Objective To investigate the mid- to long-term follow-up results of ascending aorta (AAO)-descending thoracic aorta (DTA) bypass grafting via median sternotomy incision for the treatment of complex aortic arch coarctation. Methods A retrospective analysis was conducted on the clinical data of patients with complex aortic arch coarctation who underwent AAO-DTA bypass grafting via median sternotomy incision at the First Hospital of Tsinghua University from August 2004 to May 2017. Results A total of 7 patients were enrolled, including 4 males and 3 females, aged (13.3±4.6) years, and weighted (40.2±12.2) kg. Six (85.7%) patients had concomitant upper limb hypertension. Four patients were aortic arch coarctation combined with intracardiac malformations, two were post-operative restenosis, and 1 was post-operative restenosis combined with intracardiac malformation. All patients underwent surgery under cardiopulmonary bypass. There were no perioperative deaths or major complications. The pre-operative upper-lower limb pressure difference was (39.3±19.2) mm Hg, which decreased to (2.9±2.7) mm Hg post-operatively (P<0.01). The follow-up period was (14.9±5.9) years. There were no long-term deaths or artificial graft-related complications. Except for one patient who still had mild hypertension, the blood pressure of the remaining patients returned to normal. Conclusion AAO-DTA bypass grafting via median sternotomy incision for the treatment of complex aortic arch coarctation can effectively reduce upper limb blood pressure and the upper-lower limb arterial pressure difference, has fewer complications, and demonstrates satisfactory mid- to long-term efficacy.

Anchored in the realities of contemporary medical education,this study dissects the persistent bottlenecks that impede the seamless embedding of Red Medical Culture-China's revolutionary medical ethos underpinned by humanitarian com-mitment and public-health dedication-into medical students' ideological-and-political education(IPE).Key impediments include shallow integration,misalignment with modern pedagogical paradigms,paucity of tailored resources,and a dearth of qualified fac-ulty.To counter these constraints,we articulate a multi-pronged praxis that simultaneously preserves and reinvigorates Red Medi-cal Culture.Pilot programs indicated that systematic incorporation of this heritage cultivated socially accountable professionals who internalized historical mission,upheld ethical standards,and embraced humanistic patient-centered care,while concurrently sharpening critical innovation and consolidating comprehensive professional competence.

Anchored in the realities of contemporary medical education,this study dissects the persistent bottlenecks that impede the seamless embedding of Red Medical Culture-China's revolutionary medical ethos underpinned by humanitarian com-mitment and public-health dedication-into medical students' ideological-and-political education(IPE).Key impediments include shallow integration,misalignment with modern pedagogical paradigms,paucity of tailored resources,and a dearth of qualified fac-ulty.To counter these constraints,we articulate a multi-pronged praxis that simultaneously preserves and reinvigorates Red Medi-cal Culture.Pilot programs indicated that systematic incorporation of this heritage cultivated socially accountable professionals who internalized historical mission,upheld ethical standards,and embraced humanistic patient-centered care,while concurrently sharpening critical innovation and consolidating comprehensive professional competence.

Regenerative therapy holds great promise in the development of cures of some untreatable diseases such as cardiovascular diseases, and pluripotent stem cells (PSCs) including induced PSCs (iPSCs) are the most important regenerative seed cells. Recently, differentiation of human PSCs into functional tissues and cells in vitro has been widely reported. However, although porcine reports are rare they are quite essential, as the pig is an important animal model for the in vitro generation of human organs. In this study, we reprogramed porcine embryonic fibroblasts into porcine iPSCs (piPSCs), and differentiated them into cluster of differentiation 31 (CD31)-positive endothelial cells (ECs) (piPSC-derived ECs, piPS-ECs) using an optimized single-layer culture method. During differentiation, we observed that a combination of GSK3β inhibitor (CHIR99021) and bone morphogenetic protein 4 (BMP4) promoted mesodermal differentiation, resulting in higher proportions of CD31-positive cells than those from separate CHIR99021 or BMP4 treatment. Importantly, the piPS-ECs showed comparable morphological and functional properties to immortalized porcine aortic ECs, which are capable of taking up low-density lipoprotein and forming network structures on Matrigel. Our study, which is the first trial on a species other than human and mouse, has provided an optimized single-layer culture method for obtaining ECs from porcine PSCs. Our approach can be beneficial when evaluating autologous EC transplantation in pig models.

Regenerative therapy holds great promise in the development of cures of some untreatable diseases such as cardiovascular diseases, and pluripotent stem cells (PSCs) including induced PSCs (iPSCs) are the most important regenerative seed cells. Recently, differentiation of human PSCs into functional tissues and cells in vitro has been widely reported. However, although porcine reports are rare they are quite essential, as the pig is an important animal model for the in vitro generation of human organs. In this study, we reprogramed porcine embryonic fibroblasts into porcine iPSCs (piPSCs), and differentiated them into cluster of differentiation 31 (CD31)-positive endothelial cells (ECs) (piPSC-derived ECs, piPS-ECs) using an optimized single-layer culture method. During differentiation, we observed that a combination of GSK3β inhibitor (CHIR99021) and bone morphogenetic protein 4 (BMP4) promoted mesodermal differentiation, resulting in higher proportions of CD31-positive cells than those from separate CHIR99021 or BMP4 treatment. Importantly, the piPS-ECs showed comparable morphological and functional properties to immortalized porcine aortic ECs, which are capable of taking up low-density lipoprotein and forming network structures on Matrigel. Our study, which is the first trial on a species other than human and mouse, has provided an optimized single-layer culture method for obtaining ECs from porcine PSCs. Our approach can be beneficial when evaluating autologous EC transplantation in pig models.

Animals ; Bone Morphogenetic Protein 4 ; Cardiovascular Diseases ; Endothelial Cells ; Fibroblasts ; Humans ; In Vitro Techniques ; Induced Pluripotent Stem Cells ; Lipoproteins ; Mesoderm ; Methods ; Mice ; Models, Animal ; Pluripotent Stem Cells ; Swine

A 63-year-old male patient took tamsulosin hydrochloride sustained release capsules 0.2 mg daily and Qianliexin capsules 2 g thrice daily by himself for urinary urgency and urodynia. Twenty-five days later, he developed itchy skin, deep brown urine, nausea, fatigue, and loss of appetite. Laboratory tests showed alanine aminotransferase (ALT) 265 U/L, aspartate aminotransferase (AST) 163 U/L, total bilirubin (TBil) 155.1 μmol/L, direct bilirubin (DBil) 74.7 μmol/L, indirect bilirubin (IBil) 80.4 μmol/L, alkaline phosphatase (ALP) 261 U/L, and gamma-glutamyltransferase (γ-GT) 184 U/L. Liver biopsy showed the cholestatic liver injury. He was diagnosed as acute drug-induced liver injury, which might be related to the above 2 drugs. The above 2 drugs were stopped and oral ursodeoxycholic acid 250 mg thrice daily was given. On day 42 of drug withdrawal, laboratory tests showed ALT 368 U/L, AST 179 U/L,TBil 504.9 μmol/L, DBil 382.8 μmol/L, IBil 122.1 μmol/L, ALP 201 U/L, and γ-GT 58 U/L. On day 91 of drug withdrawal, laboratory tests showed ALT 78 U/L, AST 62 U/L, TBil 138.1 μmol/L, DBil 118.2 μmol/L, IBil 20.2 μmol/L, ALP 140 U/L, and γ-GT 31 U/L. The patient′s liver function returned to normal 135 days after drug withdrawal.

A 63-year-old male patient took tamsulosin hydrochloride sustained release capsules 0.2 mg daily and Qianliexin capsules 2 g thrice daily by himself for urinary urgency and urodynia. Twenty-five days later, he developed itchy skin, deep brown urine, nausea, fatigue, and loss of appetite. Laboratory tests showed alanine aminotransferase (ALT) 265 U/L, aspartate aminotransferase (AST) 163 U/L, total bilirubin (TBil) 155.1 μmol/L, direct bilirubin (DBil) 74.7 μmol/L, indirect bilirubin (IBil) 80.4 μmol/L, alkaline phosphatase (ALP) 261 U/L, and gamma-glutamyltransferase (γ-GT) 184 U/L. Liver biopsy showed the cholestatic liver injury. He was diagnosed as acute drug-induced liver injury, which might be related to the above 2 drugs. The above 2 drugs were stopped and oral ursodeoxycholic acid 250 mg thrice daily was given. On day 42 of drug withdrawal, laboratory tests showed ALT 368 U/L, AST 179 U/L,TBil 504.9 μmol/L, DBil 382.8 μmol/L, IBil 122.1 μmol/L, ALP 201 U/L, and γ-GT 58 U/L. On day 91 of drug withdrawal, laboratory tests showed ALT 78 U/L, AST 62 U/L, TBil 138.1 μmol/L, DBil 118.2 μmol/L, IBil 20.2 μmol/L, ALP 140 U/L, and γ-GT 31 U/L. The patient′s liver function returned to normal 135 days after drug withdrawal.

The clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is a versatile genome editing tool with high efficiency. A guide sequence of 20 nucleotides (nt) is commonly used in application of CRISPR/Cas9; however, the relationship between the length of the guide sequence and the efficiency of CRISPR/Cas9 in porcine cells is still not clear. To illustrate this issue, guide RNAs of different lengths targeting the EGFP gene were designed. Specifically, guide RNAs of 17 nt or longer were sufficient to direct the Cas9 protein to cleave target DNA sequences, while 15 nt or shorter guide RNAs had loss-of-function. Full-length guide RNAs complemented with mismatches also showed loss-of-function. When the shortened guide RNA and target DNA heteroduplex (gRNA:DNA heteroduplex) was blocked by mismatch, the CRISPR/Cas9 would be interfered with. These results suggested the length of the gRNA:DNA heteroduplex was a key factor for maintaining high efficiency of the CRISPR/Cas9 system rather than weak bonding between shortened guide RNA and Cas9 in porcine cells.
Base Sequence ; Complement System Proteins ; CRISPR-Cas Systems ; DNA ; Genome ; Nucleotides ; RNA, Guide ; Swine

Objective: To explore drug utilizing regularity of traditional Chinese medicine(TCM) in treating and preventing asthenopia by analyzing the patent status of TCM in the field of asthenopia control for nearly 20 years. Method: Global patents about TCM in treating and preventing asthenopia were systematic searched in IncoPat platform.The application trend,legal status and categories of patents were analyzed.Meanwhile,the oral prescriptions and external prescriptions were performed correlation index analysis by IBM SPSS Modeler 18.0,respectively;the difference of compatibility rules between them was compared. Result: The number of global patents in treating and preventing asthenopia gradually increased,and the proportion of patents from China was more than 99%.The main patent applications were pharmaceutical composition,oral preparation,external eye patch and so on,but the ratio of licensed patents in total patents was low.In term of drug utilizing regularity,the oral prescriptions paid much attention to using TCM for nourishing the liver and kidney,while external prescriptions highlighted relieving sickness heat and detoxification. Conclusion: Patents of TCM in treating and preventing asthenopia has been kept increasing in recent years,but the authorization rate is low.Formulation based on TCM theory can be statistically summarized,which can be helpful for the development of anti-asthenopia products.