Publications by authors named "Qing Shang"

75 Publications

TEP1 is a risk gene for sporadic cerebral palsy.

J Genet Genomics 2021 Sep 17. Epub 2021 Sep 17.

Institutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, 201102, China; Shanghai Center for Women and Children's Health, Shanghai, 200062, China. Electronic address:

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http://dx.doi.org/10.1016/j.jgg.2021.08.010DOI Listing
September 2021

MicroRNA-31-3p/RhoA signaling in the dorsal hippocampus modulates methamphetamine-induced conditioned place preference in mice.

Psychopharmacology (Berl) 2021 Nov 27;238(11):3207-3219. Epub 2021 Jul 27.

Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.

Rationale: MicroRNAs (miRNAs) regulate neuroplasticity-related proteins and are implicated in methamphetamine (METH) addiction. RhoA is a small Rho GTPase that regulates synaptic plasticity and addictive behaviors. Nevertheless, the functional relationship between RhoA and upstream miRNAs of METH addiction remains unclear.

Objective: To explore the molecular biology and epigenetic mechanisms of the miR-31-3p/RhoA pathway in METH addiction.

Methods: RhoA protein and its potential upstream regulator, miR-31-3p, were detected. A dual luciferase reporter was employed to determine whether RhoA constituted a specific target of miR-31-3p. Following adeno-associated virus (AAV)-mediated knockdown or overexpression of miR-31-3p or RhoA in the dorsal hippocampus (dHIP), mice were subjected to conditioned place preference (CPP) to investigate the effects of miR-31-3p and RhoA on METH-induced addictive behaviors.

Results: RhoA protein was significantly decreased in the dHIP of CPP mice with a concomitant increase in miR-31-3p. RhoA was identified as a direct target of miR-31-3p. Knockdown of miR-31-3p in the dHIP was associated with increased RhoA protein and attenuation of METH-induced CPP. Conversely, overexpression of miR-31-3p was associated with decreased RhoA protein and enhancement of METH effects. Similarly, knockdown of RhoA in the dHIP enhanced METH-induced CPP, whereas RhoA overexpression attenuated the effects of METH. Parallel experiments using sucrose preference revealed that the effects of miR-31-3p/RhoA pathway modulation were specific to METH.

Conclusions: Our findings indicate that the miR-31-3p/RhoA pathway in the dHIP modulates METH-induced CPP in mice. Our results highlight the potential role of epigenetics represented by non-coding RNAs in the treatment of METH addiction.
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http://dx.doi.org/10.1007/s00213-021-05936-2DOI Listing
November 2021

D1R/PP2A/p-CaMKIIα signaling in the caudate putamen is involved in acute methamphetamine-induced hyperlocomotion.

Neurosci Lett 2021 08 6;760:136102. Epub 2021 Jul 6.

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, People's Republic of China; Institute of Forensic Injury, Institute of Forensic Bioevidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, People's Republic of China. Electronic address:

Drug addiction is underscored by the transition from experimental use to dependent use of addictive drugs. Acute use of methamphetamine (METH) causes a range of clinical symptoms, including hyperlocomotion. Dopamine D1 receptor (D1R)-mediated negative regulation of phosphorylated calcium/calmodulin-dependent protein kinase IIα (p-CaMKIIα, threonine [Thr] 286) is involved in the acute effects induced by single METH administration. Protein phosphatase 2A (PP2A) is a potential bridge that links D1R and p-CaMKIIα (Thr 286) after acute METH administration. However, the mechanisms underlying hyperlocomotion induced by single METH administration remain unclear. In this study, SCH23390 (a D1R inhibitor) and LB100 (a PP2A inhibitor) were administered to examine the involvement of D1R and PP2A signaling in acute METH-induced hyperlocomotion in mice. The protein levels of methylated PP2A-C (m-PP2A-C, leucine [Leu] 309), phosphorylated PP2A-C (p-PP2A-C, tyrosine [Tyr] 307), PP2A-C, p-CaMKIIα (Thr 286), and CaMKIIα in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were measured. Administration of 0.5 mg/kg SCH23390 reversed the acute METH-induced increase in protein levels of m-PP2A-C (Leu 309) and the decrease in protein levels of p-PP2A-C (Tyr 307) in the CPu, but not in the PFC and NAc. Moreover, prior administration of 0.1 mg/kg LB100 attenuated hyperlocomotion induced by single METH administration and reversed the decrease in protein levels of p-CaMKII (Thr 286) in the PFC, NAc, and CPu. Collectively, these results indicate that the D1R/PP2A/p-CaMKIIα signaling cascade in the CPu may be involved in hyperlocomotion after a single administration of METH.
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http://dx.doi.org/10.1016/j.neulet.2021.136102DOI Listing
August 2021

Spatiotemporal expression of Rap1 and Ras mediates the acquisition and reinstatement of methamphetamine-induced conditioned place preference in mice via extracellular signal-regulated kinase activation.

Neuroreport 2021 08;32(12):1035-1040

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi.

Drug addiction is a chronic recurrent brain disease characterized by compulsive drug use and a high tendency to relapse. We previously reported that the Ras-extracellular signal-regulated kinase (ERK)-ΔFosB pathway in the caudate putamen (CPu) was involved in methamphetamine-induced behavioral sensitization. Rap1, as an antagonist of Ras originally, was found to participate in neuronal synaptic plasticity recently, but the role of Rap1 in methamphetamine addiction is unclear. First, in this study, we constructed the acquisition, extinction and reinstatement of methamphetamine-induced conditioned place preference (CPP) in mice, respectively. Then, protein levels of Rap1, Ras and pERK/ERK in the prefrontal cortex (PFc), CPu and hippocampus of CPP mice on three phases were detected. We found that protein levels of Rap1, Ras and pERK/ERK in the CPu were significantly increased after repeated methamphetamine administration, as well as Rap1 and pERK/ERK in the hippocampus. However, protein levels of Rap1 and pERK/ERK in the CPu were decreased on the reinstatement of CPP mice. Therefore, Rap1 and Ras in the CPu and Rap1 in the hippocampus may participate in the regulation of the acquisition of methamphetamine-induced CPP in mice by activating ERK. Moreover, Rap1-ERK cascade in the CPu contributes to both the acquisition and reinstatement of methamphetamine-induced CPP in mice.
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http://dx.doi.org/10.1097/WNR.0000000000001686DOI Listing
August 2021

[Three-dimensional printed drill guide template assisting percutaneous pedicle screw fixation for multiple-level thoracolumbar fractures].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jun;35(6):742-749

Department of Spine Surgery, Fushun People's Hospital, Fushun Sichuan, 643200, P.R.China.

Objective: To evaluate the feasibility and safety of three-dimensional (3D) printed drill guide template-assisted percutaneous pedicle screw fixation for multiple-level thoracolumbar fractures.

Methods: Clinical data of 19 patients with multilevel thoracolumbar fracture without nerve injury who underwent surgical treatment between May 2017 and January 2019 were retrospectively analyzed. There were 9 males and 10 females and their age ranged from 22 to 63 years, with an average age of 43.6 years. Injury cause included traffic accident injury in 12 cases, and fall from height injury in 7 cases. A total of 40 fractured vertebrae were involved in T to L levels. According to AO classification, there were 29 fractures of type A1, 9 fractures of type A2, and 2 fractures of type A3. According to TANG Sanyuan classification, multiple-segment thoracolumbar fractures were classified as 17 cases of type ⅠA, 1 case of type ⅠB, and 1 case of type ⅡC. The time from injury to operation was 2-6 days, with an average of 3.1 days. The 3D-printed universal drill guide template was used for assisting percutaneous pedicle screw fixation during operation. Intraoperative blood loss, average operation time and fluoroscopy frequency of each screw were recorded. Visual analogue scale (VAS) score was used to evaluate the improvement of low back pain before operation, at 3 days after operation, and at last follow-up. According to the CT at 3 days after operation, the Gertzbein and Robbins scales were used to evaluate the accuracy of screw insertion (the grade A and grade B were regarded as accuracy, the grade A was regarded as excellent of screw insertion). The Cobb angle in sagittal plane of the fracture segment was measured, and the percentage of anterior edge of injured vertebral height was calculated. The consistency of the inclination of bilateral pedicle screws were analyzed postoperatively, and compared the angle of the intraoperative guide plate with the inclination of screw to verify the effectiveness of the guide plate in controlling the inclination.

Results: All the 19 patients completed the operation successfully, and the intraoperative blood loss was 44-67 mL, with an average of 54.3 mL. The average operation time for each screw insertion was 7.3-11.1 minutes, with an average of 9.6 minutes. The average fluoroscopy frequency of each screw insertion was 1.6-2.5 times, with an average of 2.0 times. No spinal cord, nerve root injury, infection, and other complications occurred. All patients were followed up 24-38 months, with an average of 28.7 months. The accuracy of pedicle screws was evaluated by using Gertzbein and Robbins scales: 145 screws were grade A and 11 screws were grade B. The accuracy of screw insertion was 100% and the excellent rate was 92.9%. The CT data at 3 days after operation showed no significant difference in the inclination between the left and right screws in the same vertebral body ( =0.93, =0.36). There was no significant difference between the angle of guide plate and the screw inclination ( >0.05). The VAS score, Cobb angle in sagittal plane, and the percentage of anterior edge of injured vertebral height were significantly improved at 3 days after operation and at last follow-up, and the VAS score was declined at last follow-up compared with 3 days after operation, all showing significant differences ( <0.05). There was no significant difference in the sagittal Cobb angle and the percentage of anterior edge of injured vertebral height between two postoperative time points ( >0.05). At last follow-up, no internal fixators were loosened or broken, and all fractures healed well.

Conclusion: For the multiple-level thoracolumbar fractures, 3D-printed drill guide template assisting percutaneous pedicle screw fixation can reduce the operation time, intraoperative blood loss, and fluoroscopy frequency and the screw insertion is accurate and has a good reduction effect.
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http://dx.doi.org/10.7507/1002-1892.202012081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218182PMC
June 2021

LB100 attenuates methamphetamine-induced behavioral sensitization by inhibiting the Raf1-ERK 1/2 cascade in the caudate putamen.

Neuroreport 2021 08;32(12):988-993

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center.

Methamphetamine (METH) abuse has become a serious social problem. Behavioral sensitization is a common behavioral paradigm used to study the neurobiological mechanism that underlies drug addiction. Our previous study demonstrated that the activity of protein phosphatase 2A (PP2A) and the level of phosphorylated extracellular signal-related kinase 1/2 (p-ERK 1/2) are increased in the caudate putamen (CPu) of METH-sensitive mice. However, the relationship between PP2A and ERK 1/2 in METH-induced behavioral sensitization remains unknown. Some studies have indicated that Raf1 may be involved in this process. In this study, LB100, a PP2A inhibitor for treating solid tumors, was first used to clarify the relationship between PP2A and ERK 1/2. In addition, Western blot was used to examine the levels of p-Raf1 (Ser 259) and p-ERK 1/2 (Thr 202/Tyr 204) in the CPu, hippocampus (Hip) and nucleus accumbens (NAc). Our results showed that 2 mg/kg LB100 significantly attenuated METH-induced behavioral sensitization. Furthermore, Western blot analysis revealed that pretreatment with 2 mg/kg LB100 remarkably reversed METH-induced reduction of p-Raf1, as well as upregulation of p-ERK 1/2 in the CPu. Taken together, these results indicate that PP2A plays an important role in METH-induced behavioral sensitization and phosphorylates ERK 1/2 by dephosphorylating p-Raf1 in the CPu to further regulate METH-induced behavioral sensitization.
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http://dx.doi.org/10.1097/WNR.0000000000001678DOI Listing
August 2021

[Phenotypic and genetic analysis of a boy with inv dup del(8p)].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jun;38(6):581-584

Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated of Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450003, China.

Objective: To delineate the nature and origin of a chromosomal aberration detected in a boy with mental retardation.

Methods: The proband and his parents were subjected to routine G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) analysis.

Results: The karyotype of the proband was determined as 46, XX, add(8)(p23). No karyotypic abnormality was detected in either of his parents. SNP-array has identified a 34.9 Mb duplication at 8p23.1q11.1 and a 6.78 Mb microdeletion at 8p23.1pter in the proband. No copy number variation was detected in either parent.

Conclusion: The child was diagnosed with 8p inverted duplication deletion syndrome, which might be induced by non-allelic homologous recombination between olfactory genes in the 8p23.1 region.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200109-00020DOI Listing
June 2021

Analysis of radiation force on a uniaxial anisotropic sphere by dual counter-propagating Gaussian beams.

J Opt Soc Am A Opt Image Sci Vis 2021 May;38(5):616-627

Based on Maxwell's stress tensor and the generalized Lorenz-Mie theory, a theoretical approach is introduced to study the radiation force exerted on a uniaxial anisotropic sphere illuminated by dual counter-propagating (CP) Gaussian beams. The beams propagate with arbitrary direction and are expanded in terms of the spherical vector wave functions (SVWFs) in a particle coordinate system using the coordinate rotation theorem of the SVWFs. The total expansion coefficients of the incident fields are derived by superposition of the vector fields. Using Maxwell stress tensor analysis, the analytical expressions of the radiation force on a homogeneous absorbing uniaxial anisotropic sphere are obtained. The accuracy of the theory is verified by comparing the radiation forces of the anisotropic sphere reduced to the special cases of an isotropic sphere. In order to study the equilibrium state, the effects of beam parameters, particle size parameters, and anisotropy parameters on the radiation force are discussed in detail. Compared with the isotropic particle, the equilibrium status is sensitive to the anisotropic parameters. Moreover, the properties of optical force on a uniaxial anisotropic sphere in a single Gaussian beam trap and Gaussian standing wave trap are compared. It indicates that the CP Gaussian beam trap may more easily capture or confine the anisotropic particle. However, the radiation force exerted on an anisotropic sphere exhibits very different properties when the beams do not propagate along the primary optical axis. The influence of the anisotropic parameter on the radiation force by CP Gaussian beams is different from that of a single Gaussian beam. In summary, even for anisotropic particles, the Gaussian standing wave trap also exhibits significant advantages when compared with the single Gaussian beam trap. The theoretical predictions of radiation forces exerted on a uniaxial anisotropic sphere by dual Gaussian beams provide effective ways to achieve the improvement of optical tweezers as well as the capture, suspension, and high-precision delivery of anisotropic particles.
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http://dx.doi.org/10.1364/JOSAA.418328DOI Listing
May 2021

[Acupuncture combined with powder for children with cerebral palsy and its effect on serum immune indexes and nerve growth related protein].

Zhongguo Zhen Jiu 2021 Mar;41(3):288-92

Rehabilitation Center, Children's Hospital of Zhengzhou University/Henan Children's Hospital/Zhengzhou Children's Hospital, Zhengzhou 450002, China.

Objective: To observe the efficacy of acupuncture combined with powder for children with cerebral palsy (liver- stagnation, spleen-kidney deficiency syndrome) and its effect on serum immune indexes and nerve growth related protein.

Methods: A total of 180 children with cerebral palsy were randomly divided into a combined group (60 cases, 2 cases dropped off), an acupuncture group (60 cases, 4 cases dropped off) and a Chinese medication group (60 cases, 5 cases dropped off). On the basis of conventional treatment, the children in the combined group were treated with acupuncture [Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Benshen (GB 13), 30 min each time, twice a day] and powder; the children in the acupuncture group were treated with acupuncture, and the children in the Chinese medication group were treated with powder, the treatment was same with the combined group. All the children were treated for 6 consecutive days and rest for 1 day, totaling for 8 weeks. The Gesell developmental schedules (GDS) and TCM symptom scores were recorded before treatment, after treatment and at 3-month, 6-month and 12-month follow-up visit; the serum immune indexes (IgA, IgG and IgM) and nerve growth related protein [myelin basic protein (MBP), high mobility group box-1 (HMGB), neuronspecific enolase (NSE)] were detected before and after treatment. The clinical efficacy of each group was evaluated.

Results: The total effective rate was 91.4% (53/58) in the combined group, which was higher than 80.4% (45/56) in the acupuncture group and 78.2% (43/55) in the Chinese medication group (<0.05). Compared before treatment, the GDS scores in the three groups were increased and the TCM symptom scores were reduced after treatment and at 3-month, 6-month and 12-month follow-up visit (<0.05). The GDS score in the combined group was higher than that in the acupuncture group and the Chinese medication group, and the TCM symptom score was lower than that in the acupuncture group and Chinese medication group (<0.05). After treatment, the serum levels of IgA, IgG and IgM in the combined group were increased (<0.05), and the serum levels of MBP, HMGB and NSE were decreased (<0.05), and the improvements were superior to those in the acupuncture group and the Chinese medication group (<0.05).

Conclusion: Acupuncture combined with powder could effectively improve the development quotient in children with cerebral palsy (liver- stagnation, spleen-kidney deficiency syndrome), regulate the serum immune indexes and nerve growth related protein levels.
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http://dx.doi.org/10.13703/j.0255-2930.20200301-0002DOI Listing
March 2021

Long-term neurodevelopment outcomes of hand, foot and mouth disease inpatients infected with EV-A71 or CV-A16, a retrospective cohort study.

Emerg Microbes Infect 2021 Dec;10(1):545-554

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, People's Republic of China.

Hand, foot and mouth disease (HFMD) is a common infectious disease in western Asia area and the full range of the long-term sequelae of HFMD remains poorly described. We conducted a retrospective hospital-based cohort study of HFMD patients with central nervous system (CNS) complications caused by EV-A71 or CV-A16 between 2010 and 2016. Patients were classified into three groups, including CNS only, autonomic nervous system (ANS) dysregulation, and cardiorespiratory failure. Neurologic examination, neurodevelopmental assessments, Magnetic Resonance Imaging (MRI) and lung function, were performed at follow up. Of the 176 patients followed up, 24 suffered CNS only, 133 ANS dysregulation, and 19 cardiorespiratory failure. Median follow-up period was 4.3 years (range [1.4-8.3]). The rate of neurological abnormalities was 25% (43 of 171) at discharge and 10% (17 of 171) at follow-up. The rates of poor outcome were significantly different between the three groups of complications in motor (28%, 38%, 71%) domain (p=0.020), but not for cognitive (20%, 24%, 35%), language (25%, 36%, 41%) and adaptive (24%, 16%, 26%) domains ( = 0.537,  = 0.551,  = 0.403). For children with ventilated during hospitalization, 41% patients (14 of 34) had an obstructive ventilatory defect, and one patient with scoliosis had mixed ventilatory dysfunction. Persistent abnormalities on brain MRI were 0% (0 of 7), 9% (2 of 23) and 57% (4 of 7) in CNS, ANS and cardiorespiratory failure group separately. Patients with HFMD may have abnormalities in neurological, motor, language, cognition, adaptive behaviour and respiratory function. Long-term follow-up programmes for children's neurodevelopmental and respiratory function may be warranted.
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http://dx.doi.org/10.1080/22221751.2021.1901612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009121PMC
December 2021

Fabrication of PLGA forming implants and study on their correlation of release profiles with performances.

J Biomater Sci Polym Ed 2021 06 9;32(8):994-1008. Epub 2021 Mar 9.

Chemical and Pharmaceutical Engineering Institute, Hebei University of Science and Technology, Hebei, China.

In this study, a novel PLGA forming implants (ISFIs) were fabricated and methods for testing the release profiles were also developed. The correlations between release profiles and performances ( correlation, IVIVC) were also studied. PLGA with different molecular weights were selected as the polymeric matrix. Biocompatible -methy1-2-pyrrolidone (NMP) or glyceryl triacetate (GTA) were used as the solvents with the ratios of NMP/GTA from 60/40 (vol/vol) to 20/80 (vol/vol). Eprinomectin (EPR) was chosen as the model therapeutic. release profiles of the EPR-loaded PLGA ISFIs were investigated using various methods (i.e. 'tubule' sample-and-separate and dialysis method). Sprague-Dawley rats were used to study the pharmacokinetics of EPR-loaded PLGA ISFIs. The release data obtained 'tubule' sample-separate method had a good IVIVC (Level A, > 0.99). These results showed that the 'tubule' sample-separate method was capable of discriminating the EPR-loaded ISFIs which were equivalent in formulation composition with manufacturing differences. Meanwhile, this method could be used to predict the performances of ISFIs in the investigated animal model.
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http://dx.doi.org/10.1080/09205063.2021.1889857DOI Listing
June 2021

PP2A-C may be a promising candidate for postmortem interval estimation.

Int J Legal Med 2021 May 6;135(3):837-844. Epub 2021 Jan 6.

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, Shaanxi, 710061, People's Republic of China.

Determining the postmortem interval (PMI) is an important task in forensic pathology. However, a reliable means of determining the PMI between 24 h and approximately 7 days after death has not yet been established. A previous study demonstrated that subunit A of protein phosphatase 2A (PP2A-A) is a promising candidate to estimate the PMI during the first 96 h. However, more detailed work is still needed to investigate PP2A's function in PMI estimation. PP2A is a serine/threonine phosphatase consisting of three subunits (PP2A-A, PP2A-B, and PP2A-C), and its activation is reflected by Tyr-307 phosphorylation of the catalytic subunit (P-PP2A-C). In this study, we speculated that the other two subunits of PP2A and the activation of PP2A may play different roles in estimating the PMI. For this purpose, mice were euthanized and stored at different temperatures (4, 15, and 25 °C). At each temperature, the musculus vastus lateralis was collected at different time points (0, 24, 48, and 96 h) to investigate the degradation of PP2A-B, PP2A-C, and P-PP2A-C (Tyr-307). Homocysteine (Hcy) was used to establish a hyperhomocysteinemia animal model to explore the effects of plasma Hcy on PMI estimation. The data showed not only that PP2A-C was more stable than PP2A-B, but also that it was not affected by homocysteine (Hcy). These characteristics make PP2A-C a promising candidate for short-term (24 h to 48 h) PMI estimation.
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http://dx.doi.org/10.1007/s00414-020-02466-yDOI Listing
May 2021

The Association Study of Polymorphisms With Cerebral Palsy in Chinese Population.

Front Neurosci 2020 25;14:590098. Epub 2020 Nov 25.

Institutes of Biomedical Science and Children's Hospital, Fudan University, Shanghai, China.

Cerebral palsy (CP) is a syndrome of non-progressive motor dysfunction caused by early brain development injury. Recent evidence has shown that immunological abnormalities are associated with an increased risk of CP. We recruited 782 children with CP as the case group and 770 healthy children as the control group. The association between single nucleotide polymorphisms (SNPs; namely, rs10889657, rs6682925, rs1884444, rs17375018, rs1004819, rs11805303, and rs10889677) and CP was studied by using a case-control method and SHEsis online software. Subgroup analysis based on complications and clinical subtypes was also carried out. There were differences in the allele and genotype frequencies between CP cases and controls at the rs11805303 and rs10889677 SNPs (allele = 0.014 and 0.048, respectively; genotype = 0.023 and 0.008, respectively), and the difference in genotype frequency of rs10889677 remained significant after Bonferroni correction (genotype = 0.048). Subgroup analysis revealed a more significant association of rs10889677 with CP accompanied by global developmental delay (genotype = 0.024 after correction) and neonatal encephalopathy (genotype = 0.024 after correction). The present results showed a significant association between and CP, suggesting that may play a potential role in CP pathogenesis.
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http://dx.doi.org/10.3389/fnins.2020.590098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724030PMC
November 2020

Phosphorylation of GluN2B subunits of N-methyl-d-aspartate receptors in the frontal association cortex involved in morphine-induced conditioned place preference in mice.

Neurosci Lett 2021 01 3;741:135470. Epub 2020 Nov 3.

School of Forensic Science and Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science and Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China. Electronic address:

Morphine is one of the most abused drugs in the world, which has resulted in serious social problems. The frontal association cortex (FrA) has been shown to play a key role in memory formation and drug addiction. N-Methyl-d-aspartate receptors (NMDARs) are abundant in the prefrontal cortex (PFc) and much evidence indicates that GluN2B-containing NMDARs are involved in morphine-induced conditioned place preference (CPP). However, the function of GluN2B in the FrA during morphine-induced CPP has yet to be fully investigated. In the present work, a CPP animal model was employed to measure the expression of phosphorylated (p-) GluN2B (Serine; Ser 1303) in the FrA and NAc in different phases of morphine-induced CPP. We found that p-GluN2B (Ser 1303) was increased in the FrA during the development and reinstatement phases but unchanged in the extinction phase. The use of ifenprodil, a GluN2B-specific antagonist, to block the activity of GluN2B in the two phases attenuated morphine-induced CPP and reinstatement. Furthermore, ifenprodil also blocked morphine-induced upregulation of p-GluN2B (Ser 1303) in the FrA in both phases. These results indicate that GluN2B-containing NMDARs in the FrA may be involved in the regulation of morphine-induced CPP and reinstatement.
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http://dx.doi.org/10.1016/j.neulet.2020.135470DOI Listing
January 2021

Mutations disrupting neuritogenesis genes confer risk for cerebral palsy.

Nat Genet 2020 10 28;52(10):1046-1056. Epub 2020 Sep 28.

Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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http://dx.doi.org/10.1038/s41588-020-0695-1DOI Listing
October 2020

New developments in angiography for the diagnosis and management of diabetic retinopathy.

Diabetes Res Clin Pract 2020 Sep 31;167:108361. Epub 2020 Jul 31.

Department of Ophthalmology, University of Washington Eye Institute, Seattle, WA, USA. Electronic address:

The most common microvascular complication of diabetes is diabetic retinopathy, the leading cause of blindness in adults of working age. Our understanding of the vascular changes in diabetic retinopathy was enhanced by the demonstration of fluorescein angiography (FA) in the human retina for the first time in 1961. It was subsequently integrated with digital fundoscopic imaging to become an invaluable technique in evaluation of the retinal vasculature. The recent development of OCT-angiography (OCT-A) has revolutionized the clinician's ability to examine the retinal vasculature without the need for injection of a contrast dye. By coupling OCT, which can provide noninvasive cross-sectional imaging of the central retina, with angiography in OCT-A, one can reveal retinal perfusion by allowing visualization of the depth-resolved retinal capillary plexus. OCT-A has allowed for more precise delineation of changes in the retinal microvasculature, specifically the alterations of retinal vasculature and loss of capillary perfusion from chronic microvascular occlusion in diabetic retinopathy.
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http://dx.doi.org/10.1016/j.diabres.2020.108361DOI Listing
September 2020

The effect of protein phosphatase 2A inhibitor LB100 on regulating methamphetamine induced conditioned place preference in mice.

Neurosci Lett 2020 03 4;721:134817. Epub 2020 Feb 4.

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China. Electronic address:

Protein phosphatase 2A (PP2A) is an evolutionarily conserved serine/threonine phosphatase abundant in mammalian brains. Although recent research has revealed that PP2A plays important roles in cocaine and morphine addictions, the mechanism of action of PP2A in methamphetamine (METH) addiction is unclear. LB100 is a PP2A inhibitor able to penetrate the blood-brain barrier (BBB); the role of LB100 in METH-induced conditioned place preference (CPP) has not yet been reported. Here, we explored the roles of LB100 in distinct phases of METH-induced CPP. Our findings indicate that LB100 inhibits the acquisition and reinstatement of METH-induced CPP and promotes the extinction of METH-induced CPP. Moreover, LB100 alone did not affect the natural preference of mice. Intriguingly, repeated administration of LB100 in the extinction phase did not inhibit the reinstatement of METH-induced CPP, but LB100 injection prior to METH administration could significantly block it. Taken together, we found that LB100 has significant effects on different phases of METH-induced CPP, and is therefore, a potentially promising therapeutic for METH addiction.
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http://dx.doi.org/10.1016/j.neulet.2020.134817DOI Listing
March 2020

Ifenprodil Attenuates Methamphetamine-Induced Behavioral Sensitization Through the GluN2B-PP2A-AKT Cascade in the Dorsal Striatum of Mice.

Neurochem Res 2020 Apr 24;45(4):891-901. Epub 2020 Jan 24.

School of Forensic Science and Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China.

Drug addiction can be described as a chronic and relapsing brain disease. Behavioral sensitization is believed to share similar mechanisms with relapse. Our previous studies have demonstrated that ifenprodil could attenuate methamphetamine (METH)-induced behavioral sensitization. However, the mechanism underlying this process has not been fully investigated. Protein phosphatase 2A (PP2A) is a conserved serine/threonine protein phosphatase that has been linked to many neurological diseases; however, there are few reports about PP2A in the context of drug addiction. In this study, we measured the level of phosphorylated (p-) GluN2B (Serine; Ser 1303), PP2A/B (a regulatory subunit of PP2A), and PP2A/C (a catalytic subunit of PP2A) in different brain regions such as the prefrontal cortex (PFc), nucleus accumbens (NAc), dorsal striatum (DS), and hippocampus (Hip). We also used ifenprodil, a selective antagonist of GluN2B to clarify the relationship between GluN2B and PP2A. The results showed that METH increased the level of p-GluN2B (Ser 1303) and PP2A/B in the DS and ifenprodil blocked this increase. We further examined the interaction between PP2A/B and PP2A/C in the DS and found that METH treatment increased the interaction between PP2A/B and PP2A/C, which was also blocked by ifenprodil. Then, we explored the pathway downstream of PP2A in the DS and found that p-AKT (Threonine; Thr 308) but not p-AKT (Ser 473) was dephosphorylated by PP2A. Taken together, these results indicated that the GluN2B-PP2A-AKT cascade was involved in METH-induced behavioral sensitization.
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http://dx.doi.org/10.1007/s11064-020-02966-8DOI Listing
April 2020

Autophagy-Related Gene 7 Polymorphisms and Cerebral Palsy in Chinese Infants.

Front Cell Neurosci 2019 5;13:494. Epub 2019 Nov 5.

Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Cerebral palsy (CP) is a group of non-progressive motor impairment syndromes that are secondary to brain injury in the early stages of brain development. Numerous etiologies and risk factors of CP have been reported, and genetic contributions have recently been identified. Autophagy has an important role in brain development and pathological process, and autophagy-related gene 7 () is essential for autophagosome biogenesis. The purpose of this study was to investigate the genetic association between gene single nucleotide polymorphisms (SNPs) and CP in Han Chinese children. Six SNPs (rs346078, rs1470612, rs11706903, rs2606750, rs2594972, and rs4684787) were genotyped in 715 CP patients and 658 healthy controls using the MassArray platform. Plasma ATG7 protein was determined in 73 CP patients and 79 healthy controls. The differences in the allele and genotype frequencies of the rs1470612 and rs2594972 SNPs were determined between the CP patients and controls ( = 0.02 and 0.0004, = 0.044 and 0.0012, respectively). Subgroup analysis revealed a more significant association of rs1470612 ( = 0.004, = 0.0036) and rs2594972 ( = 0.0004, < 0.0001) with male CP, and more significant differences in allele and genotype frequencies were also noticed between CP patients with spastic diplegia and controls for rs1470612 ( = 0.0024, = 0.008) and rs2594972 ( < 0.0001, = 0.006). The plasma ATG7 level was higher in CP patients compared to the controls (10.58 ± 0.85 vs. 8.18 ± 0.64 pg/mL, = 0.024). The luciferase reporter gene assay showed that the T allele of rs2594972 SNP could significantly increase transcriptional activity of the ATG7 promoter compared to the C allele ( = 0.009). These findings suggest that an association exists between genetic variants of and susceptibility to CP, which provides novel evidence for the role of ATG7 in CP and contributes to our understanding of the molecular mechanisms of this neurodevelopmental disorder.
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http://dx.doi.org/10.3389/fncel.2019.00494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848160PMC
November 2019

[Kleefstra syndrome 1 and ring chromosome 9 in a case].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Aug;36(8):837-840

Rehabilitation Center, Children' s Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450003, China.

Objective: To analyze the clinical and molecular genetic characteristics of patient with Kleefstra syndrome 1.

Methods: Clinical data, chromosomal karyotype and whole genome copy number variations (CNVs) of the patient were analyzed.

Results: The patient was found to have a karyotype of 45,XX,-9[4]/46,XX,r(9)(p24q34)[56]. Whole-genome CNVs detection revealed that she has carried a heterozygous deletion of approximately 670 kb at 9q34.3, which encompassed the entire EHMT1 gene. The region is strongly associated with Kleefstra syndrome (1/9q telomere deletion). In addition, the patient also had heterozygous deletion of 9pter, which may predispose to formation of ring chromosome 9.

Conclusion: The child was diagnosed with Kleefstra syndrome type 1 in conjunct with ring chromosome 9.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.08.021DOI Listing
August 2019

[A case of SBBYSS syndrome caused by KAT6B gene variant].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Jul;36(7):727-730

Rehabilitation Center Children's Hospital Affiliated to Zhengzhou University, Children's Hospital of Henan Province, Zhengzhou Children's Hospital, Zhengzhou, Henan 450003, China.

Objective: To analyze the clinical and molecular genetics features of a family affected with Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS).

Methods: High-throughput sequencing was used to detect copy number variations (CNVs) and pathogenic variant within the whole exome of the affected child.

Results: No pathogenic CNV was found in the child, while exome sequencing identified a heterozygous c.3367_c.3370delAGAA (p.Arg1123Argfs*6) frameshifting variant in the exon 16 of the KAT6B gene. The same variant was not found in either parent.

Conclusion: The c.3367_c.3370delAGAA (p.R1123Rfs*6) probably underlies the disease in the affected child. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.07.018DOI Listing
July 2019

Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients.

Mol Med Rep 2019 Aug 5;20(2):1178-1186. Epub 2019 Jun 5.

Department of Pediatrics, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450053, P.R. China.

Angelman syndrome (AS) is a congenital neuro-developmental disorder typically occurring due to functional defects of the UBE3A gene caused by uniparental disomy (UPD), translocation or single gene mutation. UBE3A gene exhibits imprinting expression, and only maternal inherited alleles express functional UBE3A protein in the brain. The common method to diagnose AS is single nucleotide polymorphism array or methylation‑specific multiplex ligation‑dependent probe amplification (MS‑MLPA). In recent years, whole exome sequencing (WES) has been increasingly used in the genetic diagnosis of a variety of indications, exhibiting great advantages as a comprehensive and unbiased testing method. In the present study, the cases of two unrelated patients with Robertsonian‑like translocation in chromosome 15, namely 45,XX,der(15;15)(q10;q10) and 45,XY,der(15;15)(q10;q10), are reported. The first case was diagnosed with AS by WES and validated by Sanger sequencing. In contrast to 42.84%  homozygous variants on all chromosomes, 92.69%  homozygosity variants were observed on chromosome 15. A homozygous stretch identifier was applied and identified a homozygous region across the entire chromosome 15. Sanger sequencing was used to further determine the subtype and confirm that two homozygous variants on chromosome 15 with low allele frequency (<0.01) were derived only from the father and not from the mother, thereby indicating a paternal UPD case, classified as isodisomy. MS‑MLPA results of the other AS patient with the same karyotype indicated that he had a high possibility of paternal UPD at chromosome 15. Taken together, the current study suggested the potential application of WES in detecting and facilitating the diagnosis of UPD.
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http://dx.doi.org/10.3892/mmr.2019.10339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625451PMC
August 2019

Influence of drying processes on the structures, morphology and release profiles of risperidone-loaded PLGA microspheres.

J Microencapsul 2019 Jan 18;36(1):21-31. Epub 2019 Mar 18.

a Chemical and Pharmaceutical Engineering Institute , Hebei University of Science and Technology , Hebei , China.

The purpose of this study was to investigate the influences of drying methods on the risperidone (RIS) release profiles of RIS-loaded PLGA microspheres. These microspheres were fabricated with an O/W emulsion solvent evaporation method. The wet microspheres were dried with freeze drying and vacuum drying methods. The microspheres were mono-dispersed spheres with an average diameter of 100 μm. Studies found that drying methods had great influence on the porosity, morphology, and release profiles of RIS-loaded PLGA microspheres. Specifically, the freeze-dried microspheres had higher porosity (78.46 ± 1.64%) than those vacuum-dried ones (52.45 ± 2.68%), and they showed higher RIS release rates ( < 0.05). In the accelerated release tests (45 °C), these microspheres dried under the pressures of 700 mmHg and 200 mmHg gave faster release rates than those ones dried under the pressure of 450 mmHg. Importantly, the accelerated release test (45 °C) had a high correlation with the real-time test (37 °C) ( > 0.99). These studies exhibited a significance in the precise preparation of RIS-loaded PLGA microspheres.
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http://dx.doi.org/10.1080/02652048.2019.1582723DOI Listing
January 2019

Insulin-loaded hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic acid hydrogels used as rectal suppositories to regulate the blood glucose of diabetic rats.

Int J Biol Macromol 2019 Jan 9;121:1346-1353. Epub 2018 Sep 9.

School of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, PR China.

The purpose of this study was developing a novel hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic acid (HPMC-co-PAM-co-PMAA) hydrogel, which was used as rectal suppository to regulate the blood glucose of diabetes. HPMC-co-PAM-co-PMAA hydrogel was fabricated via free-radical polymerization. Fourier transform infrared spectroscopy (FTIR) and Raman spectra were used to confirm the fabrication of HPMC-co-PAM-co-PMAA hydrogel. Their inner morphology was observed with scanning electron microscope (SEM). The extracts of hydrogel were applied to study their cell viability. The hypoglycemic effects of insulin (INS)-loaded HPMC-co-PAM-co-PMAA hydrogels were investigated by rectal administration. FTIR and Raman spectra confirmed the obtaining of HPMC-co-PAM-co-PMAA hydrogels. Many micro-pores were found in the SEM photograph of HPMC-co-PAM-co-PMAA hydrogels. Cell experiments indicated that HPMC-co-PAM-co-PMAA hydrogel was out of cytotoxicity. In vitro release profiles showed that INS-loaded hydrogel could release INS at a continuous manner in pH 7.4 buffer (rectal conditions). Animal experiments suggested that INS-loaded hydrogel had an obvious hypoglycemic effect. Therefore, as a convenient and economic method of administration, INS-loaded HPMC-co-PAM-co-PMAA hydrogels could be used as rectal suppositories to regulate blood glucose.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.09.044DOI Listing
January 2019

Effect of Achieving Minimal Disease Activity on the Progression of Subclinical Atherosclerosis and Arterial Stiffness: A Prospective Cohort Study in Psoriatic Arthritis.

Arthritis Rheumatol 2019 02 5;71(2):271-280. Epub 2019 Jan 5.

The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.

Objective: To investigate the effects of achieving minimal disease activity (MDA) on the progression of subclinical atherosclerosis and arterial stiffness in patients with psoriatic arthritis (PsA).

Methods: A total of 101 consecutive patients with PsA were recruited for this prospective cohort study. All patients received protocolized treatment targeting MDA for a period of 2 years. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. The primary outcome measure was the effect of achieving MDA at 12 months (MDA group) on the progression of subclinical atherosclerosis over a period of 24 months. Secondary objectives were to compare the changes in arterial stiffness markers over 24 months between the MDA and non-MDA groups, as well as the changes in subclinical atherosclerosis and arterial stiffness markers in patients who achieved MDA at each visit from month 12 through month 24 (sustained MDA [sMDA]).

Results: Ninety PsA patients (mean ± SD age 50 ± 11 years, 58% male [n = 52]) who completed 24 months of follow-up were included in this analysis. Fifty-seven patients (63%) had achieved MDA at 12 months. Subclinical atherosclerosis and arterial stiffness outcomes were similar between the MDA and non-MDA groups. Forty-one patients (46%) achieved sMDA. As shown by multivariate analysis, achieving sMDA had a protective effect on plaque progression (odds ratio 0.273 [95% confidence interval 0.088-0.846], P = 0.024), and less of an increase in total plaque area, mean intima-media thickness, and augmentation index values after adjustment for covariates.

Conclusion: Our results support the recommendation that once MDA is achieved, it should ideally be maintained for a prolonged period in order to prevent progression of carotid atherosclerosis and arterial stiffness in patients with PsA.
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http://dx.doi.org/10.1002/art.40695DOI Listing
February 2019

Polyelectrolyte Complex Nanoparticles Based on Methoxy Poly(Ethylene Glycol)-B-Poly (ε-Caprolactone) Carboxylates and Chitosan for Delivery of Tolbutamide.

J Biomater Sci Polym Ed 2018 10 29;29(15):1799-1811. Epub 2018 Sep 29.

c School of Chemical and Pharmaceutical Engineering , Hebei University of Science and Technology , Shijiazhuang , P.R. China.

In this study, a novel chitosan (CS)-modified nanoparticles (NPs) were developed to orally deliver tolbutamide (TOL). Methoxy poly(ethylene glycol)- b-poly(ε-caprolactone) carboxylates (mPEG-b-PCL) was synthesized via an esterification reaction. CS-modified mPEG-b-PCL-COOH NPs ([email protected]) were fabricated by injecting mPEG-b-PCL-COOH NPs suspension (1.0 mg/mL) into CS solution (1.0 mg/mL, pH 5.0). Fourier transform infrared spectroscopy (FTIR) spectra were used to confirm the obtaining of mPEG-b-PCL-COOH. Transmission electron microscope (TEM) was carried out to observe morphology of all NPs. Nano ZS90 Malvern ParticleSizer were used to monitor the size distribution of obtained NPs. Thermogravimetry analysis (TGA) was performed to investigate the thermostability of [email protected] In vitro TOL release profiles were carried out in pH 1.2 and 7.4 buffers. FTIR spectra confirmed the obtaining of mPEG-b-PCL-COOH. TGA curves indicated that the protection of CS shells improved the thermostability of mPEG-b-PCL-COOH NPs. Cell tests indicated the [email protected] had no obvious cytotoxicity, and they were easily taken up by 293T cells. In vitro release profiles showed that 91.0 ± 1.9% of encapsulated TOL were released from [email protected] in pH 7.4 buffer. Therefore, the positive potential of [email protected] could increase their combining capacity with intestinal mucosal cells. Finally, these NPs would improve the bioavailability of hydrophobic drugs.
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http://dx.doi.org/10.1080/09205063.2018.1498720DOI Listing
October 2018

Association of NOS1 gene polymorphisms with cerebral palsy in a Han Chinese population: a case-control study.

BMC Med Genomics 2018 Jun 25;11(1):56. Epub 2018 Jun 25.

Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Wanyuan Road 399, Minhang District, Shanghai, 201102, China.

Background: Cerebral palsy (CP) is the leading cause of motor disability in children; however, its pathogenesis is unknown in most cases. Growing evidence suggests that Nitric oxide synthase 1 (NOS1) is involved in neural development and neurologic diseases. The purpose of this study was to determine whether genetic variants of NOS1 contribute to CP susceptibility in a Han Chinese population.

Methods: A case-control study involving 652 CP patients and 636 healthy controls was conducted. Six SNPs in the NOS1 gene (rs3782219, rs6490121, rs2293054, rs10774909, rs3741475, and rs2682826) were selected, and the MassARRAY typing technique was applied for genotyping. Data analysis was conducted using SHEsis online software, and multiple test corrections were performed using SNPSpD online software.

Results: There were no significant differences in genotype and allele frequencies between patients and controls for the SNPs except rs6490121, which deviated from Hardy-Weinberg equilibrium and was excluded from further analyses. Subgroup analysis revealed differences in genotype frequencies between the CP with neonatal encephalopathy group (CP + NE) and control group for rs10774909, rs3741475, and rs2682826 (after SNPSpD correction, p = 0.004, 0.012, and 0.002, respectively). The T allele of NOS1 SNP rs3782219 was negatively associated with spastic quadriplegia (OR = 0.742, 95% CI = 0.600-0.918, after SNPSpD correction, p = 0.023). There were no differences in allele or genotype frequencies between CP subgroups and controls for the other genetic polymorphisms.

Conclusions: NOS1 is associated with CP + NE and spastic quadriplegia, suggesting that NOS1 is likely involved in the pathogenesis of CP and that it is a potential therapeutic target for treatment of cerebral injury.
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http://dx.doi.org/10.1186/s12920-018-0374-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019815PMC
June 2018

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

J Rheumatol 2018 08 15;45(9):1229-1239. Epub 2018 May 15.

From the Department of Medicine and Therapeutics, and Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong; Department of Medicine, Queen Elizabeth Hospital; Department of Medicine, Tai Po Hospital; Department of Medicine, Tseung Kwan O Hospital; Department of Medicine, Pamela Youde Nethersole Eastern Hospital; Department of Medicine, Kwong Wah Hospital, Hong Kong.

Objective: To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA).

Methods: This was an open-label study in which 120 patients with early RA were randomized to receive 1 year of tight control treatment. Group 1 (n = 60) aimed to achieve SDAI ≤ 3.3 and Group 2 (n = 60), DAS28 < 2.6. Pulse wave velocity (PWV) and augmentation index (AIx) were measured at baseline and 12 months. A posthoc analysis was also performed to ascertain whether achieving sustained remission could prevent progression in arterial stiffness.

Results: The proportions of patients receiving methotrexate monotherapy were significantly lower in Group 1 throughout the study period. At 12 months, the proportions of patients achieving DAS28 and SDAI remission, and the change in PWV and AIx, were comparable between the 2 groups. In view of the lack of differences between the 2 groups, a posthoc analysis was performed at Month 12, including all 110 patients with PWV, to elucidate the independent predictors associated with the change in PWV. Multivariate analysis revealed that achieving sustained DAS28 remission at months 6, 9, and 12 and a shorter disease duration were independent explanatory variables associated with less progression of PWV.

Conclusion: With limited access to biologic disease-modifying antirheumatic drugs, treatment efforts toward DAS28 and SDAI remission had similar effects in preventing the progression of arterial stiffness at 1 year. However, achieving sustained DAS28 remission was associated with a significantly greater improvement in PWV. [Clinical Trial registration: Clinicaltrial.gov NCT01768923.].
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http://dx.doi.org/10.3899/jrheum.171128DOI Listing
August 2018

Combined Analysis of Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy.

Front Neurol 2018 22;9:182. Epub 2018 Mar 22.

Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Interleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention.

Objective: The purpose of this study was to investigate whether gene polymorphisms and plasma protein expression are associated with CP and to analyze the role of IL-10 in CP.

Methods: A total of 282 CP patients and 197 healthy controls were genotyped for polymorphisms (rs1554286, rs1518111, rs3024490, rs1800871, and rs1800896). Among them, 95 CP patients and 93 healthy controls were selected for plasma IL-10 measurement.

Results: The differences in the rs3024490 ( = 0.033) and rs1800871 ( = 0.033) allele frequencies of were determined between CP patients and controls. The frequencies of allele and genotype between CP patients with spastic tetraplegia and normal controls of polymorphisms showed significant differences for rs1554286, rs151811, rs3024490, rs1800871, and rs1800896 (  = 0.015, 0.009, 0.006, 0.003, and 0.006,  = 0.039, 0.018, 0.027, 0.012, and 0.03, respectively). The plasma IL-10 protein level in CP patients was higher than normal controls (9.13 ± 0.77 vs. 6.73 ± 0.63 pg/ml,  = 0.017). IL-10 polymorphisms and protein association analysis showed that the TT genotype had higher plasma IL-10 protein levels compared to the GG + GT genotype at rs3024490 (11.14 ± 7.27 vs. 7.44 ± 6.95 pg/ml,  = 0.045, respectively) in CP cases.

Conclusion: These findings provide an important contribution toward explaining the pleiotropic role of IL-10 in the complex etiology of CP.
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http://dx.doi.org/10.3389/fneur.2018.00182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874289PMC
March 2018
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