The chemical reprogramming of unipotent adult germ cells towards authentic pluripotency and de novo establishment of imprinting

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.

Correlation Between Paraoxonase-1 Gene Q192R Polymorphism and Clopidogrel Resistance / 医药导报

Objective To investigate the correlation between Paraoxonase-1 (PON-1) gene Q192R polymorphism and clopidogrel resistance (CR). Methods A total of 118 patients with coronary artery disease diagnosed by coronary angiography or coronary artery CT angiography were enrolled. Platelet aggregation rate was assessed by ADP-induced light-transmittance aggregometry after the patients received adequate clopidogrel pretreatment.The patients were divided into (clopidogrel resistance group (CR group) and non-clopidogrel resistance group (NCR group) according to the ADP-induced platelet aggregation rate. The gene of Q192R was detected by MassARRAY Time of Flight Mass Spectrometry.The genotypes and allele frequencies between the two groups were compared. Results According to the ADP-induced platelet aggregation rate,25 patients were defined as clopidogrel resistant and 93 as non-clopidogrel resistant.The incidence of clopidogrel resistance was 21.2％.Three frequencies of genotype RR,QR and QQ were 36. 0％,52. 0％ and 12. 0％ in CR group, and 32. 2％,57. 0％ and 10. 8％ in NCR group, respectively.The frequencies of Q and R allele in CR group were 62.0％ and 38.0％,and those in NCR group were 60.8％ and 39.2％.No significant differences in genotype and allele frequency were found between CR group and NCR group (P>0.05). Conclusion The PON-1 gene Q192R polymorphism is not associated with clopidogrel resistance in patients with CHD.

Intravascular Ultrasonic Features of Unstable Atherosclerotic Plaques in Unstable Angina patients / 中国基层医药

Objective To investigate the characteristics of plaque morphology of the patients with unstable angina(UA)by intravascular ultrasound(IVUS). Methods24 patients with stable angina pectoris(SA)and 33 patients with unstable angina(UA)were examined by coronary coronary arteriograph(CAG)and intravascular ultrasound(IVUS).The culprit lesions about the characteristic of the plaque were studied,the external elastic membrane cross-sectional area and lumen cross-sectional area were measured,the plaque area,plaque burden,eccentricity index were calculated,and the remodeling index was examined. ResultsExternal elastic membrane area,plaque area and vascular remodeling ratio were significantly greater at target lesions in UA patients than in patients with SA(P＜0.05).Positive remodeling and soft plaque were predominantly in UA patients(P＜0.05). ConclusionThe morphological features of coronary artery plaques in UA group were significantly different from those in SA group.More soft plaque,plaque rupture,thrombus formation,and positive remodeling were found in UA patients compared with SA patients.

Assessment of coronary artery disease with second harmonic myocardial perfusion contrast echocardiography / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To assess the relationship between myocardial regional perfusion using second harmonic myocardial contrast echocardiography (MCE) by venous injection of Levovist and coronary artery stenosis detected by coronary angiography to determine whe ther MCE can be used to detect coronary artery disease (CAD) and its sensitivity and specificity for detecting CAD.</p><p><b>METHODS</b>Thirty-six patients who underwent coronary artery angiography and MCE formed the study groups. Ten myocardial segments (5 each in the apical two- and four-chamber views) from the images were scored for detecting myocardial perfusion as follows: 1, normal perfusion; 2, decreased perfusion; and 3, perfusion defect. The arteries were classified as normal or diseased. The diseased arteries were classified into three groups according to the perfusion scores.</p><p><b>RESULTS</b>There were significant differences in coronary diameter stenosis among the different perfusion score groups (P < 0.001). There were 10 total occluded arteries, and the myocardial perfusion scores were different because of different collateral circulation. In the normal perfusion group (Group A), the coronary diameter stenosis was 65% +/- 12%, and the myocardial perfusion score index was 1 +/- 0.00. In the decreased perfusion group (Group B), the average coronary diameter stenosis was 82% +/- 8%, and the myocardial perfusion score was 1.93 +/- 0.16. The diameter stenosis was less than 85% in 63% of the coronary arteries (including diameter stenosis < or = 75% in 12% of the vessels). The diameter stenosis was 85%-90% in 22% of the coronary arteries and > 90% in 15% of the arteries. In the perfusion defect group (Group C), the average diameter stenosis was 90% +/- 6%, and the myocardial perfusion score index was 2.89 +/- 0.24. The diameter stenosis was > or = 85% in 94% of the coronary arteries, and the diameter stenosis was < 85% and > 75% only in 6% of the coronary arteries. The overall sensitivity and specificity of MCE in identifying angiographic coronary diameter stenosis was 67% and 100%, respectively. The false negative rate was 32.6% for the 108 coronary arteries. Further subdivided analysis showed the sensitivities in Groups A, B and C were 0, 100%, and 100%, respectively. The sensitivity increased with increased lumen diameter stenosis of coronary arteries.</p><p><b>CONCLUSIONS</b>There is a close relationship between coronary artery stenosis and MCE perfusion scores. MCE with venous injection of new generation contrast can define the presence of CAD and lesion graded classifications. Some disagreements between perfusion score and coronary diameter of stenosis may indicate other factors such as different collateral circulation, which should be further investigated. As artery stenosis increases, the sensitivity of MCE is increased.</p>