3 results
Brain transcriptome-wide association study implicates novel risk genes underlying schizophrenia risk
- Chengcheng Zhang, Xiaojing Li, Liansheng Zhao, Wanjun Guo, Wei Deng, Qiang Wang, Xun Hu, Xiangdong Du, Pak Chung Sham, Xiongjian Luo, Tao Li
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- Journal:
- Psychological Medicine / Volume 53 / Issue 14 / October 2023
- Published online by Cambridge University Press:
- 24 April 2023, pp. 6867-6877
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Background
To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ).
MethodsWe systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ.
ResultsTWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ.
ConclusionsOur findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.
A comparison of cardiac post-conditioning and remote pre-conditioning in paediatric cardiac surgery
- Wanjun Luo, Ming Zhu, Rimao Huang, Yangde Zhang
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- Journal:
- Cardiology in the Young / Volume 21 / Issue 3 / June 2011
- Published online by Cambridge University Press:
- 25 January 2011, pp. 266-270
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Background
Remote ischaemic pre-conditioning and cardiac ischaemic post-conditioning provide myocardial protection in cardiac surgery. However, these two endogenous strategies have not been directly compared in a clinical setting. The purpose of this study was to compare the efficacy of remote ischaemic pre-conditioning and post-conditioning in providing myocardial protection to children undergoing cardiopulmonary bypass for surgical repair of ventricular septal defect.
MethodsWe randomly assigned 60 paediatric patients scheduled for surgical correction of congenital ventricular septal defect to the post-conditioning group (n = 20), remote pre-conditioning group (n = 20), or control group (n = 20). Post-conditioning consisted of 30 seconds of ischaemia and 30 seconds of reperfusion achieved by clamping and unclamping the aorta, repeated three times over 3 minutes immediately after cardioplegic arrest. Remote ischaemic pre-conditioning consisted of 5 minutes of lower limb ischaemia followed by 5 minutes of reperfusion using a blood-pressure cuff inflated to a pressure of 200 millimetres of mercury, also repeated three times over 30 minutes. We assayed creatine kinase-MB, troponin I.
ResultsMean age, cardiopulmonary bypass times, and aortic cross-clamp times were matched across groups. Both post-conditioning and remote ischaemic pre-conditioning reduced the peak release of creatine kinase-MB (86.1 plus or minus 24.1 units per litre and 92.8 plus or minus 20.6 units per litre, respectively, versus 111.0 plus or minus 44.6 units per litre in the control, p less than 0.05) and troponin I (0.28 plus or minus 0.10 nanogram per millilitre and 0.26 plus or minus 0.09 nanogram per millilitre, respectively, versus 0.49 plus or minus 0.19 nanogram per millilitre in the control group, p less than 0.05).
ConclusionsOur study demonstrates that ischaemic post-conditioning and remote ischaemic pre-conditioning provide comparable myocardial benefit in children undergoing cold blood cardioplegic arrest.
Does cardioplegia leave room for postconditioning in paediatric cardiac surgery?*
- Wanjun Luo, Bei Li, Guoqiang Lin, Ri Chen, Rimao Huang
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- Journal:
- Cardiology in the Young / Volume 18 / Issue 3 / June 2008
- Published online by Cambridge University Press:
- 01 June 2008, pp. 282-287
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Background
Postconditioning by brief episodes of ischaemia performed just at the time of reperfusion have been shown to reduce the size of infarcts in animal models, and in the clinical setting of percutaneous cardiac intervention. The clinical applicability of postconditioning in cardiac surgery remains to be determined. We investigated the effect of postconditioning on myocardial protection in children undergoing cardiac surgery.
MethodsWe randomly assigned 40 patients scheduled for surgical correction of congenitally malformed hearts under cold blood cardioplegic arrest to postconditioning or control treatment. Postconditioning was performed by two cycles of 30 seconds ischaemia and 30 seconds reperfusion using aortic reclamping, and declamping started 30 seconds after cardioplegic arrest. We assayed creatine kinase-MB, troponin I, transcardiac release of lactate and neutrophil counts.
ResultsThe types of procedure, age, bypass and aortic cross-clamping times were similar in both groups. The postoperative peaks of creatine kinase-MB and troponin I were lower after aortic de-clamping in the postconditioned patients compared with their controls (128 ± 48 units per liter as opposed to 199 ± 79 units per liter, p = 0.016, and 0.34 ± 0.21 nanograms per milliliter as opposed to 0.61 ± 0.53 nanograms per milliliter, p = 0.05), with reduced inotropic scores in those submitted to postconditioning compared with their controls (4.8 ± 3.1 versus 2.3 ± 1.5, p = 0.036). Transcardiac release of lactate was reduced in the postconditioned patients compared with their controls (0.10 ± 0.27 as opposed to 0.37 ± 0.43 millimols per liter, p = 0.048). No differences between groups were found for transcardiac neutrophil count during reperfusion (10.8 ± 6.3% for postconditioning versus 14.0 ± 8.7% for controls, p = 0.48).
ConclusionsOur study demonstrates that postconditioning may protect the myocardium of children undergoing cold blood cardioplegic arrest. These data support the need for a larger clinical trial of postconditiong in children undergoing cardiac surgery.