Ischemic heart disease (IHD), which has been considered to be exclusively caused by stenosis or occlusion of coronary artery, is a significant cause of morbidity and mortality worldwide. Mitochondrial dysfunction is the main pathological basis of ischemic heart disease and reperfusion injury, and moderate mitochondrial autophagy can selectively remove damage proteins and organelles to maintain intracellular homeostasis, so mitochondrial autophagy is important for maintaining the homeostasis of cardiomyocytes. Natural drugs from plants are widely used in ischemic heart disease. In recent years, more and more natural drugs have been proven to alleviate myocardial cell damage after ischemia/reperfusion through mitochondrial autophagy. This paper reviews the research progress of natural drugs from plants medicines regulating mitochondrial autophagy in the treatment of ischemia heart disease.

This study investigated the effect of puerarin on human umbilical vein endothelial cells (HUVEC) injured with hydrogen peroxide (H₂O₂). HUVEC were divided into three groups: a control group, a model group (H₂O₂ 400 μmol·L^-1) and a puerarin-treated group (3, 10, 30 and 100 μmol·L^-1). HUVEC were cultured with varied concentration of puerarin for 2 h and treated with H₂O₂ for another 24 h. Cell proliferation was detected by a CCK-8 assay. The mitochondrial membrane potential was measured by a JC-1 fluorescent probe. A transwell chamber assay was adopted to observe cell migration ability. Mitochondrial respiratory function was measured in a two-chamber titration injection respirometer (Oxygraph-2k). The expression of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) was detected by quantitative real-time PCR. The expression of pyroptosis-mediated proteins, including cleaved-cysteinyl aspartate-specific proteinase-1 (caspase-1), N-gasdermin D (N-GSDMD), NOD-like receptor protein 3 (NLRP3) and purinergic ligand-gated ion channel 7 receptor (P2X7R) was detected by Western blot. The results show that 400 μmol·L^-1 H₂O₂ treatment for 24 h causes obvious damage to HUVEC. Compared with the model group, puerarin protected against cellular injury in a dose-dependent manner, with the greatest effect at a dose of 30 and 100 μmol·L^-1. Puerarin significantly decreased the mitochondrial membrane potential and improved mitochondrial function. Puerarin inhibited cell migration induced by H₂O₂, suppressed the expression of IL-1β, IL-18 and TNF-α, and down-regulated the pyroptosis-mediated protein. These changes are statistically significant (P < 0.05). These findings demonstrate that puerarin has a protective effect against H₂O₂-induced oxidative damage of HUVEC by inhibiting the migration of HUVEC cells. The mechanism may be related to improved mitochondrial respiratory function and inhibition of pyroptosis.

This study aimed to evaluate the vasorelaxant effect and mechanisms of compound reserpine and triamterene tablets (CRTTs) and its component triamterene on isolated rat thoracic aorta rings. Isolated rat thoracic aorta rings pre-contracted by high potassium or norepinephrine (NE) were used to evaluate the vasodilatory effect of CRTTs and its component triamterene. The mechanisms concerning endothelium, potassium channels and calcium channels were studied through the interventions of several tool drugs. Animal welfare and experimental procedures followed the requirements of the Laboratory Animal Management and Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. The results showed that both CRTTs and triamterene had potent relaxant effect on KCl and NE pre-contracted vessels. Triamterene showed partial endothelium dependency, and N-nitro-L-argininemethyl ester hydrochloride (L-NAME) could influence the relaxant effect, which may be related to the opening of calcium-activated potassium channels. Meanwhile, CRTTs could inhibit intracellular Ca²⁺ release and extracellular Ca²⁺ influx. Overall, CRTTs and its component triamterene have vasorelaxant effects on vessels in vitro, and the vasorelaxant effect of CRTTs may be related to intracellular Ca²⁺ release and extracellular Ca²⁺ influx, while this effect of triamterene may depend on vascular endothelial function and may also be related to the opening of calcium-activated potassium channels.

OBJECTIVETo study the adverse effects of sleep problems and sleep insufficiency on attention in class and pupils' acadamic achievements.

METHODSA total of 1138 students from four primary schools at ages of 6-12 years were randomly sampled from four districts of Changsha city, Hunan Province June 2009 to April 2010. The inquired items included sleep problems, sleep time, sleep quality, attention in class and academic achievements. Teachers and parents observed the pupils according to the unified requirements for 3 months and then filled out the questionnaires.

RESULTSThe total valid inquiry tables were 1091 with the answering rate of 95.87%, including 549 boys and 542 girls. The sleep quality was more poor in children with sleep problems or sleep insufficiency than in children with normal sleep. The sleep quality was reduced and aggravated along with the increasing sleep problems and the reducing sleep time. The attention in class and academic achievements in children with sleep problems or sleep insufficiency were more poor than in children with normal sleep. The sleep quality index was negatively correlated with attention in class and academic achievements. The attention in class was positively correlated with academic achievements.

CONCLUSIONSThe decline in sleep quality directly affects the attention in class and reduce the academic achievements in primary school children.

Achievement ; Attention ; Child ; Child, Preschool ; Female ; Humans ; Male ; Schools ; Sleep

OBJECTIVETo screen mutations of tuberous sclerosis complex (TSC) patients to confirm a clinical diagnosis of TSC, and to perform prenatal diagnosis for families with mutations.

METHODSIn this study, PCR-denaturing high-performance liquid chromatography(DHPLC), supplemented with sequencing when necessary, was used to screen TSC1 and TSC2 mutations in 21 patients from 19 pedigrees visited author's hospital in the last five years. For novel mutations, one hundred unrelated healthy individuals were screened to exclude the possibility of polymorphism.

RESULTSSeventeen different mutations were found in 21 patients of 19 pedigrees with 13 being novel mutations, including c. 2672delA, c. 2672insA of TSC1 gene and c.4918insCGCC, c.1143delG, Intron27+1 G>A, c.1957-1958delAG, Intron5+1 G>A, c.910insCT, c.2753 C>G, c.4078dupAGCAAGTCCAGCTCCTC, Intron 11 -1 G>A, Intron 14+1 G>A, c.684 C>A of TSC2 gene, indicating a high frequency of de novo mutations in TSC. Three of these mutations were in the TSC1 gene (N762S, c.2672insA and c. 2672delA), while all remaining 14 were in the TSC2 gene. Prenatal diagnosis for TSC was performed for 7 fetuses from these pedigrees. The six fetuses that tested negative for TSC mutations were carried to term and, to date, none of these children has shown symptoms of TSC.

CONCLUSIONAuthor's data showed that a mutation detection rate of tuberous sclerosis was 89.5%(17/19) among patients in author's hospital. The ratio of TSC2 and TSC1 mutations was about 1:1 in the familial cases, but TSC2 mutation was more common than TSC1 mutation in sporadic cases. Author's data demonstrated that birth of TSC children for those with familial history of TSC could be prevented through prenatal diagnosis.

Base Sequence ; DNA Mutational Analysis ; methods ; Female ; Humans ; Male ; Pedigree ; Polymorphism, Single Nucleotide ; genetics ; Pregnancy ; Prenatal Diagnosis ; methods ; Retrospective Studies ; Tuberous Sclerosis ; diagnosis ; genetics

OBJECTIVETo investigate the clinical feasibility of cell-free fetal DNA (cffDNA)-based noninvasive prenatal diagnosis of β-thalassemia.

METHODSNine samples of amniotic fluid were obtained to detect the 8 common and 9 relatively rare mutation sites of β-thalassaemia in Guangdong Province. The maternal blood samples were also collected for extracting and purification of the cffDNA, and a duplex PCR was performed using 3 pairs of primers and the fetal β-globin genotype was analyzed by reverse dot-blot hybridization.

RESULTSAmong the 9 cases, 5 showed fetal genotypes of β-thalassemia inherited from the father by examination of the amniotic fluid, and 2 fetuses were identified to have β-thalassemia genes inherited from the father determined based on the cffDNA in the maternal blood.

CONCLUSIONSThe cffDNA-based noninvasive prenatal diagnosis is feasible for β-thalassemia, but the contamination of the maternal background DNA results in a low detection rate.

Adult ; Cell-Free System ; DNA ; blood ; Female ; Fetal Diseases ; diagnosis ; genetics ; Fetus ; Genetic Testing ; Humans ; Pregnancy ; blood ; Prenatal Diagnosis ; methods ; Young Adult ; beta-Thalassemia ; diagnosis ; genetics

OBJECTIVETo design and manufacture a new custom-made artificial articular cartilage of femoral condyle based on rapid prototyping technique and explore a method to solve the necroses of allocartilage in hemi joint allotransplantation.

METHODSDesign the new custom-made artificial articular cartilage of femoral condyle. The allograft and the patient distal femurs were scanned with Picker 6000 spiral computed tomography (CT) with 1.0 slice thickness and pitch of 1.5, reconstructed the distal femurs in Voxel Q image workstation with volume rendering technique. Then downloaded the transaxial 2D image data to personal computer at 0.1 mm interval and converted it into 2D digitized contour data by using image processing software developed by our team. The 3D wire frame and solid images of femoral condyle could be reconstructed when the 2D digitized contour data were input into image processing software Surfacer 9.0 (Imageware Company, USA). Subsequently based on the clinical experience and the need of design, the 3D contour image of articular cartilage was extracted from the surrounding. Based on the extracted 3D contour image, the computer-aided design (CAD) of the custom-made artificial articular cartilage was accomplished in Surfacer software, converted the CAD model into RP data format. Standard triangularization language, imported into the LPS600 rapid prototyping machine (Hengtong Company, Xi'an Jiaotong University, China), and the resin prototype was achieved. Then the resin model was used as a positive mould to build up a silica gel negative mould, the negative mould was sent to the factory to manufacture Ti-6Al-4V alloy articular cartilage through ordinary mould-melted founding process. Finally, the whole metal cartilage was completed after melting two special cages on it. A patient was selected to clinical applying.

RESULTSA new custom-made artificial articular cartilage of femoral condyle was made. It was press-fit well to the subchondral bone of the allograft bone. The patient's one and half year follow-up result was excellent.

CONCLUSIONSWe design and manufacture a new custom-made artificial articular cartilage of femoral condyle based on rapid prototyping technique. The result shows that the manufacturing process has the advantage of rapidness and precision that are very important for individualized artificial implant manufacturing. The artificial articular cartilage is press-fit well and could be a good idea to solve the necroses of allocartilage in hemijoint allotransplantation.

Adolescent ; Arthroplasty, Replacement, Knee ; Bone Transplantation ; Cartilage, Articular ; Computer-Aided Design ; Femoral Neoplasms ; surgery ; Follow-Up Studies ; Humans ; Knee Prosthesis ; Male ; Neoplasm Recurrence, Local ; surgery ; Osteosarcoma ; surgery ; Prosthesis Design ; methods ; Transplantation, Homologous

2',5'-Oligoadenylate Synthetase ; genetics ; Adult ; Carrier State ; virology ; Case-Control Studies ; Female ; Hepatitis B ; drug therapy ; genetics ; virology ; Hepatitis B virus ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Polymorphism, Genetic ; Recombinant Proteins

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Objective To compare the incidence of contrast-induced acute kidney injury(CI-AKI) following iso-osmolar iodixanol or low-osmolar iohexol administration in patients with acute myocardial infarction(AMI)undergoing emergent percutaneous coronary intervention(PCI). Methods The study was a prospectiverandomized controlled study.Consecutive patients with AMI were assigned to either the iodixanol group or the iohexol group randomly after they were categorized in different group according to the infarcted walls(inferior and anterior infarction)indicated by electrocardiogram. The primary end point was the incidence of CI-AKI,which is defined as serum creatinine(sCr)increase>25% or>0.5 mg/dl(44 μmol/L)from baseline witin 72 hours. Results Two hundred ninety-seven patients were enrolled and allocated to the iodixanol group(n=149)or the iohexol group(n=148),and CI-AKI occurred in 22.1% of patients in the iodixanol group and 16.9% of patients in the iohexol group (95% confidence interval –14.2% to 3.8%,P for noninferiority<0.002). The incidence of CI-AKI was higher in the anterior infarction group than in the inferior infarction group(21.4% vs. 11.6%,P<0.01). Conclusions In patients with AMI who underwent emergent PCI,iohexol was not inferior to iodixanol on the incidence of CI-AKI,and it is reasonable to avoid selection bias for assigning patients into inferior and anterior infarction group according to the infarcted walls for the future CI-AKI related clinical study.