Inhibition of the ATR-DNAPKcs-RB axis drives G1/S-phase transition and sensitizes triple-negative breast cancer (TNBC) to DNA holliday junctions.

Targeting the DNA damage response (DDR) is a promising strategy in oncotherapy, as most tumor cells are sensitive to excess damage due to their repair defects. Ataxia telangiectasia mutated and RAD3-related protein (ATR) is a damage response signal transduction sensor, and its therapeutic potential in tumor cells needs to be precisely investigated. Herein, we identified a new axis that could be targeted by ATR inhibitors to decrease the DNA-dependent protein kinase catalytic subunit (DNAPKcs), downregulate the expression of the retinoblastoma (RB), and drive G1/S-phase transition. Four-way DNA Holliday junctions (FJs) assembled in this process could trigger S-phase arrest and induce lethal chromosome damage in RB-positive triple-negative breast cancer (TNBC) cells. Furthermore, these unrepaired junctions also exerted toxic effects to RB-deficient TNBC cells when the homologous recombination repair (HRR) was inhibited. This study proposes a precise strategy for treating TNBC by targeting the DDR and extends our understanding of ATR and HJ in tumor treatment.

Case Report: Interventional therapy for coronary artery occlusion in a 6-year-old child with Kawasaki disease.

A 6-year-old girl was diagnosed with Kawasaki disease and bilateral giant coronary artery aneurysms at four months old and was subsequently referred to our hospital due to chest pain and T wave changes on electrocardiography. After admission, stress myocardial perfusion imaging showed reversible ischemia in multiple areas of the left ventricle. Coronary angiography revealed complete proximal segment occlusion of the left circumflex artery (LCX). The occluded LCX was recanalized by a Gaia 3rd micro-wire successfully passing through the occluded section to the distal end of the LCX, followed by sequential balloon dilation and drug-coated balloon angioplasty. Coronary angiography immediately after post-dilation and one-year follow-up angiography showed that the structure and blood flow of LCX was good. Although percutaneous coronary intervention (PCI) in pediatric patients with Kawasaki disease is limited in practice, PCI remains one of the treatment options for selected patients.

Comparative pharmacokinetic study of the five anti-inflammatory active ingredients of Inula cappa in a normal and an LPS-induced inflammatory cell model.

Inula cappa is a commonly used medicine in the Miao area of Guizhou Province in China. We established an in vitro inflammatory model of mouse macrophage RAW264.7 cells to study the different pharmacokinetics of five anti-inflammatory active ingredients in the I. cappa extract namely luteolin (LUT), chlorogenic acid (CA), cryptochlorogenic acid (CCA), 3,4-dicaffeoylquinic acid (3,4-DCQA) and 4,5-dicaffeoylquinic acid (4,5-DCQA), in a normal and an inflammatory cell model. First, RAW264.7 cells were treated in vitro with l µg/mL lipopolysaccharide (LPS) for 24 h to establish an inflammatory cell model. Then, the pharmacokinetic characteristics of the five ingredients were compared in normal and inflammatory cells after treatment with 200 µg/ml and 800 µg/ml of I. cappa extracts. After treatment with 1 µg/ml LPS for 24 h, the volume of RAW264.7 cells was increased, the morphology was changed, the antennae were obvious, and the secretion of inflammatory factors nitric oxide and TNF-α was increased. The pharmacokinetics results showed that the five ingredients in normal and inflammatory cells exhibited an increase in Cmax and AUC values with increasing doses, and the Cmax and AUC values of five ingredients were positively correlated with the extract concentration. Each of these five ingredients presented nonlinear pharmacokinetic characteristics. After treatment with 200 µg/ml of I. cappa extract, the uptake of five ingredients increased in inflammatory cells, Tmax was prolonged, MRT and t1/2 were prolonged, and CL_F and Vz_F were decreased, while after treatment with 800 µg/ml of I. cappa extract, the uptake of five ingredients decreased, Tmax was prolonged, absorption was faster, and MRT and t1/2 were prolonged. The five analyzed components in I. cappa extract exerted different effects on normal cells and LPS-induced inflammatory cells. Compared to normal cells, the uptake of five ingredients in inflammatory cells was faster and the AUC and Cmax values increased with increasing doses, showing a dose-dependent nonlinear pharmacokinetic profile. These results indicate that the pharmacokinetic effects of the five analyzed ingredients in I. cappa extract are changed in the inflammatory state.

Mid-aortic syndrome: a rare cause of heart failure in infants.

This case reports describe a rare disease, mid-aortic syndrome (MAS), that can cause severe heart failure and hypertension in infancy. The typical images, key points of diagnosis, and therapy methods of the disease have also been presented. We report two critical thoracoabdominal aortic coarctation cases in infants aged 2 and 11 months with severe heart failure. The patients were initially misdiagnosed as dilated myocardiopathy, with the correct diagnosis confirmed through imaging. Both patients underwent balloon angioplasty; one patient also had bare-metal stents implanted. The patient treated with balloon angioplasty alone died after the procedure, whereas the other patient recovered well. In conclusion, careful physical examinations, especially upper and lower extremity blood pressure differences and palpation of upper and lower limb pulses, are critical in unexplained infant heart failure cases. Stent implantation may be a safer and more effective treatment than simple balloon angioplasty in infants with MAS.

[Establishment of PK-PD model in anti-inflammatory active components in Inula cappa extract based on lipopolysaccharide-induced in vitro inflammation model].

In the present study, a pharmacokinetics(PK)-pharmacodynamics(PD) model in the anti-inflammatory active components in Inula cappa extract was established based on the lipopolysaccharide(LPS)-induced in vitro inflammation model in order to clarify the relationship between the dynamic changes of anti-inflammatory active components in inflammatory cells and their efficacy. Firstly, the inflammation model in vitro was induced by 1 µg·mL~(-1) LPS in RAW264.7 cells for 24 h. After treatment with 400 µg·mL~(-1) I. cappa extract, the pharmacokinetics(PK) of five anti-inflammatory active components, including luteolin(LUT), chlorogenic acid(CA), cryptochlorogenic acid(CCA), 3,4-dicaffeoylquinic acid(3,4-DCQA), and 4,5-dicaffeoylquinic acid(4,5-DCQA), in normal cells and inflammatory cells was compared. Meanwhile, the PD study was carried out by measuring the inflammatory factors NO and TNF-α in the cell supernatant at each time point, which was fitted with PK by the Phoenix Model in the WinNonlin 8.2 to establish the PK-PD model for five components including LUT, CA, CCA, 3,4-DCQA, and 4,5-DCQA. The results showed that compared with normal cells, the model cells showed increased or decreased uptake of five components, advanced T_(max), faster absorption, prolonged MRT and t_(1/2), and increasing or decreasing trend of CL_(z/F) and V_(z/F). When NO was used as the efficacy index, the PK-PD model after the integration of the multi-effect components in I. cappa was E=7.45×\[1-Ce~(5.74)/(78.24~(5.74)+Ce~(5.74))\], while with TNF-α as the efficacy index, the PK-PD model after the integration of the multi-effect components in I. cappa was E=79.28×[1-Ce~(6.45)/(85.10~(6.45)+Ce~(6.45))]. The results of the study suggested that the inflammatory state could change the cellular PK of I. cappa. The anti-inflammatory effect of active components in I. cappa might be related to the down-regulation of the secretion of NO and TNF-α in inflammatory cells, and NO and TNF-α might serve as the anti-inflammatory targets of active components of I. cappa.

Retrospective analysis of infliximab in the treatment of Kawasaki disease / 中华儿科杂志

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.

Case Report: Recurrent Left Posterior Fascicular Ventricular Tachycardia in a Newborn.

Left posterior fascicular ventricular tachycardia (LPFVT) is extremely rare in neonates. We described a 17-day-old girl with LPFVT who was initially misdiagnosed as supraventricular tachycardia (SVT). Eventually, she was successfully treated by amiodarone infusion followed by oral amiodarone with propranolol for 9 months, and LPFVT spontaneously resolved after a 1-year follow-up. This case report illustrated the basic principles and caveats in differential diagnosis of LPFVT in the neonatal age group. With proper diagnosis and therapy, neonatal LPFVT might regress in the first year of life.

Tissue Distribution Comparison of Six Active Ingredients from an Eucommiae Cortex Extract between Normal and Spontaneously Hypertensive Rats.

Eucommiae Cortex (EC), a rare, nourishing medicinal herb that is native in China, has good effect in the treatment of hypertension. In this study, we compared tissue distribution of six representative active components of EC extract-genipinic acid (GA), protocatechuic acid (PCA), neochlorogenic acid (NCA), chlorogenic acid (CA), (+)-pinoresinol di-O-ß-D-glucopyranoside (PDG), and (+)-pinoresinol 4'-O-ß-D-glucopyranoside (PG)-between normal rats and spontaneously hypertensive rats (SHRs). Each rat was intragastrically given EC extract at a dose of 5.4 g/kg. Rats were sacrificed at 10 min, 30 min, 2 h, and 8 h after administration; six rats were sacrificed at each time point. Then, we quickly harvested their major organs, including heart, liver, spleen, lungs, kidneys, and brain. Using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we determined the levels of the above mentioned six components in the organs of both types of rats and then analyzed differences in the tissue distribution. The results showed that levels of each component differed between SHRs and the normal group at each time point. As time progressed, the number of organs in which GA distribution in each tissue of SHRs differed from that of the normal group gradually increased: SHRs showed lower GA levels than normal rats. Levels of PG and PDG in both groups at 10 and 30 min were similar. NCA and CA in the SHR group and the normal group at 10 min, 30 min, and 2 h were also similar to some extent. The results indicated that the pathological state of spontaneous hypertension could affect tissue distribution of EC active components in rats.

Neonatal Kawasaki disease with multiple arterial aneurysms: a case report.

BACKGROUND: Kawasaki disease (KD) is a medium vessel vasculitis that typically occurs in children aged between 6 months and 5 years. It is extraordinarily rare in the neonatal period. KD-related systemic artery aneurysms (SAAs) have never been reported in neonates. CASE PRESENTATION: A male infant was transferred to our institution for persistent high-grade fever lasting 16 days. Symptoms started at day 14 of life, and he was admitted to a children's hospital on the second day of fever. Physical examination at the time found no signs suggestive of KD. The only laboratory parameters which were of significance were values suggestive of systemic inflammation. However, his fever persisted and inflammatory markers continued to rise despite 2 weeks of antibiotic therapy. KD as a noninfectious cause of fever was considered when he came to our institution, and echocardiographic findings of left and right medium coronary artery aneurysms (CAAs) confirmed our suspicions. Full-body magnetic resonance angiography also revealed bilateral axillary artery aneurysms. Administration of intravenous gamma globulin resulted in rapid improvement. His fever resolved on the next day and CAAs and SAAs regressed to normal at 6 months and 3 months after diagnosis, respectively. CONCLUSION: This unique case of incomplete KD highlights the importance of considering KD in neonates with unexplained prolonged fever and reinforces the need to remain vigilant for SAAs in KD.

Comparative absorption kinetics of seven active ingredients of Eucommia ulmoides extracts by intestinal in situ circulatory perfusion in normal and spontaneous hypertensive rats.

Eucommia ulmoides Oliv. (E. ulmoides) is a valuable and nourishing medicinal herb in China that has been used in the treatment of hypertension. Given the fact that most traditional Chinese medicine is mainly used to treat disease, investigating the pharmacokinetics of traditional Chinese medicines in the pathological state is more useful than that in the normal state. However, the differences in the absorption kinetics of active ingredients of E. ulmoides extract between pathological and physiological conditions have not been reported. Therefore, in this study, the rat intestinal in situ circulatory perfusion model was used to investigate the differences in absorption kinetics of seven active ingredients of E. ulmoides extract in normal and spontaneously hypertensive rats, namely, genipinic acid, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, (+)-pinoresinol di-O-ß-D-glucopyranoside and (+)-pinoresinol 4'-O-ß-D-glucopyranoside. Our results indicate that the pathological state of spontaneous hypertension may change the absorption of active components of E. ulmoides extracts, and these findings may provide a reference for improving the rational use of E. ulmoides in the clinic.

Systemic Artery Aneurysms and Kawasaki Disease.

BACKGROUND: Coronary artery aneurysms (CAAs) are a well-known complication of Kawasaki disease (KD), but there are no data on incidence or outcomes of systemic artery aneurysms (SAAs) in the current era. METHODS: From April 1, 2016, to March 31, 2019, we screened for SAAs in 162 patients with KD at risk for SAAs with magnetic resonance angiography or peripheral angiography and analyzed incidence and early outcomes of SAAs. RESULTS: Twenty-three patients had SAAs, demonstrating an incidence of 14.2% (23 of 162) in patients who were screened at 1 month after onset. The proportion of patients with SAAs was estimated to be 2% (23 of 1148) of all patients with KD. The median age at onset of KD with SAAs was 5 months. All patients with SAAs had CAAs, with z scores >8. Of patients with giant CAAs, 38.6% (17 of 44) had SAAs. A total of 129 SAAs occurred in 17 different named arteries. The most common sites for SAAs were the axillary (18.6%), common iliac (12.4%), and brachial (11.6%) arteries. During a median follow-up time of 6 months, 92.9% (79 of 85) of SAAs had some degree of regression, with 80% (68 of 85) of SAAs returning to normal. The overall regression rate was higher for medium to large SAAs than for medium to giant CAAs. CONCLUSIONS: Although the incidence of SAAs may not be as dramatically reduced as we expected compared with previous data, SAAs have a high regression rate during short-term follow-up.

Glutathione S-Transferase M1 and T1 polymorphisms and hypertension risk: an updated meta-analysis.

Recently, Glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and their interaction with hypertension risk have been focused on. However, the results of previous studies have been inconsistent. Hence, the present meta-analysis was performed to explore the association. Twenty-two case-control studies met the inclusion criteria for GSTM1 (including 3577 hypertension cases and 3784 controls), twenty-two for GSTT1 (including 3741 cases and 4444 controls), and nine for their combined effects (including 1073 cases and 781 controls). Pooled analyses on the association between GSTM1 present/null polymorphism and hypertension risk were observed to be insignificant in overall and subgroup analyses. The individual who carries the GSTT1 null-genotype had a statistically significant overall population (OR = 1.28, 95% CI: 1.03, 1.60), Indians (OR = 2.45, 95% CI: 1.08, 5.59), and hospital-based controls (OR = 1.53, 95% CI: 1.21, 1.94). For the GSTM1-GSTT1 interaction, we found that the GSTM1/GSTT1 double-null-genotype was significantly associated with hypertension risks (double-null vs. double-present: OR = 2.68, 95% CI: 1.06, 6.81). To summarize, this meta-analysis indicates that Indians with the GSTT1 null-genotype has a raised hypertension risks; the GSTM1 null/GSTT1 null-genotype is association with raised hypertension risks, while the GSTM1 null-genotype is not associated with hypertension risks. In addition, I2 > 75% cannot be eliminated for GSTM1 in Indians or Asians, hence, it will be very important to explore the GSTM1 null-genotype and hypertension susceptibility in Indians and Asians for a large new sample, on population-based control study.

Two novel mutations in parE among Shigella flexneri isolated from Jiangsu Province of China, 2016.

BACKGROUND: The study was conducted to assess the resistance capacity of quinolone against Shigella flexneri, and to investigate the involved quinolone resistance mechanism. The data were collected from Jiangsu Province, China in 2016. METHODS: The number of 81 S. flexneri was obtained from 12 cities in Jiangsu Province of China during 2016. Slide agglutination was taken for serotyping, and susceptibility test was identified by the disc diffusion method. PCR aimed to amplify the quinolone resistance-determining region (QRDR) genes and screen for plasmid-mediated quinolone resistance (PMQR) determinants. Chromosomal mutation was confirmed by sequencing and Blast comparison. RESULTS: 2a was the commonest serotype, accounting for 40.7% (33/81) of the 81 S. flexneri. 70.4% (57/81) isolates expressed resistance against nalidixic acid, and the resistance against ciprofloxacin even reached up to a high proportion of 58.0% (47/81). A total of 8 point mutations were identified, including 2 novel mutations discovered in parE (Ser458Leu and Gly408Asp). The common mutation Ser83Leu in gyrA was still the most prevalent here with a percentage of 70.4% (57/81), followed by the approximate mutation of 69.1% (56/81) in parC (Ser80Ile) and His211Tyr in gyrA. Meanwhile, 35.8% (29/81) isolates were confirmed with mutation of Gln517Arg in gyrB. In addition, qnrS positive isolates occupied a proportion of 7.4% (6/81), but only 1 strain was observed with aac(6')-Ib-cr. All PMQR positive isolates were resistant to nalidixic acid. However, 5 of them didn't stay susceptible to ciprofloxacin any more. CONCLUSIONS: This is the first time that a study researches the occurrence of mutations in parE among S. flexneri, Ser458Leu and Gly408Asp included. The study indicates that the high resistance to fluoroquinolone remains a serious problem in Jiangsu, China. Thus, the prevention and control of current infection urge for a comprehensive and systematic surveillance based on persistent surveys.

Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure.

Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß, was evaluated. Cardiac function and LV remodeling were assessed using echocardiography and collagen deposition, respectively. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) four weeks after injection were significantly increased in Ad-HGF-treated animals compared to the Ad-GFP group. HGF gene therapy improved ventricular geometry with a significantly decreased left ventricular end-diastolic diameter (LVEDD) and markedly reduced myocardial collagen deposition. Treatment with Ad-HGF significantly decreased the mRNA levels of TNF-α, IL-6, and IL-1ß in the non-infarcted region four weeks after injection. Changes of the TNF-α, IL-6, and IL-1ß levels in the non-infarcted region positively correlated with the LVEDD 4 weeks after infarction. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of MI reduced the pro-inflammatory cytokine levels and preserved cardiac function. These findings indicated that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation.

Pulse Oximetry and Auscultation for Congenital Heart Disease Detection.

OBJECTIVES: Pulse oximetry (POX) has been confirmed as a specific screening modality for critical congenital heart disease (CCHD), with moderate sensitivity. However, POX is not able to detect most serious and critical cardiac lesions (major congenital heart disease [CHD]) without hypoxemia. In this study, we investigated the accuracy and feasibility of the addition of cardiac auscultation to POX as a screening method for asymptomatic major CHD. METHODS: A multicenter prospective observational screening study was conducted at 15 hospitals in Shanghai between July 1, 2012, and December 31, 2014. Newborns with either an abnormal POX or cardiac auscultation were defined as screen positive. All screen-positive newborns underwent further echocardiography. False-negative results were identified by clinical follow-up, parents' feedback, and telephone review. We assessed the accuracy of POX plus cardiac auscultation for the detection of major CHD. RESULTS: CHD screening was completed in all 15 hospitals, with a screening rate of 94.0% to 99.8%. In total, 167 190 consecutive asymptomatic newborn infants were screened, of which 203 had major CHD (44 critical and 159 serious). The sensitivity of POX plus cardiac auscultation was 95.5% (95% confidence interval 84.9%-98.7%) for CCHD and 92.1% (95% confidence interval 87.7%-95.1%) for major CHD. The false-positive rate was 1.2% for detecting CCHD and 1.1% for detecting major CHD. CONCLUSIONS: In our current study, we show that using POX plus cardiac auscultation significantly improved the detection rate of major CHD in the early neonatal stage, with high sensitivity and a reasonable false-positive rate. It provides strong evidence and a reliable method for neonatal CHD screening.

Surgical Outcomes of Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery in Children: An Echocardiography Follow-up.

BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare but potentially life-threatening congenital heart defect. A retrospective analysis was carried out to elucidate the surgical outcomes of ALCAPA in infants and children using follow-up echocardiography. METHODS: From September 2008 to March 2017, 26 children diagnosed with ALCAPA underwent left coronary re-implantation. All surviving patients received echocardiography during follow-up. RESULTS: The mortality rate after the operation was 11.5%. Before repair, twenty patients (76.9%) presented with left ventricular (LV) dysfunction. The mean Z-score of the preoperative LV end-diastolic diameter was 4.42 ± 2.09. Mitral regurgitation (MR) was present in all patients. Two patients (7.7%), both with mitral valve prolapse, underwent mitral valve repair at the time of ALCAPA repair. Two children required postoperative extracorporeal membrane oxygenation. LV function normalized at a median time of 5.3 months (range: 0.5-36.0 months). The Z-score of the LV end-diastolic diameter decreased simultaneously. The degree of MR gradually decreased in all surviving patients. All patients had patency of the proximal left coronary artery confirmed by echocardiography at the most recent follow-up. Six patients (26.1%) showed supravalvar pulmonary stenosis and seven patients (30.4%) showed right pulmonary stenosis during follow-up. CONCLUSIONS: Coronary re-implantation was effective for rebuilding a dual coronary system in patients with ALCAPA and resulted in progressive improved LV function and reduced functional MR. Echocardiography was valuable for evaluating the outcomes. LV function, the degree of MR, and possible complications could be detected with follow-up echocardiography.

Stability of vortex rotation around a mesoscopic square superconducting ring under radially injected current and an external magnetic field.

We present the stability of vortex rotation around a mesoscopic square superconducting ring under radially injected currents and external magnetic fields based on time-dependent Ginzburg-Landau equations. We demonstrate that the vortex rotation around a square ring can lead to voltage oscillations as the vortices periodically pass by the corners. The amplitude of the time evolution of the voltage oscillations as a function of external current is studied at different magnetic fields, and the effect of thermal noise on the voltage oscillations is discussed. The rotation frequency depends linearly on external current at lower magnetic fields, whereas it is a nonlinear function of external current at higher magnetic fields. The stable vortex rotation appears in a certain range of injected currents under magnetic fields, but it is unstable at high injected currents. It is found that such a transition from stability to instability can lead to an abrupt jump in current-voltage characteristics.

Surgical Outcomes of Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery in Children: An Echocardiography Follow-up / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare but potentially life-threatening congenital heart defect. A retrospective analysis was carried out to elucidate the surgical outcomes of ALCAPA in infants and children using follow-up echocardiography.</p><p><b>METHODS</b>From September 2008 to March 2017, 26 children diagnosed with ALCAPA underwent left coronary re-implantation. All surviving patients received echocardiography during follow-up.</p><p><b>RESULTS</b>The mortality rate after the operation was 11.5%. Before repair, twenty patients (76.9%) presented with left ventricular (LV) dysfunction. The mean Z-score of the preoperative LV end-diastolic diameter was 4.42 ± 2.09. Mitral regurgitation (MR) was present in all patients. Two patients (7.7%), both with mitral valve prolapse, underwent mitral valve repair at the time of ALCAPA repair. Two children required postoperative extracorporeal membrane oxygenation. LV function normalized at a median time of 5.3 months (range: 0.5-36.0 months). The Z-score of the LV end-diastolic diameter decreased simultaneously. The degree of MR gradually decreased in all surviving patients. All patients had patency of the proximal left coronary artery confirmed by echocardiography at the most recent follow-up. Six patients (26.1%) showed supravalvar pulmonary stenosis and seven patients (30.4%) showed right pulmonary stenosis during follow-up.</p><p><b>CONCLUSIONS</b>Coronary re-implantation was effective for rebuilding a dual coronary system in patients with ALCAPA and resulted in progressive improved LV function and reduced functional MR. Echocardiography was valuable for evaluating the outcomes. LV function, the degree of MR, and possible complications could be detected with follow-up echocardiography.</p>

Nanoscale assembly of superconducting vortices with scanning tunnelling microscope tip.

Vortices play a crucial role in determining the properties of superconductors as well as their applications. Therefore, characterization and manipulation of vortices, especially at the single-vortex level, is of great importance. Among many techniques to study single vortices, scanning tunnelling microscopy (STM) stands out as a powerful tool, due to its ability to detect the local electronic states and high spatial resolution. However, local control of superconductivity as well as the manipulation of individual vortices with the STM tip is still lacking. Here we report a new function of the STM, namely to control the local pinning in a superconductor through the heating effect. Such effect allows us to quench the superconducting state at nanoscale, and leads to the growth of vortex clusters whose size can be controlled by the bias voltage. We also demonstrate the use of an STM tip to assemble single-quantum vortices into desired nanoscale configurations.

[Effect of Valerian Ligusticum Pill on angiogenesis after injury of cerebral ischemia reperfusion in rats].

This study was designed to detect the impact of Valerian Ligusticum Pill（VLP） on cerebral ischemia reperfusion injury in rats, and explore the mechanism of angiogenesis. Sixty SD male rats were randomly divided into five groups, including sham operation group, model group, VLP-low（30 mg·kg-1） group, VLP-high(50 mg·kg-1) group and nimodipine (10 mg·kg-1) group. The ischemia reperfusion injury model was induced by occlusion of middle cerebral artery with suture embolus, reperfusion after 30 minutes' ischemia. When the rats were awake, the first neurological function scores was determined with modified neurological severity score（m NSS）. The rats were given VLP(30 mg·kg-1, 50 mg·kg-1) and nimodipine（10 mg·kg-1） through intragastric administration at 2 m L, once a day for a total of 7 days, while an equal amount of distilled water was used in the sham operation group and model control group. After 7 days, the rats were given second neurological function scores, and improvement of neurological function = [the first score] - [the second score]. The rats were sacrificed to investigate the infarction volume percentage with 2,3,5-triphenyl tetrazolium chloride method; do the qualitative and half quantitative analyses for protein vascular endothelial growth factor receptor 2（VEGFR2） in the tissue of cortex infarction around by Western blot; detect the new blood vessels of cortex infarction around by ki67/lectin immunofluorescence double staining method. Results suggest that VLP could significantly improve the neurological function, reduce the percentage of infarct volume, increase the expression of VEGFR2 and number of new blood vessels in the cortex infarction around compared with model group. In conclusion, VLP may relive the acute cerebral ischemia reperfusion injury in rats by inducing angiogenesis.