Effect of kidney-reinforcing,blood-activating and stasis-removing recipes on adhesion molecule expression of bone marrow mesenchymal stem cells from chronic aplastic anemia patients

OBJECTIVE:To explore the effect of kidney-reinforcing,blood-activating and stasis-removing recipes on adhesion molecule expression of bone marrow mesenchymal stem cells(MSCs) from patients with chronic aplastic anemia(CAA).METHODS:We used threeTraditional Chinese Medicine recipes,namely a kidney-reinforcing recipe(KRR),blood-activating and stasis-removing recipe(BASRR),and kidney-reinforcing,blood-activating and stasis-removing recipe(KRBASRR),and a normal saline control to prepare herbal medicine serum in Sprague Dawley rats.Thirty CAA patients were enrolled in the experimental group,including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients.Ten healthy individuals were included in the control group.MSCs were isolated from bone marrow samples,and the cell density was observed to measure their proliferation ability by microscopy on days 2,7,and 14 after isolation.In addition,the expression of adhesion molecules of bone marrow MSCs(CD106,CD49d,CD31 and CD44) were detected by flow cytometry after 48 h of treatment with the four different herbal medicine serums.RESULTS:The proliferation of MSCs from kidney-Yang deficient and kidney-Yin deficient patients was weaker than that of MSCs from the control group.The expression of all adhesion molecules of bone marrow MSCs from CAA patients was obviously lower than that in the control group(P< 0.01).The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was lower than in those with a kidney-yang deficiency(P< 0.05 and P<0.01,respectively).For kidney-Yang deficient patients,CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group(P<0.01),while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups(P<0.01).For kidney-Yin deficient patients,CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group(P<0.05),while CD31 and CD44 expression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups(P< 0.05 and P<0.01,respectively).CONCLUSION:The bone marrow microenvironment in CAA patients is abnormal.The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin deficient patients by improving the expression levels of MSC adhesion molecules.

HPDL deficiency causes a neuromuscular disease by impairing the mitochondrial respiration

Mitochondrial diseases are caused by variants in both mitochondrial and nuclear genomes.A nuclear gene HPDL(4-hydroxyphenylpyruvate dioxygenase-like),which encodes an intermembrane mitochondrial protein,has been recently implicated in causing a neurodegenerative disease characterized by pediatric-onset spastic movement phenotypes.Here,we report six Chinese patients with bi-allelic HPDL pathogenic variants from four unrelated families showing neuropathic symptoms of variable severity,including developmental delay/intellectual disability,spasm,and hypertonia.Seven different pathogenic variants are identified,of which five are novel.Both fibroblasts and immortalized lymphocytes derived from patients show impaired mitochondrial respiratory function,which is also observed in HPDL-knockdown(KD)He La cells.In these He La cells,overexpression of a wild-type HPDL gene can rescue the respiratory phenotype of oxygen consumption rate.In addition,a decreased activity of the oxidative phosphorylation(OXPHOS)complex II is observed in patient-derived lymphocytes and HPDL-KD He La cells,further supporting an essential role of HPDL in the mitochondrial respiratory chain.Collectively,our data expand the clinical and mutational spectra of this mitochondrial neuropathy and further delineate the possible disease mechanism involving the impairment of the OXPHOS complex II activity due to the bi-allelic inactivations of HPDL.

Implementing comprehensive genetic carrier screening in China―Harnessing the power of genomic medicine for the effective prevention/management of birth defects and rare genetic diseases in China

Carrier screening had been demonstrated as a powerful practice in preventing selected severe genetic disorders. This practice is expanding its scope and impact in the era of next-generation sequencing. Empirical and theoretical data support the utility of expanded carrier screening. The authors propose a comprehensive carrier screening program as a main component of the first-tier measure in preventing severe genetic disorders and birth defects in China. We discussed the key principles and important aspects to ensure the success of such a program. The authors believe this program will play a pivotal role in our endeavor for a healthier nation.

CNVbase:Batch identification of novel and rare copy number variations based on multi-ethnic population data

Human genetic variants have long been known to play an important role in both Mendelian disorders and common diseases. Notably, pathogenic variants are not limited to single-nucleotide variants. It has become apparent that human diseases can also be caused by copy number variations （CNVs）, especially patient- specific novel CNVs （lafrate et al., 2004; Sebat et al., 2004; Redon et al., 2006; LuDski, 2007; Zhan~ et al.. 2009： Wu et al.. 2015）.

Next-generation sequencing based molecular testing is an equalizer for diagnostic service of rare genetic disorders in China

The traditional approach of clinical genetic practice,known as the phenotype-first approach,usually starts with a thorough review of electronic medical records of the patient and a complete evaluation of patient's clinical presentation,as well as a survey of family history.Often more than one experienced clinical geneticists will order a variety of additional laboratory or imaging tests to obtain relevant information in order to reach a reasonable clinical diagnosis.Finally,molecular testing often helps to confirm the clinical diagnosis.This practice requires the availability of electronic medical records,well trained clinical geneticists who are able to perform relevant clinical evaluation,order appropriate tests and understand the molecular reports.These critical components of clinical genetics are mostly lacking in China today,1 as a consequence,most of patients with genetic condition do not receive a proper evaluation by clinical geneticists,only a small percent of patients received a clinical diagnosis and the majority remains undiagnosed for life.