Heparin-free after 3000 IU heparin loaded in veno-venous ECMO supported acute respiratory failure patients with hemorrhage risk: a novel anti-coagulation strategy.

BACKGROUND: The anti-coagulation protocol of patients with hemorrhage risk primary disease who need extracorporeal membrane oxygenation (ECMO) supported is controversial. This study evaluated the feasibility of a new anti-coagulation strategy, that is heparin-free after 3000 IU heparin loaded in veno-venous ECMO (VV ECMO) supported acute respiratory failure patients with hemorrhage risk. METHODS: A retrospective study was performed in a series of hemorrhage risk patients supported with VV ECMO at the First Affiliated Hospital of Zhengzhou University, between June 2012 to Sept 2020. A total of 70 patients received a low heparin bolus of 3000 units for cannulation but without subsequent, ongoing heparin administration. Patients were divided into survival (n = 25) and non-survival group (n = 45). Data of coagulation, hemolysis and membrane lung function were calculated and analyzed. The complications of patients were recorded. Finally, the binary Logistic regression was conducted. RESULTS: The longest heparin-free time was 216 h, and the mean heparin-free time was 102 h. Compared with survivors, the non-survivors were showed higher baseline SOFA score and lower platelet counts in 0.5 h, 24 h, 48 h and 96 h after ECMO applied. However, there was no significant differences between survivors and non-survivors in ACT, APTT, INR, D-dimer, fibrinogen, LDH, blood flow rate, Δp and Ppost-MLO2 (all p < 0.05) of all different time point. Moreover, only the baseline SOFA score was significantly associated with mortality (p < 0.001, OR(95%CI): 2.754 (1.486-5.103)) while the baseline levels of ACT, APTT, INR, platelet, D-dimer, fibrinogen and LDH have no association with mortality. The percentage of thrombosis complications was 54.3% (38/70) including 3 oxygenator changed but there was no significant difference of complications in survival and non-survival groups (p > 0.05). CONCLUSIONS: The anticoagulation protocol that no heparin after a 3000 units heparin bolus in VV ECMO supported acute respiratory failure patients with hemorrhage risk is feasible.

Three-Dimensional Cuprous Lead Bromide Framework with Highly Efficient and Stable Blue Photoluminescence Emission.

Considering the instability and low photoluminescence quantum yield (PLQY) of blue-emitting perovskites, it is still challenging and attractive to construct single crystalline hybrid lead halides with highly stable and efficient blue light emission. Herein, by rationally introducing d10 transition metal into single lead halide as new structural building unit and optical emitting center, we prepared a bimetallic halide of [(NH4 )2 ]CuPbBr5 with new type of three-dimensional (3D) anionic framework. [(NH4 )2 ]CuPbBr5 exhibits strong band-edge blue emission (441 nm) with a high PLQY of 32 % upon excitation with UV light. Detailed photophysical studies indicate [(NH4 )2 ]CuPbBr5 also displays broadband red light emissions derived from self-trapped states. Furthermore, the 3D framework features high structural and optical stabilities at extreme environments during at least three years. To our best knowledge, this work represents the first 3D non-perovskite bimetallic halide with highly efficient and stable blue light emission.

LIM protein JUB promotes epithelial-mesenchymal transition in colorectal cancer.

Metastasis is the leading cause of cancer-related death in almost all types of cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep, dynamic biological event, and epithelial-mesenchymal transition (EMT) is a critical process during the cascade. Ajuba family proteins are LIM domain-containing proteins and are reported to be transcription repressors regulating different kinds of physiological processes. However, the expression and pathological roles of Ajuba family proteins in tumors, especial in tumor metastasis, remain poorly studied. Here, we found that JUB, but not the other Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell lines. Ectopic expression of JUB induced EMT and enhanced motility and invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces EMT via Snail and JUB is also required for Snail-induced EMT. The expression of JUB shows an inverse correlation with E-cadherin expression in clinical specimens. Taken together, these findings revealed that the LIM protein JUB serves as a tumor-promoting gene in CRC by promoting EMT, a critical process of metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of metastatic CRC.

Ultra-dense Motion Capture: An exploratory full-automatic approach for dense tracking of breast motion in 4D.

Understanding the dynamic deformation pattern and biomechanical properties of breasts is crucial in various fields, including designing ergonomic bras and customized prostheses, as well as in clinical practice. Previous studies have recorded and analyzed the dynamic behaviors of the breast surface using 4D scanning, which provides a sequence of 3D meshes during movement with high spatial and temporal resolutions. However, these studies are limited by the lack of robust and automated data processing methods which result in limited data coverage or error-prone analysis results. To address this issue, we identify revealing inter-frame dense correspondence as the core challenge towards conducting reliable and consistent analysis of the 4D scanning data. We proposed a fully-automatic approach named Ulta-dense Motion Capture (UdMC) using Thin-plate Spline (TPS) to augment the sparse landmarks recorded via motion capture (MoCap) as initial dense correspondence and then rectified it with a sophisticated post-alignment scheme. Two downstream tasks are demonstrated to validate its applicability: virtual landmark tracking and deformation intensity analysis. For evaluation, a dynamic 4D human breast anthropometric dataset DynaBreastLite was constructed. The results show that our approach can robustly capture the dynamic deformation characteristics of the breast surfaces, significantly outperforms baselines adapted from previous works in terms of accuracy, consistency, and efficiency. For 10 fps dataset, average error of 0.25 cm on control-landmarks and 0.33 cm on non-control (arbitrary) landmarks were achieved, with 17-70 times faster computation time. Evaluation was also carried out on 60 fps and 120 fps datasets, with consistent and large performance gaining being observed. The proposed method may contribute to advancing research in breast anthropometry, biomechanics, and ergonomics by enabling more accurate tracking of the breast surface deformation patterns and dynamic characteristics.

Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood. METHODS: In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells. RESULTS: Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1. CONCLUSIONS: Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics.

Analysis of Diabetic Foot Deformation and Plantar Pressure Distribution of Women at Different Walking Speeds.

Official guidelines state that suitable physical activity is recommended for patients with diabetes mellitus. However, since walking at a rapid pace could be associated with increased plantar pressure and potential foot pain, the footwear condition is particularly important for optimal foot protection in order to reduce the risk of tissue injury and ulceration of diabetic patients. This study aims to analyze foot deformation and plantar pressure distribution at three different walking speeds (slow, normal, and fast walking) in dynamic situations. The dynamic foot shape of 19 female diabetic patients at three walking speeds is obtained by using a novel 4D foot scanning system. Their plantar pressure distributions at the three walking speeds are also measured by using the Pedar in-shoe system. The pressure changes in the toes, metatarsal heads, medial and lateral midfoot, and heel areas are systematically investigated. Although a faster walking speed shows slightly larger foot measurements than the two other walking speeds, the difference is insignificant. The foot measurement changes at the forefoot and heel areas, such as the toe angles and heel width, are found to increase more readily than the measurements at the midfoot. The mean peak plantar pressure shows a significant increase at a faster walking speed with the exception of the midfoot, especially at the forefoot and heel areas. However, the pressure time integral decreases for all of the foot regions with an increase in walking speed. Suitable offloading devices are essential for diabetic patients, particularly during brisk walking. Design features such as medial arch support, wide toe box, and suitable insole material for specific area of the foot (such as polyurethane for forefoot area and ethylene-vinyl acetate for heel area) are essential for diabetic insole/footwear to provide optimal fit and offloading. The findings contribute to enhancing the understanding of foot shape deformation and plantar pressure changes during dynamic situations, thus facilitating the design of footwear/insoles with optimal fit, wear comfort, and foot protection for diabetic patients.

Influence of Contoured Insoles with Different Materials on Kinematics and Kinetics Changes in Diabetic Elderly during Gait.

BACKGROUND: Alterations in the lower limb kinematics and kinetics of diabetic patients have been reported in previous studies. Inappropriate choices of orthopedic insole materials, however, fail to prevent diabetic foot ulcers and modify abnormal gait. The aim of this study was to quantitatively compare the effects of contoured insoles with different materials on the kinematics of and kinetics changes in the diabetic elderly during gait. METHODS: There were 21 diabetic patients who participated in this study. Three-dimensional (3D) experimental contoured insoles constructed of soft (i.e., Nora Lunalastik EVA and PORON® Medical 4708) and rigid (i.e., Nora Lunalight A fresh and Pe-Lite) materials with Langer Biomechanics longitudinal PPT® arch pads were adopted. An eight-camera motion capture system (VICON), two force plates, and an insole measurement system-Pedar® with 99 sensors-were utilized to obtain the kinematics and kinetics data. The plug-in lower body gait model landmarks were used for dynamic data acquisition during gait. The corresponding data from five gait cycles were selected and calculated. RESULTS: The range of motions (ROMs) of the ankle joint (p = 0.001) and knee joint (p = 0.044) were significantly influenced when the contoured insoles were worn in comparison to the barefoot condition. The joint moments of the lower limbs with maximum ankle plantarflexion during the loading response and maximum knee and hip flexions were significantly influenced by the use of contoured insoles with different materials in the diabetic elderly. The peak plantar pressure (PPP) of the forefoot (p < 0.001), midfoot (p = 0.009), and rearfoot (p < 0.001) was significantly offloaded by the contoured insoles during the stance phase, whilst the PPP of the rearfoot (p < 0.001) was significantly offloaded during the swing phase. CONCLUSIONS: The contoured insoles, especially those constructed with soft materials, significantly offloaded the PPP during gait-hence accommodating certain abnormal gait patterns more effectively compared to going barefoot.

Role and Clinical Application of Metagenomic Next-Generation Sequencing in Immunocompromised Patients With Acute Respiratory Failure During Veno-Venous Extracorporeal Membrane Oxygenation.

Objectives: There are few studies of metagenomic next-generation sequencing (mNGS) in immunocompromised patients assisted by veno-venous extracorporeal membrane oxygenation (vv-ECMO). The present study is aimed to investigate the pathogen-detected effect and clinical therapy value of mNGS technologies in immunocompromised patients assisted by vv-ECMO. Methods: Our study retrospectively enrolled 46 immunocompromised patients supported by vv-ECMO from Jan 2017 to June 2021 at the First Affiliated Hospital of Zhengzhou University, respectively. Patients were divided into the deterioration group (Group D) (n = 31) and improvement group (Group I) (n = 15) according to their outcomes. Baseline characteristics and etiological data of patients during hospitalization of 2 groups were compared. The pathogens detected by mNGS and antibiotic regimens guided by mNGS in immunocompromised patients assisted by vv-ECMO were analyzed. Results: Compared with Group I, the deterioration patients showed a higher percentage of chronic obstructive pulmonary disease (COPD) (32.3% vs. 6.7%, p < 0.01) and were significantly older (47.77 ± 16.72 years vs. 32 ± 15.05 years, p < 0.01). Within 48 h of being ECMO assisted, the consistency of the samples detected by traditional culture and mNGS at the same time was good (traditional culture vs. mNGS detection, the positive rate of bronchoalveolar lavage fluid (BALF) culture: 26.1% vs. 30.4%; the positive rate of blood sample culture: 12.2% vs. 12.2%, p > 0.05). However, mNGS detected far more pathogen species and strains than conventional culture (30 strains vs. 78 strains, p < 0.01); the most popular pathogen was Klebsiella pneumoniae. Parts of patients had their antibiotic treatment adjustments, and the improvement patients showed less usage of broad-spectrum antibiotics. Conclusions: mNGS may play a relatively important role in detecting mixed pathogens and personalized antibiotic treatment in immunocompromised patients assisted by vv-ECMO.

Permutation transformations of tensors with an application.

The permutation transformation of tensors is introduced and its basic properties are discussed. The invariance under permutation transformations is studied for some important structure tensors such as symmetric tensors, positive definite (positive semidefinite) tensors, Z-tensors, M-tensors, Hankel tensors, P-tensors, B-tensors and H-tensors. Finally, as an application of permutation transformations of tensors, the canonical form theorem of tensors is given. The theorem shows that some problems of higher dimension tensors can be translated into the corresponding problems of lower dimension weakly irreducible tensors so as to handle easily.

Mir-184 post-transcriptionally regulates SOX7 expression and promotes cell proliferation in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer mortality worldwide. The development and progression of HCC is a complicated process, involving the deregulation of multiple genes that are essential to cell biological processes. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Our study showed that miR-184 is upregulated in HCC cell lines and tissues. Overexpression of miR-184 in HCC cells increased cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-184 reduced cell proliferation, tumorigenicity, and cell cycle progression. Additionally, we identified SOX7 as a direct target of miR-184. Ectopic expression of miR-184 led to downregulation of the SOX7 protein, resulting in upregulation of c-Myc, Cyclin D1, and phosphorylation of Rb. Our findings suggested that miR-184 represents a potential onco-miR and plays an important role in HCC progression by suppressing SOX7 expression.

Differential expression of stromal aromatase in obese females is regulated by DNA methylation.

Obesity increases the incidence, progression and mortality of breast cancer among postmenopausal females. This is partly due to excessive estrogen production in the adipose tissue of obese females. Aromatase is a key enzyme in estrogen biosynthesis. In the current study, the tensional force­triggered inducibility of aromatase expression was observed to vary in ASCs isolated from different disease­free individuals. In addition, this phenomenon was associated with the activation of the aromatase PII promoter and its DNA methylation load. These findings highlight the impact of tensional forces on estrogen biosynthesis in obese females.

[An investigation on correlation of severity of brain injury with the expression of activin A and C-reactive protein].

OBJECTIVE: To determine the dynamic change in serum levels of activin A (ACTA) and C-reaction protein (CRP) in patients with brain injury, and to investigate its significance. METHODS: A prospective study was conducted. A total of 57 adult patients with brain injury occurring within 24 hours admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from August 2012 to June 2013 were enrolled. The patients were allocated into three groups according to their Glasgow coma scale (GCS) as follows: minor brain injury (GCS 13-15, n=17), moderate brain injury (GCS 9-12, n=18), heavy brain injury (GCS 3-8, n=22). The clinical and related laboratory data (reflecting the function of liver, kidney, lung, blood coagulability etc.) were recorded after ICU admission. At the same time, venous samples were collected on the day 1, 2, 3, 5, 7 after ICU admission for determination of ACTA with enzyme linked immunosorbent assay (ELISA) and CRP with fluorescence immunoassay technology. The correlation between ACTA and CRP was analyzed by linear correlation. The receiver operating characteristic (ROC) curve was plotted to analyze the accuracy of ACTA and CRP as a prognostic indicator in brain injury. Fifteen healthy persons were enrolled as the control group. RESULTS: The serum levels of ACTA and CRP in patients with minor, moderate and heavy brain injury were significantly higher than those in healthy control group [ACTA (µg/L): 23.96±3.55, 42.06±5.67, 52.32±4.46 vs. 13.66±2.45, all P<0.01; CRP (mg/L): 14.12±2.45, 23.05±2.85, 30.93±2.35 vs. 3.42±2.25, all P<0.01]. As the patients' condition worsening, levels of ACTA and CRP tended to elevate (all P<0.01). Levels of ACTA and CRP in minor, moderate and heavy brain injury groups were increased after ICU admission. On day 3, levels of serum ACTA and CRP reached the peak values [ACTA (µg/L):30.62±2.54, 51.35±2.55, 60.52±2.55; CRP (mg/L): 18.62±2.64, 30.35±2.25, 37.52±2.55], and then they lowered gradually. In minor and moderate brain injury groups, the levels of ACTA and CRP were slowly descending, and on day 7, they maintained at a lower level [ACTA (µg/L): 13.68±2.54, 37.74±2.55; CRP (mg/L): 6.68±2.44, 19.74±2.55]. On the contrary, the levels of ACTA and CRP in heavy brain injury group persistently maintained at a high level on day 7 [ACTA: (42.32±2.54) µg/L, CRP: (33.32±2.56) mg/L]. There were significant differences in ACTA and CRP among different degrees of brain injury groups (all P<0.01). There was a positive correlation between ACTA and CRP (r=0.958, P=0.007). ROC curve analysis showed that the sensitivity for brain injury prediction was 93.3% for ACTA with specificity 95.0%, area under ROC curve(AUC) 0.843, and the sensitivity for CRP was 89.1% with specificity 68.2%, AUC 0.723. CONCLUSIONS: Serum levels of ACTA and CRP in patients with brain injury are strongly correlated with the severity of the injury. Furthermore, ACTA is more sensitive than CRP in detecting early brain injury. Therefore, ACTA is a specific factor for detecting brain injury.

[Evolutionary stability analysis of asymmetric hawk-dove game considering the impact of common resource].

Explaining the evolution of cooperation remains one of the important problems in both biology and social science. Classical theories mainly based on an assumption that cooperative players are symmetrically interacted. However, almost all the well-studied systems showed that cooperative players are in fact asymmetrically interacted and that asymmetric interaction might greatly affect cooperation behavior of the involved players. Considering the asymmetric interaction and the selection pressure of resources, we present a model that possesses four strategies: strength- cooperation (SC), strength-defection (SD), weakness-cooperation (WC) and weakness-defection (WD). Combining evolutionary game theory with dynamical stability theory, we find that the evolutionary results closely depend on the asymmetric interaction and selection pressure of resources as well as cost-to-benefit ratio of conflict. When the common resources are plentiful, the cost-to-benefit ratio of conflict is negatively correlated with the probability of SC, while it is positively correlated with the probability of SD and WD. With increasing the strength ratio between the strong and weak players, the proportion of SC and SD will increase, while the proportion of WD will reduce. The model developed here has intrinsically integrated Boxed Pigs game and Hawk-Dove game. When the common resource is at shortage, the Boxed Pigs game will transform into Hawk-Dove game under the increase of the strength ratio between the strong and weak players.