[Effect of Selinexor on Proliferation and Apoptosis of Acute Myeloid Leukemia Kasumi-1 Cells].

OBJECTIVE: To investigate the effects of selinexor, a inhibitor of nuclear export protein 1 (XPO1) on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia (AML). METHODS: MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points. The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry. RESULTS: Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner (r 24 h=0.7592, r 48 h=0.9456, and r 72 h=0.9425). Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner (r =0.9057 in 2.5 µmol/L group, r =0.9897 in 5 µmol/L group and r =0.9994 in 10 µmol/L group). Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner (r =0.9732), and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration. The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor. With the increase of drug concentration, the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased. CONCLUSION: Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation, inducing apoptosis and blocking cell cycle.

An analytic method to investigate hemodynamics of the cardiovascular system: Biventricular system.

Previously, we found analytic solutions for single ventricular system based on the lumped parameter model (LPM). In this study, we generalized the method to biventricular system and derived its analytic solutions. LPM is just a set of differential equations, but it is difficult to solve due to time-varying ventricular elastance and high order. Mathematically, there exist no elementary solutions for time-varying equations. It turns out that instead of differential equations, according to volume conservation, a set of algebraic equations can be carried out. The solutions of the set of equations are just physiological states at end of systolic and diastolic phases such as end systolic/diastolic pressure/volume of left ventricle. As a preliminary application, the method is utilized to deduce the hemodynamic effects of VA ECMO. Left ventricular (LV) distension, a serious complication of VA ECMO, is usually attributed to factors such as increased afterload, inadequate LV unloading, reduced myocardial contractility or aortic valve regurgitation (AR), bronchial and Thebesian return in the absence of aortic valve (AoV) opening. Among these, reduced contractility and AR are strongly associated with LV distension. However, in the absence of reduced contractility or AR, it is less clear whether increased afterload or inadequate LV unloading alone can cause LV distension. This leads to the critical question: under what conditions does LV distension occur in the absence of reduced contractility or AR? The analytic formulas derived in this study give conditions for LV distension. Furthermore, the results show that the analytic hemodynamics are coincident with simulated results.

Interaction of Th17 differentiations-related gene polymorphisms and environmental factors contributing to the disease classification, complications, and surgical risks of Crohn's disease in the Chinese Han population.

OBJECTIVES: Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals. METHODS: We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis. RESULTS: Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD. CONCLUSIONS: This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis.

Human health risk assessment of volatile organic compounds in oil-based drill cuttings of shale gas.

Waste oil-based drill cuttings contain dioxins and volatile organic compounds (VOCs), which have the potential to cause serious health effects in humans. Therefore, this paper took oil-based drill cuttings (OBDCs) as the research object and carried out the testing of VOCs and dioxins content by using GC-MS and HRGCS-HRMS and comprehensively evaluated the content, composition and distribution pattern of VOCs and dioxins and the risk to human health posed by the two pollutants in OBDCs. The results showed that the VOCs did not exceed the emission limits in ESPPI (GB 31571-2015), but it is vital to recognise that 1,2-dichloropropane has the potential to cause cancer risk, with soil and groundwater risk control values of 662.95 mg·kg-1 and 0.066 mg·kg-1, respectively. Benzene, 1,2-dichloropropane and 8 other VOCs pose a non-carcinogenic risk to humans. The levels of polychlorinated dibenzofurans (PCDFs) exceeded those of polychlorinated dibenzo-p-dioxins (PCDDs), which accounted for 95.76 percent of the total PCDD/Fs, 2,3,4,7,8-P5CDF (56.00%), 2,3,7,8-T4CDF (9.20%), 1,2,3,6,7,8-H6CDF (8.80%) and 1,2,3,7,8-P5CDF (8.00%) were the main contributing monomers. The findings of the assessment on exposure risk indicate that there is a respiratory risk to oil-based drill cuttings dioxins for adults and children exceeded the World Health Organisation (WHO) acceptable daily intake (ADI) (1-4 pgTEQ/kg/d). Finally, three aspects of solid waste pre-treatment prior to incineration, the incineration process and post incineration were used to reduce the environmental and human health risks from dioxins.

Intensive Care Unit Nurses' Attitudes Toward Truth-Telling, Life-Sustaining Treatment, and Decision-Making Intention for End-of-Life Patients: A Cross-sectional Survey.

Truth-telling and life-sustaining treatment decisions are important elements of the quality of patients' care at the end of life. As the primary caregivers of patients at the end of life in intensive care units (ICUs), ICU nurses play an important role in patient decision making and hospice care. This study aimed to investigate and analyze ICU nurses' attitudes toward truth-telling, attitudes toward end-of-life life-sustaining treatment, and end-of-life decision-making behavioral intentions. One hundred twenty-two ICU nurses participated in this cross-sectional survey. Data were collected using a validated questionnaire. The results showed that ICU nurses' attitudes toward telling patients the truth and end-of-life life-sustaining treatment were both positive, but further improvement is needed. Nurses have a higher willingness to make palliative care decisions for patients at the end of life and to help patients achieve a good death. The truth-telling attitude, the life-sustaining treatment attitude, and whether they knew that cardiopulmonary resuscitation could be legally forgone at the end of life were factors influencing ICU nurses' behavioral intention toward decision making for patients at the end of life (all P s < .05). We conclude that nurses' participation in truth-telling and end-of-life decision making should be promoted, and timely hospice care should be provided to patients to help them achieve a good death.

Three-dimensional oxygen concentration monitoring in hydrogels using low-cost phosphorescence lifetime imaging for tissue engineering.

Oxygen concentration measurement in 3D hydrogels is vital in 3D cell culture and tissue engineering. However, standard 3D imaging systems capable of measuring oxygen concentration with adequate precision are based on advanced microscopy platforms, which are not accessible in many laboratories due to the system's complexity and the high price. In this work, we present a fast and low-cost phosphorescence lifetime imaging design for measuring the lifetime of oxygen-quenched phosphorescence emission with 0.25 µs temporal precision and sub-millimeter spatial resolution in 3D. By combining light-sheet illumination and the frequency-domain lifetime measurement using a commercial rolling-shutter CMOS camera in the structure of a conventional optical microscope, this design is highly customizable to accommodate application-specific research needs while also being low-cost as compared to advanced instruments. As a demonstration, we made a fluidic device with a gas-permeable film to create an artificial oxygen gradient in the hydrogel sample. Dye-embedded beads were distributed in the hydrogel to conduct continuous emission lifetime monitoring when nitrogen was pumped through the fluidic channel and changed oxygen distribution in the sample. The dynamics of the changes in lifetime co-related with their location in the gel of size 0.5 mm×1.5 mm×700 µm demonstrate the ability of this design to measure the oxygen concentration stably and precisely in 3D samples.

In vitro comparative study of red blood cell and VWF damage on 3D printing biomaterials under different blood-contacting conditions.

Mechanical circulatory support devices (MCSDs) are often associated with hemocompatible complications such as hemolysis and gastrointestinal bleeding when treating patients with end-stage heart failure. Shear stress and exposure time have been identified as the two most important mechanical factors causing blood damage. However, the materials of MCSDs may also induce blood damage when contacting with blood. In this study, the red blood cell and von Willebrand Factor (VWF) damage caused by four 3D printing biomaterials were investigated, including acrylic, PCISO, Somos EvoLVe 128, and stainless steel. A roller pump circulation experimental platform and a rotor blood-shearing experimental platform were constructed to mimic static and dynamic blood-contacting conditions of materials in MCSDs, respectively. Free hemoglobin assay and VWF molecular weight analysis were performed on the experimental blood samples. It indicated that different 3D printing materials and technology could induce different levels of damage to red blood cells and VWF, with acrylic causing the least damage under both static and dynamic conditions. In addition, it was found that blood damage measured for the same material differed on the two platforms. Therefore, a combination of static and dynamic experiments should be used to comprehensively investigate the effects of blood damage caused by the material. It can provide a reference for the design and evaluation of materials in different components of MCSDs.

[Effect of Nucleolin on Lymphoma Proliferation by Regulating Thymidine Kinase 1].

OBJECTIVE: To investigate the mechanism of nucleolin (NCL) involved in lymphoma proliferation by regulating thymidine kinase 1 (TK1). METHODS: Twenty-three patients with diffuse large B-cell lymphoma (DLBCL) were selected and divided into initial treatment group (14 cases) and relapsed/refractory group (9 cases). Serum TK1 and C23 protein in peripheral blood mononuclear cells were detected. Cell models of CA46-NCL-KD (CA46-NCL-knockdown) and CA46-NCL-KNC (CA46-NCL-knockdown negative control) were established by lentivirus vector mediated transfection in Burkitt lymphoma cell line CA46. The half maximal inhibitory concentration (IC50) of CA46-NCL-KD, CA46-NCL-KNC, and CA46 to adriamycin were detected by cell proliferation assay (MTS). The expression of NCL mRNA and protein in CA46-NCL-KD and CA46-NCL-KNC cells were dectected by Q-PCR and Western blot, respectively. The cell cycle of CA46-NCL-KD, CA46-NCL-KNC, and CA46 cells were detected by flow cytometry. The expression of TK1 protein in CA46-NCL-KD and CA46-NCL-KNC cells was detected by an enhanced chemiluminescence (ECL) dot blot assay. RESULTS: The level of serum TK1 in the initial treatment group was 0.43(0-30-1.01) pmol/L, which was lower than 10.56(2.19-14.99) pmol/L in the relapsed/refractory group (P<0-01), and the relative expression level of NCL protein in peripheral blood was also significantly lower. The IC50 of CA46-C23-KD cells to adriamycin was (0.147±0.02) µg/ml, which was significantly lower than (0.301±0.04) µg/ml of CA46-C23-KNC cells and (0.338±0.05) µg/ml of CA46 cells (P<0.05). Compared with CA46-NCL-KNC cells, the expression of NCL mRNA and protein, TK1 protein decreased in CA46-NCL-KD cells, and the proportion of S phase and G2/M phase also decreased, while G0/G1 phase increased in cell cycle. CONCLUSION: The increased expression of NCL in DLBCL and CA46 cells indicates low sensitivity to drug. NCL may participate in regulation of lymphoma proliferation by affecting TK1 expression, thereby affecting the drug sensitivity.

Constructing and evaluating the effect of micron-scale structures on von Willebrand factor damage.

The incidence of clinical complication gastrointestinal bleeding has been proved as consequence of von Willebrand factor (VWF) damage after mechanical circulatory support in clinic. Many studies have been conducted to evaluate VWF damage, of which the most studied influencing factors are mechanical factors such as shear stress. However, in addition to mechanical factors, VWF damage may also be affected by interface factors. To address this issue, a roller pump circulation platform was established to investigate the effect of material surface micron-scale structures distribution on VWF damage in flow state. A composite micro-structure combining microngrating and micronpost was designed and constructed on the surface of Si wafer by lithography and reactive ion etching, and detailed characterization of material surfaces was also performed. Then the changes of VWF antigen, VWF ristocetin cofactor activity, and the degradation of high molecular weight VWF on these surfaces were investigated and compared. The results showed that, with the encryption of surface micro-structures arrangement, the material surface tends to be more hydrophobic, which is beneficial to reduce VWF damage. Therefore, in the design of material surface inside the mechanical circulatory support devices, it can be considered to add some surface micro-structures with a certain distribution density to change the hydrophilicity and hydrophobicity, so as to minimize the VWF damage. These results can provide important references for the evaluation of VWF damage caused by interface factors, and aid in designing material surface inside the mechanical circulatory support devices.

A comprehensive comparison of the in vitro hemocompatibility of extracorporeal centrifugal blood pumps.

Purpose: Blood damage has been associated with patients under temporary continuous-flow mechanical circulatory support. To evaluate the side effects caused by transit blood pumping, in vitro hemocompatibility testing for blood damage in pumps is considered a necessary reference before clinical trials. Methods: The hemocompatibility of five extracorporeal centrifugal blood pumps was investigated comprehensively, including four commercial pumps (the Abbott CentriMag, the Terumo Capiox, the Medos DP3, and the Medtronic BPX-80) and a pump in development (the magAssist MoyoAssist®). In vitro, hemolysis was tested with heparinized porcine blood at nominal operating conditions (5 L/min, 160 mmHg) and extreme operating conditions (1 L/min, 290 mmHg) using a circulation flow loop. Hematology analyses concerning the blood cell counts and the degradation of high-molecular-weight von Willebrand factor (VWF) during 6-h circulation were also evaluated. Results: Comparing the in vitro hemocompatibility of blood pumps at different operations, the blood damage was significantly more severe at extreme operating conditions than that at nominal operating conditions. The performance of the five blood pumps was arranged in different orders at these two operating conditions. The results also demonstrated superior hemocompatibility of CentriMag and MoyoAssist® at two operating conditions, with overall low blood damage at hemolysis level, blood cell counts, and degradation of high-molecular-weight VWF. It suggested that magnetic bearings have an advantage in hemocompatibility compared to the mechanical bearing of blood pumps. Conclusion: Involving multiple operating conditions of blood pumps in in vitro hemocompatibility evaluation will be helpful for clinical application. In addition, the magnetically levitated centrifugal blood pump MoyoAssist® shows great potential in the future as it demonstrated good in vitro hemocompatibility.

Revision and Validation of the Chinese Version of the McGill Quality of Life Questionnaire for ICU End-of-Life Patients.

BACKGROUND: Hospice care for end-of-life patients in the ICU should focus on quality of life. Currently, there are no specific quality-of-life measures for ICU end-of-life patients in China. OBJECTIVE: The aim of this study was to revise and culturally adapt the Taiwanese version of the McGill Quality of Life Questionnaire (MQOL-Taiwan) and to test its reliability and validity to provide an effective instrument for assessing the quality of life of ICU patients at the end of life. METHODS: The revision and cultural adaptation of the MQOL-Taiwan were performed to develop a Chinese version of the McGill Quality of Life Questionnaire for ICU end-of-life patients (MQOL-ICU). A total of 156 ICU doctors, 286 ICU nurses and 120 ICU family members of end-of-life patients were surveyed with the revised scale to evaluate the quality of life of ICU patients at the end of life. The content validity, construct validity, and internal consistency of the scale were measured after the revision. RESULTS: The Chinese version of the MQOL-ICU scale was formed based on the MQOL-Taiwan scale, which includes 8 items. For the Chinese version of the MQOL-ICU, the item-content validity index (I-CVI) ranged from 0.789 to 0.905, and the average scale-level content validity index (S-CVI/Ave) was 0.845. After exploratory factor analysis, the Kaiser-Meyer-Olkin (KMO) value was 0.700, and 3 dominant factors were extracted: physical and psychological symptoms, existential well-being, and support. In addition, 70.385% of the total variance was explained. The internal consistency (Cronbach's α) coefficient of the whole MQOL-ICU was 0.804, and the coefficients for the 3 domains ranged from 0.779 to 0.833. CONCLUSION: The Chinese version of the MQOL-ICU showed good reliability and validity, and it can be used to assess the quality of life of ICU patients at the end of life.

Characteristic pollutants risk assessment of modified manganese residue utilization in sintered product.

The resource disposal of electrolytic manganese residue can effectively solve the problem of environmental pollution caused by it, among which the problem of heavy metal pollution is the most prominent. In this study, a new type of eco-friendly brick mixed with electrolytic manganese residue was designed. The influence of the content of electrolytic manganese residue on its macroscopic properties, microscopic properties, and leaching characteristics was analyzed by test methods such as compressive strength test, radioactivity test, XRF, XRD, FTIR, and ICP test of bricks. The results showed that the manganese content in the EMR leachate was 8120 mg/L, which exceeded the Chinese standard. The leaching experiment of ordinary aqueous solution of sintered bricks mixed with 20% EMR showed that the content of heavy metals was far lower than the Chinese national standard. There was no non-carcinogenic risk of heavy metals in the strong acid leaching solution of sintered bricks mixed with 20% EMR. Only the carcinogenic risk values of Cr for adults and children were 4.21 × 10-4 and 9.82 × 10-4 respectively, both exceeding the USEPA limit, but the application scene of sintered bricks was difficult to achieve strong acidity, so it was judged that it had no carcinogenic risk to the human body. Characteristic heavy metals such as Mn, Cr, and As existed stably in sintered bricks through substitution and encapsulation. In addition, the compressive strength and radioactivity of EMR sintered bricks met the requirements of the Chinese national standard "Fired Ordinary Bricks." This product can be used as national standard MU20 grade brick. This study provided an efficient method for the safe and environmentally friendly disposal of EMR in a sustainable control system.

Plant invasions facilitated by suppression of root nutrient acquisition rather than by disruption of mycorrhizal association in the native plant.

Invasive species have profound negative impacts on native ranges. Unraveling the mechanisms employed by invasive plant species is crucial to controlling invasions. One important approach that invasive plants use to outcompete native plants is to disrupt mutualistic interactions between native roots and mycorrhizal fungi. However, it remains unclear how differences in the competitive ability of invasive plants affect native plant associations with mycorrhizae. Here, we examined how a native plant, Xanthium strumarium, responds to invasive plants that differed in competitive abilities (i.e., as represented by aboveground plant biomass) by measuring changes in root nitrogen concentration (root nutrient acquisition) and mycorrhizal colonization rate. We found that both root nitrogen concentration and mycorrhizal colonization rate in the native plant were reduced by invasive plants. The change in mycorrhizal colonization rate of the native plant was negatively correlated with both aboveground plant biomass of the invasive plants and the change in aboveground plant biomass of the native plant in monocultures relative to mixed plantings. In contrast, the change in root nitrogen concentration of the native plant was positively correlated with aboveground plant biomass of the invasive plants and the change in aboveground plant biomass of the native plant. When we compared the changes in mycorrhizal colonization rate and root nitrogen concentration in the native plant grown in monocultures with those of native plants grown with invasive plants, we observed a significant tradeoff. Our study shows that invasive plants can suppress native plants by reducing root nutrient acquisition rather than by disrupting symbiotic mycorrhizal associations, a novel finding likely attributable to a low dependence of the native plant on mycorrhizal fungi.

In vitro study of red blood cell and VWF damage in mechanical circulatory support devices based on blood-shearing platform.

Blood damage induced by mechanical circulatory support devices (MCSDs) remains a significant challenge to optimal clinical care. Although researchers have been conducting in vitro studies, the major determinant of blood damage is still unclear. An optimized capillary tube blood-shearing platform with custom designed parts was constructed to investigate the influence of two flow-dependent parameters (shear stress and exposure time) on the shear-induced damage of red blood cells and von Willebrand factor (VWF). Blood samples under different high shear stress and instantaneous exposure time were obtained by changing the flow rate and the length of capillary tube. Plasma free hemoglobin assay and immunoblotting of VWF were then performed on the sheared blood samples. The quantitative correlation between the hemolysis index and the two flow-dependent parameters was found following the power law mathematical model under the flow condition with high shear stress and instantaneous exposure time. The degradation of high molecular weight VWF was not obvious under high shear stress factor. However, the degradation of high molecular weight VWF was found as the result of the accumulation over exposure time under non-physiological shear stress, which was consistent with the different mechanism of VWF damage comparing to red blood cell damage. Compared to peak shear stress, exposure time has a greater effect on both red blood cell and VWF damage. To improve the hemocompatibility of MCSDs, it is more important to avoid regions of slow blood flow with non-physiological shear stress under laminar flow conditions.

Investigation into the effect of the aspect ratio of cylindrical surface microstructure on von Willebrand factor damage.

Hemorrhagic episodes in patients carrying mechanical circulatory support represent a severe clinical complication. These bleeding episodes may originate from a reduced functionality of von Willebrand factor (VWF), a multimer protein pertinent to form a hemostatic plug. The reduced functionality is due to increased loss of high molecular weight von Willebrand factor multimers (HMWM-VWF), a phenomenon that is facilitated by device-induced increases in shear stress to which VWF is exposed. However, in addition to the mechanics factors, VWF damage may also be affected by interface factors, including the properties of bulk material and the surface characteristics. In this study, the effect of cylindrical surface microstructure topography on VWF damage was investigated. In the 1 to 9 range, the high aspect ratio surface features were constructed on the polycarbonate (PC) films. The topographic surfaces were fabricated by 3D printing casting on a template. A roller pump circulation platform was built to conduct in vitro experiments. VWF antigen (VWF-Ag) and VWF ristocetin cofactor activity (VWF-Rico) on these topographic surfaces were quantified by enzyme-linked immunosorbent assay (ELISA), the loss of HMWM-VWF was quantified by immunoblotting. The lower loss of HMWM-VWF was observed on surfaces with high aspect ratio compared to the pristine PC templates and surfaces with low aspect ratio, while VWF-Ag was nearly unchanged. The topographical parameters found to significantly reduce the loss of HMWM-VWF were high aspect ratio structures of more than 5. The results signify that topographical manipulation of surfaces is a feasible approach for reducing the loss of HMWM-VWF.

Mathematical models for shear-induced blood damage based on vortex platform.

Non-physiological shear stress in Ventricular Assist Device (VAD) is considered to be an important trigger of blood damage, which has become the biggest shackle for clinical application. The researches on blood damage in literature were limited to qualitative but did not make much quantitative analysis. The purpose of this study was to investigate the quantitative influence of two flow-dependent parameters: shear stress (rotational speed) and exposure time on the shear-induced damage of red blood cells and von Willebrand Factor (vWF). A vortex blood-shearing platform was constructed to conduct in vitro experiments. Free hemoglobin assay and vWF molecular weight analysis were then performed on the sheared blood samples. MATLAB was used for regression fitting of original experimental data. The quantitative correlations between the hemolysis index, the degradation of high molecular weight vWF and the two flow-dependent parameters were found both following the power law model. The mathematic models indicated that the sensitivity of blood damage on red blood cells and vWF to exposure time was both greater than that of shear stress. Besides, the damage of vWF was more serious than that of red blood cells at the same flow condition. The models could be used to predict blood damage in blood-contacting medical devices, especially for the slow even stagnant blood flow regions in VAD, thus may provide useful guidance for VAD development and improvement. It also indicated that the vortex platform can be used to study the law of blood damage for the simple structure and easy operation.

Delayed adjuvant imatinib in patients with high risk of recurrence of gastrointestinal stromal tumor after radical surgery: a retrospective cohort study.

PURPOSE: To investigate the impact of delayed adjuvant imatinib on GIST patients with high risk of recurrence. METHOD: Adult GIST patients were retrospectively collected from our hospital between 2011 and 2018, and patients having high risk of recurrence were included for subsequent analyses. The primary endpoint was recurrence-free survival (RFS). RESULTS: According to the interval between the radical surgery and the beginning of adjuvant imatinib, 222 patients were divided into three groups: group A (≤ 2 months, n = 41), group B (2-≤ 4 months, n = 113), and group C (4-≤ 6 months, n = 68). Univariate, multivariate, and survival analyses all showed that patients in group A had significantly more favorable RFS than those in group C but not group B, and patients taking adjuvant imatinib for over 12 months were also associated with longer RFS comparing to adjuvant imatinib of ≤ 12 months. When stratified by the duration of adjuvant imatinib, no significant differences were found in RFS among groups A, B, and C for adjuvant imatinib of ≤ 12 months. While for adjuvant imatinib of over 12 months, both groups A and B had significantly more favorable RFS than group C, and no significant difference in RFS was found between group A and B. CONCLUSION: Delayed postoperative adjuvant imatinib for over 4 months in patients with high risk of recurrence of GIST may lead to worse RFS, and longer treatment with shorter delay has best results.

The influence of surface roughness on the damage of von Willebrand Factor under shear flow condition.

Despite technological advances in mechanical circulatory support devices to treat end-stage heart failure, blood damage induced by non-physiological shear stress in operation often triggered clinical hemocompatibility complications. The loss of high molecular weight von Willebrand Factor (HMW-VWF) has been considered as an essential cause of gastrointestinal bleeding. In addition to the mechanics factors, interface factors may also affect blood damage, especially the surface characteristics. In this study, the effect of surface roughness on VWF damage under flow condition was investigated. A roller pump circulation experimental platform with a roughness embedded sample chamber was constructed to provide blood shearing flow condition. VWF molecular weight analysis, VWF antigen (VWF-Ag) concentration assay, and VWF ristocetin cofactor activity (VWF-Rico) assay were performed on the sheared blood samples. These variables are the main functional indicators of VWF. It was found that the surface roughness induced VWF damage is mainly caused by the loss of HMW-VWF rather than reducing the total amount of VWF. The threshold value of surface roughness for a rapid increase in the degradation of HMW-VWF under low flow rate was obtained between Ra 0.4 and 0.6 µm, which was smaller than the threshold for hemolysis. Our findings indicated that VWF is more sensitive to the interface factor of surface roughness than red blood cells, thus has a higher requirement for blood pump design. It could provide reference for the material design and processing in developing mechanical circulatory support devices.

Expansion and Molecular Characterization of AP2/ERF Gene Family in Wheat (Triticum aestivum L.).

The AP2/ERF is a large protein family of transcription factors, playing an important role in signal transduction, plant growth, development, and response to various stresses. AP2/ERF super-family is identified and functionalized in a different plant but no comprehensive and systematic analysis in wheat (Triticum aestivum L.) has been reported. However, a genome-wide and functional analysis was performed and identified 322 TaAP2/ERF putative genes from the wheat genome. According to the phylogenetic and structural analysis, TaAP2/ERF genes were divided into 12 subfamilies (Ia, Ib, Ic, IIa, IIb, IIc, IIIa, IIIb, IIIc, IVa, IVb, and IVc). Furthermore, conserved motifs and introns/exons analysis revealed may lead to functional divergence within clades. Cis-Acting analysis indicated that many elements were involved in stress-related and plant development. Chromosomal location showed that 320 AP2/ERF genes were distributed among 21 chromosomes and 2 genes were present in a scaffold. Interspecies microsynteny analysis revealed that maximum orthologous between Arabidopsis, rice followed by wheat. Segment duplication events have contributed to the expansion of the AP2/ERF family and made this family larger than rice and Arabidopsis. Additionally, AP2/ERF genes were differentially expressed in wheat seedlings under the stress treatments of heat, salt, and drought, and expression profiles were verified by qRT-PCR. Remarkably, the RNA-seq data exposed that AP2/ERF gene family might play a vital role in stress-related. Taken together, our findings provided useful and helpful information to understand the molecular mechanism and evolution of the AP2/ERF gene family in wheat.

Validation of the Chinese Version of the Quality of Dying and Death Questionnaire for Family Members of ICU Patients.

CONTEXT: The quality of end-of-life care services directly affects the end-of-life quality of life of patients and their families. At present, there are no standard tools in China for assessing the quality of dying and death (QODD) of critical intensive care unit (ICU) patients. OBJECTIVES: This study aimed to introduce the Chinese version of the QODD questionnaire for family members of ICU patients, after transcultural adaptation and validation, to provide an effective instrument for assessing the quality of end-of-life care of ICU patients in China, fill the gap in the evaluation of the quality of end-of-life care of critical ICU patients in China, and offer a theoretical basis and practical guidance during purposeful intervention. METHODS: This study involved the main adult caregivers or principal family members of 149 dying critically ill patients. The original QODD scale was translated using the double forward and backward method. Nine cultural adaptation experts adapted the Chinese version of the QODD scale for completion by family members of ICU patients. Then, we carried out content validity, structural validity, internal consistency, confirmatory factors, and item correlation analysis of the modified scale. RESULTS: The Chinese version of the QODD for family members of ICU patients was developed after some items were deleted or modified. The content validity index was 0.93, indicating that all items were correlated with the measurement of death quality. The Kaiser-Meyer-Olkin value was 0.797, suggesting that the correlations between items were high. The Cronbach's α was 0.865, indicating good internal consistency. In confirmatory factor analysis, the fit indices were χ2 = 207.327, non-normed fit index = 0.916, root mean square error of approximation = 0.033, and comparative fit index = 0.93, indicating a good fit of the five-factor model of the Chinese version of the QODD questionnaire for family members of ICU patients. CONCLUSION: The Chinese version of the QODD questionnaire for family members of ICU patients is a reliable and effective instrument for evaluating the quality of death among patients who die in the ICU and can be applied to clinical practice and research.