基于drop-off ddPCR方法检测急性髓系白血病C-KIT基因N822位点突变及其临床应用

目的:建立急性髓系白血病(acute myeloid leukemia, AML)患者C-KIT基因N822位点突变的drop-off微滴式数字PCR(droplet digital PCR,ddPCR)定量检测方法,并评价其临床应用价值。方法:针对C-KIT基因第17外显子设计一对引物及探针,优化drop-off ddPCR反应条件及体系,评价该方法的特异性、灵敏度、重复性,使用所建立的方法对140例已行Sanger测序的AML初诊患者骨髓标本进行检测,并用二代测序(next generation sequencing, NGS)验证结果;用drop-off ddPCR对3例阳性患者化疗后C-KIT突变频率进行动态监测。结果:drop-off ddPCR检测C-KIT基因N822位点突变的最适退火温度为54℃,空白检测限为1.62拷贝数/μL,最低检测下限为10.12拷贝数/μL,线性良好。140例AML初诊患者样本中Sanger测序检出2例阳性(1.4%),而ddPCR共检出突变7例(5.0%),突变频率为0.29%~7.41%;进一步应用常规NGS方法对ddPCR阳性样本进行验证,共检出阳性3例(2.1%),等位基因频率为1.26%~8.00%。动态监测3例阳性患者C-KIT突变频率,结果显示治疗达完全缓解时C-KIT突变频率明显下降甚至降低至0。结论:本研究建立了检测C-KIT基因N822位点突变的drop-off ddPCR技术,具有良好的方法学检测性能,其灵敏度高于Sanger测序和NGS,有望用于阳性患者缓解后的可检测残留疾病监测及治疗指导。

Basic Research on the Burden of Dropping off and Picking up Children: Differences by Employment Type and Gender in the Tokyo Metropolitan Area

There is a need to reduce the burden of child drop-off and pick-up for child-rearing generations, but most studies on the actual situation in Japan are based on survey results. In this study, we analyzed differences in child drop-off and pick-up by employment type and gender, utilizing the “Metropolitan Area Person Trip Survey,” which is a statistical data set. The study targeted households in which both spouses were between 30 and 49 years old, had children under the age of 6, and included the following three groups. 1) Dual-income Group 1 (both spouses employed/on contract/temporary);2) Dual-income Group 2 (husband employed/on contract/temporary, wife part-time);3) Full-time housewife group (husband employed, wife unemployed). The analysis revealed that a) wives are almost always responsible for dropping off and picking up their children;b) husbands drop off and pick up their children less frequently in dual-income households;and c) households with children raising within 10 to 30 km of Tokyo Station have longer commuting times and need to reduce the burden of dropping off and picking up their children.

Drop-off微滴式数字PCR检测急性髓系白血病NRAS基因突变及其临床应用

目的:建立检测急性髓系白血病(acute myeloid leukemia,AML)神经母细胞瘤RAS病毒癌基因同源物(NRAS)基因突变的drop-off微滴式数字PCR(droplet digital PCR,ddPCR)方法,并评价该方法的临床应用价值。方法:针对NRAS G12和G13突变位点设计特异性drop-off ddPCR引物和探针,建立最佳反应体系,并对该方法进行性能验证。应用该方法对140例临床样本进行初筛,其检测结果与Sanger测序进行比较,并用二代测序(next generation sequencing,NGS)进行验证。结果:建立drop-off ddPCR检测NRAS基因G12/G13突变的方法,灵敏度达0.158%,重复性、线性良好,其空白限为5.40拷贝数/μL,最低检测下限为15.84拷贝数/μL。在140例初诊AML患者中,drop-off ddPCR检出NRAS突变28例(20%),其突变负荷为0.26%~52.85%(中位2.14%);而Sanger测序仅检出7例(5%)阳性,为进一步验证,将21例Sanger测序结果阴性而drop-off ddPCR检测阳性的样本进行NRAS基因NGS,检出14例阳性,而另外7例NGS阴性的样本,其drop-off ddPCR检测突变频率为0.53%~1.50%(中位1.10%)。结论:建立了drop-off ddPCR技术检测AML患者中NRAS基因突变的方法,该方法灵敏度高,可用于对NRAS基因G12/G13突变进行定量检测,有望可用于AML患者预后判断和疾病监测。

Scaling of stress drop and high-frequencyfall-off of source spectra

It has been observed for a long time that the high-frequency fall-off constant of source spectra is about 2 for 'large'earthquakes and about 3 for 'small' earthquakes. For earthquakes between 'large' and 'small', the high-frequencyfall-off constant is not an integer and varies with the size of the earthquake. In this article such a variation is explainedin the perspective of the scaling of stress drop, which proposes a new approach to the study of the scaling of stress dropusing seismic data with lower quality of completeness and high-frequency characteristics. The study on the sourcespectra of the aftershocks of the 1988 Lancang-Gengma, Yunnan, China earthquake shows that the high-frequencyfall-off of source spectra and its variation with the size of earthquake can be well explained by the model that for 'large'earthquakes the stress drop is a constant while for ',small' earthquakes the stress drop increases with the size of theearthquake.

Pump-stopping pressure drop model considering transient leak-off of fracture network

By introducing the coupling flow expressions of main fracture-matrix, secondary fracture-matrix and main fracture-secondary fracture into the traditional main fracture material balance equation, the “main fracture-secondary fracture-matrix” leak-off coupling flow model is established. The pressure-dependent fracture width equation and the wellbore injection volume equation are coupled to solve the pressure-rate continuity problem. The simulation and calculation of the bottomhole pressure drop and fracture network closure after the pump stopping in slickwater volumetric fracturing treatment are realized. The research results show that the log-log curve of pump-stopping bottomhole pressure drop derivative presents five characteristic slope segments, reflecting four dominant stages, i.e. inter-fracture crossflow, fracture network leak-off, fracture network closure and residual leak-off, after pump shutdown. At the initial time of pump shutdown for volumetric fracturing treatment of horizontal well, the crossflow between main and secondary fractures is obvious, and then the leak-off becomes dominant. The leak-off of main and secondary fractures shows a non-uniform decreasing trend. Specifically, the leak-off of main fractures is slow, while that of secondary fractures is fast;the fracture network as a whole presents the leak-off law of fast first, then slow, until close to zero. The influence of fracture network conductivity on the shape of pressure decline curve is relatively weaker than that of fracture network size. The fracture network conductivity is positively correlated with leak-off volume and fracture closure. The secondary fracture size is positively correlated with leakoff volume and closure of the secondary fracture, but negatively correlated with closure of the main fracture. Field data validation proves that the proposed model and simulation results can effectively reflect the closure characteristics of the fracture network, and the interpretation results are reliable and can reflect the non-uniform stimulation performance of each fracturing stage of an actual horizontal well.

A data-driven model of drop size prediction based on artificial neural networks using small-scale data sets

An artificial neural network(ANN)method is introduced to predict drop size in two kinds of pulsed columns with small-scale data sets.After training,the deviation between calculate and experimental results are 3.8%and 9.3%,respectively.Through ANN model,the influence of interfacial tension and pulsation intensity on the droplet diameter has been developed.Droplet size gradually increases with the increase of interfacial tension,and decreases with the increase of pulse intensity.It can be seen that the accuracy of ANN model in predicting droplet size outside the training set range is reach the same level as the accuracy of correlation obtained based on experiments within this range.For two kinds of columns,the drop size prediction deviations of ANN model are 9.6%and 18.5%and the deviations in correlations are 11%and 15%.

Buckling Properties of Water-Drop-Shaped Pressure Hulls with Various Shape Indices Under Hydrostatic External Pressure

The water-drop-shaped pressure hull has a good streamline,which has good application prospect in the underwater observatory.Therefore,this study conducted analytical,experimental and numerical investigation of the buckling properties of water-drop-shaped pressure hulls under hydrostatic pressure.A water-drop experiment was conducted to design water-drop-shaped pressure hulls with various shape indices.The critical loads for the water-drop-shaped pressure hulls were resolved by using Mushtari’s formula.Several numerical simulations including linear buckling analysis and nonlinear buckling analysis including eigenmode imperfections were performed.The results indicated that the critical loads resolved by Mushtari's formula were in good agreement with the linear buckling loads from the numerical simulations.This formula can be extended to estimate the buckling capacity of water-drop-shaped pressure hulls.In addition,three groups of pressure hulls were fabricated by using stereolithography,a rapid prototyping technique.Subsequently,three groups of the pressure hulls were subjected to ultrasonic measurements,optical scanning,hydrostatic testing and numerical analysis.The experimental results were consistent with the numerical results.The results indicate that the sharp end of the water-drop-shaped pressure hulls exhibited instability compared with the blunt end.This paper provides a new solution to the limitations of experimental studies on the water-drop-shaped pressure hulls as well as a new configuration and evaluation method for underwater observatories.

Evaluation of frictional pressure drop correlations for air-water and air-oil two-phase flow in pipeline-riser system

Accurate prediction of the frictional pressure drop is important for the design and operation of subsea oil and gas transporting system considering the length of the pipeline. The applicability of the correlations to pipeline-riser flow needs evaluation since the flow condition in pipeline-riser is quite different from the original data where they were derived from. In the present study, a comprehensive evaluation of 24prevailing correlation in predicting frictional pressure drop is carried out based on experimentally measured data of air-water and air-oil two-phase flows in pipeline-riser. Experiments are performed in a system having different configuration of pipeline-riser with the inclination of the downcomer varied from-2°to-5°to investigated the effect of the elbow on the frictional pressure drop in the riser. The inlet gas velocity ranges from 0.03 to 6.2 m/s, and liquid velocity varies from 0.02 to 1.3 m/s. A total of885 experimental data points including 782 on air-water flows and 103 on air-oil flows are obtained and used to access the prediction ability of the correlations. Comparison of the predicted results with the measured data indicate that a majority of the investigated correlations under-predict the pressure drop on severe slugging. The result of this study highlights the requirement of new method considering the effect of pipe layout on the frictional pressure drop.

A combined computational/experimental study of anode-concerned voltage drop in aqueous primary Mg-air batteries

The voltage drop appearing at Mg anode-electrolyte interface is a critical issue for the battery power and energy density of aqueous primary Mg-air batteries.The respective voltage loss is typically assigned to the deposits layer forming on the anode surface during discharge.In this work,we experimentally and computationally investigate the critical factors affecting the voltage drop at Mg anode towards a deeper understanding of the contribution of deposit and its growth.A two-dimensional(2D)mathematical model is proposed to compute the voltage drop of Mg-0.15Ca wt.%alloy(Mg-0.15Ca)by means of a semi-empirical formulas and experiments-based modification model,considering the effect of discharge current density,the negative difference effect(NDE)and surface deposits layer itself.This model is utilized to simulate the discharge potential of the anode at predefined experimental current densities.The computed voltage drop(half-cell voltage)is in good agreement with the experimental value.The applicability of the mathematical model is successfully validated on the second material(namely high-purity Mg).

Ladder Time Stepwise Inertia Coordinated Control Method of Multiple Wind Farms to Suppress System Frequency Secondary Drop

Currently,both regulated and deregulated power trading exist in China’s power system,which has caused imbalanced funds in the electricity market.In this paper,a simulation analysis of the electricity market with wind energy resources is conducted,and the calculation methods of unbalanced funds are investigated systematically.In detail,the calculation formulas of unbalanced funds are illustrated based on their definition,and a two-track electricity market clearing model is established.Firstly,the concept of the dual-track system is explained,and the specific calculation formulas of various types of unbalanced funds are provided.Next,considering the renewable energy consumption,the market clearing model based on DC power flow is constructed and solved;by combining fitting methods of mid-and long-term curves,the unbalanced funds are calculated based on clearing results and formulas.

Presentation and management outcome of foot drop with tibialis posterior tendon transfer

BACKGROUND Foot drop causes considerable disability.The ankle-dorsiflexion is either weak or lost completely.Additionally,the ankle eversion and toe extensions are also impaired.This results in a high steppage gait while walking.Overall,the gait is awkward;there is greater energy consumption;increased proneness to sustain injury of the forefoot;and more frequent falling during walking.AIM To document the clinical and epidemiological profile of foot drop patients in our population and evaluate the outcome of tibialis posterior(TP)tendon transfer for restoring the lost dorsiflexion in foot drop.METHODS The study was carried out at the National Institute of Rehabilitation Medicine in Islamabad over a period of 7 years.It included patients of all sexes and ages who presented with foot drop and had no contraindications for the procedure of TP tendon transfer.Exclusion criteria were patients who had contraindications for the operation.For instance,paralyzed posterior leg compartment muscles,Achilles tendon contracture,stiff ankle or toes,unstable ankle joint,weak gastrocnemius and scarred skin spanning over the route of planned tendon transfer.Also,patients who had the foot drop as a result of disc prolapses or brain diseases were excluded.Convenience sampling technique was used.The circum-tibial route of TP tendon transfer was employed.RESULTS Out of 37 patients,26(70.27%)were males whereas 11(29.72%)were females.The mean age was 22.59±8.19 years.Among the underlying causes of foot drop,road traffic accidents constituted the most common cause,found among 20(54.05%)patients.The share of complications included wound infections in 3(8.10%)patients and hypertrophic scars in 2(5.40%)patients.At 1-year postoperative follow-up visits,the outcome was excellent in 8(21.62%),good in 20(54.05%)and moderate in 9(24.31%).CONCLUSION The majority of cases of foot drop resulted from road traffic accidents that directly involved the common peroneal nerve.TP tendon transfer through the circumtibial route was found to be an easily executed effective operation which restored good dorsiflexion of the ankle among the majority of patients.

Efficacy of recombinant human epidermal growth factor plus sodium hyaluronate eye drops in diabetic dry eye post-cataract surgery

BACKGROUND Dry eye syndrome(DES)after diabetic cataract surgery can seriously affect the patient’s quality of life.Therefore,effective alleviation of symptoms in patients with this disease has important clinical significance.AIM To explore the clinical effect of recombinant human epidermal growth factor(rhEGF)plus sodium hyaluronate(SH)eye drops on DES after cataract surgery in patients with diabetes.METHODS We retrospectively evaluated 82 patients with diabetes who experienced DES after cataract surgery at Tianjin Beichen Hospital,Affiliated Hospital of Nankai University between April 2021 and April 2023.They were classified into an observation group(42 cases,rhEGF+SH eye drops)and a control group(40 cases,SH eye drops alone),depending on the different treatment schemes.The therapeutic efficacy,dry eye symptom score,tear film breakup time(TFBUT),basic tear secretion score[assessed using Schirmer I test(SIt)],corneal fluorescein staining(FL)score,tear inflammatory markers,adverse reactions during treat-ment,and treatment satisfaction were compared between the two groups.RESULTS Therapeutic efficacy was higher in the observation group compared with the control group.Both groups showed improved TFBUT and dry eye,as well as improved SIt and FL scores after treatment,with a more pronounced improvement in the observation group.Although no marked differences in adverse reactions were observed between the two groups,treatment satisfaction was higher in the observation group.CONCLUSION rhEGF+SH eye drops rendered clinical benefits to patients by effectively ameliorating dry eye and visual impairment with favorable efficacy,fewer adverse reactions,and high safety levels.Thus,this treatment should be promoted in clinical practice.

Flow Rate Measurement of Gravity Infusion Set and Functional Evaluation of Drop Counter: A Pilot Study

Developing a novel drop counter by introducing the Internet of Things concept has been vigorously conducted in recent years. Understanding the newly introduced drop counter’s flow rate control accuracy and flow rate count feature is essential for improving safety in infusion management. This study aimed to verify if the new drop counters could secure accurate flow rate and drip count by conducting actual flow rate measurements using gravimetry and functional evaluation. A drop counter was attached to each drip chamber of the infusion set, and an IV drip was conducted at the 100 ml/h flow rate. The weight of discharged physiological saline was measured to plot trumpet curves. Next, three different types of drop counters were evaluated to determine if they maintained drip count accuracy according to the changes in their position angles. The flow rate errors in all conditions indicated trumpet-like curves, exhibiting an overall error range within ±10% in all observation windows. Although every drop counter successfully detected and measured dripping, it was challenging in some counters to detect dripping when the drip chamber was tilted. In comparing adult and pediatric IV sets, the adult IV set was found to be less likely to detect dripping in the angled position. No significant differences in results were confirmed between high and low flow rates, suggesting that the drop count function would not be affected by the flow rate in the ranges of typical infusion practices. Doppler sensors have a wide range of measurements and high sensitivity;the dripping was detected successfully even when the drip chamber was tilted, probably due to the advantages of these sensors. In contrast, miscounts occurred in those equipped with infrared sensors, which could not detect light intensity changes in tilted positions. Understanding the tendencies in flow rate errors in infusion can be valuable information for infusion management.

Prevalence and Factors Associated with Dry Eyes Syndrome in Glaucomatous Patients on Anti-Glaucoma Eye Drops Followed up at the Garoua Regional Hospital-Northern Cameroon

Background: Dry eye and glaucoma are two common pathologies in the elderly, and are very often associated. This association suggests a link between them and between their treatments. Our purpose for this study is to determine the prevalence of dry eye in our glaucoma patients treated with eye drops and deduce the factors associated with it. Patients and Methods: We conducted a cross-sectional, analytical study from October 2022 to September 2023 in the ophthalmology department of Garoua Regional Hospital in glaucoma patients aged over 15 years able to answer the Ocular Surface Disease Index (OSDI) questionnaires and treated with antiglaucoma eye drops for more than 3 months. These patients underwent a complete ophthalmological examination and a tear film break-up time test. Results: A total of 73 patients (146 eyes) were examined. The average age of the patients was 47.2 ± 16.5 years, with a male predominance of 54.8%. The prevalence of dry eye syndrome in our patients according to the OSDI score was 56.2% (95% CI) (44.8;67.6). The prevalence of dry eye syndrome on clinical examination of the BUT in the right eye was 83.7% (95% CI) (75.1;92.1) and 79.4% (70.2;88.7) in the left eye. The duration of antiglaucoma treatment was the factor associated with dry eye syndrome (p < 0.05) in glaucoma patients in our setting. Conclusion: Dry Eye Syndrome is common in glaucoma patients on drops in our setting. Treatment duration of more than 1 year seems to be associated with dry eyes.

The Effect of Ginkgo Biloba Leaf Dropping Pill Combined with Butylphthalide Capsule on Cognitive Dysfunction in Patients after Acute Ischemic Stroke and Its Impact on Serum Cytokines

Objective: To investigate the therapeutic effect of Ginkgo biloba extract dropping pills combined with butylphthalide capsules on cognitive dysfunction in patients after acute ischemic stroke (AIS) and its impact on serum cytokines CRP, IL-6, and Hcy. Methods: This study selected 76 patients with cognitive dysfunction after ischemic stroke who were hospitalized at Zhuji People’s Hospital from January 2023 to January 2024. The patients were divided into two groups. The control group was treated with butylphthalide capsules, while the combination group received Ginkgo biloba extract dropping pills in addition to the treatment given to the control group. The neurological function, cognitive function, activities of daily living, and levels of serum cytokines CRP, IL-6, and Hcy were compared between the two groups after 1 month and 3 months of treatment. Results: The NIHSS scores, MMSE scores, ADL scores, and levels of CRP, IL-6, and Hcy in both groups showed statistically significant differences compared to before treatment (P Conclusion: The combination of Ginkgo biloba extract dropping pills and butylphthalide capsules has a better therapeutic effect on cognitive dysfunction in patients after ischemic stroke. It can improve the neurological function and cognitive function of patients, enhance their ability to perform daily activities, and reduce inflammatory responses.

Temperature Drop of Molten Metals in Open Channels

The temperature drop of molten metal flowing in open channels is numerically determined. Rectangular, trapezoidal and triangular geometries are considered. The overall heat transfer coefficients for the bottom, side walls and free surface of the channel have been taken from the literature. For each geometry, the volumetric flow rate, mean residence time and temperature drop as a function of the channel inclination angle were determined. The rectangular and trapezoidal geometries present the smallest temperature drops, while the triangular geometry presents the greatest temperature drop. The factors that most affect this drop are the value of the free surface area of the channel, and the average residence time of the molten metal in the channel.

Improvement of Temperature Drop Model Parameters for 4200mm/3500mm Rolling of Baosteel Medium and Thick Plate

Based on the temperature situation during the rolling process of 4200 mm/3500 mm medium and thick plates at Baosteel,this article analyzes the influencing factors of temperature changes during the rolling process from the perspective of heat transfer theory and the temperature change law during the rolling process.The temperature loss during the four rolling processes is tracked on site,and the temperature drop model parameters during the rolling process of 4200mm/3500mm medium and thick plates at Baosteel are quantitatively provided.It is applied to actual rolling production and has achieved good results.

Clinical Observation of Recombinant Bovine Basic Fibroblast Growth Factor Eye Gel Combined with Tobramycin Dexamethasone Eye Drops in the Treatment of Dry Eye Syndrome in Patients after Cataract Surgery

Objective:To evaluate the therapeutic effect of recombinant bovine basic fibroblast growth factor(rbFGF)eye gel combined with tobramycin-dexamethasone(TOB-Dex)eye drops on dry eye syndrome(DES)after cataract surgery.Methods:86 patients with DES after cataract surgery,admitted from November 2021 to November 2023,were randomly divided into groups.The observation group included 43 patients treated with rbFGF eye gel combined with TOB-Dex eye drops.The reference group included 43 patients treated with TOB-Dex eye drops alone.Multiple indicators,including total effective rate and clinical symptom scores,were compared between the two groups.Results:The total effective rate in the observation group was higher than in the reference group(P<0.05).Before treatment,there were no differences in clinical symptom scores,serum factors,or disease severity scores between the two groups(P>0.05).Three weeks after treatment,the observation group had lower clinical symptom scores,serum factors,and disease severity scores compared to the reference group(P<0.05).The adverse reaction rate in the observation group was lower than in the reference group(P<0.05).Conclusion:rbFGF eye gel combined with TOB-Dex eye drops can improve the clinical efficacy for patients with DES after cataract surgery,alleviate disease symptoms,reduce inflammatory responses,and have fewer adverse reactions.

Ovule Development, Formation of Pollination Drop and Pollination Process in Taxus chinensis (Taxaceae)

Pollen morphology and hydration, ovule development, formation of pollination drop and the pollination process of Taxus chinensis (Pilg.) Rehd were investigated in detail. The results showed that mature pollen was one_celled, irregular in shape, nonsaccate, and the surface was covered with orbicules. When pollen became hydrated, the intine swelled and the exine bursted. The exine usually remained on the surface of water or on the pollination drop all the time, while the rest portion of the pollen sank into the drop of water or the pollination drop. In the late August, the down_curved female buds could be observed in the field trees. The downturning of the female buds was an characteristic feature discriminating from the vegetative buds. At this stage ovular primordium was present in the female bud with a dome_shaped nucellar primordium encircled by a rudimentary integument. The integument grew fast and overgrew the nucellus. In the March of the following year, the ovule formed a micropylar canal about 1?000 μm in length, 200-300 μm in width. Except the micropyle, the other part of the ovule was enclosed by 20-25 scales. During the early stage of the ovule development, the nucellar surface clearly showed cell configuration; but a membrane_like structure covering the nucellar apex appeared in the late stage of the ovule development, and subsequently broke down with nucellar cell disintegration before pollen shedding. The disintegrated cell products might partake in the formation of the pollination drop. Before and during pollination, the nucellar cells contained abundant mitochondria, endospermic reticulum and dictysomes with vesicles; the plasma membrane was undulated and there was no accumulation of electron_dense substances in the pericytoplasm. Pollination drops usually occurred at night, and disappeared by noon in the field tree. 15 days before pollination, the in vitro ovules from the field trees already had the capability of producing pollination drops, which could last for 4-5 days indoors. However, after these drops received pollen, they did not withdraw noticeably compared with the unpollinated ones. The retraction of the pollination drop was presumed not to be a nonmetabolic outcome but rather a result of evaporation.

Drop failure modes of Sn-3.0Ag-0.5Cu solder joints in wafer level chip scale package

To reveal the drop failure modes of the wafer level chip scale packages （WLCSPs） with Sn-3.0Ag-0.5Cu solder joints, board level drop tests were performed according to the JEDEC standard. Six failure modes were identified, i.e., short FR-4 cracks and complete FR-4 cracks at the printing circuit board （PCB） side, split between redistribution layer （RDL） and Cu under bump metallization （UBM）, RDL fracture, bulk cracks and partial bulk and intermetallic compound （IMC） cracks at the chip side. For the outmost solder joints, complete FR-4 cracks tended to occur, due to large deformation of PCB and low strength of FR-4 dielectric layer. The formation of complete FR-4 cracks largely absorbed the impact energy, resulting in the absence of other failure modes. For the inner solder joints, the absorption of impact energy by the short FR-4 cracks was limited, resulting in other failure modes at the chip side.