A Novel Splicing Mutation c.335-1 G > A in the Cardiac Transcription Factor NKX2-5 Leads to Familial Atrial Septal Defect Through miR-19 and PYK2.

Mutations of NKX2-5 largely contribute to congenital heart diseases (CHDs), especially atrial septal defect (ASD). We identified a novel heterozygous splicing mutation c.335-1G > A in NKX2-5 gene in an ASD family via whole exome sequencing (WES) and linkage analysis. Utilizing the human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) as a disease model, we showed that haploinsufficiency of NKX2-5 contributed to aberrant orchestration of apoptosis and proliferation in ASD patient-derived hiPSC-CMs. RNA-seq profiling and dual-luciferase reporter assay revealed that NKX2-5 acts upstream of PYK2 via miR-19a and miR-19b (miR-19a/b) to regulate cardiomyocyte apoptosis. Meanwhile, miR-19a/b are also downstream mediators of NKX2-5 during cardiomyocyte proliferation. The novel splicing mutation c.335-1G > A in NKX2-5 and its potential pathogenic roles in ASD were demonstrated. Our work provides clues not only for deep understanding of NKX2-5 in cardia development, but also for better knowledge in the molecular mechanisms of CHDs.

Enhancing definitive hematopoiesis signals improves the efficiency of natural killer cell generation derived from human embryonic stem cells / 免疫学杂志

This study explores the effects of enhancing the definitive hematopoiesis(DH)signals during the differentiation of human embryonic stem cells(hESCs)into hematopoietic stem/progenitor cells on the generation efficiency and effector function of natural killer(NK)cells generated from hESCs(also known as hESC-NK cells).The hESC(H1)were transformed into embryoid bodies(Ebs)by centrifugation,and during the induction of K562,were used to analyze the efficiency of hematopoietic differentiation,the efficiency of NK cell generation from hESC,the in vitro effector functions,and the expression of effector function related surface receptors.Compared to the control group,the DH group had a significant increase in the number of arterial hematopoietic endothelial cells(CD34+DLL4+)and a significant decrease in primitive hematopoietic related cells(CD34-CD43+)on day 8 of hematopoietic differentiation(P<0.05).On day 28 of NK cell differentiation,the DH group demonstrated a significant increase in the number of NK cells(CD45+CD56+),while a slight increase in the expression of effector function-related molecules such as IFN-γ,Granzyme B,Perforin and CD107a without statistical significance.Furthermore,the activation receptors CD16a and CD69 were significantly increased,NKP46 was significantly decreased,the inhibitory receptor NKG2A was significantly increased,while CD96 was significantly decreased on hESC-NK cells of DH groups(P<0.05).Conclusively,enhancing the signals for definitive hematopoiesis during hESC differentiation into hematopoietic stem/progenitor cells significantly improves the yield of NK cells and the expression of CD16a without affecting their in vitro effector functions.Our study provides a new approach to improving the efficiency of hESC-NK cell or iPSC-NK cell generation.

Innovation and application of case-based PBL teaching model in the teaching of medical genetics / 中华医学教育探索杂志

Since 2008, we have carried out a systematic exploration of case-based PBL teaching model in clinical medical undergraduates. The questionnaire results show that the students are highly satisfied with the course setting and the teaching quality of teachers, and have a strong sense of gain in the cultivation of learning interest and the improvement of learning capacity. The analysis of the examination results in the past ten years also reveals that the excellent student rate of the class with case-based PBL seminars have been significantly improved. The retrospective analysis also shows that the students' knowledge level, professional background, class size, and the curriculum system settings have significant influences on the teaching effect. Therefore, for students with different academic systems and majors, PBL teaching mode should be designed differently to achieve better teaching effect.

Headway duo microcatheter combined with Onyx glue in preoperative embolization of meningiomas / 中华神经医学杂志

Objective To evaluate the clinical value of Headway duo microcatheter combined with Onyx glue in embolization ofmeningiomas.Methods A retrospective analysis on clinical data of 12 patients with meningiomas,admitted to our hospital from December 2015 to March 2017,was performed.According to the blood supply typing ofManelfe meningiomas,5 were type Ⅰ,3 were type Ⅱ,2 were type Ⅲ,and 2 were type Ⅳ.The degrees of embolization were compared by DSA tumor staining before and after embolization;and complications of embolization were recorded.Results Cerebral angiography after embolization demonstrated complete embolization in 5 patients,subtotal embolization in 5,partial embolization in 2,and small amount of embolization in 0.Only 2 had head and face pain in the process of embolization,and these syndromes disappeared once the operation stopped.The mean average blood loss in the surgery was 685 mL and the mean surgical time was 4.45 h.Conclusion Headway duo microcatheter combined with Onyx glue in the embolization of intracranial meningiomas can play a good role in blocking blood flow,and results suggest that this method is safe and effective,worth of clinical promotion.

Neuronavigation assisted endoscopic surgery of hypertensive intracerebral hemorrhage / 中华神经医学杂志

Objective To explore the clinical effect of neuronavigation assisted endoscopic surgery in treatment of patients with hypertensive intracerebral hemorrhage. Methods Fifty patients with hypertensive cerebral hemorrhage, admitted to our hospital from June 2014 to June 2016, were selected. All patients were treated with neuronavigation guided endoscopic surgery. Their clinical data and surgical efficacies were retrospectively analyzed. Results Patients' head CT was reviewed 6 h after operation, and residual hematoma volume was less than 15％among 31 patients, and in the ranges of 15％-30％among 14 patients. Re-bleeding occurred in 4 patients, and death in one patient. Glasgow outcome scale (GOS) of 49 patients 6 months after operation indicated vegetative state in 5 patients, severe disability in 9, moderate disability in 10, and good recovery in 25. Conclusion Neuronavigation assisted endoscopic surgery has good clinical effect on patients with hypertensive intracerebral hemorrhage in terms of few complications and high safety, so it is worthy of promotion and application in clinical practice.

Modified large craniectomy decompression in the treatment of malignant middle cerebral artery infarction / 中国现代医生

Objective To explore the therapeutic effect and prognosis of modified large craniectomy decompression in the treatment of patients with malignant middle cerebral artery infarction. Methods Forty malignant cerebral artery in-farction patients were treated with modified large craniectomy decompression from July 2010 to July 2013 in our hospi-tal , set as the treatment group; retrospective analyzed 40 cerebral infarction patients in our hospital from July 2006 to July 2009 which were adopted traditional operation bone flap decompression treatment as the control group. The recov-ery stage, the rapeutic effect and prognosis were compared between two group patients. Results The survival rate in the treatment group was 90%(36/40),and was significantly higher than 57.50%(23/40) in the control group, the differ-ence was statistically significant (P<0.05);Postoperative complications in treatment group were significantly lower than the control group,the differences were statistically significant(P<0.05). Conclusion Modified large craniectomy decom-pression in the treatment patients with malignant middle cerebral artery infarction ,can significantly improve the thera-peutic effect, and reduce postoperative complications, the safety is excellence,and is worth the clinical promotion.