PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Supramolecular polymer-based gel fracturing fluid with a double network applied in ultra-deep hydraulic fracturing

A gel based on polyacrylamide,exhibiting delayed crosslinking characteristics,emerges as the preferred solution for mitigating degradation under conditions of high temperature and extended shear in ultralong wellbores.High viscosity/viscoelasticity of the fracturing fluid was required to maintain excellent proppant suspension properties before gelling.Taking into account both the cost and the potential damage to reservoirs,polymers with lower concentrations and molecular weights are generally preferred.In this work,the supramolecular action was integrated into the polymer,resulting in significant increases in the viscosity and viscoelasticity of the synthesized supramolecular polymer system.The double network gel,which is formed by the combination of the supramolecular polymer system and a small quantity of Zr-crosslinker,effectively resists temperature while minimizing permeability damage to the reservoir.The results indicate that the supramolecular polymer system with a molecular weight of(268—380)×10^(4)g/mol can achieve the same viscosity and viscoelasticity at 0.4 wt%due to the supramolecular interaction between polymers,compared to the 0.6 wt%traditional polymer(hydrolyzed polyacrylamide,molecular weight of 1078×10^(4)g/mol).The supramolecular polymer system possessed excellent proppant suspension properties with a 0.55 cm/min sedimentation rate at 0.4 wt%,whereas the0.6 wt%traditional polymer had a rate of 0.57 cm/min.In comparison to the traditional gel with a Zrcrosslinker concentration of 0.6 wt%and an elastic modulus of 7.77 Pa,the double network gel with a higher elastic modulus(9.00 Pa)could be formed only at 0.1 wt%Zr-crosslinker,which greatly reduced the amount of residue of the fluid after gel-breaking.The viscosity of the double network gel was66 m Pa s after 2 h shearing,whereas the traditional gel only reached 27 m Pa s.

小儿经腹肠系膜间隙入路腹腔镜下肾盂成形术的疗效观察

目的总结经腹肠系膜间隙入路行腹腔镜下肾盂成形术的临床经验,探讨该术式治疗小儿左侧肾盂输尿管连接部狭窄导致肾盂积水的疗效。方法回顾性分析2014年5月-2020年5月该院18例采取经腹肠系膜间隙入路行腹腔镜下肾盂成形术患儿的临床资料。其中,男10例,女8例,年龄3~14岁,平均(5.7±2.9)岁,均为左侧。均采用经腹腔肠系膜间隙入路,术中将切开的肠系膜间隙用丝线悬吊于腹壁,便于手术野暴露。裁剪多余的肾盂后,采用Anderson-Hynes技术行肾盂输尿管成形术,自吻合口留置输尿管支架。统计手术时间、术中出血量、术后住院时间、术后肠道功能恢复时间,总结手术技巧及经验。术后通过彩超和发射体层仪(ECT)肾动态显像来评价手术效果。结果18例患者均顺利完成手术,无中转开腹,手术时间75~130 min,平均(98.2±17.7)min,术中出血量5~20 mL,平均(10.0±3.7)mL,术后肠道功能恢复时间1~4 d,平均(1.9±1.0)d,术后住院时间2~5 d,平均(2.1±1.2)d,术后随访6~24个月,患者临床症状逐渐消失,术后6个月复查超声:肾盂前后径(APD)(7.9±1.7)mm,较术前的(34.8±2.0)mm明显缩小(P=0.000),术后6个月复查患侧分肾功能为(40.1±2.9)%,较术前的(28.1±3.0)%明显改善(P=0.000),手术成功率为100%。结论该入路行腹腔镜下肾盂成形术安全、有效,对患儿肠道影响较小,有利于患儿术后快速康复。

Probing the influence of secondary fracture connectivity on fracturing fluid flowback efficiency

A deep understanding of the geometric impacts of fracture on fracturing fluid flowback efficiency is essential for unconventional oil development. Using nuclear magnetic resonance and 2.5-dimensional matrix-fracture visualization microfluidic models, qualitative and quantitative descriptions of the influences of connectivity between primary fracture and secondary fracture on flowback were given from core scale to pore network scale. The flow patterns of oil-gel breaking fluid two-phase flow during flowback under different fracture connectivity were analyzed. We found some counterintuitive results that non-connected secondary fracture (NCSF, not connect with artificial primary fracture and embedded in the matrix) is detrimental to flowbackefficiency. The NCSF accelerates the formation of oil channeling during flowback, resulting in a large amount of fracturing fluid trapped in the matrix, which is not beneficial for flowback. Whereas the connected secondary fracture (CSF, connected with the artificial primary fracture) is conducive to flowback. The walls of CSF become part of primary fracture, which expands the drainage area with low resistance, and delays the formation of the oil flow channel. Thus, CSF increases the high-speed flowback stage duration, thereby enhancing the flowback efficiency. The fracturing fluid flowback efficiency investigated here follows the sequence of the connected secondary fracture model (72%) > the matrix model (66%) > the non-connected secondary fracture model (38%). Our results contribute to hydraulic fracturing design and the prediction of flowback efficiency.

Giant enhancement of superconductivity in few layers MoTe2

Recently, the layered transition metal dichalcogenide 1 T MoTe2 has attracted considerable attention due to its non-saturating magnetoresistance, type-II Weyl semimetal properties, superconductivity, and potential candidate for twodimensional（2 D） topological insulator in the single-and few-layer limit. Here in this work, we perform systematic transport measurements on thin flakes of MoTe2 prepared by mechanical exfoliation. We find that MoTe2 flakes are superconducting and have an onset superconducting transition temperature Tc up to 5.3 K, which significantly exceeds that of its bulk counterpart. The in-plane upper critical field(Hc2||) is much higher than the Pauli paramagnetic limit, implying that the MoTe2 flakes have Zeeman-protected Ising superconductivity. Furthermore, the Tc and Hc2|| can be tuned by up to 320 mK and 400 mT by applying a gate voltage. Our result indicates that MoTe2 flake is a good candidate for studying exotic superconductivity with nontrivial topological properties.

Visualization of adaptive polymer flow and displacement in medium-permeable 3D core-on-a-chip

Polymer flooding has been witnessed an effective technology for enhancing oil recovery from medium-to low-permeability reservoirs;however, direct visualization of polymer solution flow in such reservoir condition is still lacking. In this work, a three-dimensional (3D) core-on-a-chip device with a permeability of around 200 mD was prepared and employed to visualize the pore-scale flow and displacement of a self-adaptive polymer (SAP, 8.7 × 106 g·mol−1)−whose microscopic association structure and macroscopic viscosity can reversibly change in response to shear action−versus partially hydrolyzed polyacrylamide (HPAM), by recording their flow curves, monitoring dynamic transportation process via particle imaging velocimetry, and building 3D structure of remaining oil. The results show that, in single-phase flow, all polymer solutions exhibit flow thinning and then thickening regions as flow rate increases, but the transition between two regimes occurs at a small Weissenberg number (10−3−10−1) in this medium-permeable condition. In contrast to HPAM-1 with close weight-average molecular weight (Mw), the adaptive character not only extends SAP's shear-govern region, allowing SAP to propagate piece by piece and achieve higher accessible pore volume, but it also enhances the elastic resistibility of polymer in the extension-dominated regime, increasing the microscopic displacement efficiency. These two effects result in 1.5–3 times more oil recovery factor for SAP than for HPAM-1. Regarding ultra-high-Mw HPAM-2 (25 × 106 g·mol−1), plugging and chain degradation do occur, thus producing lower oil recovery than SAP. This work provides a direct approach for in-situ assessment of polymer-based displacing system under a more authentic condition of practical reservoirs.

Aperture shape optimization in intensity-modulated radiation therapy planning

The gradient element of the aperture gradient map is utilized directly to generate the aperture shape without modulation.This process can be likened to choosing the direction of negative gradient descent for the generic aperture shape optimiza-tion.The negative gradient descent direction is more suitable under local conditions and has a slow convergence rate.To overcome these limitations,this study introduced conjugate gradients into aperture shape optimization based on gradient modulation.First,the aperture gradient map of the current beam was obtained for the proposed aperture shape optimiza-tion method,and the gradients of the aperture gradient map were modulated using conjugate gradients to form a modulated gradient map.The aperture shape was generated based on the modulated gradient map.The proposed optimization method does not change the optimal solution of the original optimization problem,but changes the iterative search direction when generating the aperture shape.The performance of the proposed method was verified using cases of head and neck cancer,and prostate cancer.The optimization results indicate that the proposed optimization method better protects the organs at risk and rapidly reduces the objective function value by ensuring a similar dose distribution to the planning target volume.Compared to the contrasting methods,the normal tissue complication probability obtained by the proposed optimization method decreased by up to 4.61%,and the optimization time of the proposed method decreased by 5.26%on average for ten cancer cases.The effectiveness and acceleration of the proposed method were verified through comparative experiments.According to the comparative experiments,the results indicate that the proposed optimization method is more suitable for clinical applications.It is feasible for the aperture shape optimization involving the proposed method.

Effects of Shenqi Fuzheng injection on oxidative stress after hepatic ischemia-reperfusion injury

Objective:In order to determine Shenqi Fuzheng injection’s clinical effects and explore the impact on the SOD、MDA and liver function of patients,who underwent Hepatic ischemiareperfusion injury during the surgical operation.Methods:Forty patients were collected who were treated in Oncology Surgery of Bayi Hospital from January 2019 to August 2019.These patients were divided into control group and therapy group(Shenqi Fuzheng Injection)randomly,with 20 cases in each group.In the control group,one was switched to RF treatment during operation,one was only partially blocked during operation,and the remaining 38 cases completed the study.These remained patients were all operated with Pringle maneuver,then were treated with anti-infection,liver protection,acid suppression,fluid replacement,intravenous nutrition support and other symptomatic treatment after surgery.In addition,for the patients in the therapy group,the treatment of Shenqi Fuzheng injection were added once a day,which lasted 5 days.During the perioperative period,we would record their general conditions,SOD and MDA levels;liver function(ALT、AST、LDH).These data were analyzed statistically by SPSS 21.0 statistical software.Results:There was no statistically significant difference in general indicators related to the perioperative period between the two groups of patients(P>0.05).There was no significant difference in SOD and MDA levels between the two groups(P>0.05).,but at 1d,3d,and 5d after operation,the SOD level in the observation group was significantly higher than that in the control group(both P<0.05)and The MDA level in the observation group was significantly lower than the control group.The differences were statistically significant(all P<0.05).There was no significant difference in ALT and AST levels between the two groups before and after surgery(P>0.05),while the LDH levels in the two groups were not statistically different before surgery,on the first day after surgery,and on the third day after surgery(P>0.05),while there were statistical differences on the fifth day after surgery(P<0.05).Conclusions:For the pathients who received hepatectomy with Pringle maneuver,using Shenqi Fuzheng injection could improve the activity of antioxidant enzymes in the body,reduce the production of lipid peroxides,inhibit the oxidative stress response in the process of HIRI,thus it played a role in protecting the liver and accelerated the recovery.

Mechanism of Aidi injection on hepatocellular carcinoma based on network pharmacology

Objective:To explore the active ingredients and potential mechanism of Aidi injection in the treatment of hepatocellular carcinoma by network pharmacology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID)were used to screen the active ingredients of four traditional Chinese medicines of Renshen,Huangqi,Ciwujia,and Banmao and corresponding potential targets.Screening of hepatocellular carcinoma-related targets through the Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database platforms.The drug and disease targets are merged to obtain the intersection,and the information is imported into Cytoscape 3.7.2 to construct a network diagram of the active ingredients of Aidi injection and related targets of hepatocellular carcinoma,and the topology analysis is performed.A protein-protein interaction(PPI)network was constructed and analyzed using the STRING online analysis platform.Uses the Database for Annotation,Visualization and Integrated Discovery(DAVID)to perform GO function enrichment analysis of targets and enrichment of KEGG pathways analysis.Results:A total of 33 potential active ingredients were screened from Aidi injection for treating hepatocellular carcinoma,including quercetin,kaempferol,beta-sitosterol,isorhamnetin and other important active ingredients.There are 106 potential targets for active ingredient action,6,677 disease-related targets,and 89 drug-disease common targets.Through the network diagram,it was found that the highest degree of target is PTGS1.In the PPI graph,a total of 87 nodes.Among them,the higher degree values include IL6,CASP3,VEGFA,MAPK8,JUN,EGFR,MYC,PTGS2 and FOS.A total of 60 related signal pathways were obtained by GO enrichment analysis.It mainly involves biological processes such as inhibiting abnormal proliferation and differentiation of hepatocellular carcinoma cells,inhibiting angiogenesis of hepatocellular carcinoma,regulating cell cycle and promoting apoptosis.KEGG pathway enrichment analysis screened a total of eight significantly different signal pathways.Among them,P53,VEGF,MAPK,Toll-like receptor,ErbB signaling pathways play an important role in treatment.Conclusion:This study initially revealed the potential mechanism of multi-component,multi-target and multi-pathway treatment of Aidi injection for hepatocellular carcinoma,and provided ideas for the subsequent verification of the molecular mechanism of Aidi injection for hepatocellular carcinoma.

A summary of diagnosis and treatment experience of novel coronavirus pneumonia

The current epidemic situation of the COVID-19 is still serious.As a designated unit for the diagnosis of COVID-19 in Hainan Province,We,The Second Affiliated Hospital of Hainan Medical University,established a multidisciplinary integrated individualized treatment team.We emphasized early improvement of relevant examinations,early antiviral treatment,dynamic monitoring of inflammatory markers and imaging changes.In addition,nutritional support,psychological intervention,and Chinese medicine treatment also play an important role.We summarized the experience in the diagnosis and treatment process for the reference of clinicians.

The diagnosis and treatment process of one clinical case of juvenile glycogen storage disease in current medical model in china

Glycogen storage disease type Ⅱ, also known as Pompe disease (PD), is a kind of congenital metabolic myopathy, the cause of this disease is the barrier of glycogen disintegration due to the shortage of acid alpha-1,4-glucosidase enzyme. The prevalence of PD ranges between 1:40,000 and 1:300,000 and is dependent on ethnic and geographical factors. The main clinical manifestation of this myopathy is the injury of muscle organization. According to the difference in age and developmental speed, we can divide this disease into three types: the infantile type, the juvenile type and the adult type, and the latter two types are called the late onset type. Because the symptom of the late onset form is not typical, the mutual mixture of the late onset type and some chronic myopathy always takes place, which can even cause evade diagnosis and misdiagnosis, thus it is supposed to be highly focused on. At present, there is a shortage of effective therapeutic methods to cope with this myopathy all over the world. The following part is a report about the clinical data and the rehabilitation intervention of a patient who caught the juvenile type of GSD-Ⅱ, which is combined to home and abroad literatures, the purpose of this report is to help enhance clinical physicians’ cognition of this disease in the future therapy. At the same time, we combine with the current medical mode and system in China to reflect on the prevention and treatment of such diseases.

Synthesis and biological activities of some fluorine- and piperazine-containing 1,2,4-triazole thione derivatives

A series of fluorine- and piperazine-containing 1,2,4-triazole thione derivatives were synthesized by the Mannich reaction of triazole intermediates with various substituted piperazines and formaldehyde in high yields. Structures of title compounds were confirmed by melting points, IR,~1H NMR,^（13）C NMR and elemental analysis. The preliminary bioassays for 17 novel title compounds showed that several compounds have significant fungicidal activity against Cercospora arachidicola, Physalospora piricola and Rhizoctonia cerealis at 50 mg/m L.

Low-thermal-conductivity thermal barrier coatings with a multi-scale pore design and sintering resistance following thermal exposure

High-insulation,long-life thermal barrier coatings(TBCs)decrease the service temperature of superalloys and improve the service life of gas turbines.Improvement in the thermal insulation properties of the coating mainly depends on the optimization of the TBC structure.An important challenge for TBCs is maintaining a high performance during thermal exposure without degradation,as the pore-rich structure of the topcoat would inevitably be transformed by sintering.A low-thermalconductivity anti-sintering coating can overcome the tradeoff between thermal insulation and sinter degradation.In this review,the design,preparation,and serviceability evaluation of a low-thermal-conductivity anti-sintering coating will be discussed.Furthermore,directions for potential development are introduced.This paper provides a comprehensive understanding of the structured tailoring of TBCs for better thermal insulation and anti-sintering performance.

Dynamics-based optimization of rolling schedule aiming at dual goals of chatter suppression and speed increase for a 5-stand cold tandem rolling mill

In the process of cold tandem rolling,chatter instability leads to serious impacts on enhancing rolling speed,improving product quality,reducing production cost and realizing intellectualization.Chatter occurs with the rolling speed up to a certain threshold value,but the critical speed is determined by both product specifications and rolling schedules.A 5-stand cold tandem rolling mill whose first three stands and subsequent two stands,respectively,have four and six rolls was investigated by formulating its dynamic equations with the corresponding structure-process coupling.By applying the stability-based calculation model about the critical rolling speed in each stand,the system dynamic responses around the critical rolling speed were simulated,and the system eigenvalues which represent instability and characteristic frequencies were figured out.Thereafter,via combining the critical rolling speeds with the system dynamic behavior,a dynamics-based optimization model of rolling schedule for the 5-stand cold tandem system was proposed for the purposes of both the chatter suppression and rolling speed increase.In the optimization model,eight rolling technique parameters(four strip thicknesses and four tensions between the upstream and downstream stands)were taken as design variables,and the constraint conditions were set as no chatter instability in all five stands,and the optimization goal was to maximize the outlet speed of the final stand.The pattern search method was introduced to solve the optimization model.By applying such a dynamics-based optimization model for the 5-stand cold tandem rolling process,the chatter instability was suppressed effectively and the rolling efficiency was improved considerably;therefore,such an optimization model is expected to be valuable for intelligent manufacturing of rolling process.

Rapid and nondestructive layer number identification of two-dimensional layered transition metal dichalcogenides

MoS2, MoSe2 and WSe2 thin flakes were fabricated by the standard micromechanical cleavage procedures. The thickness and the optical contrast of the atomic thin dichalcogenide flakes on SiO2/Si substrates were measured by atomic force microscopy（AFM） and spectroscopic ellipsometer. A rapid and nondestructive method by using reflection spectra was proposed to identify the layer number of 2D layered transition metal dichalcogenides on SiO2（275 nm）/Si substrates. The contrast spectra of 2D nanosheets with different layer numbers are in agreement with theoretical calculations based on Fresnel＇s law, indicating that this method provides an unambiguous and nondestructive contrast spectra fingerprint for identifying single-and few-layered transition metal dichalcogenides. The results will greatly help in fundamental research and application.

Rapidly counting atomic planes of ultra-thin MoSe2 nanosheets(1≤n≤4)on SiO2/Si substrate

The optical, thermal and electrical properties of ultra-thin two-dimensional （2D） crystal materials are highly related to their thickness. Therefore, identifying the atomic planes of few-layer crystal materials rapidly is crucial to fundamental study. Here, a simple technique was demonstrated based on optical contrast for counting atomic planes （n） of few-layer MoSe2 on SiO2/Si substrates. It is found that the optical contrast of single-layer MoSe2 depends on light wavelength and thickness of SiO2 on Si substrate. The data calculated based on a Fresnel law-based model as well as atomic force microscopy （AFM） mea- surements fit well with the values measured by spectro- scopic ellipsometer. Furthermore, the calculated and measured contrasts were integral and plotted, which can be used to determine the MoSe2 atomic planes （1 ≤ n ≤ 4） accurately and rapidly.

Extended culture of day 3 embryos improves live birth rate in in vitro fertilization-embryo transfer

To the Editor:Embryo development at the early cleavage stage is a complex and well-orchestrated biological process.During in vitro fertilization-embryo transfer(IVF-ET),embryos are routinely stratified according to morphological criteria and transferred on the morning of day 3 after fertilization.This stage of embryonic development is mainly regulated by maternal factors because the embryonic genome has not yet been fully activated.[1]Day 3 is a key period for embryos to accomplish embryonic genome activation(EGA).Embryos with higher developmental potential initiate EGA for subsequent development and implantation,while non-viable embryos undergo arrest.

Enhanced spin diffusion length by suppressing spin-flip scattering in lateral spin valves

The spin transport was investigated in permally （Py）/MgO/Ag junction with lateral spin valve structure. Non-local lateral spin valves measurement was carried out to determin, the apin accumulignal in Ag strip, and the spin dif u^sion - length in Ag of the lateral spin valves was extracted from devices with the different distances between injector and detector. The experimental results are found that spin accumulation and spin diffusion length （2s） could be significantly enhanced in Ag strip with MgO capping layer, and those effects may be attributed to the low-surface spin scattering rate in Ag with an MgO cap- ping layer.

Study on the Photolysis Route of Nano 2,2',4,4',6,6'–Hexanitrostillbene by Vibrational Spectroscopy

The understanding of the photolysis process of 2,2’,4,4’,6,6’-hexanitrostillbene(HNS,an insensitive high-energy explosive)is very important not only for enhancing the detonation performance but also for its lifetime prediction.In this work,UV-Vis light-induced photolysis of nano HNS was studied by different spectroscopic methods.Nano HNS was found to be sensitive to UV-Vis lights at 365 and 470 nm.The photolysis route of nano HNS was mostly the same as its bulk counterpart,which was likely to be the combination of the isomerization of-NO_(2)to-ONO and the breaking of the C-N bond in Ar-NO_(2)(Ar=Aromatic ring).In addition,the possible mechanism of UV-Vis-induced visible color change was explored for the first time.