Publications by authors named "Meng Mao"

168 Publications

Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis.

Autism 2021 Apr 12:13623613211004054. Epub 2021 Apr 12.

Children's Hospital of Fudan University, China.

Lay Abstract: The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services.
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http://dx.doi.org/10.1177/13623613211004054DOI Listing
April 2021

Hydrochemical characterization and quality assessment of groundwater in the hilly area of the Taihang Mountains in Henan Province, China.

Environ Sci Pollut Res Int 2021 Apr 10. Epub 2021 Apr 10.

Henan Institute of Geological Environment Monitoring, Zhengzhou, 450016, China.

This study evaluated the quality of groundwater and its suitability for drinking and irrigation in the hilly area of the Taihang Mountains in Henan Province, China. Groundwater samples were collected from 43 unconfined and 20 confined wells and analyzed. The pollution index of groundwater (PIG) was estimated based on the physicochemical parameters, and seven indices, including the sodium adsorption ratio (SAR), sodium percentage (%Na), residual sodium carbonate (RSC), permeability index (PI), magnesium ratio (MR), Kelley's ratio (KR), and corrosivity ratio (CR), were calculated to qualify the groundwater within the research area for irrigation activities. Multivariate statistical techniques were performed to better understand the hydrochemical processes. Chemical analysis showed that the dominant cation and anion were Ca and HCO, respectively, and the principal hydrochemical facies was Ca-Mg-HCO. In terms of pH, total dissolved solids, Na, Cl, F, and SO, most samples were well within the limits prescribed by Chinese standards for drinking water quality, but more than half of the unconfined samples exceeded the specified limits for total hardness and nitrate. The PIG values suggested the pollution level was insignificant for all confined water samples and 72.09% of unconfined water samples, but the PIG distribution map showed that the water in the south central part of the study area had low to moderate pollution. According to the computed values of SAR, %Na, RSC, PI, KR, and MR and the results of a salinity diagram, the results further indicated that most of the studied samples were appropriate for irrigation usage. Only the CR values rendered 41.86% of the unconfined samples and 20% of the confined samples unfit for irrigation. Hence, proper measures are needed to resolve the corrosivity problem. Factor analysis resulted in the extraction of 3 factors that explained 81% of the data variability, and the extracted factors pointed towards geogenic factors governing the groundwater quality.
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http://dx.doi.org/10.1007/s11356-021-13579-1DOI Listing
April 2021

Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKKα stability via selective autophagy.

Sci Adv 2021 Jan 20;7(4). Epub 2021 Jan 20.

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.

Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated ANXA1 could promote the beneficial phenotype polarization of microglia. Mechanistically, SUMOylated ANXA1 suppressed nuclear factor κB activation and the production of proinflammatory mediators. Further study revealed that SUMOylated ANXA1 targeted the IκB kinase (IKK) complex and selectively enhanced IKKα degradation. Simultaneously, we detected that SUMOylated ANXA1 facilitated the interaction between IKKα and NBR1 to promote IKKα degradation through selective autophagy. Further work revealed that the overexpression of SUMOylated ANXA1 in microglia/macrophages resulted in marked improvement in neurological function in a mouse model of cerebral ischemia. Collectively, our study demonstrates a previously unidentified mechanism whereby SUMOylated ANXA1 regulates microglial polarization and strongly indicates that up-regulation of ANXA1 SUMOylation in microglia may provide therapeutic benefits for cerebral ischemia.
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http://dx.doi.org/10.1126/sciadv.abc5539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817101PMC
January 2021

Prevalence of vitamin D deficiency and insufficiency among 460,537 children in 825 hospitals from 18 provinces in mainland China.

Medicine (Baltimore) 2020 Oct;99(44):e22463

Department of Children's Genetic Endocrinology and Metabolism, West China Second hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China.

This study was conducted to estimate the 25-hydroxyvitamin D (25 (OH)D) levels and explore factors related to vitamin D deficiency/insufficiency. This was a multicenter, hospital-based, cross-sectional observational study. Children admitted to hospitals for health examination were included for vitamin D measurement and the 25(OH)D concentration results were categorized into 3 groups: deficiency (<30 nmol/L), insufficiency (30-50 nmol/L), and sufficiency (>50 nmol/L). Four lakh sixty thousand five hundred thirty-seven children in 825 hospitals from 18 provinces participated in this study. The prevalence of vitamin D deficiency, insufficiency, and sufficiency were 6.69%, 15.92%, and 77.39%, respectively. Vitamin D deficiency was the most severe in the central region, followed by the north, and southwest regions; however, data for the western region were lacking.Logistic regression showed that vitamin D status was worse in girls, newborns, and those visiting the hospital in the winter. In conclusion, the prevalence of vitamin D deficiency is high among Chinese children and adolescents. Studies on population estimates, cost-effective screening strategies, and interventions for high-risk cases are needed.
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http://dx.doi.org/10.1097/MD.0000000000022463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598790PMC
October 2020

Impact of human umbilical cord-derived stem cells (HUMSCs) on host responses to a synthetic polypropylene mesh for pelvic floor reconstruction in a rat model.

Cell Tissue Res 2020 Dec 2;382(3):519-527. Epub 2020 Sep 2.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Road, Dongcheng District, Beijing, People's Republic of China.

In order to evaluate the effects of human umbilical cord-derived stem cells (HUMSCs) on the biocompatibility of and tissue response to a polypropylene (PP) mesh (Gynemesh™ PS) implanted in rat vaginas, HUMSCs were isolated and characterized in vitro and then combined with Gynemesh™ PS to create a tissue-engineered mesh. This tissue-engineered mesh and pure PP mesh were implanted in the submucosae of the posterior vaginal walls of rats. Mesh/tissue complexes were harvested at 1, 4 and 12 weeks after implantation. Histological evaluations including an assessment of the inflammatory reaction, neovascularization and fibrosis around the mesh fibers were performed and real-time quantitative polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression of genes involved in wound healing at the tissue-mesh interface. After being seeded onto the PP mesh scaffold, HUMSCs grew and proliferated well in vitro culture. One week after implantation, the HUMSC-seeded mesh elicited a greater inflammatory response than the pure PP mesh (3.33 ± 0.21 vs. 2.63 ± 0.18, p = 0.026), while 4 and 12 weeks after implantation, the inflammatory response in the HUMSC-seeded mesh was lower than that in the unseeded mesh (p < 0.05). At 12 weeks, the HUMSC-seeded mesh induced a lower expression of matrix metalloproteinase (MMP)-1 and a higher expression of anti-inflammatory cytokine interleukin (IL)-4. HUMSCs may decrease the inflammatory response and improve the biocompatibility of a conventional synthetic mesh and may have the potential to reduce postoperative complications such as mesh exposure or erosion.
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http://dx.doi.org/10.1007/s00441-020-03234-5DOI Listing
December 2020

MicroRNA-195 prevents hippocampal microglial/macrophage polarization towards the M1 phenotype induced by chronic brain hypoperfusion through regulating CX3CL1/CX3CR1 signaling.

J Neuroinflammation 2020 Aug 20;17(1):244. Epub 2020 Aug 20.

Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, 150086, Heilongjiang Province, China.

Background: Microglial polarization is a dynamic response to acute brain hypoxia induced by stroke and traumatic brain injury (TBI). However, studies on the polarization of microglia in chronic cerebral circulation insufficiency (CCCI) are limited. Our objective was to investigate the effect of CCCI on microglial polarization after chronic brain hypoperfusion (CBH) and explore the underlying molecular mechanisms.

Methods: CBH model was established by bilateral common carotid artery occlusion (2-vessel occlusion, 2VO) in rats. Using the stereotaxic injection technique, lenti-pre-miR-195 and anti-miR-195 oligonucleotide fragments (lenti-pre-AMO-miR-195) were injeted into the CA1 region of the hippocampus to construct animal models with high or low expression of miR-195. Immunofluorescence staining and flow cytometry were conducted to examine the status of microglial polarization. In vitro, Transwell co-culture system was taken to investigate the role of miR-195 on neuronal-microglial communication through CX3CL1-CX3CR1 signaling. Quantitative real-time PCR was used to detect the level of miR-195 and inflammatory factors. The protein levels of CX3CL1 and CX3CR1 were evaluated by both western blot and immunofluorescence staining.

Results: CBH induced by 2VO initiated microglial/macrophage activation in the rat hippocampus from 1 week to 8 weeks, as evaluated by increased ratio of (CD68 and CD206)/Iba-1 immunofluorescence. And the microglial/macrophage polarization was shifted towards the M1 phenotype at 8 weeks following CBH. The expression of CX3CL1 and CX3CR1 was increased in the hippocampus of 2VO rats at 8 weeks. An in vitro study in a Transwell co-culture system demonstrated that transfection of either primary-cultured neonatal rat neurons (NRNs) or microglial BV2 cells with AMO-195-induced M1 polarization of BV2 cells and increased CX3CL1 and CX3CR1 expression and that these effects were reversed by miR-195 mimics. Furthermore, the upregulation of miR-195 induced by lenti-pre-miR-195 injection prevented microglial/macrophage polarization to M1 phenotype triggered by hippocampal injection of lenti-pre-AMO-miR-195 and 2VO surgery.

Conclusions: Our findings conclude that downregulation of miR-195 in the hippocampus is involved in CBH-induced microglial/macrophage polarization towards M1 phenotype by governing communication between neurons and microglia through the regulation of CX3CL1 and CX3CR1 signaling. This indicates that miR-195 may provide a new strategy for clinical prevention and treatment of CBH.
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http://dx.doi.org/10.1186/s12974-020-01919-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439693PMC
August 2020

Growth Curves for Children with X-linked Hypophosphatemia.

J Clin Endocrinol Metab 2020 10;105(10)

Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia.

Context: We characterized linear growth in infants and children with X-linked hypophosphatemia (XLH).

Objective: Provide linear growth curves for children with XLH from birth to early adolescence.

Design: Data from 4 prior studies of XLH were pooled to construct growth curves. UX023-CL002 was an observational, retrospective chart review. Pretreatment data were collected from 3 interventional trials: two phase 2 trials (UX023-CL201, UX023-CL205) and a phase 3 trial (UX023-CL301).

Setting: Medical centers with expertise in treating XLH.

Patients: Children with XLH, 1-14 years of age.

Intervention: None.

Main Outcome Measure: Height-for-age linear growth curves, including values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles for children with XLH compared to population norms.

Results: A total of 228 patients (132 girls, 96 boys) with 2381 height measurements were included. Nearly all subjects (> 99%) reported prior management with supplementation therapy. Compared to the Center for Disease Control and Prevention growth curves, boys at age 3 months, 6 months, 9 months, 1 year, and 2 years had median height percentiles of 46%, 37%, 26%, 18%, and 5%, respectively; for girls the median height percentiles were 52%, 37%, 25%, 18%, and 7%, respectively. Annual growth in children with XLH fell below that of healthy children near 1 year of age and progressively declined during early childhood, with all median height percentiles < 8% between 2 and 12 years old.

Conclusion: Children with XLH show decreased height gain by 1 year of age and remain below population norms thereafter. These data will help evaluate therapeutic interventions on linear growth for pediatric XLH.
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http://dx.doi.org/10.1210/clinem/dgaa495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448934PMC
October 2020

Impact of intrauterine hypoxia on adolescent and adult cognitive function in rat offspring: sexual differences and the effects of spermidine intervention.

Acta Pharmacol Sin 2021 Mar 21;42(3):361-369. Epub 2020 Jul 21.

Department of Pharmacology, College of Pharmacy of Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin, 150086, China.

Intrauterine hypoxia (IUH) affects the growth and development of offspring. It remains unclear that how long the impact of IUH on cognitive function lasts and whether sexual differences exist. Spermidine (SPD) has shown to improve cognition, but its effect on the cognitive function of IUH offspring remains unknown. In the present study we investigated the influence of IUH on body weight and neurological, motor and cognitive function and the expression of APP, BACE1 and Tau5 proteins in brain tissues in 2- and 4-month-old IUH rat offspring, as well as the effects of SPD intervention on these parameters. IUH rat model was established by treating pregnant rats with intermittent hypoxia on gestational days 15-21, meanwhile pregnant rats were administered SPD (5 mg·kg·d;ip) for 7 days. Neurological deficits were assessed in the Longa scoring test; motor and cognitive functions were evaluated in coat hanger test and active avoidance test, respectively. We found that IUH decreased the body weight of rats in both sexes but merely impaired motor and cognitive function in female rats without changing neurological function in the rat offspring of either sex at 2 months of age. For 4-month-old offspring, IUH decreased body weight in males and impaired neurological function and increased cognitive function in both sexes. IUH did not affect APP, BACE1 or Tau5 protein expression in either the hippocampus or cortex of all offspring; however, it increased the cortical Tau5 level in 2-month-old female offspring. Surprisingly, SPD intervention prevented weight loss. SPD intervention reversed the motor and cognitive decline caused by IUH in 2-month-old female rat offspring. Taken together, IUH-induced cognitive decline in rat offspring is sex-dependent during puberty and can be recovered in adult rats. SPD intervention improves IUH-induced cognitive and neural function decline.
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http://dx.doi.org/10.1038/s41401-020-0437-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027377PMC
March 2021

Prevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years.

Neurosci Bull 2020 Sep 30;36(9):961-971. Epub 2020 Jun 30.

Department of Neurology, Children's Hospital of Fudan University, Shanghai, 201102, China.

This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P < 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity. Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.
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http://dx.doi.org/10.1007/s12264-020-00530-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475160PMC
September 2020

Correction to: Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts.

Mol Cell Biochem 2020 Sep;472(1-2):253-254

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.

In the original article, Fig. 4b was published incorrectly in which four to five lanes in Pi-ERK and Pi-CREB panels look very similar to each other (Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts, Mol Cell Biochem, 2008, 313:11-18). Since this image was stored in The Experiment Center of the West China Second University Hospital, Sichuan University, which was dissoluted in 2012, the original data cannot be traced. Experiments were therefore redone to verify the result and the correct version of Fig. 4b is provided in this correction.
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http://dx.doi.org/10.1007/s11010-020-03785-9DOI Listing
September 2020

Coupled effect of flow velocity and structural heterogeneity on transport and release of kaolinite colloids in saturated porous media.

Environ Sci Pollut Res Int 2020 Oct 25;27(28):35065-35077. Epub 2020 Jun 25.

College of Land Science and Technology, Key Laboratory of Arable Land Conservation (North China), Ministry of Agriculture, China Agricultural University, Beijing, 100193, China.

Understanding the behavior and fate of clay colloids in water-saturated porous media is critical to assess its environmental impact and potential risk since clay is commonly a carrier of many contaminants. Column experiments with four-packing configurations were designed to understand the coupled effects of column structural heterogeneity and the flow velocity on the transport and fate of kaolinite colloids in the saturated porous media. The results showed that the structural heterogeneity could have facilitated the transport of kaolinite colloids in saturated porous media. For the columns with strong heterogeneity, the preferential flow paths led to an early breakthrough of kaolinite. Only few kaolinite colloids were released with slow flow rate; however, the released peak concentration and release percentage of kaolinite colloids had further increased with the high flow velocity. In the layered column, there was significant kaolinite's retention at the interface where water passed from fine to coarse quartz sand. All results indicated that both flow rates and media characteristics played an important role in controlling kaolinite's fate and transport in porous media. A thorough understanding of these processes had an important significance for pollution control in subsurface natural environment where heterogeneous soil and variation in flow pattern are usually common.
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http://dx.doi.org/10.1007/s11356-020-09806-wDOI Listing
October 2020

MicroRNA-153 impairs presynaptic plasticity by blocking vesicle release following chronic brain hypoperfusion.

Cell Commun Signal 2020 04 6;18(1):57. Epub 2020 Apr 6.

Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, 150086, Heilongjiang Province, China.

Background: Chronic brain hypoperfusion (CBH) is closely related to Alzheimer's disease (AD) and vascular dementia (VaD). Meanwhile, synaptic pathology plays a prominent role in the initial stage of AD and VaD. However, whether and how CBH impairs presynaptic plasticity is currently unclear.

Methods: In the present study, we performed a battery of techniques, including primary neuronal culture, patch clamp, stereotaxic injection of the lentiviral vectors, morris water maze (MWM), dual luciferase reporter assay, FM1-43 fluorescence dye evaluation, qRT-PCR and western blot, to investigate the regulatory effect of miR-153 on hippocampal synaptic vesicle release both in vivo and in vitro. The CBH rat model was generated by bilateral common carotid artery ligation (2VO).

Results: Compared to sham rats, 2VO rats presented decreased field excitatory postsynaptic potential (fEPSP) amplitude and increased paired-pulse ratios (PPRs) in the CA3-CA1 pathway, as well as significantly decreased expression of multiple vesicle fusion-related proteins, including SNAP-25, VAMP-2, syntaxin-1A and synaptotagmin-1, in the hippocampi. The levels of microRNA-153 (miR-153) were upregulated in the hippocampi of rats following 2VO surgery, and in the plasma of dementia patients. The expression of the vesicle fusion-related proteins affected by 2VO was inhibited by miR-153, elevated by miR-153 inhibition, and unchanged by binding-site mutation or miR masks. FM1-43 fluorescence images showed that miR-153 blunted vesicle exocytosis, but this effect was prevented by either 2'-O-methyl antisense oligoribonucleotides to miR-153 (AMO-153) and miR-masking of the miR-153 binding site in the 3' untranslated region (3'UTR) of the Snap25, Vamp2, Stx1a and Syt1 genes. Overexpression of miR-153 by lentiviral vector-mediated miR-153 mimics (lenti-pre-miR-153) decreased the fEPSP amplitude and elevated the PPR in the rat hippocampus, whereas overexpression of the antisense molecule (lenti-AMO-153) reversed these changes triggered by 2VO. Furthermore, lenti-AMO-153 attenuated the cognitive decline of 2VO rats.

Conclusions: Overexpression of miR-153 controls CBH-induced presynaptic vesicle release impairment by posttranscriptionally regulating the expression of four vesicle release-related proteins by targeting the 3'UTRs of the Stx1a, Snap25, Vamp2 and Syt1 genes. These findings identify a novel mechanism of presynaptic plasticity impairment during CBH, which may be a new drug target for prevention or treatment of AD and VaD. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00551-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137307PMC
April 2020

Symbiont replacements reset the co-evolutionary relationship between insects and their heritable bacteria.

ISME J 2020 06 19;14(6):1384-1395. Epub 2020 Feb 19.

Department of Life and Environmental Sciences, University of California, Merced, 5200N Lake Rd, Merced, CA, 95343, USA.

Auchenorrhynchan insects (Hemiptera) generally depend on two bacterial symbionts for nutrition. These bacteria experience extreme genome reduction and loss of essential cell functions that require direct host support, or the replacement of failing symbionts with more capable ones. However, it remains unclear how hosts adapt to integrate symbionts into their systems, particularly when they are replaced. Here, we comparatively investigated the evolution of host-support mechanisms in the glassy-winged sharpshooter, Homalodisca vitripennis (GWSS), and the aster leafhopper, Macrosteles quadrilineatus (ALF). ALF harbors the ancestral co-symbionts of the Auchenorrhyncha that have tiny genomes, Sulcia (190 kb) and Nasuia (112 kb). In GWSS, Sulcia retains an expanded genome (245 kb), but Nasuia was replaced by the more capable Baumannia (686 kb). To support their symbionts, GWSS and ALF have evolved novel mechanisms via horizontal gene transfer, gene duplication, and co-option of mitochondrial support genes. However, GWSS has fewer support systems targeting essential bacterial processes. In particular, although both hosts use ancestral mechanisms to support Sulcia, GWSS does not encode all of the same support genes required to sustain Sulcia-ALF or Nasuia. Moreover, GWSS support of Baumannia is far more limited and tailored to its expanded capabilities. Our results demonstrate how symbiont replacements shape host genomes and the co-evolutionary process.
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http://dx.doi.org/10.1038/s41396-020-0616-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242365PMC
June 2020

[Research and application progresses on rice water quality (RICEWQ)model.]

Authors:
Wen-Yan He Meng Mao

Ying Yong Sheng Tai Xue Bao 2019 Nov;30(11):3963-3970

Department of Soil and Water Sciences, College of Resources and Environmental Sciences, China Agricultural University/Ministry of Education Key Laboratory of Plant-Soil Interactions/Ministry of Agriculture Key Laboratory of Arable Land Conservation in North China, Beijing 100193, China.

Rice production presents a unique environmental condition, with the diseases, insects and weeds being serious during production process. Many kinds of pesticides are used with high frequency. Some pesticides will leach into surrounding water, which shows a high risk for pollution. With the increasing costs of pesticide monitoring and field experiments, mathematical models have become an indispensable part during the process of pesticide registration. As the most reliable and widely used model for pesticide exposure assessment in European paddy fields, rice water quality (RICEWQ) model was mainly used to predict pesticide concentrations in flooded paddy fields and water, and had been preliminarily applied in China. In this review, system structure, the main processes of pesticide fate involved, input and output of RICEWQ model were briefly introduced, and the research progress at home and abroad were summarized. This review would promote the application of RICEWQ model in China and provide reference for related research.
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http://dx.doi.org/10.13287/j.1001-9332.201911.016DOI Listing
November 2019

The in vivo biocompatibility of titanized polypropylene lightweight mesh is superior to that of conventional polypropylene mesh.

Neurourol Urodyn 2020 01 4;39(1):96-107. Epub 2019 Oct 4.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Objective: To evaluate the histological response to and changes in the biomechanical properties of titanized polypropylene lightweight mesh and conventional polypropylene mesh at 1 and 12 weeks following implantation in the sheep vagina.

Methods: We compared a titanized polypropylene lightweight mesh (TiLOOP Mesh) to a conventional polypropylene mesh (Gynemesh PS) in a sheep vagina model. Explants were harvested after 1 and 12 weeks (n = 6/mesh type/time point) for histological observation. After 12 weeks, mesh-tissue complex specimens were biomechanically assessed by a uniaxial tension system.

Results: One week after implantation, there was no significant difference in the inflammatory response between the two groups. Twelve weeks after implantation, the TiLOOP light mesh elicited a lower inflammatory response than was observed for the Gynemesh PS (1.44 ± 0.61 vs 2.05 ± 0.80, P = .015). Twelve weeks after implantation, the collagen I/III ratio was lower in the TiLOOP light mesh group than in the Gynemesh PS group (9.41 ± 5.06 vs 15.21 ± 8.21, P = .019). The messenger RNA expression levels of the inflammatory factors interleukin 10 and tumor necrosis factor α were lower in the TiLOOP Mesh group than in the Gynemesh PS group at both 1 and 12 weeks (P < .05). There were no significant differences in any of the evaluated biomechanical characteristics between the two meshes (P > .05).

Conclusion: Although the titanized polypropylene lightweight mesh induces slightly less tissue reactivity and has better in vivo biocompatibility, further studies should be conducted including the complications and the success rate of pelvic organ prolapse in patients before recommending it in pelvic floor reconstruction.
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http://dx.doi.org/10.1002/nau.24159DOI Listing
January 2020

New species of the subgenus Osten Sacken from China (Diptera, Limoniidae).

Zookeys 2019 18;876:39-54. Epub 2019 Sep 18.

Department of Entomology, College of Plant Protection, China Agricultural University, Beijing 100193, China China Agricultural University Beijing China.

Previously 12 species of the subgenus Epiphragma (Epiphragma) Osten Sacken, 1860 were known to occur in China. The following three species are described and illustrated as new to science: E. (E.) acuminatum, E. (E.) henanensis, and E. (E.) longitubum. Epiphragma (E.) insigne van der Wulp, 1878 is reported from China for the first time and is illustrated based on additional morphological characters. An updated key to the species of the subgenus E. (Epiphragma) from China is presented.
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http://dx.doi.org/10.3897/zookeys.876.33163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761208PMC
September 2019

Tissue Composition and Biomechanical Property Changes in the Vaginal Wall of Ovariectomized Young Rats.

Biomed Res Int 2019 31;2019:8921284. Epub 2019 Jul 31.

Departments of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Ideal animal models are needed to reflect the changes in the biochemical and biomechanical properties of the vagina that occur in pelvic organ prolapse (POP). In this study, we aimed to demonstrate the short and long-term effect of menopause on the biochemical and biomechanical properties of rat anterior vaginas. Here, Sprague-Dawley rats were bilaterally ovariectomized to induce menopause. Rats without ovariectomy served as the normal control group (n=12). The histology changes and the expression of collagen I, III, and a-SMA were assessed to indicate the biochemical changes in the vagina 2 weeks, 4 weeks, and 16 weeks after ovariectomy (n=6 for 2 and 4 weeks, n=12 for 16 weeks). Uniaxial biomechanical testing was conducted in the control group and ovariectomized rats 16 weeks after ovariectomy. Compared with the control group, the ovariectomy group showed a significant increase in the expression of collagen I 2 weeks after ovariectomy, while collagen III showed a declining trend. Two weeks after ovariectomy, the smooth muscle bundles began to become disorganized, and the fraction of smooth muscle in the nonvascular muscularis of the proximal vagina was significantly decreased (P<0.001). However, there was no difference in the expression of a-SMA in the distal vagina. Compared with the control group, the ovariectomy group had stiffer vaginas with a declining trend in the ultimate load 16 weeks after ovariectomy. In conclusion, surgically induced menopause had a significant short- and long-term impact on tissue composition and biomechanical properties of the rat vagina, which may lead to increased susceptibility to POP development.
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http://dx.doi.org/10.1155/2019/8921284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699277PMC
January 2020

Correction to: The data and characteristics of the human milk banks in mainland China.

World J Pediatr 2019 Dec;15(6):624-625

West China Second Hospital of Sichuan University, Chengdu, China.

In the original publication of the article, "Hainan province" in Fig 1 was missed out. The corrected Fig. 1 is given below.
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http://dx.doi.org/10.1007/s12519-019-00307-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943390PMC
December 2019

Comparison of outcomes between single-incision sling and transobturator sling for treating stress urinary incontinence: A 10-year prospective study.

Neurourol Urodyn 2019 09 24;38(7):1852-1858. Epub 2019 Jun 24.

Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.

Aims: To evaluate and compare the clinical outcomes of the transobturator sling with the single-incision sling, for the treatment of stress urinary incontinence at a long-term follow-up.

Methods: From October 2008 to October 2010, 94 patients who were enrolled and underwent either TVT-O, one of standard mid-urethral sling or TVT-S, one of single-incision mini-sling (SIMS) procedure. The study population was followed until February 2019. Surgical outcomes were analyzed by subjective and objective evaluations and Chinese version questionnaires. Data were analyzed by IBM 23.0 SPSS Statistics. The level of statistical significance was set at P < 0.05.

Results: At the 10-year follow-up, 31(64.6%) TVT-O patients and 33(71.7%) TVT-S patients were still available. Objective cure and subjective satisfaction rate were not significantly different for TVT-O compared with TVT-S (P >  0.05). However, TVT-S showed a greater drop in success from the second to the tenth year compared with TVT-O (15.1% vs 0% and 9.2% vs 3.2%, respectively). Both groups experienced significantly improved quality of life in the TVT-O group and in the TVT-S group (P < 0.05). The total PISQ-12 scores at 10 years postoperatively of the TVT-O and TVT-S groups were 33.4(4.7) compared with 33.6(3.9) before surgery (P = 0.67 > 0.05) and 35.5(5.9) compared with 31.5(6.3) before surgery (P = 0.045 < 0.05).

Conclusions: It is difficult to state that there is superiority of one sling over another sling without a significant difference. But TVT-O showed superior objective cure and subjective satisfaction rates and a less decline in success during 10 years compared with TVT-S.
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http://dx.doi.org/10.1002/nau.24078DOI Listing
September 2019

Cicada Endosymbionts Have tRNAs That Are Correctly Processed Despite Having Genomes That Do Not Encode All of the tRNA Processing Machinery.

mBio 2019 06 18;10(3). Epub 2019 Jun 18.

Division of Biological Sciences, University of Montana, Missoula, Montana, USA

Gene loss and genome reduction are defining characteristics of endosymbiotic bacteria. The most highly reduced endosymbiont genomes have lost numerous essential genes related to core cellular processes such as replication, transcription, and translation. Computational gene predictions performed for the genomes of the two bacterial symbionts of the cicada , " Hodgkinia cicadicola" () and " Sulcia muelleri" (), have found only 26 and 16 tRNA genes and 15 and 10 aminoacyl tRNA synthetase genes, respectively. Furthermore, the original " Hodgkinia cicadicola" genome annotation was missing several essential genes involved in tRNA processing, such as those encoding RNase P and CCA tRNA nucleotidyltransferase as well as several RNA editing enzymes required for tRNA maturation. How these cicada endosymbionts perform basic translation-related processes remains unknown. Here, by sequencing eukaryotic mRNAs and total small RNAs, we show that the limited tRNA set predicted by computational annotation of " Sulcia muelleri" and " Hodgkinia cicadicola" is likely correct. Furthermore, we show that despite the absence of genes encoding tRNA processing activities in the symbiont genomes, symbiont tRNAs have correctly processed 5' and 3' ends and seem to undergo nucleotide modification. Surprisingly, we found that most " Hodgkinia cicadicola" and " Sulcia muelleri" tRNAs exist as tRNA halves. We hypothesize that " Sulcia muelleri" and " Hodgkinia cicadicola" tRNAs function in bacterial translation but require host-encoded enzymes to do so. The smallest bacterial genomes, in the range of about 0.1 to 0.5 million base pairs, are commonly found in the nutritional endosymbionts of insects. These tiny genomes are missing genes that encode proteins and RNAs required for the translation of mRNAs, one of the most highly conserved and important cellular processes. In this study, we found that the bacterial endosymbionts of cicadas have genomes which encode incomplete tRNA sets and lack genes required for tRNA processing. Nevertheless, we found that endosymbiont tRNAs are correctly processed at their 5' and 3' ends and, surprisingly, that mostly exist as tRNA halves. We hypothesize that the cicada host must supply its symbionts with these missing tRNA processing activities.
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http://dx.doi.org/10.1128/mBio.01950-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581868PMC
June 2019

Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial.

Lancet 2019 06 16;393(10189):2416-2427. Epub 2019 May 16.

Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.

Background: X-linked hypophosphataemia in children is characterised by elevated serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphataemia, rickets, lower extremity bowing, and growth impairment. We compared the efficacy and safety of continuing conventional therapy, consisting of oral phosphate and active vitamin D, versus switching to burosumab, a fully human monoclonal antibody against FGF23, in paediatric X-linked hypophosphataemia.

Methods: In this randomised, active-controlled, open-label, phase 3 trial at 16 clinical sites, we enrolled children with X-linked hypophosphataemia aged 1-12 years. Key eligibility criteria were a total Thacher rickets severity score of at least 2·0, fasting serum phosphorus lower than 0·97 mmol/L (3·0 mg/dL), confirmed PHEX (phosphate-regulating endopeptidase homolog, X-linked) mutation or variant of unknown significance in the patient or a family member with appropriate X-linked dominant inheritance, and receipt of conventional therapy for at least 6 consecutive months for children younger than 3 years or at least 12 consecutive months for children older than 3 years. Eligible patients were randomly assigned (1:1) to receive either subcutaneous burosumab starting at 0·8 mg/kg every 2 weeks (burosumab group) or conventional therapy prescribed by investigators (conventional therapy group). Both interventions lasted 64 weeks. The primary endpoint was change in rickets severity at week 40, assessed by the Radiographic Global Impression of Change global score. All patients who received at least one dose of treatment were included in the primary and safety analyses. The trial is registered with ClinicalTrials.gov, number NCT02915705.

Findings: Recruitment took place between Aug 3, 2016, and May 8, 2017. Of 122 patients assessed, 61 were enrolled. Of these, 32 (18 girls, 14 boys) were randomly assigned to continue receiving conventional therapy and 29 (16 girls, 13 boys) to receive burosumab. For the primary endpoint at week 40, patients in the burosumab group had significantly greater improvement in Radiographic Global Impression of Change global score than did patients in the conventional therapy group (least squares mean +1·9 [SE 0·1] with burosumab vs +0·8 [0·1] with conventional therapy; difference 1·1, 95% CI 0·8-1·5; p<0·0001). Treatment-emergent adverse events considered possibly, probably, or definitely related to treatment by the investigator occurred more frequently with burosumab (17 [59%] of 29 patients in the burosumab group vs seven [22%] of 32 patients in the conventional therapy group). Three serious adverse events occurred in each group, all considered unrelated to treatment and resolved.

Interpretation: Significantly greater clinical improvements were shown in rickets severity, growth, and biochemistries among children with X-linked hypophosphataemia treated with burosumab compared with those continuing conventional therapy.

Funding: Ultragenyx Pharmaceutical and Kyowa Kirin International.
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http://dx.doi.org/10.1016/S0140-6736(19)30654-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179969PMC
June 2019

Experimental study of a new original mesh developed for pelvic floor reconstructive surgery.

Int Urogynecol J 2020 01 17;31(1):79-89. Epub 2019 Apr 17.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuai Fu Road, Dongcheng District, Beijing, People's Republic of China.

Introduction And Hypothesis: Most synthetic meshes used in transvaginal surgery are made of polypropylene, which has a stable performance, but does not easily degrade in vivo. However, mesh-related complications are difficult to address and have raised serious concerns. A new biomaterial mesh with good tissue integration and few mesh-related complications is needed. To evaluate the effect of a new bacterial cellulose (BC) mesh on pelvic floor reconstruction following implantation in the vagina of sheep after 1 and 12 weeks.

Methods: The meshes were implanted in the submucosa of the posterior vagina wall of sheep. At 1 and 12 weeks after surgery, mesh-tissue complex (MTC) specimens were harvested for histological studies and biomechanical evaluation. At 12 weeks after surgery, MTC specimens were biomechanically assessed by a uniaxial tension "pulley system".

Results: The BC mesh elicited a higher inflammatory response than Gynemesh™PS at both 1 and 12 weeks after implantation. Twelve weeks after implantation, the BC mesh resulted in less fibrosis than Gynemesh™PS. Compared with the Gynemesh™PS group, the BC mesh group had increased mRNA expression of MMP-1, MMP-2, and MMP-9 (P < 0.05), but decreased expression of the anti-inflammatory factor IL-4 (P < 0.05). Twelve weeks after implantation, the ultimate load and maximum elongation percentage of the BC mesh were significantly lower than those of Gynemesh™PS.

Conclusions: The BC mesh could not be a promising biomaterial for pelvic floor reconstructive surgery unless the production process and parameters were improved.
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http://dx.doi.org/10.1007/s00192-019-03947-4DOI Listing
January 2020

Elevated homocysteine level and prognosis in patients with acute coronary syndrome: a meta-analysis.

Biomarkers 2019 Jun 6;24(4):309-316. Epub 2019 May 6.

c Department of Cardiovascular Medicine , Beijing University of Chinese Medicine Third Affiliated Hospital , Beijing , China.

Controversial results exist with respect to the association between elevated homocysteine level and adverse prognosis in acute coronary syndrome (ACS) patients. We performed a meta-analysis to evaluate the prognostic value of homocysteine level on ACS patients. A comprehensive literature search of PubMed and Embase databases was conducted prior to August 2018. Prospective observational studies reporting the association of baseline homocysteine level with major adverse cardiovascular events (MACE), cardiovascular or all-cause mortality in ACS patients were selected. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CI) were calculated for the highest versus the lowest homocysteine level. Ten studies including 4120 ACS patients were identified. ACS patients with the highest homocysteine level had an increased risk of MACE (RR 2.01; 95% CI 1.53-2.64) and all-cause mortality (RR 2.05; 95% CI 1.50-2.79) after controlling confounding factors. However, the association between elevated homocysteine level and cardiovascular mortality (RR 1.08; 95% CI 0.83-1.39) was not statistically significant. Elevated homocysteine level was associated with an increased risk of MACE and all-cause mortality among ACS patients. However, the association of elevated homocysteine level with cardiovascular mortality in ACS patients should be further confirmed in future studies.
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http://dx.doi.org/10.1080/1354750X.2019.1589577DOI Listing
June 2019

The data and characteristics of the human milk banks in mainland China.

World J Pediatr 2019 Apr 22;15(2):190-197. Epub 2019 Feb 22.

West China Second Hospital of Sichuan University, Chengdu, China.

Background: Human milk banks (HMB) have been established for over 100 years in North America and Europe. This study aimed to describe and summarize the operation and characteristics of the HMBs in mainland China since the first nonprofit HMB operated in 2013.

Methods: Operation of HMB in mainland China is based on the standards and guidelines of the Human Milk Banking Association of North America and some countries in Europe and was modified to meet the needs and circumstances in China such as donation only in the local HMB by medical staff. We reviewed the descriptive data of these 14 HMBs and the clinical characteristics of recipients, the eligible milk donors and the donor milk retrospectively.

Results: In mainland China, from March 2013 to December 2016, 14 nonprofit HMBs were developed and operational in public hospitals except one and located in the south, east, north and northwest of mainland China. In total, 2680 eligible donors donated 4608.2 L of breast milk. The mean age of these donors was 29.4 years with 60.6% receiving college education and 90.6% term delivery. A total of 4678 recipients including preterm infants (n = 2990, 63.9%), feeding intolerance (n = 711, 15.2%), maternal illness (n = 345, 7.4%), serious infection (n = 314, 6.7%), necrotising enterocolitis (n = 244, 5.2%), post-surgery (n = 38, 0.8%) and others (n = 36, 0.8%). The rate of discarded raw milk was only 4.4% because of hepatitis B and C or cytomegalovirus positivity.

Conclusions: HMB has been developing rapidly in mainland China. Donor human milk was used not only for preterm infants but also for other ill children. But the sustainability of milk banking needs proper management and more financial support by relative health authorities and the government.
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http://dx.doi.org/10.1007/s12519-019-00226-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486944PMC
April 2019

Rickets severity predicts clinical outcomes in children with X-linked hypophosphatemia: Utility of the radiographic Rickets Severity Score.

Bone 2019 05 14;122:76-81. Epub 2019 Feb 14.

Yale University School of Medicine, New Haven, CT, USA.

The Rickets Severity Score (RSS) was used to evaluate X-linked hypophosphatemic rickets (XLH), a genetic disorder mediated by increased circulating FGF23. The reliability of the RSS was assessed using data from a randomized, phase 2 clinical trial that evaluated the effects of burosumab, a fully human anti-FGF23 monoclonal antibody, in 52 children with XLH ages 5 to 12 years. Bilateral knee and wrist radiographs were obtained at baseline, week 40, and week 64. We evaluated the relationships of the RSS to the Radiographic Global Impression of Change (RGI-C), serum alkaline phosphatase (ALP), height Z-score, 6-minute walk test (6MWT) percent predicted, and the Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI). The RSS showed moderate-to-substantial inter-rater reliability (weighted kappa, 0.45-0.65; Pearson correlation coefficient (r), 0.83-0.89) and substantial intra-rater reliability (weighted Kappa, 0.66; r = 0.91). Baseline RSS correlated with serum ALP (r = 0.47). Baseline RSS identified two subgroups (higher [RSS ≥1.5] and lower RSS [RSS <1.5]) that discriminated between subjects with greater and lesser rachitic disease. Higher RSS was associated with more severe clinical features, including impaired growth (Z-score, -2.12 vs -1.44) and walking ability (6MWT percent predicted, 77% vs 86%), more severe self-reported pain (29.9 [more severe] vs 45.3 [less severe]) and less physical function (29.6 [more severe] vs 40.9 [less severe]). During burosumab treatment, greater reductions in RSS corresponded to higher RGI-C global scores (r = -0.65). Improvements in RSS correlated with decreased serum ALP (r = 0.47). These results show the reliability of the RSS in XLH, and demonstrate that higher RSS values are associated with greater biochemical, clinical, and functional impairments in children with XLH.
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http://dx.doi.org/10.1016/j.bone.2019.02.010DOI Listing
May 2019

Validation of the Chinese version of the Pelvic Floor Distress Inventory-20 (PFDI-20) according to the COSMIN checklist.

Int Urogynecol J 2019 07 4;30(7):1127-1139. Epub 2019 Feb 4.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Road, Dongcheng District, Beijing, China.

Introduction And Hypothesis: The objective of this study was to translate the short version of the Pelvic Floor Distress Inventory (PFDI-20) into Chinese and to evaluate its psychometric properties in Chinese women with symptomatic pelvic floor dysfunction according to the Consensus-Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) checklist.

Methods: Between October 2017 and May 2018, a cross-sectional analysis of the clinical data of 126 patients who met the inclusion criteria was performed. The patients completed the questionnaires at the baseline (T1), 1-2 weeks later (T2), and 3 months after surgery (T3). Reliability testing included internal consistency, test-retest reliability, and measurement error. The methodical tests for validity were content validity, criterion validity, construct validity, and hypothesis testing. Responsiveness was also taken into consideration.

Results: One hundred twenty-six patients completed all questionnaires. Internal consistency, measured by Cronbach's alpha value, was good, and the test-retest reliability was high, with an intraclass correlation coefficient (ICC) of 0.99. Construct validity was verified by factor analysis. All assumptions were confirmed, and there were no ceiling or floor effects in this study. Spearman's correlation coefficient between the PFDI-20 and the Pelvic Floor Impact Questionnaire (PFIQ-7) was 0.867, showing a significant correlation. Furthermore, the minimal important change (MIC) of 50.0 was less than the smallest detectable change (SDC) of 18.36, indicating the sufficient responsiveness.

Conclusions: The Chinese version of the PFDI-20 developed in this study is a reliable and valid instrument that provides good responsiveness to clinical changes.
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http://dx.doi.org/10.1007/s00192-018-3847-4DOI Listing
July 2019

Efficacy and safety of burosumab in children aged 1-4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial.

Lancet Diabetes Endocrinol 2019 03 9;7(3):189-199. Epub 2019 Jan 9.

Indiana University School of Medicine, Indianapolis, IN, USA.

Background: Children with X-linked hypophosphataemia have high concentrations of circulating phosphatonin fibroblast growth factor 23 (FGF23), which causes renal phosphate wasting and hypophosphataemia, rickets, skeletal deformities, and growth impairment. Burosumab, a human monoclonal antibody against FGF23, improves phosphate homoeostasis and rickets in children aged 5-12 years with X-linked hypophosphataemia. We aimed to assess the safety and efficacy of burosumab in younger children with X-linked hypophosphataemia.

Methods: In this open-label, phase 2 trial at three hospitals in the USA, children (aged 1-4 years) with X-linked hypophosphataemia received burosumab (0·8 mg/kg) via subcutaneous injection every 2 weeks for 64 weeks. The dose was increased to 1·2 mg/kg if two consecutive pre-dose serum phosphorus concentrations were below 1·03 mmol/L (3·2 mg/dL), serum phosphorus had increased by less than 0·16 mmol/L (<0·5 mg/dL) from baseline, and a dose of burosumab had not been missed. Participants could continue to receive burosumab for up to an additional 96 weeks during the extension period. Key inclusion criteria were age 1-4 years at the time of informed consent; fasting serum phosphorus concentration of less than 0·97 mmol/L (3·0 mg/dL); serum creatinine 8·8-35·4 μmol/L (0·1-0·4 mg/dL); radiographic evidence of rickets (at least five participants were required to have a Thacher Rickets Severity Score of ≥1·5 at the knee); and a confirmed PHEX mutation or a variant of unknown significance in the patient or direct relative also affected with X-linked hypophosphataemia. Conventional therapy was stopped upon enrolment. The coprimary endpoints were safety and change from baseline to week 40 in fasting serum phosphorus concentrations. Changes in rickets severity from baseline to weeks 40 and 64 (assessed radiographically using Thacher Rickets Severity Score and an adaptation of the Radiographic Global Impression of Change), and recumbent length or standing height, were key secondary outcomes. This trial is registered with ClinicalTrials.gov, number NCT02750618, and is ongoing.

Findings: Between May 16, 2016, and June 10, 2016, we enrolled 13 children with X-linked hypophosphataemia. All 13 children completed 64 weeks of treatment and were included in the efficacy and safety analysis; none exceeded 70 weeks of treatment at the time of analysis. Serum phosphorus least squares mean increase from baseline to week 40 of treatment was 0·31 mmol/L (SE 0·04; 95% CI 0·24-0·39; 0·96 mg/dL [SE 0·12]; p<0·0001). All patients had at least one adverse event. 14 treatment-related adverse events, mostly injection site reactions, occurred in five children. One serious adverse event considered unrelated to treatment (tooth abscess) occurred in a child with a history of tooth abscess. All other adverse events were mild to moderate, except a severe food allergy considered unrelated to treatment. No instances of nephrocalcinosis or noteworthy changes in the results of a standard safety chemistry panel emerged. Total Thacher Rickets Severity Score decreased by a least squares mean of -1·7 (SE 0·1; p<0·0001) from baseline to week 40 and by -2·0 (SE 0·1; p<0·0001) by week 64. The Radiographic Global Impression of Change score also indicated significant improvement, with a least squares mean score of +2·3 (SE 0·1) at week 40 and +2·2 (0·1) at week 64 (both p<0·0001). Mean length or standing height Z score was maintained from baseline to week 64.

Interpretation: Burosumab had a favourable safety profile, increased serum phosphorus, and improved rickets and prevented early declines in growth in children aged 1-4 years with X-linked hypophosphataemia. These findings could substantially alter the treatment of young children with X-linked hypophosphataemia.

Funding: Ultragenyx Pharmaceutical and Kyowa Kirin International.
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http://dx.doi.org/10.1016/S2213-8587(18)30338-3DOI Listing
March 2019

Overexpression of miR-1 in the heart attenuates hippocampal synaptic vesicle exocytosis by the posttranscriptional regulation of SNAP-25 through the transportation of exosomes.

Cell Commun Signal 2018 11 29;16(1):91. Epub 2018 Nov 29.

Department of Pharmacology, College of Pharmacy of Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin, 150086, Heilongjiang Province, China.

Background: The link between cardiac diseases and cognitive deterioration has been accepted from the concept of "cardiogenic dementia", which was proposed in the late 1970s. However, the molecular mechanism is unclarified.

Methods: The two animal models used in this study were cardiac-specific overexpression of microRNA-1-2 transgenic (Tg) mice and a myocardial infarction mouse model generated by left coronary artery ligation (LCA). First, we observed the microRNA-1 (miR-1) level and synaptic vesicles (SV) distribution in the hippocampus using in situ hybridization and transmission electron microscopy (TEM) and evaluated the expression of vesicle exocytosis related proteins by western blotting. Second, we used dual luciferase reporter assay as well as antagonist and miRNA-masking techniques to identify the posttranscriptional regulatory effect of miR-1 on the Snap25 gene. Third, FM1-43 staining was performed to investigate the effect of miR-1 on synaptic vesicle exocytosis. Lastly, we used GW4869 to inhibit the biogenesis and secretion of exosomes to determine the transportation effect of exosomes for miR-1 from the heart to the brain.

Results: Compared with the levels in age-matched WT mice, miR-1 levels were increased in both the hearts and hippocampi of Tg mice, accompanied by the redistribution of SVs and the reduction in SV exocytosis-related protein SNAP-25 expression. In vitro studies showed that SNAP-25 protein expression was down- or upregulated by miR-1 overexpression or inhibition, respectively, however, unchanged by miRNA-masking the 3'UTR of the Snap25 gene. SV exocytosis was inhibited by miR-1 overexpression, which could be prevented by co-transfection with an anti-miR-1 oligonucleotide fragment (AMO-1). The knockdown of miR-1 by hippocampal stereotaxic injection of AMO-1 carried by a lentivirus vector (lenti-pre-AMO-1) led to the upregulation of SNAP-25 expression and prevented SV concentration in the synapses in the hippocampi of Tg mice. The application of GW4869 significantly reversed the increased miR-1 level in the blood and hippocampi as well as reduced the SNAP-25 protein levels in the hippocampi of both Tg and LCA mice.

Conclusion: The overexpression of miR-1 in the heart attenuated SV exocytosis in the hippocampus by posttranscriptionally regulating SNAP-25 through the transportation of exosomes. This study contributes to the understanding of the relationship between cardiovascular disease and brain dysfunction.
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http://dx.doi.org/10.1186/s12964-018-0303-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267908PMC
November 2018

Beneficial effect of compound essential oil inhalation on central fatigue.

BMC Complement Altern Med 2018 Nov 26;18(1):309. Epub 2018 Nov 26.

Basic Medicine School, Beijing University of Chinese Medicine, Beijing, People's Republic of China.

Backgrounds: Although the physical and mental enhancement effect of essential oils have been proved, the beneficial effect of essential oil in central fatigue remains unclear. In this study, we extracted essential oils from nine aromatic plants to make a compound essential oil, and detected the therapeutic effect of central fatigue by daily aerial diffusion.

Methods: Thirty-three rats were randomly and equally divided into control group, chronic sleep deprivation group, and compound essential oil inhalation group. Central fatigue was generated by chronic sleep deprivation.

Results: After 21-day various interferences, it is found that the sleep deprivation rats showed an evident decrease in physical endurance, negative emotion, and cognitive dysfunction compared with the control group, and the group that treated with the compound essential oil behaved significantly better than central fatigue group.

Conclusion: We concluded that this formula of essential oils could alleviate central fatigue on rats, and our study provides a new direction of application of aromatic therapy, which could be expanded to insomnia, depression and other healthy issue in the further research.
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http://dx.doi.org/10.1186/s12906-018-2375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260882PMC
November 2018

Evolution of host support for two ancient bacterial symbionts with differentially degraded genomes in a leafhopper host.

Proc Natl Acad Sci U S A 2018 12 21;115(50):E11691-E11700. Epub 2018 Nov 21.

Department of Life and Environmental Sciences, University of California, Merced, CA 95343.

Plant sap-feeding insects (Hemiptera) rely on bacterial symbionts for nutrition absent in their diets. These bacteria experience extreme genome reduction and require genetic resources from their hosts, particularly for basic cellular processes other than nutrition synthesis. The host-derived mechanisms that complete these processes have remained poorly understood. It is also unclear how hosts meet the distinct needs of multiple bacterial partners with differentially degraded genomes. To address these questions, we investigated the cell-specific gene-expression patterns in the symbiotic organs of the aster leafhopper (ALF), (Cicadellidae). ALF harbors two intracellular symbionts that have two of the smallest known bacterial genomes: (112 kb) and (190 kb). Symbionts are segregated into distinct host cell types (bacteriocytes) and vary widely in their basic cellular capabilities. ALF differentially expresses thousands of genes between the bacteriocyte types to meet the functional needs of each symbiont, including the provisioning of metabolites and support of cellular processes. For example, the host highly expresses genes in the bacteriocytes that likely complement gene losses in nucleic acid synthesis, DNA repair mechanisms, transcription, and translation. Such genes are required to function in the bacterial cytosol. Many host genes comprising these support mechanisms are derived from the evolution of novel functional traits via horizontally transferred genes, reassigned mitochondrial support genes, and gene duplications with bacteriocyte-specific expression. Comparison across other hemipteran lineages reveals that hosts generally support the incomplete symbiont cellular processes, but the origins of these support mechanisms are generally specific to the host-symbiont system.
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http://dx.doi.org/10.1073/pnas.1811932115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294904PMC
December 2018