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The inherently dynamic and anisotropic microenvironment of cells imposes not only global and slow physical stimulations on cells but also acute and local perturbations. However, cell mechanical responses to transient subcellular physical signals remain unclear. In this study, acoustically activated targeted microbubbles were used to exert mechanical perturbations to single cells. The cellular contractile force was sensed by elastic micropillar arrays, while the pillar deformations were imaged using brightfield high-speed video microscopy at a frame rate of 1k frames per second for the first 10s and then confocal fluorescence microscopy. Cell mechanical responses are accompanied by cell membrane integrity changes. Both processes are determined by the perturbation strength generated by microbubble volumetric oscillations. The instantaneous cellular traction force relaxation exhibits two distinct patterns, correlated with two cell fates (survival or permanent damage). The mathematical modeling unveils that force-induced actomyosin disassembly leads to gradual traction force relaxation in the first few seconds. The perturbation may also influence the far end subcellular regions from the microbubbles and may propagate into connected cells with attenuations and delays. This study carefully characterizes the cell mechanical responses to local perturbations induced by ultrasound and microbubbles, advancing our understanding of the fundamentals of cell mechano-sensing, -responsiveness, and -transduction. STATEMENT OF SIGNIFICANCE: Subcellular physical perturbations commonly exist but haven't been fully explored yet. The subcellular perturbation generated by ultrasound and targeted microbubbles covers a wide range of strength, from mild, intermediate to intense, providing a broad biomedical relevance. With µm

This study proposes a novel micro-deep-hole drill with variable web thickness and flute width to effectively improve the problem of tool breakage and chip clogging during micro-deep-hole drilling. Firstly, the failure form and failure mechanism of micro-drill are explored by performing drilling experiments, and it is found that the torsion fracture and bending fracture are the main premature failure modes of micro-deep-hole drilling tools. The static simulation analysis of micro-drill is further conducted to investigate the influence of geometric parameters on the stiffness and strength of high-aspect-ratio micro-drill, and the results indicate that the web thickness ratio and flute width have significant effects on drill tip stiffness and spiral groove root strength. To balance the rigidity, strength and chip evacuation capability of micro-deep-hole drilling tools, the new micro-drill with variable web thickness and flute width is developed, supplemented by comparative experiments. The results confirm that the new micro-drill has better chip removal ability, greatly reduces the drilling force, torque, drill tip wear and material peeling phenomenon, and significantly enhances the machining quality of hole wall.

The reasonable distribution of benefits for the stakeholders of modern apprenticeship can satisfy the interest demands of stakeholders, contribute to the construction of a modern apprenticeship system and ultimately meet the inherent requirements of vocational education for economic and social development. To solve the enterprise participation motivation and low enthusiasm, unreasonable income distribution between enterprises and colleges, this article regard enterprises and schools as the main stakeholders involved in the modern apprenticeship, using the game theory, under a non-cooperative game and cooperative game situation, analyze the cost, net earning, enterprise effort and school subsidy coefficient of modern apprenticeship, research the income distribution problem in education of modern apprenticeship between enterprises and colleges.

Dynamic scheduling is one of the most important key technologies in production and flexible job shop is widespread. Therefore, this paper considers a dynamic flexible job shop scheduling problem considering setup time and random job arrival. To solve this problem, a dynamic scheduling framework based on the improved gene expression programming algorithm is proposed to construct scheduling rules. In this framework, the variable neighborhood search using four efficient neighborhood structures is combined with gene expression programming algorithm. And, an adaptive method adjusting recombination rate and transposition rate in the evolutionary progress is proposed. The test results on 24 groups of instances with different scales show that the improved gene expression programming performs better than the standard gene expression programming, genetic programming, and scheduling rules.

To explore the value of radiographic assessment of lung edema (RALE) score in evaluating the severity and prognosis of patients with acute respiratory distress syndrome (ARDS).A retrospective study was conducted. Patients with ARDS admitted to the department of intensive care unit (ICU) of Affiliated Nantong Third Hospital of Nantong University from January 2016 to November 2020 were enrolled. Clinical data of those patients were collected, and two senior radiologists who did not know the outcome of the patients independently scored each chest radiograph, the mean value of which was taken as the RALE score. The patients were divided into death group and survival group according to the 28-day prognosis. The differences of the basic data, PaOOf the 98 ARDS patients, 62 were included in the final analysis, 39 patients survived and 23 patients died. The 28-day mortality was 37.1%. Compared with the survival group, patients in the death group were older (years old: 72.83±12.21 vs. 64.44±14.68), had lower PaOThe RALE score is a simple and reliable non-invasive evaluation index, which can be used to evaluate the severity of ARDS patients. The difference of RALE score in early stage is helpful to identify ARDS patients with poor prognosis.

BACKGROUND Little is known about the relationship between the site of infection, type of pathogen, and the occurrence of sepsis-associated liver dysfunction (SALD). This population study aimed to identify the sites and types of infection in SALD patients. MATERIAL AND METHODS We conducted a retrospective observational study using the Medical Information Mart for Intensive Care III. Patients with sepsis were divided into a SALD group and a control group. We evaluated the effect of the location of culture-positive specimens and the distribution of pathogens on the occurrence of SALD and then compared the clinical outcomes. RESULTS A total of 14 596 admissions were included, and the incidence of SALD was 11.96%. Positive bile culture (odds ratio [OR] 7.450, P

A 63-year-old man was admitted for acute left heart failure after field operations. He rapidly developed refractory cardiogenic shock due to a large left atrial myxoma which was found by bed-side echocardiography. Veno-arteriovenous extracorporeal membrane oxygenation (ECMO) was performed immediately, and the patient was transferred for further surgery with a good outcome. Therefore, timely echocardiographic evaluation and surgical removal of myxomas is recommended, and ECMO could be used as a bridge between the transfer and perioperative period.

BACKGROUND Background: Enteritis inflammatory disease is a common multiple disease in the intestine. And the number of patients with enteritis in China has increased year by year. OBJECTIVE Objective: In order to study the effect of information services on inflammatory bowel disease under medical information support platform, the patients with enteritis were selected as the research subject. METHODS Method: The effects of nursing intervention on inflammatory bowel disease based on information support platform were studied by experimental methods such as antidiarrheal time, elimination of flatulence time, Escherichia coli, lactobacillus, SlgA (secretory immunoglobulin A) content in stool samples and colonoscopy. RESULTS Results: The results showed that the nursing intervention based on the information support platform had a significant improvement effect on inflammatory bowel disease. The time of diarrhea and flatulence was significantly reduced compared with the blank group, and other indicators were also developing in a favorable direction. CONCLUSIONS Conclusion: Compared with the blank group, the patients in the experimental group had significant improvement in the recovery of a large number of indicators. Not only that, patients have improved physical or intellectual aspects, so information intervention can be promoted clinically.

Micro mills are widely applied in the micro manufacturing and mainly fabricated using the grinding method. Cutting edges have significant influences on the performance of micro mills such as the micro mill life and machining quality. In this paper, the cutting edge damage mechanisms in the grinding of cemented carbides micro mills are investigated. The micro end mills grinding experiments are carried out and the cutting edge maximum edge damage width and surface roughness of the end teeth flank are measured. The results show that the micro fractures and micro cracks are generated in the cutting edge following micro pits in the grinding surface. The grain size and composition of cemented carbides have significant impacts on the damage of the cutting edge. The maximum edge damage width increases with the increase of Co binder content and WC grain sizes. However, a better flank quality with less micro pits is obtained as the reduction of Co binder content and grain size of WC.

The profile of drill flute has a great influence on the drilling performance of micro-drill. It is promising to obtain a desired flute profile with a standard wheel by adjusting the wheel position parameters during the grinding process. To investigate the flute profile characteristics under different wheel position parameters and its effect on the drilling performance, this paper presents a method for modeling and optimization of the micro-drill flute considering the wheel installation angle and the offset distance from the wheel origin to the drill blank origin. Based on this model, the flute profile of micro-drill is numerically simulated by MATLAB software firstly, and then, the 3D model of micro-drill with different flute profiles is established by UG software. Finally, the micro-drilling process on 304 austenitic stainless steel is simulated by DEFORM software, and the chip morphology and the drilling force are analyzed and discussed. The results show that the wheel installation angle has an obvious effect on the flute profile and its radial rake angle and flute width, and the wheel offset distance only influences the flute width evidently. The micro-drill with flute ground by smaller wheel installation angle owns straighter cutting lip shape and larger chip evacuation capacity, and its thrust force and torque are smaller than those of other micro-drills. Moreover, spiral chip is generated due to the intense side curl and up curl of the chip, resulting in the easiness of the chip removal. However, for the micro-drills with flute ground by larger wheel installation angle, the chip morphology is string and the drilling force is larger. At last, the mathematical model of the drill flute and its numerical simulation result are validated by experimentally fabricating the micro-drill flute. Then, the optimized micro-drill is manufactured by a six-axis computer numerical control (CNC) grinding machine, and its flute profile is fabricated using a standard conical grinding wheel with a smaller wheel installation angle.

Micro end milling is a main method for the fabrication of microgroove parts which are widely applied in biology, electronics, precision machinery, and other fields. However, the machining quality of microgroove is difficult to meet requirements due to size effect, and the machined grooves easily produce high surface roughness and poor form accuracy during micro milling. In this paper, in order to investigate the effects of machining inclination angles on the performance of micro ball end milling, the micro milling experiments on Ti-6Al-4V are carried out by setting the micro ball end mill with different inclination angles in feed direction, cross-feed direction, and the combination of the two directions, respectively. The results show that the tool orientation strategy has significant influences on the quality of microgroove and can reduce the roughness and improve the form accuracy. With increase of the absolute value of inclination angle along feed direction from 0° to 45°, the surface roughness has a decreasing trend, and the chips adhesion and texture becomes inconspicuous. When inclination angle along feed direction is 30° and 45°, the combination inclination angle strategy has no obvious influences on the surface roughness with increase of inclination angle along cross-feed direction. However, the combination inclination angles strategy can reduce the maximum form deviation and improve the form accuracy of the groove. Based on the results, an optimal combination inclination angles with feed direction 45° and cross-feed direction 20° strategy is proposed to machining the microgroove.

Objective: To explore the mechanism of Kangguan decoction in the treatment of coronavirus disease 2019 (COVID-19) and then perform preliminary verification. Methods: The effective compounds and target genes of Kangguan decoction were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. COVID-19 related target genes were searched in the GeneCards database. The active target genes of Kangguan decoction acting on COVID-19 were identified to perform GO function enrichment and KEGG pathway enrichment analysis. The compound-target network and protein-protein interaction were constructed;Molecular docking simulations of macromolecular protein target receptors and their corresponding compounds were performed. The clinical data of COVID-19 patients were retrieved from their electronic medical records of Nantong Third People's Hospital. Results: We screened out 137 effective compounds and 274 effective target genes of Kangguan decoction from TCMSP. The active target genes of Kangguan decoction were compared with the COVID-19 related target genes, and 63 active target genes for Kangguan decoction acting on COVID-19 were identified. GO function enrichment and KEGG pathway enrichment analysis were performed. The compound-target network and PPI network were constructed and the key compounds and key targets were selected to construct a key compound-target network. Finally, the binding of the target and its corresponding components was verified by molecular docking and two clinical cases with obvious clinical efficacy after Kangguan decoction application were demonstrated. Conclusion: The pharmacological mechanism of Kangguan decoction acting on COVID-19 has been explored, and the active compounds and targets of Kangguan decoction acting on COVID-19 and clinical efficacy for Kangguan decoction treating COVID-19 patients have been preliminarily verified.

Helical drill point is characterized by a continuous helical flank surface and an S-shape chisel edge, and its special geometry contributes to a superior drilling performance and a better grinding efficiency. However, the existing grinding processes are complicated and hard to be reproduced in practice, and it is difficult to meet the accuracy requirements as the drill diameter becomes smaller. Thus, it is crucial to research further grinding method of helical micro-drill and its drilling performance. In this paper, a grinding method of helical drill flank using a six-axis CNC grinding machine is proposed based on the mathematical model of generatrix of the helical surface. Then, this grinding process is simulated using the 3D CAD software and is validated by experimentally fabricating the helical micro-drill. The results show that this method is feasible for obtaining the micro-drill with high dimensional accuracy. For the comparison with helical micro-drill, the planar and conical micro-drills with the same geometry parameters are produced as well. The drilling experiments on 1Cr18Ni9Ti austenitic stainless steel with the planar, conical, and helical micro-drills are conducted, and the drilling force, tool wear, and hole quality are measured and analyzed. The experiment results show that the increasing rate of the radial force of helical micro-drills at the beginning of the drilling process is smaller than those of planar and conical micro-drills, the thrust force and wear of helical drill point are also smaller, and the quality of micro-holes by helical drill point is better as well. It is confirmed that the proposed grinding process is effective to fabricate the helical micro-drill with good drilling performance.

Rationale: Extensive thrombosis in the portal venous system caused by hypereosinophilic syndrome (HES) is rare, and there is no consensus on anticoagulant and thrombolytic treatments for arteriovenous thrombosis caused by HES. Patient concerns: The clinical data of a patient with extensive thrombosis in his portal venous system (superior mesenteric, splenic, hepatic, and portal veins), renal artery thrombosis, and mesenteric thrombosis caused by HES with secondary gastrointestinal bleeding and intestinal necrosis were retrospectively analyzed. Before admission, his eosinophil count increased to 7.47 × 109/L, and HES had been confirmed via bone marrow cytology. The patient experienced fever, cough, abdominal pain, massive hematemesis, and hematochezia that developed in succession. Abdominal computed tomography showed portal vein and superior mesenteric vein thromboses. Diagnosis: Hypereosinophilic syndrome; extensive thrombosis in the portal venous system; acute eosinophil-associated pneumonia; gastrointestinal bleeding; intestinal necrosis. Interventions: The patient was first treated with methylprednisolone, plasma exchange/hemofiltration, and single or combined use of unfractionated heparin and argatroban for anticoagulation. He was also administered alteplase and urokinase, successively, for thrombolytic treatment. Once the thromboses finally disappeared, the patient underwent surgery to excise a necrotic intestinal canal. Outcomes: The thromboses disappeared with these treatments, and the patient recovered after the necrotic intestinal canal was excised. Lessons: The clinical manifestations of HES are complex and varied, and this condition can cause severe and extensive arteriovenous thrombosis. Anticoagulation therapy and thrombolysis are necessary interventions, and appear to be safe and effective.

The extensive use of graphene-family nanomaterials (GFNs) in biomedicine and other fields has intentionally or unintentionally resulted in their introduction into the blood circulation system, but the effects of the biotransformation of GFNs in blood plasma on their biocompatibility, organ targeting, drug delivery and antitumor ability remain unclear. The present work discovered that GFN sheets were degraded in human blood plasma to holey sheets and aromatic hydrocarbons. The carbon atoms connected with oxygen-containing groups in the planes of GFNs were the initial attack sites for active substances (e.g., OH and O2-) in blood plasma. Subsequently, CC/CC bonds were broken. The reaction rate depended strongly on the extent of oxidization of GFNs. The pristine GFNs caused secondary structure damage to proteins and disturbances of cellular metabolic pathways. In contrast, the biotransformed nanomaterials presented high biocompatibility and were located in and targeted different tissues from their pristine forms, which influenced specific organ targeting therapy. The biotransformed nanomaterials also exhibited higher efficiencies of drug delivery (drug release and location) and killing tumor cells in vitro and in vivo. These findings provide insights into the application of nanomaterials in human healthcare using biotransformed nanomaterials.

Background This study was designed to evaluate the efficacy of exchange transfusion in patients with severe imported falciparum malaria. Twelve patients who met the diagnostic criteria for severe malaria were treated with exchange transfusion 14 times according to a conventional anti-malarial treatment. This study evaluated the efficacy of exchange transfusion for severe imported falciparum malaria. Methods Clinical data of severe imported falciparum malaria patients admitted to the intensive care unit (ICU) of Nantong Third People’s Hospital from January 2007 to December 2016 were investigated in this retrospective study. Patients were divided into the intervention group, which received exchange transfusion, and the control group. This study assessed parasite clearance and outcomes of the two groups, and levels of erythrocytes, haemoglobin, platelets, coagulation, liver function, lactate, C-reactive protein, and procalcitonin, before and after exchange transfusion in the intervention group. Results There was no significant difference in the severity of admitted patients. Exchange transfusion was successfully applied 14 times in the intervention group. Differences in the levels of erythrocytes, haemoglobin and platelets did not reach statistical significance. Exchange transfusion improved coagulation, liver function, lactic acid, C-reactive protein, and procalcitonin. No differences were observed in parasite clearance, ICU and hospital length of stay, in-hospital mortality, and costs of hospitalization between the two groups. Conclusion Exchange transfusion as adjunctive therapy for severe malaria was observed to be safe in this setting. Exchange transfusion can improve liver function and coagulation and reduce inflammation, but it failed to improve parasite clearance and the outcomes of severe imported falciparum malaria in this case series.

Considering tip relief, a finite element model of a spur gear pair in mesh is established by ANSYS software. Time-varying mesh stiffness under different amounts of tip relief is calculated based on the finite element model. Then, a finite element model of a geared rotor system is developed by MATLAB software considering the effects of time-varying mesh stiffness and constant load torque. Emphasis is given to the effects of tip relief on the lateral–torsional coupling vibration responses of the system. The results show that as the amount of tip relief increases, the saltation of time-varying mesh stiffness reduces at the position of approach action and transition mesh region from the single tooth to double tooth. A number of primary resonances and some super-harmonic of gears 1 and 2 are excited by time-varying mesh stiffness in amplitude frequency responses. As the amount of tip relief increases, some super-harmonic responses change due to the variation in the higher frequency components of time-varying mesh stiffness. After tip relief, the vibration and meshing force decrease obviously at lower mesh frequency range except at some resonance frequencies; however, tip relief is not effective in reducing the vibration at higher mesh frequency range. The amplitude fluctuation of the vibration acceleration reduces evidently after considering tip relief, which is not remarkable with the increase of meshing frequency.

Baicalin (BAI) has been reported to exert antitumor effects. However, BAI has limited water solubility, non-specific tumor targeting, and low bioavailability, which severely limited its clinical application. The aim of this study was to develop folic acid (FA) covalently conjugated-polyamidoamine (PAMAM) dendrimers (PAMAM-FA) as carrier systems for improvement of water solubility and tumor-specificity of BAI, and study the role of generation on the physiochemical properties and biological effects of PAMAM-FA/BAI complexes. In this work, four generations of PAMAM-FA were synthesized to entrap BAI. The average sizes of G3-FA/BAI, G4-FA/BAI, G5-FA/BAI, and G6-FA/BAI complexes were 174.4nm, 184.5nm, 258.8nm, and 247.5nm, respectively, and the zeta potentials of four PAMAM-FA/BAI complexes were -2.9mV, -6.6mV, -9.3mV, -9.0mV, respectively. The entrapment efficiencies of four PAMAM-FA/BAI complexes were 91.1%, 53.5%, 80.3%, and 91.9%, respectively, and the drug loading of PAMAM-FA/BAI complexes were about 22%. The formed PAMAM-FA/BAI complexes allowed sustained release of BAI in acidic PBS (pH5.4). In cellular uptake assay, PAMAM-FA/BAI complexes demonstrated increased drug uptake level in folate receptor (FR)-positive Hela cancer cells than FR-negative A549 cells, and the cellular uptake efficiency of PAMAM-FA is closely related with the generation of PAMAM. The MTT assay results showed that PAMAM-FA/BAI complexes demonstrated enhanced toxicity against Hela cells than non-FA-modified PAMAM/BAI complexes, and the G6-FA/BAI demonstrated the best inhibition efficiency. The cell cycle and cell apoptosis analysis further demonstrated the tumor-specific therapeutic efficacy of PAMAM-FA/BAI. These results suggested that the PAMAM-FA have the potential for targeted delivery of BAI into cancer cells to enhance its anti-tumor efficacy.

This paper commences with some introductory points on the relationship between cinema language and sound image. It highlights arguments put forward by film-music scholars and theoreticians such as Claudia Gorbman, Kathryn Kalinak, Sergei M. Eisenstein, Paul Willemen and Wlad Goldizh in particular. This paper also engages with these various perspectives in order to both assess their claims and outline the resultant debates on the relationship between music and image in cinema in general. Keywords—cinema language; sound image; the relationship between music and image

The discovery of complementary methods for enantioselective transition metal-catalyzed cyclization with silyloxyenynes has been accomplished using chiral phosphine ligands. Under palladium catalysis, 1,6-silyloxyenynes bearing a terminal alkyne led to the desired five-membered ring with high enantioselectivities (up to 91% ee). As for reactions under cationic gold catalysis, 1,6- and 1,5-silyloxyenynes bearing an internal alkyne furnished the chiral cyclopentane derivatives with excellent enantiomeric excess (up to 94% ee). Modification of the substrate by incorporating an α,β-unsaturation led to the discovery of a tandem cyclization. Remarkably, using silyloxy-1,3-dien-7-ynes under gold catalysis conditions provided the bicyclic derivatives with excellent diastereo- and enantioselectivities (up to >20:1 dr and 99% ee).

Novel asymmetric 5-exo-dig and 5-endo-dig cyclizations of silyloxyenynes using palladium and gold complexes are described.

Asymmetric copper-catalyzed allylic substitution with methylmagnesium bromide is employed in combination with ring-closing olefin metathesis or ene-yne metathesis to achieve the synthesis of chiral, unsaturated nitrogen heterocycles. The resulting six- to eight-membered chiral heterocycles are accessible in high yields and with excellent enantioselectivities.