Preparing Coordination Polymers with Acentric-Centric Structural Arrangements Related to SHG Response.

Three coordination polymers were successfully constructed in this work by applying biligands and were distinctly characterized through single crystal X-ray diffraction. The compounds crystallized in acentric and centric space groups under the direction of coordination bonds and adopted 1-dimensional link and 2-dimensional layer structures, as well as different coordination geometries for metal atoms. All compounds exhibited good thermal stability and luminescence properties, and compound 2 exhibited a good second harmonic generation (SHG) response. The method used in this work offers a feasible approach to using biligand and changing metal salt to obtain the microstructures of coordination materials with specific properties.

The role of the genetic variant FECH rs11660001 in the occurrence of anti-tuberculosis drug-induced liver injury.

WHAT IS KNOWN AND OBJECTIVE: The pathogenic mechanism of anti-tuberculosis drug-induced liver injury (AT-DILI) is still largely unknown. Recent studies have indicated that rifampicin and isoniazid cotreatment causes the accumulation of endogenous protoporphyrin IX in the liver through the haem biosynthesis pathway. Alanine synthase 1 (ALAS1) and ferrochelatase (FECH) are the rate-limiting enzymes in the production of haem. The present study aimed to investigate the genetic contribution of the ALAS1 and FECH genes to the risk of AT-DILI in an Eastern Chinese Han population. METHODS: A 1:4 matched case-control study was conducted, and eight SNPs in the ALAS1 and FECH genes were detected and assessed. A multivariate conditional logistic regression model was used to estimate the association between genotypes and the risk of AT-DILI by the odds ratios (ORs) with 95% confidence intervals (CIs), with liver disease history, hepatoprotectant use, smoking and drinking history as covariates. RESULTS AND DISCUSSION: Overall, 202 AT-DILI cases and 808 controls were included in this study. The female patients carrying polymorphisms of rs11660001 in FECH had an increased risk of AT-DILI under the dominant and additive models (OR = 1.831, 95% CI: 1.014-3.307, p = 0.045; OR = 1.673, 95% CI: 1.015-2.760, p = 0.044, respectively). The peak aspartate transaminase level was significantly higher in female patients carrying the GA+AA genotype of rs11660001 than in those with the GG genotype during anti-TB treatment (p = 0.032). WHAT IS NEW AND CONCLUSION: Based on this 1:4 individual matched case-control study, SNP rs11660001 in the FECH gene may be associated with susceptibility to AT-DILI in Chinese female anti-TB treatment patients. Further studies in larger varied populations are needed to validate our findings.

A first-in-human phase 1 and pharmacological study of TAS-119, a novel selective Aurora A kinase inhibitor in patients with advanced solid tumours.

BACKGROUND: This is a first-in-human study with TAS-119, an Aurora A kinase (AurA) inhibitor. METHODS: Patients with advanced, refractory, solid tumours were enrolled into 5 dose escalation cohorts (70-300 mg BID, 4 days on/3 days off, 3 out of 4 weeks or 4 out of 4 weeks). The expansion part consisted of patients with small-cell lung cancer, HER2-negative breast cancer, MYC-amplified/ß-catenin-mutated (MT) tumours or other (basket cohort). RESULTS: In the escalation part (n = 34 patients), dose-limiting toxicities were one grade 3 nausea, two grade 2 and one grade 3 ocular toxicity and a combination of fatigue, ocular toxicity and nausea in one patient (all grade 2) at dose levels of 150, 200, 250 and 300 mg, respectively. Most frequent treatment-related adverse events were fatigue (32%), diarrhoea (24%) and ocular toxicity (24%). Toxicity grade ≥3 in ≥10% of patients were diarrhoea (15%) and increased lipase (12%). The maximum tolerated dose was 250 mg BID. Due to one additional grade 1 ocular toxicity, the RP2D was set at 200 mg BID (4 days on/3 days off, 3 out of 4 weeks), which was further explored in the expansion part (n = 40 patients). Target inhibition in paired skin biopsies was shown. CONCLUSIONS: TAS-119 has a favourable and remarkably distinct safety profile from other AurA inhibitors. CLINICAL TRIAL REGISTRATION: NCT02448589.

A validation study of the UGT1A4 rs2011404 variant and the risk of anti-tuberculosis drug-induced hepatotoxicity in an Eastern Chinese Han population.

WHAT IS KNOWN AND OBJECTIVE: Anti-tuberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction. A recent study found that the rs2011404 variant of uridine 5'-diphospho-glucuronosyl-transferase 1A4 (UGT1A4) is a marker of susceptibility to ATDH. The present study aimed to validate this relationship in an Eastern Chinese Han anti-TB treatment population. METHODS: A 1:4 matched case-control study was conducted among anti-TB treatment patients in four regions of Jiangsu. ATDH was diagnosed based on the criteria from the Chinese Society of Hepatology and the updated Roussel Uclaf Causality Assessment Method. A conditional logistic regression model was used to estimate the association between rs2011404 genotypes and the risk of ATDH using odds ratios (ORs) with 95% confidence intervals (95% CIs) and smoking, drinking, hepatoprotectant use and liver diseases as covariates. RESULTS AND DISCUSSION: A total of 202 ATDH cases and 808 controls were matched according to age, sex and treatment history. After correcting for potential confounding factors, conditional logistic regression analysis indicated no significant differences in genotypes between the two groups (CC vs. TC: OR = 0.933, 95% CI: 0.457-1.905, p = 0.849). Subgroup analysis suggested that patients carrying the CC genotype at rs2011404 in UGT1A4 were at a reduced risk of moderate or severe liver injury (OR = 0.293, 95% CI: 0.093-0.921, p = 0.036). WHAT IS NEW AND CONCLUSION: Based on a 1:4 individual matched case-control study, possessing the CC genotype at rs2011404 of the UGT1A4 gene reduces the risk of moderate or severe liver injury in Eastern Chinese Han patients receiving anti-TB treatment. Further research is warranted to explain the role of the UGT1A4 gene and its contribution to individual differences in susceptibility to ATDH.

Pulmonary Hypoplasia Resulting from Pulmonary Artery Banding in Infancy: A Neonatal Rat Model Study.

The aim of this study was to establish a neonatal rat model of decreased pulmonary blood flow (PBF) for studying pulmonary pathophysiological changes in newborn lung development with reduced PBF. Horizontal thoracotomy surgery with banding of the main pulmonary artery (PA) was performed on 30 rats in the PA banding (PAB) group and without banding on another 30 rats in the sham group within 6 h after birth. The body growth and mortality were recorded. Constriction of PA was checked by echocardiography on postnatal day 7 (P7). Lung morphology was assessed with computed tomography scanning and three-dimensional reconstruction. Histological differences of two groups were evaluated using hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TdT-mediated dUTP nick-end labeling assay, and CD31 labeling with microscopic examination. PA ultrasound confirmed the establishment of constriction on P7. Relative to the sham group, the neonates' physical growth, survival fraction, and lung geometry volume were decreased in the PAB group over time (p < 0.05). Histologic appearance with reduced PBF characterized a markedly simplified alveolarization with noted lower radial alveolar count and alveolar septal thickness in the PAB group (p < 0.0001), pulmonary arteries with thinner/uneven membranous layers and smaller lumina. The deficient alveolar capillary bed, enhanced pulmonary collagen deposition, and increased apoptotic alveolar epithelium were significant in the PAB group compared to the sham group (p < 0.0001). A neonatal rat PAB model demonstrated that PBF reduction during early infancy impairs alveolarization and pulmonary microvasculature.

Preoperative Morphological Prediction of Early Reoperation Risk After Primary Repair in Tetralogy of Fallot: A Contemporary Analysis of 83 Cases.

This study was conducted to investigate the pulmonary artery (PA) variations in tetralogy of Fallot (TOF) and preoperative morphological predictors for early reoperation. Eighty-three TOF patients and 20 children with normal PA were included. The TOF group was divided into two subsets according to whether or not reoperation was performed within 3 years postoperatively. Clinical information was obtained, along with computed tomography (CT)-based three-dimensional geometry of the PA. Morphological measurements of the length of the main PA branches, the angles between them, and the cross-sectional area of each segment of the PAs were acquired using computer software. Logistic regression and receiver operating characteristic curves were applied to analysis. The TOF group showed a significantly smaller PA size and irregular PA shape, with lower Nakata and McGoon indices, than the control group. The median bifurcation angle (angle-γ) was greater than 100° in the TOF group, as compared to 66.70° in the control group (P < 0.000). Residual obstruction of the infundibulum or PAs was the main reason for early reoperation in this series. The development of the main PA and left PA was poorer in the reoperation subset than in the non-reoperation subset (P ≤ 0.01). The preoperative angle-γ in the reoperation subset was larger than that in the non-reoperation subset (median, 117.8° vs. 112.0°, P = 0.026). Higher weight (OR = 0.372) and McGoon index (OR = 0.122) were protective factors, while larger angle-γ (> 114.8°, OR = 5.040) and angle-γ normalized by body surface area (BSA) (γ/BSA > 297.9, OR = 18.860) were risk factors. This study provides an intuitive perspective of PA anatomical variations in TOF. Larger preoperative PA bifurcation angle and γ/BSA were morphological risk predictors of postoperative reoperation in patients with TOF.

Long-term results of type B aortic dissection patients with tumor after endovascular repair or optimal medical therapy: a single-center and retrospective cohort study.

BACKGROUND: The effect of thoracic endovascular aortic repair (TEVAR) for acute Type B aortic has been confirmed, However, when patients with malignant disease suffer from acute type B aortic dissection (ATBAD), the effect of TEVAR intervention is still unclear. METHODS: ATBAD patients were identified from electronic medical records between 2009 and 2019. The 5 year overall and aortic-disease free survival rates were analyzed and compared between the two groups. RESULTS: Of the 40 enrolled patients, 27 (67.5%) received TEVAR and 13 (32.5%) received OMT. The baseline characteristics of the two groups were not significantly different. Kaplan‒Meier survival curve showed that the 5 year overall survival and 5 year aortic-disease free survival of the TEVAR group were better than those of the OMT group. The Cox proportional hazard model with unadjusted risk showed an 83.0% decrease in 5 year overall mortality (HR, 0.17; 95% CI, 0.05-0.56) and a lower aortic-disease related risk (HR, 0.08; 95% CI, 0.02-0.39) in TEVAR group compared to OMT group. After adjusted for age, gender, smoking, drinking and comorbidities (diabetes mellitus, hypertension and coronary artery diseases), the hazard ratio of 5 year overall mortality was 78.0% lower (HR, 0.22; 95% CI, 0.06.0.81) and the risk of aortic-disease related mortality was 93.0% lower (HR, 0.07; 95% CI, 0.01-0.61) in TEVAR group compared to OMT group. In the cohort stratified by age, sex, the risk of the 5 year overall or aortic-disease related mortality in TEVAR group was relatively reduced compared to OMT group. CONCLUSIONS: Compared to OMT, TEVAR improves the 5 year overall and aortic-disease free survival rates in the cohort of ATBAD patients with a single type of malignant tumors.

Lin28a protects against diabetic cardiomyopathy through Mst1 inhibition.

Lin28a has been found to enhance glucose uptake and insulin sensitivity. Lin28a alleviates cardiac dysfunction under various pathological conditions. However, the effects and underlying mechanisms of Lin28a on diabetic cardiomyopathy (DCM) are not well-understood. The aim of this study was to determine whether Lin28a protects against DCM and the potential mechanisms. Two to three days old mouse neonatal primary cardiomyocytes were randomized for treatment with adenoviruses harboring Lin28a and mammalian sterile 20-like kinase 1 (Mst1) short hairpin RNA, 48 hr before culturing in normal or high glucose medium. Cardiomyocyte apoptosis, autophagy, mitochondrial morphology, adenosine triphosphate content, and cytokine levels in the high glucose or normal conditions were observed between all groups. Either Lin28a overexpression or Mst1 knockdown alleviated mitochondrial ultrastructure impairment, decreased cytokine levels, inhibited apoptosis, and enhanced autophagy in primary neonatal mouse cardiomyocytes treated with high glucose. Importantly, the protective effects of Lin28a and Mst1 disappeared after treatment with 3-methyladenine, an autophagy inhibitor. Interestingly, in Mst1 knockdown cardiomyocytes, Lin28a overexpression failed to further enhance autophagy and alleviate high glucose-induced cardiomyocyte injury, which implies the protective roles of Lin28a counteracting high glucose-induced cardiomyocyte injury are dependent on Mst1 inhibition. Furthermore, co-immunoprecipitation and immunofluorescence double staining suggested that there were no direct interactions between Mst1 and Lin28a. Lin28a increased the expression of Akt, which inhibited the activation of Mst1-mediated apoptotic pathways.

Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and ß-catenin-related pathways.

Cartilage engineering strategies using mesenchymal stem cells (MSCs) could provide preferable solutions to resolve long-segment tracheal defects. However, the drawbacks of widely used chondrogenic protocols containing TGF-ß3, such as inefficiency and unstable cellular phenotype, are problematic. In our research, to optimize the chondrogenic differentiation of human umbilical cord MSCs (hUCMSCs), kartogenin (KGN) preconditioning was performed prior to TGF-ß3 induction. hUCMSCs were preconditioned with 1 µM of KGN for 3 d, sequentially pelleted, and incubated with TGF-ß3 for 28 d. Then, the expression of chondrogenesis- and ossification-related genes was evaluated by immunohistochemistry and RT-PCR. The underlying mechanism governing the beneficial effects of KGN preconditioning was explored by phosphorylated kinase screening and validated in vitro and in vivo using JNK inhibitor (SP600125) and ß-catenin activator (SKL2001). After KGN preconditioning, expression of fibroblast growth factor receptor 3, a marker of precartilaginous stem cells, was up-regulated in hUCMSCs. Furthermore, the KGN-preconditioned hUCMSCs efficiently differentiated into chondrocytes with elevated chondrogenic gene ( SOX9, aggrecan, and collagen II) expression and reduced expression of ossific genes (collagen X and MMP13) compared with hUCMSCs treated with TGF-ß3 only. Phosphokinase screening indicated that the beneficial effects of KGN preconditioning are directly related to an up-regulation of JNK phosphorylation and a suppression of ß-catenin levels. Blocking and activating tests revealed that the prochondrogenic effects of KGN preconditioning was achieved mainly by activating the JNK/Runt-related transcription factor (RUNX)1 pathway, and antiossific effects were imparted by suppressing the ß-catenin/RUNX2 pathway. Eventually, tracheal patches, based on KGN-preconditioned hUCMSCs and TGF-ß3 encapsulated electrospun poly( l-lactic acid-co-ε-caprolactone)/collagen nanofilms, were successfully used for restoring tracheal defects in rabbit models. In summary, KGN preconditioning likely improves the chondrogenic differentiation of hUCMSCs by committing them to a precartilaginous stage with enhanced JNK phosphorylation and suppressed ß-catenin. This novel protocol consisting of KGN preconditioning and subsequent TGF-ß3 induction might be preferable for cartilage engineering strategies using MSCs.-Jing, H., Zhang, X., Gao, M., Luo, K., Fu, W., Yin, M., Wang, W., Zhu, Z., Zheng, J., He, X. Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and ß-catenin-related pathways.

Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity: validation study in a Chinese Han population.

OBJECTIVE: Antituberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism has not been elucidated thoroughly to date. A recent genome-wide association study reported that seven single-nucleotide polymorphisms (SNPs) in the family with sequence similarity 65, member B gene (FAM65B), ATP/GTP-binding protein-like 4 gene (AGBL4), and cut-like homeobox 2 gene (CUX2) were associated strongly with ATDH in Ethiopian patients. We validated this relationship in a Chinese Han anti-TB treatment population. PATIENTS AND METHODS: A 1 : 2 matched case-control study was carried out of 235 ATDH cases and 470 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATDH by odds ratios with 95% confidence intervals, and weight and hepatoprotectant use were used as covariates. RESULTS: Patients with a polymorphism at rs10946737 in the FAM65B gene were at an increased risk of moderate and severe liver injury under the dominant model (adjusted odds ratio=2.147, 95% confidence interval: 1.067-4.323, P=0.032). No other genotypes or genetic risk scores were found to be significantly related to ATDH. CONCLUSION: This is the first study to explore and validate the relationships between seven SNPs in the FAM65B, AGBL4, and CUX2 genes and ATDH in a Chinese population. On the basis of this case-control study, SNP rs10946737 in FAM65B may be associated with susceptibility to ATDH in Chinese Han anti-TB treatment patients. Further research is warranted to explain the role of the FAM65B gene and its contribution toward individual differences in susceptibility to ATDH.

Relevance of NAT2 genotype to anti-tuberculosis drug-induced hepatotoxicity in a Chinese Han population.

BACKGROUND: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction. The slow acetylator status of N-acetyl transferase 2 (NAT2) is a well-established risk factor for ATDH. One novel tagging single nucleotide polymorphism (tagging SNP), rs1495741, in NAT2 has been found to be highly predictive of the NAT2 phenotype. The present study aimed to validate the relationships between tagging SNP rs1495741 and ATDH in a Chinese Han population. METHODS: A 1:2 matched case-control study was conducted using 235 ATDH cases and 470 controls. Conditional or unconditional logistic regression analysis was used to estimate the association between genotypes and the risk of ATDH according to the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Patients carrying the AA genotype of tagging SNP rs1495741 were at higher risk of ATDH than those carrying the GG genotype (OR = 1.653, 95% CI = 1.050-2.601; p = 0.030). Subgroup analysis suggested that the AA genotype was a risk factor for ATDH in patients aged older than 50 years (OR = 2.486, 95% CI = 1.313-4.706; p = 0.005), weighing over 50 kg (OR = 1.757, 95% CI = 1.016-3.038; p = 0.044) or using a hepatoprotectant (OR = 1.611, 95% CI = 1.009-2.572; p = 0.046). Tagging SNP rs1495741 was not a significant risk factor for moderate and severe hepatotoxicity but appears to be relevant to risk of mild hepatotoxicity specifically. CONCLUSIONS: The present study is the first to validate the relationships between the tagging SNP rs1495741 and ATDH in a Chinese population. Based on this case-control study, the NAT2 rs1495741 polymorphism is a risk factor for mild but not more severe ATDH in Chinese Han patients.

Integrated model for the prenatal diagnosis and postnatal surgical treatment of total anomalous pulmonary venous connection: A multidisciplinary collaborative experience and preliminary results.

BACKGROUND: This study aimed to evaluate an integrated model for the prenatal diagnosis and postnatal treatment of total anomalous pulmonary venous connection (TAPVC). METHODS: From January 2014 to December 2018, 11 patients were considered as a prenatally diagnosed group, who would accept the integrated model for prenatal diagnosis and postnatal treatment of TAPVC. Besides, 25 patients as postnatally diagnosed group underwent emergency surgery during the corresponding period at the same age. The perioperative status, survival and risk factors for death were compared between the two groups. RESULTS: In a prenatally diagnosed group, three pregnant women chose termination; eight patients followed the integrated model, and their newborns were rapidly transported to a children's hospital within 24 hours after birth. Other than one patient who was prenatally diagnosed with infracardiac type was later confirmed as a mixed type of TAPVC, the prenatal and postnatal diagnoses of the other seven patients were consistent. The 30-day, 1-year, and 5-year survival rates in the prenatally diagnosed group were 100%, 100%, and 100%, while those in the postnatally diagnosed group were 92%, 87.8%, and 87.8%, without significant difference (P > .05). Although Fisher's exact test indicated that an oxygen saturation <70% at admission might be an independent predictor of mortality (P < .01), none of the risk factors for death were significantly different by multivariate Cox regression analysis. CONCLUSION: The integrated model of prenatal diagnosis and postnatal treatment by multidisciplinary collaboration could lead to satisfactory outcomes, and prenatal diagnosis combined with postnatal oxygen saturation evaluation would facilitate early intervention for TAPVC.

Rare Copy Number Variations Might Not be Involved in the Molecular Pathogenesis of PA-IVS in an Unselected Chinese Cohort.

Congenital heart defect (CHD) is one of the most common birth defects in China, while pulmonary atresia with intact ventricular septum (PA-IVS) is the life-threatening form of CHD. Numerous previous studies revealed that rare copy number variants (CNVs) play important roles in CHD, but little is known about the prevalence and role of rare CNVs in PA-IVS. In this study, we conducted a genome-wide scanning of rare CNVs in an unselected cohort consisted of 54 Chinese patients with PA-IVS and 20 patients with pulmonary atresia with ventricular septal defect (PA-VSD). CNVs were identified in 6/20 PA-VSD patients (30%), and three of these CNVs (15%) were considered potentially pathogenic. Two pathogenic CNVs occurred at a known CHD locus (22q11.2) and one likely pathogenic deletion located at 13q12.12. However, no rare CNVs were detected in patients with PA-IVS. Potentially pathogenic CNVs were more enriched in PA-VSD patients than in PA-IVS patients (p = 0.018). No rare CNVs were detected in patients with PA-IVS in our study. PA/IVS might be different from PA/VSD in terms of genetics as well as anatomy.

The independent and combined effects of respiratory events and cortical arousals on the autonomic nervous system across sleep stages.

PURPOSE: During sleep, respiratory events readily modulate the autonomic nervous system (ANS). Whether such modulation is caused by the respiratory event itself or the cortical arousal that follows and whether these influences differ across sleep stages are not clear. Thus, we aimed to study the independent and combined effects of respiratory events and cortical arousals on the ANS across sleep stages. METHODS: We recruited 22 male patients with sleep apnea-hypopnea syndrome (SAHS) and analyzed the differences in the indices of heart rate variability among normal respiration (NR), pathological respiratory events without cortical arousals (PR), cortical arousals without respiratory events (CA), and the coexistence of PR and CA (PR&CA), by sleep stage. RESULTS: Compared with NR, four indices of variation of the beat-to-beat interval demonstrated consistent results in all sleep stages generally: PR&CA showed the biggest difference, followed by PR and followed by CA, which exhibited the least difference. Thus, the respiratory event itself affects ANS modulation, but the cortical arousal that follows generally enhances this effect. For low-frequency power and low-frequency/high-frequency power ratio (LF/HF), PR&CA had the greatest impact. For mean beat-to-beat interval and high-frequency power (HFP), the influence of PR, CA, and PR&CA depended on sleep depth. However, PR&CA had a different influence on HFP in N2 stage vs. REM stage. CONCLUSIONS: Sleep stage also has an effect on this neuromodulatory mechanism. These findings may help clarify the relationship between SAHS and cardiovascular disease.

Outcomes of Right Ventricular Outflow Tract Reconstruction for Children with Persistent Truncus Arteriosus: A 10-Year Single-Center Experience.

The purpose of this report is to assess the mid- and long-term outcomes of right ventricular outflow tract (RVOT) reconstruction for children with persistent truncus arteriosus. Between September 2006 and 2016, 105 patients with persistent truncus arteriosus (PTA) received surgical treatment at Shanghai Children's Medical Center. Direct right ventricle-pulmonary artery anastomosis (pulmonary artery pull-down) was performed in 51 patients; a left auricle or pericardial conduit was inserted between the RVOT and pulmonary artery as a connection in 17 patients; heterograft (bovine jugular vein or Gore-tex) conduits and homograft conduits were used in 30 and 7 cases, respectively, to connect the distal pulmonary and right ventricle outflow tract; and pulmonary valve reconstruction was performed in 38 patients using a Gore-tex monocusp. There were six in-hospital deaths and one delayed death 5 months after operation. After a mean follow-up of 55.8 ± 16.5 months (6-113 months), 19 patients underwent reoperation (3 with pulmonary patch enlargement, 14 with conduit replacement and 2 with aortic valve replacement) 10-89 months after the first operation, with 1 hospital death. The actuarial survival rates were 94.2, 93.3 and 93.3% at 1, 5 and 10 years, respectively. Freedom from reoperation was 98.0, 87.8 and 82.7% at 1, 5 and 10 years, respectively. The follow-up variables included echocardiography, chest radiography, cardiac CT and cardiac function. At the last examination, most of the patients exhibited an improvement of New York Heart Association functional class from III or IV preoperatively to I or II at follow-up. Surgical treatment for PTA has an acceptable survival rate and satisfactory outcomes. Most patients exhibited an improvement in cardiac function during follow-up. Aortic arch deformity, truncal valvular regurgitation and long cardiopulmonary bypass time were regarded as risk factors for hospital mortality. Autologous tissue has a lower reoperation rate and better growth potential than extracardiac conduits. A monocusp valve effectively reduces pulmonary regurgitation in the early postoperative stage.

Perfluorinated substance assessment in sediments of a large-scale reservoir in Danjiangkou, China.

The occurrence of eight perfluorinated compounds (PFCs) in the surface sediments from 10 sampling sites spread across the Danjiangkou Reservoir was investigated by isotope dilution ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after solid-phase extraction (SPE). All the sediments from the 10 sites contained detectable levels of PFCs. The total concentration of the target PFCs in each sediment sample (C∑PFCs) ranged from 0.270 to 0.395 ng g-1 of dry weight, and the mean value of C∑PFCs was 0.324 ± 0.045 ng g-1 of dry weight for the whole reservoir. For each perfluorinated compound in one sediment, perfluorooctane sulfonate (PFOS) or perfluoro-n-butanoic acid (PFBA) consistently had a higher concentration than the other six PFCs, while perfluoro-n-octanoic acid (PFOA) was always undetectable. In terms of spatial distribution, the total and individual concentrations of PFCs in sediment from downstream sites of the Danjiangkou Reservoir were higher than those from upstream sites. Factor analysis revealed that PFCs in the sediment samples originated from electroplating and anti-fog agents in industry, food/pharmaceutical packaging and the water/oil repellent paper coating, and the deposition process. The quotient method was utilized to assess the ecological risk of PFCs in the sediments of the Danjiangkou Reservoir, which showed that the concentrations of PFCs were not considered a risk. In this study, detailed information on the concentration level and distribution of PFCs in the sediments of the Danjiangkou Reservoir, which is the source of water for the Middle Route Project of the South-to-North Water Transfer Scheme in China, was reported and analyzed for the first time. These results can provide valuable information for water resource management and pollution control in the Danjiangkou Reservoir.

Surgical strategies and outcomes of congenital supravalvular aortic stenosis.

BACKGROUND: Various surgical techniques have been introduced to treat supravalvular aortic stenosis (SVAS). However, there is no consensus upon the optimal approach. This study reviewed our institutional experience in the management of SVAS. METHODS: Ninety patients undergoing surgery for SVAS were identified between 2009 and 2016. Based on surgical techniques, patients were divided into three groups: McGoon repair (n = 63), Doty repair (n = 24), and Brom repair (n = 3). Median follow-up was 38.5 months (range, 4 months-7.5 years). Patient status, cumulative event-free survival rate, and risk factors for adverse clinical outcomes were assessed. RESULTS: The early mortality rate was 3.3%. There was one late death and two reinterventions. No differences were observed among three surgical groups. Event-free survival was 98.4% at 3 years and 96.5% at 5 years. Diffuse-type SVAS and a preoperative gradient greater than 60 mmHg were risk factors for adverse cardiac remodeling within 6 months post-surgery. Residual aortic stenosis was associated with male gender, preoperative aortic valve stenosis, and a preoperative peak gradient greater than 90 mmHg. Eleven patients (out of 30) who underwent concomitant pulmonary artery patching had a residual pulmonary gradient greater than 40 mmHg. CONCLUSIONS: Surgical repair of SVAS can be safely achieved using different techniques, with similar midterm mortality and reintervention rates. Higher preoperative gradient is associated with worse clinical results. Issues regarding surgical timing and concomitant pulmonary artery stenosis need to be further addressed.

Advances in molecular genetics for pulmonary atresia.

Genetic and environmental factors may be similar in certain CHD. It has been widely accepted that it is the cumulative effect of these risk factors that results in disease. Pulmonary atresia is a rare type of complex cyanotic CHD with a poor prognosis. Understanding the molecular mechanism of pulmonary atresia is essential for future diagnosis, prevention, and therapeutic approaches. In this article, we reviewed several related copy number variants and related genetic mutations, which were identified in patients with pulmonary atresia, including pulmonary atresia with ventricular septal defect and pulmonary atresia with intact ventricular septum.

Isolation and characterization of a Sca-1+/CD31- progenitor cell lineage derived from mouse heart tissue.

BACKGROUND: Myocardial infarction remains the leading cause of mortality in developed countries despite recent advances in its prevention and treatment. Regenerative therapies based on resident cardiac progenitor cells (CPCs) are a promising alternative to conventional treatments. However, CPCs resident in the heart are quite rare. It is unclear how these CPCs can be isolated and cultured efficiently and what the effects of long-term culture in vitro are on their 'stemness' and differentiation potential, but this is critical knowledge for CPCs' clinical application. RESULTS: Here, we isolated stem cell antigen-1 positive cells from postnatal mouse heart by magnetic active cell sorting using an iron-labeled anti-mouse Sca-1 antibody, and cultured them long-term in vitro. We tested stemness marker expression and the proliferation ability of long-term cultured Sca-1+ cells at early, middle and late passages. Furthermore, we determined the differentiation potential of these three passages into cardiac cell lineages (cardiomyocytes, smooth muscle and endothelial cells) after induction in vitro. The expression of myocardial, smooth muscle and endothelial cell-specific genes and surface markers were analyzed by RT-PCR and IF staining. We also investigated the oncogenicity of the three passages by subcutaneously injecting cells in nude mice. Overall, heart-derived Sca-1+ cells showed CPC characteristics: long-term propagation ability in vitro, non-tumorigenic in vivo, persistent expression of stemness and cardiac-specific markers, and multipotent differentiation into cardiac cell lineages. CONCLUSIONS: Our research may bring new insights to myocardium regeneration, for which even a small number of biopsy-derived CPCs could be enriched and propagated long term in vitro to obtain sufficient seed cells for cell injection or cardiac tissue engineering.

Advancing lifelong precision medicine for cardiovascular diseases through gut microbiota modulation.

The gut microbiome is known as the tenth system of the human body that plays a vital role in the intersection between health and disease. The considerable inter-individual variability in gut microbiota poses both challenges and great prospects in promoting precision medicine in cardiovascular diseases (CVDs). In this review, based on the development, evolution, and influencing factors of gut microbiota in a full life circle, we summarized the recent advances on the characteristic alteration in gut microbiota in CVDs throughout different life stages, and depicted their pathological links in mechanism, as well as the highlight achievements of targeting gut microbiota in CVDs prevention, diagnosis and treatment. Personalized strategies could be tailored according to gut microbiota characteristics in different life stages, including gut microbiota-blood metabolites combined prediction and diagnosis, dietary interventions, lifestyle improvements, probiotic or prebiotic supplements. However, to fulfill the promise of a lifelong cardiovascular health, more mechanism studies should progress from correlation to causality and decipher novel mechanisms linking specific microbes and CVDs. It is also promising to use the burgeoning artificial intelligence and machine learning to target gut microbiota for developing diagnosis system and screening for new therapeutic interventions.