and 61.5% vs. 49.3%, P = 0.006; 81.4% vs. 68.6%, P = 0.003, and 61.7% vs. 43.2%, P = 0.014, respectively). Multivariate competing risk regression identified T2DM as an independent risk factor for TTP and CSM before and after PSM (hazard ratio: 1.37 [95% confidence interval: 1.07-1.77] and 1.36 [1.05-1.75]; 1.29 [1.04-1.60] and 1.24 [1.02-1.52], respectively). T2DM worsened the long-term outcomes of patients in the cirrhosis subgroup but not those in the noncirrhosis subgroup.

Conclusions: T2DM worsened the long-term survival of intermediate-stage HCC patients who underwent TACE, especially in patients with cirrhosis.
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http://dx.doi.org/10.1016/j.diabres.2020.108375DOI Listing
November 2020

The clinical outcomes of fresh versus cryopreserved CD19-directed chimeric antigen receptor T cells in non-Hodgkin lymphoma patients.

Cryobiology 2020 10 25;96:106-113. Epub 2020 Jul 25.

Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Haidian District, Beijing, 100142, China. Electronic address:

CD19-directed chimeric antigen receptor T (CAR-T) cells have been widely reported in the therapy of relapsed/refractory non-Hodgkin lymphoma (NHL). Both cryopreserved and fresh formulations of CAR-T have been used in previous studies. However, quite a few studies investigated the effects of cryopreservation on the clinical outcomes of CAR-T cells. Here we retrospectively analyzed a phase I/II clinical trial of CD19-directed CAR-T cells in NHL patients, and compared the safety and efficacy of cryopreserved and fresh CAR-T products. All CAR-T cells were prepared using the same manufacturing process except the formulation step. Fifteen patients were infused with cryopreserved/thawed CAR-T cells, and 8 patients were treated with fresh CAR-T cells. Comparative overall response rates and in vivo expansion kinetics of CAR-T cells were observed between the cryopreserved cohort and fresh cohort. The occurrence rates of cytokine release syndrome and neurotoxicity were also similar in both groups. Patients in the fresh cohort showed higher incidence of acute hematological toxicity including anemia, hypoleukemia, and thrombocytopenia. This study demonstrated that cryopreservation showed negligible effects on the efficacy of CD19-directed CAR-T cells, but endowed CAR-T cells with higher safety in NHL patients, supporting the application of cryopreserved CAR-T products for NHL therapy.
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http://dx.doi.org/10.1016/j.cryobiol.2020.07.009DOI Listing
October 2020

Perinatal risk factors for congenital hypothyroidism: A retrospective cohort study performed at a tertiary hospital in China.

Medicine (Baltimore) 2020 Jun;99(26):e20838

Department of Pediatrics, Fujian Provincial Maternity and Child Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China.

Congenital hypothyroidism (CH) is one of the most common neonatal endocrine diseases. This retrospective cohort study aimed to identify the potential perinatal risk factors for CH and to differentiate between transient and permanent CH (TCH and PCH, respectively) as well as determine their prevalence in a southeastern Chinese population.This study was based on an 18-year surveillance of a neonatal CH screening program in a large tertiary hospital. A retrospective review of the maternal and neonatal perinatal exposures was conducted.Of the 205,834 newborns screened between 2000 and 2018, 189 were diagnosed with CH (1/1089). Among the 131 CH patients who again underwent thyroid function testing (TFT) after discontinuation of levothyroxine at the age of 3 years, 61 (46.6%) were diagnosed with PCH and 70 (53.4%) were diagnosed with TCH. In the maternal characteristics model, women aged 35 years or older and those who had thyroid disease and/or diabetes mellitus during pregnancy had increased risk of having an offspring with CH (P = .001, .000, and .001, respectively). Significant associations were found with regard to parity and the risk of CH in the offspring (P = .000). In the neonatal characteristics model, infants with female sex, preterm birth, post-term birth, low birth weight, other birth defects, and those born as part of multiple births (P = .011, .034, .001, .000, .000, and .003, respectively) had increased risk of CH. The rate of newborns with other birth defects was higher in the PCH group than that in the TCH group (P = .008), whereas the rate of maternal thyroid disease, newborns with low birth weight, and newborns with preterm birth was higher in the TCH group than that in the PCH group (P = .041, .020, and .013, respectively). The levothyroxine dose (μg/kg/day) at 1 year, 2 years, and 3 years old was significantly lower in the TCH group than that in the PCH group (P = .000, .000, and .000, respectively).Perinatal factors should be considered during the diagnosis and treatment of CH.
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http://dx.doi.org/10.1097/MD.0000000000020838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328952PMC
June 2020

Sodium butyrate protects against oxidative stress in human nucleus pulposus cells via elevating PPARγ-regulated Klotho expression.

Int Immunopharmacol 2020 Aug 15;85:106657. Epub 2020 Jun 15.

Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address:

We investigated the involvement of klotho in the inhibition of oxidative stress by sodium butyrate (NaB) in human nucleus pulposus cells (NPCs). NPCs were pretreated with different concentrations of NaB for 2 h before stimulation with tert-butyl hydroperoxide (TBHP). NaB alleviated TBHP-induced oxidative injury in the NPCs, as evident by the reduced accumulation of mitochondrial superoxide, intracellular reactive oxygen species, and malondialdehyde, and increased activities of superoxide dismutase and glutathione peroxidase. Flow cytometry and western blotting showed that TBHP-induced apoptosis of NPCs was inhibited by NaB. NaB also reduced the TBHP-induced release of proteases that degrade the extracellular matrix, including matrix metalloproteinases 3 and 13, and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs 4). Intriguingly, NaB significantly reversed TBHP-induced klotho suppression. However, the protective effects of NaB on NPCs were abolished by klotho-specific small interfering RNA (siRNA). TBHP stimulation had no obvious effects on total or nuclear expression of peroxisome proliferator-activated receptor γ (PPARγ), but significantly reduced PPARγ acetylation and transcriptional activity, which were restored by NaB. TBHP stimulation also promoted the nuclear translocation of histone deacetylase 3 (HDAC3) and enhanced the association between HDAC3 and PPARγ in the nucleus, but this interaction was substantially disrupted by NaB. siRNA-induced HDAC3 knockdown significantly increased PPARγ acetylation and transactivation, reversing the TBHP-induced suppression of klotho. Therefore, NaB alleviates TBHP-induced oxidative stress in human NPCs by elevating PPARγ-regulated klotho expression. HDAC3 may be a critical HDAC subtype that mediates the regulation of PPARγ activity by NaB under oxidative stress.
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http://dx.doi.org/10.1016/j.intimp.2020.106657DOI Listing
August 2020

Hsa_circ_0085576 promotes clear cell renal cell carcinoma tumorigenesis and metastasis through the miR-498/YAP1 axis.

Aging (Albany NY) 2020 06 15;12(12):11530-11549. Epub 2020 Jun 15.

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, P.R. China.

There is emerging evidence that circular RNAs (circRNAs) act as important regulators in various cancers. It is less clear, however, what role circRNA plays in the tumorigenesis and metastasis of clear cell renal cell carcinoma (ccRCC). In this study, using bioinformatics analysis and a series of experimental analysis, we characterized a novel circRNA, hsa_circ_0085576 was up-regulated in ccRCC tissues and cell lines. High hsa_circ_0085576 expression was significantly correlated with tumor size, clinical stage, and metastasis status and poorer survival. Knockdown of hsa_circ_0085576 notably inhibited cell proliferation, migration, invasion, whereas enhanced cell apoptosis of ccRCC cells, . In contrast, overexpression of hsa_circ_0085576 had the opposite effects. Moreover, hsa_circ_0085576 silencing significantly suppressed tumor growth and metastasis, whereas overexpression of hsa_circ_0085576 had the opposite effects, , Our results further showed that hsa_circ_0085576 acted as a competitive endogenous RNAs to interact with microRNA-498, to attenuate its repressive effect on target gene Yes-associated protein 1 (YAP1). Finally, functional studies revealed that inhibition of hsa_circ_0085576 suppressed cell growth and metastasis by regulating miR-498/YAP1 signaling, in ccRCC cells. Based on these findings, hsa_circ_0085576 may represent a valuable prognostic biomarker and a potential therapeutic target to curb the tumorigenesis and metastasis of ccRCC.
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http://dx.doi.org/10.18632/aging.103300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343478PMC
June 2020

GreenLight Laser photoselective vapo-enucleation of the prostate with front-firing emission versus plasmakinetic resection of the prostate for benign prostate hyperplasia.

Transl Androl Urol 2020 Apr;9(2):544-552

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.

Background: Although the conventional, monopolar transurethral resection of the prostate (TURP) has proven to be an effective and relatively safe treatment for patients with benign prostatic hyperplasia (BPH), many new endoscopic technologies have been introduced to treat BPH. With the development of laser, there are several alternative transurethral procedures embracing laser therapies. Herein, this study sought to explore the efficacy, safety and follow-up of GreenLight laser photoselective vapo-enucleation of the prostate (PVEP) with front-firing emission compared with plasmakinetic resection of the prostate (PKRP) used to surgically manage BPH.

Methods: Data from patients who underwent either GreenLight laser PVEP or PKRP were retrospectively collected from March 2013 to May 2018. Perioperative data from both groups were compared.

Results: Totally, 43 and 45 patients were included in the PVEP and PKRP groups, respectively. No significant difference was observed in excision efficiency ratio (resected prostate weight/operation time) between the two groups (P=0.372). The efficiency ratio of the first 20 PVEP procedures (0.36±0.09 g/min) was significantly lower than that of the second 23 PVEP procedures (0.45±0.18 g/min) (P=0.042). The PVEP group experienced a shorter duration of catheterization, postoperative hospital stay and irrigation time than the PKRP group (P<0.001, P=0.001 and P<0.001, respectively). There was no statistically significant difference between the two groups (P=0.937) in terms of overall postoperative complications. Three months after surgery, the international prostate symptoms (IPSS) score, quality of life (QOL) score, postvoid residual (PVR) volume and maximum urinary flow rate (Q) were decreased in both groups (P<0.001 for all) and were comparable between both groups (P=0.635, 0.662, 0.671 and 0.924, respectively).

Conclusions: GreenLight laser PVEP with front-firing emission was safe and effective modality in treating patients with BPH with short-term follow-up. PVEP was associated with shorter catheterization and postoperative hospital stay time compared with PKRP.
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http://dx.doi.org/10.21037/tau.2020.02.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215003PMC
April 2020

[Genetic analysis of a male infant with Menkes disease].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Apr;37(4):479-482

Department of Children's Healthcare, Fujian Provincial Maternity and Children's Hospital, the Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China.

Objective: To carry out genetic testing for a male infant suspected for Menkes disease.

Methods: Genomic DNA of the proband and his parents were extracted and subjected to family trio whole exome sequencing (WES). Microduplication and microdeletion of the ATP7A gene were detected by multiplex ligation-dependent probe amplification (MLPA). Suspected variants were subjected to bioinformatic analysis and verified by Sanger sequencing.

Results: The proband was found to harbor a de novo c.1870 -13T>G variation of the ATP7A gene, which may alter a splice site and affect its protein product.

Conclusion: The patient was diagnosed with Menkes disease due to the c.1870 -13T>G variant of the ATP7A gene. Whole exome sequencing of family trios is a powerful tool for the diagnosis of diseases with strong phenotypic heterogeneity.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.04.029DOI Listing
April 2020

Effectiveness of dignity therapy for patients with advanced cancer: A systematic review and meta-analysis of 10 randomized controlled trials.

Depress Anxiety 2020 03 6;37(3):234-246. Epub 2019 Dec 6.

Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China.

Background: Dignity is a vitally important aspect of the lives of advanced cancer patients. We conducted a systematic review and meta-analysis of the effectiveness of dignity therapy in this patient population.

Methods: We searched for randomized controlled trials comparing dignity therapy versus standard care for patients with advanced cancer in five comprehensive databases (March 2019), two clinical trial registries and one gray literature database (August 2019). The quality of the studies was assessed using the risk of bias tool recommended by the Cochrane Handbook Version 5.1.0. We used GRADE approach to assess the certainty of evidence. Meta-analysis was performed with RevMan version 5.3. Outcomes of interest included anxiety, depression, dignity-related distress and quality of life (QoL).

Results: Ten trials evaluating 904 patients (control, 449; experimental, 455) were identified. Six trials included patients with different types of advanced cancer, and four trials included patients with a single advanced cancer (lung cancer [20%], breast cancer [10%], and hepatocellular carcinoma [10%]). Compared with the standard care, dignity therapy decreased the score of anxiety, depression, and dignity-related distress of the advanced cancer patients (SMD = -1.07, 95% CI: [-1.57, -0.58], p < .05; SMD = -1.31, 95% CI: [-1.92, -0.70], p < .05; MD = -7.30, 95% CI: [- 12.04, - 2.56], p < .05). In addition, no significant differences were found in the patient's QoL (p > .05).

Conclusion: Very low certainty evidence demonstrated that dignity therapy might be a promising treatment, especially in reducing anxiety and depression in advanced cancer patients.
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http://dx.doi.org/10.1002/da.22980DOI Listing
March 2020

Long-term Effects of Repeat Hepatectomy vs Percutaneous Radiofrequency Ablation Among Patients With Recurrent Hepatocellular Carcinoma: A Randomized Clinical Trial.

JAMA Oncol 2020 02;6(2):255-263

Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital and the National Center for Liver Cancer, The Second Military Medical University, Shanghai, China.

Importance: Repeat hepatectomy and percutaneous radiofrequency ablation (PRFA) are most commonly used to treat early-stage recurrent hepatocellular carcinoma (RHCC) after initial resection, but previous studies comparing the effectiveness of the 2 treatments have reported conflicting results.

Objective: To compare the long-term survival outcomes after repeat hepatectomy with those after PRFA among patients with early-stage RHCC.

Design, Setting, And Participants: This open-label randomized clinical trial was conducted at the Eastern Hepatobiliary Surgery Hospital and the National Center for Liver Cancer of China. A total of 240 patients with RHCC (with a solitary nodule diameter of ≤5 cm; 3 or fewer nodules, each ≤3 cm in diameter; and no macroscopic vascular invasion or distant metastasis) were randomized 1:1 to receive repeat hepatectomy or PRFA between June 3, 2010, and January 15, 2013. The median (range) follow-up time was 44.3 (4.3-90.6) months (last follow-up, January 15, 2018). Data analysis was conducted from June 15, 2018, to September 28, 2018.

Interventions: Repeat hepatectomy (n = 120) or PRFA (n = 120).

Main Outcomes And Measures: The primary outcome was overall survival (OS). Secondary outcomes included repeat recurrence-free survival (rRFS), patterns of repeat recurrence, and therapeutic safety.

Results: Among the 240 randomized patients (216 men [90.0%]; median [range] age, 53.0 [24.0-59.0] years), 217 completed the trial. In the intention-to-treat (ITT) population, the 1-year, 3-year, and 5-year OS rates were 92.5% (95% CI, 87.9%-97.3%), 65.8% (95% CI, 57.8%-74.8%), and 43.6% (95% CI, 35.5%-53.5%), respectively, for the repeat hepatectomy group and 87.5% (95% CI, 81.8%-93.6%), 52.5% (95% CI, 44.2%-62.2%), and 38.5% (95% CI, 30.6%-48.4%), respectively, for the PRFA group (P = .17). The corresponding 1-year, 3-year, and 5-year rRFS rates were 85.0% (95% CI, 78.8%-91.6%), 52.4% (95% CI, 44.2%-62.2%), and 36.2% (95% CI, 28.5%-46.0%), respectively, for the repeat hepatectomy group and 74.2% (95% CI, 66.7%-82.4%), 41.7% (95% CI, 33.7%-51.5%), and 30.2% (95% CI, 22.9%-39.8%), respectively, for the PRFA group (P = .09). Percutaneous radiofrequency ablation was associated with a higher incidence of local repeat recurrence (37.8% vs 21.7%, P = .04) and early repeat recurrence than repeat hepatectomy (40.3% vs 23.3%, P = .04). In subgroup analyses, PRFA was associated with worse OS vs repeat hepatectomy among patients with an RHCC nodule diameter greater than 3 cm (hazard ratio, 1.72; 95% CI, 1.05-2.84) or an α fetoprotein level greater than 200 ng/mL (hazard ratio, 1.85; 95% CI, 1.15-2.96). Surgery had a higher complication rate than did ablation (22.4% vs 7.3%, P = .001).

Conclusions And Relevance: No statistically significant difference was observed in survival outcomes after repeat hepatectomy vs PRFA for patients with early-stage RHCC. Repeat hepatectomy may be associated with better local disease control and long-term survival in patients with an RHCC diameter greater than 3 cm or an AFP level greater than 200 ng/mL.

Trial Registration: ClinicalTrials.gov identifier: NCT00822562.
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http://dx.doi.org/10.1001/jamaoncol.2019.4477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902111PMC
February 2020

Research on correlations of MiR-203 expression with onset and prognosis of bladder cancer.

J BUON 2019 May-Jun;24(3):1210-1218

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.

Purpose: To investigate the correlations of the expression of micro ribonucleic acid (miR)-203 with the onset and prognosis of bladder cancer.

Methods: Human bladder cancer T24 cell line with miR-203 overexpression were constructed. Effects of miR-203 expression on cell proliferation and apoptosis were detected via methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Fifty-eight patients with bladder cancer treated in our hospital were selected, and para-carcinoma tissues were used as controls. The expression of miR-203 in bladder cancer tissues was detected via quantitative polymerase chain reaction (qPCR), and the survival time of patients with bladder cancer was recorded in detail. Moreover, correlations of miR-203 expression with onset and prognosis of patients were evaluated via multivariate Cox regression analysis.

Results: Results of qPCR revealed that after T24 cells were transfected with miR-203, the miR-203 expression level in the overexpression group was significantly higher than that in the control group (p<0.01), the cell proliferation capacity was significantly lower than that in the control group (p<0.01), and the apoptotic level was also significantly higher than that in the control group (p<0.01). The miR-203 expression level in carcinoma tissues of patients with bladder cancer was obviously lower than that in the para-carcinoma tissues (p<0.01). The miR-203 expression had close correlations with the tumor size, differentiation grade and tumor stage (p<0.01), and the 5-year survival rate of patients in low miR-203 expression group was remarkably lower than that in the high miR-203 expression group (p<0.01). Besides, the results of multivariate Cox regression analysis revealed that the tumor grade of differentiation, tumor-node-metastasis (TNM) stage and miR-203 expression were closely related to the prognosis of patients (p<0.01).

Conclusion: The high expression of miR-203 can significantly reduce the proliferation and promote the apoptosis of bladder cancer cells. The increased expression level of miR-203 can effectively increase the survival rate and improve the prognosis of patients.
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March 2020

Synthesis and bioactivity of indoleacetic acid-carbendazim and its effects on Cylindrocladium parasiticum.

Pestic Biochem Physiol 2019 Jul 11;158:128-134. Epub 2019 May 11.

College of Agriculture, Yangtze University, Jingzhou 434025, PR China. Electronic address:

Indoleacetic acid (IAA)-carbendazim was synthesized to assess whether this conjugate could retain the fungicidal activity of carbendazim and gain root-inducing properties upon the addition of an indoleacetic acid group. An indoor virulence test demonstrated that the conjugate retained the fungicidal activity of carbendazim towards Cylindrocladium parasiticum. The conjugate was detected in roots after soaking Ricinus communis L. leaves into a solution of the IAA-carbendazim, which confirmed its phloem mobility. The activities of the cellulase, polygalacturonase and xylanase produced by Cylindrocladium parasiticum treated with different concentrations of the conjugate were determined, and the peak activities appeared at 72 h or 96 h. More importantly, the conjugate showed the ability to promote root growth. These results revealed that indoleacetic acid-carbendazim may be useful in preventing Cylindrocladium parasiticum and other diseases.
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http://dx.doi.org/10.1016/j.pestbp.2019.05.001DOI Listing
July 2019

Systematic profiling of clinical missence mutation effects on the intermolecular interaction between human growth hormone and its receptor in isolated growth hormone deficiency.

J Mol Graph Model 2019 11 28;92:1-7. Epub 2019 Jun 28.

Department of Pediatrics, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China. Electronic address:

Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and can result from congenital or acquired causes. Among the known factors, genetic mutations in human growth hormone (hGH) remain the most frequent cause of IGHD, which influence the binding of hGH to its cognate receptor (hGHbp). Although previous studies have systematically investigated the residue importance at hGH-hGHbp complex interface, the molecular role of IGHD-associated residue mutations in the complex function still remains largely unexplored. Here, a total of 21 known hGH naturally-occurring missence mutations that have been clinically observed to be involved in IGHD disorder are collected and confirmed by original literature; they effects on the conformation, energetics and dynamics of hGH-hGHbp recognition and interaction are dissected at molecular level by using atomistic dynamics simulations, binding energy calculations and fluorescence spectroscopy assays. A systematic profile of hGH-hGHbp binding response to these clinical missence mutations is created, based on which it is revealed that (i) most mutations have appreciably unfavorable effect on the binding, which potentially destabilize the complex interaction, while only very few are predicted as moderate stabilizers for the complex system, and (ii) these disease-related mutations can locate either at complex interface or in hGH protein interior far away from the interface; both can influence the complex binding through either direct interaction or indirect allostericity. Two mutations, E100K (non-interface) and G146R (interface), are identified to address potent destabilization effect on hGH-hGHbp complex system; they can reduce the complex binding affinity by 8-fold (K changes from 0.76 to 5.9 nM) and 46-fold (K changes from 0.76 to 34.7 nM), respectively.
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http://dx.doi.org/10.1016/j.jmgm.2019.06.018DOI Listing
November 2019

Enzyme and pH dual-responsive avermectin nano-microcapsules for improving its efficacy.

Environ Sci Pollut Res Int 2019 Aug 28;26(24):25107-25116. Epub 2019 Jun 28.

School of Chemistry and Chemical Engineering, Zhongkai University of Agriculture and Engineering, Guangzhou, People's Republic of China.

The overdosage use of pesticide was harmful to the environment and human health, which was mainly caused by the low utilization rate of the pesticide. However, the pesticide microcapsule with sustained-release and stimulating response properties could effectively solve this problem. Preparation of carboxymethyl cellulose grafting dimethyldiallylammonium chloride (CMC-g-PDMDAAC) through grafting polymerization and trapping as well as encapsulation of avermectin (AVM) via electrostatic interactions resulted in the formation of AVM/CMC-g-PDMDAAC microcapsules. The results showed that the particle size was 200~300 nm. The encapsulation efficiency was as high as 72.06%. Furthermore, the remaining rate of encapsulated AVM increased from 50.0 to 81.60% after UV irradiation for 359 min. The microcapsules exhibited significant enzyme and pH stimuli responsiveness. Finally, CMC-g-PDMDAAC had no significant difference effect on the toxicity of AVM, AVM could be found, and DMDAAC featured a synergistic effect on the toxicological effects of AVM. Graphical abstract.
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http://dx.doi.org/10.1007/s11356-019-05804-9DOI Listing
August 2019

A Randomized Controlled Trial on the Effects of Low-Dose Extracorporeal Shockwave Therapy in Patients With Knee Osteoarthritis.

Arch Phys Med Rehabil 2019 09 10;100(9):1695-1702. Epub 2019 Jun 10.

Deparment of Radiology, Huashan Hospital, Fudan University, Shanghai, China.

Objective: To test the efficacy of low-dose extracorporeal shockwave therapy (ESWT) on osteoarthritis knee pain, lower limb function, and cartilage alteration for patients with knee osteoarthritis.

Design: Randomized controlled trial with placebo control.

Setting: Outpatient physical therapy clinics within a hospital network.

Participants: Eligible volunteers (N=63) with knee osteoarthritis (Kellgren-Lawrence grade II or III) were randomly assigned to 2 groups.

Interventions: Patients in the experimental group received low-dose ESWT for 4 weeks while those in the placebo group got sham shockwave therapy. Both groups maintained a usual level of home exercise.

Main Outcome Measures: Knee pain and physical function were measured using a visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lequesne index at baseline, 5 weeks, and 12 weeks. Cartilage alteration was measured analyzing the transverse relaxation time (T2) mapping.

Results: The VAS score, WOMAC, and Lequesne index of the ESWT group were significantly better than those of the placebo group at 5 and 12 weeks (P<.05). Both groups showed improvement in pain and disability scores over the 12-week follow-up period (P<.05). In terms of imaging results, there was no significant difference in T2 values between groups during the trial, although T2 values of the ESWT group at 12 weeks significantly increased compared to those at baseline (P=.004). The number and prevalence of adverse effects were similar between the 2 groups, and no serious side effects were found.

Conclusions: A 4-week treatment of low-dose ESWT was superior to placebo for pain easement and functional improvement in patients with mild to moderate knee osteoarthritis but had some negative effects on articular cartilage.
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http://dx.doi.org/10.1016/j.apmr.2019.04.020DOI Listing
September 2019

lncRNA ZEB1-AS1 promotes migration and metastasis of bladder cancer cells by post-transcriptional activation of ZEB1.

Int J Mol Med 2019 Jul 8;44(1):196-206. Epub 2019 May 8.

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

The prognosis for patients with metastatic bladder cancer (BCa) is poor, and has not been improved by current treatment methods. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including bladder cancer. However, the role of zinc finger E‑box‑binding homeobox 1‑antisense 1 (ZEB1‑AS1) in BCa progression and metastasis remains unclear. The present study determined the expression level of ZEB1‑AS1 in BCa and additionally investigated the functional role of ZEB1‑AS1 in BCa metastasis. Reverse transcription quantitative polymerase chain reaction analysis showed that ZEB1‑AS1 was upregulated in BCa cells compared with normal epithelial cells. Functionally, knockdown of ZEB1‑AS1 suppressed BCa cell migration and invasion in vitro, and metastasis in vivo. Mechanistic investigations revealed that ZEB1‑AS1 bound to heterogenous nuclear ribonucleoprotein D0 (AUF1), thereby activating the translation of ZEB1 mRNA without affecting its mRNA level. In addition, ZEB1‑AS1 was significantly upregulated in BCa tissues and muscle‑invasive BCa cases. ROC curve analysis demonstrated that ZEB1‑AS1 expression was associated with metastasis in patients with BCa. In conclusion, the data from the present study demonstrated that ZEB1‑AS1 induced BCa metastasis via an AUF1‑mediated translation activation of ZEB1 mRNA mechanism. ZEB1‑AS1 may serve as a promising target for clinical intervention in advanced BCa.
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http://dx.doi.org/10.3892/ijmm.2019.4187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559313PMC
July 2019