[Ruptured chordae tendineae of tricuspid valve in neonate with intractable persistent pulmonary hypertension: a case report and literature review].

Objective: To analyze the clinical characteristics and treatment of tricuspid valve prolapse caused by chordal rupture complicated with persistent pulmonary hypertension in neonates. Methods: The clinical data of a male neonate with tricuspid valve prolapse complicated with persistent pulmonary hypertension admitted to the Neonatal Intensive Care Unit of Children's Hospital of Hebei Province in November 2018 was analyzed retrospectively. Related literature up to September 2020 was searched with the strategy of "(neonate OR newborn) AND (tricuspid valve prolapse) AND (rupture OR necrosis) AND (papillary muscle OR chordae tendineae) AND (pulmonary hypertension)" in Wanfang, CNKI and PubMed database in Chinese and English. The characteristics of the disease were summarized. Results: A male full-term neonate was admitted due to presenting severe cyanosis for 9 hours. He was born by caesarean section and presented severe cyanosis and dyspnea at 10 min of ages, unresponsive to the positive airway pressure resuscitation. After 9 hours of mechanical ventilation, there was no improvement. Thus he was transferred to Children's Hospital of Hebei Province. On admission, the initial blood gas analysis showed an arterial partial pressure of oxygen of 22.5 mmHg (1 mmHg=0.133 kPa). The echocardiography revealed prolapsed anterior leaflet of tricuspid valve, severe tricuspid regurgitation (TR) and pulmonary artery hypertension, and right to left shunt via a patent foramen ovale. The arterial duct was closed. The chest X-ray was normal. The boy was treated with nitric oxide, milrinone, and continued mechanical ventilation initially. Addition of prostacyclin analog (treprostinil) on day 3 led to significant improvement of pulmonary blood flow, oxygenation, and stabilization, so that the extracorporeal membrane oxygenation therapy was avoided. At 11 months after birth, the boy underwent cardiac surgery. At surgery, the rupture of chordal tendineae in anterior leaflet of tricuspid valve was found. Tricuspid annuloplasty, valvuloplasty and repair of patent foramen ovale were successfully performed. The follow-up echocardiogram at postoperative 3 months showed only mild tricuspid insufficiency. The boy was well at last follow-up at 22 months of age with normal cognitive skill development. According to literature, 20 cases of papillary muscle or chordae tendineae rupture in neonates had been reported in 12 English papers. Among the total 21 neonates, there were 12 male infants and only one premature infant with gestational age of 33 weeks. They presented with profound cyanosis soon after birth. All of them received endotracheal intubation and mechanical ventilation. Other treatments included inhalation of nitric oxide, intravenous milrinone, vasoactive drugs, diuretics and prostacyclin, etc. Extracorporeal membrane oxygenation (ECMO) was used in 6 infants as a bridge to surgical treatment. Two cases reported earlier death of cardiopulmonary failure without operation and the rest 19 survived after surgery. The followed surgery or autopsy revealed that all of them had tricuspid valve prolapse, rupture of papillary muscle or chordae tendineae. Conclusions: The severe TR resulting from rupture of papillary muscle or chordate tendineae in neonates is rare and could cause severe hypoxemia. Early recognition, adequate cardiopulmonary support to stabilize the hemodynamic status and timely surgery can significantly reduce the mortality.

Inhibitory effect of the Notch pathway-inhibitor DAPT on invasion and metastasis of tongue cancer via lncRNA-KAT14 regulation.

OBJECTIVE: We aimed to identify a reliable biomarker for tongue squamous cell carcinoma (TSCC), the most common oral cancer with no established biomarkers, to predict prognosis and to select the optimal treatment. MATERIALS AND METHODS: To investigate whether DAPT exhibited antitumor functions, CAL-27 and SCC-9 cells were treated with DAPT (5 µM or 10 µM) for different times. Further, qRT-PCR was used to determine the mRNA expression levels of lncRNA-KAT14 after treatment with DAPT or si-KAT14 and both combined. Moreover, the treated cells were cultured for different times to investigate their antitumor function. The Wound-healing and Transwell assay were carried out to evaluate the migration and invasion viability of cancer cells, respectively. Finally, the Western blots were performed to determine the expression of EMT-related proteins after transfection with si-KAT14 or treatment with DAPT to investigate the effects of DAPT on EMT-related proteins. RESULTS: Proliferation was inhibited after treatment with DAPT, and the expression of lncRNA-KAT14 was upregulated. To investigate the correlation of DAPT and lncRNA-KAT14 on the metastasis and invasion in tongue cancer, the following cellular processes were assessed: proliferation, invasion, and migration ability. The Western blots were used to determine the expression of E-cadherin, N-cadherin, Vimentin, and Snail, showing that DAPT or lncRNA-KAT14 suppressed all these processes, inducing a decreased expression of N-cadherin, Vimentin, and Snail, and increased expression of E-cadherin, compared with the control group. Once transfection with si-KAT14 occurred, the evaluated cellular processes were enhanced, being this attenuated by the treatment with DAPT. CONCLUSIONS: Our results suggest that DAPT suppresses invasion and metastasis of tongue cancer by regulating lncRNA-KAT14.

[Validation and optimization of the indicator system of risk assessment for mechanical cuts].

Objective: To validation and optimization the indicator system of risk assessment for mechanical cuts. Methods: The risk assessment index system of mechanical cutting injury established earlier was used to assess the risk of mechanical cutting injury in 40 cases of mechanical cutting injury registered from January 2015 to December 2017 and 40 similar positions without accidents in the same period. The multiple stepwise regression analysis was used to screen the indicator system, and to adjust the weight coefficient of each index. The total coincidence rate and Kappa value were compared between before and after optimization respectively. Results: The new index system has 3 first-class indicators, 10 second-class indicators and 14 three-class indicators, fewer than the old index system which has 3 first-class indicators, 10 second-class indicators, 34 three-class indicators. There three indicators have revamped in the first-class. The total of coincidence rates of the new and old indicator systems were 67.50% and 90.00%, the difference was statistically significant (P<0.01). The Kappa value were 0.35 and 0.80, respectively. Conclusion: The evaluation results with new indicator systems is more consistent with the actual hazard detection the the old indicator systems, and scientific, reasonable and practical, and the indicator system of risk assessment for mechanical cuts can be used for the risk assessment of mechanical cutting injuries.

Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression by triggering Nek2 degradation through a death-trap mechanism.

Hec1 (highly expressed in cancer 1) or Nek2 (NIMA-related kinase 2) is often overexpressed in cancers with poor prognosis. Both are critical mitotic regulators, and phosphorylation of Hec1 S165 by Nek2 is required for proper chromosome segregation. Therefore, inactivation of Hec1 and Nek2 by targeting their interaction with small molecules represents an ideal strategy for tackling these types of cancers. Here we showed that new derivatives of INH (inhibitor for Nek2 and Hec1 binding) bind to Hec1 at amino acids 394-408 on W395, L399 and K400 residues, effectively blocking Hec1 phosphorylation on S165 by Nek2, and killing cancer cells at the nanomolar range. Mechanistically, the D-box (destruction-box) region of Nek2 specifically binds to Hec1 at amino acids 408-422, immediately adjacent to the INH binding motif. Subsequent binding of Nek2 to INH-bound Hec1 triggered proteasome-mediated Nek2 degradation, whereas the Hec1 binding defective Nek2 mutant, Nek2 R361L, resisted INH-induced Nek2 degradation. This finding unveils a novel drug-action mechanism where the binding of INHs to Hec1 forms a virtual death-trap to trigger Nek2 degradation and eventually cell death. Furthermore, analysis of the gene expression profiles of breast cancer patient samples revealed that co-elevated expressions of Hec1 and Nek2 correlated with the shortest survival. Treatment of mice with this kind of tumor with INHs significantly suppressed tumor growth without obvious toxicity. Taken together, the new INH derivatives are suitable for translation into clinical application.

Three-dimensional contrast-enhanced magnetic resonance angiography at 3.0T scanner: significance in the classification of peripheral arterial occlusive disease.

AIM: Aim of this study was to evaluate the clinical efficacy of three-dimensional contrast-enhanced magnetic resonance angiography (3D CE-MRA); at 3.0T scanner in the classification of peripheral arterial occlusive disease (PAOD). METHODS: Thirty-five patients diagnosed of PAOD underwent 3D CE-MRA, 30 cases underwent digital subtracted angiography (DSA) successfully, and 12 cases underwent surgery. RESULTS: The vascular tree from the distal aorta to the lower limbs was well demonstrated. The extent and grade of disease seen in 3D CE-MRA closely matched those seen in DSA and/or surgery. Compared to the results of DSA and/or surgery, the common coincidence of 3D CE-MRA in diagnosing PAOD was 96.89% (780/805), the coincidence in diagnosing mild, moderate, severe stenosis and occlusion was 90.48% (76/84), 87.14% (61/70), 95.77% (68/71), and 98.29% (115/117) respectively, the rate of overestimate in mild, moderate, and severe stenosis was 5.95% (5/84), 10% (7/70), and 2.82% (2/71) respectively, the rate of underestimate in mild, moderate, severe stenosis and occlusion was 3.57% (3/84), 2.86% (2/70), 1.41% (1/71) and 1.74% (2/115) respectively. CONCLUSION: 3D CE-MRA at 3.0T scanner is of great value in the accurate assessment of the classification of PAOD; it is a reliable and promising new technique.

First Report of Neofusicoccum vitifusiforme Causing Blueberry Blight of Blueberry in China.

In May 2008, symptoms of blueberry blight were observed on half-high blueberry (Vaccinium corymbosum L.) in a plant nursery in Anning, Yunnan Province. Symptoms included dieback and bud and branch blight. Symptomatic plant samples were washed with running tap water, disinfected with 2% sodium hypochlorite and then 70% alcohol, rinsed in sterile distilled water, plated on potato dextrose agar (PDA), and incubated at 26°C. Conidia forming on PDA were hyaline, granular, fusoid to ellipsoid, widest in the upper third with an obtuse apex and flattened, subtruncate base, and 18 to 21 × 4.5 to 8 µm. The pathogen was also identified to the species level by sequencing the ribosomal internal transcribed spacer regions 1 and 2 (ITSI-5.8S-ITS2) and the translation elongation factor 1-alpha (EF1-α). BLAST searches at GenBank showed the highest nucleotide sequence identity with Neofusicoccum vitifusiforme reference sequence (ITS: >98%, EF638785; EF1-α: 100%, EF638744 and AY343343). Representative sequences of isolates from both regions were deposited in GenBank (ITS: Accession No. HM131604; EF1-α: Accession No. HM454277). Pathogenicity tests were conducted on 2-year-old blueberry seedlings (half-high blueberry). Mycelial plugs (3 mm in diameter) of N. vitifusiforme from actively growing colonies (PDA) were applied to same-size bark wounds in the center of the stems. Inoculation wounds were wrapped with Parafilm. Control seedlings received sterile PDA plugs. Inoculated and control seedlings (five each) were kept in a greenhouse and watered as needed. After 2 weeks, all of the inoculated but none of the control blueberry seedlings showed dark vascular stem tissue. N. vitifusiforme was reisolated from symptomatic tissues, thus fulfilling Koch's postulates. N. vitifusiforme has been reported as a pathogen of olive (2), plum, peach (1), and grapevine (3). To our knowledge, this is the first report of N. vitifusiforme on blueberry in China as well as worldwide. References: (1) U. Damm et al. Mycologia 99:664, 2007. (2) C. Lazzizera et al. Plant Pathol. 57:948, 2008. (3) J. M. van Niekerk et al. Mycologia 96:781, 2004.

Lyophilized paclitaxel magnetoliposomes as a potential drug delivery system for breast carcinoma via parenteral administration: in vitro and in vivo studies.

PURPOSE: The study reports in vitro and biological evaluation of lyophilized negatively charged paclitaxel magnetic liposomes as a potential carrier for breast carcinoma via parenteral administration. METHODS: Paclitaxel in magnetoliposomes were extracted by centrifugation and quantified by high-performance liquid chromatography (HPLC). Biological properties were studied using pharmacokinetics, in vivo distribution and cytotoxicity assays, as well as a mouse model of EMT-6 breast cancer. METHODS: Pharmacokinetic studies showed that encapsulation of paclitaxel in magnetoliposomes produced marked difference over the drug in Cremophor EL/ethanol pharmacokinetics, with an increased t(1/2beta) 19.37 h against 4.11 h. For in vivo distribution, paclitaxel concentration of lyophilized magnetoliposomes in the tumor was much higher than that of lyophilized conventional liposomes or Cremophor EL/ethanol, whereas in heart it was much lower than the latter two formulations via s.c. and i.v. administration. Lyophilized paclitaxel magnetic liposomes showed more potency on the therapy of breast cancer than other formulations via s.c. and i.p. administration. CONCLUSIONS: The current study demonstrates that paclitaxel magnetoliposomes can effectively be delivered to tumor and exert a significant anticancer activity with fewer side effects in the xenograft model.

Measurements of the local convective heat flux in turbulent Rayleigh-Bénard convection.

A systematic study of the local convective heat transport in turbulent thermal convection is carried out in small-aspect-ratio cells filled with water. The local convective heat flux is obtained from the simultaneous velocity and temperature measurements over varying Rayleigh numbers and spatial positions across the entire convection cell. Large fluctuations of the local convective heat flux are found mainly in the vertical direction and they are determined primarily by the thermal plumes in the system. The experiment reveals the spatial distribution of the local convective heat flux in a closed cell and thus settles a long-debated issue on how heat is transported in small-aspect-ratio cells.

Intermittency of velocity fluctuations in turbulent thermal convection.

We analyze velocity fluctuations in turbulent Rayleigh-Bénard convection. The velocity measurements were taken at the center of an aspect-ratio-one convection cell filled with water. The measured probability density functions of the velocity difference over a time interval tau are found to change with tau, indicating that the velocity fluctuations are intermittent. The velocity intermittency can be well characterized by the She-Leveque hierarchical structure. Our analyses further show that the vertical velocity component has distinct statistical features from the horizontal components. This result indicates that the vertical direction is special and buoyancy is important even at the center of the convection cell.

Measured local heat transport in turbulent Rayleigh-Bénard convection.

Local convective heat flux in turbulent thermal convection is obtained from simultaneous velocity and temperature measurements in an aspect-ratio-one convection cell filled with water. It is found that fluctuations of the vertical heat flux are highly intermittent and are determined primarily by the thermal plumes in the system. The experiment reveals a unique mechanism for the heat transport in turbulent convection.

Temperature oscillations in turbulent Rayleigh-Bénard convection.

A systematic study of temperature oscillations in turbulent thermal convection was carried out in two aspect-ratio-one convection cells filled with water. Temperature correlation functions and local velocity fluctuations were measured over varying Rayleigh numbers and spatial positions across the entire cell. These measurements fully characterize the spatial structure of the temperature oscillation and reveal the mixing and emission dynamics of the thermal plumes near the conducting surface. A sharp transition from a random chaotic state to a correlated turbulent state of finite coherence time is found when the Rayleigh number becomes larger than a critical value Ra(c) approximately equal 5 x 10(7). Above Ra(c) the measured temperature correlation functions show a well-defined oscillation with a finite coherence time. The oscillation period is found to be twice as large as the cell crossing time. The experiment demonstrates how the thermal plumes in a closed cell organize themselves both in space and time and generate coherent oscillations in a turbulent environment.

Large-scale velocity structures in turbulent thermal convection.

A systematic study of large-scale velocity structures in turbulent thermal convection is carried out in three different aspect-ratio cells filled with water. Laser Doppler velocimetry is used to measure the velocity profiles and statistics over varying Rayleigh numbers Ra and at various spatial positions across the whole convection cell. Large velocity fluctuations are found both in the central region and near the cell boundary. Despite the large velocity fluctuations, the flow field still maintains a large-scale quasi-two-dimensional structure, which rotates in a coherent manner. This coherent single-roll structure scales with Ra and can be divided into three regions in the rotation plane: (1) a thin viscous boundary layer, (2) a fully mixed central core region with a constant mean velocity gradient, and (3) an intermediate plume-dominated buffer region. The experiment reveals a unique driving mechanism for the large-scale coherent rotation in turbulent convection.

Onset of coherent oscillations in turbulent Rayleigh-Bénard convection.

We report temperature cross correlation and velocity profile measurements in the aspect-ratio-one convection cell filled with water. A sharp transition from a random chaotic state to a correlated turbulent state of finite coherence time is found when the Rayleigh number becomes larger than a critical value Ra(c) approximately equal to 5 x 10(7). The experiment reveals a unique mechanism for the onset of coherent oscillations in turbulent Rayleigh-Bénard convection.

Effect of hyaluronidase on albumin diffusion in lung interstitium.

Albumin diffusion measured in an isolated segment of rabbit lung interstitium with a radioactive tracer ((125)I-albumin) technique was independent of albumin concentration and similar to the free diffusion of albumin in water (Qiu et al, 1998. J Appl Physiol 85: 575-583). We studied the effect of hyaluronidase on the diffusion of albumin. Isolated rabbit lungs were inflated with silicon rubber by way of airways and blood vessels, and two chambers were bonded to the sides of a approximately 0.5-cm thick slab enclosing a vessel with an interstitial cuff. One chamber was filled with 2 g/dl albumin solution containing (125)I-albumin and 0.02 g/dl hyaluronidase. Unbound (125)I was removed from the tracer by dialysis before use. The other chamber filled with Ringer's solution was placed within a NaI(Tl) scintillation detector. Diffusion of tracer was measured continuously for 120 h. Albumin diffusion coefficient (D) and interstitial area (A) were obtained by fitting the tracer-time curve with the theoretical solution of the equation describing one-dimension diffusion of a solute across a membrane. D averaged 5.2 x 10(-7) cm(2)/s for albumin diffusion with hyaluronidase, 20% less than that measured previously without hyaluronidase. Hyaluronidase had no effect on A. Results indicated an interaction between albumin and interstitial hyaluronan that was the opposite of the steric effect on albumin excluded volume measured in solution.

Effect of concentration on albumin diffusion in lung interstitium.

The transport of macromolecules through the lung interstitium depends on both bulk transport of fluid and diffusion. In the present study, we studied the diffusion of albumin. Isolated rabbit lungs were inflated with silicon rubber via airways and blood vessels, and two chambers were bonded to the sides of a 0.5-cm-thick slab that enclosed a vessel with an intersititial cuff. One chamber was filled with either albumin solution (2 or 5 g/dl) containing tracer 125I-albumin or with tracer 125I-albumin alone; the other was filled with Ringer solution. Unbound 125I was removed from the tracer by dialysis before use. The chamber with Ringer solution was placed in the well of a NaI(Tl) scintillation detector. Diffusion of tracer through the interstitium was measured continuously for 60 h. Tracer mass (M) showed a time (t) delay followed by an increase to a steady-state flow (dM/dt constant). Albumin diffusion coefficient (D) was given by L2/(6T), where T was the time intercept of the steady-state M-t line at zero M, and L was interstitial length. Interstitial cuff thickness-to-vessel radius ratio (Th0/R) was estimated by using Fick's law for steady-state diffusion. Both D and Th0/R were independent of albumin concentration. D averaged 6.6 x 10(-7) cm2/s, similar to the free D for albumin. Values of Th0/R averaged 0.047 +/- 0.024 (SD), near the values measured histologically. Thus pulmonary interstitial constituents offered no restriction to the diffusion of albumin.

Effect of hydration on lung interstitial conductivity response to electrically charged solutions.

In interstitial segments of rabbit lung, we compared the flow of a solution containing cationic protamine sulfate (0.08 mg/ml) or cationic dextran (0.1%) to that of Ringer or neutral dextran solution. Also compared, were the flow of solutions containing anionic dextran (0.1 or 1.5%) to those containing neutral dextran and the flow of hyaluronidase solution (0.02%) to that of Ringer solution, at mean interstitial pressures (Pm) between -5 and 15 cmH2O. Driving pressure was set at 5 cmH2O. Cationic protamine or cationic dextran-to-Ringer flow ratio increased with Pm (presumably as hydration increased) but in nonedematous interstitium (-5 cmH2O Pm), flow ratio was 1, indicating a viscosity-dependent flow. In contrast, the flow of anionic dextran solution decreased relative to that of neutral dextran; this decrease was constant with hydration, but was greater at the higher concentration of dextran. Interstitial conductivity to the flow of hyaluronidase increased with hydration. However, this behavior was absent after the flow of 1.5% anionic dextran, indicating an inhibitory effect of the higher concentration of anionic dextran on the hyaluronidase response. A negative charge in microvascular filtrate may control fluid clearance in normal interstitium, while a positive charge would enhance clearance only in edema formation.

Changes in dimensions and mechanical properties of bone in chicks fed high levels of niacin.

Tibia dimensions and mechanical properties were determined in White Leghorn cockerels that had been fed from 0.1 to 2.0% niacin as a supplement to standard poultry diets. Four experiments of from 20 to 38 days were conducted. No significant differences due to niacin were found in weight gain, feed consumed or feed:gain ratios. Decreases in the exterior (P < 0.009) and interior (P < 0.015) diameters of the major axes of the tibiae were found at 0.75-2.0% niacin. Exterior (P < 0.005) and interior (P < 0.001) diameters of the minor axes of the tibia were decreased at levels of 0.75 and 1%. Changes occurred in lateral wall thickness of chicks fed 0.75% niacin for 20 days (P < 0.004) and 38 days (P < 0.023) and in anterior wall thickness of 6-month-old chickens fed 1.0% niacin for 28 days (P < 0.001). Ultimate force was decreased in young chicks fed 1.0 and 1.5% niacin (P < 0.014) and 6-month-old White Leghorn chickens fed 1.0% niacin (P < 0.004). The addition of high levels of niacin to chick rations resulted in changes in dimensions, bone strength and susceptibility to fracture.