Combination of eriocalyxin B and homoharringtonine exerts synergistic anti-tumor effects against t(8;21) AML.

Understanding the molecular pathogenesis of acute myeloid leukemia (AML) with well-defined genomic abnormalities has facilitated the development of targeted therapeutics. Patients with t(8;21) AML frequently harbor a fusion gene RUNX1-RUNX1T1 and KIT mutations as "secondary hit", making the disease one of the ideal models for exploring targeted treatment options in AML. In this study we investigated the combination therapy of agents targeting RUNX1-RUNX1T1 and KIT in the treatment of t(8;21) AML with KIT mutations. We showed that the combination of eriocalyxin B (EriB) and homoharringtonine (HHT) exerted synergistic therapeutic effects by dual inhibition of RUNX1-RUNX1T1 and KIT proteins in Kasumi-1 and SKNO-1 cells in vitro. In Kasumi-1 cells, the combination of EriB and HHT could perturb the RUNX1-RUNX1T1-responsible transcriptional network by destabilizing RUNX1-RUNX1T1 transcription factor complex (AETFC), forcing RUNX1-RUNX1T1 leaving from the chromatin, triggering cell cycle arrest and apoptosis. Meanwhile, EriB combined with HHT activated JNK signaling, resulting in the eventual degradation of RUNX1-RUNX1T1 by caspase-3. In addition, HHT and EriB inhibited NF-κB pathway through blocking p65 nuclear translocation in two different manners, to synergistically interfere with the transcription of KIT. In mice co-expressing RUNX1-RUNX1T1 and KITN822K, co-administration of EriB and HHT significantly prolonged survival of the mice by targeting CD34+CD38- leukemic cells. The synergistic effects of the two drugs were also observed in bone marrow mononuclear cells (BMMCs) of t(8;21) AML patients. Collectively, this study reveals the synergistic mechanism of the combination regimen of EriB and HHT in t(8;21) AML, providing new insight into optimizing targeted treatment of AML.

Confined self-assembly of S, O co-doped GCN short nanotubes/EG composite towards HMIs electrochemical detection and removal.

In this paper, we prepared composites by confining S, O co-doped C3N4 short nanotubes (SOT) into the slit holes of expanded graphite (EG). The prepared SOT/EG composites had hierarchical pores. Macroporous and mesoporous were conducive to the permeation of heavy metal ions (HMIs) solution, while microporous were favorable for HMIs capture. In addition, EG had excellent adsorption and conductive properties. By leveraging their synergistic effect, SOT/EG composites could be used for electrochemical detection and removal of HMIs simultaneously. The excellent HMIs electrochemical detection and removal performances were due to the unique 3D microstructure and the increase of active sites such as S and O. When SOT/EG composites were prepared into modified electrodes, the limit of detections (LODs) of Pb2+ and Hg2+ were 0.038 and 0.051 µg L-1 for simultaneous detection and 0.045 and 0.057 µg L-1 for individual detection. When SOT/EG composites were used as adsorbents, the equilibrium adsorption capacity of Pb2+ and Hg2+ solution of 10 mg L-1 could reach 228.0 and 313.1 mg g-1, and the adsorption efficiency was above 90%. Due to the low raw materials cost and simple preparation method, SOT/EG composite is a very promising bifunctional material for HMIs electrochemical detection and removal.

Novel Uracil-Functionalized Poly(ionic liquid) Hydrogel: Highly Stretchable and Sensitive as a Direct Wearable Ionic Skin for Human Motion Detection.

Conductive hydrogel-based ionic skins have attracted immense attention due to their great application prospects in wearable electronic devices. However, simultaneously achieving a combination of a single hydrogel system and excellent comprehensive performance (i.e., mechanical durability, electrical sensitivity, broad-spectrum antibacterial activity, and biocompatibility) remains a challenge. Thus, a novel poly(ionic liquid) hydrogel consisting of poly(acrylamide-co-lauryl methacrylate-co-methyl-uracil-imidazolium chloride-co-2-acryloylamino-2-methyl-1-propane sulfonic acid) (AAm-LMA-MUI-AMPS) was prepared by a micellar copolymerization method. Herein, MUI serves as a supramolecular crosslinker and conductive and bacteriostatic components. Owing to the multiple supramolecular crosslinks and hydrophobic association in the network, the hydrogel exhibits excellent mechanical properties (624 kPa of breaking stress and 1243 kPa of compression stress), skin-like modulus (46.2 kPa), stretchability (1803%), and mechanical durability (200 cycles under 500% strain can be completely recovered). Moreover, with the coordinated combination of each monomer, the hydrogel exhibits the unique advantage of high conductivity (up to 59.34 mS/cm). Hence, the hydrogel was further assembled as an ionic skin sensor, which exhibited a gauge factor (GF) of 10.74 and 7.27 with and without LiCl over a broad strain range (1-1000%), respectively. Furthermore, the hydrogel sensor could monitor human movement in different strain ranges, including body movement and vocal cord vibration. In addition, the antibacterial activity and biocompatibility of the hydrogel sensor were investigated. These findings present a new strategy for the design of new-generation wearable devices with multiple functions.

Apical aneurysm formation in apical hypertrophic cardiomyopathy: Pilot study with cardiac magnetic resonance.

BACKGROUND: The dynamic changes and apical aneurysm formation in apical hypertrophic cardiomyopathy (HCM) have not been specifically described. This study aimed to describe these changes to better understand the progression of apical HCM. METHODS AND RESULTS: Seventy-two patients with apical HCM who underwent at least two cardiac magnetic resonance (CMR) examinations were retrospectively included in this study. The mean interval between the first and last CMR examinations was 50.1 ± 26.8 months (ranging from 4 to 118 months). Compared with the initial values, the left atrial diameter, maximum left ventricular wall thickness and late gadolinium enhancement extent significantly increased (all P < 0.05), while the left ventricular ejection fraction significantly decreased (P < 0.05), at the latest CMR examination. More importantly, the dynamic process of apical aneurysm formation in apical HCM was observed in a subset of patients, which may follow these four stages: starting with systolic apical cavity obliteration, then broadening of the apical slit in systole, further developing into an apical outpouching, and finally forming an apical aneurysm. Eleven patients experienced adverse cardiovascular events, including new-onset or progressive atrial fibrillation (n = 7), hospitalization with heart failure (n = 3) and implantable cardioverter defibrillator intervention (n = 1), at the time of the latest CMR examination. CONCLUSIONS: In the progression of apical HCM, cardiac structure and function will change accordingly. Apical aneurysm formation in apical HCM is a chronic and continuous dynamic process that may follow a 4-step pathway of disease progression.

Anchored growth of highly dispersed LDHs nanosheets on expanded graphite for fluoride adsorption properties and mechanism.

In this study, a new composite with layered double hydroxides (LDHs) anchored grown on expanded graphite (EG) interlayers was prepared by vacuum-assisted intercalation and hydrothermal method. Both sides of EG were completely covered by highly dispersed LDHs nanosheets and formed a sandwich-like structure. The unique structure made expanded graphite/layered double hydroxides (EG/LDHs) composites which had excellent F- adsorption performance. The adsorption performance of F- on EG/LDHs was evaluated, and the results indicated that the adsorption process was consistent with the pseudo-second-order kinetic model and the Langmuir model. Pseudo-second-order kinetic model indicated that the adsorption sites were the main factor in the adsorption process. Moreover, the maximum adsorption capacity (Qm) reached 63.21 mg·g-1 at 30 min at room temperature, which was better than most of the same type of adsorbents. The highly dispersed of LDHs anchored growth on EG overcame the disadvantage of aggregation, which exposed more adsorption sites and improved the removal efficiency of F-. In addition, the effects of pH, anion interference, different water quality, and regeneration tests on the EG/LDHs composites were also analyzed, showing that the composites have good stability.

Nomogram for preoperative estimation of histologic grade in gastrointestinal neuroendocrine tumors.

Background: The treatment strategies and prognosis for gastroenteropancreatic neuroendocrine tumors were associated with tumor grade. Preoperative predictive grading could be of great benefit in the selection of treatment options for patients. However, there is still a lack of effective non-invasive strategies to detect gastrointestinal neuroendocrine tumors (GI-NETs) grading preoperatively. Methods: The data on 147 consecutive GI-NETs patients was retrospectively collected from January 1, 2012, to December 31, 2019. Logistic regression was used to construct a predictive model of gastrointestinal neuroendocrine tumor grading using preoperative laboratory and imaging parameters.The validity of the model was assessed by area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: The factors associated with GI-NETs grading were age, tumor size, lymph nodes, neuron-specific enolase (NSE), hemoglobin (HGB) and sex, and two models were constructed by logistic regression for prediction. Combining these 6 factors, the nomogram was constructed for model 1 to distinguish between G3 and G1/2, achieving a good AUC of 0.921 (95% CI: 0.884-0.965), and the sensitivity, specificity, accuracy were 0.9167, 0.8256, 0.8630, respectively. The model 2 was to distinguish between G1 and G2/3, and the variables were age, tumor size, lymph nodes, NSE, with an AUC of 0.847 (95% CI: 0.799-0.915), and the sensitivity, specificity, accuracy were 0.7882, 0.8710, 0.8231, respectively. Two online web servers were established on the basis of the proposed nomogram to facilitate clinical use. Both models showed an excellent calibration curve through 1000 times bootstrapped dataset and the clinical usefulness were confirmed using decision curve analysis. Conclusion: The model served as a valuable non-invasive tool for differentiating between different grades of GI-NETs, personalizing the calculation which can lead to a rational treatment choice.

Utilizing Gradient Porous Graphene Substrate as the Solid-Contact Layer To Enhance Wearable Electrochemical Sweat Sensor Sensitivity.

Wearable sweat monitoring represents an attractive opportunity for personalized healthcare and for evaluating sports performance. One of the limitations with such monitoring, however, is water layer formation upon cycling of ion-selective sensors, leading to degraded sensitivity and long-term instability. Our report is the first to use chemical vapor deposition-grown, three-dimensional, graphene-based, gradient porous electrodes to minimize such water layer formation. The proposed design reduces the ion diffusion path within the polymeric ion-selective membrane and enhances the electroactive surface for highly sensitive, real-time detection of Na+ ions in human sweat with high selectivity. We obtained a 7-fold enhancement in electroactive surface against 2D electrodes (e.g., carbon, gold), yielding a sensitivity of 65.1 ± 0.25 mV decade-1 (n = 3, RSD = 0.39%), the highest to date for wearable Na+ sweat sensors. The on-body sweat sensing performance is comparable to that of ICP-MS, suggesting its feasibility for health evaluation through sweat.

Graphene-Based Ion-Selective Field-Effect Transistor for Sodium Sensing.

Field-effect transistors have attracted significant attention in chemical sensing and clinical diagnosis, due to their high sensitivity and label-free operation. Through a scalable photolithographic process in this study, we fabricated graphene-based ion-sensitive field-effect transistor (ISFET) arrays that can continuously monitor sodium ions in real-time. As the sodium ion concentration increased, the current-gate voltage characteristic curves shifted towards the negative direction, showing that sodium ions were captured and could be detected over a wide concentration range, from 10-8 to 10-1 M, with a sensitivity of 152.4 mV/dec. Time-dependent measurements and interfering experiments were conducted to validate the real-time measurements and the highly specific detection capability of our sensor. Our graphene ISFETs (G-ISFET) not only showed a fast response, but also exhibited remarkable selectivity against interference ions, including Ca2+, K+, Mg2+ and NH4+. The scalability, high sensitivity and selectivity synergistically make our G-ISFET a promising platform for sodium sensing in health monitoring.

Micellization and thermodynamics study of ester functionalized picoline-based ionic liquid surfactants in water.

A novel series of picoline-based ionic liquid surfactants, N-alkyoxycarbonyl-3-picoline bromides [C n Empy][Br] (n = 10, 12, 14), have been synthesized. The thermal stability, aggregation behavior and surface activity of the synthetic ionic liquid surfactants were investigated systematically though a series of methods, such as thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), tensiometry and conductivity. The thermodynamics of micellization of the ionic liquid surfactants solution were studied by using the conductivity method in the temperature range 278.15-318.15 K. The surface activity parameters and thermodynamics parameters were derived, respectively. The enthalpy-entropy compensation effect was further discussed by using relative thermodynamics parameters. It was found that the [C n Empy][Br] have moderate surface activity, and their critical micelle concentration (CMC) decreased with the ester-functionalized chain length and exhibited a U-shape with temperature. The calculation results of the thermodynamic parameters showed that the micellization processes of [C n Empy][Br] were spontaneous, endothermic at low temperature and exothermic at higher temperature.

Characterization of Deltacoronavirus in Black-Headed Gulls (Chroicocephalus ridibundus) in South China Indicating Frequent Interspecies Transmission of the Virus in Birds.

Deltacoronavirus (DCoV) is a genus of coronavirus (CoV) commonly found in avian and swine, but some DCoVs are capable of infecting humans, which causes the concern about interspecies transmission of DCoVs. Thus, monitoring the existence of DCoVs in animals near communities is of great importance for epidemic prevention. Black-headed gulls (Chroicocephalus ridibundus) are common migratory birds inhabiting in most urban and rural wetlands of Yunnan Province, China, which is a typical habitat for black-headed gulls to overwinter. Whether Yunnan black-headed gulls carry CoV has never been determined. In this study, we identified three strains of DCoVs in fecal samples of Yunnan black-headed gulls by reverse-transcriptional PCR and sequenced their whole genomes. Genomic analysis revealed that these three strains shared genomic identity of more than 99%, thus named DCoV HNU4-1, HNU4-2, and HNU4-3; their NSP12 showed high similarity of amino acid sequence to the homologs of falcon coronavirus UAE-HKU27 (HKU27), houbara coronavirus UAE-HKU28 (HKU28), and pigeon coronavirus UAE-HKU29 (HKU29). Since both HKU28 and HKU29 were found in Dubai, there might be cross-border transmission of these avian DCoVs through specific routes. Further coevolutionary analysis supported this speculation that HNU4 (or its ancestors) in black-headed gulls originated from HKU28 (or its homologous strain) in houbara, which was interspecies transmission between two different avian orders. In addition, interspecies transmission of DCoV, from houbara to falcon, pigeon and white-eye, from sparrow to common-magpie, and quail and mammal including porcine and Asian leopard cat, from munia to magpie-robin, was predicted. This is the first report of black-headed gull DCoV in Asia which was highly homolog to other avian DCoVs, and the very "active" host-switching events in DCoV were predicted, which provides important reference for the study of spread and transmission of DCoVs.

Transcriptomic profiling of pemphigus lesion infiltrating mononuclear cells reveals a distinct local immune microenvironment and novel lncRNA regulators.

Pemphigus is an autoimmune skin disease. Ectopic lymphoid-like structures (ELSs) were found to be commonly present in the pemphigus lesions, presumably supporting in situ desmoglein (Dsg)-specific antibody production. Yet functional phenotypes and the regulators of Lymphoid aggregates in pemphigus lesions remain largely unknown. Herein, we used microarray technology to profile the gene expression in skin lesion infiltrating mononuclear cells (SIMC) from pemphigus patients. On top of that, we compared SIMC dataset to peripheral blood mononuclear cells (PBMC) dataset to characterize the unique role of SIMC. Functional enrichment results showed that mononuclear cells in skin lesions and peripheral blood both had over-represented IL-17 signaling pathways while neither was characterized by an activation of type I Interferon signaling pathways. Cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) results showed that naïve natural killer cells (NK cells) were significantly more abundant in pemphigus lesions, and their relative abundance positively correlated with B cells abundance. Meanwhile, plasma cells population highly correlated with type 1 macrophages (M1) abundance. In addition, we also identified a lncRNA LINC01588 which might epigenetically regulate T helper 17 cells (Th17)/regulatory T cells (Treg) balance via the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Here, we provide the first transcriptomic characterization of lesion infiltrating immune cells which illustrates a distinct interplay network between adaptive and innate immune cells. It helps discover new regulators of local immune response, which potentially will provide a novel path forward to further uncover pemphigus pathological mechanisms and develop targeted therapy.

N-doped three-dimensional needle-like CoS2 bridge connection Co3O4 core-shell structure as high-efficiency room temperature NO2 gas sensor.

The N-doped three-dimensional (3D) needle bridge connection core-shell structure N-CoS2@Co3O4 synthesized in this work was prepared by simple hydrothermal and high-temperature vulcanization methods. The optimized N-CoS2@Co3O4-2 composite response to NO2 is 62.3-100 ppm, a response time of 1.3 s, the recovery time of 17.98 s, the detection limit of 5 ppb and stability of as long as 10 weeks at room temperature (RT). Its excellent NO2 sensing performance is attributed to the unique porous and bridge connection core-shell structure of the N-CoS2@Co3O4-2 with high specific surface area, interconnected internal channels, abundant exposed S edge active sites, and high catalytic performance promoted by N-doping. This simple manufacturing method of high-performance sensing materials paves the way for the design of N-doped bridge connection core-shell structures.

Study on a horizontal axial flow pump during runaway process with bidirectional operating conditions.

The ultra-low head pump stations often have bidirectional demand of water delivery, so there is a risk of runaway accident occurring in both conditions. To analyze the difference of the runaway process under forward runaway condition (FRC) and backward runaway condition (BRC), the whole flow system of a horizontal axial flow pump is considered. The Shear-Stress Transport (SST) k-ω model is adopted and the volume of fluid (VOF) model is applied to simulate the water surface in the reservoirs. Meanwhile, the torque balance equation is introduced to obtain the real time rotational speed, then the bidirectional runaway process of the pump with the same head is simulated. In addition, the vortex transport equation and swirl number are proposed to reveal the flow characteristics during the runaway process. The results show that the runaway process can be divided into five stages: the drop, braking, rising, convergence and runaway stages, according to the changing law of torque curve. In the rising stage, the pressure difference on the blade surface continues to increase, which contributes to the abnormal torque increase. In this stage, the flow hits the pressure surface (PS) at a faster speed enlarging the pressure on PS, and the flow separation takes place on the suction surface (SS) weakening the pressure on SS. During the convergence and runaway stage, the pulsation amplitude of torque and axial force under FRC is obviously larger than those under BRC. This is because the rotation frequency of the vortex rope is the same as main pressure fluctuation frequency in impeller under FRC, which enhances the pulsation amplitude. Whereas the vortices are broken due to the inhibitive effect from guide vanes under BRC.

Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

[Significance of Targeted Sequencing Assay for Patients with Suspected Myeloid Malignancies].

OBJECTIVE: To investigate the clinical significance of the targeted next-generation sequencing assay for patients with suspected myeloid malignancies. METHODS: A total of 39 hematopenia patients with suspected myeloid malignamies in Department of Hematology of The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2018 to April 2019 were treated, 20 hot spot genes of myelodysplastic syndrome (MDS) were detected. RESULTS: Regarding the diagnostic type, there were 7 cases of idiopathic cytopenia of undetermined significance (ICUS), 8 cases of clonal cytopenias of undetermined significance (CCUS) and 24 cases of myeloid myeloid malignancies which included 18 cases of MDS, 4 cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and 2 cases of acute myeloid leukemia. Positive mutation was detected in 70.8% (17/24) of myeloid malignancy patients , and 72.7% (16/22) in MDS and MDS/MPN patients. The main mutation types were ASXL1, TET2 and RUNX1. Compared with gene negative group, there were no significant differences in sex, age (＜60 years old or ≥60 years old), proportion of bone marrow blast cells (＜5% or≥5%) and cytogenetics (good, medium and poor) (P＞0.05). Furthermore, all 8 CCUS patients showed positive mutation, and the incidence of double or multiple mutation in CCUS group was significantly lower than that of the MDS and MDS/MPN group (37.5% vs 54.5%) (P=0.002). The mutation types between the two groups were similar, and there was no significant difference in variant allele frequency (P＞0.05). CONCLUSION: Our results suggest that there are high rates of double or multiple mutations in myeloid malignancies, especially in patients with MDS and MDS/MPN. Targeted sequencing assay can improve the diagnosis of myeloid malignancies, and guide clinical treatment.

Enhanced room-temperature NO2 sensing properties of biomorphic hierarchical mixed phase WO3.

WO3 with a mixed phase (m-WO3 and h-WO3) was synthesized by facile hydrothermal and annealing methods using biomass carbon (Hemp stems) as a sacrificial template. The biomorphic hierarchical structure effectively enhanced the dispersion of WO3 microspheres, which increased the contact area for the target gas molecule. The control of the mixed phase compositions was achieved by space confinement of biomass carbon and heat treatments. The synergistic effect of the mixed phase increased the mobility of carriers and promoted the separation and transport of electrons and holes. Thus, it improved the adsorption-diffusion capacity of NO2 molecules and enhanced the sensor performance at lower operating temperature effectively. The B-WO3-04 (450 °C, 4 h) exhibited an ultra-high response (Ra/Rg = 71.07) towards 100 ppm NO2 gas with excellent repeatability and appreciable long-term stability at room temperature. The significant improvement of B-WO3-04 gas sensing performance was mainly due to its unique hierarchical structure and the optimal proportion of the mixed phase composition.

[Clinical Analysis of 66 Patients with Essential Thrombocytopenia].

OBJECTIVE: To investigate the clinical characteristics of essential thrombocytopenia (ET) patients with positive mutations including JAK2, CALR, MPL, or negative mutations. METHODS: A total of 66 newly diagnosed ET cases from January 2016 to December 2018 in Department of Hematology, Huaian No.1 People's Hospital affiliated to Nanjing Medical University were analyzed. Statistical analysis data included the patient's sex, age, symptoms, thrombosis and embolism events, spleen omegaly, platelet count (Plt), leukocyte (WBC) count, hemoglobin (Hb), fibrinogen (FIB), thrombus elastic diagram (TEG), serum potassium, blood glucose (GLU), lactate dehydrogenase (LDH), JAK2, CALR and MPL mutations, treatment options, and efficacy. RESULTS: All the patients were not MPL-positive, and divided in three groups: JAK2 mutation (46 cases, 69.7%), CALR mutation (9 cases, 13.6%) and gene negative mutation (11 cases, 16.7%) group. The average age of patients in the JAK2 mutation group was 63.2 years old, and significantly higher than that in the CALR mutation group (51.8 year) and gene negative group (50.2 year) (P＜0.05). Compared with the JAK2 mutation group and gene negative group, the CALR mutation group had lower WBC count (6.3×109/L vs 13.79×109/L) (P=0.003) (6.3×109/L vs 9.70×109/L) (P=0.009). Also the Hb level of patients in CALR mutation group was lower than the JAK2 mutation group (121.22 g/L vs 136.2 g/L) (P=0.036). However, there was higher tumor burden in the CALR mutation group, compared with the gene negative mutation group (300.11 U/L vs 227.4 U/L) (P=0. 033). There was no significant difference among the three groups, such as the Plt counts, serum potassium level, GLU level and FIB level (P＞0.05). In addition, thrombus and embolism appeared in 30.3% (20/66) cases. 18.2% (12/66) cases were complicated with hyperkalemia, which significantly correlated with Plt counts (r=0.518). TEG was performed in 34 patients, of which 41.2% (14/34) had abnormal TEG and 55.9% (19/34) were accompanied by Plt count ＞ 1 000 ×109/L, but there was no significant correlation between them (r=0.134). After routine clinical treatment, all the 66 cases achieved partial or complete hematological remission, but the disease usually repeated. Until now 4.5% (3/66) cases had been converted to myelofibrosis (MF) all with JAK2 mutation, but without advancing to acute myeloid leukemia. CONCLUSION: ET patients with JAK2 mutation have higher incidence, moreover were in older age. However, the patients with CALR mutations display lower WBC count and Hb level, but higher tumor burden. In short, the multiple gene mutations of ET showed different clinical features closely relates with the prognosis, thus providing guidance for the clinical diagnosis and treatment.

A TaqMan-based quantitative real-time PCR assay for identification of the goose circovirus.

Goose circovirus (GoCV) is a potential immunosuppressive virus that poses a great hazard to the goose industry and has been shown to be widely distributed throughout China. We have established a fast, sensitive and highly specific TaqMan real-time quantitative PCR detection method for this virus. Specific primers and probes were designed against the conserved regions of the genomic GoCV Rep gene. The results showed that the assay was highly specific and sensitive for GoCV and did not cross-react with other non-targeted waterfowl viruses. The established method will be helpful for epidemiological detection and may be effective in the prevention and control of the disease.

Simultaneous differentiation and diagnosis of goose parvovirus and astrovirus in clinical samples with duplex SYBR Green I real-time PCR.

Two pairs of primers were designed to bind conserved genomic regions of goose parvovirus (GPV) and goose astrovirus (GAstV) to establish a simple, sensitive, and highly specific duplex quantitative PCR (qPCR) method to simultaneously detect the two viruses. The duplex qPCR can distinguish GPV (melting point: 82.1 °C) and GAstV (melting point: 79.8 °C) by the peaks of their individual melting curves. Mixed testing with other waterfowl viruses produced no nonspecific peaks. The established standard curves showed good linear relationships (R2 > 0.997) and the limits of detection (LOD) for GPV and GAstV were 5.74 × 101 and 6.58 × 101 copies/µL, respectively. Both intra- and inter-assay coefficients of variation were <2%, indicating that the method has good repeatability. Twenty tissue samples from diseased geese were examined with the duplex qPCR assay and conventional PCR. Duplex qPCR showed positive rates of 25% for GPV and 45% for GAstV, and the positive rate for GPV and GAstV coinfection was 15%, slightly higher than the results for conventional PCR. These results indicated that this duplex qPCR method is highly sensitive, specific, and reproducible, and is suitable for epidemiological studies to effectively control the transmission of GPV and GAstV.

Low SOX12 Expression Is Correlated With Poor Prognosis in Patients With Gastric Cancer.

BACKGROUND: SRY-related HMG box-12, which is associated with the prognosis of cancer, has been frequently described. However, both SRY-related HMG box-12 expression and its relationship with clinicopathological variables and patient survival have not been defined in gastric cancer. The aim of our study was to examine the prognostic value of SRY-related HMG box-12 expression in patients with gastric cancer. METHODS: In this study, we determined SRY-related HMG box-12 expression in 79 primary gastric cancer tissues and 79 matched adjacent nontumor tissues by immunohistochemistry and then calculated the survival rate using the Kaplan-Meier method. Cox proportional hazard regression model was used to analyze predictors of gastric cancer. Western blot and quantitative real-time polymerase chain reaction were used to investigate the difference in SRY-related HMG box-12 expression between normal gastric epithelial cells and gastric cancer cells at the protein level and RNA level, respectively. RESULTS: SRY-related HMG box-12 was downregulated in gastric cancer tissues. Low SRY-related HMG box-12 expression was significantly associated not only with lymph node metastasis (P = .027) and TNM stage (P = .021) but also with disease-specific survival in patients with gastric cancer. Multivariate analysis demonstrated TNM stage was an independent factor predicting poor survival (P = .034). CONCLUSIONS: Low SRY-related HMG box-12 expression is associated with poor clinical outcomes in gastric cancer.